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Coxsackievirus B3 HFMD animal models in Syrian hamster and rhesus monkey

Virologica Sinica 2024年第2期39卷 290-300页

作者： Suqin Duan Wei Zhang Yongjie Li Yanyan Li Yuan Zhao Weihua Jin Quan Liu Mingxue Li Wenting Sun Lixiong Chen Hongjie Xu Jie Tang Jinghan Hou Zijun Deng Fengmei Yang Shaohui Ma Zhanlong He Institute of Medical Biology Chinese Academy of Medical Sciences Medical Primate Research Center Peking Union Medical CollegeYunnan Key Laboratory of Vaccine Research Development on Severe Infectious DiseaseKunming650118China

Coxsackievirus B3(CVB3)is the pathogen causing hand,foot and mouth disease(HFMD),which manifests across a spectrum of clinical severity from mild to ***,CVB3-infected mouse models mainly demonstrate viral myocarditis and pancreatitis,failing to replicate human HFMD *** several enteroviruses have been evaluated in Syrian hamsters and rhesus monkeys,there is no comprehensive data on *** this study,we have first tested the susceptibility of Syrian hamsters to CVB3 infection via different *** results showed that Syrian hamsters were successfully infected with CVB3 by intraperitoneal injection or nasal drip,leading to nasopharyngeal colonization,acute severe pathological injury,and typical HFMD ***,the nasal drip group exhibited a longer viral excretion cycle and more severe pathological *** the subsequent study,rhesus monkeys infected with CVB3 through nasal drips also presented signs of HFMD symptoms,viral excretion,serum antibody conversion,viral nucleic acids and antigens,and the specific organ damages,particularly in the ***,there were no significant differences in myocardial enzyme levels,and the clinical symptoms resembled those often associated with common,mild *** summary,the study successfully developed severe Syrian hamsters and mild rhesus monkey models for CVB3-induced *** models could serve as a basis for understanding the disease pathogenesis,conducting pre-trial prevention and evaluation,and implementing post-exposure intervention.

关键词： Coxsackievirus B3(CVB3) Hand foot and mouth disease(HFMD) Animal models Syrian hamster Rhesus monkey

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Protectivity of Freeze Dried Inactivated Rift Valley Fever vaccine

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Open Journal of Veterinary Medicine 2024年第2期14卷 21-37页

作者： Diana M. Abulmagd Mohamed Hassan Atwa Noha Ezz Aldin Marwa Yehia Hammad Taradi Abdel Fattah Said Rift Valley Fever vaccine research Department Veterinary Serum and Vaccine Research Institute Agriculture Research Center (ARC) Cairo Egypt

Background: Vaccinations for animals are crucial for food production, animal welfare, public health, and animal health. They are an affordable way to stop animal sickness, increase food production efficiency, and lessen or stop the spread of zoonotic diseases to humans. Animal vaccines that are both safe and efficacious are vital to modern culture. The vaccine should induce a strong, protective and prolonged immune response against the antigenic factor. In order to achieve these goals, novel vaccination techniques and an efficient adjuvant are required to render the vaccine immunogenically protective and trigger a strong immune response. Aim: Our study aims to promote and enhance the immunogenicity against RVF virus disease through lyophilized inactivated RVF vaccine through induction of early cellular, high and prolonged humeral immunity in vaccinated animals using cabopol as stabilizer and Saponin or normal saline as a diluent at time of vaccination. Moreover, manufacturing of these vaccines is easy to be done. Results: The gained results revealed that RVF freeze-dried vaccine with Carbopol that reconstituted using Saponin elicited better immune response than that reconstituted using normal saline (NaCl). The cell mediated immune response as represented by lymphocyte blastogenesis and phagocytic activity were markedly increased with high levels when we used Saponin as a diluent than that in group vaccinated with vaccine diluted with NaCl, on the other side the humeral immune response in group vaccinated using the Saponin as diluent is more detected and stayed within the protective level till the end of 11th month post vaccination (1.5 TCID50) while the immune response induced after using normal saline as a diluent stayed within the protective level till the end of 10th month post vaccination (1.8 TCID50). Conclusion: The use of Saponin as a diluent for reconstitution of the freeze dried RVF vaccine is preferable than the

