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China CDC weekly 2023年第5期5卷 103-107,I0006页

作者： Xinhua Chen Xufang Bai Xinghui Chen Nan Zheng Juan Yang Juanjuan Zhang Hongjie Yu School of Public Health Fudan UniversityKey Laboratory of Public Health SafetyMinistry of EducationShanghai MunicipalityChina Shanghai Huashen Institute of Microbes and Infections Shanghai MunicipalityChina shanghai institute of Infectious Disease and Biosecurity Fudan UniversityShanghai MunicipalityChina

Summary What is already known about this topic?Previous studies have reported vaccine efficacy or effectiveness against severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)Omicron subvariants for several vaccine platforms.However,there are currently few data on estimates of inactivated platform coronavirus disease 2019(COVID-19)vaccines,especially against the globally dominant subvariant—Omicron BA.5.

关键词： vaccine acute respiratory

Atmospheric humidity regulates same-sex mating in Candida albicans through the trehalose and osmotic signaling pathways

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Science China(Life Sciences) 2023年第8期66卷 1915-1929页

作者： Chao Li Li Tao Guobo Guan Zhangyue Guan Austin M.Perry Tianren Hu Jian Bing Ming Xu Clarissa J.Nobile Guanghua Huang Department of Infectious Diseases Huashan HospitalShanghai Institute of Infectious Disease and Biosecurity and State Key Laboratory of Genetic EngineeringSchool of Life SciencesFudan UniversityShanghai 200438China State Key Laboratory of Mycology Institute of MicrobiologyChinese Academy of SciencesBeijing 100101China Department of Molecular and Cell Biology University of CaliforniaMercedMerced CA 95343USA Quantitative and Systems Biology Graduate Program University of CaliforniaMercedMerced CA 95343USA Health Sciences Research institute University of CaliforniaMercedMerced CA 95343USA shanghai Engineering Research Center of Industrial Microorganisms Shanghai 200438China Shanghai Huashen Institute of Microbes and Infections Shanghai 200052China

Sexual reproduction is prevalent in eukaryotic organisms and plays a critical role in the evolution of new traits and in the generation of genetic diversity.Environmental factors often have a direct impact on the occurrence and frequency of sexual reproduction in fungi.The regulatory effects of atmospheric relative humidity(RH)on sexual reproduction and pathogenesis in plant fungal pathogens and in soil fungi have been extensively investigated.However,the knowledge of how RH regulates the lifecycles of human fungal pathogens is limited.In this study,we report that low atmospheric RH promotes the development of mating projections and same-sex(homothallic)mating in the human fungal pathogen Candida albicans.Low RH causes water loss in C.albicans cells,which results in osmotic stress and the generation of intracellular reactive oxygen species(ROS)and trehalose.The water transporting aquaporin Aqy1,and the G-protein coupled receptor Gpr1 function as cell surface sensors of changes in atmospheric humidity.Perturbation of the trehalose metabolic pathway by inactivating trehalose synthase or trehalase promotes same-sex mating in C.albicans by increasing osmotic or ROS stresses,respectively.Intracellular trehalose and ROS signal the Hog1-osmotic and Hsf1-Hsp90 signaling pathways to regulate the mating response.We,therefore,propose that the cell surface sensors Aqy1 and Gpr1,intracellular trehalose and ROS,and the Hog1-osmotic and Hsf1-Hsp90 signaling pathways function coordinately to regulate sexual mating in response to low atmospheric RH conditions in C.albicans.

关键词： atmospheric relative humidity sexual reproduction same-sex mating Candida albicans trehalose metabolism osmotic stress

Nasopharyngeal Local Transcriptional Profile upon SARS-CoV-2 Omicron BA.2.2 Breakthrough Infection

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Infectious Diseases & Immunity 2023年第4期3卷 186-191页

作者： Yi Zhang Yang Zhou Yumeng Zhang Jiazhen Chen Jing Wu Peng Cui Shiyong Wang Yuanyuan Xu Zhongliang Shen Tao Xu Yang Li Jingwen Ai Ning Jiang Chao Qiu Wenhong Zhang Department of Infectious Diseases Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency ResponseNational Medical Center for Infectious DiseasesHuashan HospitalShanghai Medical CollegeFudan UniversityShanghai 200040China School of Life Sciences Fudan UniversityShanghai 200438China institutes of Biomedical Sciences Fudan UniversityShanghai 200032China National Clinical Research Center for Aging and Medicine Huashan HospitalFudan UniversityShanghai 200040China Shanghai Huashen Institute of Microbes and Infections Shanghai 200052China

