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The ubiquitin ligase Pelil inhibits ICOS and thereby Tfh-mediated immunity

Cellular & Molecular Immunology 2021年第4期18卷 969-978页

作者： Xinfang huang Shumeng hao Junli Liu Yuanyuan huang Manman Liu Chunyuan Xiao Yan Wang Siyu Pei Tao Yu Jing Xu haikun Wang dongfang dai Xiao Su Yichuan Xiao department of Rheumatology Shanghai East Hospital Tongji UnrversitySchool of MedicineShanghai Giina CAS Key Laboratory of Tissue Microenvironment and Tumor Shanghai Institute of Nutrition and HealthChinese Academy of SciencesUniversity of Chinese Academy of SciencesShanghaiChina CAS Key Laboratory of Molecular Virology&Immunology Unit of Respiratory Infection and ImmunityInstitut Pasteur of ShanghaiChinese Academy of SciencesUniversity of Chinese Academy of SciencesShanghaiChina department of Radiation Oncology The Affiliated Cancer Hospital of Nanjing M4edical University(Jiangsu Cancer Hospital)and Jiangsu Institute of Cancer ResearchNanjingJiangsuChina

T follicular helper(Tfh)cells are crucial for regulating autoimmune inflammation and protective immunity against viral ***,the molecular mechanism controlling Tfh cell differentiation is poorly ***,through two mixed bone marrow chimeric experiments,we identified Peli1,a T cell-enriched E3 ubiquitin ligase,as an intrinsic regulator that inhibits Tfh cell ***1 deficiency significantly promoted c-Rel-mediated inducible T-cell costimulator(ICOS)expression,and PELI1 mRNA expression was negatively associated with ICOS expression on human Cd4^(+)T ***,increased ICOS expression on Peli1-KO Cd4^(+)T cells enhanced the activation of PI3K-AKT signaling and thus suppressed the expression of Klf2,a transcription factor that inhibits Tfh ***,reconstitution of Klf2 abolished the differences in Tfh differentiation and germinal center reaction between WT and Peli1-KO *** a consequence,Peli1-deficient Cd4^(+)T cells promoted lupus-like autoimmunity but protected against h1N1 influenza virus infection in mouse ***,our findings established Peli1 as a critical negative regulator of Tfh differentiation and indicated that targeting Peli1 may have beneficial therapeutic effects in Tfhrelated autoimmunity or infectious diseases.

关键词： T follicular helper cells Peli1 ICOS

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Synthesis and self-assembly of poly(ethylene glycol)-block-poly(N-3-(methylthio)propyl glycine)and their oxidation-sensitive polymersomes

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Chinese Chemical Letters 2020年第7期31卷 1931-1935页

作者： Yangwei deng hui Chen Xinfeng Tao Sylvain Trepout Jun Ling Min-hui Li Chimie ParisTech PSL University ParisCNRSInstitut de Recherche de Chimie ParisParis 75005France MOE Key Laboratory of Macromolecular Synthesis and Functionalization Department of Polymer Science and EngineeringZhejiang UniversityHangzhou 310027China Beijing Advanced Innovation Center for Soft Matter Science and Engineering Beijing University of Chemical TechnologyBeijing 100029China institut Curie Inserm US43University Paris SaclayOrsay Cedex 91405France shanghai Key Laboratory of Advanced Polymeric Materials School of Materials Science and EngineeringEast China University of Science and TechnologyShanghai 200237China

Amphiphilic block copolymers poly(ethylene glycol)-block-poly(N-3-(methylthio)propyl glycine)(PEGb-PMeSPG)were synthesized via ring-opening polymerization of N-3-(methylthio)propyl glycine Nthiocarboxyanhydride(MeSPG-NTA)initiated by amino-terminated *** self-assemblies of three PEG-b-PMeSPG copolymers with different PMeSPG block lengths were first prepared by nanoprecipitation method using ThF and dMF,respectively,as the organic solvent,and their morphologies were studied by Cryo-EM and *** prepare polymersomes loaded with glucose oxidase(GOx),double emulsion method followed by extrusion treatment was *** oxidation-responsive disruption of polymersomes was achieved upon the introduction of glucose because of the oxidants generated insitu by GOx/glucose.

