Author: "Longping Wen" - Searchworks@Jio Institute Digital Library Search Results

164 results on '"Longping Wen"'

1. Bacteria-based multiplex system eradicates recurrent infections with drug-resistant bacteria via photothermal killing and protective immunity elicitation

Author: Youcui Xu, Yi Wu, Yi Hu, Mengran Xu, Yanyan Liu, Yuting Ding, Jing Chen, Xiaowan Huang, Longping Wen, Jiabin Li, and Chen Zhu
Subjects: Photosynthetic bacteria, Aluminum adjuvant, Rp@Al, Photothermal therapy, Protective antimicrobial immunity, Recurrent drug-resistant bacterial infections, Medical technology, R855-855.5
Abstract: Abstract Background The high mortality associated with drug-resistant bacterial infections is an intractable clinical problem resulting from the low susceptibility of these bacteria to antibiotics and the high incidence of recurrent infections. Methods Herein, a photosynthetic bacteria-based multiplex system (Rp@Al) composed of natural Rhodopseudomonas palustris (Rp) and Food and Drug Administration-approved aluminum (Al) adjuvant, was developed to combat drug-resistant bacterial infections and prevent their recurrence. We examined its photothermal performance and in vitro and in vivo antibacterial ability; revealed its protective immunomodulatory effect; verified its preventative effect on recurrent infections; and demonstrated the system’s safety. Results Rp@Al exhibits excellent photothermal properties with an effective elimination of methicillin-resistant Staphylococcus aureus (MRSA). In addition, Rp@Al enhances dendritic cell activation and further triggers a T helper 1 (TH1)/TH2 immune response, resulting in pathogen-specific immunological memory against recurrent MRSA infection. Upon second infection, Rp@Al-treated mice show significantly lower bacterial burden, faster abscess recovery, and higher survival under near-lethal infection doses than control mice. Conclusions This innovative multiplex system, with superior photothermal and immunomodulatory effects, presents great potential for the treatment and prevention of drug-resistant bacterial infections. Graphical Abstract
Published: 2023
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2. In vivo real-time monitoring of anti-factor Xa level using a microdialysis-coupled microfluidic device

Author: Xingbei Zhou, Tao Ding, Shushui Wang, and Longping Wen
Subjects: Anti-factor Xa, Microdialysis, Microfluidic, Real-time monitoring, Therapeutic drug monitoring, Analytical chemistry, QD71-142
Abstract: The feasibility of in vivo real-time monitoring of anti-factor Xa level had been explored using an integrated microdialysis-coupled microfluidic system. By customizing the dialysis membrane and utilizing a fluorogenic substrate, the performance of the integrated device was characterized and tested by continuous monitoring of the anti-factor Xa level in rats. Efficient sampling for low molecular weight heparin in the blood stream was demonstrated and the detection range of the device was determined to be 0.1-1.5 IU/ml. The anti-factor Xa profile was recorded for a period of 7 hours. Moreover, the results generated from this method agreed well with those from conventional assay. The present system provides a novel quantitative monitoring method with great precision, good reproducibility and full data coverage of treatment period. This study has paved the road for developing a bedside drug monitoring device in hospital setting.
Published: 2021
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3. Lgr5 in cancer biology: functional identification of Lgr5 in cancer progression and potential opportunities for novel therapy

Author: Liangliang Xu, Weiping Lin, Longping Wen, and Gang Li
Subjects: Lgr5, Wnt/β-catenin signaling, Cancer, Metastasis, Medicine (General), R5-920, Biochemistry, QD415-436
Abstract: Abstract Cancer remains one of the leading lethal diseases worldwide. Identifying biomarkers of cancers might provide insights into the strategies for the development of novel targeted anti-cancer therapies. Leucine-rich repeat-containing G protein-coupled receptor 5 (Lgr5) has been recently discovered as a candidate marker of cancer stem cell populations. Aberrant increased expression of Lgr5 may represent one of the most common molecular alterations in some human cancers, leading to long-term potentiation of canonical Wnt/β-catenin signaling. On the other hand, however, Lgr5-mediated suppression in canonical Wnt/β-catenin signaling has also been reported in certain cancers, such as B cell malignancies. Until now, therapeutic approaches targeting Lgr5-associated signaling axis are not yet clinically available. Increasing evidence have indicated that endogenous Lgr5+ cell population is implicated in tumor initiation, progression, and metastasis. This review is to summarize our current knowledge about the importance of Lgr5 in cancer biology and the underlying molecular mechanisms of Lgr5-mediated tumor-promoting/suppressive activities, as well as potentially useful preventive strategies in treating tumor. Therefore, targeted therapeutic modulation of Lgr5+ cancer cell population by targeting Wnt/β-catenin signaling through targeted drug delivery system or targeted genome editing might be promising for potential novel anti-cancer treatments. Simultaneously, combination of therapeutics targeting both Lgr5+ and Lgr5− cancer cells may deserve further consideration considering the plasticity of cancer cells. Also, a more specific targeting of cancer cells using double biomarkers may be much safer and more effective for anti-cancer therapy.
Published: 2019
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4. Cell blebbing upon addition of cryoprotectants: a self-protection mechanism.

Author: Renquan Ruan, Lili Zou, Sijie Sun, Jing Liu, Longping Wen, Dayong Gao, and Weiping Ding
Subjects: Medicine, Science
Abstract: In this work, the mechanism of cell bleb formation upon the addition of cryoprotectants (CPAs) was investigated, and the role of cell blebs in protecting cells was determined. The results show that after adding CPAs, the hyperosmotic stress results in the breakage of the cortical cytoskeleton and the detachment of the cell membrane from the cortical cytoskeleton, causing the formation of cell blebs. Multiple blebs decrease the intracellular hydrostatic pressure induced by the extracellular hyperosmotic shock and alleviate the osmotic damage to cells, which reduces the cell mortality rate. In the presence of a low concentration of CPAs, cell blebs can effectively protect cells. In contrast, in the presence of a high concentration of CPAs, the protective effect is limited because of severe disruption in the cortical cytoskeleton. To determine the relationship between blebs and the mortality rate of cells, we defined a bleb index and found that the bleb index of 0.065 can be regarded as a reference value for the safe addition of DMSO to HeLa cells. The bleb index can also explain why the stepwise addition of CPAs is better than the single-step addition of CPAs. Moreover, the mechanism of the autophagy of cells induced by the hyperosmotic stress was studied, and the protective effect associated with the autophagy was compared with the effect of the blebbing. The findings reported here elucidate a self-protection mechanism of cells experiencing the hyperosmotic stress in the presence of CPAs, and they provide significant evidence for cell tolerance in the field of cryopreservation.
Published: 2015
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5. GPS-SNO: computational prediction of protein S-nitrosylation sites with a modified GPS algorithm.

Author: Yu Xue, Zexian Liu, Xinjiao Gao, Changjiang Jin, Longping Wen, Xuebiao Yao, and Jian Ren
Subjects: Medicine, Science
Abstract: As one of the most important and ubiquitous post-translational modifications (PTMs) of proteins, S-nitrosylation plays important roles in a variety of biological processes, including the regulation of cellular dynamics and plasticity. Identification of S-nitrosylated substrates with their exact sites is crucial for understanding the molecular mechanisms of S-nitrosylation. In contrast with labor-intensive and time-consuming experimental approaches, prediction of S-nitrosylation sites using computational methods could provide convenience and increased speed. In this work, we developed a novel software of GPS-SNO 1.0 for the prediction of S-nitrosylation sites. We greatly improved our previously developed algorithm and released the GPS 3.0 algorithm for GPS-SNO. By comparison, the prediction performance of GPS 3.0 algorithm was better than other methods, with an accuracy of 75.80%, a sensitivity of 53.57% and a specificity of 80.14%. As an application of GPS-SNO 1.0, we predicted putative S-nitrosylation sites for hundreds of potentially S-nitrosylated substrates for which the exact S-nitrosylation sites had not been experimentally determined. In this regard, GPS-SNO 1.0 should prove to be a useful tool for experimentalists. The online service and local packages of GPS-SNO were implemented in JAVA and are freely available at: http://sno.biocuckoo.org/.
Published: 2010
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6. Crizotinib Nanomicelles Synergize with Chemotherapy through Inducing Proteasomal Degradation of Mutp53 Proteins

Author: Tianxiang Yi, Jieying Qian, Yayi Ye, Hao Zhang, Xin Jin, Meimei Wang, Zhenyu Yang, Wang Zhang, Longping Wen, and Yunjiao Zhang
Subjects: General Materials Science
Abstract: TP53 missense mutations that express highly stabilized mutant p53 protein (mutp53) driving tumorigenesis have been witnessed in a considerable percentage of human cancers. The attempt to induce degradation of mutp53 has thus been an attractive strategy to realize precise antitumor therapy, but currently, there has been no FDA-approved medication for mutp53 cancer. Herein, we discovered a small molecule compound crizotinib, an FDA-approved antitumor drug, exhibited outstanding mutp53-degrading capability. Crizotinib induced ubiquitination-mediated proteasomal degradation of wide-spectrum mutp53 but not the wild-type p53 protein. Degradation of mutp53 by crizotinib eliminated mutp53-conferred gain-of-function (GOF), leading to reduced cell proliferation, migration, demise, and cell cycle arrest, as well as enhanced sensitivity to doxorubicin-elicited killing in mutp53 cancer. To alleviate the side effects and improve the therapeutic effect, we adopted poly(ethylene glycol)-polylactide
Published: 2022
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7. Proteasomal and autophagy-mediated degradation of mutp53 proteins through mitochondria-targeting aggregation-induced-emission materials

Author: Meimei Wang, Zhenyu Yang, Yang Song, Pengfei Wei, Nestor Ishiwme, Liansheng Wang, Hao Zhang, Manman Jing, Meng Gao, Longping Wen, and Yunjiao Zhang
Subjects: Proteasome Endopeptidase Complex, Biomedical Engineering, General Medicine, Biochemistry, Mitochondria, Biomaterials, Mice, Cell Line, Tumor, Mutation, Autophagy, Animals, Humans, Mutant Proteins, Tumor Suppressor Protein p53, Molecular Biology, Biotechnology
Abstract: Close to half of human cancers harbor point mutations in the tumor-suppressor p53 gene, giving rise to the cellular accumulation of mutant p53 (mutp53) proteins with novel neomorphic gain-of-function (GOF) properties. The destruction of mutp53 proteins through either autophagic or proteasomal degradation is a viable strategy for the targeted therapy of p53-mutated cancers. Several nanomaterials, including zinc-iron and ZIF-8 nanoparticles (NPs), have been reported to induce the proteasomal degradation of mutp53 proteins. However, how autophagy, the other major cellular degradative pathway, influences NP-induced mutp53 degradation has not been investigated. This article shows that AIE-Mit-TPP, a mitochondria-targeting material with aggregation-induced emission (AIE) characteristics, elicits ubiquitination-dependent proteasomal degradation of a broad range of mutp53 proteins. Meanwhile, AIE-Mit-TPP also induces massive mitochondrial damage and autophagy. The inhibition of autophagy further increases AIE-Mit-TPP-elicited mutp53 degradation, revealing the negative impact of autophagy on AIE-Mit-TPP-induced mutp53 degradation. As expected, the degradation of mutp53 proteins by AIE-Mit-TPP abrogated mutp53-manifested GOF, leading to reductions in cell proliferation and migration and increases in cell cycle arrest and cell death. Consequently, AIE-Mit-TPP inhibited the growth of mutp53 tumors. This paper unravels the interesting interplay between the proteasomal and autophagic degradative pathways and pinpoints the modulation of autophagy as a potential strategy for optimizing NP-induced mutp53 degradation and p53-targeted cancer therapy. STATEMENT OF SIGNIFICANCE: We have designed three different types of AIE materials: non-targeting (AIE-Br), mitochondria-targeting (AIE-Mit-TPP), lysosome-targeting (AIE-Lyso). Our results proved that mitochondria-targeting AIE material induced degradation of mutp53 proteins via the proteasome degradation pathway and abrogated mutp53-conferred GOF phenotypes. Furthermore, we performed in vitro studies on the effect of the tested materials in mutp53-expressing cancer cells and demonstrated our findings via in vivo investigations in a mouse subcutaneous p53supR175H/supTOV112D ovarian cancer model. Our results confirmed the link between the proteasome pathway and autophagy and thus proposed a strategy of combining AIE-Mit-TPP with autophagy inhibitors for the targeted treatment of mutp53-associated tumors. Finally, we found that AIE-Mit-TPP could induce degradation of a wide-spectrum mutp53 proteins, which makes mitochondria-targeting AIE materials an effective therapeutic strategy for p53-mutated cancers.
Published: 2022
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8. Bacteria-based multiplex system eradicates recurrent infections with drug-resistant bacteria via photothermal killing and protective immunity elicitation

Author: Chen Zhu, Youcui Xu, Yi Wu, Yi Hu, Mengran Xu, Yanyan Liu, Yuting Ding, Longping Wen, and Jiabin Li
Abstract: Background: The high mortality associated with drug-resistant bacterial infections is an intractable clinical problem because of the low susceptibility of the bacteria involved to antibiotics and high incidence of recurrent infections. Methods: Herein, a photosynthetic bacteria-based multiplex system composed of natural Rhodopseudomonas palustris (Rp) and Food and Drug Administration-approved aluminum adjuvant (Rp@Al), was developed to combat drug-resistant bacterial infections and prevent their recurrence. We examined its photothermal performance, in vitro and in vivo antibacterial ability; revealed its protective immunomodulatory effect; verified its prevention effect on recurrent infections; demonstrated the system safety. Results: Rp@Al exhibits excellent photothermal properties with an effective elimination of methicillin-resistant Staphylococcus aureus (MRSA). In addition, Rp@Al elicits the activation of dendritic cells and further triggers a T helper 1 (TH1)/TH2 immune response, resulting in pathogen-specific immunological memory against recurrent MRSA infection. Upon second infection, Rp@Al-treated mice show significantly lower bacterial burden, faster abscess recovery, and higher survival under near-lethal infection doses than control mice. Conclusions: This innovative multiplex system, with superior photothermal and immunomodulatory effects, presents great potential for the treatment and prevention of drug-resistant bacterial infections.
Published: 2022
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9. Melatonin attenuates prostatic inflammation and pelvic pain via Sirt1‐dependent inhibition of the NLRP3 inflammasome in an EAP mouse model

Author: Chang-Sheng Zhan, Yi Liu, Chaozhao Liang, Jing Chen, Li Zhang, Meng Zhang, Hexi Du, Longping Wen, Ligang Zhang, and Xianguo Chen
Subjects: Male, Inflammasomes, Urology, Anti-Inflammatory Agents, Prostatitis, Pharmacology, Pelvic Pain, Proinflammatory cytokine, Melatonin, Mice, Sirtuin 1, Chronic prostatitis/chronic pelvic pain syndrome, Prostate, NLR Family, Pyrin Domain-Containing 3 Protein, medicine, Animals, Pain Measurement, business.industry, Pelvic pain, Inflammasome, medicine.disease, Disease Models, Animal, medicine.anatomical_structure, Allodynia, Oncology, Cytokines, medicine.symptom, business, medicine.drug
Abstract: Background Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a common male genitourinary system disease. As a neuroendocrine hormone, melatonin possesses a variety of biological functions, among which its anti-inflammatory effects have recently drawn substantial attention. The purpose of the current research was to study the effect of melatonin on CP/CPPS and the underlying mechanisms using a mouse model of experimental autoimmune prostatitis (EAP). Methods The EAP mouse model was successfully established by subcutaneously injecting a mixture of prostate antigen and complete Freund's adjuvant. On Day 42, hematoxylin-eosin staining was used to evaluate the histological appearance of prostate tissues. Chronic pelvic pain development was assessed by suprapubic allodynia. The levels of inflammation-related cytokines, such as interferon-γ, interleukin (IL)-17, and IL-1β, were detected by enzyme-linked immunosorbent assay. Then, we explored the anti-inflammatory effects of melatonin on CP/CPPS by Western blotting and immunohistochemical staining, by measuring the expression of silent information regulator 1 (Sirt1) and NLRP3 inflammasome-related proteins in EAP mice. Results The EAP model mice exhibited severe diffuse leukocyte infiltration and significantly increased pelvic pain compared to the control mice. In the melatonin treatment group, the histological appearance of the prostate tissues, pelvic pain development, and the levels of proinflammatory cytokines were significantly alleviated compared to the EAP + dimethyl sulfoxide group. Furthermore, we found that the protective effects of melatonin were achieved through activation of the Sirt1 pathway and downregulation of the NLRP3 inflammasome. Conclusions The results indicated that melatonin could attenuate prostate inflammation and pelvic pain by inhibiting the NLRP3 inflammasomes signaling pathway through the activation of Sirt1 in mice with EAP, and these efforts should provide a promising therapeutic strategy for CP/CPPS.
Published: 2021
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10. A blood circulation-prolonging peptide anchored biomimetic phage-platelet hybrid nanoparticle system for prolonged blood circulation and optimized anti-bacterial performance

Author: Wenbin Zhang, Sha Rui, Longping Wen, Peipei Jin, Yunjiao Zhang, Jieying Qian, Nestor Ishimwe, Jing Qian, Liu Liu, and Liansheng Wang
Subjects: 0301 basic medicine, Blood Platelets, Male, Phage display, phage therapy, Phage therapy, medicine.medical_treatment, Integrin, Medicine (miscellaneous), Peptide, Rats, Sprague-Dawley, 03 medical and health sciences, 0302 clinical medicine, In vivo, biomimetic nanoparticle, anti-bacterial, medicine, Escherichia coli, Animals, Platelet, Pharmacology, Toxicology and Pharmaceutics (miscellaneous), Escherichia coli Infections, RGD motif, chemistry.chemical_classification, biology, hybrid, Chemistry, In vitro, Peptide Fragments, Cell biology, Anti-Bacterial Agents, Rats, prolonged blood circulation, 030104 developmental biology, 030220 oncology & carcinogenesis, biology.protein, Nanoparticles, Microorganisms, Genetically-Modified, Genetic Engineering, Research Paper, Bacteriophage M13
Abstract: Phage therapy holds great promise for resolving the ever-worsening crisis of antibiotic resistance, but it also faces many challenges. One of the issues hampering phage therapy is the short blood residence time of bacteriophages. We have previously identified, through in vivo phage display, a blood circulation-prolonging peptide (BCP1) that was capable of significantly prolonging the blood retention time of a doxorubicin-loaded human ferritin nanocage, leading to enhanced therapeutic efficacy against tumors. Herein, we aimed to extend the application of BCP1 to anti-bacterial phage therapy. Methods: A genetically engineered M13 phage, BCP1-BGL, that displayed the BCP-1 peptide and expressed the restriction endonuclease Bgl II, was constructed. Taking advantage of the fact that BCP1 harbors an RGD motif (a three amino-acid sequence Arg-Gly-Asp with the ability to bind to integrins) and exerts its circulation-prolonging activity primarily through interaction with platelets, we further designed and fabricated a biomimetic phage-platelet hybrid nanoparticle (PPHN) via the physical binding of the BCP1-BGL phage to the platelet membrane nanoparticles derived via a repeated freeze-thaw procedure. A series of experiments in vitro and in vivo were conducted to reveal the long circulation and anti-bacterial capacities of BCP1-BGL phages and PPHNs. Results: The resulting PPHNs possessed a hydrodynamic size of 368 nm in deionized water, with each spherical membranous nanoparticle harboring approximately 12 rod-shaped phage particles stably bound to its surface. PPHNs, which were superior to the BCP1-BGL phages that displayed significantly prolonged anti-bacterial action in vivo against Escherichia coli infection, exhibited further extended blood retention time and optimal anti-bacterial performance in both the prophylactic and treatment approaches. Conclusion: Our work demonstrated a novel strategy in engineering biomimetic phage-based nanoparticles with improved blood retention and anti-bacterial performance and may have implications in phage therapy.
Published: 2021

11. CPLA 1.0: an integrated database of protein lysine acetylation.

Author: Zexian Liu, Jun Cao, Xinjiao Gao, Yanhong Zhou, Longping Wen, Xiangjiao Yang, Xuebiao Yao, Jian Ren 0002, and Yu Xue 0001
Published: 2011
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12. MiCroKit 3.0: an integrated database of midbody, centrosome and kinetochore.

Author: Jian Ren 0002, Zexian Liu, Xinjiao Gao, Changjiang Jin, Mingliang Ye, Hanfa Zou, Longping Wen, Zhaolei Zhang, Yu Xue 0001, and Xuebiao Yao
Published: 2010
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13. Nano vaccines and nano materials for vaccines

Author: Bin Huang, Ning Gu, LongPing Wen, He Ding, and Yan Li
Subjects: Organic polymer, Engineering, Low toxicity, business.industry, Nano, technology, industry, and agriculture, Treatment strategy, natural sciences, Pharmacology (medical), Nanotechnology, business, Nanomaterials
Abstract: Vaccines are important biological treatment strategies for effectively preventing or curing a variety of diseases, and are key means to curb the spread of new diseases such as the new coronavirus pneumonia. Compared with conventional vaccines, nano materials-based vaccines have obvious advantages such as high antigen loading and targeting efficiency, low toxicity, and diverse administration methods. In the past decade, research on nanovaccines has received increasing attention, especially more and more nanovaccines with potential applications are emerging. Nano vaccines can be classified into anti-viral nano vaccines, anti-tumor nano vaccines, anti-bacterial nano vaccines and so on. Recently, more and more nanomaterials have been reported to be applicable in preparation of nano vaccines, including organic polymer nanomaterials, lipid nanomaterials, natural nanomaterials, inorganic nanomaterials, etc. Some of these nanomaterials exhibit excellent functions, not only as a carrier for antigens, but also as immune adjuvants. In this review, we have summarized the research status of nano vaccines, focusing on analyzing different design schemes and effects of nano vaccines. In addition, we summarized the characteristics of commonly used nano materials for vaccines is summarized and perspective for the development of novel nano vaccines is prospected. This article will provide a basis for using nano vaccines to prevent or treat various new infectious diseases, including new coronaviruses, and help accelerate the discovery of new vaccines.
Published: 2020
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14. FAAH served a key membrane-anchoring and stabilizing role for NLRP3 protein independently of the endocannabinoid system

Author: Yangyang Zhu, Hao Zhang, Huawei Mao, Suqin Zhong, Yubing Huang, Sirong Chen, Kai Yan, Zhibin Zhao, Xiaohan Hao, Yue Zhang, Han Yao, Xiaowan Huang, Meimei Wang, Wenbin Zhang, Juan Li, Guangxun Meng, Xiaohua Qin, Zhiming Ye, Jiani Shen, Yang Song, Youcui Xu, Zhenyu Yang, Liansheng Wang, Yunjiao Zhang, and Longping Wen
Subjects: Cell Biology, Molecular Biology
Abstract: NLRP3, the sensor protein of the NLRP3 inflammasome, plays central roles in innate immunity. Over-activation of NLRP3 inflammasome contributes to the pathogenesis of a variety of inflammatory diseases, while gain-of-function mutations of NLRP3 cause cryopyrin-associated periodic syndromes (CAPS). NLRP3 inhibitors, particularly those that inhibit inflammasome assembly and activation, are being intensively pursued, but alternative approaches for targeting NLRP3 would be highly desirable. During priming NLRP3 protein is synthesized on demand and becomes attached to the membranes of ER and mitochondria. Here, we show that fatty acid amide hydrolase (FAAH), the key integral membrane enzyme in the endocannabinoid system, unexpectedly served the critical membrane-anchoring and stabilizing role for NLRP3. The specific interaction between NLRP3 and FAAH, mediated by the NACHT and LRR domains of NLRP3 and the amidase signature sequence of FAAH, was essential for preventing CHIP- and NBR1-mediated selective autophagy of NLRP3. Heterozygous knockout of FAAH, resulting in ~50% reduction in both FAAH and NLRP3 expression, was sufficient to substantially inhibit the auto-inflammatory phenotypes of the NLRP3-R258W knock-in mice, while homozygous FAAH loss almost completely abrogates these phenotypes. Interestingly, select FAAH inhibitors, in particular URB597 and PF-04457845, disrupted NLRP3-FAAH interaction and induced autophagic NLRP3 degradation, leading to diminished inflammasome activation in mouse macrophage cells as well as in peripheral blood mononuclear cells isolated from CAPS patients. Our results unraveled a novel NLRP3-stabilizing mechanism and pinpointed NLRP3-FAAH interaction as a potential drug target for CAPS and other NLRP3-driven diseases.
Published: 2022

15. 2D-CuPd nanozyme overcome tamoxifen resistance in breast cancer by regulating the PI3K/AKT/mTOR pathway

Author: Wenwei Jiang, Suqin Zhong, Ziying Chen, Jieying Qian, Xiaowan Huang, Hao Zhang, Longping Wen, Yunjiao Zhang, and Guangyu Yao
Subjects: Biomaterials, Mechanics of Materials, Biophysics, Ceramics and Composites, Bioengineering
Published: 2023
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16. PEGylated Manganese–Zinc Ferrite Nanocrystals Combined with Intratumoral Implantation of Micromagnets Enabled Synergetic Prostate Cancer Therapy via Ferroptotic and Immunogenic Cell Death

Author: Hui Wang, Yu Guan, Chun Li, Jia Chen, Shaoyu Yue, Jieying Qian, Bangshun Dai, Changqin Jiang, Chenghao Wen, Longping Wen, Chaozhao Liang, Yunjiao Zhang, and Li Zhang
Subjects: Biomaterials, General Materials Science, General Chemistry, Biotechnology
Published: 2023
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17. In vivo real-time monitoring of anti-factor Xa level using a microdialysis-coupled microfluidic device

