|
|
|
题名
|
作者
|
年代
|
出处
|
被引量
|
| 1 | Boceprevir,GC-376,and calpain inhibitors Ⅱ,Ⅻ inhibit SARS-CoV-2 viral replication by targeting the viral main protease显示文摘A new coronavirus SARS-CoV-2,also called novel coronavirus 2019(2019-nCoV),started to circulate among humans around December 2019,and it is now widespread as a global pandemic.The disease caused by SARS-CoV-2 virus is called COVID-19,which is highly contagious and has an overall mortality rate of 6.35%as of May 26,2020.There is no vaccine or antiviral available for SARS-CoV-2.In this study,we report our discovery of inhibitors targeting the SARS-CoV-2 main protease(Mpro).Using the FRET-based enzymatic assay,several inhibitors including boceprevir,GC-376,and calpain inhibitorsⅡ,andⅫwere identified to have potent activity with single-digit to submicromolar ICs0 values in the enzymatic assay.The mechanism of action of the hits was further characterized using enzyme kinetic studies,thermal shift binding assays,and native mass spectrometry.Significantly,four compounds(boceprevir,GC-376,calpain inhibitorsⅡandⅫ)inhibit SARS-CoV-2 viral replication in cell culture with EC50 values ranging from 0.49 to 3.37μM.Notably,boceprevir,calpain inhibitorsⅡandⅫrepresent novel chemotypes that are distinct from known substrate-based peptidomimetic Mpro inhibitors.A complex crystal structure of SARS-CoV-2 Mpro with GC-376,determined at 2.15(A)resolution with three protomers per asymmetric unit,revealed two unique binding configurations,shedding light on the molecular interactions and protein conformational flexibility underlying substrate and inhibitor binding by Mpro.Overall,the compounds identified herein provide promising starting points for the further development of SARS-CoV-2 therapeutics. | Chunlong Ma Michael Dominic Sacco Brett Hurst Julia Alma Townsend Yanmei Hu Tommy Szeto Xiujun Zhang Bart Tarbet Michael Thomas Marty Yu Chen Jun Wang | 2020 | Cell Research2020，30，8： | 13 |
| 2 | Micro RNA profiles and potential regulatory pattern during the early stage of spermatogenesis in mice显示文摘Spermatogenesis is a complicated and poorly understood process that relies on the precise regulation of the self-renewal and differentiation of spermatogonia. In many organisms, micro RNAs(mi RNAs) are involved in multiple developmental processes as critical regulators of transcriptional and post-transcriptional gene silencing. This study investigated the expression pattern of mi RNAs in type B spermatogonia cells(BSc) and primary spermatocytes(PSc) of mice, using a high-throughput small RNA sequencing system. The results revealed that the expression levels of Let-7 family mi RNAs were remarkably high in both cell types. Furthermore, the expression levels of mi R-21, mi R-140-3p, mi R-103, mi R-30 a, mi R-101 b and mi R-99 b were decreased during the transformation from BSc to PSc. These mi RNAs target vital genes that participate in apoptosis, cell proliferation and differentiation, junction assembly and cell cycle regulation. These results highlight the indispensable role of mi RNAs in spermatogenesis. | LUO MengMeng HAO LiLi HU Fen DONG YaNan GOU LiXia ZHANG WenDian WANG Xin ZHAO YuHui JIA MengChun HU SongNian ZHANG XiuJun | 2015 | Science China(Life Sciences)2015，58，5： | 6 |
| 3 | Role of VEGF-A/C and CCR-7 in the enhanced metastasis of A549 cells induced by 2 and 4 Gy X-rays in vitro and in vivo显示文摘Radiotherapy is a common strategy in treating lung cancer.Accumulating evidence suggested that radiotherapy has the potential to promote the metastasis and invasion of carcinoma cells.In this study,we aimed to testify the role of vascular endothelial growth factor(VEGF)and C-C chemokine receptor-7(CCR-7)in the metastasis of human adenocarcinoma A549 cells in vivo and in vitro.Nude mice were injected with A549 cells irradiated by 0,2 and 4 Gy X-rays,respectively.Quantitative detections of VEGF-A/C and CCR-7 mRNA from lung sample were performed by real-time RT-PCR.Small interfering RNA(siRNA)transfection technology was further used to testify the role of the genes in the metastasis of A549 cells.VEGF and CCR-7mRNA could only be detected 10 weeks post injection in vivo when visible tumor foci scattered in lung.In addition,VEGF-A/C mRNA expressed significantly higher in mice injected with A549 cells irradiated by 2 and 4 