The Omicron variants have continued to cause severe acute respiratory syndrome coronavirus 2 infections.To better understand the anti-viral effects of vaccination on host-virus interactions during the outbreak of BA.2.2 Omicron,we conducted RNA-seq transcriptome analysis on nasopharyngeal swabs from COVID-19 patients in shanghai.This study was performed on selected cases from unvaccinated,fully vaccinated,and booster groups with the same founder virus infection background.We observed predominant immune cell chemotaxis and interleukin-1 production,as well as mucosal keratinization and epidermis development,in unvaccinated patients.In contrast,fully vaccinated subjects exhibited an obvious T-cell activation in the local immune response,whereas B-cell activation was higher in booster-vaccinated cases.In conclusion,our findings suggest that full or booster vaccination provides better adaptive immunity and relieve inflammation at the nasopharyngeal site,thereby reducing the risk of cytokine storm during breakthrough infection.

关键词： SARS-CoV-2 Local immune response Transcriptome Inflammation

Neutralizing antibodies against SARS-CoV-2 virus after vaccination in patients with neurofibromatosis type 1

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Signal Transduction and Targeted Therapy 2023年第7期8卷 3215-3217页

作者： Qiao-ling Ruan Zhi-chao Wang Cheng-jiang Wei Wei Wang Qing-luan Yang Jing Wu Yan-min Wan Ling-ling Ge Wen-hong Zhang Qing-feng Li Department of Infectious Diseases National Medical Center for Infectious DiseasesShanghai Key Laboratory of Infectious Diseases and Biosafety Emergency ResponseHuashan HospitalFudan UniversityShanghaiPeople’s Republic of China Department of Plastic and Reconstructive Surgery Shanghai Ninth People’s HospitalShanghai Jiao Tong University School of MedicineShanghaiPeople’s Republic of China Shanghai Huashen Institute of Microbes and Infections ShanghaiPeople’s Republic of China

Dear Editor,The severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)has triggered a COVID-19 pandemic that has caused high morbidity and mortality worldwide.1 COVID-19 vaccines are urgently needed to protect all susceptible populations from SARS-CoV-2 infection.Neurofibromatosis type 1(NF1)is a hereditary dominant disease that affects approximately one in every 3000 newborns.

关键词： mortality acute respiratory

Origin,virological features,immune evasion and intervention of SARS-CoV-2 Omicron sublineages

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Signal Transduction and Targeted Therapy 2022年第8期7卷 2673-2679页

作者： Shuai Xia Lijue Wang Yun Zhu Lu Lu Shibo Jiang Key Laboratory of Medical Molecular Virology(MOE/NHC/CAMS) Shanghai Institute of Infectious Disease and BiosecuritySchool of Basic Medical SciencesShanghai Frontiers Science Center of Pathogenic Microbes and InfectionFudan UniversityShanghaiChina National Key Laboratory of Biomacromolecules CAS Center for Excellence in BiomacromoleculesInstitute of BiophysicsChinese Academy of SciencesBeijingChina

Recently,a large number of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)variants continuously emerged and posed a major threat to global public health.Among them,particularly,Omicron variant(B.1.1.529),first identified in November 2021,carried numerous mutations in its spike protein(S),and then quickly spread around the world.Currently,Omicron variant has expanded into more than one hundred sublineages,such as BA.1,BA.2,BA.2.12.1,BA.4 and BA.5,which have already become the globally dominant variants.Different from other variants of concern(VOCs)of SARS-CoV-2,the Omicron variant and its sublineages exhibit increased transmissibility and immune escape from neutralizing antibodies generated through previous infection or vaccination,and have caused numerous re-infections and breakthrough infections.In this prospective,we have focused on the origin,virological features,immune evasion and intervention of Omicron sublineages,which will benefit the development of nextgeneration vaccines and therapeutics,including pan-sarbecovirus and universal anti-CoV therapeutics,to combat currently circulating and future emerging Omicron sublineages as well as other SARS-CoV-2 variants.

