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New strategies for asymmetric photocatalysis: asymmetric organocatalytic/photoredox relay catalysis for efficient synthesis of polycyclic compounds containing vicinal amino alcohols

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Science China Chemistry 2024年第3期67卷 945-952页

作者： Jia-Lu Zhang Wen-Bo He Xiu-Qin Hu Peng-Fei Xu State key Laboratory of Applied Organic Chemistry College of Chemistry and Chemical EngineeringLanzhou UniversityLanzhou 730000China State key Laboratory of veterinary Etiological Biology College of Veterinary MedicineLanzhou UniversityLanzhou Veterinary Research InstituteChinese Academy of Agricultural SciencesLanzhou 730000China MOE Frontiers Science Center for Rare Isotopes Lanzhou UniversityLanzhou 730000China

An asymmetric catalytic strategy in photocatalysis utilizing a chirality-induced approach through an organocatalytic/photoredox relay catalysis strategy is successfully achieved for the rapid construction of polycyclic compounds containing vicinal amino alcohols in a one-pot protocol. This methodology facilitates the efficient synthesis of diverse substituted polycyclic tetrahydroquinoline and benzofuran-derived vicinal amino alcohols, each containing five consecutive chiral centers, with high yields,excellent diastereoselectivities and enantioselectivities(up to 95% yield, >20:1 dr and 98% ee), under mild reaction conditions driven by sequential bifunctional squaramide organocatalyst-catalyzed [4+2] annulation and photocatalyst-catalyzed ketyl radical addition cyclization reaction process. Furthermore, investigations into the stereoselectivity mechanism and high-resolution mass spectrometry(HRMS) experiments on free radical trapping have provided evidence for elucidating the detailed mechanism of chirality-induced processes and chiral intermediate conversions in this procedure.

关键词： enantioselective photocatalysis asymmetric organocatalytic/photocatalysis relay catalysis five consecutive chiral centers chirality-induced strategy chirality vicinal amino alcohols

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M6PR interacts with the HA2 subunit of influenza A virus to facilitate the fusion of viral and endosomal membranes

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Science China(Life Sciences) 2024年第3期67卷 579-595页

作者： Yuzhen Hu Li Jiang Guangwen Wang Yangming Song Zhibo Shan Xuyuan Wang Guohua Deng Jianzhong Shi Guobin Tian Xianying Zeng Liling Liu Hualan Chen Chengjun Li State key Laboratory for Animal Disease Control and Prevention Harbin Veterinary Research InstituteChinese Academy of Agricultural SciencesHarbin 150069China

Influenza A virus(IAV) commandeers numerous host cellular factors for successful replication. However, very few host factors have been revealed to be involved in the fusion of viral envelope and late endosomal membranes. In this study, we identified cation-dependent mannose-6-phosphate receptor(M6PR) as a crucial host factor for the replication of IAV. We found that siRNA knockdown of M6PR expression significantly reduced the growth titers of different subtypes of IAV, and that the inhibitory effect of M6PR siRNA treatment on IAV growth was overcome by the complement of exogenously expressed M6PR. When A549 cells were treated with siRNA targeting M6PR,the nuclear accumulation of viral nucleoprotein(NP) was dramatically inhibited at early timepoints post-infection, indicating that M6PR engages in the early stage of the IAV replication cycle. By investigating the role of M6PR in the individual entry and post-entry steps of IAV replication, we found that the downregulation of M6PR expression had no effect on attachment, internalization, early endosome trafficking,or late endosome acidification. However, we found that M6PR expression was critical for the fusion of viral envelope and late endosomal membranes. Of note, M6PR interacted with the hemagglutinin(HA) protein of IAV, and further studies showed that the lumenal domain of M6PR and the ectodomain of HA2 mediated the interaction and directly promoted the fusion of the viral and late endosomal membranes,thereby facilitating IAV replication. Together, our findings highlight the importance of the M6PR–HA interaction in the fusion of viral and late endosomal membranes during IAV replication.