Author: Shushui Wang, Longping Wen, Xingbei Zhou, and Ding Tao
Subjects: Reproducibility, Microdialysis, Materials science, QD71-142, medicine.drug_class, Microfluidics, Continuous monitoring, Low molecular weight heparin, Real-time monitoring, Therapeutic drug monitoring, Dialysis tubing, Microfluidic, In vivo, Anti factor Xa level, medicine, Analytical chemistry, Anti-factor Xa, Biomedical engineering
Abstract: The feasibility of in vivo real-time monitoring of anti-factor Xa level had been explored using an integrated microdialysis-coupled microfluidic system. By customizing the dialysis membrane and utilizing a fluorogenic substrate, the performance of the integrated device was characterized and tested by continuous monitoring of the anti-factor Xa level in rats. Efficient sampling for low molecular weight heparin in the blood stream was demonstrated and the detection range of the device was determined to be 0.1-1.5 IU/ml. The anti-factor Xa profile was recorded for a period of 7 hours. Moreover, the results generated from this method agreed well with those from conventional assay. The present system provides a novel quantitative monitoring method with great precision, good reproducibility and full data coverage of treatment period. This study has paved the road for developing a bedside drug monitoring device in hospital setting.
Published: 2021

18. PSMA-targeted arsenic nanosheets: a platform for prostate cancer therapy via ferroptosis and ATM deficiency-triggered chemosensitization

Author: Li Zhang, Zhengbao Zha, Zhaohua Miao, Longping Wen, Zunfu Ke, Run Lin, Meng Zhang, Chaozhao Liang, Hang Liu, Hui Wang, Jialin Meng, and Qiong He
Subjects: Male, Programmed cell death, 02 engineering and technology, Ataxia Telangiectasia Mutated Proteins, GPX4, Arsenic, 03 medical and health sciences, chemistry.chemical_compound, Prostate cancer, Ataxia Telangiectasia, Chemosensitization, medicine, Ferroptosis, Humans, General Materials Science, Doxorubicin, Electrical and Electronic Engineering, Arsenic trioxide, 030304 developmental biology, chemistry.chemical_classification, 0303 health sciences, Reactive oxygen species, Process Chemistry and Technology, Prostatic Neoplasms, Glutathione, 021001 nanoscience & nanotechnology, medicine.disease, chemistry, Mechanics of Materials, Cancer research, 0210 nano-technology, medicine.drug
Abstract: Ferroptosis, a newly recognized form of non-apoptotic cell death, has recently been introduced for effective cancer therapy. The reported ferroptosis-inducing nanomaterials mainly consisted of metal-based components. Herein, we designed an inorganic metal-free nanoplatform, PSMA-targeted arsenic nanosheets (PMANs), which simultaneously increased glutathione (GSH) consumption, suppressed solute carrier family 7 member 11 (SLC7A11) and glutathione-dependent peroxidase 4 (GPX4) expression, and promoted the generation of reactive oxygen species (ROS) and lipid peroxides (LPO). In addition, owing to the large surface area, PMANs efficiently transported doxorubicin (DOX) to prostate cancer for synergistic therapy. Surprisingly, we found that PMANs could sensitize prostate cancer cells to DOX through downregulating the expression of ataxia telangiectasia mutated (ATM), which further augmented the GPX4 downregulation-mediated ferroptotic tumoricidal effect. Given that arsenic trioxide has been routinely and successfully used in the clinical treatment of leukemia for a long time, we anticipate that PMANs will offer a promising strategy for prostate cancer therapy.
Published: 2021

19. Pro-Death or Pro-Survival: Contrasting Paradigms on Nanomaterial-Induced Autophagy and Exploitations for Cancer Therapy

Author: Li Zhang, Jinhao Gao, Longping Wen, and Yunjiao Zhang
Subjects: Cell type, Programmed cell death, Cell Survival, 010405 organic chemistry, Cell, Autophagy, Cellular homeostasis, General Medicine, General Chemistry, Biology, Cell fate determination, 010402 general chemistry, 01 natural sciences, Nanostructures, 0104 chemical sciences, Cell biology, Nanomedicine, medicine.anatomical_structure, Cell Death Process, Neoplasms, Cancer cell, medicine, Animals, Lysosomes
Abstract: Autophagy is a critical lysosome-mediated cellular degradation process for the clearance of damaged organelles, obsolete proteins, and invading pathogens and plays important roles in the pathogenesis and treatment of human diseases including cancer. While not a cell death process per se, autophagy is nevertheless intimately linked to a cell's live/die decision. Basal autophagy, operating constitutively at low levels in essentially every mammalian cell, is vital for maintaining cellular homeostasis and promotes cell survival. On the other hand, elevated level of autophagy is frequently observed in cells responding to a physical, chemical, or biological stress. This "induced" autophagy, a hallmark under a variety of pathological and pathophysiological conditions, may be either pro-death or pro-survival, two contrasting paradigms for cell fate determination. Research in our laboratory and other groups around the world over the last 15 years has revealed nanomaterials as a unique class of autophagy inducers, with the capability of elevating the cellular autophagy to extremely high levels. In this Account we focus on the contrasting cell fate decision impacted by nanomaterial-induced autophagy. First, we give a brief introduction to nanomaterial-induced autophagy and summarize our current understanding on how it affects a cell's live/die decision. Autophagy induced by nanomaterials, in most cases, promotes cell death, but a significant number of nanomaterials are also able to elicit pro-survival autophagy. Although not a common feature, some nanomaterials may induce pro-death autophagy in one cell type while eliciting pro-survival autophagy in a different cell type. The ability to control the level of the induced autophagy, and furthermore its pro-death/pro-survival nature, is critically important for nanomedicine. Second, we discuss several possible mechanistic insights on the pro-death/pro-survival decision for nanomaterial-induced autophagy. "Disrupted" autophagic processes, with a "block" or perhaps "diversion" at the various stages, may be a characteristic hallmark for nanomaterial-induced autophagy, rendering it intrinsically pro-death in nature. On the other hand, autophagy-mediated upregulation and activation of pro-survival factors or signaling pathways, overriding the intrinsic pro-death nature, may be a common mechanism for nanomaterial-induced pro-survival autophagy. In addition, cargo degradation and reactive oxygen species may also play important roles in the pro-death/pro-survival decision impacted by nanomaterial-induced autophagy. Finally, we focus on the situation where nanomaterials induce autophagy in cancer cells and summarize the different strategies in exploiting the pro-death or pro-survival nature of nanomaterial-induced autophagy to enhance the various modalities of cancer therapy, including direct cancer cell killing, chemotherapy and radiotherapy, photothermal therapy, and integrated diagnosis and therapy. While the details vary, the basic principle is simple and straightforward. If the induced autophagy is pro-death, maximize it. Otherwise, inhibit it. Effective exploitation of nanomaterial-induced autophagy has the potential to become a new weapon in our ever-increasing arsenal to fight cancer, particularly difficult-to-treat and drug-resistant cancer.
Published: 2019
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20. Lgr5 in cancer biology: functional identification of Lgr5 in cancer progression and potential opportunities for novel therapy

Author: Longping Wen, Liangliang Xu, Gang Li, and Weiping Lin
Subjects: 0301 basic medicine, Population, Medicine (miscellaneous), Review, Tumor initiation, Biochemistry, Genetics and Molecular Biology (miscellaneous), Receptors, G-Protein-Coupled, Metastasis, lcsh:Biochemistry, 03 medical and health sciences, Lgr5, 0302 clinical medicine, Cancer stem cell, Neoplasms, Biomarkers, Tumor, medicine, Humans, lcsh:QD415-436, education, Wnt Signaling Pathway, Cancer, education.field_of_study, lcsh:R5-920, business.industry, Wnt signaling pathway, Cell Biology, medicine.disease, 030104 developmental biology, Targeted drug delivery, 030220 oncology & carcinogenesis, Cancer cell, Disease Progression, Neoplastic Stem Cells, Cancer research, Molecular Medicine, business, lcsh:Medicine (General), Wnt/β-catenin signaling
Abstract: Cancer remains one of the leading lethal diseases worldwide. Identifying biomarkers of cancers might provide insights into the strategies for the development of novel targeted anti-cancer therapies. Leucine-rich repeat-containing G protein-coupled receptor 5 (Lgr5) has been recently discovered as a candidate marker of cancer stem cell populations. Aberrant increased expression of Lgr5 may represent one of the most common molecular alterations in some human cancers, leading to long-term potentiation of canonical Wnt/β-catenin signaling. On the other hand, however, Lgr5-mediated suppression in canonical Wnt/β-catenin signaling has also been reported in certain cancers, such as B cell malignancies. Until now, therapeutic approaches targeting Lgr5-associated signaling axis are not yet clinically available. Increasing evidence have indicated that endogenous Lgr5+ cell population is implicated in tumor initiation, progression, and metastasis. This review is to summarize our current knowledge about the importance of Lgr5 in cancer biology and the underlying molecular mechanisms of Lgr5-mediated tumor-promoting/suppressive activities, as well as potentially useful preventive strategies in treating tumor. Therefore, targeted therapeutic modulation of Lgr5+ cancer cell population by targeting Wnt/β-catenin signaling through targeted drug delivery system or targeted genome editing might be promising for potential novel anti-cancer treatments. Simultaneously, combination of therapeutics targeting both Lgr5+ and Lgr5− cancer cells may deserve further consideration considering the plasticity of cancer cells. Also, a more specific targeting of cancer cells using double biomarkers may be much safer and more effective for anti-cancer therapy.
Published: 2019
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21. Plasmonic MoO3−x nanoparticles incorporated in Prussian blue frameworks exhibit highly efficient dual photothermal/photodynamic therapy

Author: Kuang Liang, Gang Wang, Youcui Xu, An-Wu Xu, Jun Lin, Longping Wen, Akif Zeb, Atheer Hameid Odda, and Naseeb Ullah
Subjects: Prussian blue, Materials science, Nanocomposite, medicine.medical_treatment, Biomedical Engineering, Nanoparticle, Photodynamic therapy, Nanotechnology, 02 engineering and technology, General Chemistry, General Medicine, Photothermal therapy, 010402 general chemistry, 021001 nanoscience & nanotechnology, 01 natural sciences, 0104 chemical sciences, Nanomaterials, chemistry.chemical_compound, chemistry, medicine, General Materials Science, Surface plasmon resonance, 0210 nano-technology, Plasmon
Abstract: Development of near infrared (NIR) light-responsive nanomaterials for high performance multimodal phototherapy within a single nanoplatform is still challenging in technology and biomedicine. Herein, a new phototherapeutic nanoagent based on FDA-approved Prussian blue (PB) functionalized oxygen-deficient molybdenum oxide nanoparticles (MoO3−x NPs) is strategically designed and synthesized by a facile one-pot size/morphology-controlled process. The as-prepared PB-MoO3−x nanocomposites (NCs) with a uniform particle size of ∼90 nm and high water dispersibility exhibited strong optical absorption in the first biological window, which is induced by plasmon resonance in an oxygen-deficient MoO3−x semiconductor. More importantly, PB-MoO3−x NCs not only exhibited a high photothermal conversion efficiency of ∼63.7% and photostability but also offered a further approach for the generation of reactive oxygen species (ROS) upon singular NIR light irradiation which significantly improved the therapeutic efficiency of the PB agent. Furthermore, PB-MoO3−x NCs showed a negligible cytotoxic effect in the dark, but an excellent therapeutic effect toward two triple-negative breast cancer (TNBC) cell lines at a low concentration (20 μg mL−1) of NCs and a moderate NIR laser power density. Additionally, efficient tumor ablation and metastasis inhibition in a 4T1 TNBC mouse tumor model can also be realized by synergistic photothermal/photodynamic therapy (PTT/PDT) under a single continuous NIR wave laser. Taken together, this study paved the way for the use of a single nanosystem for multifunctional therapy.
Published: 2019
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22. Enhancing tumor chemotherapy and overcoming drug resistance through autophagy-mediated intracellular dissolution of zinc oxide nanoparticles

Author: Bensheng Qiu, Weiping Ding, Longping Wen, Jiqian Zhang, Jun Lin, Pengfei Wei, Yi Hu, Mengran Xu, Li Zhang, Yunjiao Zhang, Hou-Rui Zhang, and Liang Dong
Subjects: Programmed cell death, Autophagic Cell Death, Antineoplastic Agents, 02 engineering and technology, Vacuole, 010402 general chemistry, 01 natural sciences, Wortmannin, Mice, chemistry.chemical_compound, medicine, Animals, Humans, General Materials Science, Doxorubicin, chemistry.chemical_classification, Mice, Inbred BALB C, Reactive oxygen species, Autophagy, Neoplasms, Experimental, 021001 nanoscience & nanotechnology, 0104 chemical sciences, Cell biology, chemistry, Drug Resistance, Neoplasm, Cancer cell, MCF-7 Cells, Nanoparticles, Female, Zinc Oxide, Reactive Oxygen Species, 0210 nano-technology, Intracellular, HeLa Cells, medicine.drug
Abstract: Autophagy may represent a common cellular response to nanomaterials. In the present study, it was demonstrated that zinc oxide nanoparticle (ZON)-elicited autophagy contributes to tumor cell killing by accelerating the intracellular dissolution of ZONs and reactive oxygen species (ROS) generation. In particular, ZONs could promote Atg5-regulated autophagy flux without the impairment of autophagosome-lysosome fusion, which is responsible for ZON-elicited cell death in cancer cells. On the other hand, a further study revealed that a significant free zinc ion release in lysosomal acid compartments and sequential ROS generation in cells treated with ZONs were also associated with tumor cytotoxicity. Intriguingly, the colocalization between FITC-labeled ZONs and autophagic vacuoles indicates that the intracellular fate of ZONs is associated with autophagy. Moreover, the chemical or genetic inhibition of autophagy significantly reduced the level of intracellular zinc ion release and ROS generation separately, demonstrating that ZON-induced autophagy contributed toward cancer cell death by accelerating zinc ion release and sequentially increasing intracellular ROS generation. The modulation of autophagy holds great promise for improving the efficacy of tumor chemotherapy. Herein, ZONs were verified to enhance chemotherapy in both normal and drug-resistant cancer cells via synergistic autophagy elicitation. Further, this elicitation resulted in tremendous zinc ion release and ROS generation, which accounted for enhancing the tumor chemotherapy and overcoming drug resistance. No obvious changes in the expression level of P-gp proteins or the amount of doxorubicin uptake induced by ZONs in MCF-7/ADR cells also indicated that the increased zinc ion release and ROS generation via synergistic autophagy induction were responsible for overcoming the drug resistance. Finally, in vivo experiments involving animal models of 4T1 tumor cells revealed that the antitumor therapeutic effect of a combinatory administration obviously outperformed those of ZONs or free doxorubicin treatment alone at the same dose, which could be attenuated by the autophagy inhibitor wortmannin or ion-chelating agent EDTA. Taken together, our results reveal the mechanism wherein the autophagy induction by ZONs potentiates cancer cell death and a novel biological application for ZONs in adjunct chemotherapy in which autophagy reinforces zinc ion release and ROS generation.
Published: 2019
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23. Autophagy Impairment through Lysosome Dysfunction by Brucine Induces Immunogenic Cell Death (ICD)

Author: Manman Jing, Hao Zhang, Nestor Ishimwe, Longping Wen, Meimei Wang, Liansheng Wang, Pengfei Wei, and Yunjiao Zhang
Subjects: Programmed cell death, MAP Kinase Signaling System, ATG5, Cellular homeostasis, Autophagy-Related Protein 5, 03 medical and health sciences, Mice, 0302 clinical medicine, Lysosome, Cell Line, Tumor, Neoplasms, medicine, Autophagy, Animals, Humans, HMGB1 Protein, 030304 developmental biology, 0303 health sciences, Cell Death, business.industry, General Medicine, Strychnine, medicine.anatomical_structure, Complementary and alternative medicine, 030220 oncology & carcinogenesis, Gene Knockdown Techniques, Cancer cell, Cancer research, Immunogenic cell death, Immunotherapy, Signal transduction, business, Calreticulin, Lysosomes, Drugs, Chinese Herbal, Phytotherapy
Abstract: Autophagy is an important tightly controlled cellular process that regulates cellular homeostasis and is involved in deciding cell fate such as cell survival and death. The role of autophagy in many intracellular signaling pathways explains its interaction with other different types of cell death, including apoptosis and immunogenic cell death (ICD). The reports showed the complex and intriguing relationship existing between autophagy and immune system signaling pathways. However, the role of autophagy in ICD remains to be clearly elucidated. In this study, we demonstrated that Brucine, a clinically-used small molecule in traditional Chinese medicine, elicited autophagy inhibition. Brucine also triggered cell stress and induced features of ICD, including calreticulin (CRT) exposure and high-mobility group box 1 (HMGB1) release in MDA-MB-231 and CT26 cancer cells. Brucine impaired autolysosomal degradation and exerted a feedback regulation of ERK1/2-mTOR-p70S6K signaling cascade. Brucine-elicited ICD was confirmed by the rejection of CT26 tumor cells, implanted in the mice after vaccination with Brucine-treated CT26 cells. The impaired autophagy contributed to Brucine-induced ICD, as knock-down of Atg5 significantly reduced Brucine-elicited CRT exposure and HMGB1 release. Our results revealed Brucine as a novel autophagy regulator, ICD inducer and hitherto undocumented role of autophagy in ICD. Thus, these results imply the importance of Brucine in cancer immunotherapy. Therefore, Brucine may be used as an ICD inducer and improve its application in cancer treatment with minimized toxicity.
Published: 2020

24. mTORC1-dependent TFEB nucleus translocation and pro-survival autophagy induced by zeolitic imidazolate framework-8

Author: Xiaowan Huang, Wenwei Jiang, Hao Pan, Jing Qian, Shanzi Luo, Liansheng Wang, Longping Wen, Yang Song, Guangyu Yao, Hao Zhang, Yunjiao Zhang, and He Ding
Subjects: Programmed cell death, ATG5, Biomedical Engineering, 02 engineering and technology, mTORC1, Mechanistic Target of Rapamycin Complex 1, HeLa, 03 medical and health sciences, Lysosome, medicine, Autophagy, Humans, General Materials Science, 030304 developmental biology, 0303 health sciences, biology, Chemistry, Basic Helix-Loop-Helix Leucine Zipper Transcription Factors, 021001 nanoscience & nanotechnology, biology.organism_classification, Cell biology, medicine.anatomical_structure, Doxorubicin, Cancer cell, Zeolites, TFEB, 0210 nano-technology, HeLa Cells
Abstract: A great variety of nanoparticles are known to induce autophagy, leading to either pro-death or pro-survival. Zeolitic imidazolate framework-8 (ZIF-8), a type of porous metal–organic framework (MOF) material and a promising drug delivery vector, has reportedly shown excellent efficacy for cancer therapy. However, less attention has been paid to the potential biological effect of ZIF-8 per se, and if so, how the effect impacts cell fate and therapy outcomes. Herein, we showed that ZIF-8 induced autophagy in HeLa cells, characterized by increased autophagosome formation without disruption of autophagic flux, in a dose- and time-dependent fashion. ZIF-8 also caused dephosphorylation of the transcription factor EB (TFEB) at serine-142 and serine-211, leading to the nucleus translocation of TFEB, an event that promoted lysosome biogenesis and is necessary for autophagy induction. We further pinpointed the inhibition of mTORC1 as the critical event upstream of ZIF-8-elicited TFEB dephosphorylation and the subsequent nucleus translocation. Furthermore, autophagy induced by ZIF-8 promoted cell survival, as inhibiting autophagy by either 3-methyladenine (3-MA) or ATG5 knockdown significantly enhanced ZIF-8-elicited HeLa cell death. Most importantly, doxorubicin-encapsulated ZIF-8 (DOX@ZIF-8) also elicited strong pro-survival autophagy, and the co-delivery of an autophagic inhibitor (3-MA) dramatically enhanced the cytotoxicity of DOX@ZIF-8 in HeLa cells. Our results revealed the unique ability of ZIF-8, both in a free and drug-loaded form, to induce pro-survival autophagy in certain cancer cells, a finding with important implications for potential clinical studies that utilize ZIF-8 as a drug carrier.
Published: 2020

25. Rationally designed rapamycin-encapsulated ZIF-8 nanosystem for overcoming chemotherapy resistance

Author: Min Wu, Jingjing Wu, Pengfei Wei, Bensheng Qiu, Mengran Xu, Jun Lin, Longping Wen, Ping Li, Yi Hu, Fenfen Li, and Weiping Ding
Subjects: medicine.medical_treatment, Biophysics, Bioengineering, 02 engineering and technology, Biomaterials, 03 medical and health sciences, Mice, medicine, Animals, Doxorubicin, PI3K/AKT/mTOR pathway, 030304 developmental biology, chemistry.chemical_classification, Sirolimus, 0303 health sciences, Chemotherapy, Reactive oxygen species, Drug Carriers, Chemistry, Autophagy, 021001 nanoscience & nanotechnology, Mechanics of Materials, Drug delivery, Ceramics and Composites, Cancer research, Zeolites, Nanoparticles, 0210 nano-technology, Intracellular, medicine.drug, Zeolitic imidazolate framework
Abstract: Zeolitic imidazolate framework-8 (ZIF-8) nanoparticles are widely reported as a pH-sensitive drug delivery carrier with high loading capacity for tumor therapy. However, the mechanism of intracellular corrosion of ZIF-8 and the corresponding biological effects especially for autophagy response have been rarely reported. Herein, the as-synthesized ZIF-8 was demonstrated to induce mTOR independent and pro-death autophagy. Interestingly, the autophagic process participated in the corrosion of ZIF-8. Subsequently, zinc ion release and the generation of reactive oxygen species due to its corrosion in the acidic compartments were directly responsible for tumor cell killing. In addition, ZIF-8 could sensitize tumor cells to chemotherapy by switching cytoprotective to death promoting autophagy induced by doxorubicin. The mTOR signaling pathway activation was demonstrated to restrict tumor chemotherapy efficiency. Hence, a combined platform rapamycin encapsulated zeolitic imidazolate frameworks (Rapa@ZIF-8) was constructed and demonstrated a more significant chemo-sensitized effect relative to ZIF-8 nanoparticles or rapamycin treatment alone. Lastly, the combined administration of Rapa@ZIF-8 and doxorubicin exhibited an outstanding synergistic antitumor effect without any obvious toxicity to the major organs of mice. Collectively, the optimized nanoplatform, Rapa@ZIF-8, provides a proof of concept for intentionally interfering mTOR pathway and utilizing the switch of survival-to death-promoting autophagy for adjunct chemotherapy.
Published: 2020

26. Impact of Morphology on Iron Oxide Nanoparticles-Induced Inflammasome Activation in Macrophages

Author: Jinhao Gao, Xiaomin Zhao, Rui Sha, Yangyang Zhu, Longping Wen, Liu Liu, Yunjiao Zhang, and Lijiao Yang
Subjects: 0301 basic medicine, Morphology (linguistics), Materials science, Inflammasomes, THP-1 Cells, Interleukin-1beta, Nanoparticle, 02 engineering and technology, 03 medical and health sciences, chemistry.chemical_compound, In vivo, medicine, Humans, General Materials Science, Magnetite Nanoparticles, Innate immune system, Macrophages, Pyroptosis, Inflammasome, 021001 nanoscience & nanotechnology, 030104 developmental biology, chemistry, Biophysics, Efflux, Lysosomes, 0210 nano-technology, Iron oxide nanoparticles, medicine.drug
Abstract: Inflammasomes, a critical component of the innate immune system, mediate much of the inflammatory response manifested by engineered nanomaterials. Iron oxide nanoparticles (IONPs), a type of nanoparticles that have gained widespread acceptance in preclinical and clinical settings, are known to induce inflammasome activation, but how morphology affects the inflammasome-activating property of IONPs has not been addressed. In this report, we have synthesized four morphologically distinct IONPs having the same aspect ratio and similar surface charge, thus offering an ideal system to assess the impact of morphology on nanoparticle-elicited biological effect. We show that morphology was a critical determinant for IONP-induced IL-1β release and pyroptosis, with the octapod and plate IONPs exhibiting significantly higher activity than the cube and sphere IONPs. The inflammasome-activating capacity of different IONPs correlated with their respective ability to elicit intracellular reactive oxygen species generation, lysosomal damage, and potassium efflux, three well-known mechanisms for nanoparticle-facilitated inflammasome activation. Furthermore, we demonstrate that the release of IL-1β induced by IONPs was only partly mediated by NLRP3, suggesting that inflammasomes other than NLRP3 are also involved in IONP-induced inflammasome activation. Our results may have implications for designing safer nanoparticles for in vivo applications.
Published: 2018
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27. Harnessing copper-palladium alloy tetrapod nanoparticle-induced pro-survival autophagy for optimized photothermal therapy of drug-resistant cancer

Author: Weiguo Xu, Jie Zeng, Wenbin Zhang, Jianxun Ding, Jie Cao, Rui Sha, Rui Zhang, Yunjiao Zhang, Guangyu Yao, Lan Zhang, Peipei Jin, Longping Wen, Fanchen Luo, Jun Lin, and Jing Qian
Subjects: Cell Survival, Science, Blotting, Western, General Physics and Astronomy, Nanoparticle, chemistry.chemical_element, Apoptosis, Breast Neoplasms, Mice, SCID, 02 engineering and technology, Drug resistance, 010402 general chemistry, 01 natural sciences, Article, General Biochemistry, Genetics and Molecular Biology, Photothermal conversion, Mice, Alloys, Autophagy, In Situ Nick-End Labeling, medicine, Animals, Humans, lcsh:Science, Mice, Inbred BALB C, Multidisciplinary, Chemistry, Cancer, General Chemistry, Phototherapy, Photothermal therapy, 021001 nanoscience & nanotechnology, medicine.disease, Palladium alloy, Copper, 0104 chemical sciences, Drug Resistance, Neoplasm, MCF-7 Cells, Cancer research, Nanoparticles, Female, lcsh:Q, Reactive Oxygen Species, 0210 nano-technology, Palladium, HeLa Cells
Abstract: Chemo-PTT, which combines chemotherapy with photothermal therapy, offers a viable approach for the complete tumor eradication but would likely fail in drug-resistant situations if conventional chemotherapeutic agents are used. Here we show that a type of copper (Cu)-palladium (Pd) alloy tetrapod nanoparticles (TNP-1) presents an ideal solution to the chemo-PTT challenges. TNP-1 exhibit superior near-infrared photothermal conversion efficiency, thanks to their special sharp-tip structure, and induce pro-survival autophagy in a shape- and composition-dependent manner. Inhibition of autophagy with 3-methyl adenine or chloroquine has a remarkable synergistic effect on TNP-1-mediated PTT in triple-negative (4T1), drug-resistant (MCF7/MDR) and patient-derived breast cancer models, achieving a level of efficacy unattainable with TNP-2, the identically-shaped CuPd nanoparticles that have a higher photothermal conversion efficiency but no autophagy-inducing activity. Our results provide a proof-of-concept for a chemo-PTT strategy, which utilizes autophagy inhibitors instead of traditional chemotherapeutic agents and is particularly useful for eradicating drug-resistant cancer., “Conventional chemotherapy-photothermal therapy combination has limited efficacy in drug resistant cancers. Here they develop Copper-palladium tetrapod nanoparticles to overcome these challenges and show them to work in synergy with autophagy inhibitors to treat drug resistant cancers”
Published: 2018
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28. Microwave-Assisted Facile Synthesis of Eu(OH)3 Nanoclusters with Pro-Proliferative Activity Mediated by miR-199a-3p

