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Integrated Single-cell multiomic Analysis of HIV latency reversal reveals Novel regulators of Viral reactivation

Genomics, proteomics & bioinformatics 2024年第1期22卷 67-88页

作者： manickam Ashokkumar Wenwen mei jackson j.peterson yuriko Harigaya David m.murdoch David m.margolis Caleb Kornfein Alex Oesterling Zhicheng guo Cynthia D.rudin yuchao jiang Edward p.browne Department of medicine University of North Carolina at Chapel HillChapel HillNC 27599USA HIV Cure Center University of North Carolina at Chapel HillChapel HillNC 27599USA Department of biostatistics University of North Carolina at Chapel HillChapel HillNC 27599USA Department of microbiology and Immunology University of North Carolina at Chapel HillChapel HillNC 27599USA Department of Genetics University of North Carolina at Chapel HillChapel HillNC 27599USA Department of medicine Duke UniversityDurhamNC 27708USA Department of Computer Science Duke UniversityDurhamNC 27708USA Department of Statistics Texas A&M UniversityCollege StationTX 77843USA Department of biology Texas A&M UniversityCollege StationTX 77843USA Department of biomedical Engineering Texas A&M UniversityCollege StationTX 77843USA

Despite the success of antiretroviral therapy,human immunodeficiency virus(HIV)cannot be cured because of a reservoir of latently infected cells that evades *** understand the mechanisms of HIV latency,we employed an integrated single-cell rNA sequencing(scrNA-seq)and single-cell assay for transposase-accessible chromatin with sequencing(scATAC-seq)approach to simultaneously profile the transcriptomic and epigenomic characteristics of~125,000 latently infected primary CD4^(+)T cells after reactivation using three different latency reversing *** expressed genes and differentially accessible motifs were used to examine transcriptional pathways and transcription factor(TF)activities across the cell *** identified cellular transcripts and TFs whose expression/activity was correlated with viral reactivation and demonstrated that a machine learning model trained on these data was 75%-79%accurate at predicting viral ***,we validated the role of two candidate HIV-regulating factors,FOXp1 and GATA3,in viral *** data demonstrate the power of integrated multimodal single-cell analysis to uncover novel relationships between host cell factors and HIV latency.

关键词： HIV latency reversal primary CD4þT cell Single-cell multiomics HIV-regulating factor machine learning

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Evidence for particle acceleration approaching peV energies in the W51 complex

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Science bulletin 2024年第18期69卷 2833-2841页