关键词： Rift Valley Fever Saponin Cabopol Binary Ethylenemine Serum Neutralization Test

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Examining the“revisability”benefit of hip resurfacing arthroplasty

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World Journal of Orthopedics 2024年第6期15卷 554-559页

作者： Jose George Adam J Taylor Thomas P Schmalzried Department of Orthopedics Harbor UCLA Medical CenterTorranceCA 90509United States

BACKGROUND Hip resurfacing arthroplasty(HRA)is an alternative to total hip arthroplasty(THA)that is typically reserved for young active patients because it preserves ***,the benefits of HRA only hold true if conversion THA after failed HRA provides acceptable *** To compare patient reported outcomes for conversion THA after HRA failure to primary *** A retrospective review of 36 patients(37 hips)that underwent conversion THA for failed HRA between October 2006 and May 2019 by a single surgeon was *** reported outcomes[modified Harris Hip Score(mHHS),University of California Los Angeles(ucla)activity score]were obtained via an email-based responder-anonymous *** were compared to normative data of a primary THA cohort with similar *** analysis was performed comparing outcomes of conversion THA for adverse local tissue reaction(ALTR)vs all other causes for *** The study group had a lower mHHS than the control group(81.7±13.8 vs 90.2±11.6,Pucla activity levels(7.5±2.3 vs 7.2±1.6,P=0.51).Patients that underwent conversion for non-ATLR causes had similar mHHS(85.2±11.5 vs 90.2±11.6,P=0.11)and higher ucla activity levels(8.5±1.8 vs 7.2±1.6,Pucla activity levels(6.1±2.3 vs 7.2±1.6,P=0.05)when compared to the control *** Patient outcomes equivalent to primary THA can be achieved following HRA conversion to ***,inferior outcomes were demonstrated for ALTR-related HRA *** selection and perhaps further studies examining alternative HRA bearing surfaces should be considered.

关键词： Total hip arthroplasty Hip resurfacing arthroplasty Conversion total hip arthroplasty Adverse local tissue reaction Patient reported outcome measures

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Nasal vaccination of triple-RBD scaffold protein with flagellin elicits long-term protection against SARS-CoV-2 variants including JN.1

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Signal Transduction and Targeted Therapy 2024年第5期9卷 2312-2323页

作者： Xian Li Mengxin Xu Jingyi Yang Li Zhou Lin Liu Min Li Shasha Wang Mei-Qin Liu Zhixiang Huang Zhen Zhang Shuning Liu Yunqi Hu Haofeng Lin Bowen Liu Ying Sun Qingguo Wu Zheng-Li Shi Ke Lan Yu Chen Huimin Yan Yao-Qing Chen Wuhan Institute of Virology Chinese Academy of SciencesWuhanChina vaccine and Immunology research center Translational Medical Research InstituteShanghai Public Health Clinical CenterFudan UniversityShanghaiChina University of Chinese Academy of Sciences BeijingChina School of Public Health(Shenzhen) Shenzhen Campus of Sun Yat-sen UniversityShenzhenGuangdongChina State Key Laboratory of Virology Modern Virology Research CenterCollege of Life SciencesWuhan UniversityWuhanChina Aerosol Bio-Tech(Suzhou)Co. LTDSuzhouJiangsuChina National Medical Products Administration Key Laboratory for Quality Monitoring and Evaluation of vaccines and Biological Products Sun Yat-sen UniversityGuanzhouChina