关键词： Polypeptoid Self-assembly Polymersome Oxidation-responsive Glucose oxidase

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Repurposing of antitumor drug candidate Quisinostat lead to novel spirocyclic antimalarial agents

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Chinese Chemical Letters 2021年第5期32卷 1660-1664页

作者： Ruoxi Li dazheng Ling Tongke Tang Zhenghui huang Manjiong Wang Fei Mao Jin Zhu Lubin Jiang Jian Li Xiaokang Li State Key Laboratory of Bioreactor Engineering Shanghai Key Laboratory of New Drug DesignSchool of PharmacyEast China University of Science and TechnologyShanghai 200237China Key Laboratory of Molecular Virology and Immunology Institut Pasteur of ShanghaiUniversity of Chinese Academy of SciencesChinese Academy of SciencesShanghai 200031China College of Pharmacy and Chemistry Dali UniversityDali 671000China Frontiers Science Center for Materiobiology and dynamic Chemistry East China University of Science and TechnologyShanghai 200237China School of Life Science and Technology ShanghaiTech UniversityShanghai 201210China

Antimalarial chemotherapies endowed with effectiveness against drug-resistant parasites and good safety are urgently required in *** previous research revealed that clinical phaseⅡantitumor drug Quisinostat was a promising antimalarial prototype by inhibiting the activity of Plasmodium falciparum(***)histone deacetylase(PfhdAC).herein,30 novel spirocyclic linker derivatives were designed and synthesized based on Quisinostat as lead compound,and then their antimalarial activities and cytotoxicity were systematically *** them,compounds 8 and 27 could effectively eliminate wild-type and multi-drug resistant *** parasites,and display weakened cytotoxicity and good metabolic *** blot assay demonstrated that they could inhibit PfhdAC activity like *** addition,both 8 and 27 showed certain antimalarial efficacy in rodent malaria model,and the animal toxicity of 8 was significantly improved compared with ***,8 and 27 were structurally novel PfhdAC inhibitors and provided prospective prototype for further antimalarial drug research.

关键词： Malaria PfhdAC inhibitor drug repurposing Epigenetic modulator Erythrocytic therapy

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drug nanoclusters formed in confined nano-cages of Cd-MOF: dramatic enhancement of solubility and bioavailability of azilsartan

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Acta Pharmaceutica Sinica B 2019年第1期9卷 97-106页

作者： Yuanzhi he Wei Zhang Tao Guo Guoqing Zhang Wei Qin Liu Zhang Caifen Wang Weifeng Zhu Ming Yang Xiaoxiao hu Vikramjeet Singh Li Wu Ruxandra Gref Jiwen Zhang Key Laboratory of Modern Preparation of TCM Ministry of Education Jiangxi University of Traditional Chinese Medicine Center for drug delivery Systems Shanghai Institute of Materia Medica Chinese Academy of Sciences School of Chemistry and Environmental Engineering Shanghai Institute of Technology institut des Sciences Moléculaires d'Orsay UMR 8214 CNRS Université Paris-Sud Université Paris-Saclay School of Pharmacy Key Laboratory of Molecular Pharmacology and Drug Evaluation Ministry of Education Yantai University

