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Bimolecular charge recombination is one of the most important loss processes in organic solar cells. However, the bimolecular recombination rate in solar cells based on novel non-fullerene acceptors is mostly unclear. Moreover, the origin of the reduced-Langevin recombination rate in bulk heterojunction solar cells in general is still poorly understood. Here, we investigate the bimolecular recombination rate and charge transport in a series of high-performance organic solar cells based on non-fullerene acceptors. From steady-state dark injection measurements and drift–diffusion simulations of the current–voltage characteristics under illumination, Langevin reduction factors of up to over two orders of magnitude are observed. The reduced recombination is essential for the high fill factors of these solar cells. The Langevin reduction factors are observed to correlate with the quadrupole moment of the acceptors, which is responsible for band bending at the donor–acceptor interface, forming a barrier for charge recombination. Overall these results therefore show that suppressed bimolecular recombination is essential for the performance of organic solar cells and provide design rules for novel materials.

The vertical shear instability (VSI) is a robust phenomenon in irradiated protoplanetary disks (PPDs). The majority of previous numerical simulations have focused on the turbulent properties of its saturated state. However, the saturation of the VSI manifests as large-scale coherent radially travelling inertial waves. In this paper, we study inertial-wave-disk interactions and their impact on VSI saturation. Inertial-wave linear theory is developed and applied to a representative global 2D simulation using the Athena++ code. It is found that the VSI saturates by separating the disk into several radial wave zones roughly demarcated by corotation resonances (turning points); this structure also manifests in modest radial variations in the vertical turbulence strength. Future numerical work should employ large radial domains to accommodate this radial structure of the VSI, while concurrently adopting sufficiently fine resolutions to resolve the parametric instability that attacks the saturated VSI inertial waves., Comment: 8 pages, 6 figures, accepted for publication in MNRAS

Fangfang Liu,1,* Lumin Tang,2,* Mengyu Tao,3,* Chuang Cui,1 Di He,2 Longxia Li,2 Yahui Liao,4 Yamin Gao,5 Jing He,5 Fan Sun,6 Houwen Lin,6 He Li1,2 1Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 2Traditional Chinese Medicine Department, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127, People’s Republic of China; 3Department of Gynecology and Obstetrics, Shanghai Key Laboratory of Gynecology Oncology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127, People’s Republic of China; 4Shanghai Ocean University, Shanghai, People’s Republic of China; 5Shenyang Pharmaceutical University, Benxi, People’s Republic of China; 6Research Center for Marine Drugs, State Key Laboratory of Oncogenes and Related Genes, Department of Pharmacy, RenJi Hospital, School of Medicine, Shanghai JiaoTong University, Shanghai, People’s Republic of China*These authors contributed equally to this workCorrespondence: He Li; Fan Sun Tel +86 21 51322222; +86 21 68383339Email lihe1972@hotmail.com; sunfan2017@163.comPurpose: Stichoposide C (STC) is a triterpene glycoside isolated from Thelenota ananas, which is previously demonstrated to wide spectrum of anticancer effects against various tumor cells. However, the antitumor effects and underlying molecular mechanisms in ovarian cancer (OC) cells are not fully understood. Here, we examined if and through which mechanisms STC exerts anticancer effects on OC.Methods: CCK-8 and colony formation assays were used to detect cell viability and proliferation. Flow cytometry was used to detect apoptosis and cell cycle arrest. Protein expression and phosphorylation were measured by Western blotting analysis. Confocal fluorescence microscopy was used to observe the autophagy flux. Autophagosome formation was observed via transmission electron microscopy. Antitumor effect of STC was investigated in patient-derived organoids (PDOs) and A2780 subcutaneous xenograft tumors.Results: STC was found that not only exerted antiproliferation activity and apoptosis but also induced autophagy. Mechanistically, STC induced autophagy via inhibited the AKT/mTOR signaling pathway in ovarian cancer cells. In addition, STC and an autophagy inhibitor 3-methyladenine (3-MA) combination treatment showed significant synergetic effects on inhibiting proliferation and promoting apoptosis in vitro. Consistent with cell experiments, STC also inhibited the growth of two OC PDOs. Finally, STC markedly reduced the growth of A2780 subcutaneous xenograft tumors without organ toxicity and activated autophagy in vivo.Conclusion: Stichoposide C exerts in vitro and in vivo anticancer effects on ovarian cancer by inducing autophagy via inhibiting AKT/mTOR pathway. The findings warrant further prove for STC as a potential therapeutic agent for ovarian cancer.Keywords: ovarian cancer, stichoposide C, autophagy, apoptosis, AKT/mTOR

The Mei-yu season, typically occurring from mid-June to mid-July, on average, contributes to 32% of the annual precipitation over the Yangtze–Huai River Valley (YHRV) and represents one of the three heavy-rainfall periods in China. Here, we briefly review the large-scale background, synoptic pattern, moisture transport, and cloud and precipitation characteristics of the Mei-yu frontal systems in the context of the ongoing Integrative Monsoon Frontal Rainfall Experiment (IMFRE) field campaign. Phase one of the campaign, IMFRE-I, was conducted from 10 June to 10 July 2018 in the middle reaches of the YHRV. Led by the Wuhan Institute of Heavy Rain (IHR) with primary support from the National Natural Science Foundation of China, IMFRE-I maximizes the use of our observational capacity enabled by a suite of ground-based and remote sensing instruments, most notably the IHR Mesoscale Heavy Rainfall Observing System (MHROS), including different wavelengths of radars, microwave radiometers, and disdrometers. The KA350 (Shanxi King-Air) aircraft participating in the campaign is equipped with Ka-band cloud radar and different probes. The comprehensive datasets from both the MHROS and aircraft instruments are combined with available satellite observations and model simulations to answer the three scientific questions of IMFRE-I. Some highlights from a previously published special issue are included in this review, and we also briefly introduce the IMFRE-II field campaign, conducted during June–July 2020, where the focus was on the spatiotemporal evolutions of the mei-yu frontal systems over the middle and lower reaches of the YHRV., The 28th IUGG General Assembly (IUGG2023) (Berlin 2023)

Changqing Zhang,1 Changqi Cui,1 Qi Yao2 1School of Economics and Business Administration, Chongqing University, Chongqing, 400030, People’s Republic of China; 2School of Economics and Management, Chongqing Jiaotong University, Chongqing, 400074, People’s Republic of ChinaCorrespondence: Changqi CuiSchool of Economics and Business Administration, Chongqing University, Shazheng Street, No. 174, Shapingba District, Chongqing, 400030, People’s Republic of ChinaTel +86 13752905059Email cuichangqi@cqu.edu.cnPurpose: In the big data era, many institutions (ie, hospitals) and firms use various methods to encourage people to disclose more personal information to gain competitive advantages in many businesses, such as healthcare and the Internet of Things (IoT) devices. Discussions on antecedents of individuals’ willingness to reveal private data from individual differences perspective are limited. Drawing on information boundary theory, we examine how self-construal prompts a different regulatory focus (promotion focus versus prevention focus), thus, affects individuals’ willingness to disclose private data.Methods: A mixed-method approach was used to examine our hypothesis. Study 1 (N = 93, participants in China) manipulated self-construal in lab experiments and examined participants’ actual disclosure behavior in the emerging IoT context of connected cars. Study 2 (an online survey, N = 200, participants in US) measured chronic self-construal in another disclosure context (healthcare app), replicating the preliminary effect and examined the mediating effect of the regulatory focus. Study 3 (an online experiment, N = 284, participants in US) tested the moderating effect of message framing.Results: Study 1 showed that participants primed an independent self-construal were more willing to share private information, whether it is real driving data or private identity information. Study 2 showed that independent (interdependent) self-construal individuals tend to have promotion focus (prevention focus), thus leading to higher (lower) willingness to disclose personal health information. Study 3 demonstrated that independent (interdependent) self-construal individuals are more willing to share information when presented with gain-framing (loss-framing) information.Conclusion: Independent (interdependent) self-construal positively (negatively) affects individuals’ willingness to disclose and these effects will be mediated by regulatory focus and moderated by message farming. Our study provides a theoretical paradigm that is new to the willingness to disclose literature, and offers an effective, actionable strategy on how institutions and firms can facilitate individuals’ personal information disclosure.Keywords: self-construal, willingness to disclose, regulatory focus, information boundary theory, message framing, privacy

Lingyao Qi, Hanxiong Liu, Lianchao Cheng, Caiyan Cui, Xu Chen, Siqi Yang, Lin Cai Department of Cardiology, Affiliated Hospital of Southwest Jiaotong University, The Third People’s Hospital of Chengdu, Chengdu, Sichuan, People’s Republic of ChinaCorrespondence: Lin CaiDepartment of Cardiology, Affiliated Hospital of Southwest Jiaotong University, The Third People’s Hospital of Chengdu, Chengdu, Sichuan, People’s Republic of ChinaTel/Fax +86 28-67575956Email clin63@hotmail.comPurpose: Chronic kidney disease (CKD) is common in patients admitted with acute coronary syndrome (ACS), and it is associated with poor outcomes. However, data are limited. Hence, we examined the long-term prognostic significance of estimated glomerular filtration rate (eGFR) among Chinese patients hospitalized with ACS.Patients and Methods: This is a multicenter, observational study that included 1860 ACS patients enrolled between March 2014 and June 2019 from 11 hospitals in Chengdu. CKD-EPI equation was used to calculate the baseline eGFR. Patients were divided into three groups: eGFR ≥ 90 mL/min (normal renal function), eGFR 60 to < 90 mL/min (mild impaired renal function), and eGFR < 60 mL/min (moderate or severe renal dysfunction). The endpoint was all-cause death during follow-up.Results: At baseline, 714 patients had normal renal function, while 746 patients had mild impaired renal function, and 400 patients had moderate or severe renal dysfunction. In the follow-up of 15 months (10 months, 22 months), 261 (14.0%) patients died;, 139 (34.8%) in the moderate or severe renal dysfunction group, 94 (12.6%) in the mild impaired renal function group, and 28 (3.9%) in the normal renal function group (log-rank p-value from Kaplan–Meier analysis < 0.001). In multivariable Cox Proportional hazard analysis, age, systolic blood pressure (SBP), heart rate, eGFR, ST-elevation myocardial infarction (STEMI), and percutaneous coronary intervention (PCI) were independent predictors of all-cause death.Conclusion: In this study, among Chinese patients with ACS, renal insufficiency was associated with unfavorable long-term prognosis. Age, SBP, heart rate, eGFR, STEMI, and PCI could identify those at risk.Keywords: renal insufficiency, acute coronary syndrome, long-term prognosis, retrospective study

