96 results on '"Aijie Liu"'
Search Results
2. Transformable nanodrugs for overcoming the biological barriers in the tumor environment during drug delivery
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Xuejian Li, Zhenkun Huang, Zhihuan Liao, Aijie Liu, and Shuaidong Huo
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General Materials Science - Abstract
Transformable nanodrugs with changeable sizes and shapes allow for overcoming multiple biological barriers for enhanced drug delivery. This review aims to present an overview of the most recent development of smart nanodrugs in this emerging field.
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- 2023
3. Excited-state and charge-carrier dynamics in binary conjugated polymer dots towards efficient photocatalytic hydrogen evolution
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Aijie Liu, Sicong Wang, Hongwei Song, Yawen Liu, Lars Gedda, Katarina Edwards, Leif Hammarström, and Haining Tian
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Fysikalisk kemi ,General Physics and Astronomy ,Physical and Theoretical Chemistry ,Physical Chemistry - Abstract
Aqueous dispersed conjugated polymer dots (Pdots) have shown promising application in photocatalytic hydrogen evolution. To efficiently extract photogenerated charges from type-II heterojunction Pdots for hydrogen evolution, the mechanistic study of photophysical processes is essential for Pdot optimization. Within this work, we use a PFODTBT donor (D) polymer and an ITIC small molecule acceptor (A) as a donor/acceptor (D/A) model system to study their excited states and charge/energy transfer dynamics via steady-state and time-resolved photoluminescence spectroscopy, respectively. Charge-carrier generation and the recombination dynamics of binary Pdots with different D/A ratios were followed using femtosecond transient absorption spectroscopy. A significant spectral relaxation of photoluminescence was observed for individual D Pdots, implying an energetic disorder by nature. However, this was not seen for charge carriers in binary Pdots, probably due to the ultrafast charge generation process at an early time (
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- 2023
4. Photosynthetic Polymer Dots–Bacteria Biohybrid System Based on Transmembrane Electron Transport for Fixing CO2 into Poly-3-hydroxybutyrate
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Wen Yu, Mariia V. Pavliuk, Aijie Liu, Yue Zeng, Shengpeng Xia, Yiming Huang, Haotian Bai, Fengting Lv, Haining Tian, and Shu Wang
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General Materials Science - Published
- 2022
5. Detecting genomic mosaicism in 'de novo' genetic epilepsy by amplicon-based deep sequencing
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Jiaoyang, Chen, Yi, Chen, Ying, Yang, Xueyang, Niu, Jing, Zhang, Qi, Zeng, Aijie, Liu, Xiaojing, Xu, Xiaoxu, Yang, Shupin, Li, Xiaoling, Yang, Yi, Wang, and Yuehua, Zhang
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Genetics ,Genetics (clinical) - Abstract
To investigate the occurrence of mosaicism in epilepsy probands and their parents using amplicon-based deep sequencing (ADS).Patients were recruited from the outpatient of Peking University First Hospital. Two hundred and sixty-four probands with pathogenic variants tested by next-generation sequencing (NGS) were enrolled.Mosaic variants were detected in seventeen disease-associated genes from 20 probands, 5 paternal, and 6 maternal parents. The frequency of mosaicism was 11.74% (31/264). Mosaicism in 11 genes was identified from 20 probands with the mutant allelic fractions (MAFs) of 12.95-38.00% in autosomal dominant genes. Five paternal mosaicisms were identified in genes with a MAF of 6.30-20.99%, and six maternal mosaic individuals with a MAF of 2.07-21.90%. Only four mosaic parents had milder seizure history. The affected sibling had the same phenotype consistent with that of the proband, who inherited the variant of SLC1A2 or STXBP1 from their unaffected mosaic mothers, respectively.Mosaic phenomenon is not rare in families with epilepsy. Phenotypes of mosaic parents were milder or normal. Mosaicism detection is helpful to identify the mutation origin and it provides a theoretical basis for prenatal diagnosis of family reproduction. ADS is a reliable way of mosaicism detection for clinical application.
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- 2022
6. Performance evaluation of a renewable driven standalone combined power and water supply system with cascade electricity and heat storage
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Pan Zhao, Wenpan Xu, Aijie Liu, Wenze Wu, Jiangfeng Wang, and Zhequan Yan
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Renewable Energy, Sustainability and the Environment - Published
- 2022
7. Performance analysis of a pumped hydro assisted near‐isothermal compressed carbon dioxide energy storage system with gas/liquid phase change process
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Pan Zhao, Shiqiang Zhang, Wenpan Xu, Aijie Liu, Wenze Wu, and Jiangfeng Wang
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Fuel Technology ,Nuclear Energy and Engineering ,Renewable Energy, Sustainability and the Environment ,Energy Engineering and Power Technology - Published
- 2022
8. Supplemental Figures S1-4 from Prevention of Carcinogen and Inflammation-Induced Dermal Cancer by Oral Rapamycin Includes Reducing Genetic Damage
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Tyler J. Curiel, Zelton D. Sharp, Paul Hasty, Aijie Liu, Danielle Callaway, Sherry Dodds, Vincent Hurez, Yang Liu, Srilakshmi Pandeswara, and Vinh Dao
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Supplemental Figures S1-4. Supplementary Figure S1: eRapa prevents DMBA/TPA-induced dermal neoplasia and malignant degeneration in WT mice. Supplementary Figure S2: eRapa does not suppress mTORC1 signaling in whole skin. Supplementary Figure S3: eRapa is not a calorie restriction mimetic. Supplementary Figure S4: eRapa prevents DMBA/TPA-induced dermal neoplasia in T cell deficient mice.
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- 2023
9. Data from Immune-Stimulatory Effects of Rapamycin Are Mediated by Stimulation of Antitumor γδ T Cells
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Tyler J. Curiel, Vincent Hurez, Aijie Liu, Jonathan A. Gelfond, Robert S. Svatek, Srilakshmi Pandeswara, Yang Liu, and Vinh Dao
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The FDA-approved mTOR inhibitor rapamycin mediates important immune effects, but its contributions to the anticancer effects of the drug are unclear. Here we report evidence that rapamycin-mediated cancer protection relies upon stimulation of γδ T cells. In a well-established mouse model of carcinogen and inflammation-driven skin carcinogenesis, IFNγ recruited γδ TCRmid T cells to the epidermis where rapamycin boosted their perforin-dependent antitumor properties. These antitumor cells were mostly Vγ5−Vγ4−Vγ1− in phenotype. IFNγ signals were required in both hematopoietic and nonhematopoietic cells for rapamycin to optimally promote epidermal infiltration of γδ TCRmid T cells, as mediated by CXCR3–CXCL10 interactions, along with the antitumor effects of these cells. In mouse xenograft models of human squamous cell carcinoma, rapamycin improved human γδ T-cell–mediated cancer cell killing. Our results identify immune mechanisms for the cancer prevention and treatment properties of rapamycin, challenging the paradigm that mTOR inhibition acts primarily by direct action on tumor cells. Cancer Res; 76(20); 5970–82. ©2016 AACR.
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- 2023
10. supplemental figures combined from Immune-Stimulatory Effects of Rapamycin Are Mediated by Stimulation of Antitumor γδ T Cells
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Tyler J. Curiel, Vincent Hurez, Aijie Liu, Jonathan A. Gelfond, Robert S. Svatek, Srilakshmi Pandeswara, Yang Liu, and Vinh Dao
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S1 shows DMBA/TPA modulation of epidermal alphabeta and gammadelta TCRhi T cells in WT and CXCR3-/- mice. S2 shows epidermal chemokines in WT and IFN-gamma-/- mice treated with Eudragit control or eRapa. S3 shows mTOR signaling in epidermal and draining lymph node T cells. S4 shows human gammadelta TCR expression in gammadelta T cells.
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- 2023
11. Supplementary Figures 1 through 11 from Biphasic Rapamycin Effects in Lymphoma and Carcinoma Treatment
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Tyler J. Curiel, Vincent Hurez, Aijie Liu, Shunhua Lao, Justin M. Drerup, Álvaro Padrón, Vinh Dao, Srilakshmi Pandeswara, and Yang Liu
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Supplementary figure 1. Rapamycin reduces EL4 bone marrow infiltration. Supplementary figure 2. HD rapamycin impairs T cell activation and infiltration. Supplementary figure 3. Effects of rapamycin on mTOR signals and Ki67 (proliferation) in EL4 cells studied ex vivo. Supplementary figure 4. Dose response effects of rapamycin on EL4 in vivo. Supplementary figure 5. EL4 is refractory to many standard immunotherapies. Supplementary figure 6. LD rapamycin plus DD-mediated EL4 cell death is not blocked by anti-CD25 in vivo. Supplementary figure 7. LD rapamycin improves DD treatment efficacy of B16F10. Supplementary figure 8. Rapamycin + DD killing of EL4 and B16 cells is blocked with anti-CD25 + anti-CD22 in vitro. Supplementary figure 9. CD25 and CD122 expression are not upregulated by rapamycin treatment in vitro in mouse tumor lines B16F10 or ID8agg. Supplementary figure 10. CD25 and CD122 expression are not upregulated by rapamycin treatment in vivo in mouse challenged with B16F10. Supplementary figure 11. CD25 and CD122 expression on human NM001 and Jurkat cell lines is unchanged with temsirolimus in vitro.
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- 2023
12. Data from Biphasic Rapamycin Effects in Lymphoma and Carcinoma Treatment
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Tyler J. Curiel, Vincent Hurez, Aijie Liu, Shunhua Lao, Justin M. Drerup, Álvaro Padrón, Vinh Dao, Srilakshmi Pandeswara, and Yang Liu
- Abstract
mTOR drives tumor growth but also supports T-cell function, rendering the applications of mTOR inhibitors complex especially in T-cell malignancies. Here, we studied the effects of the mTOR inhibitor rapamycin in mouse EL4 T-cell lymphoma. Typical pharmacologic rapamycin (1–8 mg/kg) significantly reduced tumor burden via direct suppression of tumor cell proliferation and improved survival in EL4 challenge independent of antitumor immunity. Denileukin diftitox (DD)–mediated depletion of regulatory T cells significantly slowed EL4 growth in vivo in a T-cell–dependent fashion. However, typical rapamycin inhibited T-cell activation and tumor infiltration in vivo and failed to boost DD treatment effects. Low-dose (LD) rapamycin (75 μg/kg) increased potentially beneficial CD44hiCD62L+ CD8+ central memory T cells in EL4 challenge, but without clinical benefit. LD rapamycin significantly enhanced DD treatment efficacy, but DD plus LD rapamycin treatment effects were independent of antitumor immunity. Instead, rapamycin upregulated EL4 IL2 receptor in vitro and in vivo, facilitating direct DD tumor cell killing. LD rapamycin augmented DD efficacy against B16 melanoma and a human B-cell lymphoma, but not against human Jurkat T-cell lymphoma or ID8agg ovarian cancer cells. Treatment effects correlated with IL2R expression, but mechanisms in some tumors were not fully defined. Overall, our data define a distinct, biphasic mechanisms of action of mTOR inhibition at doses that are clinically exploitable, including in T-cell lymphomas. Cancer Res; 77(2); 520–31. ©2016 AACR.