Tremendous efforts have been devoted to the enhancement of drug solubility using nanotechnologies, but few of them are capable to produce drug particles with sizes less than a few nanometers. This challenge has been addressed here by using biocompatible versatile γ-cyclodextrin(γ-Cd) metal-organic framework(Cd-MOF) large molecular cages in which azilsartan(AZL) was successfully confined producing clusters in the nanometer range. This strategy allowed to improve the bioavailability of AZL in Sprague–dawley rats by 9.7-fold after loading into Cd-MOF. The apparent solubility of AZL/Cd-MOF was enhanced by 340-fold when compared to the pure drug. Based on molecular modeling, a dual molecular mechanism of nanoclusterization and complexation of AZL inside the Cd-MOF cages was proposed, which was confirmed by small angle X-ray scattering(SAXS) and synchrotron radiation-Fourier transform infrared spectroscopy(SR-FTIR) techniques. In a typical cage-like unit of Cd-MOF, three molecules of AZL were included by the γ-Cd pairs, whilst other three AZL molecules formed a nanocluster inside the 1.7 nm sized cavity surrounded by six γ-Cds. This research demonstrates a dual molecular mechanism of complexation and nanoclusterization in Cd-MOF leading to significant improvement in the bioavailability of insoluble drugs.

关键词： γ-Cyclodextrin metal-organic framework Nanoclusterization Azilsartan Mechanism Solubility Bioavailability Molecular modeling

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On the constituent counting rule for hard exclusive processes involving multi-quark states

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Chinese Physics C 2017年第5期41卷 91-96页

作者：郭奉坤 Ulf-G.Mei?ner 王伟 State Key Laboratory of Theoretical Physics Institute of Theoretical PhysicsChinese Academy of Sciences helmholtz-institut fr Strahlen- und Kernphysik and Bethe Center for Theoretical Physics Universitt Bonn institute for Advanced Simulation Institut fr Kernphysik and Jlich Center for Hadron PhysicsForschungszentrum Jlich INPAC Shanghai Key Laboratory for Particle Physics and CosmologyDepartment of Physics and AstronomyShanghai Jiao-Tong University

At high energy,the cross section at finite scattering angle of a hard exclusive process falls off as a power of the Manderstam variable *** all involved quark-gluon compositions undergo hard momentum transfers,the fall-off scaling is determined by the underlying valence structures of the initial and final hadrons,known as the constituent counting *** spite of the complication due to helicity conservation,it has been argued that when applied to exclusive process with exotic multiquark states,the counting rule is a powerful way to determine the valence degrees of freedom inside hadron *** this work,we demonstrate that for hadrons with hidden flavors,the naive application of the constituent counting rule is problematic,since it is not mandatory for all components to participate in hard scattering at the scale s1/*** illustrate the problems in the viewpoint based on effective field *** clarify the misleading results that may be obtained from the constituent counting rule in exclusive processes with exotic candidates such as Z_c~±（cd/cu）,Z_b~±（bd/bdu）,X（3872）,etc.

关键词： quark exclusive constituent hadron meson exotic problematic clarify momentum valence

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heteromerization of short-chain trans-prenyltransferase controls precursor allocation within a plastidial terpenoid network

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Journal of Integrative Plant Biology 2023年第5期65卷 1170-1182页

作者： Yihua Ma Qingwen Chen Yaoyao Wang Fengxia Zhang Chengyuan Wang Guodong Wang State Key Laboratory of Plant Genomics Institute of Genetics and Developmental BiologyThe Innovative Academy of Seed DesignChinese Academy of SciencesBeijing 100101China UniversityofChineseAcademyof Sciences Beijing100039China Center for Microbes Development and HealthInstitut Pasteur of ShanghaiChinese Academy of SciencesShanghai 200031China

Terpenes are the largest and most diverse class of plant specialized ***(C25),which are derived from the plastid methylerythritol phosphate pathway,were recently characterized in *** Arabidopsis thaliana,four genes encoding geranylfarnesyl diphosphate synthase(GFPPS)(AtGFPPS1 to 4)are responsible for the production of GFPP,which is the common precursor for sesterterpene ***,the interplay between sesterterpenes and other known terpenes remain ***,we first provide genetic evidence to demonstrate that GFPPSs are responsible for sesterterpene production in *** of the sesterterpene pathway at the GFPPS step increased the production of geranylgeranyl diphosphate(GGPP)-derived ***,co-expression of sester TPSs in GFPPSOE(overexpression)plants rescued the phenotypic changes of GFPPS-OE plants by restoring the endogenous *** further demonstrated that,in addition to precursor(dMAPP/IPP)competition by GFPPS and GGPP synthase(GGPPS)in plastids,GFPPS directly decreased the activity of GGPPS through protein-protein interaction,ultimately leading to GGPP deficiency in *** study provides a new regulatory mechanism of the plastidial terpenoid network in plant cells.

