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80篇 您的检索式:作者名="Zhe Rui"
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1Role of gut microbiota via the gut-liver-brain axis in digestive diseases显示文摘The gut-brain axis is a bidirectional information interaction system between the central nervous system(CNS) and the gastrointestinal tract, in which gut microbiota plays a key role. The gut microbiota forms a complex network with the enteric nervous system, the autonomic nervous system, and the neuroendocrine and neuroimmunity of the CNS, which is called the microbiota-gut-brain axis. Due to the close anatomical and functional interaction of the gut-liver axis, the microbiota-gut-liver-brain axis has attracted increased attention in recent years. The microbiota-gut-liver-brain axis mediates the occurrence and development of many diseases, and it offers a direction for the research of disease treatment. In this review, we mainly discuss the role of the gut microbiota in the irritable bowel syndrome, inflammatory bowel disease, functional dyspepsia, non-alcoholic fatty liver disease, alcoholic liver disease, cirrhosis and hepatic encephalopathy via the gut-liver-brain axis, and the focus is to clarify the potential mechanisms and treatment of digestive diseases based on the further understanding of the microbiota-gut-liver-brain axis.Jian-Hong Ding Zhe Jin Xiao-Xu Yang Jun Lou Wei-Xi Shan Yan-Xia Hu Qian Du Qiu-Shi Liao Rui Xie Jing-Yu Xu 2020World Journal of Gastroenterology2020,26,40:13
2Optimal planning of energy storage system in active distribution system based on fuzzy multi-objective bi-level optimization显示文摘A fuzzy multi-objective bi-level optimization problem is proposed to model the planning of energy storage system(ESS) in active distribution systems(ADS). The proposed model enables us to take into account how optimal operation strategy of ESS in the lower level can affect and be affected by the optimal allocation of ESS in the upper level. The power characteristic model of micro-grid(MG)and typical daily scenarios are established to take full consideration of time-variable nature of renewable energy generations(REGs) and load demand while easing the burden of computation. To solve the bi-level mixed integer problem, a multi-subgroup hierarchical chaos hybrid algorithm is introduced based on differential evolution(DE) and particle swarm optimization(PSO). The modified IEEE-33 bus benchmark distribution system is utilized to investigate the availability and effectiveness of the proposed model and the hybrid algorithm. Results indicate that the planningmodel gives an adequate consideration to the optimal operation and different roles of ESS, and has the advantages of objectiveness and reasonableness.Rui LI Wei WANG Zhe CHEN Xuezhi WU 2018Journal of Modern Power Systems and Clean Energy2018,6,2:9
3Two-Dimensional Tellurium:Progress,Challenges,and Prospects显示文摘Since the successful fabrication of two-dimensional(2D)tellurium(Te)in 2017,its fascinating properties including a thickness dependence bandgap,environmental stability,piezoelectric effect,high carrier mobility,and photoresponse among others show great potential for various applications.These include photodetectors,field-effect transistors,piezoelectric devices,modulators,and energy harvesting devices.However,as a new member of the 2D material family,much less known is about 2D Te compared to other 2D materials.Motivated by this lack of knowledge,we review the recent progress of research into 2D Te nanoflakes.Firstly,we introduce the background and motivation of this review.Then,the crystal structures and synthesis methods are presented,followed by an introduction to their physical properties and applications.Finally,the challenges and further development directions are summarized.We believe that milestone investigations of 2D Te nanoflakes will emerge soon,which will bring about great industrial revelations in 2D materials-based nanodevice commercialization.Zhe Shi Rui Cao Karim Khan Ayesha Khan Tareen Xiaosong Liu Weiyuan Liang Ye Zhang Chunyang Ma Zhinan Guo Xiaoling Luo Han Zhang 2020Nano-Micro Letters2020,12,8:8