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- 2023
13. Supplementary Data from CD122-Selective IL2 Complexes Reduce Immunosuppression, Promote Treg Fragility, and Sensitize Tumor Response to PD-L1 Blockade
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Tyler J. Curiel, Harshita Gupta, Vincent Hurez, José R. Conejo-Garcia, Wanjiao Chen, Curtis A. Clark, Aijie Liu, Jenny Mendez, Xinyue Zhang, Ryan M. Reyes, Álvaro S. Padrón, Sri Lakshmi Pandeswara, Yilun Deng, and Justin M. Drerup
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Supplementary figures 1-10. Figure S1. IL-2c increases conventional CD4 T cell in ascites three weeks after final IL-2c, but does not affect ascites Treg and effector T cell numbers at one week after final IL-2c administration. Figure S2. IL-2c treatment increases CD8+ central and effector memory T cells in the ascites, and central memory T cells in TDLN. Fig S3. Additional Treg phenotype in ascites and TDLN after IL-2c treatment. Fig S4. IL-2c directly inhibits Treg suppression specifically in the tumor microenvironment. Fig S5. IL-2 signaling is not impaired in TDLN after IL-2c treatment. Figure S6. Specific Treg depletion is highly effective against ID8agg. Figure S7. αCD25 attenuates IL-2c-induced tumor rejection and T cell function in ID8agg OC. Figure S8. IL-2c promotes intratumoral T cell infiltration. Figure S9. IL-2c reduces intratumoral Treg activation and functional molecules in B16 melanoma. Figure S10. IL-2c increases TIGIT+LAG-3+PD-1+ CD8+ T cells in B16 tumors.
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- 2023
14. Supplementary Methods from CD73 on Tumor Cells Impairs Antitumor T-Cell Responses: A Novel Mechanism of Tumor-Induced Immune Suppression
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Bin Zhang, Tyler J. Curiel, Tahiro Shin, Benjamin J. Daniel, Aijie Liu, Linda F. Thompson, Long Wang, Jie Fan, and Dachuan Jin
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Supplementary Methods from CD73 on Tumor Cells Impairs Antitumor T-Cell Responses: A Novel Mechanism of Tumor-Induced Immune Suppression
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- 2023
15. Supplementary Figures 1-7 from CD73 on Tumor Cells Impairs Antitumor T-Cell Responses: A Novel Mechanism of Tumor-Induced Immune Suppression
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Bin Zhang, Tyler J. Curiel, Tahiro Shin, Benjamin J. Daniel, Aijie Liu, Linda F. Thompson, Long Wang, Jie Fan, and Dachuan Jin
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Supplementary Figures 1-7 from CD73 on Tumor Cells Impairs Antitumor T-Cell Responses: A Novel Mechanism of Tumor-Induced Immune Suppression
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- 2023
16. Design and Off-Design Performance Analysis of a Liquid Carbon Dioxide Energy Storage System Integrated with Low-Grade Heat Source
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Wenpan Xu, Pan Zhao, Aijie Liu, Wenze Wu, and Jiangfeng Wang
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Energy Engineering and Power Technology ,Industrial and Manufacturing Engineering - Published
- 2023
17. Photosynthetic Polymer Dots-Bacteria Biohybrid System Based on Transmembrane Electron Transport for Fixing CO
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Wen, Yu, Mariia V, Pavliuk, Aijie, Liu, Yue, Zeng, Shengpeng, Xia, Yiming, Huang, Haotian, Bai, Fengting, Lv, Haining, Tian, and Shu, Wang
- Abstract
Organic semiconductor-microbial photosynthetic biohybrid systems show great potential in light-driven biosynthesis. In such a system, an organic semiconductor is used to harvest solar energy and generate electrons, which can be further transported to microorganisms with a wide range of metabolic pathways for final biosynthesis. However, the lack of direct electron transport proteins in existing microorganisms hinders the hybrid system of photosynthesis. In this work, we have designed a photosynthetic biohybrid system based on transmembrane electron transport that can effectively deliver the electrons from organic semiconductor across the cell wall to the microbe. Biocompatible organic semiconductor polymer dots (Pdots) are used as photosensitizers to construct a ternary synergistic biochemical factory in collaboration with
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- 2022
18. IL6 supports long-term expansion of hepatocytes in vitro
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Ren Guo, Mengmeng Jiang, Gang Wang, Bing Li, Xiaohui Jia, Yan Ai, Shanshan Chen, Peilan Tang, Aijie Liu, Qianting Yuan, and Xin Xie
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Mice ,Multidisciplinary ,Interleukin-6 ,Stem Cells ,Hepatocytes ,Animals ,General Physics and Astronomy ,Cell Differentiation ,General Chemistry ,General Biochemistry, Genetics and Molecular Biology ,Clone Cells - Abstract
Hepatocytes are very difficult to expand in vitro. A few studies have demonstrated that chemical cocktails with growth factors or Wnt ligands can support long-term expansion of hepatocytes via dedifferentiation. However, the culture conditions are complex, and clonal expansion of hepatic progenitors with full differentiation capacity are rarely reported. Here, we discover IL6, combined with EGF and HGF, promotes long-term expansion (>30 passages in ~150 days with theoretical expansion of ~1035 times) of primary mouse hepatocytes in vitro in simple 2D culture, by converting hepatocytes into induced hepatic progenitor cells (iHPCs), which maintain the capacity of differentiation into hepatocytes. IL6 also supports the establishment of single hepatocyte-derived iHPC clones. The summation of the downstream STAT3, ERK and AKT pathways induces a number of transcription factors which support rapid growth. This physiological and simple way may provide ideas for culturing previously difficult-to-culture cell types and support their future applications.
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- 2022
19. PCDH19-related epilepsy in mosaic males: The phenotypic implication of genotype and variant allele frequency
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Yi Chen, Xiaoxu Yang, Jiaoyang Chen, Xiaoling Yang, Ying Yang, Aijie Liu, Xiaoli Zhang, Wenjuan Wu, Dan Sun, Zhixian Yang, Yuwu Jiang, and Yuehua Zhang
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Epilepsy ,phenotype ,genotype ,Intellectual and Developmental Disabilities (IDD) ,Clinical Sciences ,Neurosciences ,variant allele frequency ,Neurodegenerative ,Brain Disorders ,mosaicism ,male ,Neurology ,Clinical Research ,Genetics ,2.1 Biological and endogenous factors ,Psychology ,Neurology (clinical) ,Aetiology ,PCDH19 gene - Abstract
ObjectiveTo analyze the genotypes and phenotypes of mosaic male patients with PCDH19-related epilepsy (PCDH19-RE) and explore the correlation between genotype, variant allele frequency (VAF), and phenotypic severity.MethodsClinical data and peripheral blood samples of 11 male mosaic patients were collected and analyzed in our study. The VAF of the PCDH19 gene from peripheral blood was quantified using amplicon-based deep sequencing. Additional 20 mosaic male patients with PCDH19-RE were collected from the published literature, with 10 patients whose VAFs of the PCDH19 gene were available for analytic purposes.ResultsIn our cohort of 11 patients, 10 variants were identified, and four were novel. The VAF of the PCDH19 gene from peripheral blood ranged from 27 to 90%. The median seizure onset age was 6 months (range: 4–9 months). Clinical manifestations included cluster seizures (100%), fever sensitivity (73%), focal seizures (91%), developmental delay/intellectual disability (DD/ID, 82%), and autistic features (45%). Thirty-one mosaic male patients collected from our cohort and the literature developed seizures mostly (87%) within one year of age. Variant types included missense variants (42%), truncating variants (52%), splice variants (3%), and whole PCDH19 deletion (3%). Among 21 patients with a definite VAF from our cohort and the literature, nine had a low VAF ( ≤ 50%) and 12 had a high VAF (> 50%). Seventy-five percent of variants from the high VAF group were missense, whereas 89% of those from the low VAF group were truncations. The median seizure onset age was 6 months in the low VAF group and 9 months in the high VAF group (p = 0.018). Forty-four percent (4/9) of patients from the low VAF group achieved seizure-free for ≥1 year, whereas none of the 12 patients from the high VAF group did (p = 0.021). DD/ID was present in 83% (10/12) of the high VAF group and 56% (5/9) of the low VAF group (p = 0.331).ConclusionThe predominant variant types were truncating and missense variants. Missense variants tended to have higher VAFs. Patients with a high VAF were more likely to have a more severe epileptic phenotype. Our findings shed light on the phenotypic implications of VAF in mosaic males with PCDH19-RE.
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- 2022
20. Polymer Dots as Photoactive Membrane Vesicles for [FeFe]-Hydrogenase Self-Assembly and Solar-Driven Hydrogen Evolution
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Mariia V. Pavliuk, Marco Lorenzi, Dustin R. Morado, Lars Gedda, Sina Wrede, Sara H. Mejias, Aijie Liu, Moritz Senger, Starla Glover, Katarina Edwards, Gustav Berggren, and Haining Tian
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Fysikalisk kemi ,Iron-Sulfur Proteins ,Colloid and Surface Chemistry ,Photosensitizing Agents ,Hydrogenase ,Polymers ,General Chemistry ,Biochemistry ,Physical Chemistry ,Catalysis ,Chlamydomonas reinhardtii ,Hydrogen - Abstract
A semiartificial photosynthesis approach that utilizes enzymes for solar fuel production relies on efficient photosensitizers that should match the enzyme activity and enable long-term stability. Polymer dots (Pdots) are biocompatible photosensitizers that are stable at pH 7 and have a readily modifiable surface morphology. Therefore, Pdots can be considered potential photosensitizers to drive such enzyme-based systems for solar fuel formation. This work introduces and unveils in detail the interaction within the biohybrid assembly composed of binary Pdots and the HydA1 [FeFe]-hydrogenase from Chlamydomonas reinhardtii. The direct attachment of hydrogenase on the surface of toroid-shaped Pdots was confirmed by agarose gel electrophoresis, cryogenic transmission electron microscopy (Cryo-TEM), and cryogenic electron tomography (Cryo-ET). Ultrafast transient spectroscopic techniques were used to characterize photoinduced excitation and dissociation into charges within Pdots. The study reveals that implementation of a donor-acceptor architecture for heterojunction Pdots leads to efficient subpicosecond charge separation and thus enhances hydrogen evolution (88 460 mu mol(H2).g(H2ase)(-1).h(-1)). Adsorption of [FeFe]-hydrogenase onto Pdots resulted in a stable biohybrid assembly, where hydrogen production persisted for days, reaching a TON of 37 500 +/- 1290 in the presence of a redox mediator. This work represents an example of a homogeneous biohybrid system combining polymer nanoparticles and an enzyme. Detailed spectroscopic studies provide a mechanistic understanding of light harvesting, charge separation, and transport studied, which is essential for building semiartificial photosynthetic systems with efficiencies beyond natural and artificial systems.