关键词： Arabidopsis geranylfarnesyl diphosphate synthase geranylgeranyl pyrophosphate synthase plastid sesterterpene terpene network

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Epigenetic regulation of covalently closed circular dNA minichromosome in hepatitis B virus infection

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Biophysics Reports 2020年第4期6卷 115-126页

作者： Zhaoning Wang Weiwei Wang Lanfeng Wang School of Life Sciences Shanghai University The Center for Microbes Development and Health CAS Key Laboratory of Molecular Virology & ImmunologyInstitut Pasteur of Shanghai Chinese Academy of Sciences

hepatitis B is caused by hepatitis B virus(hBV), and persistent hBV infection is a global public health problem, with 257 million people as hBV chronic carriers. Viral covalently closed circular dNA(cccdNA) is a key factor to establish persistent infection in infected hepatocytes. Current antiviral therapies have no direct impact on pre-existing cccdNA reservoir, which can be assembled into minichromosome by hijacking host factors. Understanding the mechanisms of epigenetic regulation in cccdNA minichromosome is crucial to develop new therapy on cccdNA, an attractive target for hBV cure. This review summarizes the current advances in epigenetic regulation of cccdNA minichromosome, which might provide clues to novel druggable targets to cure hepatitis B by either silencing or eliminating cccdNA reservoir.

关键词： hBV cccdNA Minichromosome Epigenetic regulation

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A Novel 2-dimensional Multiplex qPCR Assay for Single-Tube detection of Nine human herpesviruses

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Virologica Sinica 2021年第4期36卷 746-754页

作者： Yingxue Li Zhenzhou Wan Lulu Zuo Shenwei Li honglian Liu Yingying Ma Lianqun Zhou Xia Jin Yuye Li Chiyu Zhang shanghai Public health Clinical Center Fudan UniversityShanghai201508China CAS Key Laboratory of Bio-Medical diagnostics Suzhou Institute of Biomedical Engineering and TechnologyChinese Academy of SciencesSuzhou215163China School of Biomedical Engineering University of Science and Technology of ChinaHefei260026China Medical Laboratory of Taizhou Fourth People's hospital Taizhou225300China Viral hemorrhagic Fevers Research Unit Institut Pasteur of ShanghaiChinese Academy of SciencesShanghai200031China shanghai International Travel healthcare Center Shanghai200335China department of dermatology and Venereology First Affiliated Hospital of Kunming Medical UniversityKunming650032China

human herpesviruses are double-stranded dNA viruses that are classified into nine *** than 90%of adults are ever infected with one or more *** symptoms of infection with different herpesviruses are diverse ranging from mild or asymptomatic infections to deadly diseases such as aggressive lymphomas and *** and accurate detection of herpesvirus infection is critical for clinical management and *** this study,we established a single-tube nonuple qPCR assay for detection of all nine herpesviruses using a 2-d multiplex qPCR method with a house-keeping gene as the internal *** novel assay can detect and distinguish different herpesviruses with 30 to 300 copies per 25µL single-tube reaction,and does not cross-react with 20 other human viruses,including dNA and RNA *** robustness of the novel assay was evaluated using 170 clinical *** novel assay showed a high consistency(100%)with the single qPCR assay for hhVs *** features of simple,rapid,high sensitivity,specificity,and low cost make this assay a high potential to be widely used in clinical diagnosis and patient treatment.