Fuqiang Liu,1– 4 Feng Han,4,5 Xiaoli Liu,4,5 Lina Yang,4,5 Caixia Jiang,4,5 Chen Cui,1– 4 Fang Yuan,1– 4 Xin Zhang,1– 4 Lei Gong,1– 4 Xinguo Hou,1– 4 Yuan Liu,1– 4 Li Chen1– 4 1Department of Endocrinology, Qilu Hospital of Shandong University, Jinan, Shandong, 250012, People’s Republic of China; 2Institute of Endocrine and Metabolic Diseases of Shandong University, Jinan, Shandong, 250012, People’s Republic of China; 3Key Laboratory of Endocrine and Metabolic Diseases, Shandong Province Medicine & Health, Jinan, Shandong, 250012, People’s Republic of China; 4Jinan Clinical Research Center for Endocrine and Metabolic Diseases, Jinan, Shandong, 250012, People’s Republic of China; 5Department of Endocrinology, Zhangqiu District People’s Hospital, Jinan, 250200, People’s Republic of ChinaCorrespondence: Yuan Liu; Li Chen Email liuyuan198735@163.com; chenli3@medmail.com.cnBackground: To investigate the correlation between serum interleukin-17A (IL-17A) levels and diabetic retinopathy (DR) in elderly individuals with type 2 diabetes mellitus (T2DM).Methods: The study included 194 elderly patients (94 males and 100 females) with T2DM. Digital retinal photography as well as fundus fluorescein angiography was employed to distinguish between nonproliferative diabetic retinopathy (NPDR) and proliferative diabetic retinopathy (PDR). In addition, multiple logistic regression analysis was conducted to determine the correlation between serum IL-17A levels and DR status.Results: The average age of the study cohort was 69.14 ± 6.33 years, of which 52.08% were male. The study participants with the highest IL-17A (Q4) levels had higher TC, DBP, and low-density lipoprotein cholesterol (LDL-C) values than those the other groups. Analysis using unadjusted and adjusted linear regression revealed that the effect size of 1.09 for DR in the unadjusted model indicates that IL-17A is associated with an increase of 1.09 in DR (mmol/L) (β 1.09, 95% confidence interval (CI) 1.03, 1.16). Using the minimum-adjusted model (the model 2), as IL-17A increased, DR was higher by 1.11 (β 1.11, 95% CI 1.04, 1.18). With the fully adjusted model (the model 3), for each additional IL-17A increase, DR was higher by 1.15 (β 1.15, 95% CI 1.06, 1.24).Conclusion: Serum IL-17A levels are apparently positively correlated to DR in Chinese elderly individuals with T2DM.Keywords: interleukin-17A, diabetic retinopathy, type 2 diabetes mellitus

Xin Yang,1– 3 Yifan Wang,1– 3 Si Chen,1– 3 Shuang Zhang,1– 3 Chunying Cui1– 3 1School of Pharmaceutical Sciences, Capital Medical University, Beijing, 100069, People’s Republic of China; 2Engineering Research Center of Endogenous Prophylactic of Ministry of Education of China, Beijing, 100069, People’s Republic of China; 3Beijing Area Major Laboratory of Peptide and Small Molecular Drugs, Beijing, 100069, People’s Republic of ChinaCorrespondence: Chunying Cui; Shuang ZhangDepartment of Pharmaceutics, School of Pharmaceutical Science, Capital Medical University, No. 10 Youanmenwai Street, Fengtai, Beijing, 100069, People’s Republic of ChinaTel/Fax +86-10-8391-1668; +86-10-8391-1673Email ccy@ccmu.edu.cn; zshuang@ccmu.edu.cnBackground: Breast cancer is the most prevalent cancer among women. Doxorubicin (DOX) is a common chemotherapeutic drug used to treat many different cancers. However, multidrug resistance limits the treatment of breast cancer. MDR1 siRNA (siMDR1) combinatorial therapy has attracted significant attention as a breakthrough therapy for multidrug resistance in tumors. However, naked siRNA is easily degraded by enzymatic hydrolysis requiring an siRNA carrier for its protection. Human serum albumin (HSA) was selected as the carrier due to its excellent biocompatibility, non-toxicity, and non-immunogenicity. Cetuximab was used to modify the HSA nanoparticles in order to target the tumor tissues.Methods: This study used a central composite design response surface methodology (CCD-RSM) to investigate the optimal formula for HSA NPs preparation. Cex-HSA/DOX/MDR1 siRNA (C-H/D/M) was characterized by dynamic light scattering and transmission electron microscopy. The efficacy of C-H/D/M tumor growth inhibitory activity was investigated in vitro and in vivo using confocal imaging, MTT assay, and an MCF-7/ADR tumor-bearing mice model. RT–qPCR, ELISA analysis, and flow cytometry were used to investigate the in vitro antitumor mechanisms of C-H/D/M.Results: The diameter and PDI of the C-H/D/M were 173.57 ± 1.30 nm and 0.027 ± 0.004, respectively. C-H/D/M promoted and maintained the sustained release and the uptake of DOX significantly. After transfection, the MDR1 mRNA and P-gp expression levels were down-regulated by 44.31 ± 3.6% (P < 0.01) and 38.08 ± 2.4% (P < 0.01) in an MCF-7/ADR cell line. The fluorescent images of the treated BALB/c nude mice revealed that C-H/D/M achieved targeted delivery of siMDR1 and DOX into the tumor tissue. The in vivo tumor inhibition results demonstrated that the tumor inhibition rate of the C-H/D/M treated group was 54.05% ± 1.25%. The biosafety results indicated that C-H/D/M did not induce significant damages to the main organs in vivo.Conclusion: C-H/D/M can be used as an ideal non-viral tumor-targeting vector to overcome MDR and enhance the antitumor effect.Keywords: human serum albumin, HSA, multidrug resistance, MDR, co-delivery carrier, small interfere RNA, gene silencing

Xin Chen,1,2,&ast; Zhicheng Yu,1,3,&ast; Jianhua Wang,1 Wenjing Cui,1 Can Cui,1 Yajie Wang,1 Yongkang Liu,1 Hao Zhou,1 Cheng Wang,4 Zhongqiu Wang,1 Xiao Chen1 1Department of Radiology, The Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, 210029, People’s Republic of China; 2Department of Radiology, Shanghai Jiaotong University Affiliated Sixth People’s Hospital, Shanghai, 200233, People’s Republic of China; 3Department of Radiology, Jiading Central Hospital, Shanghai University of Medicine & Health Sciences, Shanghai, 201800, People’s Republic of China; 4Department of Radiology, Nanjing Drum Tower Hospital the Affiliated Hospital of Nanjing University Medical School, Nanjing, 210008, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhongqiu Wang; Xiao ChenDepartment of Radiology, The Affiliated Hospital of Nanjing University of Chinese Medicine, 155 Hanzhong Road, Nanjing, 210029, People’s Republic of ChinaTel +86-025-86619843Email zhqwang001@126.com; chxwin@163.comPurpose: The purpose of this study was to analyze the prevalence of and risk factors for incidental pancreatic cystic lesions (PCLs) in the Chinese general population. Furthermore, the association between baseline imaging findings and PCL progression was also investigated.Patients and Methods: A total of 9826 individuals who underwent computed tomography (CT) examinations for lung cancer screening between January 1, 2018 and January 1, 2019 were included in this study. The participants’ CT imaging findings and biochemical biomarker levels were reviewed and analyzed. PCLs detected during the screening were followed up for 12 months. Associations between imaging findings and clinical factors with PCL progression were explored.Results: PCLs were observed in 172 of the 9826 participants. The crude prevalence of PCLs in total population was 1.75%. In subjects aged > 60 years, the prevalence of PCLs was 3.2% (102/3151). The occurrence of PCLs was significantly increased with an increase of age in both men and women (p < 0.001). High-risk PCLsL commonly located in pancreatic head showed extrapancreatic growth, and had high urea levels (p = 0.005, p = 0.015, p = 0.002, respectively) compared with low-risk PCLs. Location in the pancreatic head (odds ratio (OR) = 6.286, 95% confidence interval (CI): 1.842– 21.452) and extrapancreatic growth (OR = 4.049, 95% CI: 1.235– 13.333) were risk factors for PCL progression.Conclusion: PCLs are not uncommon in the Chinese general population. Location in the pancreatic head and extrapancreatic growth are the independent predictors of high-risk of PCLs and PCL progression.Keywords: pancreatic cystic lesion, computed tomography, prevalence, progression, Chinese population

Yan Song, Tao Qu, Honggang Zhang, Yongkun Sun, Chengxu Cui, Yihebali Chi, Wen Zhang, Xingyuan Wang, Lin Yang Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, People’s Republic of ChinaCorrespondence: Lin Yang; Tao QuDepartment of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, People’s Republic of ChinaEmail linyang@cicams.ac.cn; thomasqu1972@hotmail.comBackground: In FRESCO trial, a phase III study of fruquintinib demonstrated a significant improvement on the overall survival (OS) of patients with metastatic colorectal cancer (mCRC) who failed to response to available standard treatments. The aim of the current study was to evaluate the safety and effectiveness of fruquintinib in Chinese mCRC patients in the real-world setting.Methods: Patients with mCRC treated with fruquintinib at our hospital were retrospectively reviewed. Patient demographics, treatment, adverse events and survival data were collected. OS and progression-free survival (PFS) were estimated using the Kaplan–Meier method.Results: In total, 76 patients were evaluated from December 2018 to January 2020. The median (range) age was 59.5 (34– 86) years, ECOG PS 0-1/2 was 86.8%/13.2%, and 38 (50%)/30 (39.5%) patients had experienced more than two prior therapies for mCRC. The median treatment duration was 3.6 cycles. Treatment-related adverse events (TRAEs) resulted in dose reduction were 17.1% of the patients without any treatment discontinuation. The most common grade 3 or 4 TRAEs were hypertension (9.2%), hand-foot skin reaction (7.9%), thrombocytopenia (3.9%), anaemia (2.6%), increased ALT (1.3%), oral mucositis (1.3%), proteinuria (1.3%) and neutropenia (1.3%). The median PFS was 5.1 months (95% CI 3.8– 6.4 months), and the median OS was 12.0 months (95% CI 8.0– 16.1 months). In patients with hypertension or hypothyroidism, a survival extension approximate to 6 months was observed, but the difference is not yet statistically significant. CEA decreased after fruquintinib treatment could be considered as a potential predictor for better OS.Conclusion: The outcome of this real-life study was consistent with that of the randomised controlled trial. There were no new safety concerns. Future studies of fruquintinib should be conducted to identify patients who tend to obtain more benefits from fruquintinib alone or in combination with other agents.Keywords: fruquintinib, metastatic colorectal cancer, real-world settings, toxicities