4Interaction between Schwann cells and other cells during repair of peripheral nerve injury显示文摘Peripheral nerve injury(PNI)is common and,unlike damage to the central nervous system injured nerves can effectively regenerate depending on the location and severity of injury.Peripheral myelinating glia,Schwann cells(SCs),interact with various cells in and around the injury site and are important for debris elimination,repair,and nerve regeneration.Following PNI,Wallerian degeneration of the distal stump is rapidly initiated by degeneration of damaged axons followed by morphologic changes in SCs and the recruitment of circulating macrophages.Interaction with fibroblasts from the injured nerve microenvironment also plays a role in nerve repair.The replication and migration of injury-induced dedifferentiated SCs are also important in repairing the nerve.In particular,SC migration stimulates axonal regeneration and subsequent myelination of regenerated nerve fibers.This mobility increases SC interactions with other cells in the nerve and the exogenous environment,which influence SC behavior post-injury.Following PNI,SCs directly and indirectly interact with other SCs,fibroblasts,and macrophages.In addition,the inter-and intracellular mechanisms that underlie morphological and functional changes in SCs following PNI still require further research to explain known phenomena and less understood cell-specific roles in the repair of the injured peripheral nerve.This review provides a basic assessment of SC function post-PNI,as well as a more comprehensive evaluation of the literature concerning the SC interactions with macrophages and fibroblasts that can influence SC behavior and,ultimately,repair of the injured nerve.Wen-Rui Qu Zhe Zhu Jun Liu De-Biao Song Heng Tian Bing-Peng Chen Rui Li Ling-Xiao Deng 2021Neural Regeneration Research2021,16,1:8
5Predictive factors associated with gefitinib response in patients with advanced non-small-cell lung cancer(NSCLC)显示文摘Purpose: A number of different clinical characteristics have been reported to singly correlate with therapeutic activity of epidermal growth factor receptor(EGFR) tyrosine kinase inhibitors(TKIs) in advanced non-small-cell lung cancer(NSCLC). This study aimed to identify predictive factors associated with prognostic benefits of gefitinib.Patients and methods: EGFR gene typing in 33 advanced NSCLC patients received gefitinib(250 mg/day) were analyzed with mutant-enriched PCR assay. Gefitinib response was evaluated with potential predictive factors retrospectively.Results: The overall objective response rate(ORR) and median progression-free survival(PFS) in the 33 patients treated by gefitinib were 45.5% and 3.0(2.0-4.0) months. The ORR and median PFS in EGFR gene mutation patients were significantly higher/longer than those in EGFR gene wild-type patients(P<0.01). Similarly, the ORR and median PFS in non-smoker patients were significantly higher/longer than those in smoker patients(P<0.05, P<0.01, respectively). However, no difference for ORR and median PFS occurred between male and female patients. Logistic multivariate analysis showed that only EGFR mutated gene was significantly associated with the ORR(P<0.01). Both EGFR mutated gene and non-smoker were the major factors that contributed to PFS(P<0.05). Conclusions: EGFR mutated gene and non-smoker status are potential predictors for gefitinib response in NSCLC patients.Lian Chen Rui Chen Zhe Zhu Yichen Zhang Zhengwei Wen Yun Li Xiaoming Li Yuwen Luo Liyu Ma Shuguang Lin Xin Chen 2014Chinese Journal of Cancer Research2014,26,4:7