作者： Cao, Zhen Aharonian, F. Axikegu bai, y.X. bao, y.W. bastieri, D. bi, X.j. bi, y.j. bian, W. bukevich, A.V. Cao, q. Cao, W.y. Cao, Zhe Chang, j. Chang, j.F. Chen, A.m. Chen, E.S. Chen, H.X. Chen, liang Chen, lin Chen, long Chen, m.j. Chen, m.l. Chen, q.H. Chen, S. Chen, S.H. Chen, S.Z. Chen, T.l. Chen, y. Cheng, N. Cheng, y.D. Cui, m.y. Cui, S.W. Cui, X.H. Cui, y.D. Dai, b.Z. Dai, H.l. Dai, Z.G. Danzengluobu Dong, X.q. Duan, K.K. Fan, j.H. Fan, y.Z. Fang, j. Fang, j.H. Fang, K. Feng, C.F. Feng, H. Feng, l. Feng, S.H. Feng, X.T. Feng, y. Feng, y.l. Gabici, S. Gao, b. Gao, C.D. Gao, q. Gao, W. Gao, W.K. Ge, m.m. Geng, l.S. Giacinti, G. Gong, G.H. Gou, q.b. Gu, m.H. guo, F.l. guo, X.l. guo, y.q. guo, y.y. Han, y.A. Hasan, m. He, H.H. He, H.N. He, j.y. He, y. Hor, y.K. Hou, b.W. Hou, C. Hou, X. Hu, H.b. Hu, q. Hu, S.C. Huang, D.H. Huang, T.q. Huang, W.j. Huang, X.T. Huang, X.y. Huang, y. ji, X.l. jia, H.y. jia, K. jiang, K. jiang, X.W. jiang, Z.j. jin, m. Kang, m.m. Karpikov, I. Kuleshov, D. Kurinov, K. li, b.b. li, C.m. li, Cheng li, Cong li, D. li, F. li, H.b. li, H.C. li, jian li, jie li, K. li, S.D. li, W.l. li, X.r. li, Xin li, y.Z. li, Zhe li, Zhuo liang, E.W. liang, y.F. lin, S.j. liu, b. liu, C. liu, D. liu, D.b. liu, H. liu, H.D. liu, j. liu, j.l. liu, m.y. liu, r.y. liu, S.m. liu, W. liu, y. liu, y.N. luo, q. luo, y. lv, H.K. ma, b.q. ma, l.l. ma, X.H. mao, j.r. min, Z. mitthumsiri, W. mu, H.j. Nan, y.C. Neronov, A. Ou, l.j. pattarakijwanich, p. pei, Z.y. qi, j.C. qi, m.y. qiao, b.q. qin, j.j. raza, A. ruffolo, D. Sáiz, A. Saeed, m. Semikoz, D. Shao, l. Shchegolev, O. Sheng, X.D. Shu, F.W. Song, H.C. Stenkin, yu.V. Stepanov, V. Su, y. Sun, D.X. Sun, q.N. Sun, X.N. Sun, Z.b. Takata, j. Tam, p.H.T. Key laboratory of particle Astrophysics & Experimental physics Division & Computing Center Institute of High Energy Physics Chinese Academy of Sciences Beijing 100049 China University of Chinese Academy of Sciences Beijing 100049 China TIANFU Cosmic ray research Center Chengdu China Dublin Institute for Advanced Studies 31 Fitzwilliam Place 2 Dublin Ireland max-planck-Institut for Nuclear physics P.O. Box 103980 Heidelberg 69029 Germany School of physical Science and Technology & School of Information Science and Technology Southwest Jiaotong University Chengdu 610031 China School of Astronomy and Space Science Nanjing University Nanjing 210023 China Center for Astrophysics Guangzhou University Guangzhou 510006 China Tsung-Dao lee Institute & School of physics and Astronomy Shanghai Jiao Tong University Shanghai 200240 China Institute for Nuclear research of russian Academy of Sciences Moscow 117312 Russia Hebei Normal University Shijiazhuang 050024 China University of Science and Technology of China Hefei 230026 China State Key laboratory of particle Detection and Electronics China Key laboratory of Dark matter and Space Astronomy & Key laboratory of radio Astronomy Purple Mountain Observatory Chinese Academy of Sciences Nanjing 210023 China research Center for Astronomical Computing Zhejiang Laboratory Hangzhou 311121 China Key laboratory for research in Galaxies and Cosmology Shanghai Astronomical Observatory Chinese Academy of Sciences Shanghai 200030 China School of physics and Astronomy Yunnan University Kunming 650091 China Key laboratory of Cosmic rays (Tibet University) Ministry of Education Lhasa 850000 China National Astronomical Observatories Chinese Academy of Sciences Beijing 100101 China School of physics and Astronomy (Zhuhai) & School of physics (Guangzhou) & Sino-French Institute of Nuclear Engineering and Technology (Zhuhai) Sun Yat-sen University Zhuhai 519000 & Guangzhou 510275 Guangdong China Institute of Frontier and

The γ-ray emission from the W51 complex is widely acknowledged to be attributed to the interaction between the cosmic rays (Crs) accelerated by the shock of supernova remnant (SNr) W51C and the dense molecular clouds in the adjacent star-forming region, W51b. However, the maximum acceleration capability of W51C for Crs remains elusive. based on observations conducted with the large High Altitude Air Shower Observatory (lHAASO), we report a significant detection of γ rays emanating from the W51 complex, with energies from 2 to 200 TeV. The lHAASO measurements, for the first time, extend the γ-ray emission from the W51 complex beyond 100 TeV and reveal a significant spectrum bending at tens of TeV. by combining the "π0-decay bump" featured data from Fermi-lAT, the broadband γ-ray spectrum of the W51 region can be well-characterized by a simple pp-collision model. The observed spectral bending feature suggests an exponential cutoff at ∼400 TeV or a power-law break at ∼200 TeV in the Cr proton spectrum, most likely providing the first evidence of SNrs serving as Cr accelerators approaching the peV regime. Additionally, two young star clusters within W51b could also be theoretically viable to produce the most energetic γ rays observed by lHAASO. Our findings strongly support the presence of extreme Cr accelerators within the W51 complex and provide new insights into the origin of Galactic Crs. © 2024 Science China press