Yifan Wang,1– 3 Si Chen,1– 3 Xin Yang,1– 3 Shuang Zhang,1– 3 Chunying Cui1– 3 1Department of Pharmaceutics, School of Pharmaceutical Sciences, Capital Medical University, Beijing, People’s Republic of China; 2Engineering Research Center of Endogenous Prophylactic of Ministry of Education of China, Beijing, People’s Republic of China; 3Beijing Area Major Laboratory of Peptide and Small Molecular Drugs, Beijing, People’s Republic of ChinaCorrespondence: Chunying Cui; Shuang ZhangDepartment of Pharmaceutics, School of Pharmaceutical Science, Capital Medical University, Number 10 Youanmenwai Street, Fengtai, Beijing, 100069, People’s Republic of ChinaTel +86-10-8391-1668; +86-10-8391-1673Fax +86-10-8391-1668; +86-10-8391-1673Email ccy@ccmu.edu.cn; zshuang@ccmu.edu.cnBackground: siRNA brings hope for cancer therapy. However, there are many obstacles for application of siRNA in clinical. Because of the excellent biocompatibility, non-toxicity and non-immunogenicity of bovine serum albumin (BSA), BSA-based nanoparticles have been widely designed as a drug carrier system.Methods: The optimal formula for BSA NPs preparation was investigated by central composite design response surface methodology (CCD-RSM), BSA-based survivin-siRNA delivery system (BSA NPs/siRNA) was characterized by dynamic light scattering, atomic force microscope, transmission electron microscope and Bradford method. The in vitro anti-tumor effect and mechanism of BSA NPs were investigated by confocal microscopic imaging, MTT assay, RT-qPCR and ELISA analysis. Moreover, the anti-tumor effect, distribution and biosafety of BSA NPs were studied in vivo.Results: The optimal formula for BSA NPs was settled to be 20 mg/mL for BSA concentration, 9 for pH value, 136% for crosslinking degree and 1.6 mL/min for speed of ethanol addition. BSA NPs/siRNA could remain stable at 4°C for 4 weeks and protect siRNA from degradation by RNase A. Besides, BSA NPs/siRNA could maintain a sustained release of siRNA and promote the uptake of siRNA significantly. The survivin-mRNA level and the survivin-protein level were decreased by 55% ± 1.6% and 54% ± 1.6% separately. The in vivo tumor inhibition results suggested that the tumor inhibition rate of BSA NPs/siRNA-treated group was 54% ± 12% and was similar with that of DOX-treated group (57% ± 9.2%, P > 0.05). The biosafety results confirmed that BSA NPs/siRNA could not induce significant damages to the main organs and blood in vivo.Conclusion: These results demonstrated that CCD-RSM was an effective tool for preparation analysis, and the BSA NPs/siRNA was a promising system for siRNA-based gene therapy.Keywords: bovine serum albumin, BSA, CCD-RSM, survivin-siRNA, nanoparticles, RNAi

Kai Liu,1,* Guo-Liang Cai,2,3 Zhe Zhuang,4,* Si-Ying Pei,1 Sheng-Nan Xu,5 Ya-Nan Wang,1 Hong Wang,1 Xin Wang,1 Cheng Cui,5 Man-Chao Sun,5 Si-Hui Guo,5 Kun-Ping Jia,1 Xiu-Zhen Wang,1 Guo-Feng Cai1 1Hanan Branch of Second Affiliated Hospital of Heilongjiang University of Traditional Chinese Medicine, Harbin, 150001, People’s Republic of China; 2Postdoctoral Research Workstation of Harbin Sport University, Harbin, 150001, People’s Republic of China; 3Department of Sport Science and Health, Harbin Sport University, Harbin, 150008, People’s Republic of China; 4Second Affiliated Hospital of Heilongjiang University of Traditional Chinese Medicine, Harbin, 150001, People’s Republic of China; 5Heilongjiang University of Traditional Chinese Medicine, Harbin, 150001, People’s Republic of China*These authors contributed equally to this workCorrespondence: Guo-Feng CaiHanan Branch of Second Affiliated Hospital of Heilongjiang University of Traditional Chinese Medicine, Harbin, 150001, People’s Republic of ChinaEmail cangjiong1973@163.comBackground: Interleukin-1β (IL-1)-treated mesenchymal stem cells (MSCs) and IL-1-MSCs-conditioned medium (CM) exert anti-inflammatory roles. Astrocytes are essential for the modulation of synaptic activity and neuronal homeostasis in the brain. Exosomes are the critical mediators in intercellular communication. However, the mechanism underlying the anti-inflammatory effect of IL-1-treated MSCs remains unknown.Methods: In this study, exosomes (IL-1-Exo) were isolated from IL-1-treated MSCs. In addition, lipopolysaccharide (LPS)-treated hippocampal astrocytes and status epilepticus (SE) mice were treated with IL-1-Exo. Inflammatory activity, astrogliosis, and cognitive performance were measured to determine the effect of IL-1-Exo on inflammation.Results: The results revealed that IL-1-Exo significantly inhibited LPS-induced astrogliosis and inflammatory responses of astrocytes. Also, IL-1-Exo reversed the LPS-induced effect on calcium signaling. The Nrf2 signaling pathway was associated with the effect of IL-1-Exo in LPS-treated astrocytes. Furthermore, IL-1-Exo reduced the inflammatory response and improved the cognitive performance of SE mice.Conclusion: The results suggest that IL-1-Exo inhibited LPS-induced inflammatory responses in astrocytes and SE mice and that the effect of IL-1-Exo was primarily mediated through the Nrf-2 signaling pathway. This study provides a new understanding of the molecular mechanism of inflammation-associated brain diseases and an avenue to develop nanotherapeutic agents for the treatment of inflammatory conditions in the brain.Keywords: mesenchymal stem cells, interleukin-1β, exosome, astrocyte, inflammation, Nrf-2

Polycyclic aromatic hydrocarbons (PAHs) are a group of common recalcitrant pollutant in industrial saline wastewater that raised significant concerns, whereas traditional activated sludge (AS) has limited tolerance to high salinity and PAHs toxicity, restricting its capacity to degrade PAHs. It is therefore urgent to develop a bioaugmented sludge (BS) system to aid in the effective degradation of these types of compounds under saline condition. In this study, a novel bioaugmentation strategy was developed by using halophilic Martelella sp. AD-3 for effectively augmented phenanthrene (PHE) degradation under 3% salinity. It was found that a 0.5∼1.5% (w/w) ratio of strain AD-3 to activated sludge was optimal for achieving high PHE degradation activity of the BS system with degradation rates reaching 2.2 mg⋅gVSS-1⋅h-1, nearly 25 times that of the AS system. Although 1-hydroxy-2-naphthoic acid (1H2N) was accumulated obviously, the mineralization of PHE was more complete in the BS system. Reads-based metagenomic coupled metatranscriptomic analysis revealed that the expression values of ndoB, encoding a dioxygenase associated with PHE ring-cleavage, was 5600-fold higher in the BS system than in the AS system. Metagenome assembly showed the members of the Corynebacterium and Alcaligenes genera were abundant in the strain AD-3 bioaugmented BS system with expression of 10.3±1.8% and 1.9±0.26%, respectively. Moreover, phdI and nahG accused for metabolism of 1H2N have been annotated in both above two genera. Degradation assays of intermediates of PHE confirmed that the activated sludge actually possessed considerable degradation capacity for downstream intermediates of PHE including 1H2N. The degradation capacity ratio of 1H2N to PHE was 87% in BS system, while it was 26% in strain AD-3. These results indicated that strain AD-3 contributed mainly in transforming PHE to 1H2N in BS system, while species in activated sludge utilized 1H2N as substrate to grow, thus establishing a syntrophic interaction with strain AD-3 and achieving the complete mineralization of PHE. Long-term continuous experiment confirmed a stable PHE removal efficiency of 93% and few 1H2N accumulation in BS SBR system. This study demonstrated an effective bioaugmented strategy for the bioremediation of saline wastewater containing PAHs.

Chunmei Geng,1 Yujin Guo,1 Changshui Wang,2 Changmeng Cui,3 Wenxiu Han,1 Dehua Liao,4 Pei Jiang1 1Department of Pharmacy, Jining First People’s Hospital, Jining Medical University, Jining 272000, People’s Republic of China; 2Department of Clinical Translational Medicine, Jining Life Science Center, Jining 272000, People’s Republic of China; 3Department of Neurosurgery, Affiliated Hospital of Jining Medical University, Jining Medical University, Jining 272000, People’s Republic of China; 4Department of Pharmacy, Hunan Cancer Hospital, Central South University, Changsha 410011, People’s Republic of ChinaCorrespondence: Pei JiangDepartment of Pharmacy, Jining First People’s Hospital, Jining Medical University, Jining 272000, People’s Republic of ChinaTel/Fax +86 537 2106208Email jiangpeicsu@sina.comPurpose: Substantial evidence indicates that lipopolysaccharide (LPS) exposure can lead to systemic inflammatory response syndrome (SIRS) and multiple organ failure. Previous metabolomic studies have mainly focused on LPS-induced depression or hepatic and renal effects. However, no comprehensive metabolomics-based analysis of the serum, liver, kidney, hippocampus, and heart following exposure to LPS has been undertaken to date.Material and Methods: Male Sprague–Dawley rats were randomly allocated to a control and a LPS-treated group (n=8). LPS for 2 weeks (0.5 mg/kg every other day) was given via intraperitoneal injection. Gas chromatography–mass spectrometry (GC–MS) was used for metabolite determination, while multivariate statistical analysis was performed to identify differentially expressed metabolites between the two groups.Results: Our study revealed that 24, 13, 12, 7, and 12 metabolites were differentially expressed between the LPS treatment group and the control group in the serum, liver, kidney, hippocampus, and heart, respectively. We further identified that these metabolic changes were mainly involved with aminoacyl-tRNA biosynthesis; glutathione metabolism; glyoxylate and dicarboxylate metabolism; glycine, serine, and threonine metabolism; arginine biosynthesis; bile acid biosynthesis; and glycerolipid metabolism.Conclusion: We have systematically elucidated the metabolic changes underlying LPS-induced SIRS, thereby providing insight into the mechanisms associated with these alterations.Keywords: systemic inflammatory response syndrome, metabolites, gas chromatography–mass spectrometry, multivariate statistical analysis

Fuqiang Liu,1– 4 Lei Gong,1– 4 Weidong Qin,5 Chen Cui,1– 4 Li Chen,1– 4 Mingxiang Zhang5 1Department of Endocrinology, Qilu Hospital, Shandong University, Jinan 250012, People’s Republic of China; 2Institute of Endocrine and Metabolic Diseases, Shandong University, Jinan 250012, People’s Republic of China; 3Key Laboratory of Endocrine and Metabolic Diseases, Shandong Province Medicine and Health, Jinan, People’s Republic of China; 4Jinan Clinical Research Center for Endocrine and Metabolic Diseases, Jinan, People’s Republic of China; 5Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Public Health, Qilu Hospital, Shandong University, Jinan Shandong 250012, People’s Republic of ChinaCorrespondence: Li ChenDepartment of Endocrinology, Qilu Hospital of Shandong University, 107 Wen Hua Xi Road, Jinan, Shandong 250012, People’s Republic of China, Tel +86-531-8216-9255Fax +86-531-86169356Email chenli191125@126.comMingxiang ZhangKey Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Public Health, Qilu Hospital, Shandong University, 107 Wen Hua Xi Road, Jinan, Shandong 250012, People’s Republic of China, Tel +86-531-8216-9255Fax +86-531-86169356Email zhangmingxiang2019@126.comAim: Glucagon-like peptide-1 (GLP1) is known to decrease glucagon release and may be beneficial for the reduction of elevated blood glucose. However, its role and mechanism of action in diabetes remain elusive. This study aimed to examine the function of GLP1 and analyze the mechanism of effect that GLP1exerts on inducible nitric oxide synthase (iNOS) in diabetic mice.Methods: A diabetes model was established in ApoE–/– mice fed a high-fat diet and treated with GLP1 and/or lentivirus-expressing PARP1. PARP1, iNOS, and inflammatory factors in islets were detected by Western blot and ELISA. Islet α cells and β cells and CD8+ T lymphocytes were detected by immunostaining. Islet-cell apoptosis was detected by TUNEL.Results: GLP1 inhibited the expression of PARP1 and iNOS in islets, alleviated decrease in β cells, and suppressed cell apoptosis induced by the high-fat diet. Moreover, GLP1 recovered the decline in insulin sensitivity and glucose tolerance in ApoE–/– mice fed the high-fat diet, and the effects of GLP1 were related to the inhibition of COX2 and NFκB expression.Conclusion: GLP1 significantly alleviated the decrease in β-cell numbers, suppressed β-cell apoptosis induced by the high-fat diet, inhibited the expression of iNOS, and alleviated inflammatory islet injury via inhibiting the COX2–NFκB pathway.Keywords: GLP1, islet function, PARP1