6Hydrochemical regime and its mechanism in Yamzhog Yumco Basin, South Tibet显示文摘The hydrochemistry of alpine lakes reflects water characteristic and its response to climatic change. Over 300 water samples had been collected from 52 sites of 5 lakes and 7 inflowing rivers in the Yamzhog Yumco Basin, South Tibet, during 2009–2014, basing which the hydrochemical regime and its mechanism were analyzed along with the adoption of hydrological investigations in 1979 and 1984 as well. Results revealed that the waters were hard with weak alkalinity for the Yamzhog Yumco Basin. Most of them were fresh, and the rest were slightly saline. The hydrochemical types of 5 lakes(i.e., Lake Yamzhog Yum Co, Puma Yum Co, Bajiu Co, Kongmu Co, and Chen Co) were SO_4^(2–)–HCO_3~––Mg^(2+)–Na^+, HCO_3~–– SO2–2+4–Mg^(2+)–Ca, SO_4^(2–)–Mg^(2+)–Na^+, SO_4^(2–)–HCO_3~––Ca^(2+), and SO_4^(2–)–Na^+–Mg^(2+)–Ca^(2+), respectively. As for rivers, HCO_3~– and SO_4^(2–) were the major anions, and Ca^(2+) was the dominant cation. Lake Yamzhog Yum Co, the largest lake in the basin, exhibited remarkable spatial variations in hydrochemistry at its surface but irregular changes with depth. The weathering of evaporates and carbonates, together with evaporation and crystallization, were the major mechanisms controlling the hydrochemistry of waters in the Yamzhog Yumco Basin. Global warming also had significant impacts on hydrochemical variations.ZHE Meng ZHANG Xueqin WANG Buwei SUN Rui ZHENG Du 2017Journal of Geographical Sciences2017,27,9:7
7Salvianolic acid B protects the myelin sheath around injured spinal cord axons显示文摘Salvianolic acid B,an active pharmaceutical compound present in Salvia miltiorrhiza,exerts a neuroprotective effect in animal models of brain and spinal cord injury.Salvianolic acid B can promote recovery of neurological function;however,its protective effect on the myelin sheath after spinal cord injury remains poorly understood.Thus,in this study,in vitro tests showed that salvianolic acid B contributed to oligodendrocyte precursor cell differentiation,and the most effective dose was 20 μg/m L.For in vivo investigation,rats with spinal cord injury were intraperitoneally injected with 20 mg/kg salvianolic acid B for 8 weeks.The amount of myelin sheath and the number of regenerating axons increased,neurological function recovered,and caspase-3 expression was decreased in the spinal cord of salvianolic acid B-treated animals compared with untreated control rats.These results indicate that salvianolic acid B can protect axons and the myelin sheath,and can promote the recovery of neurological function.Its mechanism of action is likely to be associated with inhibiting apoptosis and promoting the differentiation and maturation of oligodendrocyte precursor cells.Zhe Zhu Lu Ding Wen-feng Qiu Hong-fu Wu Rui Li 2016Neural Regeneration Research2016,11,3:6
8Rational development of a human antibody cocktail that deploys multiple functions to confer Pan-SARS-CoVs protection显示文摘Structural principles underlying the composition and synergistic mechanisms of protective monoclonal antibody cocktails are poorly defined.Here,we exploited antibody cooperativity to develop a therapeutic antibody cocktail against SARS-CoV-2.On the basis of our previously identified humanized cross-neutralizing antibody H014,we systematically an a lyzed a fully human n aive antibody library and rationally identified a potent neutralizing antibody partner,P17,which confers effective protection in animal model.Cryo-EM studies dissected the nature of the P17 epitope,which is SARS-CoV-2 specific and distinctly different from that of HOI4.High-resolution structure of the SARS-CoV-2 spike in complex with HOM and P17,together with functional investigations revealed that in a two-antibody cocktail,synergistic neutralization was achieved by S1 shielding and conformational locking,thereby blocking receptor attachment and viral membrane fusion,conferring high potency as well as robustness against viral mutation escape.Furthermore,cluster analysis identified a hypothetical 3rd antibody partner for further reinforcing the cocktail as pan-SARS-CoVs therapeutics.Hangping Yao Yao Sun Yong-Qiang Deng Nan Wang Yongcong Tan Na-Na Zhang Xiao-Feng Li Chao Kong Yan-Peng Xuc Qi Chen Tian-Shu Cao Hui Zhao Xintian Yan Lei Cao Zhe Lv Dandan Zhu Rui Feng Nanping Wu Wenhai Zhang Yuhao Hu Keda Chen Rong-Rong Zhang Qingyu Lv Shihui Sun Yunhua Zhou Run Yan Guan Yang Xinglu Chanjuan Liu Xiangyun Lu Linfang Cheng Hongying Qiu Xing-Yao Huang Tianhao Weng Danrong Shi Weidong Jiang Junbin Shao Lei Wang Jie Zhang Tao Jiang Guojun Lang Cheng-Feng Qinc Lanjuan Li Xiangxi Wang 2021Cell Research2021,31,1:5
