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Asialoglycoprotein receptor 1 promotes SARS-CoV-2 Infection of human normal hepatocytes

Signal Transduction and Targeted Therapy 2024年第3期9卷 1199-1208页

作者： Xinyi Yang Xu Zheng Yuqi Zhu Xiaying Zhao Jun Liu Jiangna Xun Songhua Yuan Jun Chen Hanyu Pan Jinlong Yang Jing Wang Zhimin Liang Xiaoting Shen Yue Liang Qinru Lin Huitong Liang Min Li Fei Peng Daru Lu Jianqing Xu Hongzhou Lu Shibo Jiang Ping Zhao Huanzhang Zhu State Key Laboratory of Genetic Engineering and Engineering Research Center of Gene Technology Ministry of EducationInstitute of GeneticsSchool of Life SciencesYiwu Research InstituteFudan UniversityShanghaiChina Department of Microbiology Faculty of Naval MedicineNaval Medical UniversityShanghai 200433China Scientific Research Center Shanghai Public Health Clinical CenterFudan UniversityShanghaiChina Department of Infectious Diseases and Immunology Shanghai Public Health Clinical CenterFudan UniversityShanghaiChina Changzheng Hospital Naval Medical UniversityShanghaiChina Key Laboratory of Medical Molecular Virology(MOE/NHC/CAMS) Shanghai Institute of Infectious Disease and BiosecuritySchool of Basic Medical SciencesFudan UniversityShanghaiChina Department of Infectious Diseases and Nursing Research Institution National Clinical Research Center for Infectious DiseasesThe Third People’s Hospital of ShenzhenShenzhenGuangdongChina

Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)causes multi-organ damage,which includes hepatic dysfunction,as observed in over 50%of COVID-19 patients.Angiotensin I converting enzyme(peptidyl-dipeptidase A)2(ACE2)is the primary receptor for SARS-CoV-2 entry into host cells,and studies have shown the presence of intracellular virus particles in human hepatocytes that express ACE2,but at extremely low levels.Consequently,we asked if hepatocytes might express receptors other than ACE2 capable of promoting the entry of SARS-CoV-2 into cells.To address this question,we performed a genome-wide CRISPR-Cas9 activation library screening and found that Asialoglycoprotein receptor 1(ASGR1)promoted SARS-CoV-2 pseudovirus Infection of HeLa cells.In Huh-7 cells,simultaneous knockout of ACE2 and ASGR1 prevented SARS-CoV-2 pseudovirus Infection.In the immortalized THLE-2 hepatocyte cell line and primary hepatic parenchymal cells,both of which barely expressed ACE2,SARSCoV-2 pseudovirus could successfully establish an Infection.However,after treatment with ASGR1 antibody or siRNA targeting ASGR1,the Infection rate significantly dropped,suggesting that SARS-CoV-2 pseudovirus infects hepatic parenchymal cells mainly through an ASGR1-dependent mechanism.We confirmed that ASGR1 could interact with Spike protein,which depends on receptor binding domain(RBD)and N-terminal domain(NTD).Finally,we also used Immunohistochemistry and electron microscopy to verify that SARS-CoV-2 could infect primary hepatic parenchymal cells.After inhibiting ASGR1 in primary hepatic parenchymal cells by siRNA,the Infection efficiency of the live virus decreased significantly.Collectively,these findings indicate that ASGR1 is a candidate receptor for SARS-CoV-2 that promotes Infection of hepatic parenchymal cells.

关键词： ACE2 Infection glycoprotein

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Typical hemophagocytic syndrome associated with cytomegalovirus Infection in an immunocompetent patient: a case report and literature review

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2023年第12期24卷 1159-1164页

作者： Fangfang GENG Meifang YANG Xuan ZHANG Hong ZHAO De ZHOU Jianhua HU State Key Laboratory for Diagnosis and Treatment of Infectious Diseases National Clinical Research Center for Infectious DiseasesNational Medical Center for Infectious DiseasesCollaborative Innovation Center for Diagnosis and Treatment of Infectious DiseasesDepartment of Infectious Diseasesthe First Affiliated HospitalZhejiang University School of MedicineHangzhou 310003China Department of Hematology the First Affiliated HospitalZhejiang University School of MedicineHangzhou 310003China

Cytomegalovirus(CMV)Infection is currently prevalent in populations throughout the world,and 56%-94%of the global population is seropositive for CMV.CMV Infection mainly affects immunocompromised hosts.In these cases,it can cause significant symptoms,tissue-invasive disease,and many sequelae including death(Dioverti and Razonable,2016).The vast majority of healthy adults with CMV Infection experience an asymptomatic course;when symptomatic,it manifests as a mononucleosis-like syndrome in approximately 10%of patients(Sridhar et al.,2018).