Sha Zhang,1 Liang Yan,1 Can Cui,2 Zhen Wang,1 Jianhui Wu,1 Ang Lv,1 Min Zhao,3 Bin Dong,4 Wenlong Zhang,5 Xiaoya Guan,1 Xiuyun Tian,1 Chunyi Hao1 1Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Hepato-Pancreato-Biliary Surgery, Peking University Cancer Hospital & Institute, Beijing 100142, People’s Republic of China; 2Department of Breast Oncology, Tianjin Medical University Cancer Institute and Hospital, Key Laboratory of Breast Cancer Prevention and Therapy, Tianjin Medical University, Ministry of Education, Key Laboratory of Cancer Prevention and Therapy, Tianjin, People’s Republic of China; 3Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Pathology, Peking University Cancer Hospital & Institute, Beijing, People’s Republic of China; 4Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Central Laboratory, Peking University Cancer Hospital & Institute, Beijing, People’s Republic of China; 5Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Laboratory Animal, Peking University Cancer Hospital & Institute, Beijing 100142, People’s Republic of ChinaCorrespondence: Chunyi Hao; Xiuyun TianDepartment of Hepato-Pancreato-Biliary Surgery, Peking University Cancer Hospital & Institute, No. 52, Fucheng Road, Haidian District, Beijing 100142, People’s Republic of ChinaTel +86-10-88196182; +86-10-88196841Fax +86-10-88196548Email haochunyi@bjmu.edu.cn; xiuyunt@126.comBackground: Retroperitoneal liposarcoma (RLPS) is a rare tumor with high recurrence rate. Ribonucleotide reductase small subunit M2 (RRM2) protein is essential for DNA synthesis and replication. Our previous study has demonstrated that RRM2 downregulation inhibited the proliferation of RLPS cells, but further association between RRM2 and RLPS and relevant mechanisms remains to be explored.Methods: RRM2 expression was evaluated in RLPS tumor tissues and cell lines by using real-time PCR and immunohistochemical analysis. The effect of RRM2 downregulation on cell proliferation, apoptosis, cell cycle, cell migration and invasion was tested by lentivirus. The effect of RRM2 inhibition on tumor growth in vivo was assessed by using patient-derived tumor xenograft (PDX) of RLPS and RRM2 inhibitor. The underlying mechanisms of RRM2 in RLPS were explored by protein microarray and Western blotting.Results: The results showed that RRM2 mRNA expression was higher in RLPS tissues than in normal fatty tissues (P< 0.001). RRM2 expression was higher in the dedifferentiated, myxoid/round cell, and pleomorphic subtypes (P=0.027), and it was also higher in the high-grade RLPS tissues compared to that in the low-grade RLPS tissues (P=0.004). There was no correlation between RRM2 expression and overall survival (OS) or disease-free survival (DFS) in this group of RLPS patients (P> 0.05). RRM2 downregulation inhibited cell proliferation, promoted cell apoptosis, facilitated cell cycle from G1 phase to S phase and inhibited cell migration and invasion. Inhibition of RRM2 suppressed tumor growth in NOD/SCID mice. Protein microarray and Western blot verification showed that activity of Akt/mammalian target of rapamycin/eukaryotic translation initiation factor 4E binding protein 1 (Akt/mTOR/4EBP1) pathway was downregulated along with RRM2 downregulation.Conclusion: RRM2 was overexpressed in RLPS tissues, and downregulation of RRM2 could inhibit RLPS progression. In addition, suppression of RRM2 is expected to be a promising treatment for RLPS patients.Keywords: retroperitoneal liposarcoma, ribonucleotide reductase small subunit M2, tumor progression, Akt/mTOR/4EBP1 pathway

Yong Wang, Hong-wei Zhao, Cheng-fu Wang, Xiao-jiao Zhang, Jie Tao, Chun-sheng Cui, Qing-kun Meng, Yu Zhu, De-feng Luo, Ai-jie Hou, Bo Luan Department of Cardiology, The People’s Hospital of China Medical University, The People’s Hospital of Liaoning Province, Shenyang City, Liaoning Province, 110016, People’s Republic of ChinaCorrespondence: Ai-jie Hou; Bo LuanDepartment of Cardiology, The People’s Hospital of China Medical University, the People’s Hospital of Liaoning Province, No. 33, Wenyiroad, Shenhe District, Shenyang City, Liaoning Province 110016, People’s Republic of ChinaTel +86-17702488970Email 1758624242@qq.com; luanbo2016@163.comBackground: The incidence and prognosis of coronary slow-flow (CSF) and no-reflow phenomenon (NRP) in patients with coronary chronic total occlusion (CTO) who underwent percutaneous coronary intervention (PCI) remain unclear.Methods: This single-center prospective study aimed to investigate the incidence of CSF/NRP during CTO interventional therapy, determine predictors of CSF/NRP, and evaluate its effect on patient outcomes.Results: In this study, 552 patients with CTO who underwent PCI were included. CSF/NRP occurred in 16.1% of them. They had higher incidences of diabetes mellitus (53.9% vs 36.3%, p=0.002) and hypertension (50.6% vs 37.1%, p=0.018) and a lower incidence of retrograde filling grade > 2 (34.8% vs 47.1%, p=0.036). Patients with CSF/NRP had a higher neutrophil ratio (55.6± 19.4 vs 52.4± 18.3, p=0.038) and levels of low-density lipoprotein (LDL; 3.0± 0.8 vs 2.8± 0.6, p=0.029), fasting glucose (FG; 8.3± 1.3 vs 6.8± 1.1, p=0.005), uric acid (332.6± 82.9 vs 308.2± 62.8, p=0.045), and high-sensitivity C-reactive protein (Hs-CRP; 9.8± 4.8 vs 7.3± 3.9, p=0.036). A multivariate logistic regression analysis revealed that diabetes mellitus (odds ratio [OR], 1.962; 95% confidence interval [CI]: 1.198– 2.721; p=0.042), mean platelet volume (MPV; OR,1.284; 95% CI, 1.108– 1.895; p=0.046), LDL cholesterol (LDL-C; OR, 1.383; 95% CI, 1.105– 2.491; p=0.036), FG (OR, 2.095; 95% CI, 1.495– 2.899; p=0.018), Hs-CRP(OR, 2.218; 95% CI, 1.556– 3.519; p=0.029), and retrograde filling of grade > 2 (OR, 0.822; 95% CI, 0.622– 0.907; p=0.037) were independent predictors of CSF/NRP in CTO patients who underwent PCI. Kaplan-Meier analysis revealed that the patients in the CSF/NRP group had a significantly lower cumulative major cardiac and cerebrovascular events (MACCE)-free survival than those in the non-CSF/NRP group (p< 0.0001).Conclusion: Of the patients with CTO who underwent PCI, 16.1% developed CSF/NRP and had a significantly lower cumulative MACCE-free survival rate. Diabetes mellitus; higher levels of MPV, LDL-C, FG, and Hs-CRP; and a lower incidence of retrograde filling grade > 2 were independent predictors of CSF/NRP in CTO patients who underwent PCI. Thus, they can be used for risk stratification.Keywords: coronary slow-flow, no-reflow phenomenon, coronary chronic total occlusion, PCI, prognosis

Immunotherapies, such as chimeric antigen receptor (CAR) modified T cells and antibody-drug conjugates (ADCs), have revolutionized the treatment of cancer, especially of lymphoid malignancies. The application of targeted immunotherapy to patients with acute myeloid leukemia (AML) has been limited in particular by the lack of a tumor-specific target antigen. Gemtuzumab ozogamicin (GO), an ADC targeting CD33, is the only approved immunotherapeutic agent in AML. In our study, we introduce a CD33-directed third-generation CAR T-cell product (3G.CAR33-T) for the treatment of patients with AML. 3G.CAR33-T cells could be expanded up to the end-of-culture, that is, 17 days after transduction, and displayed significant cytokine secretion and robust cytotoxic activity when incubated with CD33-positive cells including cell lines, drug-resistant cells, primary blasts as well as normal hematopoietic stem and progenitor cells (HSPCs). When compared to second-generation CAR33-T cells, 3G.CAR33-T cells exhibited higher viability, increased proliferation and stronger cytotoxicity. Also, GO exerted strong antileukemia activity against CD33-positive AML cells. Upon genomic deletion of CD33 in HSPCs, 3G.CAR33-T cells and GO preferentially killed wildtype leukemia cells, while sparing CD33-deficient HSPCs. Our data provide evidence for the applicability of CD33-targeted immunotherapies in AML and its potential implementation in CD33 genome-edited stem cell transplantation approaches.