Author: Wanglai Hu, Li Zhang, Song Yonghong, Longping Wen, Song Fan, Liang Dong, Chaozhao Liang, Ya-Dong Wu, Zongyao Hao, Pengfei Wei, and Yang Lu
Subjects: 0301 basic medicine, Materials science, Biocompatibility, Cell growth, Ligand, chemistry.chemical_element, Nanoparticle, 02 engineering and technology, 021001 nanoscience & nanotechnology, Combinatorial chemistry, Nanoclusters, Nanomaterials, 03 medical and health sciences, chemistry.chemical_compound, 030104 developmental biology, Dextran, chemistry, General Materials Science, 0210 nano-technology, Europium
Abstract: As a pharmaceutical excipient, dextran serves as an efficient ligand for stabilizing some clinically available inorganic nanomaterials such as iron oxide nanocrystals. Herein, dextran-capped nanosized europium(III) hydroxides [Eu(OH)3] nanoclusters (NCs) composed of 5 nm Eu(OH)3 nanoparticles have been large-scale synthesized via a microwave-accelerated hydrothermal reaction. The as-synthesized Eu(OH)3 NCs exhibited excellent physiological stability and biocompatibility both in vitro and in vivo and possessed considerable pro-proliferative activities in human umbilical vein endothelial cells (HUVECs). To investigate the epigenetic modulation of Eu(OH)3 NCs-elicited proliferation, the newly developed high-throughput next generation sequencing technology was employed herein. As a result, we have screened 371 dysregulated miRNAs in Eu(OH)3 NCs-treated HUVECs and obtained 26 potentially functional miRNAs in promoting cell proliferation. Furthermore, upregulated miR-199a-3p was predicted, validated, and eventu...
Published: 2018
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29. Photoresponsive PAMAM‐Assembled Nanocarrier Loaded with Autophagy Inhibitor for Synergistic Cancer Therapy

Author: Weiping Wang, Hao Zhang, Liansheng Wang, Yunjiao Zhang, Meimei Wang, Longping Wen, Nestor Ishimwe, Yafei Li, Xiaowan Huang, Pengfei Wei, Manman Jing, and Yang Zhou
Subjects: Chemistry, Autophagy, Normal tissue, Cancer therapy, Light irradiation, General Chemistry, In vitro, Biomaterials, Chloroquine, In vivo, medicine, Cancer research, General Materials Science, Nanocarriers, Biotechnology, medicine.drug
Abstract: As one of the most promising drug-delivery carriers due to its small size, easy surface modifiability, and hydrophobic interior, cationic poly(amidoamine) (PAMAM) per se, demonstrated by previous reports and the authors' present study, indicate potential anticancer capability, however, which are restricted by autophagy elicitation. Besides, its side-toxicity profile, having also been extensively documented, limits its translation into the clinic. Herein, the authors design a photoresponsive PAMAM-assembled nanoparticle loaded with the autophagy inhibitor (chloroquine, CQ), which exhibits light responsiveness for precisely controlling drug release and superior dark biosafety. Upon light irradiation, the nanoparticle can dissociate into charged small PAMAM for a significant antitumor effect. Meanwhile, the released CQ can inhibit pro-survival autophagy induced by PAMAM to achieve an excellent synergistic anticancer efficacy in vitro and in vivo. The authors' study provided a vision of utilizing PAMAM as self-carried anticancer therapeutics in combination with an autophagy inhibitor and proposing a cancer therapy with high antitumor efficacy and low side effects to normal tissues.
Published: 2021
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30. Photoresponsive PAMAM‐Assembled Nanocarrier Loaded with Autophagy Inhibitor for Synergistic Cancer Therapy

Author: Manman Jing, Yafei Li, Meimei Wang, Hao Zhang, Pengfei Wei, Yang Zhou, Nestor Ishimwe, Xiaowan Huang, Liansheng Wang, Longping Wen, Weiping Wang, and Yunjiao Zhang
Subjects: Biomaterials, Dendrimers, Drug Carriers, Neoplasms, Autophagy, Humans, Nanoparticles, General Materials Science, General Chemistry, Biotechnology
Abstract: As one of the most promising drug-delivery carriers due to its small size, easy surface modifiability, and hydrophobic interior, cationic poly(amidoamine) (PAMAM) per se, demonstrated by previous reports and the authors' present study, indicate potential anticancer capability, however, which are restricted by autophagy elicitation. Besides, its side-toxicity profile, having also been extensively documented, limits its translation into the clinic. Herein, the authors design a photoresponsive PAMAM-assembled nanoparticle loaded with the autophagy inhibitor (chloroquine, CQ), which exhibits light responsiveness for precisely controlling drug release and superior dark biosafety. Upon light irradiation, the nanoparticle can dissociate into charged small PAMAM for a significant antitumor effect. Meanwhile, the released CQ can inhibit pro-survival autophagy induced by PAMAM to achieve an excellent synergistic anticancer efficacy in vitro and in vivo. The authors' study provided a vision of utilizing PAMAM as self-carried anticancer therapeutics in combination with an autophagy inhibitor and proposing a cancer therapy with high antitumor efficacy and low side effects to normal tissues.
Published: 2021
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31. Curcumin improves alcoholic fatty liver by inhibiting fatty acid biosynthesis

Author: Longxin Qiu, Tianxing Hu, Jingfan Ma, Longping Wen, Qionghong Zhong, Mengyuan Zhao, Tong Chen, and Chang Guo
Subjects: Male, 0301 basic medicine, Curcumin, Glucuronate, Linoleic acid, Glyoxylate and dicarboxylate metabolism, Pentose phosphate pathway, Biology, Toxicology, Pentose Phosphate Pathway, Mice, 03 medical and health sciences, chemistry.chemical_compound, Glucuronic Acid, Animals, Metabolomics, Pharmacology, Ethanol, Anti-Inflammatory Agents, Non-Steroidal, Fatty Acids, Central Nervous System Depressants, Galactose, Oleic acid, 030104 developmental biology, Liver, chemistry, Biochemistry, Alcoholic fatty liver, Drug metabolism, Fatty Liver, Alcoholic
Abstract: Alcoholic fatty liver is a threat to human health. It has been long known that abstinence from alcohol is the most effective therapy, other effective therapies are not available for the treatment in humans. Curcumin has a great potential for anti-oxidation and anti-inflammation, but the effect on metabolic reconstruction remains little known. Here we performed metabolomic analysis by gas chromatography/mass spectrometry and explored ethanol pathogenic insight as well as curcumin action pattern. We identified seventy-one metabolites in mouse liver. Carbohydrates and lipids were characteristic categories. Pathway analysis results revealed that ethanol-induced pathways including biosynthesis of unsaturated fatty acids, fatty acid biosynthesis and pentose and glucuronate interconversions were suppressed by curcumin. Additionally, ethanol enhanced galactose metabolism and pentose phosphate pathway. Glyoxylate and dicarboxylate metabolism and pyruvate metabolism were inhibited in mice fed ethanol diet plus curcumin. Stearic acid, oleic acid and linoleic acid were disease biomarkers and therapical biomarkers. These results reflect the landscape of hepatic metabolism regulation. Our findings illustrate ethanol pathological pathway and metabolic mechanism of curcumin therapy.
Published: 2017
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32. Antioxidant and anti-inflammatory activities of ethyl acetate extract of Gynura formosana (Kitam) leaves

Author: Longxin Qiu, Longping Wen, Jingfan Ma, Chang Guo, Danyan Lin, and Yinlai Pan
Subjects: 0301 basic medicine, Cancer Research, Antioxidant, medicine.drug_class, medicine.medical_treatment, General Medicine, Glutathione, Biology, Pharmacology, Anti-inflammatory, Proinflammatory cytokine, Lipid peroxidation, Superoxide dismutase, 03 medical and health sciences, chemistry.chemical_compound, 030104 developmental biology, Immunology and Microbiology (miscellaneous), chemistry, Biochemistry, Catalase, Lactate dehydrogenase, medicine, biology.protein
Abstract: Gynura formosana Kitam (family Compositae) has traditionally been used for the prevention of diabetes, cancer and inflammation in China. However, there are few reports of its anti-inflammatory effects. In the present study, after assessing the in vitro antioxidant activities of extracts from Gynura formosana Kitam leaves, the anti-inflammatory and antioxidant activities of ethyl acetate extract of Gynura formosana Kitam leaves (EAEG) were further investigated in rats using a cotton pellet-induced model of granuloma. EAEG significantly inhibited the formation of cotton pellet-induced granuloma in rats in a dose-dependent manner. Moreover, EAEG treatment significantly decreased the level of plasma C-reactive protein and suppressed the activities of plasma glutamate pyruvate transaminase and lactate dehydrogenase in model groups. Furthermore, EAEG increased the hepatic levels of anti-oxidative enzymes or antioxidants, including catalase, superoxide dismutase and reduced glutathione, and reduced the level of lipid peroxidation in the rat model of inflammation. In addition, EAEG decreased plasma levels of tumor necrosis factor-α and interleukin-1β in the rat model of inflammation. Therefore, our results indicated that EAEG had potent anti-inflammatory effects, which was achieved at least in part through activating antioxidant enzyme activities and suppressing the production of proinflammatory mediators by macrophages.
Published: 2017
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33. Caspase mediated beclin-1 dependent autophagy tuning activity and apoptosis promotion by surface modified hausmannite nanoparticle

Author: Souvik Mondal, Anupam Giri, Longping Wen, Wei Zhou, Yunjiao Zhang, and Samir Kumar Pal
Subjects: 0301 basic medicine, Cell signaling, Materials science, biology, Autophagy, Metals and Alloys, Biomedical Engineering, 02 engineering and technology, 021001 nanoscience & nanotechnology, Cleavage (embryo), Cell biology, Biomaterials, 03 medical and health sciences, chemistry.chemical_compound, 030104 developmental biology, chemistry, Apoptosis, Cleave, Ceramics and Composites, biology.protein, splice, 0210 nano-technology, Caspase, Hausmannite
Abstract: Hidden effects of nano-materials to induced autophagy, a lysosomal degradative pathway, remain an exciting topic, in the level of material-protein interaction and subsequent cellular signaling features. Here, our studies show that surface modified hausmannite nanoparticles (Mn3 O4 NPs) can uniformly cleave/splice Beclin-1 protein and alter cellular mechanism on the emphasis of tuning autophagy and subsequently promote enhancement of apoptosis. Details investigation of Beclin-1 dependency and its uniform cleavage/splice pattern by surface modified Mn3 O4 NPs, shows tuning of cellular mechanism on emphasis of caspase mediated autophagy tuning. Our findings will also clarify the conflict between apoptosis-autophagy on the basis of its unique property derived from surface chemistry modulation, in context of Beclin-1 eminent cleavage/splice which remarks novel effect of Beclin-1 dependent tuning of autophagosomes formation and switch to enhance apoptotic index, mediates by PI3KC3 cleavage and caspase activation. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 1299-1310, 2017.
Published: 2017
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34. Autophagy regulation as a promising approach for improving cancer immunotherapy

Author: Wenbin Zhang, Longping Wen, Nestor Ishimwe, Jieying Qian, and Yunjiao Zhang
Subjects: 0301 basic medicine, Cancer Research, medicine.medical_treatment, Cellular homeostasis, Biology, 03 medical and health sciences, 0302 clinical medicine, Immune system, Antigen, Cancer immunotherapy, Neoplasms, medicine, Autophagy, Tumor Microenvironment, Cytotoxic T cell, Animals, Homeostasis, Humans, Tumor microenvironment, 030104 developmental biology, Oncology, 030220 oncology & carcinogenesis, Cancer research, Immunogenic cell death, Immunotherapy
Abstract: Autophagy plays a critical role in intracellular metabolism and maintaining cellular homeostasis. Certain tumor cells present a higher basal autophagy rate and autophagy inhibition can lead to impaired metabolic dysfunction in autophagy-dependent tumor cells. Autophagy status in immune cells dictates their fate and response to antigen; however, autophagy in immune cells may be beneficial or detrimental depending on the developmental stage of the cell and more specifically its degree of differentiation. Autophagy-deficient hosts present variations in many metabolites, proteins and enzymes that may have tumor-promoting or -inhibiting effects. The centrality of autophagy in the metabolism of some cancers and immune cells poses as a critical target whose mechanisms must be further unraveled to optimize patient response and prevent tumor recurrence.
Published: 2019

35. Blood Circulation-Prolonging Peptides for Engineered Nanoparticles Identified via Phage Display

Author: Yunpeng Bian, Yanchun Liu, Jieying Qian, Peipei Jin, Li Ren, Wenbin Zhang, Longping Wen, Shiheng Yin, Jing Qian, Rui Sha, Yunjiao Zhang, Jun Lin, Nestor Ishimwe, Yi Hu, and Liu Liu
Subjects: Phage display, Glycine, Bioengineering, Peptide, 02 engineering and technology, Arginine, In vivo, Peptide Library, Neoplasms, Humans, General Materials Science, Platelet, Amino Acid Sequence, chemistry.chemical_classification, Aspartic Acid, M13 bacteriophage, biology, Chemistry, Mechanical Engineering, Biological Transport, General Chemistry, 021001 nanoscience & nanotechnology, Condensed Matter Physics, biology.organism_classification, Engineered nanoparticles, Biochemistry, Doxorubicin, Blood circulation, Ferritins, Nucleic acid, Nanoparticles, 0210 nano-technology, Cell Surface Display Techniques, Peptides, Bacteriophage M13
Abstract: Sustaining blood retention for theranostic nanoparticles is a big challenge. Various approaches have been attempted and have demonstrated some success but limitations remain. We hypothesized that peptides capable of increasing blood residence time for M13 bacteriophage, a rod-shaped nanoparticle self-assembled from proteins and nucleic acids, should also prolong blood circulation for engineered nanoparticles. Here we demonstrate the feasibility of this approach by identifying a series of blood circulation-prolonging (BCP) peptides through in vivo screening of an M13 peptide phage display library. Intriguingly, the majority of the identified BCP peptides contained an arginine-glycine-aspartic acid (RGD) motif, which was necessary but insufficient for the circulation-prolonging activity. We further demonstrated that the RGD-mediated specific binding to platelets was primarily responsible for the enhanced blood retention of BCP1. The utility of the BCP1 peptide was demonstrated by fusion of the peptide to human heavy-chain ferritin (HFn), leading to significantly improved pharmacokinetic profile, enhanced tumor cell uptake and optimum anticancer efficacy for doxorubicin encapsulated in the HFn nanocage. Our results provided a proof-of-concept for an innovative yet simple strategy, which utilizes phage display to discover novel peptides with the capability of substantially prolonging blood circulation for engineered theranostic nanoparticles.
Published: 2019

36. Inhibition of inhaled halloysite nanotube toxicity by trehalose through enhanced autophagic clearance of p62

Author: Yunjiao Zhang, Longping Wen, Qixing Zhang, Yongming Zhang, Xiaowen Hu, Wenjie Yang, Yi Hu, and Rui Rong
Subjects: Male, Biomedical Engineering, Apoptosis, Mice, Inbred Strains, 02 engineering and technology, 010501 environmental sciences, Pharmacology, Toxicology, medicine.disease_cause, 01 natural sciences, chemistry.chemical_compound, Mice, In vivo, Macrophages, Alveolar, Sequestosome-1 Protein, medicine, Autophagy, Animals, 0105 earth and related environmental sciences, Inhalation exposure, Inhalation Exposure, Nanotubes, Dose-Response Relationship, Drug, Chemistry, Trehalose, 021001 nanoscience & nanotechnology, In vitro, Oxidative Stress, Toxicity, Clay, 0210 nano-technology, Bronchoalveolar Lavage Fluid, Oxidative stress
Abstract: Nanomaterials are widely used in an ever-increasing number of consumer and industrial products. It is therefore essential that the toxic effects of nanomaterials are understood in order to improve product safety. Here we evaluate the toxicity of inhaled halloysite nanotubes (HNTs) by applying a purpose designed inhalation exposure system and succeed in suppressing HNTs toxicity using trehalose. By assessing apoptosis, oxidative stress, inflammatory response, and autophagy, it is found that HNTs can cause sub-chronic toxicity in mice. Further investigations indicate that HNTs induce autophagy blockade that results in the accumulation of sequestosome-1 (p62), which is responsible for the excessive apoptosis, inflammatory response and oxidative stress. We found that p62 can be eliminated by trehalose and the application of trehalose in vitro and in vivo successfully inhibits toxicity by accelerating the clearance of p62. Trehalose shows great potential for reducing nanoparticle toxicity.
Published: 2019

37. Inhibition of CaMKIIα Activity Enhances Antitumor Effect of Fullerene C60 Nanocrystals by Suppression of Autophagic Degradation

Author: Zhengdong Cai, Yingchao Zhang, Longping Wen, Jianxun Ding, Min Mao, Binhui Lin, Yanyan Miao, Jing Xu, Yingqi Hua, Dongqing Zuo, Yu Shrike Zhang, Suoyuan Li, Yi Hu, Tao Zhang, Gangyang Wang, Zhuoying Wang, Fei Yin, and Hongsheng Wang
Subjects: Autophagosome, Programmed cell death, autophagy, fullerene C60 nanocrystals, General Chemical Engineering, General Physics and Astronomy, Medicine (miscellaneous), chemistry.chemical_element, 02 engineering and technology, Calcium, 010402 general chemistry, 01 natural sciences, Biochemistry, Genetics and Molecular Biology (miscellaneous), General Materials Science, osteosarcoma therapy, Cytotoxicity, Protein kinase A, chemistry.chemical_classification, Gene knockdown, Reactive oxygen species, Full Paper, Chemistry, Autophagy, General Engineering, calcium/calmodulin‐dependent protein kinase IIα, Full Papers, 021001 nanoscience & nanotechnology, 0104 chemical sciences, Cell biology, autophagic degradation, 0210 nano-technology
Abstract: Fullerene C60 nanocrystals (nano‐C60) possess various attractive bioactivities, including autophagy induction and calcium/calmodulin‐dependent protein kinase IIα (CaMKIIα) activation. CaMKIIα is a multifunctional protein kinase involved in many cellular processes including tumor progression; however, the biological effects of CaMKIIα activity modulated by nano‐C60 in tumors have not been reported, and the relationship between CaMKIIα activity and autophagic degradation remains unclear. Herein, nano‐C60 is demonstrated to elicit reactive oxygen species (ROS)‐dependent cytotoxicity and persistent activation of CaMKIIα in osteosarcoma (OS) cells. CaMKIIα activation, in turn, produces a protective effect against cytotoxicity from nano‐C60 itself. Inhibition of CaMKIIα activity by either the chemical inhibitor KN‐93 or CaMKIIα knockdown dramatically promotes the anti‐OS effect of nano‐C60. Moreover, inhibition of CaMKIIα activity causes lysosomal alkalinization and enlargement, and impairs the degradation function of lysosomes, leading to autophagosome accumulation. Importantly, excessive autophagosome accumulation and autophagic degradation blocking are shown to play an important role in KN‐93‐enhanced‐OS cell death. The synergistic anti‐OS efficacy of KN‐93 and nano‐C60 is further revealed in an OS‐xenografted murine model. The results demonstrate that CaMKIIα inhibition, along with the suppression of autophagic degradation, presents a promising strategy for improving the antitumor efficacy of nano‐C60.
Published: 2019

38. Inhibition of lanthanide nanocrystal-induced inflammasome activation in macrophages by a surface coating peptide through abrogation of ROS production and TRPM2-mediated Ca2+ influx

Author: Longping Wen, Han Yao, Pengfei Wei, Wei Zhou, Jun Lin, Peipei Jin, Yunjiao Zhang, Xi Liu, Youcui Xu, and Liu Liu
Subjects: 0301 basic medicine, Materials science, Inflammasomes, media_common.quotation_subject, Biophysics, Caspase 1, TRPM Cation Channels, Bioengineering, 02 engineering and technology, Bone marrow-derived macrophage, Lanthanoid Series Elements, Cathepsin B, Cell Line, Biomaterials, Mice, 03 medical and health sciences, Coated Materials, Biocompatible, medicine, Animals, Humans, TRPM2, Internalization, media_common, integumentary system, Macrophages, Autophagy, hemic and immune systems, Inflammasome, Macrophage Activation, 021001 nanoscience & nanotechnology, Cell biology, Surface coating, 030104 developmental biology, Mechanics of Materials, Immunology, Ceramics and Composites, Nanoparticles, Calcium, Crystallization, Peptides, Reactive Oxygen Species, 0210 nano-technology, tissues, medicine.drug
Abstract: Lanthanide-based nanoparticles (LNs) hold great promise in medicine. A variety of nanocrystals, including LNs, elicits potent inflammatory response through activation of NLRP3 inflammasome. We have previously identified an LNs-specific surface coating peptide RE-1, with the sequence of ‘ACTARSPWICG’, which reduced nanocrystal-cell interaction and abrogated LNs-induced autophagy and toxicity in both HeLa cells and liver hepatocytes. Here we show that RE-1 coating effectively inhibited LNs-induced inflammasome activation, mostly mediated by NLRP3, in mouse bone marrow derived macrophage (BMDM) cells, human THP-1 cells and mouse peritoneal macrophages and also reduced LNs-elicited inflammatory response in vivo. RE-1 coating had no effect on cellular internalization of LNs in BMDM cells, in contrast to the situation in HeLa cells where cell uptake of LNs was significantly inhibited by RE-1. To elucidate the molecular mechanism underlying the inflammasome-inhibiting effect of RE-1, we assessed several parameters known to influence nanocrystal-induced NLRP3 inflammasome activation. RE-1 coating did not reduce potassium efflux, which occurred after LNs treatment in BMDM cells and was necessary but insufficient for LNs-induced inflammasome activation. RE-1 did decrease lysosomal damage induced by LNs, but the inhibitor of cathepsin B did not affect LNs-elicited caspase 1 activation and IL-1β release, suggesting that lysosomal damage was not critically important for LNs-induced inflammasome activation. On the other hand, LNs-induced elevation of intracellular reactive oxygen species (ROS), critically important for inflammasome activation, was largely abolished by RE-1 coating, with the reduction on NADPH oxidase-generated ROS playing a more prominent role for RE-1's inflammasome-inhibiting effect than the reduction on mitochondria-generated ROS. ROS generation further triggered Ca2+ influx, an event that was mediated by Transient Receptor Potential M2 (TRPM2) and was necessary for inflammasome activation, and this event was completely inhibited by RE-1 coating. We conclude from these studies that inhibition of ROS production, and the subsequent abrogation of TRPM2-mediated Ca2+ influx, is the primary mechanism underlying RE-1's inhibitory effect on LNs-induced inflammasome activation. The ability of regulating the inflammatory response of nanocrystals through peptide surface coating may be of great value for in vivo applications of LNs and other engineered nanomaterials.
Published: 2016
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39. Reactive oxygen species acts as executor in radiation enhancement and autophagy inducing by AgNPs

Author: Jun Ma, Hao Wu, Ning Gu, Peidang Liu, Longping Wen, Peng Zhao, Jun Lin, Haizhen Jin, and Zhihai Huang
Subjects: 0301 basic medicine, Radiation-Sensitizing Agents, Programmed cell death, Silver, Biophysics, Metal Nanoparticles, Bioengineering, 02 engineering and technology, Bioinformatics, Silver nanoparticle, Biomaterials, 03 medical and health sciences, In vivo, Cell Line, Tumor, Glioma, Autophagy, medicine, Humans, chemistry.chemical_classification, Reactive oxygen species, Brain Neoplasms, business.industry, 021001 nanoscience & nanotechnology, medicine.disease, In vitro, 030104 developmental biology, chemistry, Mechanics of Materials, Apoptosis, Ceramics and Composites, Cancer research, Reactive Oxygen Species, 0210 nano-technology, business
Abstract: Malignant glioma is one of the most common intracranial tumor with a dismal prognosis. The radiosensitizing effect of silver nanoparticles (AgNPs) on glioma both in vitro and in vivo were demonstrated in the previous studies of our group. However, the underlying mechanism is still unclear. In this present study, the use of antioxidants is employed for the regulating of reactive oxygen species (ROS) in U251 cells treated with various agents, and the results shows that ROS played an essential role in the autophagy inducing and radiosensitization effect of AgNPs. Moreover, the inhibition of protective autophagy with 3-MA is another way to increase ROS, resulting in the increasing of cell death and apoptosis. Taken together, understanding the relationship between the elevated ROS and autophagy and the effect of ROS should be useful to the clinical applications of AgNPs. These findings could potentially be exploited for new therapeutic strategies in glioma radiotherapy.
Published: 2016
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40. Dendritic Platinum-Copper Alloy Nanoparticles as Theranostic Agents for Multimodal Imaging and Combined Chemophotothermal Therapy