9DeST 3.0:A new-generation building performance simulation platform显示文摘Buildings contribute to almost 30%of total energy consumption worldwide.Developing building energy modeling programs is of great significance for lifecycle building performance assessment and optimization.Advances in novel building technologies,the requirements of high-performance computation,and the demands for multi-objective models have brought new challenges for building energy modeling software and platforms.To meet the increasing simulation demands,DeST 3.0,a new-generation building performance simulation platform,was developed and released.The structure of DeST 3.0 incorporates four simulation engines,including building analysis and simulation(BAS)engine,HVAC system engine,combined plant simulation(CPS)engine,and energy system(ES)engine,connected by air loop and water loop balancing iterations.DeST 3.0 offers numerous new simulation features,such as advanced simulation modules for building envelopes,occupant behavior and energy systems,cross-platform and compatible simulation kernel,FMI/FMU-based co-simulation functionalities,and high-performance parallel simulation architecture.DeST 3.0 has been thoroughly evaluated and validated using code verification,inter-program comparison,and case-study calibration.DeST 3.0 has been applied in various aspects throughout the building lifecycle,supporting building design,operation,retrofit analysis,code appliance,technology adaptability evaluation as well as research and education.The new generation building simulation platform DeST 3.0 provides an efficient tool and comprehensive simulation platform for lifecycle building performance analysis and optimization.Da Yan Xin Zhou Jingjing An Xuyuan Kang Fan Bu Youming Chen Yiqun Pan Yan Gao Qunli Zhang Hui Zhou Kuining Qiu Jing Liu Yan Liu Honglian Li Lei Zhang Hong Dong Lixin Sun Song Pan Xiang Zhou Zhe Tian Wenjie Zhang Ruhong Wu Hongsan Sun Yu Huang Xiaohong Su Yongwei Zhang Rui Shen Diankun Chen Guangyuan Wei Yixing Chen Jinqing Peng 2022Building Simulation2022,15,11:5
10Patient-derived non-small cell lung cancer xenograft mirrors complex tumor heterogeneity显示文摘Objective:Patient-derived xenograft(PDX)models have shown great promise in preclinical and translational applications,but their consistency with primary tumors in phenotypic,genetic,and pharmacodynamic heterogeneity has not been well-studied.This study aimed to establish a PDX repository for non-small cell lung cancer(NSCLC)and to further elucidate whether it could preserve the heterogeneity within and between tumors in patients.Methods:A total of 75 surgically resected NSCLC specimens were implanted into immunodeficient NOD/SCID mice.Based on the successful establishment of the NSCLC PDX model,we compared the expressions of vimentin,Ki67,EGFR,and PD-L1 proteins between cancer tissues and PDX models using hematoxylin and eosin staining and immunohistochemical staining.In addition,we detected whole gene expression profiling between primary tumors and PDX generations.We also performed whole exome sequencing(WES)analysis in 17 first generation xenografts to further assess whether PDXs retained the patient heterogeneities.Finally,paclitaxel,cisplatin,doxorubicin,atezolizumab,afatininb,and AZD4547 were used to evaluate the responses of PDX models to the standard-of-care agents.Results:A large collection of serially transplantable PDX models for NSCLC were successfully developed.The histology and pathological immunohistochemistry of PDX xenografts were consistent with the patients’tumor samples.WES and RNA-seq further confirmed that PDX accurately replicated the molecular heterogeneities of primary tumors.Similar to clinical patients,PDX models responded differentially to the standard-of-care treatment,including chemo-,targeted-and immuno-therapeutics.Conclusions:Our established PDX models of NSCLC faithfully reproduced the molecular,histopathological,and therapeutic characteristics,as well as the corresponding tumor heterogeneities,which provides a clinically relevant platform for drug screening,biomarker discovery,and translational research.Xuanming Chen Cheng Shen Zhe Wei Rui Zhang Yongsheng Wang Lili Jiang Ke Chen Shuang Qiu Yuanli Zhang Ting Zhang Bin Chen Yanjun Xu Qiyi Feng Jinxing Huang Zhihui Zhong Hongxia Li Guowei Che Kai Xiao 2021Cancer Biology & Medicine2021,18,1:5