关键词： Infection immuno

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Evidence of bisphosphonate-conjugated sitafloxacin eradication of established methicillin-resistant S.aureus Infection with osseointegration in murine models of implant-associated osteomyelitis

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Bone Research 2023年第4期11卷 751-763页

作者： Youliang Ren Jason Weeks Thomas Xue Joshua Rainbolt Karen L.de Mesy Bentley Ye Shu Yuting Liu Elysia Masters Philip Cherian Charles E.McKenna Jeffrey Neighbors Frank H.Ebetino Edward M.Schwarz Shuting Sun Chao Xie Center for Musculoskeletal Research University of Rochester Medical CenterRochesterNY 14642USA Department of Orthopaedics University of Rochester Medical CenterRochesterNY 14642USA Department of Pathology and Center for Advanced Research Technologies University of Rochester Medical CenterRochesterNY 14642USA BioVinc LLCPasadenaCA 91107USA Department of Chemistry University of Southern CaliforniaLos AngelesCA 90089USA Department of Pharmacology Pennsylvania State UniversityHersheyPA 17033USA Department of Chemistry University of RochesterRoche

Eradication of MRSA osteomyelitis requires elimination of distinct biofilms.To overcome this,we developed bisphosphonateconjugated sitafloxacin(BCS,BV600072)and hydroxybisphosphonate-conjugate sitafloxacin(HBCS,BV63072),which achieve“target-and-release”drug delivery proximal to the bone Infection and have prophylactic efficacy against MRSA static biofilm in vitro and in vivo.Here we evaluated their therapeutic efficacy in a murine 1-stage exchange femoral plate model with bioluminescent MRSA(USA300LAC::lux).Osteomyelitis was confirmed by CFU on the explants and longitudinal bioluminescent imaging(BLI)after debridement and implant exchange surgery on day 7,and mice were randomized into seven groups:1)Baseline(harvested at day7,no treatment);2)HPBP(bisphosphonate control for BCS)+vancomycin;3)HPHBP(hydroxybisphosphonate control for HBCS)+vancomycin;4)vancomycin;5)sitafloxacin;6)BCS+vancomycin;and 7)HBCS+vancomycin.BLI confirmed Infection persisted in all groups except for mice treated with BCS or HBCS+vancomycin.Radiology revealed catastrophic femur fractures in all groups except mice treated with BCS or HBCS+vancomycin,which also displayed decreases in peri-implant bone loss,osteoclast numbers,and biofilm.To confirm this,we assessed the efficacy of vancomycin,sitafloxacin,and HBCS monotherapy in a transtibial implant model.The results showed complete lack of vancomycin efficacy while all mice treated with HBCS had evidence of Infection control,and some had evidence of osseous integrated septic implants,suggestive of biofilm eradication.Taken together these studies demonstrate that HBCS adjuvant with standard of care debridement and vancomycin therapy has the potential to eradicate MRSA osteomyelitis.

关键词： implant Infection overcome

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Asymptomatic Norovirus Infection Among Children in Kindergartens and Primary Schools—Beijing Municipality,China,2021

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China CDC weekly 2023年第8期5卷 171-175页

作者： Qingrui Wu Xiuxia Wei Jianjun Zhang Zhenjiang Xin Xiaoxing Yang Ling Zhang Meng Qin Xiaogen Dong Hanqiu Yan Zhiyong Gao Fengtai District Center for Disease Control and Prevention BeijingChina Fangzhuang Community Health Service Center BeijingChina Beijing Center for Disease Control and Prevention BeijingChina School of Public Health Capital Medical UniversityBeijingChina

Summary What is already known about this topic?Children in kindergartens and primary schools are the high-incidence groups of norovirus acute gastroenteritis.However,asymptomatic norovirus Infection among them is seldom reported.What is added by this report?The norovirus positive rate was 3.48% among asymptomatic children in kindergartens and primary schools in Beijing Municipality in June 2021,the most common genotype was GII.4 Sydney,and no acute gastroenteritis outbreak was reported over the study period.