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- 2022
21. Pattern recognition receptor-initiated innate immune responses in mouse prostatic epithelial cells
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Fei Wang, Daishu Han, Wenjing Zhang, Maolei Gong, Ruiqin Han, Xiaoqin Yu, Ran Chen, Han Wu, Yongmei Chen, Aijie Liu, and Weihua Liu
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Male ,0301 basic medicine ,Chemokine ,Inflammation ,Mice ,03 medical and health sciences ,0302 clinical medicine ,medicine ,Animals ,Innate immune system ,biology ,Monocyte ,Prostate ,Pattern recognition receptor ,Epithelial Cells ,Cell Biology ,General Medicine ,Immunity, Innate ,Mice, Inbred C57BL ,030104 developmental biology ,medicine.anatomical_structure ,Reproductive Medicine ,TLR5 ,Receptors, Pattern Recognition ,030220 oncology & carcinogenesis ,TLR3 ,TLR4 ,biology.protein ,Cancer research ,medicine.symptom - Abstract
Three major pathogenic states of the prostate, including benign prostatic hyperplasia, prostate cancer, and prostatitis, are related to the local inflammation. However, the mechanisms underlying the initiation of prostate inflammation remain largely unknown. Given that the innate immune responses of the tissue-specific cells to microbial infection or autoantigens contribute to local inflammation, this study focused on pattern recognition receptor (PRR)-initiated innate immune responses in mouse prostatic epithelial cells (PECs). Primary mouse PECs abundantly expressed Toll-like receptor 3 (TLR3), TLR4, TLR5, melanoma differentiation-associated protein 5 (MDA5), and IFN-inducible protein 16 (p204 in mouse). These PRRs can be activated by their respective ligands: lipopolysaccharide (LPS) and flagellin of Gram-negative bacteria for TLR4 and TLR5, polyinosinicpolycytidylic acid (poly(I:C)) for TLR3 and MDA5, and herpes simplex virus DNA analog (HSV60) for p204. LPS and flagellin predominantly induced the expression of inflammatory cytokines, including tumor necrosis factor alpha (TNFA), interleukin 6 (IL6), chemokines monocyte chemoattractant protein-1 (MCP1), and C-X-C motif chemokine 10 (CXCL10). Poly(I:C) and HSV60 predominantly induced the expression of type 1 interferons (IFNA and IFNB) and antiviral proteins: Mx GTPase 1, 2′,5′-oligoadenylate synthetase 1, and IFN-stimulated gene 15. The replication of mumps virus in PECs was inhibited by type 1 IFN signaling. These findings provide insights into the mechanisms underlying innate immune response in the prostate.Summary sentenceToll-like receptors 4, 5 and nucleic acid sensors initiate innate immune responses in prostatic epithelial cells after challenge with their respective ligands, which may be associated with inflammation in the prostate.
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- 2021
22. CD122-Selective IL2 Complexes Reduce Immunosuppression, Promote Treg Fragility, and Sensitize Tumor Response to PD-L1 Blockade
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Alvaro Padron, Tyler J. Curiel, Ryan Reyes, Vincent Hurez, Curtis A. Clark, Justin M. Drerup, Aijie Liu, Harshita Gupta, Xinyue Zhang, Jenny Mendez, Yilun Deng, Jose R. Conejo-Garcia, Srilakshmi Pandeswara, and wanjiao chen
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0301 basic medicine ,Cancer Research ,medicine.medical_treatment ,T cell ,Melanoma, Experimental ,chemical and pharmacologic phenomena ,CD8-Positive T-Lymphocytes ,T-Lymphocytes, Regulatory ,Article ,B7-H1 Antigen ,Immune tolerance ,Mice ,Random Allocation ,03 medical and health sciences ,0302 clinical medicine ,Cancer immunotherapy ,T-Lymphocyte Subsets ,PD-L1 ,Immune Tolerance ,Tumor Microenvironment ,Animals ,Medicine ,Ovarian Neoplasms ,Immunity, Cellular ,biology ,business.industry ,Effector ,Melanoma ,Ascites ,Receptors, Interleukin-2 ,hemic and immune systems ,Immunotherapy ,medicine.disease ,Interleukin-2 Receptor beta Subunit ,Mice, Inbred C57BL ,Phenotype ,030104 developmental biology ,medicine.anatomical_structure ,Oncology ,030220 oncology & carcinogenesis ,Cancer research ,biology.protein ,Interleukin-2 ,Female ,business ,Immunologic Memory ,CD8 - Abstract
The IL2 receptor (IL2R) is an attractive cancer immunotherapy target that controls immunosuppressive T regulatory cells (Treg) and antitumor T cells. Here we used IL2Rβ-selective IL2/anti-IL2 complexes (IL2c) to stimulate effector T cells preferentially in the orthotopic mouse ID8agg ovarian cancer model. Despite strong tumor rejection, IL2c unexpectedly lowered the tumor microenvironmental CD8+/Treg ratio. IL2c reduced tumor microenvironmental Treg suppression and induced a fragile Treg phenotype, helping explain improved efficacy despite numerically increased Tregs without affecting Treg in draining lymph nodes. IL2c also reduced Treg-mediated, high-affinity IL2R signaling needed for optimal Treg functions, a likely mechanism for reduced Treg suppression. Effector T-cell IL2R signaling was simultaneously improved, suggesting that IL2c inhibits Treg functions without hindering effector T cells, a limitation of most Treg depletion agents. Anti-PD-L1 antibody did not treat ID8agg, but adding IL2c generated complete tumor regressions and protective immune memory not achieved by either monotherapy. Similar anti-PD-L1 augmentation of IL2c and degradation of Treg functions were seen in subcutaneous B16 melanoma. Thus, IL2c is a multifunctional immunotherapy agent that stimulates immunity, reduces immunosuppression in a site-specific manner, and combines with other immunotherapies to treat distinct tumors in distinct anatomic compartments. Significance: These findings present CD122-targeted IL2 complexes as an advancement in cancer immunotherapy, as they reduce Treg immunosuppression, improve anticancer immunity, and boost PD-L1 immune checkpoint blockade efficacy in distinct tumors and anatomic locations.
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- 2020
23. Flexible Lead Bromide Perovskite Solar Cells
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Aijie Liu, Hua Wu, Yawen Liu, Erik M. J. Johansson, Huimin Zhu, Byeong Jo Kim, and Lin Yuan
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Fysikalisk kemi ,Solid-state chemistry ,FAPbBr(3) ,Materials science ,Doping ,Lead bromide ,Materialkemi ,Energy Engineering and Power Technology ,doping ,perovskite solar cells ,Physical Chemistry ,MACl ,Chemical engineering ,Materials Chemistry ,Electrochemistry ,MABr ,Chemical Engineering (miscellaneous) ,Electrical and Electronic Engineering ,flexible solar cells ,Perovskite (structure) - Abstract
Lead bromide perovskite solar cells (PSCs) have attracted increasing interest partly because of the high open-circuit voltage that has been obtained. Here, we present a simple way to prepare PSCs based on formamidinium lead tribromide, FAPbBr(3), by adding methylammonium chloride and methylammonium bromide into the precursor solution. With this method, high-quality and pin-hole free perovskite films with large crystal sizes were prepared. These additives result in a power conversion efficiency (PCE) of 7.9%, almost free of hysteresis, for a device on a rigid glass substrate. The first flexible lead bromide PSC is also prepared in this work and the flexible PSC exhibited a high PCE of 5.0%.
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- 2020
24. Thermo-economic analysis of a combined cooling, heating and power system based on self-evaporating liquid carbon dioxide energy storage
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Wenpan Xu, Pan Zhao, Feifei Gou, Aijie Liu, Wenze Wu, and Jiangfeng Wang
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General Energy ,Mechanical Engineering ,Building and Construction ,Management, Monitoring, Policy and Law - Published
- 2022
25. Performance analysis of a power generation system for pressure energy recovery at natural gas city gate stations
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Wenpan Xu, Pan Zhao, Feifei Gou, Aijie Liu, Wenze Wu, and Jiangfeng Wang
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Energy Engineering and Power Technology ,Industrial and Manufacturing Engineering - Published
- 2022
26. Natural history and genetic study of LAMA2-related muscular dystrophy in a large Chinese cohort
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Bing Mao, Dandan Tan, Bo Jin, Kai Gao, Chunde Li, Haipo Yang, Ying Zhu, Xiru Wu, Cuijie Wei, Zhen Huang, Shuo Wang, Anne Rutkowski, Xingzhi Chang, Yuwu Jiang, Xiaoli Zhang, Xueying Li, Ying Hua, Hui Xiong, Shuang Wang, Carsten G. Bönnemann, Juan Ding, Yanbin Fan, Yanjuan Wang, Lin Ge, Aijie Liu, Yun Yuan, Bingbing Zhang, Wenhua Zhu, Chengli Que, and Cheng Zhang
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0301 basic medicine ,China ,medicine.medical_specialty ,DNA Copy Number Variations ,Genotype ,Natural history ,Muscular Dystrophies ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,medicine ,Humans ,Missense mutation ,Pharmacology (medical) ,Copy-number variation ,LAMA2 ,Muscular dystrophy ,Child ,Genetics (clinical) ,Muscle contracture ,business.industry ,Research ,Infant ,General Medicine ,medicine.disease ,Rare diseases ,030104 developmental biology ,Muscular Dystrophies, Limb-Girdle ,Child, Preschool ,Cohort ,Congenital muscular dystrophy ,Medicine ,Laminin ,business ,030217 neurology & neurosurgery - Abstract
Background LAMA2-related muscular dystrophy including LAMA2-related congenital muscular dystrophy (LAMA2-CMD) and autosomal recessive limb-girdle muscular dystrophy-23 (LGMDR23) is caused by LAMA2 pathogenic variants. We aimed to describe the natural history and establish genotype–phenotype correlations in a large cohort of Chinese patients with LAMA2-related muscular dystrophy. Methods Clinical and genetic data of LAMA2-related muscular dystrophy patients enrolled from ten research centers between January 2003 and March 2021 were collected and analyzed. Results One hundred and thirty patients (116 LAMA2-CMD and 14 LGMDR23) were included. LAMA2-CMD group had earlier onset than LGMDR23 group. Head control, independent sitting and ambulation were achieved in 76.3%, 92.6% and 18.4% of LAMA2-CMD patients at median ages of 6.0 months (range 2.0–36.0 months), 11.0 months (range 6.0–36.0 months), and 27.0 months (range 18.0–84.0 months), respectively. All LGMDR23 patients achieved independent ambulation at median age of 18.0 months (range 13.0–20.0 months). Motor regression in LAMA2-CMD mainly occurred concurrently with rapid progression of contractures during 6–9 years old. Twenty-four LAMA2-related muscular dystrophy patients died, mostly due to severe pneumonia. Seizures occurred in 35.7% of LGMDR23 and 9.5% of LAMA2-CMD patients. Forty-six novel and 97 known LAMA2 disease-causing variants were identified. The top three high-frequency disease-causing variants in Han Chinese patients were c.7147C > T (p.R2383*), exon 4 deletion, and c.5156_5159del (p.K1719Rfs*5). In LAMA2-CMD, splicing variants tended to be associated with a relatively mild phenotype. Nonsense variants were more frequent in LAMA2-CMD (56.9%, 66/116) than in LGMDR23 (21.4%, 3/14), while missense disease-causing variants were more frequent in LGMDR23 (71.4%, 10/14) than in LAMA2-CMD (12.9%, 15/116). Copy number variations were identified in 26.4% of survivors and 50.0% of nonsurvivors, suggesting that copy number variations were associated with lower rate of survival (p = 0.029). Conclusions This study provides better understandings of natural history and genotype–phenotype correlations in LAMA2-related muscular dystrophy, and supports therapeutic targets for future researches.