11LIN28A inhibits DUSP family phosphatases and activates MAPK signaling pathway to maintain pluripotency in porcine induced pluripotent stem cells显示文摘LIN28A,an RNA-binding protein,plays an important role in porcine induced pluripotent stem cells(piPSCs).However,the molecular mechanism underlying the function of LIN28A in the maintenance of pluripotency in piPSCs remains unclear.Here,we explored the function of LIN28A in piPSCs based on its overexpression and knockdown.We performed total RNA sequencing(RNA-seq)of piPSCs and detected the expression levels of relevant genes by quantitative real-time polymerase chain reaction(qRT-PCR),western blot analysis,and immunofluorescence staining.Results indicated that piPSC proliferation ability decreased following LIN28A knockdown.Furthermore,when LIN28A expression in the shLIN28A2 group was lower(by 20%)than that in the negative control knockdown group(shNC),the pluripotency of piPSCs disappeared and they differentiated into neuroectoderm cells.Results also showed that LIN28A overexpression inhibited the expression of DUSP(dual-specificity phosphatases)family phosphatases and activated the mitogen-activated protein kinase(MAPK)signaling pathway.Thus,LIN28A appears to activate the MAPK signaling pathway to maintain the pluripotency and proliferation ability of piPSCs.Our study provides a new resource for exploring the functions of LIN28A in piPSCs.Xiao-Long Wu Zhen-Shuo Zhu Xia Xiao Zhe Zhou Shuai Yu Qiao-Yan Shen Ju-Qing Zhang Wei Yue Rui Zhang Xin He Sha Peng Shi-Qiang Zhang Na Li Ming-Zhi Liao Jin-Lian Hua 2021Zoological Research2021,42,3:5
12High-Q microresonators on 4H-silicon-carbide-on-insulator platform for nonlinear photonics显示文摘The realization of high-quality(Q)resonators regardless of the underpinning material platforms has been a ceaseless pursuit,because the high-Q resonators provide an extreme environment for confining light to enable observations of many nonlinear optical phenomenon with high efficiencies.Here,photonic microresonators with a mean Q factor of 6.75×10^(6)were demonstrated on a 4H-silicon-carbide-on-insulator(4H-SiCOI)platform,as determined by a statistical analysis of tens of resonances.Using these devices,broadband frequency conversions,including second-,third-,and fourth-harmonic generations have been observed.Cascaded Raman lasing has also been demonstrated in our SiC microresonator for the first time,to the best of our knowledge.Meanwhile,by engineering the dispersion properties of the SiC microresonator,we have achieved broadband Kerr frequency combs covering from 1300 to 1700nm.Our demonstration represents a significant milestone in the development of SiC photonic integrated devices.Chengli Wang Zhiwei Fang Ailun Yi Bingcheng Yang Zhe Wang Liping Zhou Chen Shen Yifan Zhu Yuan Zhou Rui Bao Zhongxu Li Yang Chen Kai Huang Jiaxiang Zhang Ya Cheng Xin Ou 2021Light(Science & Applications)2021,10,8:4
13The Emergence, Epidemiology, and Etiology of Haff Disease显示文摘Haff disease is a type of human rhabdomyolysis characterized by the sudden onset of unexplained muscular rigidity and an elevated serum creatine kinase level within 24 h after consuming cooked aquatic products. Here, we reviewed a previous study on Haff disease and summarized the clinical manifestations,epidemiological characteristics, and etiological data to confirm the incidence and global epidemiology of the disease and identify the most common seafood vectors. Future directions for Haff disease study will include further prospective etiological studies and the development of prevention and control strategies.PEI Pei LI Xiao Yan LU Shuang Shuang LIU Zhe WANG Rui LU Xuan Cheng LU Kai 2019Biomedical and Environmental Sciences2019,32,10:4