关键词： Cosmic rays

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metallographic investigationof first full-sizehigh-jc Nb_(3)Sn cable-in-conduit conductor aftercyclicloadingtests

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Superconductivity 2024年第1期9卷 1-8页

作者： Chao Dai yunhao liu Zichuan guo yu Wu Arend Nijhuis Tianjun Xue Zuojiafeng Wu jinggang qin Huainan New Energy research Center Huainan 232000People’s Republic of China University of Twente EnergyMaterials and SystemsFaculty of Science and TechnologyEnschede 7500AENetherlands University of Science and Technology of China Hefei 230026People’s Republic of China baiyin Non-ferrous Changtong Wire&Cable Co.ltd BaiyinGansu 730900People’s Republic of China longteng mechanical and Electrical Co. LtdYiChun 336000People’s Republic of China

In order to verify the feasibility of applying high-jc Nb_(3)Sn strand in fusion magnet,a full-size cable-in-conduit conductor(CICC)with short twist pitch(STp)cable pattern was manufactured and tested in SUlTAN facility at SpC,*** levels of cyclic electromagnetic(Em)load were applied on the sample stepwise,no visible decrease of current sharing temperature(TcsT was observed until the Em load increased to 80 kA×10.8 T,after that the Tcs decreased dramatically with the Em cycles,which suggested that irreversible deformation,causing a change in the strain state,or even damage has occurred in the superconducting *** investigating the reason which caused the conductor performance degradation,the tested conductor was dissected for metallographic *** segments which subjected to different Em loads were extracted from one of the legs,the geometric feature changes of the cable cross-sections were analyzed and compared.A good correlation was found between the decrease of the Tcs and deformation of the cable cross section.A mass of cracks were found on the sub-elements of strands in the segment which subjected to highest Em load,but the amount of crack is much lower in other *** the analyses,it is speculated that the critical Em load which causes irreversible degradation is between 850 kN/m and 870 kN/m for this *** results could be a reference in high-jc Nb_(3)Sn CICC design.

关键词： High‐jc Nb_(3)Sn Cable‐in‐conduit conductor metallography

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Dual-functional microneedle with programmatic regulation of macrophage for autoimmune psoriasis treatment

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Nano research 2024年第8期17卷 7436-7448页

作者： Ze qiang Zhao bo Zhi Chen jia li Gan yun Hao Feng ling liang lingyun yu Zi yi Wang Samin Abbaszadeh mohammad-Ali Shahbazi ruixing yu Xin Dong guo State Key laboratory of Organic-Inorganic Composites Beijing University of Chemical TechnologyBeijing 100029China beijing laboratory of biomedical materials College of Materials Science and EngineeringBeijing University of Chemical TechnologyBeijing 100029China China-japan Friendship Hospital Chinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100029China Department of Dermatology China-Japan Friendship HospitalBeijing 100029China Department of pharmaceutical biomaterials School of PharmacyZanjan University of Medical SciencesZanjan 45139-56184Iran Department of biomaterials and biomedical Technology University Medical Center GroningenUniversity of GroningenAntonius Deusinglaan 19713 AV GroningenThe Netherlands W.j.Kolff Institute for biomedical Engineering and materials Science University of GroningenAntonius Deusinglaan 19713 AV GroningenThe Netherlands

modulating the immune microenvironment to establish sustained positive feedback within immune pathways represents a promising avenue for the treatment of ***,the precise and efficient delivery of therapeutic systems to the subcutaneous basal layer to modulate immune disorders is a major challenge in the treatment of autoimmune *** this project,we introduce a dual-functional microneedle(DF-mN)designed to combine mNs with multiple release kinetics and immunotherapy,the programmed treatment is achieved through segmented design of the mN structure,realizing the unification of rapid and long-lasting treatment of autoimmune *** vivo imaging results showed that GelmA@m-CSF showed fluorescent signals after 5 days of delivery to subcutaneous tissues,whereas HA@Il-13 showed minimal fluorescent signals after 2 *** multistage release behavior of mNs and the diffusion mechanism of drugs were explained at the molecular level,in combination with coarse-grained molecular ***,DF-mN can successfully induce macrophage reprogramming in vitro and ameliorate overall symptoms in a psoriasis mice model,suggesting that it has the potential to be an effective strategy for the treatment of psoriasis and portends to be a transformative platform for the treatment of other autoimmune diseases.