关键词： acute Sydney Infection

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Toxoplasma gondii Infection induces cell apoptosis via multiple pathways revealed by transcriptome analysis

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2022年第4期23卷 315-327页

作者： Kaige DU Fei LU Chengzuo XIE Haojie DING Yu SHEN Yafan GAO Shaohong LU Xunhui ZHUO School of Basic Medical Sciences and Forensic Medicine Hangzhou Medical CollegeHangzhou 310053China Shandong Center for Disease Control and Prevention Jinan 250021China

Toxoplasma gondii is a worldwide parasite that can infect almost all kinds of mammals and cause fatal toxoplasmosis in immunocompromised patients.Apoptosis is one of the principal strategies of host cells to clear pathogens and maintain organismal homeostasis,but the mechanism of cell apoptosis induced by T.gondii remains obscure.To explore the apoptosis influenced by T.gondii,Vero cells infected or uninfected with the parasite were subjected to apoptosis detection and subsequent dual RNA sequencing(RNA-seq).Using high-throughput Illumina sequencing and bioinformatics analysis,we found that pro-apoptosis genes such as DNA damage-inducible transcript 3(DDIT3),growth arrest and DNA damage-inducibleα(GADD45 A),caspase-3(CASP3),and high-temperature requirement protease A2(Htr A2)were upregulated,and anti-apoptosis genes such as poly(adenosine diphosphate(ADP)-ribose)polymerase family member 3(PARP3),B-cell lymphoma 2(Bcl-2),and baculoviral inhibitor of apoptosis protein(IAP)repeat containing 5(BIRC5)were downregulated.Besides,tumor necrosis factor(TNF)receptor-associated factor 1(TRAF1),TRAF2,TNF receptor superfamily member 10 b(TNFRSF10 b),disabled homolog2(DAB2)-interacting protein(DAB2 IP),and inositol 1,4,5-trisphosphate receptor type 3(ITPR3)were enriched in the upstream of TNF,TNF-related apoptosis-inducing ligand(TRAIL),and endoplasmic reticulum(ER)stress pathways,and TRAIL-receptor2(TRAIL-R2)was regarded as an important membrane receptor influenced by T.gondii that had not been previously considered.In conclusion,the T.gondii RH strain could promote and mediate apoptosis through multiple pathways mentioned above in Vero cells.Our findings improve the understanding of the T.gondii Infection process through providing new insights into the related cellular apoptosis mechanisms.

关键词： Toxoplasma gondii Transcriptome analysis Apoptosis Infection

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Emerging vaccine nanotechnology: From defense against Infection to sniping cancer

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Acta Pharmaceutica Sinica B 2022年第5期12卷 2206-2223页

作者： Chan Feng Yongjiang Li Bijan Emiliano Ferdows Dylan Neal Patel Jiang Ouyang Zhongmin Tang Na Kong Enguo Chen Wei Tao Department of Respiratory Medicine Sir Run Run Shaw HospitalZhejiang University School of MedicineHangzhou 310016China Center for Nanomedicine and Department of Anesthesiology Brigham and Women’s HospitalHarvard Medical SchoolBostonMA 02115USA Cancer Center Zhejiang UniversityHangzhou 310058China Department of Pharmacy the Second Xiangya Hospital of Central South UniversityChangsha 410011China

Looking retrospectively at the development of humanity, vaccination is an unprecedented medical landmark that saves lives by harnessing the human immune system. During the ongoing coronavirus disease 2019(COVID-19) pandemic, vaccination is still the most effective defense modality. The successful clinical application of the lipid nanoparticle-based Pfizer/BioNTech and Moderna mRNA COVID-19 vaccines highlights promising future of nanotechnology in vaccine development. Compared with conventional vaccines, nanovaccines are supposed to have advantages in lymph node accumulation,antigen assembly, and antigen presentation;they also have, unique pathogen biomimicry properties because of well-organized combination of multiple immune factors. Beyond infectious diseases, vaccine nanotechnology also exhibits considerable potential for cancer treatment. The ultimate goal of cancer vaccines is to fully mobilize the potency of the immune system as a living therapeutic to recognize tumor antigens and eliminate tumor cells, and nanotechnologies have the requisite properties to realize this goal.In this review, we summarize the recent advances in vaccine nanotechnology from infectious disease prevention to cancer immunotherapy and highlight the different types of materials, mechanisms, administration methods, as well as future perspectives.