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- 2021
27. Thousands of induced germline mutations affecting immune cells identified by automated meiotic mapping coupled with machine learning
- Author
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Sara Schneider, Xue Zhong, Emre E. Turer, Jeffrey A. SoRelle, Sydney Cooper, Miao Tang, Jamie Russell, Stephen Aplin Lyon, Xiaoming Zhan, Zhao Zhang, Priscilla Anderton, Katie Keller, Andrew Sakla, Jennifer Cardin, Bruce Beutler, Lei Sun, Jiexia Quan, Roxana Farokhnia, Sara Mazal, Carol Wise, Duanwu Zhang, Lijing Su, Jin Huk Choi, Qihua Sun, Baifang Qin, Braden Hayse, Hexin Shi, Brandon Nguyen, Xiaohong Li, Hannah Coco, Andrew Wadley, Darui Xu, Meron Tadesse, William McAlpine, Eva Marie Y. Moresco, Tao Yue, Gabrielle Coolbaugh, Ying Wang, Chun Hui Bu, Sara Hildebrand, Evan Nair-Gill, Rochelle Simpson, Elena Mahrt, Aijie Liu, Jonathan J. Rios, Jianhui Wang, Takuma Misawa, Edward Rodriguez, Sara Ludwig, Mihwa Choi, Lindsay Scott, Amanda Press, Dawson Medler, Tiffany Collie, and Kuan Wen Wang
- Subjects
Male ,0301 basic medicine ,Cosegregation ,Biology ,Quantitative trait locus ,medicine.disease_cause ,Germline ,Machine Learning ,Automation ,03 medical and health sciences ,0302 clinical medicine ,Germline mutation ,Gene mapping ,Leukocytes ,medicine ,Animals ,Gene ,Germ-Line Mutation ,Probability ,Genetics ,Mutation ,Multidisciplinary ,Reproducibility of Results ,Biological Sciences ,Flow Cytometry ,Phenotype ,Mice, Inbred C57BL ,Meiosis ,030104 developmental biology ,Female ,Algorithms ,Software ,030217 neurology & neurosurgery - Abstract
Forward genetic studies use meiotic mapping to adduce evidence that a particular mutation, normally induced by a germline mutagen, is causative of a particular phenotype. Particularly in small pedigrees, cosegregation of multiple mutations, occasional unawareness of mutations, and paucity of homozygotes may lead to erroneous declarations of cause and effect. We sought to improve the identification of mutations causing immune phenotypes in mice by creating Candidate Explorer (CE), a machine-learning software program that integrates 67 features of genetic mapping data into a single numeric score, mathematically convertible to the probability of verification of any putative mutation–phenotype association. At this time, CE has evaluated putative mutation–phenotype associations arising from screening damaging mutations in ∼55% of mouse genes for effects on flow cytometry measurements of immune cells in the blood. CE has therefore identified more than half of genes within which mutations can be causative of flow cytometric phenovariation in Mus musculus. The majority of these genes were not previously known to support immune function or homeostasis. Mouse geneticists will find CE data informative in identifying causative mutations within quantitative trait loci, while clinical geneticists may use CE to help connect causative variants with rare heritable diseases of immunity, even in the absence of linkage information. CE displays integrated mutation, phenotype, and linkage data, and is freely available for query online.
- Published
- 2021
28. Serum protein profiles suggest a possible link between qi deficiency constitution and Pi-qi-deficiency syndrome of chronic superficial gastritis
- Author
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Leiming You, Ting Wang, Aijie Liu, Anlong Xu, Xinhui Gao, Ting’an Li, Kunyu Li, Guangrui Huang, Xiaopu Sang, and Shen Zhang
- Subjects
0303 health sciences ,education.field_of_study ,Quantitative proteomics ,Population ,Serum protein ,Chronic superficial gastritis ,Computational biology ,Biology ,lcsh:RZ409.7-999 ,Immunoglobulin light chain ,030226 pharmacology & pharmacy ,03 medical and health sciences ,0302 clinical medicine ,Immune system ,Complementary and alternative medicine ,Pi ,KEGG ,education ,lcsh:Miscellaneous systems and treatments ,030304 developmental biology - Abstract
Objective: To identify potential serum protein candidates involved in linking the traditional Chinese medicine (TCM)-defined qi deficiency constitution (QDC) to Pi-qi-deficiency syndrome (PQDS) of chronic superficial gastritis (CSG). Methods: Using participants with the TCM-defined balanced constitution as a control population, label-free quantitative proteomics was adopted to identify differentially expressed proteins (DEPs) in serum samples from two case populations: case population 1 (participants with QDC) and case population 2 (patients with PQDS of CSG). The DEPs discovered in both case populations were analyzed to identify common DEPs as potential candidates for proteins involved in the link between QDC and PQDS. Based on Kyoto Encyclopedia of Genes and Genomes pathway (KEGG) and Gene Ontology (GO) enrichment analysis and analysis of protein–protein interaction networks, we evaluated the possible functions of these potential serum candidates. Results: We discovered 24 and 28 proteins that were differentially expressed in case populations 1 and 2, respectively, compared with the control population. Hierarchical clustering analysis showed that the expression profile of DEPs of individuals from the same population clustered well, while those from different populations were segregated. Furthermore, GO analysis revealed the 10 DEPs that were common to both case populations to be mainly associated with negative regulation of cellular metabolic and immune system processes while KEGG analysis indicated these proteins to be associated with complement and coagulation cascades and peroxisome proliferator-activated receptor signaling. Notably, serum levels of C4b-binding protein beta chain, glycosylphosphatidylinositol-specific phospholipase D1 and MS-F1 light chain variable region proteins were notably higher in the two case populations compared with the control, particularly in the case of CSG with PQDS. Conclusion: The results presented here provide new insights into the molecular mechanisms underlying development of PQDS of CSG from QDC, and suggest candidate serum biomarkers for future application in integrative medicine. Keywords: Qi deficiency constitution, Pi-qi-deficiency syndrome, Chronic superficial gastritis, Serum biomarker
- Published
- 2019
29. Ameliorative effect of sevoflurane on endoplasmic reticulum stress mediates cardioprotection against ischemia–reperfusion injury
- Author
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Lin-Zhang Li, De-zhang Zhu, Guo-Qiang Liu, Shiduan Wang, Aijie Liu, Chun-qin Chu, Chun-Xia Pang, and Yan Dong
- Subjects
Male ,Cardiotonic Agents ,Physiology ,Eukaryotic Initiation Factor-2 ,Ischemia ,Apoptosis ,Myocardial Reperfusion Injury ,030204 cardiovascular system & hematology ,Pharmacology ,Sevoflurane ,Rats, Sprague-Dawley ,eIF-2 Kinase ,03 medical and health sciences ,0302 clinical medicine ,In vivo ,Physiology (medical) ,medicine ,Animals ,Protein kinase B ,Cardioprotection ,Chemistry ,Myocardium ,Endoplasmic reticulum ,Heart ,General Medicine ,Endoplasmic Reticulum Stress ,medicine.disease ,Activating Transcription Factor 4 ,Coronary Vessels ,Rats ,030220 oncology & carcinogenesis ,Proto-Oncogene Proteins c-akt ,Signal Transduction ,medicine.drug - Abstract
We aimed to investigate whether the cardioprotection of sevoflurane against ischemia–reperfusion (IR) injury is via inhibiting endoplasmic reticulum stress. The rat in vivo model of myocardial IR injury was induced by ligation of the left anterior descending coronary artery. Sevoflurane significantly ameliorated the reduced cardiac function, increased infarct size, and elevated troponin I level and lactate dehydrogenase activity in plasma induced by IR injury. Sevoflurane suppressed the IR-induced myocardial apoptosis. The increased protein levels of glucose-regulated protein 78 and C/EBP homologous protein (CHOP) after myocardial IR were significantly reduced by sevoflurane. The protein levels of phosphorylated protein kinase RNA-like endoplasmic reticulum kinase (PERK), phosphorylated eukaryotic initiation factor 2 (eIF2α), and activating transcription factor 4 (ATF4) were significantly increased in rats with IR and attenuated by sevoflurane treatment. The phosphorylation of Akt was further activated by sevoflurane. The cardioprotection of sevoflurane could be blocked by wortmannin, a PI3K/Akt inhibitor. Our results suggest that the cardioprotection of sevoflurane against IR injury might be mediated by suppressing PERK/eIF2a/ATF4/CHOP signaling via activating the Akt pathway, which helps in understanding the novel mechanism of the cardioprotection of sevoflurane.
- Published
- 2019
30. A combined heating and power system based on compressed carbon dioxide energy storage with carbon capture: Exploring the technical potential
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Wenpan Xu, Pan Zhao, Feifei Gou, Wenze Wu, Aijie Liu, and Jiangfeng Wang
- Subjects
Fuel Technology ,Nuclear Energy and Engineering ,Renewable Energy, Sustainability and the Environment ,Energy Engineering and Power Technology - Published
- 2022
31. Muscle magnetic resonance imaging in patients with LAMA2-related muscular dystrophy
- Author
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Ying Zhu, Yanbin Fan, Haipo Yang, Jiangxi Xiao, Hui Xiong, Aijie Liu, Cuijie Wei, Dandan Tan, and Lin Ge
- Subjects
musculoskeletal diseases ,Male ,Adolescent ,Hamstring Muscles ,Biceps ,Quadriceps Muscle ,Atrophy ,Edema ,medicine ,Humans ,Muscular dystrophy ,Child ,Muscle, Skeletal ,Genetics (clinical) ,medicine.diagnostic_test ,business.industry ,Magnetic resonance imaging ,Anatomy ,musculoskeletal system ,medicine.disease ,Magnetic Resonance Imaging ,Neurology ,Lower Extremity ,Muscular Dystrophies, Limb-Girdle ,Thigh ,Child, Preschool ,Pediatrics, Perinatology and Child Health ,Congenital muscular dystrophy ,Female ,Neurology (clinical) ,Fatty infiltration ,medicine.symptom ,Differential diagnosis ,business - Abstract
LAMA2-related muscular dystrophy (LAMA2-MD) is classified into congenital muscular dystrophy type 1A (MDC1A) and autosomal recessive limb-girdle muscular dystrophy-23 (LGMDR23). The purpose of this study was to identify the involvement pattern of thigh muscles of LAMA2-MD patients on magnetic resonance imaging. Fourteen MDC1A and 3 LGMDR23 patients were included, with 21 known and 8 novel LAMA2 disease-causing variants. In LAMA2-MD, the gluteus maximus, anterior (quadriceps femoris) and posterior (adductor magnus and biceps femoris) thigh muscles were extensively and severely affected with fatty infiltration, with relatively sparing of the adductor longus. The pattern of muscle involvement was similar between MDC1A and LGMDR23, but more severe in MDC1A, as well as in LAMA2-MD patients without ambulation. The rather peculiar pattern of the adductor magnus and long head of the biceps femoris first and severely affected in the mid-thigh level was found in LGMDR23. Strong correlation between fatty infiltration and age as well as disease duration was observed for the adductor longus in MDC1A. Edema and atrophy selectively involved in some muscles. The pattern of fatty infiltration on thigh muscle MRI of LAMA2-MD could provide important information for the diagnosis, differential diagnosis and assessment of clinical severity.