Author: Yunjiao Zhang, Longping Wen, Qiang Zhang, Yang Yan, Zhengjie Zhou, Yiyun Cheng, Rui Ma, Kewen Hu, and Bing Ni
Subjects: Multimodal imaging, Materials science, Photothermal effect, Cancer therapy, Nanoparticle, Nanotechnology, 02 engineering and technology, Photothermal therapy, 010402 general chemistry, 021001 nanoscience & nanotechnology, Condensed Matter Physics, 01 natural sciences, 0104 chemical sciences, Electronic, Optical and Magnetic Materials, Biomaterials, In vivo, Copper alloy, Electrochemistry, medicine, Doxorubicin, 0210 nano-technology, medicine.drug
Abstract: Theranostic nanoparticles that possess multiple diagnostic modalities and allow spatiotemporally controlled therapies can significantly improve therapeutic outcomes and reduce adverse effects. Here, an intelligent and biocompatible theranostic formulation is developed based on dendritic platinum–copper alloy nanoparticles (DPCN) for cancer therapy. DPCN have excellent photothermal effect, and can load anticancer drugs such as doxorubicin in their porous structure and release the loaded drugs in response to near infrared light or moderate acidic stimulus. They also inherently have multimodal imaging modalities. Upon the guidance of photoacoustic imaging, DPCN-mediated photothermal treatment efficiently inhibits tumor growth in vivo. Furthermore, doxorubicin-loaded DPCN completely suppress the tumor growth even under a low treatment temperature, which avoids hypothermia-induced damage to normal tissues. Our study develops an excellent theranostic nanoparticle with inherent multimodal imaging and therapeutic modalities for chemophotothermal cancer therapy.
Published: 2016
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41. Autophagic lysosomal reformation depends on mTOR reactivation in H2O2-induced autophagy

Author: Peipei Jin, Na Man, Longping Wen, Jiqian Zhang, Yunjiao Zhang, Jun Lin, Ming Chen, Wei Zhou, and Pengfei Wei
Subjects: 0301 basic medicine, Recombinant Fusion Proteins, Green Fluorescent Proteins, Biology, Biochemistry, Clathrin, 03 medical and health sciences, chemistry.chemical_compound, Phosphatidylinositol Phosphates, Genes, Reporter, Phagosomes, Lysosome, Autophagy, medicine, Homeostasis, Humans, Phosphatidylinositol, Microautophagy, PI3K/AKT/mTOR pathway, TOR Serine-Threonine Kinases, Late stage, rab7 GTP-Binding Proteins, Hydrogen Peroxide, Cell Biology, Culture Media, Cell biology, 030104 developmental biology, medicine.anatomical_structure, Gene Expression Regulation, chemistry, rab GTP-Binding Proteins, biology.protein, Lysosomes, Microtubule-Associated Proteins, HeLa Cells, Signal Transduction
Abstract: Autophagic lysosomal reformation, a key cellular process for maintaining lysosome homeostasis in elevated autophagy, so far has only been reported for cells under certain forms of starvation. For this reason, it is controversial that whether this phenomenon is starvation-specific and its importance in lysosomal regeneration at the late stage of autophagy is often challenged. Here we show that exogenous hydrogen peroxide (H2O2) induced lysosome depletion and recovery characteristic of autophagic lysosomal reformation, and we confirmed the occurrence of autophagic lysosomal reformation after H2O2 treatment by demonstrating Rab7 dissociation from autolysosomes, recruitment of Phosphatidylinositol 4-phosphate (PI4P) and clathrin to the surface of autolysosomes, and the existence of tubular "pro-lysosome" structures extending from autolysosomes. Similar to starvation, H2O2 caused an initial deactivation and a subsequent reactivation for mTOR, and mTOR reactivation was essential for ALR. Our results provided a first non-starvation example of autophagic lysosomal reformation and provide evidence for its importance for some autophagic processes other than that of starvation.
Published: 2016
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42. Enhancing Chemotherapy of p53‐Mutated Cancer through Ubiquitination‐Dependent Proteasomal Degradation of Mutant p53 Proteins by Engineered ZnFe‐4 Nanoparticles

Author: Zijian Zhou, Jinhao Gao, Xiaowan Huang, Hao Zhang, Wenbin Zhang, He Ding, Longping Wen, Meimei Wang, Jieying Qian, Yang Song, Tianxiang Yi, Lijiao Yang, Guangyu Yao, Suqin Zhong, Pengfei Wei, and Yunjiao Zhang
Subjects: Chemotherapy, Materials science, biology, medicine.medical_treatment, Mutant, Nanoparticle, Cancer, Condensed Matter Physics, medicine.disease, Electronic, Optical and Magnetic Materials, Cell biology, Biomaterials, Ubiquitin, P53 protein, Electrochemistry, biology.protein, medicine, Degradation (geology)
Published: 2020
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43. Iron oxide nanoparticles promote macrophage autophagy and inflammatory response through activation of toll-like Receptor-4 signaling

Author: Bin Song, Jimei Duan, Yu Nie, Li Yang, Longping Wen, Rongrong Jin, Danyang Li, Hua Ai, Zhongyuan Cai, Wencheng Zhu, Yunjiao Zhang, Li Liu, Qiyong Gong, and James M. Anderson
Subjects: Endosome, Cell Survival, p38 mitogen-activated protein kinases, Blotting, Western, Biophysics, Fluorescent Antibody Technique, Bioengineering, 02 engineering and technology, Ferric Compounds, Proinflammatory cytokine, Biomaterials, 03 medical and health sciences, Mice, Downregulation and upregulation, Autophagy, Macrophage, Animals, 030304 developmental biology, Inflammation, 0303 health sciences, Toll-like receptor, Chemistry, Reverse Transcriptase Polymerase Chain Reaction, Macrophages, 021001 nanoscience & nanotechnology, Immunohistochemistry, Cell biology, Toll-Like Receptor 4, RAW 264.7 Cells, Mechanics of Materials, Ceramics and Composites, TLR4, Nanoparticles, 0210 nano-technology
Abstract: Nanoparticle-induced autophagy is crucial for its metabolism, cytotoxicity and therapy potency, but little is known about how the host immune system would respond to it. In this study, we demonstrated that two clinically used superparamagnetic iron oxide nanoparticles (SPIONs) specifically induced macrophage autophagy through activation of TLR4, followed by phosphorylation of p38 and nucleus translocation of Nrf2, leading to upregulation of p62/SQSTM1 and macrophage scavenger receptor SR-AI mRNA expression. Overexpressed p62 conjugated with LC3 to form aggresome-like induced structures (ALIS) and then fused with SPIONs containing endosomes and lysosomes to form autolysosomes for degradation of endocytosed nanoparticles. More importantly, SPIONs also could promote macrophage autophagy in mouse liver which is their imaging target. We also discovered that SPIONs could stimulate the expression of inflammatory cytokines through activation of TLR4 signaling in macrophage. In general, our findings indicate that SPIONs would interact with TLR4 on the macrophage membrane and trigger its downstream signaling pathway, independent of the classic autophagic p62 reduction pathway. The observed autophagy and induced inflammatory responses in macrophages provide unique and novel perspectives in optimizing imaging/therapy nanoparticle performance in addition to analysis by traditional biochemical evaluation methods. It also enriches our understanding of NP/macrophage interaction mechanisms in reticular endothelial system (RES) organs.
Published: 2018

44. Microwave-Assisted Facile Synthesis of Eu(OH)

Author: Li, Zhang, Wanglai, Hu, Yadong, Wu, Pengfei, Wei, Liang, Dong, Zongyao, Hao, Song, Fan, Yonghong, Song, Yang, Lu, Chaozhao, Liang, and Longping, Wen
Subjects: MicroRNAs, Human Umbilical Vein Endothelial Cells, Humans, Nanoparticles, Microwaves, Cell Proliferation
Abstract: As a pharmaceutical excipient, dextran serves as an efficient ligand for stabilizing some clinically available inorganic nanomaterials such as iron oxide nanocrystals. Herein, dextran-capped nanosized europium(III) hydroxides [Eu(OH)
Published: 2018

45. The Ethyl Acetate Extract of Gynura formosana Kitam. Leaves Inhibited Cervical Cancer Cell Proliferation via Induction of Autophagy

Author: Longping Wen, Jing Fan Ma, Yang Lv, Pengfei Wei, Long Xin Qiu, Yuan Peng Shi, and Chang Guo
Subjects: 0301 basic medicine, Article Subject, General Immunology and Microbiology, Apoptosis Inhibitor, biology, Chemistry, Cell growth, Autophagy, lcsh:R, lcsh:Medicine, General Medicine, Pharmacology, biology.organism_classification, General Biochemistry, Genetics and Molecular Biology, HeLa, 03 medical and health sciences, 030104 developmental biology, Downregulation and upregulation, Apoptosis, Cell culture, DNA fragmentation
Abstract: Gynura formosana Kitam. belongs to the Compositae family and has been traditionally used for the prevention of cancer, diabetes, and inflammation in China. Previous studies had indicated that the ethyl acetate extract of Gynura formosana Kitam. leaves (EAEG) exhibited antioxidant and anti-inflammatory activity. In this report, we demonstrated that EAEG possessed potent anticancer activity through autophagy-mediated inhibition of cell proliferation. EAEG induced a strong cytostatic effect towards HeLa cells and, to a lesser extent, HepG2 and MCF-7 cells. This cytostatic effect of EAEG was not a consequence of increased apoptosis, as neither DNA fragmentation nor change in protein expression level for a number of apoptosis-related genes including Bid, Bax, Bcl-2, and caspase-3 was observed after EAEG treatment, and the apoptosis inhibitor Z-VAD-FMK did not inhibit the EAEG-elicited cytostatic effect. On the other hand, EAEG induced autophagy in a dose-dependent fashion, as shown by increased GFP puncta formation, enhanced conversion of the microtubule-associated protein light chain LC3-I to LC3-II, and downregulation of the p62 protein. Treating the HeLa cells with EAEG together with Chloroquine (CQ) further accelerated LC3 conversion and p62 clearance, indicating that EAEG induced complete autophagy flux. Importantly, the autophagy inhibitor 3-methyladenine (3MA) significantly abrogated the cytostatic effect of EAEG, strongly suggesting that EAEG inhibited HeLa cell proliferation through the induction of autophagy rather than apoptosis. Our results provided a novel and interesting mechanistic insight into the anticancer action of EAEG, supporting the traditional use of this plant for the treatment of the cancer.
Published: 2018

46. The Application of In Vivo Extracellular Recording Technique to Study the Biological Effects of Nanoparticles in Brain

Author: Han Zhao, Longping Wen, Ju-Tao Chen, Yanyan Miao, and Ming Wang
Subjects: In vivo, Chemistry, Extracellular, Biophysics, Nanoparticle
Published: 2018
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47. Differential ERK activation during autophagy induced by europium hydroxide nanorods and trehalose: Maximum clearance of huntingtin aggregates through combined treatment

Author: Jiqian Zhang, Jun Lin, Chitta Ranjan Patra, Li Zhang, Renquan Ruan, Peipei Jin, Ayan Kumar Barui, Yi Hu, Shan-shan Shi, Wei Zhou, Pengfei Wei, Yunjiao Zhang, Longping Wen, and Hou-Rui Zhang
Subjects: MAPK/ERK pathway, Huntingtin, Cell Survival, Green Fluorescent Proteins, Biophysics, Nerve Tissue Proteins, Bioengineering, Biology, Autophagy-Related Protein 5, Biomaterials, Mice, chemistry.chemical_compound, Europium, Cell Line, Tumor, Phagosomes, Nitriles, Autophagy, Butadienes, Hydroxides, Huntingtin Protein, Animals, Humans, Phosphorylation, RNA, Small Interfering, Extracellular Signal-Regulated MAP Kinases, PI3K/AKT/mTOR pathway, Nanotubes, Adenine, TOR Serine-Threonine Kinases, Trehalose, Chloroquine, Neurodegenerative Diseases, Cell biology, Androstadienes, Microscopy, Fluorescence, chemistry, Mechanics of Materials, Ceramics and Composites, Macrolides, Signal transduction, Lysosomes, Wortmannin, Microtubule-Associated Proteins, HeLa Cells, Signal Transduction
Abstract: Accelerating the clearance of intracellular protein aggregates through elevation of autophagy represents a viable approach for the treatment of neurodegenerative diseases. In our earlier report, we have demonstrated the enhanced degradation of mutant huntingtin protein aggregates through autophagy process induced by europium hydroxide nanorods [EHNs: Eu(III)(OH)3], but the underlying molecular mechanism of EHNs mediated autophagy was unclear. The present report reveals that EHNs induced autophagy does not follow the classical AKT-mTOR and AMPK signaling pathways. The inhibition of ERK1/2 phosphorylation using the specific MEK inhibitor U0126 partially abrogates the autophagy as well as the clearance of mutant huntingtin protein aggregates mediated by EHNs suggesting that nanorods stimulate the activation of MEK/ERK1/2 signaling pathway during autophagy process. In contrast, another mTOR-independent autophagy inducer trehalose has been found to induce autophagy without activating ERK1/2 signaling pathway. Interestingly, the combined treatment of EHNs and trehalose leads to more degradation of mutant huntingtin protein aggregates than that obtained with single treatment of either nanorods or trehalose. Our results demonstrate the rational that further enhanced clearance of intracellular protein aggregates, needed for diverse neurodegenerative diseases, may be achieved through the combined treatment of two or more autophagy inducers, which stimulate autophagy through different signaling pathways.
Published: 2015
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48. Oxidative stress, apoptosis, and cell cycle arrest are induced in primary fetal alveolar type II epithelial cells exposed to fine particulate matter from cooking oil fumes

Author: Fang-Biao Tao, Dao-Jun Chen, Qihong Zhao, Zhen Che, Longping Wen, Yan-Yan Chen, Ying Liu, Cijiang Yao, Xiaoxia Zhu, and Jiyu Cao
Subjects: China, Programmed cell death, Cell cycle checkpoint, Health, Toxicology and Mutagenesis, Cell, Apoptosis, medicine.disease_cause, complex mixtures, Cell Line, medicine, Animals, Environmental Chemistry, Cooking, Lung, Air Pollutants, Chemistry, Endoplasmic reticulum, Epithelial Cells, Cell Cycle Checkpoints, General Medicine, Pollution, Cell biology, Oxidative Stress, medicine.anatomical_structure, Cell culture, Immunology, Unfolded protein response, Particulate Matter, Oxidative stress
Abstract: Epidemiological studies demonstrate a linkage between morbidity and mortality and particulate matter (PM), particularly fine particulate matter (PM2.5) that can readily penetrate into the lungs and are therefore more likely to increase the incidence of respiratory and cardiovascular diseases. The present study investigated the compositions of cooking oil fume (COF)-derived PM2.5, which is the major source of indoor pollution in China. Furthermore, oxidative stress, cytotoxicity, apoptosis, and cell cycle arrest induced by COF-derived PM2.5 in primary fetal alveolar type II epithelial cells (AEC II cells) were also detected. N-acetyl-L-cysteine (NAC), a radical scavenger, was used to identify the role of oxidative stress in the abovementioned processes. Our results suggested that compositions of COF-derived PM2.5 are obviously different to PM2.5 derived from other sources, and COF-derived PM2.5 led to cell death, oxidative stress, apoptosis, and G0/G1 cell arrest in primary fetal AEC II cells. Furthermore, the results also showed that COF-derived PM2.5 induced apoptosis through the endoplasmic reticulum (ER) stress pathway, which is indicated by the increased expression of ER stress-related apoptotic markers, namely GRP78 and caspase-12. Besides, the induction of oxidative stress, cytotoxicity, apoptosis, and cell cycle arrest was reversed by pretreatment with NAC. These findings strongly suggested that COF-derived PM2.5-induced toxicity in primary fetal AEC II cells is mediated by increased oxidative stress, accompanied by ER stress which results in apoptosis.
Published: 2015
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49. Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition)