Jing Wang,1,2,* Jie Huang,1,3,* Shuang Yang,1,3 Chang Cui,1,3 Ling Ye,1,3 Sai-ying Wang,4 Guo-ping Yang,1,3 Qi Pei1,2 1Center for Clinical Pharmacology, The Third Xiangya Hospital, Central South University, Changsha, Hunan 410013, People’s Republic of China; 2Department of Pharmacy, The Third Xiangya Hospital, Central South University, Changsha, Hunan 410013, People’s Republic of China; 3Clinical Trails Center, The Third Xiangya Hospital, Central South University, Changsha, Hunan 410013, People’s Republic of China; 4Department of Anesthesiology, The Third Xiangya Hospital, Central South University, Changsha, Hunan 410013, People’s Republic of China*These authors contributed equally to this workCorrespondence: Guo-ping Yang; Qi PeiThe Third Xiangya Hospital, Central South University, Yinpenling Street, Yuelu District, Changsha, Hunan 410013, People’s Republic of ChinaTel +86 131 7041 9804Fax +86 731 8861 8326Email ygp9880@126.com; peiqi1028@126.comPurpose: To assess the pharmacokinetics and safety of pure S-ketamine (esketamine) in Chinese patients undergoing painless gastroscopy and evaluate the potential advantage of esketamine in clinical treatment compared with racemate ketamine hydrochloride injection.Patients and methods: A randomized, open-label, parallel-controlled, Phase I study was performed with 32 patients undergoing painless gastroscopy. Patients received a single dose of esketamine (0.5 mg/kg) or racemic ketamine (1 mg/kg, esketamine:R-ketamine=1:1), injected in 10 s. Blood samples were collected for pharmacokinetic analysis. The concentrations of esketamine, R-ketamine, S-norketamine, and R-norketamine were measured with a validated liquid chromatography with tandem mass spectrometry (LC-MS/MS) method.Results: After administering a single dose of esketamine and racemate ketamine, the pharmacokinetics parameters of esketamine and S-norketamine are both similar in treatment groups. The clearance of esketamine in two groups was 18.1±3.2 and 18.4±3.4 mL/min•kg, respectively. However, in the ketamine group, esketamine has a larger clearance than R-ketamine (18.4±3.4 mL/min·kg vs 15.8±3.1 mL/min·kg, P

Yingjian Song,1,* Huimin Liu,2,* Chunling Cui,3 Xiaonu Peng,1 Chaoyang Wang,1 Xudong Tian,4 Wenjun Li1 1Department of Thoracic Surgery, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai 264000, Shandong, People’s Republic of China; 2Department of Gastroenterology, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai 264000, Shandong, People’s Republic of China; 3Library, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai 264000, Shandong, People’s Republic of China; 4Department of Thoracic Surgery, Liaocheng People’s Hospital, Liaocheng 252000, Shandong, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xudong TianDepartment of Thoracic Surgery, Liaocheng People’s Hospital, No. 67, Changxi Road, Liaocheng, Shandong 252000, People’s Republic of ChinaTel +86-15653112705Email zhangding553977@126.comWenjun LiDepartment of Thoracic Surgery, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, No. 20 Yuhungding East Road, Zhifu District, Yantai 264000, Shandong, People’s Republic of ChinaTel +86-18653525277Email liwenjun90808@163.comObjective: To study the effect of peroxiredoxin 1 (PRDX1) on esophageal squamous carcinoma cells and determine whether it plays a role in regulating the PI3K/AKT signaling pathway.Methods: Three esophageal squamous cell carcinoma cell lines (Eca-109, EC9706, and KYSE150) and one normal cell line (human esophageal epithelial cells) were selected. The protein expression of peroxiredoxin 1 (PRDX1) and the activity of the PI3K/AKT pathway were detected via Western blotting. The proliferation ability of cells was detected through the MTT assay and cell clone formation. Apoptosis was detected using flow cytometry. Subsequently, cells were treated with a PI3K/AKT pathway inhibitor and activator, alone or in combination with silencing of PRDX1, and the above indicators were re-tested.Results: The expression of PRDX1 and activity of PI3K/AKT pathway-associated proteins were higher in esophageal cancer cells than in normal esophageal epithelial cells. Compared with normal human esophageal epithelial cells, the proliferation of the three types of esophageal cancer cells was increased, whereas their level of apoptosis was decreased (p

We present a new theoretical and numerical framework for modelling mechanically-assisted corrosion in elastic–plastic solids. Both pitting and stress corrosion cracking (SCC) can be captured, as well as the pit-to-crack transition. Localised corrosion is assumed to be dissolution-driven and a formulation grounded upon the film rupture–dissolution–repassivation mechanism is presented to incorporate the influence of film passivation. The model incorporates, for the first time, the role of mechanical straining as the electrochemical driving force, accelerating corrosion kinetics. The computational complexities associated with tracking the evolving metal–electrolyte interface are resolved by making use of a phase field paradigm, enabling an accurate approximation of complex SCC morphologies. The coupled electro-chemo-mechanical formulation is numerically implemented using the finite element method and an implicit time integration scheme; displacements, phase field order parameter and concentration are the primary variables. Five case studies of particular interest are addressed to showcase the predictive capabilities of the model, revealing an excellent agreement with analytical solutions and experimental measurements. By modelling these paradigmatic 2D and 3D boundary value problems we show that our formulation can capture: (i) the transition from activation-controlled corrosion to diffusion-controlled corrosion, (ii) the sensitivity of interface kinetics to mechanical stresses and strains, (iii) the role of film passivation in reducing corrosion rates, and (iv) the dependence of the stability of the passive film to local strain rates. The influence of these factors in driving the shape change of SCC defects, including the pit-to-crack transition, is a natural outcome of the model, laying the foundations for a mechanistic assessment of engineering materials and structures.

Can Cui,1 Xiaojing Cheng,2 Liang Yan,1 Huirong Ding,3 Xiaoya Guan,1 Wenlong Zhang,4 Xiuyun Tian,1 Chunyi Hao11Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Hepato-Pancreato-Biliary Surgery, Peking University Cancer Hospital & Institute, Beijing 100142, People’s Republic of China; 2Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Gastrointestinal Carcinoma Translational Research Laboratory, Peking University Cancer Hospital & Institute, Beijing, People’s Republic of China; 3Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Central Laboratory, Peking University Cancer Hospital & Institute, Beijing 100142, People’s Republic of China; 4Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Laboratory Animal, Peking University Cancer Hospital & Institute, Beijing 100142, People’s Republic of ChinaBackground: Colorectal cancer (CRC) is one of the most prevalent gastrointestinal malignancies. The incidence of CRC has been rapidly increasing in China. Transferrin receptor 1 (TfR1) is a key regulator of cellular iron homeostasis. Several studies have demonstrated TfR1 overexpression in a variety of human tumors, but the association between TfR1 and CRC remains unclear.Methods: TfR1 expression was evaluated in six CRC cell lines and tumor tissues. A total of 201 CRC patients were included for immunohistochemistry and 19 pairs of frozen tissues were used for real-time PCR. Cell proliferation, cell cycle, cell migration and invasion, and in vivo carcinogenesis were tested after downregulation of TfR1 by lentivirus. Protein microarray and Western blot analyses were used to explore the underlying mechanisms of TfR1 in CRC.Results: TfR1 expression was higher in CRC tissues than in normal tissues (57.2% vs 22.9%, P＜0.001). TfR1 expression was obviously higher in CRC tissues with well differentiation (P＝0.008), no lymph node metastasis (P＝0.002), no distant metastasis (P＝0.006), no vascular invasion (P＜0.001) and early TNM stage (P＝0.013). CRC patients with TfR1-positive expression had a better survival than those with TfR1-negative expression (P＝0.044). Downregulation of TfR1 expression inhibited cell proliferation, promoted cells from G1 phase to S phase and facilitated cell migration and invasion. Knockdown of TfR1 also suppressed tumor growth in BALB/C-nu mice. Protein microarray and Western blot analyses showed that the Janus protein tyrosine kinase/signal transducer and activator of transcription pathway was activated along with downregulation of TfR1 expression.Conclusion: Though TfR1 was overexpressed in colorectal cancer tissues, there was evidence that downregulation of TfR1 could promote cancer progression.Keywords: colorectal cancer, transferrin receptor 1, tumor progression, JAK/STAT pathway

Wenze Li,1,* Shuren Li,1,* Jie Yang,1 Chunyan Cui,2 Miao Yu,3 Yadong Zhang41Department of Urinary Surgery, The First hospital of Xiangtan city, Xiangtan 411101, People’s Republic of China; 2Department of Radiology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, People’s Republic of China; 3Center for Private Medical Service and Healthcare, The First Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510080, People’s Republic of China; 4Department of Andrology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, People’s Republic of China*These authors contributed equally tothis work Background: Integrin beta-like 1 (ITGBL1) was extensively demonstrated to contribute the metastasis and progression in a variety of cancers. However, its role of ITGBL1 in prostate cancer (PCa) is still not reported.Methods: Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blot were performed to detect ITGBL1 expression in PCa tissues and cell lines. Immunohistochemical (IHC) staining of ITGBL1 in 174 PCa tissues was performed. The influence of ITGL1 expression in PCa cells epithelial-mesenchymal transition (EMT), migration and invasion was investigated. Notably, the possible mechanisms underlying the action of ITGBL1 in vivo and vitro assays were explored.Results: We analyzed PCa dataset from The Cancer Genome Atlas (TCGA) and found that ITGBL1 was upregulated in PCa tissues. Overexpression of ITGBL1 is positively associated with the progression and lymph node metastasis in PCa patients. Furthermore, upregulating ITGBL1 enhanced the invasion, migration abilities and EMT in PCa cells. Conversely, downregulating ITGBL1 exhibited an opposite effect. Our findings further demonstrated that ITGBL1 promoted invasion and migration via activating NF-κB signaling in PCa cells.Conclusion: Therefore, our results identify a novel metastasis-related gene in PCa, which will help to develop a novel therapeutic strategy in metastatic PCa.Keywords: ITGBL1, EMT, NF-κB signaling, lymph node metastasis and prostate cancer

Yigang Wang,1 Binrong Wang,1 Junnan Liang,2 Caixia Cui,3 Chang Ying,1 Fang Huang,4 Buyun Ma,1 Xiumei Zhou,1 Liang Chu21College of Life Sciences, Zhejiang Sci-Tech University, Hangzhou 310018, People’s Republic of China; 2Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, People’s Republic of China; 3Department of Otorhinolaryngology, Affiliated Hospital of Hangzhou Normal University, Hangzhou 310015, People’s Republic of China; 4Department of Pathology, Zhejiang Provincal People’s Hospital, Hangzhou 310014, People’s Republic of ChinaBackground: Oncolytic virus can specifically replicate in and then lyse tumor cells, but seldom in normal cells. Further studies have shown the significant therapeutic effect of oncolytic virotherapy combining with other strategies, such as chemo-, radio-, and immunotherapy et al. In this study, we investigated the combinational effect of oncolytic virus ZD55-TRAIL and chemotherapy drug doxorubicin (DOX) on human laryngeal squamous cell carcinoma (LSCC).Methods: The effect of ZD55-TRAIL combined with DOX on cell growth was assessed in LSCC Hep2 cells and normal cells by MTT assay. Hochest 33342 staining was performed to observe cell morphological changes. Western blot was used to detect the expression of apoptotic activation proteins. The in vivo antitumor efficacy of combination treatment was estimated in laryngeal cancer xenograft models.Results: The combination of ZD55-TRAIL and DOX exhibited enhanced inhibitory effects on laryngocarcinoma cell growth, and had few side effects to normal cells in vitro. Chemotherapy drug increased the inducement of tumor cell apoptosis mediated by oncolytic virus. In vivo experiment confirmed that the combination treatment significantly inhibited Hep2 laryngocarcinoma xenografts growth in mice.Conclusion: The oncolytic viro-chemotherapy is a potent therapeutic approach for in vitro cytotoxicity evaluation of Hep2 cells and xenograft growth in vivo.Keywords: laryngocarcinoma, oncolytic virus, ZD55-TRAIL, doxorubicin