- Published
- 2021
32. Characterization of an Antiviral Component in Human Seminal Plasma
- Author
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Baoxing Liu, Ran Chen, Xiaoqin Yu, Wei Lu, Aijie Liu, Ruiqin Han, Yongmei Chen, Fei Wang, Maolei Gong, Song Chen, Han Wu, Daishu Han, Weihua Liu, Wenjing Zhang, and Yunxiao Gao
- Subjects
lcsh:Immunologic diseases. Allergy ,Male ,Sexual transmission ,prostate fluid ,viruses ,Immunology ,Mumps virus ,Biology ,Dengue virus ,medicine.disease_cause ,Antiviral Agents ,Virus ,HeLa ,Seminal vesicle ,Semen ,Cell Line, Tumor ,Chlorocebus aethiops ,medicine ,Animals ,Humans ,Immunology and Allergy ,antiviral factor ,Vero Cells ,Cells, Cultured ,Original Research ,Epithelial Cells ,biology.organism_classification ,Virology ,sexual transmission ,Mice, Inbred C57BL ,Herpes simplex virus ,medicine.anatomical_structure ,Cell culture ,Host-Pathogen Interactions ,Viruses ,seminal plasma ,lcsh:RC581-607 ,HeLa Cells - Abstract
Numerous types of viruses have been found in human semen, which raises concerns about the sexual transmission of these viruses. The overall effect of semen on viral infection and transmission have yet to be fully investigated. In the present study, we aimed at the effect of seminal plasma (SP) on viral infection by focusing on the mumps viral (MuV) infection of HeLa cells. MuV efficiently infected HeLa cells in vitro. MuV infection was strongly inhibited by the pre-treatment of viruses with SP. SP inhibited MuV infection through the impairment of the virus’s attachment to cells. The antiviral activity of SP was resistant to the treatment of SP with boiling water, Proteinase K, RNase A, and DNase I, suggesting that the antiviral factor would not be proteins and nucleic acids. PNGase or PLA2 treatments did not abrogate the antiviral effect of SP against MuV. Further, we showed that the prostatic fluid (PF) showed similar inhibition as SP, whereas the epididymal fluid and seminal vesicle extract did not inhibit MuV infection. Both SP and PF also inhibited MuV infection of other cell types, including another human cervical carcinoma cell line C33a, mouse primary epididymal epithelial cells, and Sertoli cell line 15P1. Moreover, this inhibitory effect was not specific to MuV, as the herpes simplex virus 1, dengue virus 2, and adenovirus 5 infections were also inhibited by SP and PF. Our findings suggest that SP contains a prostate-derived pan-antiviral factor that may limit the sexual transmission of various viruses.
- Published
- 2021
33. Candidate Explorer: a tool for discovery, evaluation, and display of mutations causing significant immune phenotypes
- Author
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Priscilla Anderton, Stephen Aplin Lyon, Zhao Zhang, Takuma Misawa, Meron Tadesse, Duanwu Zhang, Tao Yue, Miao Tang, Lindsay Scott, Jeffrey A. SoRelle, Hexin Shi, Jennifer Cardin, Sydney Cooper, Jiexia Quan, Jin Huk Choi, Nathan Stewart, Emre E. Turer, Chun Hui Bu, Sara Schneider, Xue Zhong, Dawson Medler, Katie Keller, Alexyss Johnson, Brandon Nguyen, Darui Xu, Braden Hayse, Bruce Beutler, Lei Sun, Jianhui Wang, Evan Nair-Gill, Edward Rodriguez, Aijie Liu, Sara Hildebrand, Qihua Sun, Andrew Wadley, Sara Mazal, Xiaohong Li, Gabrielle Coolbaugh, Ying Wang, Rochelle Simpson, Eva Marie Y. Moresco, John Santoyo, Baifang Qin, Roxana Farokhnia, Andrew Sakla, Amy Bronikowski, and Hannah Coco
- Subjects
Genetics ,Linkage (software) ,Mutation ,Immune system ,Software tool ,medicine ,Biology ,Quantitative trait locus ,medicine.disease_cause ,Gene ,Phenotype ,Selection (genetic algorithm) - Abstract
When applied to immunity, forward genetic studies use meiotic mapping to provide strong statistical evidence that a particular mutation is causative of a particular immune phenotype. Notwithstanding this, co-segregation of multiple mutations, occasional unawareness of mutations, and paucity of homozygotes may lead to erroneous declarations of cause and effect. We sought to improve the selection of authentic causative mutations using a machine learning software tool, Candidate Explorer (CE), which integrates 65 data features into a single numeric score, mathematically convertible to the likelihood of verification of any putative mutation-phenotype association. CE has identified most genes within which mutations can be causative of flow cytometric phenovariation in Mus musculus. The majority of these genes were not previously known to support immune function or homeostasis. Mouse geneticists will find CE data informative in identifying causative mutations within quantitative trait loci, while clinical geneticists may use CE to help connect causative variants with rare heritable diseases of immunity, even in the absence of linkage information. CE displays integrated mutation, phenotype, and linkage data, and is freely available for query online.
- Published
- 2020
34. Mechanism of negative regulation of NF-κB by N4BP1
- Author
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Miao Tang, Sara Hildebrand, Priscilla Anderton, Xiaoming Zhan, Jiexia Quan, Sara Ludwig, Bruce Beutler, Lei Sun, Eva Marie Y. Moresco, Hexin Shi, Aijie Liu, Ying Wang, and Xiaohong Li
- Subjects
TLR2 ,chemistry.chemical_compound ,Ubiquitin ,biology ,TRIF ,Chemistry ,Kinase ,biology.protein ,NF-κB ,Caspase 8 ,Caspase ,Proinflammatory cytokine ,Cell biology - Abstract
Many immune responses depend upon activation of NF-κB, a key transcription factor in the elicitation of a cytokine response. Here we demonstrate that N4BP1 inhibited TLR-dependent activation of NF-κB by interacting with the NF-κB signaling essential modulator (NEMO, also known as IκB kinase γ) to attenuate NEMO-NEMO dimerization or oligomerization. The UBA-like (ubiquitin associated-like) and CUE-like (ubiquitin conjugation to ER degradation) domains in N4BP1 mediated the interaction with the NEMO COZI domain. Both in vitro and in mice, N4bp1 deficiency specifically enhanced TRIF-independent (TLR2, TLR7, or TLR9-mediated), but not TRIF-dependent (TLR3 or TLR4-mediated), NF-κB activation leading to increased production of proinflammatory cytokines. In response to TLR4 or TLR3 activation, TRIF caused activation of caspase 8, which cleaved N4BP1 distal to residues D424 and D490 and abolished its inhibitory effect. N4bp1-/- mice also exhibited diminished numbers of T cells in the peripheral blood. Our work identifies N4BP1 as an inhibitory checkpoint protein that must be overcome to activate NF-κB, and a TRIF-initiated caspase 8-dependent mechanism by which this is accomplished.
- Published
- 2020
35. The clinical outcome and neuroimaging of acute encephalopathy after status epilepticus in Dravet syndrome
- Author
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Xiaoling Yang, Xiaoyan Liu, Xiru Wu, Yuehua Zhang, Xiaojuan Tian, Qi Zeng, Jintang Ye, Zhixian Yang, Jing Zhang, and Aijie Liu
- Subjects
Male ,Pediatrics ,medicine.medical_specialty ,Acute encephalopathy ,Epilepsies, Myoclonic ,Status epilepticus ,03 medical and health sciences ,Status Epilepticus ,0302 clinical medicine ,Developmental Neuroscience ,Neuroimaging ,Dravet syndrome ,030225 pediatrics ,Image Processing, Computer-Assisted ,medicine ,Humans ,Age of Onset ,Child ,Coma ,Brain Diseases ,medicine.diagnostic_test ,business.industry ,Mortality rate ,Infant ,Magnetic resonance imaging ,medicine.disease ,Magnetic Resonance Imaging ,Child, Preschool ,Pediatrics, Perinatology and Child Health ,Female ,Neurology (clinical) ,medicine.symptom ,Age of onset ,business ,030217 neurology & neurosurgery - Abstract
Aim To analyze the clinical outcome and neuroimaging over a long duration follow-up in the currently largest series of acute encephalopathy after status epilepticus in patients with Dravet syndrome. Method Clinical and neuroimaging data of patients with Dravet syndrome with a history of acute encephalopathy (coma >24h) after status epilepticus from February 2005 to December 2016 at Peking University First Hospital were reviewed retrospectively. Results Thirty-five patients (15 males, 20 females) with a history of acute encephalopathy were enrolled from a total of 624 patients with Dravet syndrome (5.6%). The median onset age of acute encephalopathy was 3 years 1 month. The duration of status epilepticus varied between 40 minutes to 12 hours. Thirty-four patients had a high fever when status epilepticus occurred, and only one had a normal temperature. Coma lasted from 2 to 20 days. Twelve patients died and 23 survived with massive neurological regression. The median follow-up time was 2 years 1 month. Neuroimaging of 20 out of 23 survivors during the recovery phase showed diverse degrees of cortical atrophy with or without subcortical lesions. Interpretation Acute encephalopathy after status epilepticus is more prone to occur in patients with Dravet syndrome who had a high fever. The mortality rate is high in severe cases. Survivors are left with severe neurological sequelae but often with either no seizure or low seizure frequency. What this paper adds Acute encephalopathy is more prone to occur in patients with Dravet syndrome with a high fever. The mortality rate is high for acute encephalopathy after status epilepticus in patients with Dravet syndrome. Survivors have neurological sequelae.
- Published
- 2018
36. Methylammonium Bromide Assisted Crystallization for Enhanced Lead‐Free Double Perovskite Photovoltaic Performance
- Author
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Hua Wu, Yunfei Wang, Aijie Liu, Junxin Wang, Byeong Jo Kim, Yawen Liu, Yuan Fang, Xiaoliang Zhang, Gerrit Boschloo, and Erik M. J. Johansson
- Subjects
Biomaterials ,trap site density ,solar cells ,Cs2AgBiBr6 ,Materials Chemistry ,Electrochemistry ,Materialkemi ,lead-free double perovskites ,Condensed Matter Physics ,power conversion efficiency ,Electronic, Optical and Magnetic Materials - Abstract
Cs2AgBiBr6, has recently gained wide attention as a possible alternative to lead-halide perovskites, considering the nontoxicity and improved stability. However, this double perovskite suffers from defects, especially deep electron traps, severely hampering the photovoltaic performance. This work reports a simple method to control the double perovskite crystallization by adding volatile salts into the precursor solution. X-ray diffraction patterns reveal that the organic cation with suitable radius (such as methylammonium, MA(+)) is introduced into the perovskite lattice, forming an organic/inorganic mixed double perovskite intermediate phase. The organic salt is thereafter fully evaporated during high temperature annealing, and the all-inorganic double perovskite is obtained with dense surface and less pin-holes. From optical and electrical characterization, it is concluded that the Cs2AgBiBr6 film exhibits high quality, with higher light absorptance and emission. Reduced trap density and longer carrier lifetime are also observed. The improved Cs2AgBiBr6 film is beneficial for efficient carrier collection with suppressed defect-assisted recombination. With this strategy, a power conversion efficiency (PCE) of 2.53% is achieved for the champion Cs2AgBiBr6-based solar cell device, which is significantly higher compared to the control device with 1.43% PCE. This work is therefore helpful for further improvement of inorganic lead-free perovskite materials for optoelectronic applications.