Developing a mucosal vaccine against SARS-CoV-2 is critical for combatting the ***,we investigated long-term immune responses and protection against SARS-CoV-2 for the intranasal vaccination of a triple receptor-binding domain(RBD)scaffold protein(3R-NC)adjuvanted with a flagellin protein(KFD)(3R-NC+KFDi.n).In mice,the vaccination elicited RBD-specific broad-neutralizing antibody responses in both serum and mucosal sites sustained at high level over a *** long-lasting humoral immunity was correlated with the presence of long-lived RBD-specific IgG-and IgA-producing plasma cells,alongside the Th17 and Tfh17-biased T-cell responses driven by the KFD *** upon these preclinical findings,an open labeled clinical trial was conducted in individuals who had been primed with the inactivated SARS-CoV-2(IAV)*** a favorable safety profile,the 3R-NC+KFDi.n boost elicited enduring broad-neutralizing IgG in plasma and IgA in salivary *** meet the challenge of frequently emerged variants,we further designed an updated triple-RBD scaffold protein with mutated RBD combinations,which can induce adaptable antibody responses to neutralize the newly emerging variants,including *** findings highlight the potential of the KFD-adjuvanted triple-RBD scaffold protein is a promising prototype for the development of a mucosal vaccine against SARS-CoV-2 infection.

关键词： vaccination vaccine sustained

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Plasma Metabonomics of Human Adenovirus-infected Patients with Pneumonia and Upper Respiratory Tract Infection

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Current Medical Science 2024年第1期44卷 121-133页

作者： Ting-ting WEI Wen XU Bo TU Wan-xue ZHANG Xin-xin YANG Yiguo ZHOU Shan-shan ZHANG Jun-lian YANG Ming-zhu XIE Juan DU Wei-wei CHEN Qing-bin LU Department of Epidemiology and Biostatistics School of Public HealthPeking UniversityBeijing 100191China Department of Infectious Disease The Fifth Medical Center of Chinese PLA General HospitalNational Clinical Research Center for Infectious DiseasesBeijing 100039China Department of Laboratorial Science and Technology&vaccine research center School of Public HealthPeking UniversityBeijing 100191China Department of Health Policy and Management School of Public HealthPeking UniversityBeijing 100191China Global center for Infectious Disease and Policy research&Global Health and Infectious Diseases Group Peking UniversityBeijing 100191China Key Laboratory of Epidemiology of Major Diseases(Peking University) Ministry of EducationBeijing 100191China

Objective Human adenovirus(HAdV)infection is common and can develop to serious conditions with high mortality,yet the mechanism of HAdV infection remains *** the present study,the serum metabolite profiles of HAdV-7-infected patients with pneumonia or upper respiratory tract infection(URTI)were *** In total,35 patients were enrolled in the study following an outbreak of HAdV-7 in the army,of whom 14 had pneumonia and 21 had *** samples were collected at the acute stage and at the recovery stage and were analyzed by untargeted *** Over 90% of the differential metabolites identified between the pneumonia patients and URTI patients were lipids and lipid-like molecules,including glycerophospholipids,fatty acyls,and *** metabolic pathways that were significantly enriched were primarily the lipid metabolism pathways,including sphingolipid metabolism,glycerophospholipid metabolism,and linoleic acid *** sphingolipid metabolism was identified as a significantly differential pathway between the pneumonia patients and URTI patients and between the acute and recovery stages for the pneumonia patients,but not between the acute and recovery stages for the URTI *** and lactosylceramide,involved in sphingolipid metabolism,were significantly higher in the pneumonia patients than in the URTI patients with good discrimination abilities[area under curve(AUC)0.742 and 0.716,respectively;combination AUC 0.801].Conclusion Our results suggested that HAdV modulated lipid metabolism for both the patients with URTI and pneumonia,especially the sphingolipid metabolism involving ceramide and lactosylceramide,which might thus be a potential intervention target in the treatment of HAdV infection.

关键词： human adenovirus metabonomic lipids pneumonia upper respiratory tract infection

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Natural evidence of coronaviral 2′-O-methyltransferase activity affecting viral pathogenesis via improved substrate RNA binding

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Signal Transduction and Targeted Therapy 2024年第6期9卷 2819-2834页

作者： Jikai Deng Shimin Yang Yingjian Li Xue Tan Jiejie Liu Yanying Yu Qiang Ding Chengpeng Fan Hongyun Wang Xianyin Chen Qianyun Liu Xiao Guo Feiyu Gong Li Zhou Yu Chen State Key Laboratory of Virology RNA InstituteCollege of Life Sciences and Frontier Science Center for Immunology and MetabolismWuhan UniversityWuhanChina School of Medicine Tsinghua UniversityBeijingChina School of Basic Medical Sciences Wuhan UniversityWuhanChina Animal Bio-Safety Level Ⅲ Laboratory/Institute for vaccine research Wuhan University School of MedicineWuhanChina