Author: Daniel J. Klionsky, Kotb Abdelmohsen, Akihisa Abe, Md Joynal Abedin, Hagai Abeliovich, Abraham Acevedo Arozena, Hiroaki Adachi, Christopher M. Adams, Peter D. Adams, Khosrow Adeli, Peter J. Adhihetty, Sharon G. Adler, Galila Agam, Rajesh Agarwal, Manish K. Aghi, Maria Agnello, Patrizia Agostinis, Patricia V. Aguilar, Julio Aguirre Ghiso, Edoardo M. Airoldi, Slimane Ait Si Ali, Takahiko Akematsu, Emmanuel T. Akporiaye, Mohamed Al Rubeai, Guillermo M. Albaiceta, Chris Albanese, Diego Albani, Matthew L. Albert, Jesus Aldudo, Hana Algül, Mehrdad Alirezaei, Iraide Alloza, Alexandru Almasan, Maylin Almonte Beceril, Emad S. Alnemri, Covadonga Alonso, Nihal Altan Bonnet, Dario C. Altieri, Silvia Alvarez, Lydia Alvarez Erviti, Sandro Alves, Giuseppina Amadoro, Atsuo Amano, Consuelo Amantini, Santiago Ambrosio, Ivano Amelio, Amal O. Amer, Mohamed Amessou, Angelika Amon, Zhenyi An, Frank A. Anania, Stig U. Andersen, Usha P. Andley, Catherine K. Andreadi, Nathalie Andrieu Abadie, Alberto Anel, David K. Ann, Shailendra Anoopkumar Dukie, Manuela Antonioli, Hiroshi Aoki, Nadezda Apostolova, Saveria Aquila, Katia Aquilano, Koichi Araki, Eli Arama, Agustin Aranda, Jun Araya, Alexandre Arcaro, Esperanza Arias, Hirokazu Arimoto, Aileen R. Ariosa, Jane L. Armstrong, Thierry Arnould, Ivica Arsov, Katsuhiko Asanuma, Valerie Askanas, Eric Asselin, Ryuichiro Atarashi, Sally S. Atherton, Julie D. Atkin, Laura D. Attardi, Patrick Auberger, Georg Auburger, Laure Aurelian, Riccardo Autelli, Laura Avagliano, Maria Laura Avantaggiati, Limor Avrahami, Suresh Awale, Neelam Azad, Tiziana Bachetti, Jonathan M. Backer, Dong Hun Bae, Jae sung Bae, Ok Nam Bae, Soo Han Bae, Eric H. Baehrecke, Seung Hoon Baek, Stephen Baghdiguian, Agnieszka Bagniewska Zadworna, Hua Bai, Jie Bai, Xue Yuan Bai, Yannick Bailly, Kithiganahalli Narayanaswamy Balaji, Walter Balduini, Andrea Ballabio, Rena Balzan, Rajkumar Banerjee, Gábor Bánhegyi, Haijun Bao, Benoit Barbeau, Maria D. Barrachina, Esther Barreiro, Bonnie Bartel, Alberto Bartolomé, Diane C. Bassham, Maria Teresa Bassi, Robert C. Bast Jr, Alakananda Basu, Maria Teresa Batista, Henri Batoko, Maurizio Battino, Kyle Bauckman, Bradley L. Baumgarner, K. Ulrich Bayer, Rupert Beale, Jean François Beaulieu, George R. Beck Jr, Christoph Becker, J. David Beckham, Pierre André Bédard, Patrick J. Bednarski, Thomas J. Begley, Christian Behl, Christian Behrends, Georg MN Behrens, Kevin E. Behrns, Eloy Bejarano, Amine Belaid, Francesca Belleudi, Giovanni Bénard, Guy Berchem, Daniele Bergamaschi, Matteo Bergami, Ben Berkhout, Laura Berliocchi, Amélie Bernard, Monique Bernard, Francesca Bernassola, Anne Bertolotti, Amanda S. Bess, Sébastien Besteiro, Saverio Bettuzzi, Savita Bhalla, Shalmoli Bhattacharyya, Sujit K. Bhutia, Caroline Biagosch, Michele Wolfe Bianchi, Martine Biard Piechaczyk, Viktor Billes, Claudia Bincoletto, Baris Bingol, Sara W. Bird, Marc Bitoun, Ivana Bjedov, Craig Blackstone, Lionel Blanc, Guillermo A. Blanco, Heidi Kiil Blomhoff, Emilio Boada Romero, Stefan Böckler, Marianne Boes, Kathleen Boesze Battaglia, Lawrence H. Boise, Alessandra Bolino, Andrea Boman, Paolo Bonaldo, Matteo Bordi, Jürgen Bosch, Luis M. Botana, Joelle Botti, German Bou, Marina Bouché, Marion Bouchecareilh, Marie Josée Boucher, Michael E. Boulton, Sebastien G. Bouret, Patricia Boya, Michaël Boyer Guittaut, Peter V. Bozhkov, Nathan Brady, Vania MM Braga, Claudio Brancolini, Gerhard H. Braus, José M. Bravo San Pedro, Lisa A. Brennan, Emery H. Bresnick, Patrick Brest, Dave Bridges, MarieAgnès Bringer, Marisa Brini, Glauber C. Brito, Bertha Brodin, Paul S. Brookes, Eric J. Brown, Karen Brown, Hal E. Broxmeyer, Alain Bruhat, Patricia Chakur Brum, John H. Brumell, Nicola Brunetti Pierri, Robert J. Bryson Richardson, Shilpa Buch, Alastair M. Buchan, Hikmet Budak, Dmitry V. Bulavin, Scott J. Bultman, Geert Bultynck, Vladimir Bumbasirevic, Yan Burelle, Robert E. Burke, Margit Burmeister, Peter Bütikofer, Laura Caberlotto, Ken Cadwell, Monika Cahova, Dongsheng Cai, Jingjing Cai, Qian Cai, Sara Calatayud, Nadine Camougrand, Michelangelo Campanella, Grant R. Campbell, Matthew Campbell, Silvia Campello, Robin Candau, Isabella Caniggia, Lavinia Cantoni, Lizhi Cao, Allan B. Caplan, Michele Caraglia, Claudio Cardinali, Sandra Morais Cardoso, Jennifer S. Carew, Laura A. Carleton, Cathleen R. Carlin, Silvia Carloni, Sven R. Carlsson, Didac Carmona Gutierrez, Leticia AM Carneiro, Oliana Carnevali, Serena Carra, Alice Carrier, Bernadette Carroll, Caty Casas, Josefina Casas, Giuliana Cassinelli, Perrine Castets, Susana Castro Obregon, Gabriella Cavallini, Isabella Ceccherini, Francesco Cecconi, Arthur I. Cederbaum, Valentín Ceña, Simone Cenci, Claudia Cerella, Davide Cervia, CETRULLO, SILVIA, Hassan Chaachouay, Han Jung Chae, Andrei S. Chagin, Chee Yin Chai, Gopal Chakrabarti, Georgios Chamilos, Edmond YW Chan, Matthew TV Chan, Dhyan Chandra, Pallavi Chandra, Chih Peng Chang, Raymond Chuen Chung Chang, Ta Yuan Chang, John C. Chatham, Saurabh Chatterjee, Santosh Chauhan, Yongsheng Che, Michael E. Cheetham, Rajkumar Cheluvappa, Chun Jung Chen, Gang Chen, Guang Chao Chen, Guoqiang Chen, Hongzhuan Chen, Jeff W. Chen, Jian Kang Chen, Min Chen, Mingzhou Chen, Peiwen Chen, Qi Chen, Quan Chen, Shang Der Chen, Si Chen, Steve S. L. Chen, Wei Chen, Wei Jung Chen, Wen Qiang Chen, Wenli Chen, Xiangmei Chen, Yau Hung Chen, Ye Guang Chen, Yin Chen, Yingyu Chen, Yongshun Chen, Yu Jen Chen, Yue Qin Chen, Yujie Chen, Zhen Chen, Zhong Chen, Alan Cheng, Christopher HK Cheng, Hua Cheng, Heesun Cheong, Sara Cherry, Jason Chesney, Chun Hei Antonio Cheung, Eric Chevet, Hsiang Cheng Chi, Sung Gil Chi, Fulvio Chiacchiera, Hui Ling Chiang, Roberto Chiarelli, Mario Chiariello, Marcello Chieppa, Lih Shen Chin, Mario Chiong, Gigi NC Chiu, Dong Hyung Cho, Ssang Goo Cho, William C. Cho, Yong Yeon Cho, Young Seok Cho, Augustine MK Choi, Eui Ju Choi, Eun Kyoung Choi, Jayoung Choi, Mary E. Choi, Seung Il Choi, Tsui Fen Chou, Salem Chouaib, Divaker Choubey, Vinay Choubey, Kuan Chih Chow, Kamal Chowdhury, Charleen T. Chu, Tsung Hsien Chuang, Taehoon Chun, Hyewon Chung, Taijoon Chung, Yuen Li Chung, Yong Joon Chwae, Valentina Cianfanelli, Roberto Ciarcia, Iwona A. Ciechomska, Maria Rosa Ciriolo, Mara Cirone, Sofie Claerhout, Michael J. Clague, Joan Clària, Peter GH Clarke, Robert Clarke, Emilio Clementi, Cédric Cleyrat, Miriam Cnop, Eliana M. Coccia, Tiziana Cocco, Patrice Codogno, Jörn Coers, Ezra EW Cohen, David Colecchia, Luisa Coletto, Núria S. Coll, Emma Colucci Guyon, Sergio Comincini, Maria Condello, Katherine L. Cook, Graham H. Coombs, Cynthia D. Cooper, J. Mark Cooper, Isabelle Coppens, Maria Tiziana Corasaniti, Marco Corazzari, Ramon Corbalan, Elisabeth Corcelle Termeau, Mario D. Cordero, Cristina Corral Ramos, Olga Corti, Andrea Cossarizza, Paola Costelli, Safia Costes, Susan L. Cotman, Ana Coto Montes, Sandra Cottet, Eduardo Couve, Lori R. Covey, L. Ashley Cowart, Jeffery S. Cox, Fraser P. Coxon, Carolyn B. Coyne, Mark S. Cragg, Rolf J. Craven, Tiziana Crepaldi, Jose L. Crespo, Alfredo Criollo, Valeria Crippa, Maria Teresa Cruz, Ana Maria Cuervo, Jose M. Cuezva, Taixing Cui, Pedro R. Cutillas, Mark J. Czaja, Maria F. Czyzyk Krzeska, Ruben K. Dagda, Uta Dahmen, Chunsun Dai, Wenjie Dai, Yun Dai, Kevin N. Dalby, Luisa Dalla Valle, Guillaume Dalmasso, Marcello D'Amelio, Markus Damme, Arlette Darfeuille Michaud, Catherine Dargemont, Victor M. Darley Usmar, Srinivasan Dasarathy, Biplab Dasgupta, Srikanta Dash, Crispin R. Dass, Hazel Marie Davey, Lester M. Davids, David Dávila, Roger J. Davis, Ted M. Dawson, Valina L. Dawson, Paula Daza, Jackie de Belleroche, Paul de Figueiredo, Regina Celia Bressan Queiroz de Figueiredo, José de la Fuente, Luisa De Martino, Antonella De Matteis, Guido RY De Meyer, Angelo De Milito, Mauro De Santi, Wanderley de Souza, Vincenzo De Tata, Daniela De Zio, Jayanta Debnath, Reinhard Dechant, Jean Paul Decuypere, Shane Deegan, Benjamin Dehay, Barbara Del Bello, Dominic P. Del Re, Régis Delage Mourroux, Lea MD Delbridge, Louise Deldicque, Elizabeth Delorme Axford, Yizhen Deng, Joern Dengjel, Melanie Denizot, Paul Dent, Channing J. Der, Vojo Deretic, Benoît Derrien, Eric Deutsch, Timothy P. Devarenne, Rodney J. Devenish, Sabrina Di Bartolomeo, Nicola Di Daniele, Fabio Di Domenico, Alessia Di Nardo, Simone Di Paola, Antonio Di Pietro, Livia Di Renzo, Aaron DiAntonio, Guillermo Díaz Araya, Ines Díaz Laviada, Maria T. Diaz Meco, Javier Diaz Nido, Chad A. Dickey, Robert C. Dickson, Marc Diederich, Paul Digard, Ivan Dikic, Savithrama P. Dinesh Kumar, Chan Ding, Wen Xing Ding, Zufeng Ding, Luciana Dini, Jörg HW Distler, Abhinav Diwan, Mojgan Djavaheri Mergny, Kostyantyn Dmytruk, Renwick CJ Dobson, Volker Doetsch, Karol Dokladny, Svetlana Dokudovskaya, Massimo Donadelli, X. Charlie Dong, Xiaonan Dong, Zheng Dong, Terrence M. Donohue Jr, Kelly S. Doran, Gabriella D'Orazi, Gerald W. Dorn II, Victor Dosenko, Sami Dridi, Liat Drucker, Jie Du, Li Lin Du, Lihuan Du, André du Toit, Priyamvada Dua, Lei Duan, Pu Duann, Vikash Kumar Dubey, Michael R. Duchen, Michel A. Duchosal, Helene Duez, Isabelle Dugail, Verónica I. Dumit, Mara C. Duncan, Elaine A. Dunlop, William A. Dunn Jr, Nicolas Dupont, Luc Dupuis, Raúl V. Durán, Thomas M. Durcan, Stéphane Duvezin Caubet, Umamaheswar Duvvuri, Vinay Eapen, Darius Ebrahimi Fakhari, Arnaud Echard, Leopold Eckhart, Charles L. Edelstein, Aimee L. Edinger, Ludwig Eichinger, Tobias Eisenberg, Avital Eisenberg Lerner, N. Tony Eissa, Wafik S. El Deiry, Victoria El Khoury, Zvulun Elazar, Hagit Eldar Finkelman, Chris JH Elliott, Enzo Emanuele, Urban Emmenegger, Nikolai Engedal, Anna Mart Engelbrecht, Simone Engelender, Jorrit M. Enserink, Ralf Erdmann, Jekaterina Erenpreisa, Rajaraman Eri, Jason L. Eriksen, Andreja Erman, Ricardo Escalante, Eeva Liisa Eskelinen, Lucile Espert, Lorena Esteban Martínez, Thomas J. Evans, Mario Fabri, Gemma Fabrias, Cinzia Fabrizi, Antonio Facchiano, Nils J. Færgeman, Alberto Faggioni, W. Douglas Fairlie, Chunhai Fan, Daping Fan, Jie Fan, Shengyun Fang, Manolis Fanto, Alessandro Fanzani, Thomas Farkas, Mathias Faure, Francois B. Favier, Howard Fearnhead, Massimo Federici, Erkang Fei, Tania C. Felizardo, Hua Feng, Yibin Feng, Yuchen Feng, Thomas A. Ferguson, Álvaro F. Fernández, Maite G. Fernandez Barrena, Jose C. Fernandez Checa, Arsenio Fernández López, Martin E. Fernandez Zapico, Olivier Feron, Elisabetta Ferraro, Carmen Veríssima Ferreira Halder, Laszlo Fesus, Ralph Feuer, Fabienne C. Fiesel, Eduardo C. Filippi Chiela, Giuseppe Filomeni, Gian Maria Fimia, John H. Fingert, Steven Finkbeiner, Toren Finkel, Filomena Fiorito, Paul B. Fisher, Marc Flajolet, FLAMIGNI, FLAVIO, Oliver Florey, Salvatore Florio, R. Andres Floto, Marco Folini, Carlo Follo, Edward A. Fon, Francesco Fornai, Franco Fortunato, Alessandro Fraldi, Rodrigo Franco, Arnaud Francois, Aurélie François, Lisa B. Frankel, Iain DC Fraser, Norbert Frey, Damien G. Freyssenet, Christian Frezza, Scott L. Friedman, Daniel E. Frigo, Dongxu Fu, José M. Fuentes, Juan Fueyo, Yoshio Fujitani, Yuuki Fujiwara, Mikihiro Fujiya, Mitsunori Fukuda, Simone Fulda, Carmela Fusco, Bozena Gabryel, Matthias Gaestel, Philippe Gailly, Malgorzata Gajewska, Sehamuddin Galadari, Gad Galili, Inmaculada Galindo, Maria F. Galindo, Giovanna Galliciotti, Lorenzo Galluzzi, Luca Galluzzi, Vincent Galy, Noor Gammoh, Sam Gandy, Anand K. Ganesan, Swamynathan Ganesan, Ian G. Ganley, Monique Gannagé, Fen Biao Gao, Feng Gao, Jian Xin Gao, Lorena García Nannig, Eleonora García Véscovi, Marina Garcia Macía, Carmen Garcia Ruiz, Abhishek D. Garg, Pramod Kumar Garg, Ricardo Gargini, Nils Christian Gassen, Damián Gatica, Evelina Gatti, Julie Gavard, Evripidis Gavathiotis, Liang Ge, Pengfei Ge, Shengfang Ge, Po Wu Gean, Vania Gelmetti, Armando A. Genazzani, Jiefei Geng, Pascal Genschik, Lisa Gerner, Jason E. Gestwicki, David A. Gewirtz, Saeid Ghavami, Eric Ghigo, Debabrata Ghosh, Anna Maria Giammarioli, Francesca Giampieri, Claudia Giampietri, Alexandra Giatromanolaki, Derrick J. Gibbings, Lara Gibellini, Spencer B. Gibson, Vanessa Ginet, Antonio Giordano, Flaviano Giorgini, Elisa Giovannetti, Stephen E. Girardin, Suzana Gispert, Sandy Giuliano, Candece L. Gladson, Alvaro Glavic, Martin Gleave, Nelly Godefroy, Robert M. Gogal Jr, Kuppan Gokulan, Gustavo H. Goldman, Delia Goletti, Michael S. Goligorsky, Aldrin V. Gomes, Ligia C. Gomes, Hernando Gomez, Candelaria Gomez Manzano, Rubén Gómez Sánchez, Dawit AP Gonçalves, Ebru Goncu, Qingqiu Gong, Céline Gongora, Carlos B. Gonzalez, Pedro Gonzalez Alegre, Pilar Gonzalez Cabo, Rosa Ana González Polo, Ing Swie Goping, Carlos Gorbea, Nikolai V. Gorbunov, Daphne R. Goring, Adrienne M. Gorman, Sharon M. Gorski, Sandro Goruppi, Shino Goto Yamada, Cecilia Gotor, Roberta A. Gottlieb, Illana Gozes, Devrim Gozuacik, Yacine Graba, Martin Graef, Giovanna E. Granato, Gary Dean Grant, Steven Grant, Giovanni Luca Gravina, Douglas R. Green, Alexander Greenhough, Michael T. Greenwood, Benedetto Grimaldi, Frédéric Gros, Charles Grose, Jean Francois Groulx, Florian Gruber, Paolo Grumati, Tilman Grune, Jun Lin Guan, Kun Liang Guan, Barbara Guerra, Carlos Guillen, Kailash Gulshan, Jan Gunst, Chuanyong Guo, Lei Guo, Ming Guo, Wenjie Guo, Xu Guang Guo, Andrea A. Gust, Åsa B. Gustafsson, Elaine Gutierrez, Maximiliano G. Gutierrez, Ho Shin Gwak, Albert Haas, James E. Haber, Shinji Hadano, Monica Hagedorn, David R. Hahn, Andrew J. Halayko, Anne Hamacher Brady, Kozo Hamada, Ahmed Hamai, Andrea Hamann, Maho Hamasaki, Isabelle Hamer, Qutayba Hamid, Ester M. Hammond, Feng Han, Weidong Han, James T. Handa, John A. Hanover, Malene Hansen, Masaru Harada, Ljubica Harhaji Trajkovic, J. Wade Harper, Abdel Halim Harrath, Adrian L. Harris, James Harris, Udo Hasler, Peter Hasselblatt, Kazuhisa Hasui, Robert G. Hawley, Teresa S. Hawley, Congcong He, Cynthia Y. He, Fengtian He, Gu He, Rong Rong He, Xian Hui He, You Wen He, Yu Ying He, Joan K. Heath, Marie Josée Hébert, Robert A. Heinzen, Gudmundur Vignir Helgason, Michael Hensel, Elizabeth P. Henske, Chengtao Her, Paul K. Herman, Agustín Hernández, Carlos Hernandez, Sonia Hernández Tiedra, Claudio Hetz, P. Robin Hiesinger, Katsumi Higaki, Sabine Hilfiker, Bradford G. Hill, Joseph A. Hill, William D. Hill, Keisuke Hino, Daniel Hofius, Paul Hofman, Günter U. Höglinger, Jörg Höhfeld, Marina K. Holz, Yonggeun Hong, David A. Hood, Jeroen JM Hoozemans, Thorsten Hoppe, Chin Hsu, Chin Yuan Hsu, Li Chung Hsu, Dong Hu, Guochang Hu, Hong Ming Hu, Hongbo Hu, Ming Chang Hu, Yu Chen Hu, Zhuo Wei Hu, Fang Hua, Ya Hua, Canhua Huang, Huey Lan Huang, Kuo How Huang, Kuo Yang Huang, Shile Huang, Shiqian Huang, Wei Pang Huang, Yi Ran Huang, Yong Huang, Yunfei Huang, Tobias B. Huber, Patricia Huebbe, Won Ki Huh, Juha J. Hulmi, Gang Min Hur, James H. Hurley, Zvenyslava Husak, Sabah NA Hussain, Salik Hussain, Jung Jin Hwang, Seungmin Hwang, Thomas IS Hwang, Atsuhiro Ichihara, Yuzuru Imai, Carol Imbriano, Megumi Inomata, Takeshi Into, Valentina Iovane, Juan L. Iovanna, Renato V. Iozzo, Nancy Y. Ip, Javier E. Irazoqui, Pablo Iribarren, Yoshitaka Isaka, Aleksandra J. Isakovic, Harry Ischiropoulos, Jeffrey S. Isenberg, Mohammad Ishaq, Hiroyuki Ishida, Isao Ishii, Jane E. Ishmael, Ciro Isidoro, Ken ichi Isobe, Erika Isono, Shohreh Issazadeh Navikas, Koji Itahana, Eisuke Itakura, Andrei I. Ivanov, Anand Krishnan V. Iyer, José M. Izquierdo, Yotaro Izumi, Valentina Izzo, Marja Jäättelä, Nadia Jaber, Daniel John Jackson, William T. Jackson, Tony George Jacob, Thomas S. Jacques, Chinnaswamy Jagannath, Ashish Jain, Nihar Ranjan Jana, Byoung Kuk Jang, Alkesh Jani, Bassam Janji, Paulo Roberto Jannig, Patric J. Jansson, Steve Jean, Marina Jendrach, Ju Hong Jeon, Niels Jessen, Eui Bae Jeung, Kailiang Jia, Lijun Jia, Hong Jiang, Hongchi Jiang, Liwen Jiang, Teng Jiang, Xiaoyan Jiang, Xuejun Jiang, Ying Jiang, Yongjun Jiang, Alberto Jiménez, Cheng Jin, Hongchuan Jin, Lei Jin, Meiyan Jin, Shengkan Jin, Umesh Kumar Jinwal, Eun Kyeong Jo, Terje Johansen, Daniel E. Johnson, Gail VW Johnson, James D. Johnson, Eric Jonasch, Chris Jones, Leo AB Joosten, Joaquin Jordan, Anna Maria Joseph, Bertrand Joseph, Annie M. Joubert, Dianwen Ju, Jingfang Ju, Hsueh Fen Juan, Katrin Juenemann, Gábor Juhász, Hye Seung Jung, Jae U. Jung, Yong Keun Jung, Heinz Jungbluth, Matthew J. Justice, Barry Jutten, Nadeem O. Kaakoush, Kai Kaarniranta, Allen Kaasik, Tomohiro Kabuta, Bertrand Kaeffer, Katarina Kågedal, Alon Kahana, Shingo Kajimura, Or Kakhlon, Manjula Kalia, Dhan V. Kalvakolanu, Yoshiaki Kamada, Konstantinos Kambas, Vitaliy O. Kaminskyy, Harm H. Kampinga, Mustapha Kandouz, Chanhee Kang, Rui Kang, Tae Cheon Kang, Tomotake Kanki, Thirumala Devi Kanneganti, Haruo Kanno, Anumantha G. Kanthasamy, Marc Kantorow, Maria Kaparakis Liaskos, Orsolya Kapuy, Vassiliki Karantza, Md Razaul Karim, Parimal Karmakar, Arthur Kaser, Susmita Kaushik, Thomas Kawula, A. Murat Kaynar, Po Yuan Ke, Zun Ji Ke, John H. Kehrl, Kate E. Keller, Jongsook Kim Kemper, Anne K. Kenworthy, Oliver Kepp, Andreas Kern, Santosh Kesari, David Kessel, Robin Ketteler, Isis do Carmo Kettelhut, Bilon Khambu, Muzamil Majid Khan, Vinoth KM Khandelwal, Sangeeta Khare, Juliann G. Kiang, Amy A. Kiger, Akio Kihara, Arianna L. Kim, Cheol Hyeon Kim, Deok Ryong Kim, Do Hyung Kim, Eung Kweon Kim, Hye Young Kim, Hyung Ryong Kim, Jae Sung Kim, Jeong Hun Kim, Jin Cheon Kim, Jin Hyoung Kim, Kwang Woon Kim, Michael D. Kim, Moon Moo Kim, Peter K. Kim, Seong Who Kim, Soo Youl Kim, Yong Sun Kim, Yonghyun Kim, Adi Kimchi, Alec C. Kimmelman, Tomonori Kimura, Jason S. King, Karla Kirkegaard, Vladimir Kirkin, Lorrie A. Kirshenbaum, Shuji Kishi, Yasuo Kitajima, Katsuhiko Kitamoto, Yasushi Kitaoka, Kaio Kitazato, Rudolf A. Kley, Walter T. Klimecki, Michael Klinkenberg, Jochen Klucken, Helene Knævelsrud, Erwin Knecht, Laura Knuppertz, Jiunn Liang Ko, Satoru Kobayashi, Jan C. Koch, Christelle Koechlin Ramonatxo, Ulrich Koenig, Young Ho Koh, Katja Köhler, Sepp D. Kohlwein, Masato Koike, Masaaki Komatsu, Eiki Kominami, Dexin Kong, Hee Jeong Kong, Eumorphia G. Konstantakou, Benjamin T. Kopp, Tamas Korcsmaros, Laura Korhonen, Viktor I. Korolchuk, Nadya V. Koshkina, Yanjun Kou, Michael I. Koukourakis, Constantinos Koumenis, Attila L. Kovács, Tibor Kovács, Werner J. Kovacs, Daisuke Koya, Claudine Kraft, Dimitri Krainc, Helmut Kramer, Tamara Kravic Stevovic, Wilhelm Krek, Carole Kretz Remy, Roswitha Krick, Malathi Krishnamurthy, Janos Kriston Vizi, Guido Kroemer, Michael C. Kruer, Rejko Kruger, Nicholas T. Ktistakis, Kazuyuki Kuchitsu, Christian Kuhn, Addanki Pratap Kumar, Anuj Kumar, Ashok Kumar, Deepak Kumar, Dhiraj Kumar, Rakesh Kumar, Sharad Kumar, Mondira Kundu, Hsing Jien Kung, Atsushi Kuno, Sheng Han Kuo, Jeff Kuret, Tino Kurz, Terry Kwok, Taeg Kyu Kwon, Yong Tae Kwon, Irene Kyrmizi, Albert R. La Spada, Frank Lafont, Tim Lahm, Aparna Lakkaraju, Truong Lam, Trond Lamark, Steve Lancel, Terry H. Landowski, Darius JR Lane, Jon D. Lane, Cinzia Lanzi, Pierre Lapaquette, Louis R. Lapierre, Jocelyn Laporte, Johanna Laukkarinen, Gordon W. Laurie, Sergio Lavandero, Lena Lavie, Matthew J. LaVoie, Betty Yuen Kwan Law, Helen Ka wai Law, Kelsey B. Law, Robert Layfield, Pedro A. Lazo, Laurent Le Cam, Karine G. Le Roch, Hervé Le Stunff, Vijittra Leardkamolkarn, Marc Lecuit, Byung Hoon Lee, Che Hsin Lee, Erinna F. Lee, Gyun Min Lee, He Jin Lee, Hsinyu Lee, Jae Keun Lee, Jongdae Lee, Juhyun Lee, Jun Hee Lee, Michael Lee, Myung Shik Lee, Patty J. Lee, Sam W. Lee, Seung Jae Lee, Shiow Ju Lee, Stella Y. Lee, Sug Hyung Lee, Sung Sik Lee, Sung Joon Lee, Sunhee Lee, Ying Ray Lee, Yong J. Lee, Young H. Lee, Christiaan Leeuwenburgh, Sylvain Lefort, Renaud Legouis, Jinzhi Lei, Qun Ying Lei, David A. Leib, Gil Leibowitz, Istvan Lekli, Stéphane D. Lemaire, John J. Lemasters, Marius K. Lemberg, Antoinette Lemoine, Shuilong Leng, Guido Lenz, Paola Lenzi, Lilach O. Lerman, Daniele Lettieri Barbato, Julia I. Ju Leu, Hing Y. Leung, Beth Levine, Patrick A. Lewis, Frank Lezoualc'h, Chi Li, Faqiang Li, Feng Jun Li, Jun Li, Ke Li, Lian Li, Min Li, Qiang Li, Rui Li, Sheng Li, Wei Li, Xiaotao Li, Yumin Li, Jiqin Lian, Chengyu Liang, Qiangrong Liang, Yulin Liao, Joana Liberal, Pawel P. Liberski, Pearl Lie, Andrew P. Lieberman, Hyunjung Jade Lim, Kah Leong Lim, Kyu Lim, Raquel T. Lima, Chang Shen Lin, Chiou Feng Lin, Fang Lin, Fangming Lin, Fu Cheng Lin, Kui Lin, Kwang Huei Lin, Pei Hui Lin, Tianwei Lin, Wan Wan Lin, Yee Shin Lin, Yong Lin, Rafael Linden, Dan Lindholm, Lisa M. Lindqvist, Paul Lingor, Andreas Linkermann, Lance A. Liotta, Marta M. Lipinski, Vitor A. Lira, Michael P. Lisanti, Paloma B. Liton, Bo Liu, Chong Liu, Chun Feng Liu, Fei Liu, Hung Jen Liu, Jianxun Liu, Jing Jing Liu, Jing Lan Liu, Ke Liu, Leyuan Liu, Liang Liu, Quentin Liu, Rong Yu Liu, Shiming Liu, Shuwen Liu, Wei Liu, Xian De Liu, Xiangguo Liu, Xiao Hong Liu, Xinfeng Liu, Xu Liu, Xueqin Liu, Yang Liu, Yule Liu, Zexian Liu, Zhe Liu, Juan P. Liuzzi, Gérard Lizard, Mila Ljujic, Irfan J. Lodhi, Susan E. Logue, Bal L. Lokeshwar, Yun Chau Long, Sagar Lonial, Benjamin Loos, Carlos López Otín, Cristina López Vicario, Mar Lorente, Philip L. Lorenzi, Péter