X-rays than those with 0 Gy X-rays irradiation.On the other hand,A549 cells with or without X-rays irradiation transfected with VEGF siRAN and CCR-7 siRNA showed a dramatic decrease of invasiveness compared to normal A549 cells with or without irradiation.The migration indexes were?0.7,?0.48,?0.34 and?0.32 for A549 cells with CCR-7 siRNA,VEGF siRNA,X-rays combined CCR-7 siRNA and X-rays combined VEGF-siRNA respectively.These results demonstrated that X-rays could promote the metastasis of A549 cells,and VEGF-A/C and CCR-7 mRNA were closely related to the metastasis of A549 cells in vivo and in vitro. | LV Jin JIANG QiSheng SONG XiuJun WANG CuiLan GUO LiJie WANG SiNian LI FengSheng HU WenWei | 2014 | Science China(Technological Sciences)2014，57，5： | 4 |
| 4 | The P132H mutation in the main protease of Omicron SARSCoV-2 decreases thermal stability without compromising catalysis or small-molecule drug inhibition显示文摘Dear Editor,The ongoing SARS-CoV-2 pandemic continues to be a significant threat to global health.First reported in November 2021,the Omicron variant(B.1.1.529)is more transmissible and can evade immunity better than previous SARS-CoV-2 variants,fueling an unprecedented surge in cases.To produce functional proteins from its polyprotein,SARS-CoV-2 relies on the cysteine proteases Nsp3/papain-like protease(PLpro)and Nsp5/main protease(Mpro)/3C-like protease to cleave at three and more than 11 sites,respectively.1 Therefore,Mpro and PLpro inhibitors are considered to be one of the most promising SARS-CoV-2 antivirals.On December 22,2021,the Food and Drug Administration(FDA)issued an Emergency Use Authorization(EUA)for PAXLOVID,a ritonavir-boosted formulation of nirmatrelvir.Nirmatrelvir is a first-in-class orally bioavailable SARSCoV-2 Mpro inhibitor.2 Thus,the scientific community must vigilantly monitor potential mechanisms of drug resistance,especially because SARS-CoV-2 is naïve to Mpro inhibitors.Mutations have been well identified in variants to this point.3 Notably,Omicron Mpro(OMpro)harbors a single mutation—P132H.In this study,we characterized the enzymatic activity,drug inhibition,and structure of OMpro while evaluating the past and future implications of Mpro mutations. | Michael Dominic Sacco Yanmei Hu Maura Verenice Gongora Flora Meilleur Michael Trent Kemp Xiujun Zhang Jun Wang Yu Chen | 2022 | Cell Research2022，32，5： | 3 |
| 5 | 2020 Roadmap on two-dimensional nanomaterials for environmental catalysis显示文摘Environmental catalysis has drawn a great deal ofattention due to its clean ways to produce useful chemicals or carry out some chemical processes.Photocatalysis and electrocatalysis play important roles in these fields.They can decompose and remove organic pollutants from the aqueous environment,and prepare some fine chemicals.Moreover,they also can carry out some important reactions,such as 02 reduction reaction(ORR),O2 evolution reaction(OER),H2 evolution reaction(HER),CO2 reduction reaction(C02 RR),and N2 fixation(NRR).For catalytic reactions,it is the key to develop high-performance catalysts to meet the demand fortargeted reactions.In recentyears,two-dimensional(2 D) materials have attracted great interest in environmental catalysis due to their unique layered structures,which offer us to make use of their electronic and structural characteristics.Great progress has been made so far,including graphene,black phosphorus,oxides,layered double hydroxides(LDHs),chalcogenides,bismuth-based layered compounds,MXenes,metal organic frameworks(MOFs),covalent organic frameworks(COFs),and others.This content drives us to invite many famous groups in these fields to write the roadmap on two-dimensional nanomaterials for environmental catalysis.We hope that this roadmap can give the useful guidance to researchers in future researches,and provide the research directions. | Yulu Yang Mingguang Wu Xingwang Zhu Hui Xu Si Ma Yongfeng Zhi Hong Xia Xiaoming Liu Jun Pan Jie-Yinn Tang Siang-Piao Chai Leonardo Palmisano Francesco Parrino Junli Liu Jianzhong Ma Ze-Lin Wang Ling Tan Yu-Fei Zhao Yu-Fei Song Pardeep Singh Pankaj Raizada Deli Jiang Di Li R.A.Geioushy Jizhen Ma Jintao Zhang Song Hu Rongjuan Feng Gang Liu Minghua Liu Zhenhua Li Mingfei Shao Neng Li Jiahe Peng Wee-Jun Ong Nikolay Kornienko Zhenyu Xing Xiujun Fan Jianmin Ma | 2019 | Chinese Chemical Letters2019，30，12： | 2 |