关键词： Vaccine Nanotechnology Infection Cancer Nanovaccines Vaccination Diseases prevention Immunotherapy

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Exploration of the common gene and potential molecular mechanisms between Herpes simplex virus 1 Infection and Alzheimer's disease

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Genes & Diseases 2023年第3期10卷 746-749页

作者： Weizheng Liang Xiushen Li Hao Wang Shuangqing Wang Qingxue Meng Ruoqing Feng Jingbo Zhai Mengzhou Xue Chunfu Zheng Institute of Animal Health Guangdong Academy of Agricultural SciencesKey Laboratory of Livestock Disease Prevention of Guangdong ProvinceScientific Observation and Experiment Station of Veterinary Drugs and Diagnostic Techniques of Guangdong ProvinceMinistry of Agriculture and Rural AffairsGuangzhouGuangdong 510640China Central Laboratory The First Affiliated Hospital of Hebei North UniversityZhangjiakouHebei 075000China Department of Obstetrics and Gynecology Shenzhen University General HospitalShenzhenGuangdong 518055China Shenzhen Key Laboratory Shenzhen University General HospitalShenzhenGuangdong 518055China Department of Neurology Shenzhen University General HospitalShenzhen UniversityShenzhenGuangdong 518055China Key Laboratory of Zoonose Prevention and Control at Universities of Inner Mongolia Autonomous Region TongliaoMongolia 028000China Department of Cerebrovascular Diseases The Second Affiliated Hospital of Zhengzhou UniversityZhengzhouHenan 450001China Department of Microbiology Immunology and Infectious DiseasesUniversity of CalgaryCalgaryAlberta T2N 1N4Canada

Herpes simplex virus 1(HSV-1)is highly infectious.More than 70%of the world's population has been infected with HSV-1.1 Most patients with HSV-1 have no obvious clinical symptoms.However,HSV-1 Infection can lead to se... 详细信息

关键词： Infection Alzheimer simplex

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A CRISPR activation screen identifies genes that enhance SARS-CoV-2 Infection

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Protein & Cell 2023年第1期14卷 64-68页

作者： Fei Feng Yunkai Zhu Yanlong Ma Yuyan Wang Yin Yu Xinran Sun Yuanlin Song Zhugui Shao Xinxin Huang Ying Liao Jingyun Ma Yuping He Mingyuan Wang Longhai Tang Yaowei Huang Jincun Zhao Qiang Ding Youhua Xie Qiliang Cai Hui Xiao Chun Li Zhenghong Yuan Rong Zhang Key Laboratory of Medical Molecular Virology(MOE/NHC/CAMS) School of Basic Medical SciencesShanghai Medical CollegeShanghai Institute of Infectious Disease and BiosecurityFudan UniversityShanghai 200032China Department of Pulmonary Medicine Zhongshan HospitalShanghai Key Laboratory of Lung Inflammation and InjuryFudan UniversityShanghai 200032China The Center for Microbes Development and HealthCAS Key Laboratory of Molecular Virology&ImmunologyInstitute Pasteur of ShanghaiCAS Center for Excellence in Molecular Cell ScienceUniversity of Chinese Academy of SciencesChinese Academy of SciencesShanghai 200031China Technical Center for Animal Plant and Food Inspection and Quarantine of Shanghai CustomsShanghai 200032China Shanghai Veterinary Research Institute CAASShanghai 200241China College of Animal Science South China Agricultural UniversityGuangzhou 510642China Shanghai International Travel Healthcare Center Shanghai 200335China Suzhou Blood Center Suzhou 215006China Key Laboratory of Animal Virology of Ministry of Agriculture College of Animal SciencesZhejiang UniversityHangzhou 310058China State Key Laboratory of Respiratory Disease National Clinical Research Center for Respiratory DiseaseGuangzhou Institute of Respiratory Healththe First Affiliated Hospital of Guangzhou Medical UniversityGuangzhou 510182China Center for Infectious Disease Research School of MedicineTsinghua UniversityBeijing 100086China

Dear Editor,Identifying the host factors that are utilized for virus Infection and mapping their cell-type expression profile can help to understand the viral tissue/organ tropism and pathogenesis.Much effort has been devoted to the identification of SARS-CoV-2 Infection-dependent host factors.CRISPR-based activation(Konermann et al.,2015).