Lõrincz, Marek Los, Michael T. Lotze, Penny E. Lovat, Binfeng Lu, Bo Lu, Jiahong Lu, Qing Lu, She Min Lu, Shuyan Lu, Yingying Lu, Frédéric Luciano, Shirley Luckhart, John Milton Lucocq, Paula Ludovico, Aurelia Lugea, Nicholas W. Lukacs, Julian J. Lum, Anders H. Lund, Honglin Luo, Jia Luo, Shouqing Luo, Claudio Luparello, Timothy Lyons, Jianjie Ma, Yi Ma, Yong Ma, Zhenyi Ma, Juliano Machado, Glaucia M. Machado Santelli, Fernando Macian, Gustavo C. MacIntosh, Jeffrey P. MacKeigan, Kay F. Macleod, John D. MacMicking, Lee Ann MacMillan Crow, Frank Madeo, Muniswamy Madesh, Julio Madrigal Matute, Akiko Maeda, Tatsuya Maeda, Gustavo Maegawa, Emilia Maellaro, Hannelore Maes, Marta Magariños, Kenneth Maiese, Tapas K. Maiti, Luigi Maiuri, Maria Chiara Maiuri, Carl G. Maki, Roland Malli, Walter Malorni, Alina Maloyan, Fathia Mami Chouaib, Na Man, Joseph D. Mancias, Eva Maria Mandelkow, Michael A. Mandell, Angelo A. Manfredi, Serge N. Manié, Claudia Manzoni, Kai Mao, Zixu Mao, Zong Wan Mao, Philippe Marambaud, Anna Maria Marconi, Zvonimir Marelja, Gabriella Marfe, Marta Margeta, Eva Margittai, Muriel Mari, Francesca V. Mariani, Concepcio Marin, Sara Marinelli, Guillermo Mariño, Ivanka Markovic, Rebecca Marquez, MARTELLI, ALBERTO MARIA, Sascha Martens, Katie R. Martin, Seamus J. Martin, Shaun Martin, Miguel A. Martin Acebes, Paloma Martín Sanz, Camille Martinand Mari, Wim Martinet, Jennifer Martinez, Nuria Martinez Lopez, Ubaldo Martinez Outschoorn, Moisés Martínez Velázquez, Marta Martinez Vicente, Waleska Kerllen Martins, Hirosato Mashima, James A. Mastrianni, Giuseppe Matarese, Paola Matarrese, Roberto Mateo, Satoaki Matoba, Naomichi Matsumoto, Takehiko Matsushita, Akira Matsuura, Takeshi Matsuzawa, Mark P. Mattson, Soledad Matus, Norma Maugeri, Caroline Mauvezin, Andreas Mayer, Dusica Maysinger, Guillermo D. Mazzolini, Mary Kate McBrayer, Kimberly McCall, Craig McCormick, Gerald M. McInerney, Skye C. McIver, Sharon McKenna, John J. McMahon, Iain A. McNeish, Fatima Mechta Grigoriou, Jan Paul Medema, Diego L. Medina, Klara Megyeri, Maryam Mehrpour, Jawahar L. Mehta, Yide Mei, Ute Christiane Meier, Alfred J. Meijer, Alicia Meléndez, Gerry Melino, Sonia Melino, Edesio Jose Tenorio de Melo, Maria A. Mena, Marc D. Meneghini, Javier A. Menendez, Regina Menezes, Liesu Meng, Ling hua Meng, Songshu Meng, Rossella Menghini, A. Sue Menko, Rubem FS Menna Barreto, Manoj B. Menon, Marco A. Meraz Ríos, Giuseppe Merla, Luciano Merlini, Angelica M. Merlot, Andreas Meryk, Stefania Meschini, Joel N. Meyer, Man tian Mi, Chao Yu Miao, Lucia Micale, Simon Michaeli, Carine Michiels, FRANCO MIGLIACCIO, ANNA RITA, Anastasia Susie Mihailidou, Dalibor Mijaljica, Katsuhiko Mikoshiba, Enrico Milan, Leonor Miller Fleming, Gordon B. Mills, Ian G. Mills, Georgia Minakaki, Berge A. Minassian, Xiu Fen Ming, Farida Minibayeva, Elena A. Minina, Justine D. Mintern, Saverio Minucci, Antonio Miranda Vizuete, Claire H. Mitchell, Shigeki Miyamoto, Keisuke Miyazawa, Noboru Mizushima, Katarzyna Mnich, Baharia Mograbi, Simin Mohseni, Luis Ferreira Moita, Marco Molinari, Maurizio Molinari, Andreas Buch Møller, Bertrand Mollereau, Faustino Mollinedo, Marco Mongillo, Martha M. Monick, Serena Montagnaro, Craig Montell, Darren J. Moore, Michael N. Moore, Rodrigo Mora Rodriguez, Paula I. Moreira, Etienne Morel, Maria Beatrice Morelli, Sandra Moreno, Michael J. Morgan, Arnaud Moris, Yuji Moriyasu, Janna L. Morrison, Lynda A. Morrison, Eugenia Morselli, Jorge Moscat, Pope L. Moseley, Serge Mostowy, Elisa Motori, Denis Mottet, Jeremy C. Mottram, Charbel E. H. Moussa, Vassiliki E. Mpakou, Hasan Mukhtar, Jean M. Mulcahy Levy, Sylviane Muller, Raquel Muñoz Moreno, Cristina Muñoz Pinedo, Christian Münz, Maureen E. Murphy, James T. Murray, Aditya Murthy, Indira U. Mysorekar, Ivan R. Nabi, Massimo Nabissi, Gustavo A. Nader, Yukitoshi Nagahara, Yoshitaka Nagai, Kazuhiro Nagata, Anika Nagelkerke, Péter Nagy, Samisubbu R. Naidu, Sreejayan Nair, Hiroyasu Nakano, Hitoshi Nakatogawa, Meera Nanjundan, Gennaro Napolitano, Naweed I. Naqvi, Roberta Nardacci, Derek P. Narendra, Masashi Narita, Anna Chiara Nascimbeni, Ramesh Natarajan, Luiz C. Navegantes, Steffan T. Nawrocki, Taras Y. Nazarko, Volodymyr Y. Nazarko, Thomas Neill, Luca M. Neri, Mihai G. Netea, Romana T. Netea Maier, Bruno M. Neves, Paul A. Ney, Ioannis P. Nezis, Hang TT Nguyen, Huu Phuc Nguyen, Anne Sophie Nicot, Hilde Nilsen, Per Nilsson, Mikio Nishimura, Ichizo Nishino, Mireia Niso Santano, Hua Niu, Ralph A. Nixon, Vincent CO Njar, Takeshi Noda, Angelika A. Noegel, Elsie Magdalena Nolte, Erik Norberg, Koenraad K. Norga, Sakineh Kazemi Noureini, Shoji Notomi, Lucia Notterpek, Karin Nowikovsky, Nobuyuki Nukina, Thorsten Nürnberger, Valerie B. O'Donnell, Tracey O'Donovan, Peter J. O'Dwyer, Ina Oehme, Clara L. Oeste, Michinaga Ogawa, Besim Ogretmen, Yuji Ogura, Young J. Oh, Masaki Ohmuraya, Takayuki Ohshima, Rani Ojha, Koji Okamoto, Toshiro Okazaki, F. Javier Oliver, Karin Ollinger, Stefan Olsson, Daniel P. Orban, Paulina Ordonez, Idil Orhon, Laszlo Orosz, Eyleen J. O'Rourke, Helena Orozco, Angel L. Ortega, Elena Ortona, Laura D. Osellame, Junko Oshima, Shigeru Oshima, Heinz D. Osiewacz, Takanobu Otomo, Kinya Otsu, Jing hsiung James Ou, Tiago F. Outeiro, Dong yun Ouyang, Hongjiao Ouyang, Michael Overholtzer, Michelle A. Ozbun, P. Hande Ozdinler, Bulent Ozpolat, Consiglia Pacelli, Paolo Paganetti, Guylène Page, Gilles Pages, Ugo Pagnini, Beata Pajak, Stephen C. Pak, Karolina Pakos Zebrucka, Nazzy Pakpour, Zdena Palková, Francesca Palladino, Kathrin Pallauf, Nicolas Pallet, Marta Palmieri, Søren R. Paludan, Camilla Palumbo, Silvia Palumbo, Olatz Pampliega, Hongming Pan, Wei Pan, Theocharis Panaretakis, Aseem Pandey, Areti Pantazopoulou, Zuzana Papackova, Daniela L. Papademetrio, Issidora Papassideri, Alessio Papini, Nirmala Parajuli, Julian Pardo, Vrajesh V. Parekh, Giancarlo Parenti, Jong In Park, Junsoo Park, Ohkmae K. Park, Roy Parker, Rosanna Parlato, Jan B. Parys, Katherine R. Parzych, Jean Max Pasquet, Benoit Pasquier, Kishore BS Pasumarthi, Daniel Patschan, Cam Patterson, Sophie Pattingre, Scott Pattison, Arnim Pause, Hermann Pavenstädt, Flaminia Pavone, Zully Pedrozo, Fernando J. Peña, Miguel A. Peñalva, Mario Pende, Jianxin Peng, Fabio Penna, Josef M. Penninger, Anna Pensalfini, Salvatore Pepe, Gustavo JS Pereira, Paulo C. Pereira, Verónica Pérez de la Cruz, María Esther Pérez Pérez, Diego Pérez Rodríguez, Dolores Pérez Sala, Celine Perier, Andras Perl, David H. Perlmutter, Ida Perrotta, Shazib Pervaiz, Maija Pesonen, Jeffrey E. Pessin, Godefridus J. Peters, Morten Petersen, Irina Petrache, Basil J. Petrof, Goran Petrovski, James M. Phang, Mauro Piacentini, Marina Pierdominici, Philippe Pierre, Valérie Pierrefite Carle, Federico Pietrocola, Felipe X. Pimentel Muiños, Mario Pinar, Benjamin Pineda, Ronit Pinkas Kramarski, Marcello Pinti, Paolo Pinton, Bilal Piperdi, James M. Piret, Leonidas C. Platanias, Harald W. Platta, Edward D. Plowey, Stefanie Pöggeler, Marc Poirot, Peter Polčic, Angelo Poletti, Audrey H. Poon, Hana Popelka, Blagovesta Popova, Izabela Poprawa, Shibu M. Poulose, Joanna Poulton, Scott K. Powers, Ted Powers, Mercedes Pozuelo Rubio, Krisna Prak, Reinhild Prange, Mark Prescott, Muriel Priault, Sharon Prince, Richard L. Proia, Tassula Proikas Cezanne, Holger Prokisch, Vasilis J. Promponas, Karin Przyklenk, Rosa Puertollano, Subbiah Pugazhenthi, Luigi Puglielli, Aurora Pujol, Julien Puyal, Dohun Pyeon, Xin Qi, Wen bin Qian, Zheng Hong Qin, Yu Qiu, Ziwei Qu, Joe Quadrilatero, Frederick Quinn, Nina Raben, Hannah Rabinowich, Flavia Radogna, Michael J. Ragusa, Mohamed Rahmani, Komal Raina, Sasanka Ramanadham, Rajagopal Ramesh, Abdelhaq Rami, Sarron Randall Demllo, Felix Randow, Hai Rao, V. Ashutosh Rao, Blake B. Rasmussen, Tobias M. Rasse, Edward A. Ratovitski, Pierre Emmanuel Rautou, Swapan K. Ray, Babak Razani, Bruce H. Reed, Fulvio Reggiori, Markus Rehm, Andreas S. Reichert, Theo Rein, David J. Reiner, Eric Reits, Jun Ren, Xingcong Ren, Maurizio Renna, Jane EB Reusch, Jose L. Revuelta, Leticia Reyes, Alireza R. Rezaie, Robert I. Richards, Des R. Richardson, Clémence Richetta, Michael A. Riehle, Bertrand H. Rihn, Yasuko Rikihisa, Brigit E. Riley, Gerald Rimbach, Maria Rita Rippo, Konstantinos Ritis, Federica Rizzi, Elizete Rizzo, Peter J. Roach, Jeffrey Robbins, Michel Roberge, Gabriela Roca, Maria Carmela Roccheri, Sonia Rocha, Cecilia MP Rodrigues, Clara I. Rodríguez, Santiago Rodriguez de Cordoba, Natalia Rodriguez Muela, Jeroen Roelofs, Vladimir V. Rogov, Troy T. Rohn, Bärbel Rohrer, Davide Romanelli, Luigina Romani, Patricia Silvia Romano, M. Isabel G. Roncero, Jose Luis Rosa, Alicia Rosello, Kirill V. Rosen, Philip Rosenstiel, Magdalena Rost Roszkowska, Kevin A. Roth, Gael Roué, Mustapha Rouis, Kasper M. Rouschop, Daniel T. Ruan, Diego Ruano, David C. Rubinsztein, Edmund B. Rucker III, Assaf Rudich, Emil Rudolf, Ruediger Rudolf, Markus A. Ruegg, Carmen Ruiz Roldan, Avnika Ashok Ruparelia, Paola Rusmini, David W. Russ, Gian Luigi Russo, Giuseppe Russo, Rossella Russo, Tor Erik Rusten, Victoria Ryabovol, Kevin M. Ryan, Stefan W. Ryter, David M. Sabatini, Michael Sacher, Carsten Sachse, Michael N. Sack, Junichi Sadoshima, Paul Saftig, Ronit Sagi Eisenberg, Sumit Sahni, Pothana Saikumar, Tsunenori Saito, Tatsuya Saitoh, Koichi Sakakura, Machiko Sakoh Nakatogawa, Yasuhito Sakuraba, María Salazar Roa, Paolo Salomoni, Ashok K. Saluja, Paul M. Salvaterra, Rosa Salvioli, Afshin Samali, Anthony MJ Sanchez, José A. Sánchez Alcázar, Ricardo Sanchez Prieto, Marco Sandri, Miguel A. Sanjuan, Stefano Santaguida, Laura Santambrogio, Giorgio Santoni, Claudia Nunes dos Santos, Shweta Saran, Marco Sardiello, Graeme Sargent, Pallabi Sarkar, Sovan Sarkar, Maria Rosa Sarrias, Minnie M. Sarwal, Chihiro Sasakawa, Motoko Sasaki, Miklos Sass, Ken Sato, Miyuki Sato, Joseph Satriano, Niramol Savaraj, Svetlana Saveljeva, Liliana Schaefer, Ulrich E. Schaible, Michael Scharl, Hermann M. Schatzl, Randy Schekman, Wiep Scheper, Alfonso Schiavi, Hyman M. Schipper, Hana Schmeisser, Jens Schmidt, Ingo Schmitz, Bianca E. Schneider, E. Marion Schneider, Jaime L. Schneider, Eric A. Schon, Miriam J. Schönenberger, Axel H. Schönthal, Daniel F. Schorderet, Bernd Schröder, Sebastian Schuck, Ryan J. Schulze, Melanie Schwarten, Thomas L. Schwarz, Sebastiano Sciarretta, Kathleen Scotto, A. Ivana Scovassi, Robert A. Screaton, Mark Screen, Hugo Seca, Simon Sedej, Laura Segatori, Nava Segev, Per O. Seglen, Jose M. Seguí Simarro, Juan Segura Aguilar, Ekihiro Seki, Iban Seiliez, Christian Sell, Clay F. Semenkovich, Gregg L. Semenza, Utpal Sen, Andreas L. Serra, Ana Serrano Puebla, Hiromi Sesaki, Takao Setoguchi, Carmine Settembre, John J. Shacka, Ayesha N. Shajahan Haq, Irving M. Shapiro, Shweta Sharma, Hua She, C. K. James Shen, Chiung Chyi Shen, Han Ming Shen, Sanbing Shen, Weili Shen, Rui Sheng, Xianyong Sheng, Zu Hang Sheng, Trevor G. Shepherd, Junyan Shi, Qiang Shi, Qinghua Shi, Yuguang Shi, Shusaku Shibutani, Kenichi Shibuya, Yoshihiro Shidoji, Jeng Jer Shieh, Chwen Ming Shih, Yohta Shimada, Shigeomi Shimizu, Dong Wook Shin, Mari L. Shinohara, Michiko Shintani, Takahiro Shintani, Tetsuo Shioi, Ken Shirabe, Ronit Shiri Sverdlov, Orian Shirihai, Gordon C. Shore, Chih Wen Shu, Deepak Shukla, Andriy A. Sibirny, Valentina Sica, Christina J. Sigurdson, Einar M. Sigurdsson, Puran Singh Sijwali, Beata Sikorska, Wilian A. Silveira, Sandrine Silvente Poirot, Gary A. Silverman, Jan Simak, Thomas Simmet, Anna Katharina Simon, Hans Uwe Simon, Cristiano Simone, Matias Simons, Anne Simonsen, Rajat Singh, Shivendra V. Singh, Shrawan K. Singh, Debasish Sinha, Sangita Sinha, Frank A. Sinicrope, Agnieszka Sirko, Kapil Sirohi, Balindiwe JN Sishi, Annie Sittler, Parco M. Siu, Efthimios Sivridis, Anna Skwarska, Ruth Slack, Iva Slaninová, Nikolai Slavov, Soraya S. Smaili, Keiran SM Smalley, Duncan R. Smith, Stefaan J. Soenen, Scott A. Soleimanpour, Anita Solhaug, Kumaravel Somasundaram, Jin H. Son, Avinash Sonawane, Chunjuan Song, Fuyong Song, Hyun Kyu Song, Ju Xian Song, Wei Song, Kai Y. Soo, Anil K. Sood, Tuck Wah Soong, Virawudh Soontornniyomkij, Maurizio Sorice, Federica Sotgia, David R. Soto Pantoja, Areechun Sotthibundhu, Maria João Sousa, Herman P. Spaink, Paul N. Span, Anne Spang, Janet D. Sparks, Peter G. Speck, Stephen A. Spector, Claudia D. Spies, Wolfdieter Springer, Daret St Clair, Alessandra Stacchiotti, Bart Staels, Michael T. Stang, Daniel T. Starczynowski, Petro Starokadomskyy, Clemens Steegborn, John W. Steele, Leonidas Stefanis, Joan Steffan, Christine M. Stellrecht, Harald Stenmark, Tomasz M. Stepkowski, Stęphan T. Stern, Craig Stevens, Brent R. Stockwell, Veronika Stoka, Zuzana Storchova, Björn Stork, Vassilis Stratoulias, Dimitrios J. Stravopodis, Pavel Strnad, Anne Marie Strohecker, Anna Lena Ström, Per Stromhaug, Jiri Stulik, Yu Xiong Su, Zhaoliang Su, Carlos S. Subauste, Srinivasa Subramaniam, Carolyn M. Sue, Sang Won Suh, Xinbing Sui, Supawadee Sukseree, David Sulzer, Fang Lin Sun, Jiaren Sun, Jun Sun, Shi Yong Sun, Yang Sun, Yi Sun, Yingjie Sun, Vinod Sundaramoorthy, Joseph Sung, Hidekazu Suzuki, Kuninori Suzuki, Naoki Suzuki, Tadashi Suzuki, Yuichiro J. Suzuki, Michele S. Swanson, Charles Swanton, Karl Swärd, Ghanshyam Swarup, Sean T. Sweeney, Paul W. Sylvester, Zsuzsanna Szatmari, Eva Szegezdi, Peter W. Szlosarek, Heinrich Taegtmeyer, Marco Tafani, Emmanuel Taillebourg, Stephen WG Tait, Krisztina Takacs Vellai, Yoshinori Takahashi, Szabolcs Takáts, Genzou Takemura, Nagio Takigawa, Nicholas J. Talbot, Elena Tamagno, Jerome Tamburini, Cai Ping Tan, Lan Tan, Mei Lan Tan, Ming Tan, Yee Joo Tan, Keiji Tanaka, Masaki Tanaka, Daolin Tang, Dingzhong Tang, Guomei Tang, Isei Tanida, Kunikazu Tanji, Bakhos A. Tannous, Jose A. Tapia, Inmaculada Tasset Cuevas, Marc Tatar, Iman Tavassoly, Nektarios Tavernarakis, Allen Taylor, Graham S. Taylor, Gregory A. Taylor, J. Paul Taylor, Mark J. Taylor, Elena V. Tchetina, Andrew R. Tee, Fatima Teixeira Clerc, Sucheta Telang, Tewin Tencomnao, Ba Bie Teng, Ru Jeng Teng, Faraj Terro, Gianluca Tettamanti, Arianne L. Theiss, Anne E. Theron, Kelly Jean Thomas, Marcos P. Thomé, Paul G. Thomes, Andrew Thorburn, Jeremy Thorner, Thomas Thum, Michael Thumm, Teresa LM Thurston, Ling Tian, Andreas Till, Jenny Pan yun Ting, Vladimir I. Titorenko, Lilach Toker, Stefano Toldo, Sharon A. Tooze, Ivan Topisirovic, Maria Lyngaas Torgersen, Liliana Torosantucci, Alicia Torriglia, Maria Rosaria Torrisi, Cathy Tournier, Roberto Towns, Vladimir Trajkovic, Leonardo H. Travassos, Gemma Triola, Durga Nand Tripathi, Daniela Trisciuoglio, Rodrigo Troncoso, Ioannis P. Trougakos, Anita C. Truttmann, Kuen Jer Tsai, Mario P. Tschan, Yi Hsin Tseng, Takayuki Tsukuba, Allan Tsung, Andrey S. Tsvetkov, Shuiping Tu, Hsing Yu Tuan, Marco Tucci, David A. Tumbarello, Boris Turk, Vito Turk, Robin FB Turner, Anders A. Tveita, Suresh C. Tyagi, Makoto Ubukata, Yasuo Uchiyama, Andrej Udelnow, Takashi Ueno, Midori Umekawa, Rika Umemiya Shirafuji, Benjamin R. Underwood, Christian Ungermann, Rodrigo P. Ureshino, Ryo Ushioda, Vladimir N. Uversky, Néstor L. Uzcátegui, Thomas Vaccari, Maria I. Vaccaro, Libuše Váchová, Helin Vakifahmetoglu Norberg, Rut Valdor, Enza Maria Valente, Francois Vallette, Angela M. Valverde, Greet Van den Berghe, Ludo Van Den Bosch, Gijs R. van den Brink, F. Gisou van der Goot, Ida J. van der Klei, Luc JW van der Laan, Wouter G. van Doorn, Marjolein van Egmond, Kenneth L. van Golen, Luc Van Kaer, Menno van Lookeren Campagne, Peter Vandenabeele, Wim Vandenberghe, Ilse Vanhorebeek, Isabel Varela Nieto, M. Helena Vasconcelos, Radovan Vasko, Demetrios G. Vavvas, Ignacio Vega Naredo, Guillermo Velasco, Athanassios D. Velentzas, Panagiotis D. Velentzas, Tibor Vellai, Edo Vellenga, Mikkel Holm Vendelbo, Kartik Venkatachalam, Natascia Ventura, Salvador Ventura, Patrícia ST Veras, Mireille Verdier, Beata G. Vertessy, Andrea Viale, Michel Vidal, Helena LA Vieira, Richard D. Vierstra, Nadarajah Vigneswaran, Neeraj Vij, Miquel Vila, Margarita Villar, Victor H. Villar, Joan Villarroya, Cécile Vindis, Giampietro Viola, Maria Teresa Viscomi, Giovanni Vitale, Dan T. Vogl, Olga V. Voitsekhovskaja, Clarissa von Haefen, Karin von Schwarzenberg, Daniel E. Voth, Valérie Vouret Craviari, Kristina Vuori, Jatin M. Vyas, Christian Waeber, Cheryl Lyn Walker, Mark J. Walker, Jochen Walter, Lei Wan, Xiangbo Wan, Bo Wang, Caihong Wang, Chao Yung Wang, Chengshu Wang, Chenran Wang, Chuangui Wang, Dong Wang, Fen Wang, Fuxin Wang, Guanghui Wang, Hai jie Wang, Haichao Wang, Hong Gang Wang, Hongmin Wang, Horng Dar Wang, Jing Wang, Junjun Wang, Mei Wang, Mei Qing Wang, Pei Yu Wang, Peng Wang, Richard C. Wang, Shuo Wang, Ting Fang Wang, Xian Wang, Xiao jia Wang, Xiao Wei Wang, Xin Wang, Xuejun Wang, Yan Wang, Yanming Wang, Ying Wang, Ying Jan Wang, Yipeng Wang, Yu Wang, Yu Tian Wang, Yuqing Wang, Zhi Nong Wang, Pablo Wappner, Carl Ward, Diane McVey Ward, Gary Warnes, Hirotaka Watada, Yoshihisa Watanabe, Kei Watase, Timothy E. Full Terms, Conditions of access, use can be found at h.t.t.p.:././.w.w.w. t.a.n.d.f.o.n.l.i.n.e. com/action/journalInformation?journalCode=kaup20 Download by: [Alma Mater Studiorum Università di Bologna] Date: 23 September 2016, At: 06:43 Weaver, Colin D. Weekes, Jiwu Wei, Thomas Weide, Conrad C. Weihl, Günther Weindl, Simone Nardin Weis, Longping Wen, Xin Wen, Yunfei Wen, Benedikt Westermann, Cornelia M. Weyand, Anthony R. White, Eileen White, J. Lindsay Whitton, Alexander J. Whitworth, Joëlle Wiels, Franziska Wild, Manon E. Wildenberg, Tom Wileman, Deepti Srinivas Wilkinson, Simon Wilkinson, Dieter Willbold, Chris Williams, Katherine Williams, Peter R. Williamson, Konstanze F. Winklhofer, Steven S. Witkin, Stephanie E. Wohlgemuth, Thomas Wollert, Ernst J. Wolvetang, Esther Wong, G. William Wong, Richard W. Wong, Vincent Kam Wai Wong, Elizabeth A. Woodcock, Karen L. Wright, Chunlai Wu, Defeng Wu, Gen Sheng Wu, Jian Wu, Junfang Wu, Mian Wu, Min Wu, Shengzhou Wu, William KK Wu, Yaohua Wu, Zhenlong Wu, Cristina PR Xavier, Ramnik J. Xavier, Gui Xian Xia, Tian Xia, Weiliang Xia, Yong Xia, Hengyi Xiao, Jian Xiao, Shi Xiao, Wuhan Xiao, Chuan Ming Xie, Zhiping Xie, Zhonglin Xie, Maria Xilouri, Yuyan Xiong, Chuanshan Xu, Congfeng Xu, Feng Xu, Haoxing Xu, Hongwei Xu, Jian Xu, Jianzhen Xu, Jinxian Xu, Liang Xu, Xiaolei Xu, Yangqing Xu, Ye Xu, Zhi Xiang Xu, Ziheng Xu, Yu Xue, Takahiro Yamada, Ai Yamamoto, Koji Yamanaka, Shunhei Yamashina, Shigeko Yamashiro, Bing Yan, Bo Yan, Xianghua Yan, Zhen Yan, Yasuo Yanagi, Dun Sheng Yang, Jin Ming Yang, Liu Yang, Minghua Yang, Pei Ming Yang, Peixin Yang, Qian Yang, Wannian Yang, Wei Yuan Yang, Xuesong Yang, Yi Yang, Ying Yang, Zhifen Yang, Zhihong Yang, Meng Chao Yao, Pamela J. Yao, Xiaofeng Yao, Zhenyu Yao, Zhiyuan Yao, Linda S. Yasui, Mingxiang Ye, Barry Yedvobnick, Behzad Yeganeh, Elizabeth S. Yeh, Patricia L. Yeyati, Fan Yi, Long Yi, Xiao Ming Yin, Calvin K. Yip, Yeong Min Yoo, Young Hyun Yoo, Seung Yong Yoon, Ken Ichi Yoshida, Tamotsu Yoshimori, Ken H. Young, Huixin Yu, Jane J. Yu, Jin Tai Yu, Jun Yu, Li Yu, W. Haung Yu, Xiao Fang Yu, Zhengping Yu, Junying Yuan, Zhi Min Yuan, Beatrice YJT Yue, Jianbo Yue, Zhenyu Yue, David N. Zacks, Eldad Zacksenhaus, Nadia Zaffaroni, Tania Zaglia, Zahra Zakeri, Vincent Zecchini, Jinsheng Zeng, Min Zeng, Qi Zeng, Antonis S. Zervos, Donna D. Zhang, Fan Zhang, Guo Zhang, Guo Chang Zhang, Hao Zhang, Hong Zhang, Hongbing Zhang, Jian Zhang, Jiangwei Zhang, Jianhua Zhang, Jing pu Zhang, Li Zhang, Lin Zhang, Long Zhang, Ming Yong Zhang, Xiangnan Zhang, Xu Dong Zhang, Yan Zhang, Yang Zhang, Yanjin Zhang, Yingmei Zhang, Yunjiao Zhang, Mei Zhao, Wei Li Zhao, Xiaonan Zhao, Yan G. Zhao, Ying Zhao, Yongchao Zhao, Yu xia Zhao, Zhendong Zhao, Zhizhuang J. Zhao, Dexian Zheng, Xi Long Zheng, Xiaoxiang Zheng, Boris Zhivotovsky, Qing Zhong, Guang Zhou Zhou, Guofei Zhou, Huiping Zhou, Shu Feng Zhou, Xu jie Zhou, Hongxin Zhu, Hua Zhu, Wei Guo Zhu, Wenhua Zhu, Xiao Feng Zhu, Yuhua Zhu, Shi Mei Zhuang, Xiaohong Zhuang, Elio Ziparo, Christos E. Zois, Teresa Zoladek, Wei Xing Zong, Antonio Zorzano, Susu M. Zughaier, Life Sciences Institute and Department of Molecular, Cellular, and Developmental Biology and Biological Chemistry, University of Michigan [Ann Arbor], University of Michigan System-University of Michigan System, Tokyo Medical University, The Hebrew University of Jerusalem (HUJ), Mammalian Genetics Unit, Medical Research Council Harwell, University of Occupational and Environmental Health School of Medicine, Partenaires INRAE, University of Toronto, Ben-Gurion University of the Negev (BGU), University of Colorado [Boulder], Cell Death Research & Therapy (CDRT) Lab, Université Catholique de Louvain = Catholic University of Louvain (UCL), University of Vienna [Vienna], Conway Institute of Biomolecular and Biomedical Research and School of Chemical and Bioprocess Engineering, University College Dublin [Dublin] (UCD), Georgetown University, Candiolo Cancer Institute (IRCCS), Centro de Investigacion Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Instituto de Salud Carlos III [Madrid] (ISC), Ikerbasque - Basque