关键词： features breakthrough expanded

Metagenomic analysis reveals oropharyngeal microbiota alterations in patients with COVID-19

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Signal Transduction and Targeted Therapy 2021年第6期6卷 1822-1832页

作者： Shengli Ma Fan Zhang Fengxia Zhou Hui Li Wenyu Ge Rui Gan Huan Nie Biao Li Yindong Wang Meng Wu Duo Li Dongmei Wang Zheng Wang Yuhong You Zhiwei Huang Heilongjiang Provincial Hospital Harbin Institute of TechnologyHarbinChina School of Life Science and Technology Harbin Institute of TechnologyHarbinChina School of Energy Science and Engineering Harbin Institute of TechnologyHarbinChina Department of Stomatology Zhongshan HospitalFudan UniversityShanghaiChina

COVID-19 remains a serious emerging global health problem,and little is known about the role of oropharynx commensal microbes in infection susceptibility and severity.Here,we present the oropharyngeal microbiota characteristics identified by shotgun metagenomic sequencing analyses of oropharynx swab specimens from 31 COVID-19 patients,29 influenza B patients,and 28 healthy controls.Our results revealed a distinct oropharyngeal microbiota composition in the COVID-19 patients,characterized by enrichment of opportunistic pathogens such as Veillonella and Megasphaera and depletion of Pseudopropionibacterium,Rothia,and Streptococcus.Based on the relative abundance of the oropharyngeal microbiome,we built a microbial classifier to distinguish COVID-19 patients from flu patients and healthy controls with an AUC of 0.889,in which Veillonella was identified as the most prominent biomarker for COVID-19 group.Several members of the genus Veillonella,especially Veillonella parvula which was highly enriched in the oropharynx of our COVID-19 patients,were also overrepresented in the BALF of COVID-19 patients,indicating that the oral cavity acts as a natural reservoir for pathogens to induce co-infections in the lungs of COVID-19 patients.We also found the increased ratios of Klebsiella sp.,Acinetobacter sp.,and Serratia sp.were correlated with both disease severity and elevated systemic inflammation markers(neutrophil-lymphocyte ratio,NLR),suggesting that these oropharynx microbiota alterations may impact COVID-19 severity by influencing the inflammatory response.Moreover,the oropharyngeal microbiome of COVID-19 patients exhibited a significant enrichment in amino acid metabolism and xenobiotic biodegradation and metabolism.In addition,all 26 drug classes of antimicrobial resistance genes were detected in the COVID-19 group,and were significantly enriched in critical cases.In conclusion,we found that oropharyngeal microbiota alterations and functional differences were associated with COVID-19 severity.

关键词： alterations patients severity

Human leukocyte antigen-DP loci are associated with the persistent infection of hepatitis B virus in Chinese population

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微生物与感染 2012年第1期7卷 18-27页

作者： LING Yun LIAO Xiang-Wei LI Xin-Hua HAN Yue YANG Zhi-Tao KONG Xiao-Fei GU Lei-Lei YU De-Ming YAO Bi-Lian ZHANG Dong-Hua JIN Gen-Di GONG Qi-Ming ZHANG Xin-Xin Department of Infectious Diseases Ruijin Hospital Shanghai Jiao Tong University School of Medicine Shanghai 200025 China institute of Infectious and Respiratory Diseases Ruijin Hospital Shanghai Jiao Tong University School of Medicine Shanghai 200025 China Sino-French Laboratory of Life Science and Genomics Ruijin Hospital Shanghai Jiao Tong University School of Medicine Shanghai 200025 China