- Published
- 2021
37. Biphasic Rapamycin Effects in Lymphoma and Carcinoma Treatment
- Author
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Alvaro Padron, Srilakshmi Pandeswara, Yang Liu, Tyler J. Curiel, Aijie Liu, Vinh Dao, Justin M. Drerup, Vincent Hurez, and Shunhua Lao
- Subjects
Male ,0301 basic medicine ,Cancer Research ,medicine.medical_specialty ,Recombinant Fusion Proteins ,T-Lymphocytes ,Biology ,Lymphocyte Activation ,Lymphoma, T-Cell ,Jurkat cells ,Article ,Jurkat Cells ,Mice ,03 medical and health sciences ,0302 clinical medicine ,Denileukin diftitox ,In vivo ,Cell Line, Tumor ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Animals ,Humans ,Diphtheria Toxin ,IL-2 receptor ,PI3K/AKT/mTOR pathway ,Cell Proliferation ,Mice, Knockout ,Sirolimus ,Antibiotics, Antineoplastic ,Flow Cytometry ,medicine.disease ,Lymphoma ,Mice, Inbred C57BL ,Disease Models, Animal ,030104 developmental biology ,Endocrinology ,Oncology ,Cell culture ,030220 oncology & carcinogenesis ,Cancer research ,Interleukin-2 ,Immunotherapy ,CD8 ,medicine.drug - Abstract
mTOR drives tumor growth but also supports T-cell function, rendering the applications of mTOR inhibitors complex especially in T-cell malignancies. Here, we studied the effects of the mTOR inhibitor rapamycin in mouse EL4 T-cell lymphoma. Typical pharmacologic rapamycin (1–8 mg/kg) significantly reduced tumor burden via direct suppression of tumor cell proliferation and improved survival in EL4 challenge independent of antitumor immunity. Denileukin diftitox (DD)–mediated depletion of regulatory T cells significantly slowed EL4 growth in vivo in a T-cell–dependent fashion. However, typical rapamycin inhibited T-cell activation and tumor infiltration in vivo and failed to boost DD treatment effects. Low-dose (LD) rapamycin (75 μg/kg) increased potentially beneficial CD44hiCD62L+ CD8+ central memory T cells in EL4 challenge, but without clinical benefit. LD rapamycin significantly enhanced DD treatment efficacy, but DD plus LD rapamycin treatment effects were independent of antitumor immunity. Instead, rapamycin upregulated EL4 IL2 receptor in vitro and in vivo, facilitating direct DD tumor cell killing. LD rapamycin augmented DD efficacy against B16 melanoma and a human B-cell lymphoma, but not against human Jurkat T-cell lymphoma or ID8agg ovarian cancer cells. Treatment effects correlated with IL2R expression, but mechanisms in some tumors were not fully defined. Overall, our data define a distinct, biphasic mechanisms of action of mTOR inhibition at doses that are clinically exploitable, including in T-cell lymphomas. Cancer Res; 77(2); 520–31. ©2016 AACR.
- Published
- 2017
38. The clinical spectrum of female epilepsy patients withPCDH19mutations in a Chinese population
- Author
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Yuwu Jiang, Xiaoling Yang, Xiaoyan Liu, Yuehua Zhang, Liping Wei, Xiru Wu, Ye Wu, Zhixian Yang, Xiaojing Xu, and Aijie Liu
- Subjects
0301 basic medicine ,Proband ,Genetics ,Pediatrics ,medicine.medical_specialty ,Chinese population ,Mutation ,business.industry ,medicine.disease ,medicine.disease_cause ,Asymptomatic ,03 medical and health sciences ,Epilepsy ,030104 developmental biology ,0302 clinical medicine ,Dravet syndrome ,medicine ,Autism ,Family history ,medicine.symptom ,business ,030217 neurology & neurosurgery ,Genetics (clinical) - Abstract
Mutations in PCDH19, which encodes protocadherin 19, have been identified in epilepsy, mainly in affected females. We summarized the clinical spectrum of female epilepsy patients with PCDH19 mutations in a Chinese population. We screened for PCDH19 mutations in 75 girls diagnosed as Dravet Syndrome (DS) without a SCN1A mutation and 29 girls with fever-sensitive and cluster seizures. We identified 11 novel and 7 reported mutations in 21 of 104 probands (20.2%), including 6 (6/75, 8%) DS girls and 15 (15/29, 51.7%) girls with fever-sensitive epilepsy. The mutations were inherited in 9 probands, de novo in 11, and undetermined in the remaining patient. Shared clinical features included early onset seizures (5–18 months), seizures sensitive to fever, focal seizures or generalized tonic-clonic seizures in clusters and brief seizures. Mental retardation was present in 17 probands. Three patients had features of autism. Two of the nine probands with inherited mutations had no family history of epilepsy, one inherited the mutation from her transmitting father and the other inherited from her asymptomatic mother. Our results confirmed that the clinical spectrum of PCDH19 mutations includes female DS patients, epilepsy and mental retardation limited to females, epilepsy with normal development and asymptomatic female carriers.
- Published
- 2016
39. CHD2-related epilepsy: novel mutations and new phenotypes
- Author
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Qi Zeng, Xiaoling Yang, Jiaoyang Chen, Zhixian Yang, Xiru Wu, Liping Zhang, Yuehua Zhang, Jing Zhang, Aijie Liu, and Hua Li
- Subjects
Male ,030506 rehabilitation ,Pediatrics ,medicine.medical_specialty ,Genotype ,Developmental Disabilities ,03 medical and health sciences ,Epilepsy ,0302 clinical medicine ,Genotype-phenotype distinction ,Developmental Neuroscience ,medicine ,Humans ,Child ,Exome sequencing ,business.industry ,Brain ,Infant ,West Syndrome ,medicine.disease ,Pedigree ,DNA-Binding Proteins ,Epileptic spasms ,Phenotype ,CHD2 ,Child, Preschool ,Pediatrics, Perinatology and Child Health ,Mutation ,Autism ,Female ,Neurology (clinical) ,0305 other medical science ,business ,Spasms, Infantile ,030217 neurology & neurosurgery - Abstract
The aim of this report was to refine the genotypes and phenotypes of chromodomain helicase DNA-binding protein 2 (CHD2)-related epilepsy. Seventeen patients with CHD2 mutations were enrolled. CHD2 mutations were identified by application of next-generation sequencing of epilepsy or whole exome sequencing. Sixteen mutations were identified, among which 15 have not yet been reported. Thirteen mutations were de novo. Age at seizure onset ranged from 3 months to 10 years 5 months. Seizures observed were generalized tonic-clonic, myoclonic, atonic, atypical absence, focal, and myoclonic-atonic. Epileptic spasms occurred in two patients. Developmental disability was present in 14 patients. Autism features were observed in seven patients. Video electroencephalogram was abnormal in 15 patients. Five patients were diagnosed with non-specific epileptic encephalopathy, two with epilepsy with myoclonic-atonic seizures, two with Lennox-Gastaut syndrome, two with febrile seizures plus, and one with West syndrome. Seizures were controlled in nine patients. Q1392TfsX17 may be a hot-spot mutation of CHD2. West syndrome was observed as a new phenotype of CHD2 mutation. The severity of the phenotypes of CHD2 mutations ranged from mild febrile seizures to severe epileptic encephalopathy. WHAT THIS PAPER ADDS: Q1392TfsX17 maybe the hot-spot mutation of CHD2. West syndrome could be a new phenotype of CHD2 mutation.CHD2基因突变相关癫痫的新突变和新表型: 本文研究的目的是总结CHD2基因突变相关癫痫的基因型和表型特点。采用靶向捕获二代测序癫痫基因检测包或全外显子组测序的方法发现17例患儿携带CHD2基因突变,共包括16种突变,其中15种为新突变,13种为新生突变。癫痫发作起病年龄为生后3个月-10岁5个月。病程中出现的发作类型包括全面强直阵挛发作、肌阵挛发作、失张力发作、不典型失神、局灶性发作和肌阵挛-失张力发作。2例患儿出现痉挛发作。14例患儿有不同程度的运动、智力发育落后,7例有孤独症样表现。15例患儿脑电图异常。癫痫综合征诊断符合非特异性早发癫痫性脑病5例,癫痫伴肌阵挛-失张力发作2例,Lennox-Gastaut综合征2例,热性惊厥附加症2例,婴儿痉挛症1例。9例患儿发作控制。 Q1392TfsX17 可能是CHD2基因的热点突变。婴儿痉挛症是CHD2基因突变相关癫痫的新表型。CHD2基因突变相关癫痫既可见于较轻的热性惊厥,也可以见于严重的癫痫性脑病。.
- Published
- 2019
40. Mutual inhibition between Prkd2 and Bcl6 controls T follicular helper cell differentiation
- Author
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Evan Nair-Gill, Aijie Liu, Jeffrey A. SoRelle, Jamie Russell, Koichi Tabeta, Jin Huk Choi, Tao Yue, Liyang Yu, Eva Marie Y. Moresco, Lijing Su, Miao Tang, Feiya Ou, Takuma Misawa, Anne R. Murray, Bruce Beutler, Sara Hildebrand, Subhajit Poddar, Emre E. Turer, Xiaohong Li, Sara Ludwig, Xiaoming Zhan, Kuan Wen Wang, William McAlpine, Jianhui Wang, and Bret M. Evers
- Subjects
0301 basic medicine ,CD4-Positive T-Lymphocytes ,Male ,Cellular differentiation ,Immunology ,Immunoglobulins ,Mice, Transgenic ,Immunoglobulin E ,Immunotherapy, Adoptive ,Article ,03 medical and health sciences ,0302 clinical medicine ,immune system diseases ,hemic and lymphatic diseases ,medicine ,Animals ,Humans ,B cell ,Bone Marrow Transplantation ,B-Lymphocytes ,T follicular helper cell differentiation ,biology ,Chemistry ,Germinal center ,Cell Differentiation ,General Medicine ,Acquired immune system ,BCL6 ,Germinal Center ,Molecular biology ,030104 developmental biology ,medicine.anatomical_structure ,HEK293 Cells ,030220 oncology & carcinogenesis ,Mutation ,biology.protein ,Proto-Oncogene Proteins c-bcl-6 ,Female ,Antibody ,Protein Kinases ,Protein Kinase D2 - Abstract
T follicular helper cells (TFH) participate in germinal center (GC) development and are necessary for B cell production of high-affinity, isotype-switched antibodies. In a forward genetic screen, we identified a missense mutation in Prkd2, encoding the serine/threonine kinase protein kinase D2, which caused elevated titers of immunoglobulin E (IgE) in the serum. Subsequent analysis of serum antibodies in mice with a targeted null mutation of Prkd2 demonstrated polyclonal hypergammaglobulinemia of IgE, IgG1, and IgA isotypes, which was exacerbated by the T cell-dependent humoral response to immunization. GC formation and GC B cells were increased in Prkd2-/- spleens. These effects were the result of excessive cell-autonomous TFH development caused by unrestricted Bcl6 nuclear translocation in Prkd2-/- CD4+ T cells. Prkd2 directly binds to Bcl6, and Prkd2-dependent phosphorylation of Bcl6 is necessary to constrain Bcl6 to the cytoplasm, thereby limiting TFH development. In response to immunization, Bcl6 repressed Prkd2 expression in CD4+ T cells, thereby committing them to TFH development. Thus, Prkd2 and Bcl6 form a mutually inhibitory positive feedback loop that controls the stable transition from naive CD4+ T cells to TFH during the adaptive immune response.