14A statistical approach to fit Gaussian part of full-energy peaks from Si(PIN) and SDD X-ray spectrometers显示文摘A new statistical fitting approach,named Statistical Distribution-Based Analytic(SDA)method,is proposed to fit single Gaussian-shaped Kαand KβX-ray peaks recorded by Si(PIN)and silicon drift detector(SDD).In this method,we use the discrete distribution theory to calculate standard deviation of energy resolutionσ.The calibration ofσand energy(E)for two detectors between the energy ranges of 4.5–26 keV are also completed by measuring characteristic X-ray spectra of nineteen types of pure elements.With the spectrum fraction(SF)parameter proposed in this paper,the SDA method can be used to resolve overlapping peaks.In measured spectra,the Gaussian part of X-ray peaks can be fitted by a Gaussian function with two parameters,σand SF.This new fitting approach is simpler than traditional methods and it achieves relatively good results when fitting the complex X-ray spectra of national standard alloy samples detected by Si(PIN)and SDD detectors.The2r values are obtained for each spectrum to assess fitting results,and the SDA fitting method gives a preferable fit for the SDD detector.LI Zhe TUO XianGuo SHI Rui YANG JianBo 2014Science China(Technological Sciences)2014,57,1:4
15Increased circulating level of interleukin-6 and CD8+T cell exhaustion are associated with progression of COVID-19显示文摘Background: Coronavirus disease 2019(COVID-19)is pandemic.It is critical to identify COVID-19 patients who are most likely to develop a severe disease.This study was designed to determine the clinical and epidemiological features of COVID-19 patients associated with the development of pneumonia and factors associated with disease progression.Methods:: Seventy consecutive patients with etiologically confirmed COVID-19 admitted to PLA General Hospital in Beijing,China from December 27,2019 to March 12,2020 were enrolled in this study and followed-up to March 16,2020.Differences in clinical and laboratory findings between COVID-19 patients with pneumonia and those without were determined by theχ2 test or the Fisher exact test(categorical variables)and independent group t test or Mann–Whitney U test(continuous variables).The Cox proportional hazard model and Generalized Estimating Equations were applied to evaluate factors that predicted the progression of COVID-19.Results: The mean incubation was 8.67(95%confidence interval,6.78–10.56)days.Mean duration from the first test severe acute respiratory syndrome coronavirus 2-positive to conversion was 11.38(9.86–12.90)days.Compared to pneumonia-free patients,pneumonia patients were 16.5 years older and had higher frequencies of having hypertension,fever,and cough and higher circulating levels of neutrophil proportion,interleukin-6,low count(<190/µl)of CD8+T cells,and neutrophil/lymphocyte ratio.Thirteen patients deteriorated during hospitalization.Cox regression analysis indicated that older age and higher serum levels of interleukin-6,C-reactive protein,procalcitonin,and lactate at admission significantly predicted the progression of COVID-19.During hospitalization,circulating counts of T lymphocytes,CD4+T cells,and CD8+T cells were lower,whereas neutrophil proportion,neutrophil/lymphocyte ratio,and the circulating levels of interleukin-6,C-reactive protein,and procalcitonin were higher,in pneumonia patients than in pneumonia-free patients.CD8+lymphocyte count in pneumonia patients did not recover when discharged.Conclusions: Older age and higher levels of C-reactive protein,procalcitionin,interleukin-6,and lactate might predict COVID-19 progression.T lymphocyte,especially CD8+cell-mediated immunity is critical in recovery of COVID-19.This study may help in predicting disease progression and designing immunotherapy for COVID-19.Peng-Hui Yang Yi-Bo Ding Zhe Xu Rui Pu Ping U Jin Yan Ji-Luo Liu Fan-Ping Meng Lei Huang Lei Shi Tian-Jun Jiang En-Qiang Qin Min Zhao Da-Wei Zhang Peng Zhao Ling-Xiang Yu Zhao-Hai Wang Zhi-Xian Hong Zhao-Hui Xiao Qing Xi De-Xi Zhao Peng Yu Cai-Zhong Zhu Zhu Chen Shao-Geng Zhang Jun-Sheng Ji Fu-Sheng Wang Guang-Wen Cao 2020Infectious Diseases of Poverty2020,9,6:3