Ran Xu,1,2,* Chen Xu,1,* Chuntong Liu,3 Can Cui,4 Jing Zhu51Medical School of Nantong University, Jiangsu 226001, China; 2Huai’an Key Laboratory of Gastrointestinal Cancer, Jiangsu 223001, China; 3XuZhou Medical University, Jiangsu 221000, China; 4Macau University of Science and Technology, Macau 519020, China; 5Department of Oncology, The Affiliated Huaian NO 1 People’s Hospital of Nanjing Medical University, Jiangsu 223001, China *These authors contributed equally to this work Aim: The use of bevacizumab in combination therapy is an emerging trend in metastatic colorectal cancer treatment. However, the clinical value of different combination types remains under debate. Thus, a meta-analysis of randomized controlled trials (RCTs) comparing bevacizumab-based combination therapy with monotherapy (therapy that uses one type of treatment, such as chemotherapy or surgery alone, to treat metastatic colorectal cancer) was performed, aiming to evaluate the safety and efficacy of bevacizumab-based combination therapy and to find a more beneficial combination.Methods: We searched for clinical studies that evaluated bevacizumab-based combination therapy in metastatic colorectal cancer. We extracted data from these studies to evaluate the relative risk (RR) of overall response rate (ORR) and grade 3/4 treatment-related adverse events (AEs), HRs of overall survival (OS), and progression-free survival (PFS).Results: Eight RCTs were identified (n=3,424). Treatments included combinations of bevacizumab and oxaliplatin, fluorouracil, and leucovorin (FOLFOX4), combinations of bevacizumab and capecitabine and oxaliplatin, combinations of bevacizumab and fluorouracil/leucovorin, combinations of bevacizumab and irinotecan, fluorouracil, and leucovorin (IFL), and combinations of bevacizumab and capecitabine. Bevacizumab-based combination therapy showed higher ORR (RR: 1.40; 95% CI: 1.10–1.78; P=0.005), PFS (HR: 0.64; 95% CI: 0.55–0.73; P=0.000), and OS (HR: 0.82; 95% CI: 0.73–0.92; P=0.001) values than monotherapy. However, higher grade3/4 treatment-related AEs (RR: 1.27; 95% CI: 1.15–1.41; P=0.000) were observed in combination therapy than in monotherapy.Conclusion: This meta-analysis showed that the addition of IFL to bevacizumab better benefits PFS and safety. Adding FOLFOX4 was associated with better ORR and OS. The efficacy and safety of an IFL–bevacizumab–FOLFOX4 combination should be given greater weight in future clinical trials, guidelines, and clinical practice.Keywords: combination therapy, bevacizumab, metastatic colorectal cancer, meta-analysis

Jie Huang,1,2,* Cheng-xiao Fu,1,2,* Xiao-yan Yang,1,2 Chan Cui,1,2 Shuang Yang,1,2 Yun Kuang,1,2 Cheng-xian Guo,1,2 Pei Hu,3 Qi Pei,2,4 Guo-ping Yang1,2 1Center of Clinical Pharmacology, The Third Xiangya Hospital, Central South University, Changsha, Hunan 410013, People’s Republic of China; 2Center for Clinical Drug Evaluation, Central South University, Changsha, Hunan 410013, People’s Republic of China; 3Clinical Pharmacology Research Center, Peking Union Medical College Hospital, Beijing 100032, People’s Republic of China; 4Department of Pharmacy, The Third Xiangya Hospital, Central South University, Changsha, Hunan 410013, People’s Republic of China *These authors contributed equally to this work Purpose: To determine the pharmacokinetic properties of the common tablet of roflumilast administered in single and multiple oral doses in Chinese subjects.Subjects and methods: Both the single- and multiple-dose studies included 12 adults (6 males and 6 females). In this single-center, open-label study, single doses of 0.25, 0.375, and 0.5 mg were administered using a randomized, three-way crossover design, and then, the 0.375 mg dose was continued for 11 days once daily. The pharmacokinetic parameters for roflumilast and roflumilast N-oxide were determined and the safety evaluation included adverse events assessed by monitoring, physical examination, vital sign tests, and clinical laboratory tests.Results: After every single dose, the time to the maximum concentration (Cmax) of roflumilast (Tmax) was 0.25–2.0 hours; thereafter, the concentration declined, with a mean half-life (t1/2) of 19.7–20.9 hours over the range of 0.25–0.50 mg. As for roflumilast N-oxide, the mean t1/2 was 23.2–26.2 hours. The area under curve from the beginning to 24 hours (AUC0–24 h), the AUC until infinity (AUCinf), and the Cmax of roflumilast and roflumilast N-oxide increased in a dose-proportional manner. After multiple doses, the accumulation index (Rac) on the 11th day of the steady state was ~1.63 for roflumilast and 3.20 for roflumilast N-oxide. No significant sex differences were observed in the pharmacokinetic parameters of roflumilast and roflumilast N-oxide. In addition, there were no serious adverse events across the trial.Conclusion: Roflumilast was safe and well-tolerated in healthy volunteers, and a linear increase in its Cmax and AUC values was observed at doses ranging from 0.25 to 0.50 mg. Keywords: pharmacokinetics, roflumilast, roflumilast N-oxide, healthy volunteer, phosphodiesterase 4 inhibitor

T lymphocytes play an important role in cellular and adaptive immunity in vertebrates. The mechanisms of the fish immune system are little studied because of the lack of population-specific antibodies. This study examined the expression of two T lymphocyte markers, TCRα (PoTCRα) and CD8α (PoCD8α) in the Japanese flounder (Paralichthys olivaceus). The expression of PoTCRα and PoCD8α was mainly detected in immune/mucosal tissues. Recombinant PoTCRα and PoCD8α were expressed in pET32a and pET259, respectively. Then, rabbit anti-PoTCRα serum and rat anti-PoCD8α serum were prepared. Using serum, the characteristics of TCR+ and CD8+ head kidney leucocytes (HKLs) were investigated. The results of laser scanning confocal microscopy (LSCM) demonstrated that TCRα and CD8α were transmembrane proteins localized on the cell surface. The populations of CD8α

In strong contrast to the limited repair within the mammalian central nervous system, the spinal cord of adult zebrafish is capable of regeneration following injury. Understanding the mechanism underlying neural regeneration and functional recovery in spinal cord-injured zebrafish may lead to effective therapies for human spinal cord injury (SCI). Since neuropeptide Y (NPY) plays a protective role in the pathogenesis of several neurological diseases, in the present study, the effects of NPY on neuronal repair and subsequent recovery of motor function in adult zebrafish post-SCI were evaluated. Real-time quantitative PCR (qRT-PCR), in situ hybridization (ISH) and immunostaining of NPY revealed decreased NPY expression at 12 hours (h), 6 days (d) and 21 d after SCI. Double-immunostaining for NPY and Islet-1, a motoneuron marker, showed that NPY was expressed in spinal cord motoneurons. NPY morpholino (MO) treatment resulted in suppressed locomotor recovery and axon regrowth. PCNA and Islet-1 double-staining showed suppressed motoneuron proliferation in NPY-MO zebrafish. Similar to NYP, the mRNA level for NPY1R was also expressed within motoneurons and downregulated at 12 h and 21 d after SCI. Collectively, these data suggest that NPY expression in motoneurons promotes locomotor recovery and axon regrowth in adult zebrafish, possibly by regulating motoneuron proliferation through the activation of NPY1R.

Correlation analysis has long been a question of great interest in measuring the relationship among different variables and has been applied in many fields, such as dimension reduction, classification, and so on. However, current methods of correlation analysis take into account the linear relationship between multiple variables and only few works on nonlinear interaction of two variables have been considered. In this article, we first present a nonlinear analysis method of multiple (two or more) variables based on mutual information for tensor analysis (MITA). In addition, we extend the mutual‐information matrix analysis directly to MITA and show the multivariable mutual information formula based on Venn diagram. Experiments on multiview dimension reduction, including attacking internet traffic prediction, advertisement classification, and biometric structure prediction illustrate the effectiveness of the proposed method, especially in the case of low‐dimensional subspace.

A series of novel red-emitting phosphors BaZrGe3O9 : Mn4+ (BZG : Mn4+) were synthesized through high-temperature solid-state reaction method in order to explore their capabilities for application as red-emitting phosphors. The phosphors were characterized by X-ray diffraction, photoluminescence spectra, and decay curve measurements at the temperature ranging from 80 to 500 K. The luminescence intensity increases to maximum at doping concentration of 0.2 mol.%, and then decreases with concentration. Serious thermal quenching was also revealed. Keywords: red-emitting phosphor, germanate, Mn4+, concentration quenching, thermal stability.

Xiaoli Wang,1–3 Qi Sun,1–3 Chunying Cui,1–3 Jing Li,1–3 Yifan Wang1–3 1Department of Pharmaceutics, School of Pharmaceutical Sciences, Capital Medical University, Beijing, China; 2Beijing Area Major Laboratory of Peptide and Small Molecular Drugs, Capital Medical University, Beijing, China; 3Engineering Research Center of Endogenous Prophylactic of Ministry of Education of China, Capital Medical University, Beijing, China Background: The success of gene therapy is mostly dependent on the development of gene carrier. Graphene oxide (GO) possesses excellent aqueous solubility and biocompatibility, which is important for its biochemical and medical applications. Our previous work proved that GO can deliver siRNA into cells efficiently and downregulate the expression of desired protein.Methods: In this study, a novel delivery carrier, GO-R8/anti-HER2 (GRH), was developed by conjugating octaarginine (R8) and anti-HER2 antibody with GO as a tumor active-targeting vector for survivin-siRNA delivery.Results: GRH/survivin-siRNA formed nanoglobes of 195±10nm in diameter. Real-time polymerase chain reaction analysis revealed that survivin messenger RNA expression showed a 42.4%±2.69% knockdown. The expression of survivin protein was downregulated to 50.86%±2.94% in enzyme-linked immunosorbent assay. In MTT tests, GRH exhibited no testable cytotoxicity. In vivo, GRH/survivin-siRNA showed gene silencing and inhibition of tumor growth.Conclusion: The in vitro and in vivo results consistently demonstrated that GRH/survivin-siRNA has potential to be an efficient gene silencing carrier for siRNA delivery in cancer therapy. Keywords: graphene oxide, GO, survivin-siRNA, anti-HER2 antibody, small interfering RNA, gene delivery, nanocarrier

Lateral inhibition is an important functionality in neuromorphic computing, modeled after the biological neuron behavior that a firing neuron deactivates its neighbors belonging to the same layer and prevents them from firing. In most neuromorphic hardware platforms lateral inhibition is implemented by external circuitry, thereby decreasing the energy efficiency and increasing the area overhead of such systems. Recently, the domain wall -- magnetic tunnel junction (DW-MTJ) artificial neuron is demonstrated in modeling to be inherently inhibitory. Without peripheral circuitry, lateral inhibition in DW-MTJ neurons results from magnetostatic interaction between neighboring neuron cells. However, the lateral inhibition mechanism in DW-MTJ neurons has not been studied thoroughly, leading to weak inhibition only in very closely-spaced devices. This work approaches these problems by modeling current- and field- driven DW motion in a pair of adjacent DW-MTJ neurons. We maximize the magnitude of lateral inhibition by tuning the magnetic interaction between the neurons. The results are explained by current-driven DW velocity characteristics in response to external magnetic field and quantified by an analytical model. Finally, the dependence of lateral inhibition strength on device parameters is investigated. This provides a guideline for the optimization of lateral inhibition implementation in DW-MTJ neurons. With strong lateral inhibition achieved, a path towards competitive learning algorithms such as the winner-take-all are made possible on such neuromorphic devices., 8 pages, 5 figures