- Published
- 2019
41. Pattern recognition receptor-mediated innate immune responses in seminal vesicle epithelial cell and their impacts on cellular function†
- Author
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Yongmei Chen, Xiaoqin Yu, Aijie Liu, Daishu Han, Fei Wang, Weihua Liu, Han Wu, Ran Chen, Maolei Gong, Wenjing Zhang, and Ruiqin Han
- Subjects
0301 basic medicine ,Male ,Chemokine ,Mice, 129 Strain ,Biology ,03 medical and health sciences ,Mice ,0302 clinical medicine ,Seminal vesicle ,medicine ,CXCL10 ,Animals ,Receptor ,Cells, Cultured ,Inflammation ,Mice, Knockout ,Innate immune system ,Monocyte ,Pattern recognition receptor ,Seminal Vesicles ,Epithelial Cells ,Cell Biology ,General Medicine ,Immunity, Innate ,Cell biology ,Mice, Inbred C57BL ,030104 developmental biology ,medicine.anatomical_structure ,Poly I-C ,Reproductive Medicine ,Receptors, Pattern Recognition ,biology.protein ,030217 neurology & neurosurgery ,Interferon regulatory factors ,Signal Transduction - Abstract
The seminal vesicles can be infected by microorganisms, thereby resulting in vesiculitis and impairment in male fertility. Innate immune responses in seminal vesicles cells to microbial infections, which facilitate vesiculitis, have yet to be investigated. The present study aims to elucidate pattern recognition receptor–mediated innate immune responses in seminal vesicles epithelial cells. Various pattern recognition receptors, including Toll-like receptor 3, Toll-like receptor 4, cytosolic ribonucleic acid, and deoxyribonucleic acid sensors, are abundantly expressed in seminal vesicles epithelial cells. These pattern recognition receptors can recognize their respective ligands, thus activating nuclear factor kappa B and interferon regulatory factor 3. The pattern recognition receptor signaling induces expression of pro-inflammatory cytokines, such as tumor necrosis factor alpha (Tnfa) and interleukin 6 (Il6), chemokines monocyte chemoattractant protein-1 (Mcp1) and C–X–C motif chemokine 10 (Cxcl10), and type 1 interferons Ifna and Ifnb. Moreover, pattern recognition receptor-mediated innate immune responses up-regulated the expression of microsomal prostaglandin E synthase and cyclooxygenase 2, but they down-regulated semenogelin-1 expression. These results provide novel insights into the mechanism underlying vesiculitis and its impact on the functions of the seminal vesicles.
- Published
- 2019
42. Excessive endosomal TLR signaling causes inflammatory disease in mice with defective SMCR8-WDR41-C9ORF72 complex function
- Author
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Jamie Russell, Eva Marie Y. Moresco, William McAlpine, Sarah Grace McAlpine, Emre E. Turer, Jianhui Wang, Miguel San Miguel, Xue Zhong, Braden Hayse, Bruce Beutler, Lei Sun, Ruchi Jain, Jin Huk Choi, Mihwa Choi, Aijie Liu, Xiaohong Li, Miao Tang, Zhao Zhang, Kuan Wen Wang, Sara Ludwig, and Xiaoming Zhan
- Subjects
0301 basic medicine ,Phagocytosis ,Autophagy-Related Proteins ,Inflammation ,medicine.disease_cause ,Autoimmune Diseases ,Proinflammatory cytokine ,Autoimmunity ,Mice ,03 medical and health sciences ,Phagosome maturation ,medicine ,Animals ,Mice, Knockout ,Toll-like receptor ,Multidisciplinary ,C9orf72 Protein ,Chemistry ,Dextran Sulfate ,Toll-Like Receptors ,Intracellular Signaling Peptides and Proteins ,Colitis ,Hematopoiesis ,Cell biology ,TLR2 ,030104 developmental biology ,PNAS Plus ,Gene Expression Regulation ,Mutation ,TLR4 ,medicine.symptom ,Carrier Proteins ,Signal Transduction - Abstract
The SMCR8-WDR41-C9ORF72 complex is a regulator of autophagy and lysosomal function. Autoimmunity and inflammatory disease have been ascribed to loss-of-function mutations of Smcr8 or C9orf72 in mice. In humans, autoimmunity has been reported to precede amyotrophic lateral sclerosis caused by mutations of C9ORF72. However, the cellular and molecular mechanisms underlying autoimmunity and inflammation caused by C9ORF72 or SMCR8 deficiencies remain unknown. Here, we show that splenomegaly, lymphadenopathy, and activated circulating T cells observed in Smcr8(−/−) mice were rescued by triple knockout of the endosomal Toll-like receptors (TLRs) TLR3, TLR7, and TLR9. Myeloid cells from Smcr8(−/−) mice produced excessive inflammatory cytokines in response to endocytosed TLR3, TLR7, or TLR9 ligands administered in the growth medium and in response to TLR2 or TLR4 ligands internalized by phagocytosis. These defects likely stem from prolonged TLR signaling caused by accumulation of LysoTracker-positive vesicles and by delayed phagosome maturation, both of which were observed in Smcr8(−/−) macrophages. Smcr8(−/−) mice also showed elevated susceptibility to dextran sodium sulfate-induced colitis, which was not associated with increased TLR3, TLR7, or TLR9 signaling. Deficiency of WDR41 phenocopied loss of SMCR8. Our findings provide evidence that excessive endosomal TLR signaling resulting from prolonged ligand–receptor contact causes inflammatory disease in SMCR8-deficient mice.
- Published
- 2018
43. Self-Assembly of Proteins: Towards Supramolecular Materials
- Author
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Jeroen J. L. M. Cornelissen, Pascal Jonkheijm, Shuqin Cao, Liulin Yang, Aijie Liu, Rindia M. Putri, Biomolecular Nanotechnology, Molecular Nanofabrication, and Faculty of Science and Technology
- Subjects
Models, Molecular ,Scaffold ,Chemistry ,Organic Chemistry ,Supramolecular chemistry ,Proteins ,RNA ,Nanotechnology ,Chemical conjugation ,02 engineering and technology ,General Chemistry ,010402 general chemistry ,021001 nanoscience & nanotechnology ,01 natural sciences ,Catalysis ,0104 chemical sciences ,Native protein ,DNA origami ,Peptides ,0210 nano-technology - Abstract
The study of protein self-assembly has attracted great interest over the decades, due to the important role that proteins play in life. In contrast to the major achievements that have been made in the fields of DNA origami, RNA, and synthetic peptides, methods for the design of self-assembling proteins have progressed more slowly. This Concept article provides a brief overview of studies on native protein and artificial scaffold assemblies and highlights advances in designing self-assembling proteins. The discussions are focused on design strategies for self-assembling proteins, including protein fusion, chemical conjugation, supramolecular, and computational-aided de novo design.
- Published
- 2016
44. Highly secretory expression of recombinant cowpea chlorotic mottle virus capsid proteins in Pichia pastoris and in-vitro encapsulation of ruthenium nanoparticles for catalysis
- Author
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Kun Yang, Linsong Yang, Qinghuan Zhao, Aijie Liu, Jie Zhu, Xiaoxue Lu, and Biomolecular Nanotechnology
- Subjects
0106 biological sciences ,Viral protein ,Metal Nanoparticles ,chemistry.chemical_element ,Capsules ,Hybrid nanocatalyst ,4-Nitrophenol reduction ,medicine.disease_cause ,01 natural sciences ,Catalysis ,Ruthenium ,Pichia pastoris ,law.invention ,03 medical and health sciences ,Reaction rate constant ,law ,010608 biotechnology ,medicine ,Cowpea chlorotic mottle virus ,Secretion ,030304 developmental biology ,0303 health sciences ,biology ,Virus-like particles ,biology.organism_classification ,Bromovirus ,Recombinant Proteins ,n/a OA procedure ,Capsid ,chemistry ,Saccharomycetales ,Recombinant DNA ,Capsid Proteins ,Biotechnology ,Nuclear chemistry - Abstract
The applications of viral protein cages have expanded rapidly into the fields of bionanotechnology and materials science. However, the low-cost production of viral capsid proteins (CPs) on a large scale is always a challenge. Herein, we develop a highly efficient expression system by constructing recombinant Pichia pastoris cells as a “factory” for the secretion of soluble cowpea chlorotic mottle virus (CCMV) CPs. Under optimal induction conditions (0.9 mg/mL of methanol concentration at 30 °C for 96 h), a high yield of approximately 95 mg/L of CCMV CPs was harvested from the fermentation supernatant with CPs purity >90%, which has significantly simplified the rest of the purification process. The resultant CPs are employed to encapsulate Ruthenium (Ru) nanoparticles (NPs) via in-vitro self-assembly to prepare hybrid nanocatalyst, i.e. Ru@virus-like particles (VLPs). The catalytic activity over Ru@VLPs was evaluated by reducing 4-nitrophenol (4-NP) to 4-aminophenol (4-AP). The results indicate that, with the protection of protein cages, Ru NPs were highly stabilized during the catalytic reaction. This results in enhanced catalytic activity (reaction rate constant k = 0.14 min−1) in comparison with unsupported citrate-stabilized Ru NPs (Ru-CA) (k = 0.08 min−1). Additionally, comparatively lower activation energy over Ru@VLPs (approximately 32 kJ/mol) than that over Ru-CA (approximately 39 kJ/mol) could be attributed to the synergistic effect between Ru NPs and some functional groups such as amino groups (–NH2) on CPs that weakened the activation barrier of 4-NP reduction. Therefore, enhanced activity and decreased activation energy over Ru@VLPs demonstrated the superiority of Ru@VLPs to unsupported Ru-CA.
- Published
- 2020
45. Damaged male germ cells induce epididymitis in mice
- Author
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Fei Wang, Wenjing Zhang, Weihua Liu, Maolei Gong, Xiaoqin Yu, Aijie Liu, Daishu Han, Ruiqin Han, Ran Chen, Yongmei Chen, and Han Wu
- Subjects
Male ,Chemokine ,Urology ,Interleukin-1beta ,030232 urology & nephrology ,lcsh:RC870-923 ,male infertility ,Mice ,03 medical and health sciences ,0302 clinical medicine ,Cell Movement ,medicine ,Animals ,CXCL10 ,busulfan ,Chemokine CCL2 ,Epididymitis ,030219 obstetrics & reproductive medicine ,Innate immune system ,biology ,Interleukin-6 ,Tumor Necrosis Factor-alpha ,business.industry ,Monocyte ,male germ cell ,General Medicine ,lcsh:Diseases of the genitourinary system. Urology ,medicine.disease ,Epididymis ,Monocyte Chemoattractant Proteins ,Chemokine CXCL10 ,Mice, Inbred C57BL ,Germ Cells ,medicine.anatomical_structure ,Immunology ,innate immune response ,biology.protein ,Cytokines ,Original Article ,Tumor necrosis factor alpha ,business ,epididymitis ,Germ cell - Abstract
Epididymitis can be caused by infectious and noninfectious etiological factors. While microbial infections are responsible for infectious epididymitis, the etiological factors contributing to noninfectious epididymitis remain to be defined. The present study demonstrated that damaged male germ cells (DMGCs) induce epididymitis in mice. Intraperitoneal injection of the alkylating agent busulfan damaged murine male germ cells. Epididymitis was observed in mice 4 weeks after the injection of busulfan and was characterized by massive macrophage infiltration. Epididymitis was coincident with an accumulation of DMGCs in the epididymis. In contrast, busulfan injection into mice lacking male germ cells did not induce epididymitis. DMGCs induced innate immune responses in epididymal epithelial cells (EECs), thereby upregulating the pro-inflammatory cytokines such as tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β), as well as the chemokines such as monocyte chemotactic protein-1 (MCP-1), monocyte chemotactic protein-5 (MCP-5), and chemokine ligand-10 (CXCL10). These results suggest that male germ cell damage may induce noninfectious epididymitis through the induction of innate immune responses in EECs. These findings provide novel insights into the mechanisms underlying noninfectious epididymitis, which might aid in the diagnosis and treatment of the disease.