16Television News Coverage of Obesity in China,1982-2009显示文摘Objective The purpose of this study was to explore how obesity was covered in television news in China,including the trends over me and the characteris cs of obesity-related news.Methods The frame analysis was adopted to assess the content of obesity-related news broadcasted in China Central Television (CCTV) from 1982 to 2009.To inves gate the characteris cs of the news,the obesity-related news was divided into subgroups according to popula ons concerned,as well as the period in which the news was broadcasted.The differences between subgroups were examined.Results A total of 1 599 pieces of news reported obesity,in which 1 278 pieces (79.92%) aired in 'wealthy' period (2006-2009).More news was concerned with adults (1 134,70.92%). 'Individual behavior' dominated most of the cause frames (389,24.33%),solu on frames (522,32.65%),and responsibility frames (860,53.78%).There was more news men oning individual factors in news aired in 'wealthy' period and news concerning children.The coverage of social-structure causes was higher in news concerning children,while the coverage of social-structure solu ons was higher in news concerning children and news aired in 'wealthy' period.Conclusion Although the coverage of obesity was modest,it showed an incremental trend as the economy grew.Obesity was mostly depicted as an individual problem in terms of responsibility,causes and solu ons.YI Zhe XU Rui Qing ZHAO Kun LIKe Ji 2012Biomedical and Environmental Sciences2012,25,3:3
17Azvudine is a thymus-homing anti-SARS-CoV-2 drug effective in treating COVID-19 patients显示文摘Azvudine(FNC)is a nucleoside analog that inhibits HIV-1 RNA-dependent RNA polymerase(RdRp).Recently,we discovered FNC an agent against SARS-CoV-2,and have taken it into Phase III trial for COVID-19 patients.FNC monophosphate analog inhibited SARS-CoV-2 and HCoV-OC43 coronavirus with an EC_(50) between 1.2 and 4.3 μM,depending on viruses or cells,and selective index(SI)in 15-83 range.Oral administration of FNC in rats revealed a substantial thymus-homing feature,with FNC triphosphate(the active form)concentrated in the thymus and peripheral blood mononuclear cells(PBMC).Treating SARS-CoV-2 infected rhesus macaques with FNC(0.07 mg/kg, qd,orally)reduced viral load,recuperated the thymus,improved lymphocyte profiles,alleviated in flammation and orga n damage,and lessened grou nd・glass opacities in chest X-ray.Sin gle-cell seque ncing suggested the promotion of thymus function by FNC.A randomized,single-arm clinical trial of FNC on compassionate use(n=31)showed that oral FNC(5 mg,qd)cured all COVID-19 patients,with 100%viral ribonucleic acid negative conversion in 3.29±2.22 days(range:1-9 days)and 100%hospital discharge rate in 9.00±4.93 days(range:2-25 days).The side-effect of FNC is minor and transient dizziness and nausea in 16.12%(5/31)patients.Thus,FNC might cure COVID-19 through its anti-SARS-CoV-2 activity concentrated in the thymus,followed by promoted immunity.Jin-Lan Zhang Yu-Huan Li Lu-Lu Wang Hong-Qi Liu Shuai-Yao Lu Yong Liu Ke Li Bin Liu Su-Yun Li Feng-Min Shao Kun Wang Ning Sheng Rui Li Jin-Jin Cui Pei-Chun Sun Chun-Xia Ma Bo Zhu Zhe Wang Yuan-Hao Wan Shi-Shan Yu Yongsheng Che Chao-Yang Wang Chen Wang Qiangqian Zhang Li-Min Zhao Xiao-Zhong Peng Zhenshun Cheng Jun-Biao Chang Jian-Dong Jiang 2022Signal Transduction and Targeted Therapy2022,7,1:3
18A post-ingestive amino acid sensor promotes food consumption in Drosophila显示文摘Zhe Yang Rui Huang Xin Fu Gaohang Wang Wei Qi Decai Mao Zhaomei Shi Wei L. Shen Liming Wang 2018Cell Research2018,28,10:3
19Membrane-type Ⅰ matrix metalloproteinase(MT1-MMP),lipid metabolism,and therapeutic implications显示文摘Lipids exert many essential physiological functions,such as serving as a structural component of biological membranes,storing energy,and regulating cell signal transduction.Dysregulation of lipid metabolism can lead to dyslipidemia related to various human diseases,such as obesity,diabetes,and cardiovascular disease.Therefore,lipid metabolism is strictly regulated through multiple mechanisms at different levels,including the extracellular matrix.Membrane-type I matrix metalloproteinase(MT1-MMP),a zinc-dependent endopeptidase,proteolytically cleaves extracellular matrix components,and non-matrix proteins,thereby regulating many physiological and pathophysiological processes.Emerging evidence supports the