关键词： microneedle psoriasis m2 macrophage immunoregulation

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Association of acute glycemic parameters at admission with cardiovascular mortality in the oldest old with acute myocardial infarction

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journal of Geriatric Cardiology 2024年第3期21卷 349-358页

作者： Hui-Hui lIU meng ZHANG yuan-lin guo Cheng-Gang ZHU Na-qiong WU ying GAO rui-Xia XU jie qIAN Ke-Fei DOU jian-jun lI Cardiometabolic Center State Key Laboratory of Cardiovascular DiseaseFuwai HospitalNational Center for Cardiovascular DiseasesNational Clinical Research Center for Cardiovascular DiseasesChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina

ObjECTIVES Stress-related glycemic indicators,including admission blood glucose(AbG),stress-hyperglycemia ratio(SHr),and glycemic gap(GG),have been associated with worse outcomes after acute myocardial infarction(AmI).However,data regarding their prognostic value in the oldest old with AmI are ***,this study aimed to investigate the association of stress-related glycemic indicators with short-and long-term cardiovascular mortality(CVm)in the oldest old(≥80 years)with *** In this prospective study,a total of 933 consecutive old patients with AmI admitted to FuWai hospital(beijing,China)were *** admission,AbG,SHr,and GG were assessed and all participants were classified according to their ***-meier,restricted cubic splines(rCS),and multivariate Cox regression analyses were performed to evaluate the association between these glycemic indicators and CVm within 30 days and long-term *** During an average of 1954 patient-years of follow-up,a total of 250 cardiovascular deaths were ***-meier analyses showed the lowest CVm in quartile 1 of AbG and in quartile 2 of SHr and *** adjusting for potential covariates,patients in quartile 4 of AbG,SHr,and GG had a respective 1.67-fold(95%CI:1.03-2.69;p=0.036),1.80-fold(95%CI:1.16-2.79;p=0.009),and 1.78-fold(95%CI:1.14-2.79;p=0.011)higher risk of long-term CVm risk compared to those in the reference groups(quartile 1 of AbG and quartile 2 of SHr and GG).Furthermore,rCS suggested a j-shaped relationship of AbG and a Ushaped association of SHr and GG with long-term ***,we observed similar associations of these acute glycemic parameters with 30-day *** Our data first indicated that SHr and GG consistently had a U-shaped association with both 30-day and longterm CVm among the oldest old with AmI,suggesting that they may be useful for risk stratification in this special population.

关键词： admitted infarction shaped

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The infection kinetics and transmission potential of two Guaico Culex viruses in Culex quinquefasciatus mosquitoes

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Virologica Sinica 2024年第2期39卷 228-234页

作者： ru-yi Chen Teng Zhao jing-jing guo Feng Zhu Na-Na Zhang Xiao-Feng li Hai-Tao liu Fei Wang yong-qiang Deng Cheng-Feng qin College of bioscience and bioengineering Jiangxi Agricultural UniversityNanchang330045China State Key laboratory of pathogen and biosecurity Beijing Institute of Microbiology and EpidemiologyAMMSBeijing100071China School of life Sciences Southwest Forestry UniversityKunming650224China

Guaico Culex virus(GCXV)is a newly identified segmented jingmenvirus from Culex *** in Central and South *** genome of GCXV is composed of four or five single-stranded positive rNA ***,the infection kinetics and transmission capability of GCXV in mosquitoes remain *** this study,we used reverse genetics to rescue two GCXVs(4S and 5S)that contained four and five rNA segments,respectively,in C6/36 *** in vitro characterization revealed that the two GCXVs exhibited comparable replication kinetics,protein expression and viral ***,GCXV rNAs were detected in the bodies,salivary glands,midguts and ovaries of Culex quinquefasciatus at 4–10 days after oral *** addition,two GCXVs can colonize *** eggs,resulting in positive rates of 15%–35%for the second gonotrophic *** conclusion,our results demonstrated that GCXVs with four or five rNA segments can be detected in *** eggs during the first and second gonotrophic cycles after oral infection.