A genome-wide association study recently showed that genetic variants in human leukocyte antigen (HLA)-DP loci were strongly associated with a risk of persistent infection of hepatitis B virus (HBV) in Japanese and Thai individuals and variants in interleukin 28B (IL-28B) have been associated with responses to anti-hepatitis C virus (HCV) treatment. The aim of this study was to investigate whether the HLA-DP loci and IL-28B were associated with different outcomes of chronic HBV infection (CHB) in Chinese subjects. The rs9277535 near HLA-DPB1,rs3077 near HLA-DPA1, and rs12979860 near IL-28B were genotyped by direct sequencing in 185 CHB patients and 193 self-limited hepatitis B virus (SLHBV)-infected subjects who recovered from HBV infection. The rs9277535 near HLA-DPB1 was strongly associated with CHB (P=0.000 018 1, OR=1.905). This association was observed independent of HBV e antigen (HBeAg) status and HBV viral loads in HBeAg-positive CHB patients (P=0.000 4, OR=1.956), in HBeAg-negative CHB patients (P=0.000 9, OR=1.857), and in HBeAg-negative CHB individuals without detectable levels of HBV DNA in serum (P=0.001 1, OR=2.05). The rs3077 near HLA-DPA1 was associated with CHB (P=0.020 6, OR=0.686 5) and HBeAg-positive CHB infection status (P=0.014 3, OR=0.604 7). Meanwhile, a genetic variation of insertion-deletion (INDEL) polymorphism (rs361527, -/ATAAATGTTGA) near HLA-DPA1 was found to be associated with CHB (P=0.030 7, OR=0.702 8) and HBeAg-positive CHB infection status (P=0.023 3, OR=0.619). However,the rs12979860 genotype near IL-28B had no correlation with CHB. This study demonstrated that in the Han Chinese populations, HLA-DP loci, but not IL-28B, were associated with persistence of infection in different outcomes of HBV-infected patients; however, the mechanism needs to be further investigated.

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Bioengineered materials with selective antimicrobial toxicity in biomedicine

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Military Medical Research 2023年第6期10卷 798-817页

作者： Pooyan Makvandi Hao Song Cynthia K.Y.Yiu Rossella Sartorius Ehsan Nazarzadeh Zare Navid Rabiee Wei-Xi Wu Ana Cláudia Paiva-Santos Xiang-Dong Wang Cheng-Zhong Yu Franklin R.Tay The Quzhou Affiliated Hospital of Wenzhou Medical University Quzhou People’s HospitalQuzhou 324000ZhejiangChina Istituto Italiano di Tecnologia Centre for Materials InterfacesPontedera 56025Italy Australian institute for Bioengineering and Nanotechnology The University of QueenslandBrisbaneQLD 4072Australia Paediatric Dentistry and Orthodontics Faculty of DentistryThe University of Hong KongPrince Philip Dental HospitalHong Kong SARChina institute of Biochemistry and Cell Biology(IBBC) National Research Council(CNR)80131 NaplesItaly School of Chemistry Damghan UniversityDamghan 36716‑45667Iran School of Engineering Macquarie UniversitySydneyNSW 2109Australia Centre for Molecular Medicine and Innovative Therapeutics Murdoch UniversityPerthWA 6150Australia Department of Pharmaceutical Technology Faculty of Pharmacy of the University of CoimbraUniversity of Coimbra3000‑548 CoimbraPortugal REQUIMTE/LAQV Group of Pharmaceutical TechnologyFaculty of Pharmacy of the University of CoimbraUniversity of Coimbra3000‑548 CoimbraPortugal Department of Pulmonary and Critical Care Medicine Zhongshan HospitalFudan University Shanghai Medical CollegeShanghai 200032China School of Chemistry and Molecular Engineering East China Normal UniversityShanghai 200241China The Graduate School Augusta UniversityAugustaGA 30912USA

Fungi and bacteria afflict humans with innumerous pathogen-related infections and ailments.Most of the commonly employed microbicidal agents target commensal and pathogenic microorganisms without discrimination.To distinguish and fight the pathogenic species out of the microflora,novel antimicrobials have been developed that selectively target specific bacteria and fungi.The cell wall features and antimicrobial mechanisms that these microorganisms involved in are highlighted in the present review.This is followed by reviewing the design of antimicrobials that selectively combat a specific community of microbes including Gram-positive and Gram-negative bacterial strains as well as fungi.Finally,recent advances in the antimicrobial immunomodulation strategy that enables treating microorganism infections with high specificity are reviewed.These basic tenets will enable the avid reader to design novel approaches and compounds for antibacterial and antifungal applications.