关键词： human herpesviruses(hhVs) 2-d multiplex qPCR Melting temperature(Tm) Fluorescence probe Melting curve

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Pediatric Wilson disease presenting as acute liver failure:Prognostic indices

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World Journal of Clinical Cases 2021年第14期9卷 3273-3286页

作者： Wei-Yuan Fang Kuerbanjiang Abuduxikuer Peng Shi Yi-Ling Qiu Jing Zhao Yu-Chuan Li Xue-Yuan Zhang Neng-Li Wang Xin-Bao Xie Yi Lu A S Knisely Jian-She Wang Center for Pediatric Liver diseases Children’s Hospital of Fudan UniversityShanghai 201102China Medical Statistics department Children’s Hospital of Fudan UniversityShanghai 201102China institut für Pathologie Medizinische Universität GrazGraz 8010Austria

BACKGROUNd Acute liver failure(ALF)can be a primary presentation of Wilson disease(Wd).Mortality rates are high in Wd with ALF(WdALF).Predictions of mortality in WdALF vary by model and are sometimes contradictory,perhaps because few patients are studied or Wd diagnoses are *** To determine the outcomes among well-documented WdALF patients and assess mortality model performance in this *** We reviewed the medical records of our pediatric WdALF patients(n=41 over 6-years-old,single-center retrospective study)and compared seven prognostic models(King’s College hospital Criteria,model for end-stage liver disease/pediatric end-stage liver disease scoring systems,Liver Injury Unit[LIU]using prothrombin time[PT]or international normalized ratio[INR],admission LIU using PT or INR,and devarbhavi model)with one *** Among the 41 han Chinese patients with ALF,Wd was established by demonstrating ATP7B variants in *** 5 others,Kayser-Fleischer rings and Coombs-negative hemolytic anemia permitted *** died during hospitalization and three underwent liver transplantation(LT)within 1 mo of presentation and survived(7.3%each);35(85.4%)survived without LT when given enteral d-penicillamine and zinc-salt therapy with or without urgent *** significantly correlated with mortality included encephalopathy,coagulopathy,and gamma-glutamyl transpeptidase activity,bilirubin,ammonia,and serum sodium *** under the receiver operating curves varied among seven prognostic models from 0.981 to 0.748 with positive predictive values from 0.214 to *** WdALF children can survive and recover without LT when given d-penicillamine and Zn with or without plasmapheresis,even after enlisting for LT.

关键词： Acute liver failure ATP7B d-penicillamine Liver transplant Wilson disease Zinc

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The Application of a Safe Neutralization Assay for Ebola Virus Using Lentivirus-Based Pseudotyped Virus

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Virologica Sinica 2021年第6期36卷 1648-1651页

作者： Zengguo Cao hongli Jin Gary Wong Ying Zhang Cuicui Jiao Na Feng Fangfang Wu Shengnan Xu hang Chi Yongkun Zhao Tiecheng Wang Weiyang Sun Yuwei Gao Songtao Yang Xianzhu Xia hualei Wang Key Laboratory of Zoonosis Research Ministry of EducationCollege of Veterinary MedicineJilin UniversityChangchun 130062China Key Laboratory of Jilin Province for Zoonosis Prevention and Control Institute of Military VeterinaryAcademy of Military Medical SciencesChangchun 130122China institut Pasteur of shanghai Chinese Academy of SciencesShanghai 200031China département de Microbiologie-Infectiologie Et d'immunologie UniversitéLavalQuébecQC G1V 0A6Canada Jiangsu Co-Innovation Center for the Prevention and Control of Important Animal Infectious disease and Zoonose Yangzhou UniversityYangzhou 225009China

dear Editor,Zaire Ebola virus(EBOV)is a negative-sense singlestranded RNA virus that is capable of causing acute hemorrhagic fever with a frightening fatality rate that can reach up to 90%.due to its high lethality and frequent recurrence,EBOV is a substantial threat to public *** about live EBOV is restricted to BSL-4 laboratories;therefore,conventional serological detection methods do not provide a safe way to evaluate neutralizing activity,resulting in a bottleneck in antibody-based detection of viruses such as ***,we aim to develop and apply a neutralization assay for EBOV using a generated lentivirus-based pseudotyped EBOV bearing GP on its surface.

关键词： Ebola acute hemorrhagic

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