关键词： influenza A virus M6PR HA membrane fusion late endosome

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Control of highly pathogenic avian influenza through vaccination

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Journal of Integrative Agriculture 2024年第5期23卷 1447-1453页

作者： Xianying Zeng Jianzhong Shi Hualan Chen State key Laboratory for Animal Disease Control and Prevention Harbin Veterinary Research InstituteChinese Academy of Agricultural SciencesHarbin150069China

The stamping-out strategy has been used to control highly pathogenic avian influenza viruses in many countries,driven by the belief that vaccination would not be successful against such viruses and fears that avian influenza virus in vaccinated birds would evolve more rapidly and pose a greater risk to *** this review,we summarize the successes in controlling highly pathogenic avian influenza in China and make suggestions regarding the requirements for vaccine selection and *** addition,we present evidence that vaccination of poultry not only eliminates human infection with avian influenza virus,but also significantly reduces and abolishes some harmful characteristics of avian influenza virus.

关键词： avian influenza control highly pathogenic vaccination

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KIF5B-mediated internalization of FMDV promotes virus infection

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Virologica Sinica 2024年第3期39卷 378-389页

作者： Wei Zhang Fan Yang Yang Yang Weijun Cao Wenhua Shao Jiali Wang Mengyao Huang Zhitong Chen Xiaoyi Zhao Weiwei Li Zixiang Zhu Haixue Zheng State key Laboratory for Animal Disease Control and Prevention College of Veterinary MedicineLanzhou UniversityLanzhou Veterinary Research InstituteChinese Academy of Agricultural SciencesLanzhou 730000China Gansu Province research Center for Basic Disciplines of Pathogen Biology Lanzhou 730046China

Foot-and-mouth disease(FMD)is a highly contagious and economically important disease,which is caused by the FMD virus(FMDV).Although the cell receptor for FMDV has been identified,the specific mechanism of FMDV internalization after infection remains *** this study,we found that kinesin family member 5B(KIF5B)plays a vital role during FMDV ***,we confirmed the interaction between KIF5B and FMDV structural protein VP1 by co-immunoprecipitation(Co-IP)and co-localization in FMDV-infected *** particular,the stalk[amino acids(aa)413–678]domain of KIF5B was indispensable for KIF5B-VP1 ***,overexpression of KIF5B dramatically enhanced FMDV replication;consistently,knockdown or knockout of KIF5B suppressed FMDV ***,we also demonstrated that KIF5B promotes the internalization of FMDV via regulating clathrin ***5B also promotes the transmission of viral particles to early and late endosomes during the early stages of *** conclusion,our results demonstrate that KIF5B promotes the internalization of FMDV via regulating clathrin uncoating and intracellular *** study may provide a new therapeutic target for developing FMDV antiviral drugs.

关键词： FMDV VP1 protein KIF5B Endosome Clathrin

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Inactivated H9N2 vaccines developed with early strains do not protect against recent H9N2 viruses:Call for a change in H9N2 control policy

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Journal of Integrative Agriculture 2024年第6期23卷 2144-2148页

作者： Yanjing Liu Qingqing Yu Xiangyu Zhou Wenxin Li Xinwen He Yan Wang Guohua Deng Jianzhong Shi Guobin Tian Xianying Zeng Hualan Chen College of veterinary Medicine Gansu Agricultural UniversityLanzhou 730070China State key Laboratory for Animal Disease Control and Prevention Key Laboratory for Prevention and Control of Avian Influenza and Other Major Poultry DiseasesMinistry of Agriculture and Rural Affairs/Harbin Veterinary Research InstituteChinese Academy of Agricultural SciencesHarbin 150009China National Poultry Laboratory Animal Resource Center Harbin Veterinary Research InstituteChinese Academy of Agricultural SciencesHarbin 150009China Harbin Weike biotechnology Co. Ltd.Harbin 150009China

H9N2 virus has been widely distributed in wild birds and poultry around the world since its first emergence in the United States of America in 1966(Gu et al.2017;Carnaccini and Perez 2020).The virus appeared in chickens in China in the early 1990s,and over the last two decades has gradually become the dominant epidemic subtype(Sun and Liu 2015;Bi et al.2020).Although H9N2 virus infection alone cannot cause severe disease or death in poultry,H9N2 virus-infected birds experience a degree of egg production drop and can be easily infected by other pathogens,thus causing economic losses for poultry industry.