- Published
- 2020
46. Deletion of exon 4 in LAMA2 is the most frequent mutation in Chinese patients with laminin α2-related muscular dystrophy
- Author
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Shujuan Song, Feng Zhang, Kai Gao, Ling Zhang, Aijie Liu, Hui Xiong, Renqian Du, Yanbin Fan, Xiaona Fu, Haipo Yang, Xiru Wu, Bing Mao, Lin Ge, Dandan Tan, Xiaoli Zhang, Jian Wu, Yuwu Jiang, Juan Ding, and Ying Hua
- Subjects
Male ,0301 basic medicine ,China ,DNA Copy Number Variations ,lcsh:Medicine ,Article ,Muscular Dystrophies ,03 medical and health sciences ,Exon ,Mutation Rate ,Laminin ,medicine ,Humans ,Copy-number variation ,Allele ,Muscular dystrophy ,lcsh:Science ,Child ,Gene ,Alleles ,Sequence Deletion ,Gene Rearrangement ,Genetics ,Multidisciplinary ,biology ,lcsh:R ,Breakpoint ,Haplotype ,Infant, Newborn ,High-Throughput Nucleotide Sequencing ,Infant ,Exons ,medicine.disease ,030104 developmental biology ,Haplotypes ,Child, Preschool ,Mutation ,biology.protein ,lcsh:Q ,Female - Abstract
Although recessive mutations in LAMA2 are already known to cause laminin α2-related muscular dystrophy, a rare neuromuscular disorder, large deletions or duplications within this gene are not well-characterized. In this study, we applied next-generation sequencing-based copy number variation profiling in 114 individuals clinically diagnosed with laminin α2-related muscular dystrophy, including 96 who harboured LAMA2 mutations and 34 who harboured intragenic rearrangements. In total, we detected 18 distinct LAMA2 copy number variations that have been reported only among Chinese, 10 of which are novel. The frequency of CNVs in the cohort was 19.3%. Deletion of exon 4 was detected in 10 alleles of eight patients, accounting for 27% of all copy number variations. These patients are Han Chinese and were found to have the same haplotype and sequence at the breakpoint junction, suggesting that exon 4 deletion is a founder mutation in Chinese Han and a mutation hotspot. Moreover, the data highlight our approach, a modified next-generation sequencing assay, as a robust and sensitive tool to detect LAMA2 variants; the assay identifies 85.7% of breakpoint junctions directly alongside sequence information. The method can be applied to clinical samples to determine causal variants underlying various Mendelian disorders.
- Published
- 2018
47. Adjuvant effect of the novel TLR1/TLR2 agonist Diprovocim synergizes with anti–PD-L1 to eliminate melanoma in mice
- Author
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Kuan Wen Wang, Hexin Shi, Xiaohong Li, Sara Ludwig, Hong Zhang, Kejin Zhou, Daniel J. Siegwart, Brian T. Jones, Eva Marie Y. Moresco, Aijie Liu, Ying Wang, Jianhui Wang, Bruce Beutler, Dale L. Boger, Matthew D. Morin, Sara Hildebrand, Miao Tang, Yuto Mifune, Xiaoming Zhan, and Lijing Su
- Subjects
0301 basic medicine ,Agonist ,Ovalbumin ,THP-1 Cells ,medicine.drug_class ,medicine.medical_treatment ,Antigen presentation ,Melanoma, Experimental ,Kaplan-Meier Estimate ,B7-H1 Antigen ,03 medical and health sciences ,0302 clinical medicine ,Adjuvants, Immunologic ,Cancer immunotherapy ,Cell Line, Tumor ,medicine ,Animals ,Humans ,Cytotoxic T cell ,Cells, Cultured ,Mice, Knockout ,Multidisciplinary ,Innate immune system ,Chemistry ,Antibodies, Monoclonal ,Drug Synergism ,Dendritic cell ,Toll-Like Receptor 1 ,Toll-Like Receptor 2 ,Mice, Inbred C57BL ,TLR2 ,030104 developmental biology ,PNAS Plus ,030220 oncology & carcinogenesis ,Cancer research ,Cytokine secretion ,Immunotherapy - Abstract
Successful cancer immunotherapy entails activation of innate immune receptors to promote dendritic cell (DC) maturation, antigen presentation, up-regulation of costimulatory molecules, and cytokine secretion, leading to activation of tumor antigen-specific cytotoxic T lymphocytes (CTLs). Here we screened a synthetic library of 100,000 compounds for innate immune activators using TNF production by THP-1 cells as a readout. We identified and optimized a potent human and mouse Toll-like receptor (TLR)1/TLR2 agonist, Diprovocim, which exhibited an EC(50) of 110 pM in human THP-1 cells and 1.3 nM in primary mouse peritoneal macrophages. In mice, Diprovocim-adjuvanted ovalbumin immunization promoted antigen-specific humoral and CTL responses and synergized with anti–PD-L1 treatment to inhibit tumor growth, generating long-term antitumor memory, curing or prolonging survival of mice engrafted with the murine melanoma B16-OVA. Diprovocim induced greater frequencies of tumor-infiltrating leukocytes than alum, of which CD8 T cells were necessary for the antitumor effect of immunization plus anti–PD-L1 treatment.
- Published
- 2018
48. Nanoreactors via Encapsulation of Catalytic Gold Nanoparticles within Cowpea Chlorotic Mottle Virus Protein Cages
- Author
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Aijie, Liu, Mark V, de Ruiter, Stan J, Maassen, and Jeroen J L M, Cornelissen
- Subjects
Spectrum Analysis ,Metal Nanoparticles ,Capsid Proteins ,Gold ,Ligands ,Bromovirus ,Catalysis - Abstract
Viral protein cage-based nanoreactors can be generated by encapsulation of catalytic metal nanoparticles within the capsid structure. In this method, coat proteins of the cowpea chlorotic mottle virus (CCMV) are used to sequester gold nanoparticles (Au NPs) in buffered solutions at neutral pH to form CCMV-Au hybrid nanoparticles. This chapter describes detailed methods for the encapsulation of Au NPs into CCMV protein cages. Protocols for the reduction of nitroarenes by using CCMV-Au NPs as catalyst are described as an example for the catalytic activity of Au NPs in the protein cages.
- Published
- 2018
49. LanceletDB: an integrated genome database for lancelet, comparing domain types and combination in orthologues among lancelet and other species
- Author
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Guangrui Huang, Zirui Yue, Anlong Xu, Yuchao Feng, Xiaopu Sang, Ting’an Li, Ting Yu, Jiaqi Chi, Xinhui Gao, Leiming You, Aijie Liu, Shengfeng Huang, and Shangwu Chen
- Subjects
0303 health sciences ,Genome ,biology ,Lancelet ,030302 biochemistry & molecular biology ,Protein domain ,Molecular Sequence Annotation ,Gene Annotation ,Genome browser ,Genome project ,biology.organism_classification ,General Biochemistry, Genetics and Molecular Biology ,03 medical and health sciences ,Evolutionary biology ,Branchiostoma floridae ,Databases, Genetic ,Animals ,Original Article ,General Agricultural and Biological Sciences ,030304 developmental biology ,Information Systems ,Lancelets - Abstract
Lancelet (amphioxus) represents the most basally divergent extant chordate (cephalochordates) that diverged from the other two chordate lineages (urochordates and vertebrates) more than half a billion years ago. As it occupies a key position in evolution, it is considered as one of the best proxies for understanding the chordate ancestral state. Thus, the construction of a database with multiple lancelet genomes and gene annotation data, including protein domains, is urgently needed to investigate the loss and gain of domains in orthologues among species, especially ancient domain types (non-vertebrate-specific domains) and novel domain combination, which is helpful for providing new insight into the chordate ancestral state and vertebrate evolution. Here, we present an integrated genome database for lancelet, LanceletDB, which provides reference haploid genome sequence and annotation data for lancelet (Branchiostoma belcheri), including gene models and annotation, protein domain types, gene expression pattern in embryogenesis, different expression sequence tag sets and alternative polyadenylation (APA) sites profiled by the sequencing APA sites method. Especially, LanceletDB allows comparison of domain types and combination in orthologues among type species so as to decode the ancient domain types and novel domain combination during evolution. We also integrated the released diploid lancelet genome annotation data (Branchiostoma floridae) to expand LanceletDB and extend its usefulness. These data are available through the search and analysis page, basic local alignment search tool page and genome browser to provide an integrated display.
- Published
- 2018
50. [Analysis of SCN1A deletions or duplications in patients with Dravet syndrome]
- Author
-
Qi, Zeng, Yuehua, Zhang, Xiaoling, Yang, Xiaojing, Xu, Jing, Zhang, Xiaojuan, Tian, Aijie, Liu, Xiaoyan, Liu, Yuwu, Jiang, and Xiru, Wu
- Subjects
Male ,NAV1.1 Voltage-Gated Sodium Channel ,Gene Duplication ,Humans ,Infant ,Epilepsies, Myoclonic ,Female ,Multiplex Polymerase Chain Reaction ,Gene Deletion - Abstract
To determine the type and frequency of SCN1A deletions and duplications among patients with Dravet syndrome (DS).For DS patients in which no mutations of the SCN1A gene were detected by PCR-DNA sequencing, SCN1A deletions and duplications were detected by multiplex ligation-dependent probe amplification (MLPA).In 680 DS patients, 489 had SCN1A mutations identified by PCR-DNA sequencing. In 191 patients who were negative for the SCN1A PCR-DNA sequencing, 15 (15/191, 7.9%) were detected with heterozygous SCN1A deletions or duplications, which included 14 (14/15, 93.3%) SCN1A deletions and 1 SCN1A duplication. There were 13 types of mutations, including whole SCN1A deletions in 3 patients, partial SCN1A deletions in 11 patients and partial SCN1A duplications in one patient. By testing the parents, 14 mutations were found to be de novo. For the remaining case, no SCN1A deletion or duplication was found in the mother, while the father was not available.Approximately 8% of Chinese patients who were negative for SCN1A mutation by PCR-sequencing have SCN1A deletions or duplications. The MLPA analysis should be considered as an important strategy for such patients. SCN1A deletions are more common than SCN1A duplications among DS patients, and the most common types are whole SCN1A deletions. The majority of SCN1A deletions or duplications are de novo.
- Published
- 2017
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