vital role of MT1-MMP in lipid metabolism.For example,MT1-MMP mediates ectodomain shedding of low-density lipoprotein receptor and increases plasma low-density lipoprotein cholesterol levels and the development of atherosclerosis.It also increases the vulnerability of atherosclerotic plaque by promoting collagen cleavage.Furthermore,it can cleave the extracellular matrix of adipocytes,affecting adipogenesis and the development of obesity.Therefore,the activity of MT1-MMP is strictly regulated by multiple mechanisms,such as autocatalytic cleavage,endocytosis and exocytosis,and post-translational modifications.Here,we summarize the latest advances in MT1-MMP,mainly focusing on its role in lipid metabolism,the molecular mechanisms regulating the function and expression of MT1-MMP,and their pharmacotherapeutic implications.Xiao-Dan Xia Adekunle Alabi Maggie Wang Hong-Mei Gu Rui Zhe Yang Gui-Qing Wang Da-Wei Zhang 2021Journal of Molecular Cell Biology2021,13,7:3
20Melatonin combined with chondroitin sulfate ABC promotes nerve regeneration after root-avulsion brachial plexus injury显示文摘After nerve-root avulsion injury of the brachial plexus, oxidative damage, inflammatory reaction, and glial scar formation can affect nerve regeneration and functional recovery. Melatonin(MT) has been shown to have good anti-inflammatory, antioxidant, and neuroprotective effects. Chondroitin sulfate ABC(ChABC) has been shown to metabolize chondroitin sulfate proteoglycans and can reduce colloidal scar formation. However, the effect of any of these drugs alone in the recovery of nerve function after injury is not completely satisfactory. Therefore, this experiment aimed to explore the effect and mechanism of combined application of melatonin and chondroitin sulfate ABC on nerve regeneration and functional recovery after nerve-root avulsion of the brachial plexus. Fifty-two Sprague-Dawley rats were selected and their C5–7 nerve roots were avulsed. Then, the C6 nerve roots were replanted to construct the brachial plexus nerve-root avulsion model. After successful modeling, the injured rats were randomly divided into four groups. The first group(injury) did not receive any drug treatment, but was treated with a pure gel-sponge carrier nerve-root implantation and an ethanol-saline solution via intraperitoneal(i.p.) injection. The second group(melatonin) was treated with melatonin via i.p. injection. The third group(chondroitin sulfate ABC) was treated with chondroitin sulfate ABC through local administration. The fourth group(melatonin + chondroitin sulfate ABC) was treated with melatonin through i.p. injection and chondroitin sulfate ABC through local administration. The upper limb Terzis grooming test was used 2–6 weeks after injury to evaluate motor function. Inflammation and oxidative damage within 24 hours of injury were evaluated by spectrophotometry. Immunofluorescence and neuroelectrophysiology were used to evaluate glial scar, neuronal protection, and nerve regeneration. The results showed that the Terzis grooming-test scores of the three groups that received treatment were better than those of the injury only group. Additionally, these three groups showed lower levels of C5–7 intramedullary peroxidase and malondialdehyde. Further, glial scar tissue in the C6 spinal segment was smaller and the number of motor neurons was greater. The endplate area of the biceps muscle was larger and the structure was clear. The latency of the compound potential of the myocutaneous nerve-biceps muscle was shorter. All these indexes were even greater in the melatonin + chondroitin sulfate ABC group than in the melatonin only or chondroitin sulfate ABC only groups. Thus, the results showed that melatonin combined with chondroitin sulfate ABC can promote nerve regeneration after nerve-root avulsion injury of the brachial plexus, which may be achieved by reducing oxidative damage and inflammatory reaction in the injury area and inhibiting glial scar formation.Wen-Lai Guo Zhi-Ping Qi Li Yu Tian-Wen Sun Wen-Rui Qu Qian-Qian Liu Zhe Zhu Rui Li 2019Neural Regeneration Research2019,14,2:3
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