关键词： H9N2 poultry policy

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Establishment and application of a surrogate model for human Ebola virus disease in BSL-2 laboratory

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Virologica Sinica 2024年第3期39卷 434-446页

作者： Wanying Yang Wujian Li Wujie Zhou Shen Wang Weiqi Wang Zhenshan Wang Na Feng Tiecheng Wang Ying Xie Yongkun Zhao Feihu Yan Xianzhu Xia Hebei key Lab of Laboratory Animal Science Department of Laboratory Animal ScienceHebei Medical UniversityShijiazhuang050017China key Laboratory of Jilin Province for Zoonosis Prevention and Control Changchun Veterinary Research InstituteChinese Academy of Agricultural SciencesChangchun130122China College of veterinary Medicine Jilin UniversityChangchun130062China College of veterinary Medicine Jilin Agricultural UniversityChangchun130118China

The Ebola virus(EBOV)is a member of the Orthoebolavirus genus,Filoviridae family,which causes severe hemorrhagic diseases in humans and non-human primates(NHPs),with a case fatality rate of up to 90%.The development of countermeasures against EBOV has been hindered by the lack of ideal animal models,as EBOV requires handling in biosafety level(BSL)-4 ***,accessible and convenient animal models are urgently needed to promote prophylactic and therapeutic approaches against *** this study,a recombinant vesicular stomatitis virus expressing Ebola virus glycoprotein(VSV-EBOV/GP)was constructed and applied as a surrogate virus,establishing a lethal infection in *** infection with VSV-EBOV/GP,3-week-old female Syrian hamsters exhibited disease signs such as weight loss,multi-organ failure,severe uveitis,high viral loads,and developed severe systemic diseases similar to those observed in human EBOV *** animals succumbed at 2–3 days post-infection(dpi).Histopathological changes indicated that VSV-EBOV/GP targeted liver cells,suggesting that the tissue tropism of VSV-EBOV/GP was comparable to wild-type EBOV(WT EBOV).Notably,the pathogenicity of the VSV-EBOV/GP was found to be species-specific,age-related,gender-associated,and challenge ***,equine anti-EBOV immunoglobulins and a subunit vaccine were validated using this ***,this surrogate model represents a safe,effective,and economical tool for rapid preclinical evaluation of medical countermeasures against EBOV under BSL-2 conditions,which would accelerate technological advances and breakthroughs in confronting Ebola virus disease.

关键词： Ebola virus(EBOV) Recombinant vesicular stomatitis virus Pathogenicity Syrian hamster Surrogate models Vaccine evaluation and drug screening

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First identification of the oxazolidinone/phenicol resistance gene optrA in Streptococcus pluranimalium worldwide

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Journal of Integrative Agriculture 2024年第2期23卷 731-734页

作者： Kuan Zhao Longyu Zhou Shixia Zhang Wanjiang Zhang Yao Zhu College of veterinary Medicine Hebei Agricultural UniversityBaoding 071001China State key Laboratory for Animal Disease Control and Prevention Harbin Veterinary Research InstituteChinese Academy of Agricultural SciencesHarbin 150069China College of veterinary Medicine Xinjiang Agricultural UniversityUrumqi 830052China

Oxazolidinones are highly effective antimicrobial agents for the treatment of serious infections caused by Gram-positive organisms,including methicillin-resistant Staphylococcus aureus(MRSA),vancomycin-resistant enterococci(VRE),multidrug-resistant(MDR)pneumococci and MDR mycobacteria(Brenciani et al.2022).However,the emergence and prevalence of acquired oxazolidinone resistance genes.