| 6 | Genetically modified CD7-targeting allogeneic CAR-T cell therapy with enhanced efficacy for relapsed/refractory CD7-positive hematological malignancies:a phase I clinical study显示文摘Chimeric antigen receptor(CAR)-T cell therapy against T cell malignancies faces major challenges including fratricide between CAR-T cells and product contamination from the blasts.Allogeneic CAR-T cells,generated from healthy donor T cells,can provide ready-to-use,blast-free therapeutic products,but their application could be complicated by graft-versus-host disease(GvHD)and host rejection.Here we developed healthy donor-derived,CD7-targeting CAR-T cells(RD13-01)with genetic modifications to resist fratricide,GvHD and allogeneic rejection,as well as to potentiate antitumor function.A phase I clinical trial(NCT04538599)was conducted with twelve patients recruited(eleven with T cell leukemia/lymphoma,and one with CD7-expressing acute myeloid leukemia).All patients achieved pre-set end points and eleven proceeded to efficacy evaluation.No dose-limiting toxicity,GvHD,immune effector cell-associated neurotoxicity or severe cytokine release syndrome(grade≥3)were observed.28 days post infusion,81.8%of patients(9/11)showed objective responses and the complete response rate was 63.6%(7/11,including the patient with AML).3 of the responding patients were bridged to allogeneic hematopoietic stem cell transplantation.With a median follow-up of 10.5 months,4 patients remained in complete remission.Cytomegalovirus(CMV)and/or Epstein-Barr virus(EBV)reactivation was observed in several patients,and one died from EBV-associated diffuse large B-cell lymphoma(DLBCL).Expansion of CD7-negative normal T cells was detected post infusion.In summary,we present the first report of a Phase I clinical trial using healthy donor-derived CD7-targeting allogeneic CAR-T cells to treat CD7^(+)hematological malignancies.Our results demonstrated the encouraging safety and efficacy profiles of the RD13-01 allogeneic CAR-T cells for CD7^(+)tumors. | Yongxian Hu Yali Zhou Mingming Zhang Houli Zhao Guoqing Wei Wengang Ge Qu Cui Qitian Mu Gong Chen Lu Han Tingting Guo Jiazhen Cui Xiaoyan Jiang Xiujun Zheng Shuhui Yu Xiaolong Li Xingwang Zhang Mingxi Chen Xiuju Li Ming Gao Kang Wang Cheng Zu Hao Zhang Xiaohong He Yanbin Wang Dongrui Wang Jiangtao Ren He Huang | 2022 | Cell Research2022，32，11： | 2 |
| 7 | Combined firstprinciples calculation and neuralnetwork correction approach for heat of formation显示文摘 | Hu Lihong Wang Xiujun Wong Laiho | 2003 | Journal of Chemical Physics2003，119，11： | 1 |
| 8 | Combined first-principles calculation and neural-network correction approach for heat of formation显示文摘 | HU Lihong WANG Xiujun WONG Laiho | 2003 | Journal of Chemical Physics2003，119，11： | 1 |
| 9 | Analysis of promoters and CREB/AP-1 binding sites of the human TMEM174gene显示文摘 | Fen Hu Yanan Meng Lixia Gou Xiujun Zhang | 2013 | Experimental and Therapeutic Medicine2013，，5： | 1 |
| 10 | Identification of publication characteristics and research trends in the management of gallbladder cancer显示文摘Background:To date,no comprehensive analysis of gallbladder cancer(GBC)management has been reported.We aimed to identify the publication characteristics and research trends in managing GBC over the past three decades.Methods:We selected the 100 most cited articles and performed a bibliometric analysis to summarize the publication characteristics,explore research hotspots,and identify research trends in the management of GBC.Results:The total citations of the included articles ranged from 123 to 1822.Period II(2001–2010)yielded the highest number of included articles,whereas the lowest was in Period III(2011–2020).The United States and Japan published the most papers,in which the Memorial Sloan–Kettering Cancer Center and Nagoya University were the leading institutions,respectively.The most influential authors were Blumgart LH and Fong YM from the United States.Cooperation among countries,institutions,and authors was weak.The Annals of Surgery contributed the most articles with the highest number of total citations.The most researched topic was surgery,followed by systemic therapy and adjuvant therapy.Since Period I,the percentage of surgery-related publications continuously decreased(Periods II and III versus Period I,both p<0.001),with a concomitant increase in those of adjuvant therapy(Period III versus Period I,p=0.004)and systemic therapy(Period II versus Period I,p=0.004;Period III versus Period I,p=0.002).Conclusions:Surgery remains the preferred treatment,while there is a tendency toward adjuvant and systemic therapy in GBC management.An increase in local and international collaboration for managing GBC is required. | Jiasheng Cao Jiahao Hu Jiliang Shen Bin Zhang Win Topatana Shijie Li Tianen Chen Sarun Jeungpanich Yitong Tian Ziyi Lu Shuyou Peng Xiujun Cai Mingyu Chen | 2022 | iLIVER2022，1，2： | 0 |