关键词： Antimicrobial nanotechnology Immumodualtion Selective toxicity Smart nanomaterials Targeting microorganism

Three-dimensional structures of virulence proteins of Legionella establish targets for new antibacterials

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微生物与感染 2012年第1期7卷 2-12页

作者： Guido Hansen Rolf Hilgenfeld institute of Biochemistry Center for Structural and Cell Biology in MedicineUniversity of LübeckLübeck 23538Germany German Centre for Infection Research(DZIF) University of LübeckLübeck 23538Germany shanghai institute of Materia Medica Chinese Academy of SciencesShanghai 201203China Laboratory for Structural Biology of Infection and Inflammation c/o DESYHamburg 22603Germany

Legionella pneumophila,the causative agent of Legionnaires' disease,has been recognized as a major health problem responsible for an estimated number of 15 000-30 000 cases of severe pneumonia per year in Germany alone.Despite of the high clinical relevance,many aspects of the intracellular life cycle of Legionella,especially details on interactions with host cells,are not well understood.Structural information on virulence proteins helps unravel basal pathogenicity mechanisms and is a prerequisite for the rational development of effective drug molecules.Here we discuss structures of three important virulence proteins of Legionella that have been determined in our laboratory.The structure of the macrophage infectivity potentiator(Mip) protein of Legionella pneumophila is the first of a novel subgroup within the family of FK506-binding protein(FKBP) peptidyl-prolyl cis/trans isomerases.On the basis of the Mip structure,promising antibacterial agents are being designed.Recently,structures of two equally exciting Legionella proteins have been reported.The ferrous iron transport protein FeoB is a transmembrane protein responsible for Fe2+ aquisition after entry of the pathogen into the host cell.The structure of the cytoplasmic domain of FeoB provides insights into the family of prokaryotic G proteins and allows a detailed comparison with structures of related FeoBs.Furthermore,the characterization of DegQ,a periplasmatic chaperone-protease involved in protein quality control represents an intriguing example of how enzymatic activity is regulated by oligomerization as well as by an intrinsic loop activation cascade,depending on subtle conformational rearrangements.

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Modulation of Gut Microbiota in Pathological States

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Engineering 2017年第1期3卷 83-89页

作者： Yulan Wang BaohongWang Junfang wu xiangyang Jiang Huiru Tang Ole H. Nielsen Key Laboratory of Magnetic Resonance in Biological Systems State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics National Center for Magnetic Resonance Wuhan Institute of Physics and Mathematics Chinese Academy of Sciences Wuhan 430071 China National Collaborative Innovation Center for Diagnosis and Treatment of lnfectious Diseases State Key Laboratory for Diagnosis and Treatment of lnfectious Diseases The First Affiliated Hospital School of Medicine Zhejiang University Hangzhou 310003 China State Key Laboratory of Genetic Engineering Zhongshan Hospital and School of Life Sciences Fudan University Collaborative Innovation Center of Genetics and Development Shanghai International Center for Molecular Phenomics Shanghai 200433 China Department of Gastroenterology Medical Section Heriev Hospital University of Copenhagen Copenhagen 1017 Denmark

人类微生态是寄居在人体中的微生物聚集体,且主要存在于胃肠道(GIT)中。肠道微生态随着人体发育而演化,并在人类健康和疾病中起着重要作用。近年来,由于微生态会影响宿主代谢、生理学和免疫系统发育,而且微生态紊乱可能导致许多疾病,其... 详细信息

人类微生态是寄居在人体中的微生物聚集体,且主要存在于胃肠道(GIT)中。肠道微生态随着人体发育而演化,并在人类健康和疾病中起着重要作用。近年来,由于微生态会影响宿主代谢、生理学和免疫系统发育,而且微生态紊乱可能导致许多疾病,其越来越受到人们的关注。肠道微生态可能与恶性肿瘤有一定联系,如胃癌和结直肠癌;也可能与其他一些疾病有关,如非酒精性脂肪肝(NAFLD)、被称为工业化世界'生活方式疾病'的肥胖和糖尿病、冠心病以及中枢神经系统紊乱。虽然分子技术革命为我们更准确地研究肠道微生态提供了必要的工具,但是我们需要更精确地阐明其与某些人类疾病病理变化的关系,明确微生态在不同疾病中的作用是新的治疗策略发展的基础。本文概述了肠道微生态对人类健康的重要影响以及调整肠道菌群结构的潜在用途,如菌群移植用于治疗耐药艰难梭菌(C.difficile)的感染。通过微生态干预调整肠道区域以改善人类健康的概念虽刚刚兴起,但其治疗意义显著。因此,抑制有害菌、促进有益菌可能会保护人类健康,并且这些努力将为探索发展更加合理的治疗方案打下基础。

关键词：肠道菌群疾病菌群调节