关键词： Infection al. activation

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Genome-wide identification and characterization of basic helix-loop-helix transcription factors in Spodoptera litura upon pathogen Infection

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Insect Science 2022年第4期29卷 977-992页

作者： Jie Zhang Mengyao Zhu Qilin Li Ting Tang Liang Wen Jielai Zhong Ruonan Zhang Xiao-Qiang Yu Yuzhen Lu Guangdong Provincial Key Laboratory of Insect Developmental Biology and Applied Technology Institute of Insect Science and TechnologySchool of Life SciencesSouth China Normal UniversityGuangzhouChina Guangzhou Key Laboratory of Insect Development Regulation and Application Research Institute of Insect Science and TechnologySchool of Life SciencesSouth China Normal UniversityGuangzhouChina

Basic helix-loop-helix(bHLH)transcription factors play an important role in a wide range of metabolic and developmental processes in eukaryotes,and bHLH proteins also participate in immune responses,especially in plants.However,their roles in insects upon entomopathogen Infection are unknown.In this study,54 bHLH genes in 41 families were identified in a polyphagous pest,Spodoptera litura,including a new bHLH gene in group B,which is specifically present in Lepidoptera and was thus named Lep.The conserved amino acids in the bHLH domain,structural architecture,and chromosomal distribution of bHLH genes in S.litura were analyzed.The bHLH genes in Plutella xylostella and Apis mellifera were also updated,and genome-wide comparison and phylogenetic analysis of bHLH members in 5 holometabolous insects were performed.The expression profiles of S.litura bHLH(SlbHLH)genes in 3 tissues at different developmental stages and their responses to S.litura nucleopolyhedrovirus(SpltNPV),Nomuraea rileyi(Nr),and Bacillus thuringiensis(Bt)Infection were investigated.More SlbHLHs in group B were expressed and differentially expressed during pathogen Infections,and SlbHLHs tended to be downregulated in the midgut of S.litura larvae after B.thuringiensis treatment.Our study provides an overview of bHLH family members in S.litura and their responses to different pathogens used for pest biocontrol.These findings on bHLH members may contribute to uncovering the mechanism of host-pathogen interaction.

关键词： basic helix-loop-helix entomopathogen Infection pest biocontrol Spodoptera liura

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Association between influenza vaccination and SARS-CoV-2 Infection and its outcomes: systematic review and meta-analysis

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Chinese Medical Journal 2022年第19期135卷 2282-2293页

作者： Binshan Jiang Qiangru Huang Mengmeng Jia Xinai Xue Qing Wang Weizhong Yang Luzhao Feng School of Population Medicine and Public Health Chinese Academy of Medical Sciences&Peking Union Medical CollegeBejing 100730China Department of Medical Records Peking Union Medical College HospitalChinese Academy of Medical SciencesBeijing 100730China.

Background:World Health Organization recommends that influenza vaccines should benefit as much of the population as possible,especially where resources are limited.Corona virus disease 2019(COVID-19)has become one of the greatest threats to health systems worldwide.The present study aimed to extend the evidence of the association between influenza vaccination and COVID-19 to promote the former.Methods:In this systematic review,four electronic databases,including the Cochrane Library,PubMed,Embase,and Web of Science,were searched for related studies published up to May 2022.All odds ratios(ORs)with 95%confidence intervals(CIs)were pooled by meta-analysis.Results:A total of 36 studies,encompassing 55,996,841 subjects,were included in this study.The meta-analysis for severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)Infection provided an OR of 0.80(95%CI:0.73–0.87).The statistically significant estimates for clinical outcomes were 0.83(95%CI:0.72–0.96)for intensive care unit admission,0.69(95%CI:0.57–0.84)for ventilator support,and 0.69(95%CI:0.52–0.93)for fatal Infection,while no effect seen in hospitalization with an OR of 0.87(95%CI:0.68–1.10).Conclusion:Influenza vaccination helps limit SARS-CoV-2 Infection and severe outcomes,but further studies are needed.Registration:PROSPERO,CRD42022333747.

关键词： Influenza vaccine COVID-19 Infection Outcomes Prevention

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