关键词： Guaico Culex virus(GCXV) jingmenvirus Culex quinquefasciatus Vertical transmission

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In situ TEm investigation of electron irradiation and aging-induced high-density nanoprecipitates in an mg-10Gd-3y-1Zn-0.5Zr alloy

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journal of magnesium and Alloys 2024年第5期12卷 1841-1853页

作者： m.lv H.l.Ge q.q.jin X.H.Shao y.T.Zhou b.Zhang X.l.ma Shenyang National laboratory for materials Science Institute of Metal ResearchChinese Academy of Sciences72 Wenhua RoadShenyang 110016China School of materials Science and Engineering University of Science and Technology of ChinaShenyang 110016China materials Science and Engineering research Center Guangxi University of Science and TechnologyLiuzhou 545006China

In-situ electron irradiation and aging are applied to introduce high-density precipitates in an mg-10Gd-3y-1Zn-0.5Zr(GWZ1031K,wt.%)alloy to improve the *** results show that the hardness of the mg alloy after irradiation for 10 h and aging for 9 h at 250℃ is 1.64 Gpa,which is approximately 64% higher than that of the samples before being *** is mainly attributed to γ'precipitates on the basal plane after irradiation and the high-density nanoscale β'precipitates on the prismatic plane after aging,which should be closely related to the irradiation-induced homogenous *** latter plays a key role in precipitation *** result paves a way to improve the mechanical properties of metallic materials by tailoring the precipitation through irradiation and aging.

关键词： mg alloy Electron beam irradiation Hardening precipitates In-situ TEm

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Solid-liquid extraction for yttrium recovery using porous polymeric resin(XAD-7) functionalized with D_(2)EHpA

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journal of rare Earths 2024年第9期42卷 1764-1773,I0005页

作者： p.A.martínez-montoya r.G.Sanchez-Alvarado D.y.medina-Velazquez m.l.Carrera-jota p.Garnica-Chávez A.de j.morales-ramirez Higher School of Chemical Engineering and Extractive Industries ESIQIEIPNDepartment of Metallurgical EngineeringUPALM S/NCol.LindavistaGustavo A.Madero Cd.de MéxicoC.P07738Mexico metropolitan Autonomous University Department of MaterialsBasic Sciences and EngineeringAv.San Pablo No.180Col.Reynosa TamaulipasCd.de MéxicoC.P02200Mexico Center for research and Technological Innovation CIITECIPNCda.de CECATIs/nSanta CatarinaAzcapotzalcoC.P02250CDMXMexico

The recovery of yttrium is proposed by applying a solid-liquid extraction process using di-2-ethyl hexylphosphoric acid(D2EHpA) as extracting *** extracting agents were supported on a macro porous polymeric resin XAD-7(solid phase).yttrium ions extraction and discharge tests were performed,firstly from a synthetic aqueous solution of 100 mg/l y(liquid phase) at 25℃ with *** effects of pH of aqueous solutions bearing yttrium,volume fraction of extracting agents and the solid/liquid(S/l)ratio on the yttrium recovery were *** most favorable conditions for yttrium ions extraction are;20 vol% D_(2)EHpA functionalized resin,pH=1.5 and an S/l ratio of 10 mg/ml The discharge of yttrium ions was done under the same conditions of extraction stage,using a 2 mol/l [H_(2)SO_(4)] as stripping *** to 80% yttrium is extracted,while 75% yttrium is recovered in the striping *** all experiments,the reaction equilibrium is reached after 20 min,and the kinetics for the extraction stage was determined as a second-order ***,experiments were carried out to discharge the yttriumloaded resins,and it has been determined that the best pH value to strip the y ions is *** tests of extraction and discharge for yttrium ions show that the functionalized resin can work at least five cycles without decreasing its ***,the proposed process was tested in a real solution with y ions fro m a waste fluorescent la mp powder leached in H_(2)SO_(4),demonstrating the ability to effectively recover yttrium,separating it from various metals from the studied residue.

关键词： yttrium recovery rare earth solid-liquid extraction XAD-7 resin Fluorescent lamps recycling Solid-liquid kinetics extraction

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Side-Chain-Type polyimide-Cu Complexes with Suppressed Activation Energy of relaxation for Advanced High-Temperature Capacitor

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Chinese journal of polymer Science 2024年第8期42卷 1038-1048页

作者： bai-yang Zhou Ze-Tong ma Shi-long Zhong Zhen-jie Huang qi guo Deng-Chong Feng Zhong-Ke yuan Shao-lin lu yu-Zhao yang Cheng Wang Ding-Shan yu Xu-Dong Chen Key laboratory for polymeric Composite and Functional materials of ministry of Education Guangdong Engineering Technology Research Centre for High Performance Organic and Polymer Photoelectric Functional FilmsSchool of ChemistrySun Yat-sen UniversityGuangzhou 510275China School of Chemical Engineering and light Industry Guangdong University of TechnologyGuangzhou 510006China Guangdong provincial laboratory of Chemistry and Fine Chemical Industry jieyang Centre Jieyang 515200China Chemistry and Chemical Engineering Guangdong laboratory Shantou 515031China