关键词： resistance prevalence

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DeepSecE:A Deep-Learning-Based Framework for Multiclass Prediction of Secreted Proteins in Gram-Negative Bacteria

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research 2024年第3期2023卷 243-257页

作者： Yumeng Zhang Jiahao Guan Chen Li Zhikang Wang Zixin Deng Robin BGasser Jiangning Song Hong-Yu Ou state key Laboratory of Microbial Metabolism Joint International Laboratory on Metabolic&Developmental SciencesSchool of Life Sciences and BiotechnologyShanghai Jiao Tong UniversityShanghai 200240China Shanghai key Laboratory of veterinary biotechnology Shanghai Jiao Tong UniversityShanghai 200240China Biomedicine Discovery institute and Department of Biochemistry and Molecular Biology Monash UniversityMelbourneViC 3800Australia Monash Data Futures institute Monash UniversityMelbourneViC 3800Australia Melbourne veterinary School Faculty of ScienceThe University of MelbourneParkvilleVIC 3010Australia.

Proteins secreted by Gram-negative bacteria are tightly linked to the virulence and adaptability of these microbes to environmental *** identification of such secreted proteins can facilitate the investigations of infections and diseases caused by these bacterial ***,current bioinformatic methods for predicting bacterial secreted substrate proteins have limited computational efficiency and application scope on a genome-wide ***,we propose a novel deep-learning-based framework—DeepSecE—for the simultaneous inference of multiple distinct groups of secreted proteins produced by Gram-negative *** remarkably improves their classification from nonsecreted proteins using a pretrained protein language model and transformer,achieving a macro-average accuracy of 0.883 on 5-fold *** benchmarking suggests that DeepSecE achieves competitive performance with the state-of-the-art binary predictors specialized for individual types of secreted *** attention mechanism corroborates salient patterns and motifs at the N or C termini of the protein *** this pipeline,we further investigate the genome-wide prediction of novel secreted proteins and their taxonomic distribution across~1,000 Gram-negative bacterial *** present analysis demonstrates that DeepSecE has major potential for the discovery of disease-associated secreted proteins in a diverse range of Gram-negative *** online web server of DeepSecE is also publicly available to predict and explore various secreted substrate proteins via the input of bacterial genome sequences.

关键词： Deep server competitive

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The virulence regulator AbsR in avian pathogenic Escherichia coli has pleiotropic effects on bacterial physiology

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Journal of Integrative Agriculture 2024年第2期23卷 649-668页

作者： Dongfang Zhao Haobo Zhang Xinyang Zhang Fengwei Jiang Yijing Li Wentong Cai Ganwu Li State key Laboratory for Animal Disease Control and Prevention Harbin Veterinary Research InstituteChinese Academy of Agricultural SciencesHarbin 150069China College of veterinary Medicine Northeast Agricultural UniversityHarbin 150038China National Animal Tuberculosis Reference Laboratory Division of Zoonoses SurveillanceChina Animal Health and Epidemiology CenterQingdao 266032China Department of veterinary Diagnostic and Production Animal Medicine College of Veterinary MedicineIowa State UniversityAmesIowa 50011-1134the United States