Sifan Yu,* Tianxiao Xu,* Jie Dai, Meng Ma, Huan Tang, Zhihong Chi, Lu Si, Chuanliang Cui, Xinan Sheng, Yan Kong, Jun Guo Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Renal Cancer and Melanoma, Peking University Cancer Hospital & Institute, Beijing 100142, China *These authors contributed equally to this work Background: Asian populations are more likely to develop acral melanoma (AM) than Caucasians. The high-dose interferon (HD-IFN) α-2b regimen is the main adjuvant treatment for AM. TERT encodes the catalytic subunit of telomerase reverse transcriptase, which plays an important role in melanoma. Frequent TERT mutation and increased TERT gene expression have been described in AM. Our study aimed to investigate the status and the clinical significance of TERT copy number in a large cohort of patients with AM and to analyze the relationship between TERT copy number gain and the efficiency of HD-IFN.Patients and methods: A total of 573 melanoma samples were retrospectively collected and analyzed for TERT copy number via Sanger sequencing. Clinical data of patients were also collected.Results: TERT copy gain (copy number >2) was detected in 257 of the 573 patients with AM (44.9%). Of the 573 patients, 81 (14.1%) had a high copy gain (copy number >4). Patients with ulceration showed a significantly higher copy gain rate of TERT compared to the patients without ulceration (P=0.028). Patients with a tumor thicker than 4 mm also had a higher copy number rate of TERT than those with

Qi Sun,1–3 Xiaoli Wang,1–3 Chunying Cui,1–3 Jing Li,1–3 Yifan Wang1–3 1Department of Pharmaceutics, School of Pharmaceutical Sciences, Capital Medical University, Beijing, China; 2Beijing Area Major Laboratory of Peptide and Small Molecular Drugs, Beijing, China; 3Engineering Research Center of Endogenous Prophylactic of Ministry of Education of China, Beijing, China Background: Graphene oxide (GO) has attracted intensive interest in biological and medical fields in recent years due to its unique physical, chemical, and biological properties. In our previous work, we proved that GO could deliver small interfering RNA (siRNA) into cells and downregulate the expression of the desired gene. Methods: This study investigated the potential of a modified GO nanocarrier for co-delivery of siRNA and doxorubicin (DOX) for enhanced cancer therapy. Fourier transform infrared spectroscopy, laser particle size analyzer, UV-visible spectroscopy, gel electrophoresis retardation, and in vitro release assay were studied. Results: The results of real-time polymerase chain reaction revealed that the expression of vascular endothelial growth factor (VEGF) mRNA was decreased 46.84%±3.72% (mean ± SD). Enzyme-linked immunosorbent assay indicated that the expression of VEGF protein was downregulated to 52.86%±1.10% (mean ± SD) in vitro. In vivo tumor growth assay GO-poly-L-lysine hydrobromide/folic acid (GPF)/DOX/siRNA exhibited gene silencing and tumor inhibition (66.95%±2.35%, mean ± SD) compared with naked siRNA (1.62%±1.47%, mean ± SD) and DOX (33.63%±5.85%, mean ± SD). GPF/DOX/siRNA exhibited no testable cytotoxicity. Conclusion: The results indicated that co-delivery of siRNA and DOX by GPF could be a promising application in tumor clinical therapy. Keywords: graphene oxide, siRNA delivery, co-delivery carrier, cervical carcinoma

Chunmei Cui, Hong Lu Department of Ophthalmology, Beijing Chao-Yang Hospital, Beijing, China Purpose: Conbercept is a new anti-vascular endothelial growth factor (VEGF) drug approved for the treatment of age-related macular degeneration (AMD). Although this novel drug has been widely used in clinic, unlike other anti-VEGF drugs, validation and consensus on its method of clinical application and clinical safety have not yet been achieved.Methods: Relevant literature was searched on PubMed, Web of Science, China National Knowledge Internet, and Wanfang Data. Stata 12.0 was used for data analysis. Random- and fixed-effect models were employed to evaluate heterogeneity. Best-corrected visual acuity (BCVA) and central retinal thickness (CRT) were utilized to measure the improvement of AMD patients.Results: In this study, we analyzed conbercept administration and compared its application with other control clinical methods for AMD treatment. Ranibizumab, triamcinolone, and traditional transpupillary thermotherapy (TTT) were administered in the control group. No differences were found in the BCVA and CRT improvement between the groups treated with conbercept and ranibizumab. However, the conbercept group had a lower serum VEGF level. After 3 months of treatment, conbercept led to a more significant BCVA and CRT improvement than triamcinolone. A more considerable BCVA improvement was observed in the group treated with conbercept than in the group treated with TTT. Moreover, even 6 months after the treatment, the effect of conbercept on CRT improvement was still more pronounced than that of TTT.Conclusion: In AMD patients, conbercept exerts considerably more positive effects on the long-term BCVA and CRT improvement than triamcinolone and TTT. The serum VEGF level in the conbercept group was lower than that in the ranibizumab group. Keywords: AMD, VEGF, conbercept, BCVA, CRT

Bo Wu,1,2 Shu-Ting Lu,1 Kai Deng,2 Hui Yu,2 Can Cui,2 Yang Zhang,2 Ming Wu,2 Ren-Xi Zhuo,2 Hai-Bo Xu,1 Shi-Wen Huang2 1Department of Radiology, Zhongnan Hospital of Wuhan University, 2Key Laboratory of Biomedical Polymers, Ministry of Education, Department of Chemistry, Wuhan University, Wuhan, People’s Republic of China Abstract: In recent years, there has been increasing interest in developing a multifunctional nanoscale platform for cancer monitoring and chemotherapy. However, there is still a big challenge for current clinic contrast agents to improve their poor tumor selectivity and response. Herein, we report a new kind of Gd complex and folate-coated redox-sensitive lipid-polymer hybrid nanoparticle (Gd-FLPNP) for tumor-targeted magnetic resonance imaging and therapy. Gd-FLPNPs can simultaneously accomplish diagnostic imaging, and specific targeting and controlled release of doxorubicin (DOX). They exhibit good monodispersity, excellent size stability, and a well-defined core-shell structure. Paramagnetic nanoparticles based on gadolinium-diethylenetriaminepentaacetic acid-bis-cetylamine have paramagnetic properties with an approximately two-fold enhancement in the longitudinal relaxivity compared to clinical used Magnevist. For targeted and reduction-sensitive drug delivery, Gd-FLPNPs released DOX faster and enhanced cell uptake in vitro, and exhibited better antitumor effect both invitro and in vivo. Keywords: redox-sensitive, tumor-targeted, gadolinium, contrast agents, PLGA

Jianyu Lin,1,* Jing Wang,2,* Peng Yue,3 Xingmao Zhang,4 Ren Lang,4 Yuan Wang,4 Chen Cui,4 Qiang He4 1Integrated Department, 2Patient Service Center, The Affiliated Hospital to Capital Medical University, Beijing Chaoyang Hospital, 3School of Nursing, Department of Basic Nursing, Capital Medical University, 4Department of Hepatobiliary Surgery, The Affiliated Hospital to Capital Medical University, Beijing Chaoyang Hospital, Beijing, People’s Republic of China *These authors contributed equally to this work Objective: Intestinal perforation is a rare complication after liver transplantation. This study was designed to calculate the incidence and investigate the outcomes of intestinal perforation in adult liver transplant patients.Materials and methods: The clinical records of liver transplant recipients between January 2014 and June 2016 were obtained. The incidence of intestinal perforation was calculated, and high risk factors were analyzed.Results: The mean operative time was 8.5h (range: 6–11h). The mean portal vein occlusion time was 66.5min (range: 58–72min), and the mean cold ischemia time was 7.9h (range: 6.5–9.5h). Four (2.7%) patients developed intestinal perforation from 9 to 14days postliver transplant. All perforations were single and repaired by interrupted silk sutures. Two patients uneventfully recovered, but intestinal perforation recurred in two other patients. Simple repair was undertaken in one patient, and terminal ileum resection and ileostomy were performed in the other patient. There were no perioperative deaths.Conclusion: The incidence of intestinal perforation after liver transplantation is low. Prompt diagnosis and treatment should be carried out to reduce comorbidities and mortality. Keywords: liver transplant, intestinal perforation, incidence, treatment, nursing

Xiaojie Lv,1 Ming Zhao,1,2 Yuiji Wang,1 Xi Hu,1 Jianhui Wu,1 Xueyun Jiang,1 Shan Li,1 Chunying Cui,1 Shiqi Peng1 1Beijing Area Major Laboratory of Peptide and Small Molecular Drugs, Engineering Research Center of Endogenous Prophylactic of Ministry of Education of China, Beijing Laboratory of Biomedical Materials, College of Pharmaceutical Sciences, Capital Medical University, Beijing, People’s Republic of China; 2Department of Biomedical Science and Environmental Biology, Kaohsiung Medical University, Kaohsiung, Taiwan Abstract: In the treatment of cancer patients, cisplatin (CDDP) exhibits serious cardiac and renal toxicities, while classical combinations related to CDDP are unable to solve these problems and may result in worse prognosis. Alternately, this study covalently conjugated 6-mercaptopurine (6MP) onto the surface of mercapto-modified mesoporous silica nanoparticles (MSNS) to form MSNS-6MP and loaded CDDP into the holes on the surface of MSNS-6MP to form MSNS-6MP/CDDP, a tumor-targeting nano-releasing regime for CDDP and 6MP specifically. In the S180 mouse model, the anti-tumor activity and overall survival of MSNS-6MP/CDDP (50mg·kg-1·day-1, corresponding to 1mg·kg-1·day-1 of 6MP and 5mg·kg-1·day-1 of CDDP) were significantly higher than those of CDDP alone (5mg·kg-1·day-1) or CDDP (5mg·kg-1·day-1) plus 6MP (1mg·kg-1·day-1). The assays of serum alanine aminotransferase, aspartate aminotransferase and creatinine, as well as the images of myocardium and kidney histology, support that MSNS-6MP/CDDP is able to completely eliminate liver, kidney and heart toxicities induced by CDDP alone or CDDP plus 6MP. Keywords: 6-mercaptopurine, cisplatin, mesoporous silica nanoparticles, cancer therapy, nanomedicine