Foundation for Science, Cleveland Clinic, Sidney Kimmel Cancer Center, Jefferson (Philadelphia University + Thomas Jefferson University), Universidad de Buenos Aires (UBA), Department of Clinical Neurosciences, University College of London [London] (UCL)-Institute of Neurology, Thérapie génique, Génomique et Epigénomique (U 1169), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Consiglio Nazionale delle Ricerche (CNR), Osaka University, Department of Experimental Medicine and Public Health, University of Camerino, University of Barcelona, Institut Universitaire d'Hématologie (IUH), Université Paris Diderot - Paris 7 (UPD7), Génomique Fonctionnelle des Tumeurs Solides (U1162), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Descartes - Paris 5 (UPD5), Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Physics, Technical University of Denmark [Lyngby] (DTU), University of Zaragoza - Universidad de Zaragoza [Zaragoza], Department of Pharmaco-Biology, Università della Calabria [Arcavacata di Rende] (Unical), Fondation Universitaire Notre Dame de la Paix (FUNDP), Facultés Universitaires Notre Dame de la Paix (FUNDP), USC Neuromuscular Center, Department of Neurology, University of Southern California (USC), Physiopathologie de la survie et de la mort cellulaire et infection virale, Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-IFR50-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Côte d'Azur (UCA), Giannina Gaslini Institute, Institut des Sciences de l'Evolution de Montpellier (UMR ISEM), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université de Montpellier (UM)-Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Centre National de la Recherche Scientifique (CNRS)-Institut de recherche pour le développement [IRD] : UR226, Inner Mongolia Agricultural University (IMAU), Politecnico di Milano [Milan] (POLIMI), Department of Civil, Geological, and Mining Engineering, École Polytechnique de Montréal (EPM)-NSERC Industrial Chair on Drinking Water, Institut de Recherche sur le Cancer et le Vieillissement (IRCAN), COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), Department of Molecular Medicine, Institut Pasteur, Fondation Cenci Bolognetti - Istituto Pasteur Italia, Fondazione Cenci Bolognetti, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome], Physiopathologie du système nerveux central - Institut François Magendie, Université Bordeaux Segalen - Bordeaux 2-IFR8-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratory of Experimental Virology - Department of Medical Microbiology [Amsterdam, The Netherlands], Academic Medical Center - Academisch Medisch Centrum [Amsterdam] (AMC), University of Amsterdam [Amsterdam] (UvA)-University of Amsterdam [Amsterdam] (UvA)-Center for Infection and Immunity Amsterdam - CINIMA [Amsterdam, The Netherlands], Centre de résonance magnétique biologique et médicale (CRMBM), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Centre National de la Recherche Scientifique (CNRS), Dynamique des interactions membranaires normales et pathologiques (DIMNP), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Université Montpellier 2 - Sciences et Techniques (UM2)-Université Montpellier 1 (UM1), Department of Internal Medicine, Hospital Universitario Infanta Sofía, Celullar and Molecular Medicine, Infection bactérienne, inflammation, et carcinogenèse digestive, University of Edinburgh, Unité de Nutrition Humaine (UNH), Institut National de la Recherche Agronomique (INRA)-Université d'Auvergne - Clermont-Ferrand I (UdA)-Clermont Université, Faculty of Engineering and Natural Sciences, Sabanci University [Istanbul], University of Science and Technology Beijing [Beijing] (USTB), Centre for Computational and Systems Biology (COSBI), Sun Yat-Sen University [Guangzhou] (SYSU), Dynamique Musculaire et Métabolisme (DMEM), Université de Montpellier (UM)-Institut National de la Recherche Agronomique (INRA), CAS Institute of Oceanology (IOCAS), Chinese Academy of Sciences [Beijing] (CAS), Polytechnic University of Marche, Centre de Recherche en Cancérologie de Marseille (CRCM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Cell Biology, Physiology and Immunology, Department of Experimental Oncology and Molecular Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, University of Pisa - Università di Pisa, Dulbecco Telethon Institute/Department of Biology, Fondation de Recherche Cancer et Sang - Hôpital Kirchberg, China University of Petroleum, Unilever R&D, University of Queensland [Brisbane], University of Minnesota [Twin Cities] (UMN), University of Minnesota System, Laboratoire de Génie des Procédés et Matériaux - EA 4038 (LGPM), CentraleSupélec, Institute for Advanced Study [Tsinghua], Tsinghua University [Beijing] (THU), Nanayang Technological University (NTU), Nanayang Technological University, Institute of Microelectronics [Beijing] (IMETU), Laboratoire de photonique et de nanostructures (LPN), Centre National de la Recherche Scientifique (CNRS), Institut de biologie moléculaire des plantes (IBMP), Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA), Northwestern Polytechnical University [Xi'an] (NPU), University of Pennsylvania [Philadelphia], City University of Hong Kong (CityU), Department of Mathematics [Berkeley], University of California [Berkeley], University of California-University of California, ZJU-ENS Joint Laboratory of Medicinal Chemistry, Zhejiang University, University of Cincinnati (UC), Réponses immunes : régulation et développement, Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), The University of New Mexico [Albuquerque], Centre de Recherche de l'Institut du Cerveau et de la Moelle épinière (CRICM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Dipartimento di Scienze Biomediche, Università degli Studi di Modena e Reggio Emilia (UNIMORE), Department of Experimental Medicine and Oncology, University of Turin, Institut de Génomique Fonctionnelle (IGF), Université de Montpellier (UM)-Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 2 - Sciences et Techniques (UM2)-Centre National de la Recherche Scientifique (CNRS), CNV, University of Valparaiso, Université Paris 1 Panthéon-Sorbonne - UFR d'Arts plastiques et sciences de l'art (UP1 UFR04), Université Paris 1 Panthéon-Sorbonne (UP1), Department of General, Visceral and Vascular Surgery [Jena], Friedrich-Schiller-Universität Jena, Récepteurs nucléaires, maladies cardiovasculaires et diabète - U 1011 (RNMCD), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Institut National de la Santé et de la Recherche Médicale (INSERM), Réseau International des Instituts Pasteur (RIIP), Macrophages et Développement de l’Immunité, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Immunobiologie des Cellules Dendritiques, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre d'infectiologie Necker-Pasteur [CHU Necker], Institut Pasteur [Paris]-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Pasteur [Paris], Trafic membranaire et Division cellulaire - Membrane Traffic and Cell Division, Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris], Cibles thérapeutiques, formulation et expertise pré-clinique du médicament (CITHEFOR), Université de Lorraine (UL), This work was supported in part by the National Institutes of Health, including Public Health Service grant GM053396 to D.J.K. Due to space and other limitations, it is not possible to include all other sources of financial support., In a rapidly expanding and highly dynamic field such as autophagy, it is possible that some authors who should have been included on this article have been missed. D.J.K. extends his apologies to researchers in the field of autophagy who, due to oversight or any other reason, could not be included on this article. I also note that two of our colleagues on this manuscript have passed away: Arlette Darfeuille-Michaud and Wouter van Doorn., Life Sciences Institute [Ann Arbor, MI, USA], Laboratoire de Biogenèse Membranaire, CNRS UMR 5200, Université de Bordeaux, INRA Bordeaux Aquitaine, Villenave d'Ornon, France., Amelio, Ivano [0000-0002-9126-5391], Beale, Rupert [0000-0002-6705-8560], Floto, Andres [0000-0002-2188-5659], Frezza, Christian [0000-0002-3293-7397], Ktistakis, Nicholas [0000-0001-9397-2914], Melino, Gerry [0000-0001-9428-5972], Narita, Masashi [0000-0001-7764-577X], Rubinsztein, David [0000-0001-5002-5263], Underwood, Benjamin [0000-0003-3427-9487], Whitworth, Alex [0000-0002-1154-6629], Apollo - University of Cambridge Repository, Université Catholique de Louvain, Facultés Universitaires Notre-Dame de la Paix, Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR50-Université Nice Sophia Antipolis (... - 2019) (UNS), Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-École pratique des hautes études (EPHE)-Université de Montpellier (UM)-Institut de recherche pour le développement [IRD] : UR226-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Nice Sophia Antipolis (... - 2019) (UNS), Department of Clinical and Molecular Medicine, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Università degli Studi di Roma 'La Sapienza' [Rome], Université Montpellier 1 (UM1)-Université Montpellier 2 - Sciences et Techniques (UM2)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA)-IFR50-Institut National de la Santé et de la Recherche Médicale (INSERM), Unité de Nutrition Humaine - Clermont Auvergne (UNH), Institut National de la Recherche Agronomique (INRA)-Université Clermont Auvergne (UCA), Sun Yat-Sen University (SYSU), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Aix Marseille Université (AMU), University of Minnesota [Twin Cities], Tsinghua University [Beijing], Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Université Panthéon-Sorbonne - UFR d'Arts plastiques et sciences de l'art (UP1 UFR04), Université Panthéon-Sorbonne (UP1), Récepteurs nucléaires, maladies cardiovasculaires et diabète (EGID), Université de Lille, Droit et Santé-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), CHU Necker - Enfants Malades [AP-HP], Trafic membranaire et Division cellulaire, Institut de Biologie du Développement de Marseille (IBDM), Aix Marseille Université (AMU)-Collège de France (CdF)-Centre National de la Recherche Scientifique (CNRS), Klionsky, D., Abdelmohsen, K., Abe, A., Abedin, M., Abeliovich, H., Acevedo Arozena, A., Adachi, H., Adams, C., Adams, P., Adeli, K., Adhihetty, P., Adler, S., Agam, G., Agarwal, R., Aghi, M., Agnello, M., Agostinis, P., Aguilar, P., Aguirre-Ghiso, J., Airoldi, E., Ait-Si-Ali, S., Akematsu, T., Akporiaye, E., Al-Rubeai, M., Albaiceta, G., Albanese, C., Albani, D., Albert, M., Aldudo, J., Algül, H., Alirezaei, M., Alloza, I., Almasan, A., Almonte-Beceril, M., Alnemri, E., Alonso, C., Altan-Bonnet, N., Altieri, D., Alvarez, S., Alvarez-Erviti, L., Alves, S., Amadoro, G., Amano, A., Amantini, C., Ambrosio, S., Amelio, I., Amer, A., Amessou, M., Amon, A., An, Z., Anania, F., Andersen, S., Andley, U., Andreadi, C., Andrieu-Abadie, N., Anel, A., Ann, D., Anoopkumar-Dukie, S., Antonioli, M., Aoki, H., Apostolova, N., Aquila, S., Aquilano, K., Araki, K., Arama, E., Aranda, A., Araya, J., Arcaro, A., Arias, E., Arimoto, H., Ariosa, A., Armstrong, J., Arnould, T., Arsov, I., Asanuma, K., Askanas, V., Asselin, E., Atarashi, R., Atherton, S., Atkin, J., Attardi, L., Auberger, P., Auburger, G., Aurelian, L., Autelli, R., Avagliano, L., Avantaggiati, M., Avrahami, L., Awale, S., Azad, N., Bachetti, T., Backer, J., Bae, D., Bae, J., Bae, O., Bae, S., Baehrecke, E., Baek, S., Baghdiguian, S., Bagniewska-Zadworna, A., Bai, H., Bai, J., Bai, X., Bailly, Y., Balaji, K., Balduini, W., Ballabio, A., Balzan, R., Banerjee, R., Bánhegyi, G., Bao, H., Barbeau, B., Barrachina, M., Barreiro, E., Bartel, B., Bartolomé, A., Bassham, D., Bassi, M., Bast, R., Basu, A., Batista, M., Batoko, H., Battino, M., Bauckman, K., Baumgarner, B., Bayer, K., Beale, R., Beaulieu, J., Beck, G., Becker, C., Beckham, J., Bédard, P., Bednarski, P., Begley, T., Behl, C., Behrends, C., Behrens, G., Behrns, K., Bejarano, E., Belaid, A., Belleudi, F., Bénard, G., Berchem, G., Bergamaschi, D., Bergami, M., Berkhout, B., Berliocchi, L., Bernard, A., Bernard, M., Bernassola, F., Bertolotti, A., Bess, A., Besteiro, S., Bettuzzi, S., Bhalla, S., Bhattacharyya, S., Bhutia, S., Biagosch, C., Bianchi, M., Biard-Piechaczyk, M., Billes, V., Bincoletto, C., Bingol, B., Bird, S., Bitoun, M., Bjedov, I., Blackstone, C., Blanc, L., Blanco, G., Blomhoff, H., Boada-Romero, E., Böckler, S., Boes, M., Boesze-Battaglia, K., Boise, L., Bolino, A., Boman, A., Bonaldo, P., Bordi, M., Bosch, J., Botana, L., Botti, J., Bou, G., Bouché, M., Bouchecareilh, M., Boucher, M., Boulton, M., Bouret, S., Boya, P., Boyer-Guittaut, M., Bozhkov, P., Brady, N., Braga, V., Brancolini, C., Braus, G., Bravo-San Pedro, J., Brennan, L., Bresnick, E., Brest, P., Bridges, D., Bringer, M., Brini, M., Brito, G., Brodin, B., Brookes, P., Brown, E., Brown, K., Broxmeyer, H., Bruhat, A., Brum, P., Brumell, J., Brunetti-Pierri, N., Bryson-Richardson, R., Buch, S., Buchan, A., Budak, H., Bulavin, D., Bultman, S., Bultynck, G., Bumbasirevic, V., Burelle, Y., Burke, R., Burmeister, M., Bütikofer, P., Caberlotto, L., Cadwell, K., Cahova, M., Cai, D., Cai, J., Cai, Q., Calatayud, S., Camougrand, N., Campanella, M., Campbell, G., Campbell, M., Campello, S., Candau, R., Caniggia, I., Cantoni, L., Cao, L., Caplan, A., Caraglia, M., Cardinali, C., Cardoso, S., Carew, J., Carleton, L., Carlin, C., Carloni, S., Carlsson, S., Carmona-Gutierrez, D., Carneiro, L., Carnevali, O., Carra, S., Carrier, A., Carroll, B., Casas, C., Casas, J., Cassinelli, G., Castets, P., Castro-Obregon, S., Cavallini, G., Ceccherini, I., Cecconi, F., Cederbaum, A., Ceña, V., Cenci, S., Cerella, C., Cervia, D., Cetrullo, S., Chaachouay, H., Chae, H., Chagin, A., Chai, C., Chakrabarti, G., Chamilos, G., Chan, E., Chan, M., Chandra, D., Chandra, P., Chang, C., Chang, R., Chang, T., Chatham, J., Chatterjee, S., Chauhan, S., Che, Y., Cheetham, M., Cheluvappa, R., Chen, C., Chen, G., Chen, H., Chen, J., Chen, M., Chen, P., Chen, Q., Chen, S., Chen, W., Chen, X., Chen, Y., Chen, Z., Cheng, A., Cheng, C., Cheng, H., Cheong, H., Cherry, S., Chesney, J., Cheung, C., Chevet, E., Chi, H., Chi, S., Chiacchiera, F., Chiang, H., Chiarelli, R., Chiariello, M., Chieppa, M., Chin, L., Chiong, M., Chiu, G., Cho, D., Cho, S., Cho, W., Cho, Y., Choi, A., Choi, E., Choi, J., Choi, M., Choi, S., Chou, T., Chouaib, S., Choubey, D., Choubey, V., Chow, K., Chowdhury, K., Chu, C., Chuang, T., Chun, T., Chung, H., Chung, T., Chung, Y., Chwae, Y., Cianfanelli, V., Ciarcia, R., Ciechomska, I., Ciriolo, M., Cirone, M., Claerhout, S., Clague, M., Clària, J., Clarke, P., Clarke, R., Clementi, E., Cleyrat, C., Cnop, M., Coccia, E., Cocco, T., Codogno, P., Coers, J., Cohen, E., Colecchia, D., Coletto, L., Coll, N., Colucci-Guyon, E., Comincini, S., Condello, M., Cook, K., Coombs, G., Cooper, C., Cooper, J., Coppens, I., Corasaniti, M., Corazzari, M., Corbalan, R., Corcelle-Termeau, E., Cordero, M., Corral-Ramos, C., Corti, O., Cossarizza, A., Costelli, P., Costes, S., Cotman, S., Coto-Montes, A., Cottet, S., Couve, E., Covey, L., Cowart, L., Cox, J., Coxon, F., Coyne, C., Cragg, M., Craven, R., Crepaldi, T., Crespo, J., Criollo, A., Crippa, V., Cruz, M., Cuervo, A., Cuezva, J., Cui, T., Cutillas, P., Czaja, M., Czyzyk-Krzeska, M., Dagda, R., Dahmen, U., Dai, C., Dai, W., Dai, Y., Dalby, K., Dalla Valle, L., Dalmasso, G., D'Amelio, M., Damme, M., Darfeuille-Michaud, A., Dargemont, C., Darley-Usmar, V., Dasarathy, S., Dasgupta, B., Dash, S., Dass, C., Davey, H., Davids, L., Dávila, D., Davis, R., Dawson, T., Dawson, V., Daza, P., de Belleroche, J., de Figueiredo, P., de Figueiredo, R., de la Fuente, J., De Martino, L., De Matteis, A., De Meyer, G., De Milito, A., De Santi, M., de Souza, W., De Tata, V., De Zio, D., Debnath, J., Dechant, R., Decuypere, J., Deegan, S., Dehay, B., Del Bello, B., Del Re, D., Delage-Mourroux, R., Delbridge, L., Deldicque, L., Delorme-Axford, E., Deng, Y., Dengjel, J., Denizot, M., Dent, P., Der, C., Deretic, V., Derrien, B., Deutsch, E., Devarenne, T., Devenish, R., Di Bartolomeo, S., Di Daniele, N., Di Domenico, F., Di Nardo, A., Di Paola, S., Di Pietro, A., Di Renzo, L., Diantonio, A., Díaz-Araya, G., Díaz-Laviada, I., Diaz-Meco, M., Diaz-Nido, J., Dickey, C., Dickson, R., Diederich, M., Digard, P., Dikic, I., Dinesh-Kumar, S., Ding, C., Ding, W., Ding, Z., Dini, L., Distler, J., Diwan, A., Djavaheri-Mergny, M., Dmytruk, K., Dobson, R., Doetsch, V., Dokladny, K., Dokudovskaya, S., Donadelli, M., Dong, X., Dong, Z., Donohue, T., Doran, K., D'Orazi, G., Dorn, G., Dosenko, V., Dridi, S., Drucker, L., Du, J., Du, L., du Toit, A., Dua, P., Duan, L., Duann, P., Dubey, V., Duchen, M., Duchosal, M., Duez, H., Dugail, I., Dumit, V., Duncan, M., Dunlop, E., Dunn, W., Dupont, N., Dupuis, L., Durán, R., Durcan, T., Duvezin-Caubet, S., Duvvuri, U., Eapen, V., Ebrahimi-Fakhari, D., Echard, A., Eckhart, L., Edelstein, C., Edinger, A., Eichinger, L., Eisenberg, T., Eisenberg-Lerner, A., Eissa, N., El-Deiry, W., El-Khoury, V., Elazar, Z., Eldar-Finkelman, H., Elliott, C., Emanuele, E., Emmenegger, U., Engedal, N., Engelbrecht, A., Engelender, S., Enserink, J., Erdmann, R., Erenpreisa, J., Eri, R., Eriksen, J., Erman, A., Escalante, R., Eskelinen, E., Espert, L., Esteban-Martínez, L., Evans, T., Fabri, M., Fabrias, G., Fabrizi, C., Facchiano, A., Færgeman, N., Faggioni, A., Fairlie, W., Fan, C., Fan, D., Fan, J., Fang, S., Fanto, M., Fanzani, A., Farkas, T., Faure, M., Favier, F., Fearnhead, H., Federici, M., Fei, E., Felizardo, T., Feng, H., Feng, Y., Ferguson, T., Fernández, Á., Fernandez-Barrena, M., Fernandez-Checa, J., Fernández-López, A., Fernandez-Zapico, M., Feron, O., Ferraro, E., Ferreira-Halder, C., Fesus, L., Feuer, R., Fiesel, F., Filippi-Chiela, E., Filomeni, G., Fimia, G., Fingert, J., Finkbeiner, S., Finkel, T., Fiorito, F., Fisher, P., Flajolet, M., Flamigni, F., Florey, O., Florio, S., Floto, R., Folini, M., Follo, C., Fon, E., Fornai, F., Fortunato, F., Fraldi, A., Franco, R., Francois, A., François, A., Frankel, L., Fraser, I., Frey, N., Freyssenet, D., Frezza, C., Friedman, S., Frigo, D., Fu, D., Fuentes, J., Fueyo, J., Fujitani, Y., Fujiwara, Y., Fujiya, M., Fukuda, M., Fulda, S., Fusco, C., Gabryel, B., Gaestel, M., Gailly, P., Gajewska, M., Galadari, S., Galili, G., Galindo, I., Galindo, M., Galliciotti, G., Galluzzi, L., Galy, V., Gammoh, N., Gandy, S., Ganesan, A., Ganesan, S., Ganley, I., Gannagé, M., Gao, F., Gao, J., García Nannig, L., García Véscovi, E., Garcia-Macía, M., Garcia-Ruiz, C., Garg, A., Garg, P., Gargini, R., Gassen, N., Gatica, D., Gatti, E., Gavard, J., Gavathiotis, E., Ge, L., Ge, P., Ge, S., Gean, P., Gelmetti, V., Genazzani, A., Geng, J., Genschik, P., Gerner, L., Gestwicki, J., Gewirtz, D., Ghavami, S., Ghigo, E., Ghosh, D., Giammarioli, A., Giampieri, F., Giampietri, C., Giatromanolaki, A., Gibbings, D., Gibellini, L., Gibson, S., Ginet, V., Giordano, A., Giorgini, F., Giovannetti, E., Girardin, S., Gispert, S., Giuliano, S., Gladson, C., Glavic, A., Gleave, M., Godefroy, N., Gogal, R., Gokulan, K., Goldman, G., Goletti, D., Goligorsky, M., Gomes, A., Gomes, L., Gomez, H., Gomez-Manzano, C., Gómez-Sánchez, R., Gonçalves, D., Goncu, E., Gong, Q., Gongora, C., Gonzalez, C., Gonzalez-Alegre, P., Gonzalez-Cabo, P., González-Polo, R., Goping, I., Gorbea, C., Gorbunov, N., Goring, D., Gorman, A., Gorski, S., Goruppi, S., Goto-Yamada, S., Gotor, C., Gottlieb, R., Gozes, I., Gozuacik, D., Graba, Y., Graef, M., Granato, G., Grant, G., Grant, S., Gravina, G., Green, D., Greenhough, A., Greenwood, M., Grimaldi, B., Gros, F., Grose, C., Groulx, J., Gruber, F., Grumati, P., Grune, T., Guan, J., Guan, K., Guerra, B., Guillen, C., Gulshan, K., Gunst, J., Guo, C., Guo, L., Guo, M., Guo, 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Shieh, Jj, Shih, Cm, Shimada, Y, Shimizu, S, Shin, Dw, Shinohara, Ml, Shintani, M, Shintani, T, Shioi, T, Shirabe, K, Shiri Sverdlov, R, Shirihai, O, Shore, Gc, Shu, Cw, Shukla, D, Sibirny, Aa, Sica, V, Sigurdson, Cj, Sigurdsson, Em, Sijwali, P, Sikorska, B, Silveira, Wa, Silvente Poirot, S, Silverman, Ga, Simak, J, Simmet, T, Simon, Ak, Simon, Hu, Simone, C, Simons, M, Simonsen, A, Singh, R, Singh, Sv, Singh, Sk, Sinha, D, Sinha, S, Sinicrope, Fa, Sirko, A, Sirohi, K, Sishi, Bj, Sittler, A, Siu, Pm, Sivridis, E, Skwarska, A, Slack, R, Slaninová, I, Slavov, N, Smaili, S, Smalley, K, Smith, Dr, Soenen, Sj, Soleimanpour, Sa, Solhaug, A, Somasundaram, K, Son, Jh, Sonawane, A, Song, C, Song, F, Song, Hk, Song, Jx, Song, W, Soo, Ky, Sood, Ak, Soong, Tw, Soontornniyomkij, V, Sorice, M, Sotgia, F, Soto Pantoja, Dr, Sotthibundhu, A, Sousa, Mj, Spaink, Hp, Span, Pn, Spang, A, Sparks, Jd, Speck, Pg, Spector, Sa, Spies, Cd, Springer, W, Clair, D, Stacchiotti, A, Staels, B, Stang, Mt, 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Berghe, G, Van Den Bosch, L, van den Brink, Gr, van der Goot, Fg, van der Klei, Ij, van der Laan, Lj, van