Avian pathogenic Escherichia coli(APEC)belonging to extraintestinal pathogenic ***(ExPEC)can cause severe infections in extraintestinal tissues in birds and humans,such as the lungs and ***(microcin production regulation,locus A,herein renamed AbsR,a blood survival regulator),a member of the MarR(multiple antibiotic resistance regulator)transcriptional regulator family,governs the expression of capsule biosynthetic genes in human ExPEC and represents a promising druggable target for ***,a deep understanding of the AbsR regulatory mechanism as well as its regulon is *** this study,we present a systems-level analysis of the APEC AbsR regulon using ChIP-Seq(chromatin immunoprecipitation sequencing)and RNA-Seq(RNA sequencing)*** found that AbsR directly regulates 99 genes and indirectly regulates 667 ***,we showed that:1)AbsR contributes to antiphagocytotic effects by macrophages and virulence in a mouse model for systemic infection by directly activating the capsular gene cluster;2)AbsR positively impacts biofilm formation via direct regulation of the T2SS(type II secretion system)but plays a marginal role in virulence;and 3)AbsR directly upregulates the acid tolerance signaling system EvgAS to withstand acid stress but is dispensable in ExPEC ***,our data indicate that the role of AbsR in virulence gene regulation is relatively conserved in ExPEC ***,this study provides a comprehensive analysis of the AbsR regulon and regulatory mechanism,and our data suggest that AbsR likely influences virulence primarily through the control of capsule ***,we found that AbsR severely represses the expression of the type I-F CRISPR(clustered regularly interspaced short palindromic repeats)-Cas(CRISPR associated)systems,which could have implications in CRISPR biology and application.

关键词： avian pathogenic Escherichia coli(APEC) extraintestinal pathogenic Escherichia coli(ExPEC) AbsR RNA-Seq ChIP-Seq gene regulation

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Changes in structural plasticity of hippocampal neurons in an animal model of multiple sclerosis

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Zoological research 2024年第2期45卷 398-414页

作者： Poornima D.E.Weerasinghe-Mudiyanselage Sohi Kang Joong-Sun Kim Sung-Ho Kim Hongbing Wang Taekyun Shin Changjong Moon Department of veterinary Anatomy and Animal Behavior College of Veterinary Medicine and BK21 FOUR ProgramChonnam National UniversityGwangju 61186Republic of Korea Department of Anatomy and Convergence Medical Science Institute of Health SciencesCollege of MedicineGyeongsang National UniversityJinju 52727Republic of Korea Department of Physiology and Neuroscience Program Michigan State UniversityEast LansingMI 48824USA Department of veterinary Anatomy College of Veterinary Medicine and Veterinary Medical Research InstituteJeju National UniversityJeju 63243Republic of Korea

Structural plasticity is critical for the functional diversity of neurons in the *** autoimmune encephalomyelitis(EAE)is the most commonly used model for multiple sclerosis(MS),successfully mimicking its key pathological features(inflammation,demyelination,axonal loss,and gliosis)and clinical symptoms(motor and non-motordysfunctions).Recentstudieshave demonstrated the importance of synaptic plasticity in EAE *** the present study,we investigated the features of behavioral alteration and hippocampal structural plasticity in EAE-affected mice in the early phase(11 days post-immunization,DPI)and chronic phase(28DPI).EAE-affected mice exhibited hippocampus-related behavioral dysfunction in the open field test during both early and chronic *** complexity was largely affected in the cornu ammonis 1(CA1)and CA3 apical and dentate gyrus(DG)subregions of the hippocampus during the chronic phase,while this effect was only noted in the CA1 apical subregion in the early ***,dendritic spine density was reduced in the hippocampal CA1 and CA3 apical/basal and DG subregions in the early phase of EAE,but only reduced in the DG subregion during the chronic ***,mRNA levels of proinflammatory cytokines(Il1β,Tnfα,and Ifnγ)and glial cell markers(Gfap and Cd68)were significantly increased,whereas the expression of activity-regulated cytoskeletonassociated protein(ARC)was reduced during the chronic ***,exposure to the aforementioned cytokines in primary cultures of hippocampal neurons reduced dendritic complexity and ARC *** cultures of hippocampal neurons also showed significantly reduced extracellular signal-regulated kinase(ERK)phosphorylation upon treatment with proinflammatory ***,these results suggest that autoimmune neuroinflammation alters structural plasticity in the hippocampus,possibly through the ERK-ARC pathway,indicating that this alteration may be associated with hi

关键词： Activity-regulated cytoskeleton-associated protein Anxiety-like behavior Experimental autoimmune encephalomyelitis Hippocampal dysfunction Neuroinflammation

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