The burgeoning growth of the new energy vehicles and aviation industry has escalated the need for energy storage capacitors capable of stable operation in harsh *** advent of metal-polyimide complexes has illuminated a novel approach for preparing tem perature-resistant ***,the general application of these metal-polyimide com plexes is impeded by the high dielectric loss and low breakdown strength,consequences of main-chain coordination and excessive metal ions ***,our study proposes a novel polyimideCu complex material(pOp-Cu)predicated on side-chain-type pyridine-Cu coordination,utilizing the structural backbone pmDA-ODA of mature commercial pI(Kapton)with reliable *** to the high degree of freedom afforded by the side chain with suppressed relaxation activation energy and the long-range electron delocalization formed by d-πcoordination,the dielectric constant of this material containing merely 2.7 mol%Cu increases from 3.25(pOpI)to 5.58,while maintaining a remarkably low dielectric loss of ***,this material exhibits a substantial DC breakdown strength of 436.2 mV·m^(-1)and a high energy density of 5.42 j·cm^(-3),coupled with superior mechanical and thermal *** at 150℃,it retains over 90%of its room-temperature energy density,demon strating notable dielectric stability under high *** attributes underscore its promising application for capacitors operating in harsh environments.

关键词： Dielectric performance polyimide complexes Side-Chain-Type High-temperature capacitor

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Drug repurposing screen identifies vidofludimus calcium and pyrazofurin as novel chemical entities for the development of hepatitis E interventions

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Virologica Sinica 2024年第1期39卷 123-133页

作者： Hongbo guo Dan liu Kuan liu yao Hou Chunyang li qiudi li Xiaohui Ding monique m.A.Verstegen jikai Zhang lingli Wang yibo Ding renxian Tang Xiucheng pan Kuiyang Zheng luc j.Wvan der laan qiuwei pan Wenshi Wang Department of pathogen biology and Immunology Jiangsu Key Laboratory of Immunity and MetabolismJiangsu International Laboratory of Immunity and MetabolismXuzhou Medical UniversityXuzhou221004China Department of Gastroenterology and Hepatology Erasmus MC-University Medical CenterRotterdamNL-3015 CNthe Netherlands Department of Surgery Erasmus MC Transplant InstituteUniversity Medical CenterRotterdam3015CENL-3015 CNthe Netherlands Department of Infectious Diseases The Affiliated Hospital of Xuzhou Medical UniversityXuzhou221002China

Hepatitis E virus(HEV)infection can cause severe complications and high mortality,particularly in pregnant women,organ transplant recipients,individuals with pre-existing liver disease and immunosuppressed ***,there are still unmet needs for treating chronic HEV ***,we screened a best-in-class drug repurposing library consisting of 262 drugs/*** screening,we identified vidofludimus calcium and pyrazofurin as novel anti-HEV *** calcium is the next-generation dihydroorotate dehydrogenase(DHODH)inhibitor in the phase 3 pipeline to treat autoimmune diseases or SArS-CoV-2 *** selectively targets uridine monophosphate synthetase(UmpS).Their anti-HEV effects were further investigated in a range of cell culture models and human liver organoids models with wild type HEV strains and ribavirin treatment failure-associated HEV ***,both drugs exhibited a sizeable therapeutic window against *** instance,the IC50 value of vidofludimus calcium is 4.6–7.6-fold lower than the current therapeutic doses in ***,their anti-HEV mode of action depends on the blockage of pyrimidine ***,two drugs robustly inhibited ribavirin treatment failure-associated HEV mutants(y1320H,G1634r).Their combination with IFN-αresulted in synergistic antiviral *** conclusion,we identified vidofludimus calcium and pyrazofurin as potent candidates for the treatment of HEV *** on their antiviral potency,and also the favorable safety profile identified in clinical studies,our study supports the initiation of clinical studies to repurpose these drugs for treating chronic hepatitis E.

关键词： Hepatitis Evirus(HEV) Drug repurposing Vidofludimus calcium pyrazofurin pyrimidine biosynthesis

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