| 11 | Effects of water and nitrogen coupling on growth,physiology and yield of rice显示文摘Water and nitrogen fertilizer are two essential factors for quality and yield formation of rice.Experimental study was carried out to investigate the effects of water and nitrogen fertilizer coupling on yield-related factors,such as growth(height),physiological indicators(chlorophyll and leaf area index(LAI))and yield composition indicators(productive panicles,thousand grain weight and total grains per panicle).Results showed that,the height difference under two irrigation regimes was not significant,and it showed no difference until the tillering stage(p>0.05).The water control method for controlled and mid-gathering irrigation(CMI)was favorable for nutrients converting to rice grain.Meanwhile the height difference for CMI and conventional irrigation(CVI)was the biggest at 80 d after rice transplantation.Variance analysis showed the effect of fertilization on height was significant(p<0.05).With organic fertilizer application,it could control plant growth and promote the nutrients converting to the panicle.The change curve of LAI was similar to chlorophyll content.Organic fertilizer application could not only promote chlorophyll content and LAI,but also delay leaf fading and promote yield.Nitrogen fertilizer factors showed significant difference on rice yield,compared to irrigation regimes showing no significance.Considering the irrigation and fertilizer factors together,the interaction was significant.The descending orders for the effects of water and nitrogen on rice yield were fertilizer,water and fertilizer,water.Regression analysis showed that the productive panicles and total grains per panicle of rice were extremely significant on rice yield,and the direct effect of total grains per panicle on yield was greater than that of productive panicle.This study results could provide theoretical basis for water and nitrogen management to improve rice production. | Yuanyuan Li Xiaohou Shao Daoxi Li Menghua Xiao Xiujun Hu Jing He | 2019 | International Journal of Agricultural and Biological Engineering2019，12，3： | 0 |
| 12 | Development of synthetic lethality in cancer:molecular and cellular classification显示文摘Recently,genetically targeted cancer therapies have been a topic of great interest.Synthetic lethality provides a new approach for the treatment of mutated genes that were previously considered unable to be targeted in traditional genotype-targeted treatments.The increasing researches and applications in the clinical setting made synthetic lethality a promising anticancer treatment option.However,the current understandings on different conditions of synthetic lethality have not been systematically assessed and the application of synthetic lethality in clinical practice still faces many challenges.Here,we propose a novel and systematic classification of synthetic lethality divided into gene level,pathway level,organelle level,and conditional synthetic lethality,according to the degree of specificity into its biological mechanism.Multiple preclinical findings of synthetic lethality in recent years will be reviewed and classified under these different categories.Moreover,synthetic lethality targeted drugs in clinical practice will be briefly discussed.Finally,we will explore the essential implications of this classification as well as its prospects in eliminating existing challenges and the future directions of synthetic lethality. | Shijie Li Win Topatana Sarun Juengpanich Jiasheng Cao Jiahao Hu Bin Zhang Diana Ma Xiujun Cai Mingyu Chen | 2020 | Signal Transduction and Targeted Therapy2020，5，1： | 0 |
您所在的机构暂未开通此部分的功能，请联系管理员