Ciren Yangzong,1,2 Sanguan Lerkiatbundit,3 Ouzhu Luobu,4 Chaoying Cui,4 Tippawan Liabsuetrakul,2 Baima Kangzhuo,4 Deji Quzong,4 Luobu Zhandui,5 Pu Zhen,6 Virasakdi Chongsuvivatwong2 1Department of Preventive Medicine, Medical College, Tibet University, Lhasa, Tibet Autonomous Region, People’s Republic of China; 2Epidemiology Unit, Faculty of Medicine, 3Department of Pharmacy Administration, Faculty of Pharmaceutical Science, Prince of Songkla University, Songkhla, Thailand; 4High Altitude Research Centre, 5Experimental Centre, 6Department of Pharmaceutical Science, Medical College, Tibet University, Lhasa, Tibet Autonomous Region, People’s Republic of China Abstract: Parenting style experienced during childhood has profound effects on children’s futures. Scales developed in other countries have never been validated in the Tibetan context. The present study aimed to examine the construct validity and reliability of a Tibetan translation of the 23-item short form of the Egna Minnen Beträffande Uppfostran [One’s Memories of Upbringing] (s-EMBU) and to test the correlation between the parenting styles of fathers and mothers. A cross-sectional study was conducted in a sample of 847 students aged 12–21 years from Lhasa, Tibet, during September and October 2015 with a participation rate of 97.7%. The Tibetan translation of self-completed s-EMBU was administered. Confirmatory factor analysis was employed to test the scale’s validity on the first half of the sample and was then cross-validated with the second half of the sample. The final model consisted of six factors: three (rejection, emotional warmth, and overprotection) for each parent, equality constrained on factor loadings, factor correlations, and error variance between father and mother. Father–mother correlation coefficients ranged from 0.81 to 0.86, and the level of consistency ranged from 0.62 to 0.82. Thus, the slightly modified s-EMBU is suitable for use in the Tibetan culture where both the father and the mother have consistent parenting styles. Keywords: Tibetan, parenting style, s-EMBU, validity, reliability, Egna Minnen Beträffande Uppfostran

All-polymer organic solar cells offer exceptional stability. Unfortunately, the use of bulk heterojunction (BHJ) structure has the intrinsic challenge to control the side-chain entanglement and backbone orientation to achieve sophisticated phase separation in all-polymer blends. Here, we revealed that the P-i-N structure can outperform the BHJ ones with a nearly 50% efficiency improvement, reaching a power conversion efficiency approaching 10%. This P-i-N structure can also provide an enhanced internal electric field and remarkably stable morphology under harsh thermal stress. We have further demonstrated generality of the P-i-N structure in several other all-polymer systems. Considering the adjustable polymer molecular weight and solubility, the P-i-N device structure can be more beneficial for all-polymer systems. With the design of more crystalline polymers, the antiquated P-i-N structure can further show its strength in all-polymer systems by simplified morphology control and improved carrier extraction, becoming a more favorite device structure than the dominant BHJ structure.

Correlation analysis has been proposed to measure the relationship among different variables, with application in multi-view dimension reduction. However, the existing methods usually are used by covariance in a linear way rather than the nonlinear effects being considered among multiple variables and only few works on nonlinear interaction of two variables have been considered. In this paper we propose a nonlinear analysis of multiple (more than two) variables based on mutual information for tensors analysis (MITA) firstly. In addition, we extend the mutual information matrix analysis directly to mutual information tensor analysis and show the mutual information formula for multiple variables theoretically. Experiment on multi-view dimension reduction, including attacking internet traffic detection, has been done to illustrate the effectiveness of the proposed method, especially in the case of low dimensional subspace.

Ning Song,1 Ming Zhao,1,2 Yuji Wang,1 Xi Hu,1 Jianhui Wu,1 Xueyun Jiang,1 Shan Li,1 Chunying Cui,1 Shiqi Peng1 1Beijing Area Major Laboratory of Peptide and Small Molecular Drugs, Engineering Research Center of Endogenous Prophylactic of Ministry of Education of China, Beijing Laboratory of Biomedical Materials, College of Pharmaceutical Sciences of Capital Medical University, Beijing, People’s Republic of China; 2Department of Biomedical Science and Environmental Biology, Kaohsiung Medical University, Kaohsiung, Taiwan Abstract: In spite of the usual combination form of methotrexate (MTX)/mitoxantrone (MIT) and various complex combination regimens of MTX/MIT with other anticancer drugs, the survival period, cure rate, and systemic toxicity still need to be improved. For this purpose, a nanostructured amino group-modified mesoporous silica nanoparticles (MSNN)–MTX/MIT was designed. In the preparation, the surface of mesoporous silica nanoparticles (MSNs) was modified with amino groups to form MSNN. The covalent modification of the amino groups on the surface of MSNN with MTX resulted in MSNN–MTX. The loading of MIT into the surface pores of MSNN–MTX produced nanostructured MSNN–MTX/MIT. Compared with the usual combination form (MTX/MIT), nanostructured MSNN–MTX/MIT increased the survival period greatly, heightened the cure rate to a great extent, and lowered the systemic toxicity of the treated S180 mice, significantly. These superior in vivo properties of nanostructured MSNN–MTX/MIT over the usual combination form (MTX/MIT) were correlated with the former selectively releasing MTX and MIT in tumor tissue and inside cancer cells in vitro. The chemical structure and the nanostructure of MSNN–MTX/MIT were characterized using infrared and differential scanning calorimeter spectra as well as transmission electron microscope images, respectively. Keywords: mitoxantrone, methotrexate, mesoporous silica nanoparticles, cancer therapy, nanomedicine

Background: Myelination, degeneration and regeneration are implicated in crucial responses to injury in the peripheral nervous system. Considering the progression of amyotrophic lateral sclerosis (ALS), we used the superoxide dismutase 1 (SOD1)-G93A transgenic mouse model of ALS to investigate the effects of mutant SOD1 on the peripheral nerves. Methods: Changes in peripheral nerve morphology were analyzed in SOD1 mutant mice at various stages of the disease by toluidine blue staining and electron microscopy (EM). Schwann cell proliferation and recruitment of inflammatory factors were detected by immunofluorescence staining and quantitative reverse transcription PCR and were compared between SOD1 mutant mice and control mice. Furthermore, western blotting (WB) and TUNEL staining were used to investigate axonal damage and Schwann cell survival in the sciatic nerves of mice in both groups. Results: An analysis of the peripheral nervous system in SOD1-G93A mice revealed the following novel features: (i) Schwann cells and axons in mutant mice underwent changes that were similar to those seen in the control mice during the early development of peripheral nerves. (ii) The peripheral nerves of SOD1-G93A mice developed progressive neuropathy, which presented as defects in axons and myelin, leading to difficulty in walking and reduced locomotor capacity at a late stage of the disease. (iii) Macrophages were recruited and accumulated, and nerve injury and a deficit in the blood-nerve barrier were observed. (iv) Proliferation and the inflammatory micro-environment were inhibited, which impaired the regeneration and remyelination of axons after crush injury in the SOD1-G93A mice. Conclusions: The mutant human SOD1 protein induced axonal and myelin degeneration during the progression of ALS and participated in axon remyelination and regeneration in response to injury.

Functionalized poly(ethylene dioxythiophene) (f-PEDOT) was copolymerized with two vinyl monomers of different hydrophilicity, acrylic acid and hydroxyethyl methacrylate, to produce electroconductive hydrogels with a range of physical and electronic properties. These hydrogels not only possessed tailored physical properties, such as swelling ratios and mechanical properties, but also displayed electroactivity dependent on the chemical composition of the network. Raman spectroscopy indicated that the functional PEDOT in the hydrogels is in an oxidized form, most likely accounting for the good electrochemical response of the hydrogels observed in physiological buffer. In vitro cell studies showed that cardiac cells respond differently when seeded on hydrogel substrates with different compositions. This study presents a facile approach for the fabrication of electroconductive hydrogels with a range of properties, paving the way for scaffolds that can meet the requirements of different electroresponsive tissues.

© 2017 IEEE. A new wake-up receiver (WuRx) designed in 0.13 μm CMOS process is hybrid-integrated with a micro-electromechanical system (MEMS) RF resonator. While only consuming 166 nW of power (18.8 nW for the comparator and 147 nW for periphery), the WuRx is capable of detecting RF signals as weak as -60 dBm. In order to achieve this sensitivity, a passive voltage-boosting network comprised of a high quality factor (high-Q) piezoelectric MEMS resonator is utilized, in place of an inductor, to amplify the received voltages applied to a CMOS rectifier. The output of the rectifier is then applied to a low-power comparator used to set a logical bit that indicates when an RF signal has been detected. The trade-offs in designing the voltage boosting network are explained and an equation for the optimum number of rectifier stages is derived.

This paper analyses the migration intentions of university graduates using the Theory of Planned Behaviour not just to unravel their intention but also to uncover how subjective perceptions enter the decision-making process. The results suggest that perceived parental and peer pressures have strong direct effects on the formation of the intention, and exert indirect effects by shaping positive attitudes about staying in the city. In terms of behavioural control, the expected difficulty in finding a satisfactory job does not influence the intention. The perceived difficulty in finding affordable housing, however, acts as a barrier to the intention to stay. (C) 2016 Elsevier Ltd. All rights reserved.

This paper analyses the migration intentions of university graduates using the Theory of Planned Behaviour not just to unravel their intention but also to uncover how subjective perceptions enter the decision-making process. The results suggest that perceived parental and peer pressures have strong direct effects on the formation of the intention, and exert indirect effects by shaping positive attitudes about staying in the city. In terms of behavioural control, the expected difficulty in finding a satisfactory job does not influence the intention. The perceived difficulty in finding affordable housing, however, acts as a barrier to the intention to stay.

With the deepening of economic restructuring and the expansion of higher education, skilled migrants comprise an increasingly significant part of the internal migrant population. With the aim to settle down permanently in the city, skilled migrants need to be considered “prospective citizens”, who compete with locals to achieve homeownership in the urban housing market. An individual’s housing career is an outcome of the interactions between the resources and restrictions at the micro level and the complex institutional circumstances at the macro level. A better understanding of the housing career of skilled migrants has important implications for the establishment of a well-functioning housing market, the optimization of labour mobility, the efficient allocation of resources and the reshaping of urban social space (Li & Siu, 2001; Sánchez & Andrews, 2011). This research demonstrates the ambiguous position of skilled migrants in the urban housing market. Skilled migrants are better off than unskilled migrants when it comes to access to the formal city, since they are less constrained by institutional barriers and have access to good quality housing. However, an evident gap is observed in this research between skilled migrants and their local counterparts. Skilled migrants experience a high level of residential mobility, and take more time and steps to enter homeownership. This delay can be attributed foremost to the limited intergenerational transmission of wealth, while restricted knowledge about the local housing market and later partnership also play a role. Furthermore, this dissertation contributes to the debate on the influence of market versus institutional factors on housing consumption in China. Using the dataset obtained in Nanjing in 2012, when commodity housing has emerged as a major pathway to homeownership in urban China, Chapters 4 and 5 show an up-to-date picture that market factors that are closely related to life course trajectories play a more decisive role than institutional factors in shaping individuals’ housing behaviour.

© 2014 by the American Society of Nephrology. Despite the increasing prevalence of CKD in the United States, there is a declining interest among United States medical graduates in nephrology as a career choice. Effective programs are needed to generate interest at early educational stages when career choices can be influenced. The Kidney Disease Screening and Awareness Program (KDSAP) is a novel program initiated at Harvard College that increases student knowledge of and interest in kidney health and disease, interest in nephrology career paths, and participation in kidney disease research. This model, built on physician mentoring, kidney screening of underserved populations, direct interactions with kidney patients, and opportunities to participate in kidney research, can be reproduced and translated to other workforce-challenged subspecialties.