Doorn, Wg, van Egmond, M, van Golen, Kl, Van Kaer, L, van Lookeren Campagne, M, Vandenabeele, P, Vandenberghe, W, Vanhorebeek, I, Varela Nieto, I, Vasconcelos, Mh, Vasko, R, Vavvas, Dg, Vega Naredo, I, Velasco, G, Velentzas, Ad, Velentzas, Pd, Vellai, T, Vellenga, E, Vendelbo, Mh, Venkatachalam, K, Ventura, N, Ventura, S, Veras, P, Verdier, M, Vertessy, Bg, Viale, A, Vidal, M, Vieira, H, Vierstra, Rd, Vigneswaran, N, Vij, N, Vila, M, Villar, M, Villar, Vh, Villarroya, J, Vindis, C, Viola, G, Viscomi, Mt, Vitale, G, Vogl, Dt, Voitsekhovskaja, Ov, von Haefen, C, von Schwarzenberg, K, Voth, De, Vouret Craviari, V, Vuori, K, Vyas, Jm, Waeber, C, Walker, Cl, Walker, Mj, Walter, J, Wan, L, Wan, X, Wang, B, Wang, C, Wang, Cy, Wang, D, Wang, F, Wang, G, Wang, Hj, Wang, H, Wang, Hg, Wang, Hd, Wang, J, Wang, M, Wang, Mq, Wang, Py, Wang, P, Wang, Rc, Wang, S, Wang, Tf, Wang, X, Wang, Xj, Wang, Xw, Wang, Y, Wang, Yj, Wang, Yt, Wang, Zn, Wappner, P, Ward, C, Ward, Dm, Warnes, G, Watada, H, Watanabe, Y, Watase, K, Weaver, Te, Weekes, Cd, Wei, J, Weide, T, Weihl, Cc, Weindl, G, Weis, Sn, Wen, L, Wen, X, Wen, Y, Westermann, B, Weyand, Cm, White, Ar, White, E, Whitton, Jl, Whitworth, Aj, Wiels, J, Wild, F, Wildenberg, Me, Wileman, T, Wilkinson, D, Wilkinson, S, Willbold, D, Williams, C, Williams, K, Williamson, Pr, Winklhofer, Kf, Witkin, S, Wohlgemuth, Se, Wollert, T, Wolvetang, Ej, Wong, E, Wong, Gw, Wong, Rw, Wong, Vk, Woodcock, Ea, Wright, Kl, Wu, C, Wu, D, Wu, G, Wu, J, Wu, M, Wu, S, Wu, Wk, Wu, Y, Wu, Z, Xavier, Cp, Xavier, Rj, Xia, Gx, Xia, T, Xia, W, Xia, Y, Xiao, H, Xiao, J, Xiao, S, Xiao, W, Xie, Cm, Xie, Z, Xilouri, M, Xiong, Y, Xu, C, Xu, F, Xu, H, Xu, J, Xu, L, Xu, X, Xu, Y, Xu, Zx, Xu, Z, Xue, Y, Yamada, T, Yamamoto, A, Yamanaka, K, Yamashina, S, Yamashiro, S, Yan, B, Yan, X, Yan, Z, Yanagi, Y, Yang, D, Yang, Jm, Yang, L, Yang, M, Yang, Pm, Yang, P, Yang, Q, 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Other departments, CCA -Cancer Center Amsterdam, Center of Experimental and Molecular Medicine, Radiotherapy, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, Medical Biochemistry, ANS - Cellular & Molecular Mechanisms, Cell Biology and Histology, Gastroenterology and Hepatology, Tytgat Institute for Liver and Intestinal Research, Daniel J Klionsky, Kotb Abdelmohsen, Akihisa Abe, Md Joynal Abedin, Hagai Abeliovich, Abraham Acevedo Arozena, Hiroaki Adachi, Christopher M Adam, Peter D Adam, Khosrow Adeli, Peter J Adhihetty, Sharon G Adler, Galila Agam, Rajesh Agarwal, Manish K Aghi, Maria Agnello, Patrizia Agostini, Patricia V Aguilar, Julio Aguirre-Ghiso, Edoardo M Airoldi, Slimane Ait-Si-Ali, Takahiko Akematsu, Emmanuel T Akporiaye, Mohamed Al-Rubeai, Guillermo M Albaiceta, Chris Albanese, Diego Albani, Matthew L Albert, Jesus Aldudo, Hana Algül, Mehrdad Alirezaei, Iraide Alloza, Alexandru Almasan, Maylin Almonte-Beceril, Emad S Alnemri, Covadonga Alonso, Nihal Altan-Bonnet, Dario C Altieri, Silvia Alvarez, Lydia Alvarez- Erviti, Sandro Alve, Giuseppina Amadoro, Atsuo Amano, Consuelo Amantini, Santiago Ambrosio, Ivano Amelio, Amal O Amer, Mohamed Amessou, Angelika Amon, Zhenyi An, Frank A Anania, Stig U Andersen, Usha P Andley, Catherine K Andreadi, Nathalie Andrieu- Abadie, Alberto Anel, David K Ann, Shailendra Anoopkumar-Dukie, Manuela Antonioli, Hiroshi Aoki, Nadezda Apostolova, Saveria Aquila, Katia Aquilano, Koichi Araki, Eli Arama, Agustin Aranda, Jun Araya, Alexandre Arcaro, Esperanza Aria, Hirokazu Arimoto, Aileen R Ariosa, Jane L Armstrong, Thierry Arnould, Ivica Arsov, Katsuhiko Asanuma, Valerie Askana, Eric Asselin, Ryuichiro Atarashi, Sally S Atherton, Julie D Atkin, Laura D Attardi, Patrick Auberger, Georg Auburger, Laure Aurelian, Riccardo Autelli, Laura Avagliano, Maria Laura Avantaggiati, Limor Avrahami, Suresh Awale, Neelam Azad, Tiziana Bachetti, Jonathan M Backer, Dong- Hun Bae, Jae-sung Bae, Ok-Nam Bae, Soo Han Bae, Eric H Baehrecke, Seung-Hoon Baek, Stephen Baghdiguian, Agnieszka Bagniewska-Zadworna, Hua Bai, Jie Bai, Xue-Yuan Bai, Yannick Bailly, Kithiganahalli Narayanaswamy Balaji, Walter Balduini, Andrea Ballabio, Rena Balzan, Rajkumar Banerjee, Gábor Bánhegyi, Haijun Bao, Benoit Barbeau, Maria D Barrachina, Esther Barreiro, Bonnie Bartel, Alberto Bartolomé, Diane C Bassham, Maria Teresa Bassi, Robert C Bast Jr, Alakananda Basu, Maria Teresa Batista, Henri Batoko, Maurizio Battino, Kyle Bauckman, Bradley L Baumgarner, K Ulrich Bayer, Rupert Beale, Jean-François Beaulieu, George R. Beck Jr, Christoph Becker, J David Beckham, Pierre-André Bédard, Patrick J Bednarski, Thomas J Begley, Christian Behl, Christian Behrend, Georg MN Behren, Kevin E Behrn, Eloy Bejarano, Amine Belaid, Francesca Belleudi, Giovanni Bénard, Guy Berchem, Daniele Bergamaschi, Matteo Bergami, Ben Berkhout, Laura Berliocchi, Amélie Bernard, Monique Bernard, Francesca Bernassola, Anne Bertolotti, Amanda S Be, Sébastien Besteiro, Saverio Bettuzzi, Savita Bhalla, Shalmoli Bhattacharyya, Sujit K Bhutia, Caroline Biagosch, Michele Wolfe Bianchi, Martine Biard-Piechaczyk, Viktor Bille, Claudia Bincoletto, Baris Bingol, Sara W Bird, Marc Bitoun, Ivana Bjedov, Craig Blackstone, Lionel Blanc, Guillermo A Blanco, Heidi Kiil Blomhoff, Emilio Boada-Romero, Stefan Böckler, Marianne Boe, Kathleen Boesze-Battaglia, Lawrence H Boise, Alessandra Bolino, Andrea Boman, Paolo Bonaldo, Matteo Bordi, Jürgen Bosch, Luis M Botana, Joelle Botti, German Bou, Marina Bouché, Marion Bouchecareilh, Marie- Josée Boucher, Michael E Boulton, Sebastien G Bouret, Patricia Boya, Michaël Boyer-Guittaut, Peter V Bozhkov, Nathan Brady, Vania MM Braga, Claudio Brancolini, Gerhard H Brau, José M Bravo-San Pedro, Lisa A Brennan, Emery H Bresnick, Patrick Brest, Dave Bridge, MarieAgnès Bringer, Marisa Brini, Glauber C Brito, Bertha Brodin, Paul S Brooke, Eric J Brown, Karen Brown, Hal E Broxmeyer, Alain Bruhat, Patricia Chakur Brum, John H Brumell, Nicola Brunetti-Pierri, Robert J Bryson-Richardson, Shilpa Buch, Alastair M Buchan, Hikmet Budak, Dmitry V Bulavin, Scott J Bultman, Geert Bultynck, Vladimir Bumbasirevic, Yan Burelle, Robert E Burke, Margit Burmeister, Peter Bütikofer, Laura Caberlotto, Ken Cadwell, Monika Cahova, Dongsheng Cai, Jingjing Cai, Qian Cai, Sara Calatayud, Nadine Camougrand, Michelangelo Campanella, Grant R Campbell, Matthew Campbell, Silvia Campello, Robin Candau, Isabella Caniggia, Lavinia Cantoni, Lizhi Cao, Allan B Caplan, Michele Caraglia, Claudio Cardinali, Sandra Morais Cardoso, Jennifer S Carew, Laura A Carleton, Cathleen R Carlin, Silvia Carloni, Sven R Carlsson, Didac Carmona-Gutierrez, Leticia AM Carneiro, Oliana Carnevali, Serena Carra, Alice Carrier, Bernadette Carroll, Caty Casa, Josefina Casa, Giuliana Cassinelli, Perrine Castet, Susana Castro-Obregon, Gabriella Cavallini, Isabella Ceccherini, Francesco Cecconi, Arthur I Cederbaum, Valentín Ceña, Simone Cenci, Claudia Cerella, Davide Cervia, Silvia Cetrullo, Hassan Chaachouay, Han-Jung Chae, Andrei S Chagin, Chee-Yin Chai, Gopal Chakrabarti, Georgios Chamilo, Edmond YW Chan, Matthew TV Chan, Dhyan Chandra, Pallavi Chandra, Chih-Peng Chang, Raymond Chuen-Chung Chang, Ta Yuan Chang, John C Chatham, Saurabh Chatterjee, Santosh Chauhan, Yongsheng Che, Michael E Cheetham, Rajkumar Cheluvappa, Chun-Jung Chen, Gang Chen, Guang-Chao Chen, Guoqiang Chen, Hongzhuan Chen, Jeff W Chen, Jian-Kang Chen, Min Chen, Mingzhou Chen, Peiwen Chen, Qi Chen, Quan Chen, Shang- Der Chen, Si Chen, Steve S-L Chen, Wei Chen, Wei-Jung Chen, Wen Qiang Chen, Wenli Chen, Xiangmei Chen, Yau-Hung Chen, Ye-Guang Chen, Yin Chen, Yingyu Chen, Yongshun Chen, Yu- Jen Chen, Yue-Qin Chen, Yujie Chen, Zhen Chen, Zhong Chen, Alan Cheng, Christopher HK Cheng, Hua Cheng, Heesun Cheong, Sara Cherry, Jason Chesney, Chun Hei Antonio Cheung, Eric Chevet, Hsiang Cheng Chi, Sung-Gil Chi, Fulvio Chiacchiera, Hui-Ling Chiang, Roberto Chiarelli, Mario Chiariello, Marcello Chieppa, Lih-Shen Chin, Mario Chiong, Gigi NC Chiu, Dong-Hyung Cho, Ssang-Goo Cho, William C Cho, Yong-Yeon Cho, Young-Seok Cho, Augustine MK Choi, Eui-Ju Choi, Eun-Kyoung Choi, Jayoung Choi, Mary E Choi, Seung-Il Choi, Tsui-Fen Chou, Salem Chouaib, Divaker Choubey, Vinay Choubey, Kuan-Chih Chow, Kamal Chowdhury, Charleen T Chu, Tsung-Hsien Chuang, Taehoon Chun, Hyewon Chung, Taijoon Chung, Yuen-Li Chung, Yong-Joon Chwae, Valentina Cianfanelli, Roberto Ciarcia, Iwona A Ciechomska, Maria Rosa Ciriolo, Mara Cirone, Sofie Claerhout, Michael J Clague, Joan Clària, Peter GH Clarke, Robert Clarke, Emilio Clementi, Cédric Cleyrat, Miriam Cnop, Eliana M Coccia, Tiziana Cocco, Patrice Codogno, Jörn Coer, Ezra EW Cohen, David Colecchia, Luisa Coletto, Núria S Coll, Emma Colucci-Guyon, Sergio Comincini, Maria Condello, Katherine L Cook, Graham H Coomb, Cynthia D Cooper, J Mark Cooper, Isabelle Coppen, Maria Tiziana Corasaniti, Marco Corazzari, Ramon Corbalan, Elisabeth Corcelle-Termeau, Mario D Cordero, Cristina Corral-Ramo, Olga Corti, Andrea Cossarizza, Paola Costelli, Safia Coste, Susan L Cotman, Ana Coto-Monte, Sandra Cottet, Eduardo Couve, Lori R Covey, L Ashley Cowart, Jeffery S Cox, Fraser P Coxon, Carolyn B Coyne, Mark S Cragg, Rolf J Craven, Tiziana Crepaldi, Jose L Crespo, Alfredo Criollo, Valeria Crippa, Maria Teresa Cruz, Ana Maria Cuervo, Jose M Cuezva, Taixing Cui, Pedro R Cutilla, Mark J Czaja, Maria F Czyzyk-Krzeska, Ruben K Dagda, Uta Dahmen, Chunsun Dai, Wenjie Dai, Yun Dai, Kevin N Dalby, Luisa Dalla Valle, Guillaume Dalmasso, 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Vincent CO Njar, Takeshi Noda, Angelika A Noegel, Elsie Magdalena Nolte, Erik Norberg, Koenraad K Norga, Sakineh Kazemi Noureini, Shoji Notomi, Lucia Notterpek, Karin Nowikovsky, Nobuyuki Nukina, Thorsten Nürnberger, Valerie B O'Donnell, Tracey O'Donovan, Peter J O'Dwyer, Ina Oehme, Clara L Oeste, Michinaga Ogawa, Besim Ogretmen, Yuji Ogura, Young J Oh, Masaki Ohmuraya, Takayuki Ohshima, Rani Ojha, Koji Okamoto, Toshiro Okazaki, F Javier Oliver, Karin Ollinger, Stefan Olsson, Daniel P Orban, Paulina Ordonez, Idil Orhon, Laszlo Orosz, Eyleen J O'Rourke, Helena Orozco, Angel L Ortega, Elena Ortona, Laura D Osellame, Junko Oshima, Shigeru Oshima, Heinz D Osiewacz, Takanobu Otomo, Kinya Otsu, Jing-hsiung James Ou, Tiago F Outeiro, Dong-yun Ouyang, Hongjiao Ouyang, Michael Overholtzer, Michelle A Ozbun, P Hande Ozdinler, Bulent Ozpolat, Consiglia Pacelli, Paolo Paganetti, Guylène Page, Gilles Page, Ugo Pagnini, Beata Pajak, Stephen C Pak, Karolina Pakos-Zebrucka, Nazzy Pakpour, Zdena 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Rohrer, Davide Romanelli, Luigina Romani, Patricia Silvia Romano, M Isabel G Roncero, Jose Luis Rosa, Alicia Rosello, Kirill V Rosen, Philip Rosenstiel, Magdalena Rost-Roszkowska, Kevin A Roth, Gael Roué, Mustapha Roui, Kasper M Rouschop, Daniel T Ruan, Diego Ruano, David C Rubinsztein, Edmund B Rucker III, Assaf Rudich, Emil Rudolf, Ruediger Rudolf, Markus A Ruegg, Carmen Ruiz-Roldan, Avnika Ashok Ruparelia, Paola Rusmini, David W Ru, Gian Luigi Russo, Giuseppe Russo, Rossella Russo, Tor Erik Rusten, Victoria Ryabovol, Kevin M Ryan, Stefan W Ryter, David M Sabatini, Michael Sacher, Carsten Sachse, Michael N Sack, Junichi Sadoshima, Paul Saftig, Ronit Sagi-Eisenberg, Sumit Sahni, Pothana Saikumar, Tsunenori Saito, Tatsuya Saitoh, Koichi Sakakura, Machiko Sakoh-Nakatogawa, Yasuhito Sakuraba, María Salazar-Roa, Paolo Salomoni, Ashok K Saluja, Paul M Salvaterra, Rosa Salvioli, Afshin Samali, Anthony MJ Sanchez, José A Sánchez-Alcázar, Ricardo Sanchez-Prieto, Marco Sandri, Miguel A 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L Semenza, Utpal Sen, Andreas L Serra, Ana Serrano-Puebla, Hiromi Sesaki, Takao Setoguchi, Carmine Settembre, John J Shacka, Ayesha N Shajahan-Haq, Irving M Shapiro, Shweta Sharma, Hua She, C-K James Shen, Chiung-Chyi Shen, Han-Ming Shen, Sanbing Shen, Weili Shen, Rui Sheng, Xianyong Sheng, Zu-Hang Sheng, Trevor G Shepherd, Junyan Shi, Qiang Shi, Qinghua Shi, Yuguang Shi, Shusaku Shibutani, Kenichi Shibuya, Yoshihiro Shidoji, Jeng- Jer Shieh, Chwen-Ming Shih, Yohta Shimada, Shigeomi Shimizu, Dong Wook Shin, Mari L Shinohara, Michiko Shintani, Takahiro Shintani, Tetsuo Shioi, Ken Shirabe, Ronit Shiri-Sverdlov, Orian Shirihai, Gordon C Shore, Chih-Wen Shu, Deepak Shukla, Andriy A Sibirny, Valentina Sica, Christina J Sigurdson, Einar M Sigurdsson, Puran Singh Sijwali, Beata Sikorska, Wilian A Silveira, Sandrine Silvente-Poirot, Gary A Silverman, Jan Simak, Thomas Simmet, Anna Katharina Simon, Hans-Uwe Simon, Cristiano Simone, Matias Simon, Anne Simonsen, Rajat Singh, Shivendra V Singh, 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Tsai, Mario P Tschan, Yi-Hsin Tseng, Takayuki Tsukuba, Allan Tsung, Andrey S Tsvetkov, Shuiping Tu, Hsing-Yu Tuan, Marco Tucci, David A Tumbarello, Boris Turk, Vito Turk, Robin FB Turner, Anders A Tveita, Suresh C Tyagi, Makoto Ubukata, Yasuo Uchiyama, Andrej Udelnow, Takashi Ueno, Midori Umekawa, Rika Umemiya-Shirafuji, Benjamin R Underwood, Christian Ungermann, Rodrigo P. Ureshino, Ryo Ushioda, Vladimir N Uversky, Néstor L Uzcátegui, Thomas Vaccari, Maria I Vaccaro, Libuše Váchová, Helin Vakifahmetoglu-Norberg, Rut Valdor, Enza Maria Valente, Francois Vallette, Angela M Valverde, Greet Van den Berghe, Ludo Van Den Bosch, Gijs R van den Brink, F Gisou van der Goot, Ida J van der Klei, Luc JW van der Laan, Wouter G van Doorn, Marjolein van Egmond, Kenneth L van Golen, Luc Van Kaer, Menno van Lookeren Campagne, Peter Vandenabeele, Wim Vandenberghe, Ilse Vanhorebeek, Isabel Varela-Nieto, M Helena Vasconcelo, Radovan Vasko, Demetrios G Vavva, Ignacio Vega- Naredo, Guillermo Velasco, Athanassios D Velentza, Panagiotis D Velentza, Tibor Vellai, Edo Vellenga, Mikkel Holm Vendelbo, Kartik Venkatachalam, Natascia Ventura, Salvador Ventura, Patrícia ST Vera, Mireille Verdier, Beata G Vertessy, Andrea Viale, Michel Vidal, Helena LA Vieira, Richard D Vierstra, Nadarajah Vigneswaran, Neeraj Vij, Miquel Vila, Margarita Villar, Victor H Villar, Joan Villarroya, Cécile Vindi, Giampietro Viola, Maria Teresa Viscomi, Giovanni Vitale, Dan T Vogl, Olga V Voitsekhovskaja, Clarissa von Haefen, Karin von Schwarzenberg, Daniel E Voth, Valérie Vouret-Craviari, Kristina Vuori, Jatin M Vya, Christian Waeber, Cheryl Lyn Walker, Mark J Walker, Jochen Walter, Lei Wan, Xiangbo Wan, Bo Wang, Caihong Wang, Chao-Yung Wang, Chengshu Wang, Chenran Wang, Chuangui Wang, Dong Wang, Fen Wang, Fuxin Wang, Guanghui Wang, Hai-jie Wang, Haichao Wang, Hong-Gang Wang, Hongmin Wang, Horng-Dar Wang, Jing Wang, Junjun Wang, Mei Wang, Mei-Qing Wang, Pei-Yu Wang, Peng Wang, Richard C Wang, Shuo Wang, Ting-Fang Wang, Xian Wang, Xiao-jia Wang, Xiao-Wei Wang, Xin Wang, Xuejun Wang, Yan Wang, Yanming Wang, Ying Wang, Ying-Jan Wang, Yipeng Wang, Yu Wang, Yu Tian Wang, Yuqing Wang, Zhi-Nong Wang, Pablo Wappner, Carl Ward, Diane McVey Ward, Gary Warne, Hirotaka Watada, Yoshihisa Watanabe, Kei Watase, Timothy E Full Terms & Conditions of access and use can be found at http://www.tandfonline.com/action/journalInformation?journalCode=kaup20 Download by: [Alma Mater Studiorum - Università di Bologna] Date: 23 September 2016, At: 06:43 Weaver, Colin D Weeke, Jiwu Wei, Thomas Weide, Conrad C Weihl, Günther Weindl, Simone Nardin Wei, Longping Wen, Xin Wen, Yunfei Wen, Benedikt Westermann, Cornelia M Weyand, Anthony R White, Eileen White, J Lindsay Whitton, Alexander J Whitworth, Joëlle Wiel, Franziska Wild, Manon E Wildenberg, Tom Wileman, Deepti Srinivas Wilkinson, Simon Wilkinson, Dieter Willbold, Chris William, Katherine William, Peter R Williamson, Konstanze F Winklhofer, Steven S Witkin, Stephanie E Wohlgemuth, Thomas Wollert, Ernst J Wolvetang, Esther Wong, G William Wong, Richard W Wong, Vincent Kam Wai Wong, Elizabeth A Woodcock, Karen L Wright, Chunlai Wu, Defeng Wu, Gen Sheng Wu, Jian Wu, Junfang Wu, Mian Wu, Min Wu, Shengzhou Wu, William KK Wu, Yaohua Wu, Zhenlong Wu, Cristina PR Xavier, Ramnik J Xavier, Gui-Xian Xia, Tian Xia, Weiliang Xia, Yong Xia, Hengyi Xiao, Jian Xiao, Shi Xiao, Wuhan Xiao, Chuan-Ming Xie, Zhiping Xie, Zhonglin Xie, Maria Xilouri, Yuyan Xiong, Chuanshan Xu, Congfeng Xu, Feng Xu, Haoxing Xu, Hongwei Xu, Jian Xu, Jianzhen Xu, Jinxian Xu, Liang Xu, Xiaolei Xu, Yangqing Xu, Ye Xu, Zhi-Xiang Xu, Ziheng Xu, Yu Xue, Takahiro Yamada, Ai Yamamoto, Koji Yamanaka, Shunhei Yamashina, Shigeko Yamashiro, Bing Yan, Bo Yan, Xianghua Yan, Zhen Yan, Yasuo Yanagi, Dun-Sheng Yang, Jin-Ming Yang, Liu Yang, Minghua Yang, Pei-Ming Yang, Peixin Yang, Qian Yang, Wannian Yang, Wei Yuan Yang, Xuesong Yang, Yi Yang, Ying Yang, Zhifen Yang, Zhihong Yang, Meng-Chao Yao, Pamela J Yao, Xiaofeng Yao, Zhenyu Yao, Zhiyuan Yao, Linda S Yasui, Mingxiang Ye, Barry Yedvobnick, Behzad Yeganeh, Elizabeth S Yeh, Patricia L Yeyati, Fan Yi, Long Yi, Xiao-Ming Yin, Calvin K Yip, Yeong-Min Yoo, Young Hyun Yoo, Seung-Yong Yoon, Ken-Ichi Yoshida, Tamotsu Yoshimori, Ken H Young, Huixin Yu, Jane J Yu, Jin-Tai Yu, Jun Yu, Li Yu, W Haung Yu, Xiao-Fang Yu, Zhengping Yu, Junying Yuan, Zhi-Min Yuan, Beatrice YJT Yue, Jianbo Yue, Zhenyu Yue, David N Zack, Eldad Zacksenhau, Nadia Zaffaroni, Tania Zaglia, Zahra Zakeri, Vincent Zecchini, Jinsheng Zeng, Min Zeng, Qi Zeng, Antonis S Zervo, Donna D Zhang, Fan Zhang, Guo Zhang, Guo-Chang Zhang, Hao Zhang, Hong Zhang, Hongbing Zhang, Jian Zhang, Jiangwei Zhang, Jianhua Zhang, Jing-pu Zhang, Li Zhang, Lin Zhang, Long Zhang, Ming-Yong Zhang, Xiangnan Zhang, Xu Dong Zhang, Yan Zhang, Yang Zhang, Yanjin Zhang, Yingmei Zhang, Yunjiao Zhang, Mei Zhao, Wei-Li Zhao, Xiaonan Zhao, Yan G Zhao, Ying Zhao, Yongchao Zhao, Yu-xia Zhao, Zhendong Zhao, Zhizhuang J Zhao, Dexian Zheng, Xi-Long Zheng, Xiaoxiang Zheng, Boris Zhivotovsky, Qing Zhong, Guang-Zhou Zhou, Guofei Zhou, Huiping Zhou, Shu-Feng Zhou, Xu-jie Zhou, Hongxin Zhu, Hua Zhu, Wei- Guo Zhu, Wenhua Zhu, Xiao-Feng Zhu, Yuhua Zhu, Shi-Mei Zhuang, Xiaohong Zhuang, Elio Ziparo, Christos E Zoi, Teresa Zoladek, Wei-Xing Zong, and Antonio Zorzano & Susu M Zughaier
Subjects: [SDV]Life Sciences [q-bio], autophagosome, Review Article, ddc:616.07, stress, stre, LC3, MESH: Animals, Settore MED/49 - Scienze Tecniche Dietetiche Applicate, Settore BIO/06 - Anatomia Comparata E Citologia, chaperone-mediated autophagy, ComputingMilieux_MISCELLANEOUS, Settore BIO/11, Pharmacology. Therapy, Settore BIO/13, standards [Biological Assay], autolysosome, MESH: Autophagy*/physiology, lysosome, methods [Biological Assay], Biological Assay, Settore BIO/17 - ISTOLOGIA, Erratum, Human, Biochemistry & Molecular Biology, Settore BIO/06, physiology [Autophagy], Chaperonemediated autophagy, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, NO, autophagy, guidelines, molecular biology, ultrastructure, flux, macroautophagy, phagophore, vacuole, MESH: Biological Assay/methods, MESH: Computer Simulation, ddc:570, Autolysosome, Autophagosome, Chaperonemediated autophagy, Flux, LC3, Lysosome, Macroautophagy, Phagophore, Stress, Vacuole, Autophagy, Animals, Humans, Computer Simulation, Settore BIO/10, ddc:612, Biology, MESH: Humans, Animal, 0601 Biochemistry And Cell Biology, MESH: Biological Assay/standards, Human medicine
Abstract: Seuls les 100 premiers auteurs dont les auteurs INRA ont été entrés dans la notice. La liste complète des auteurs et de leurs affiliations est accessible sur la publication.; International audience; In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes.For example, a key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process versus those that measure flux through the autophagy pathway (i.e., the complete process including the amount and rate of cargo sequestered and degraded). In particular, a block in macroautophagy that results in autophagosome accumulation must be differentiated from stimuli that increase autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. It is worth emphasizing here that lysosomal digestion is a stage of autophagy and evaluating its competence is a crucial part of the evaluation of autophagic flux, or complete autophagy.Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. Along these lines, because of the potential for pleiotropic effects due to blocking autophagy through genetic manipulation, it is imperative to target by gene knockout or RNA interference more than one autophagy-related protein. In addition, some individual Atg proteins, or groups of proteins, are involved in other cellular pathways implying that not all Atg proteins can be used as a specific marker for an autophagic process. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular assays, we hope to encourage technical innovation in the field.
Published: 2016
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50. A blood circulation-prolonging peptide anchored biomimetic phage-platelet hybrid nanoparticle system for prolonged blood circulation and optimized anti-bacterial performance.

Author: Peipei Jin, Liansheng Wang, Rui Sha, Liu Liu, Jieying Qian, Nestor Ishimwe, Wenbin Zhang, Jing Qian, Yunjiao Zhang, and Longping Wen
Published: 2021
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