Previous studies through targeted mutagenesis of K-D-K-E motif have demonstrated that 2′-O-MTase activity is essential for efficient viral replication and immune ***,the K-D-K-E catalytic motif of 2′-O-MTase is highly conserved across numerous viruses,including flaviviruses,vaccinia viruses,coronaviruses,and extends even to ***,we observed a stronger 2′-O-MTase activity in SARS-CoV-2 compared to SARS-CoV,despite the presence of a consistently active catalytic *** further identified critical residues(Leu-36,Asn-138 and Ile-153)which served as determinants of discrepancy in 2′-O-MTase activity between SARS-CoV-2 and *** residues significantly enhanced the RNA binding affinity of 2′-O-MTase and boosted its versatility toward RNA *** interest,a triple substitution(Leu^(36)→Ile^(36),Asn^(138)→His^(138),Ile^(153)→Leu^(153),from SARS-CoV-2 to SARS-CoV)within nsp16 resulted in a proportional reduction in viral 2′-O-methylation and impaired viral ***,it led to a significant upregulation of type I interferon(IFN-I)and proinflammatory cytokines both in vitro and vivo,relying on the cooperative sensing of melanoma differentiation-associated protein 5(MDA5)and laboratory of genetics and physiology 2(LGP2).In conclusion,our findings demonstrated that alterations in residues other than K-D-K-E of 2′-O-MTase may affect viral replication and subsequently influence *** changes in nsp16 residues is crucial as it may aid in identifying and assessing future alteration in viral pathogenicity resulting from natural mutations occurring in nsp16.

关键词： pathogenesis impaired alterations

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Intranasal boosting with RBD-HR protein vaccine elicits robust mucosal and systemic immune responses

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Genes & Diseases 2024年第4期11卷 327-339页

作者： Li Chen Wenyan Ren Hong Lei Jiayu Wang Haiying Que Dandan Wan Aqu Alu Dandan Peng Minyang Fu Weiqi Hong Yuhe Huang Xiangrong Song Guangwen Lu Xiawei Wei Laboratory of Aging research and Cancer Drug Target State Key Laboratory of Biotherapy and Cancer CenterNational Clinical Research Center for GeriatricsWest China HospitalSichuan UniversityChengduSichuan 610041China

The emergence of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)variants has decreased the efficacy of SARs-CoV-2 vaccines in containing coronavirus disease 2019(CoVID-19)over time,and booster vaccination strategies are urgently necessitated to achieve sufficient *** immunization can improvemucosal immunity,offer-ing protection against the infection and sustaining the spread of *** this study,an intranasal booster of the RBD-HR vaccine after two doses of the mRNA vaccine significantly increased the levels of specific binding antibodies in serum,nasal lavage fluid,and bronchoal-veolar lavage fluid compared with only two doses of mRNA *** intranasal boosting with the RBD-HR vaccine,the levels of serum neutralizing antibodies against prototype and variant strains of SARS-Cov-2 pseudoviruses weremarkedly higher than those in mice receiving mRNA vaccine alone,and intranasal boosting with the RBD-HR vaccine also inhibited the bind-ing of RBD to hACE2 ***,the heterologous intranasal immunization regimen promoted extensive memory T cell responses and activated CD103+dendritic cells in the respiratory mucosa,and potently enhanced the formation of T follicular helper cells and germinal center B cells in vital immune organs,including mediastinal lymph nodes,inguinal lymph nodes,and ***,these data infer that heterologous intranasal boosting with the RBD-HR vaccine elicited broad protective immunity against SARS-CoV-2 both locallyandsystemically.

关键词： Heterologous immunization Intranasal immunization mRNA vaccine SARS-CoV-2 Subunitprotein vaccine

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The SARS-CoV-2 spike protein induces lung cancer migration and invasion in a TLR2-dependent manner

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Cancer Communications 2024年第2期44卷 273-277页

作者： Mi-Jeong Kim Ji Young Kim Ji Hye Shin Juhee Son Yeeun Kang Soo-Kyung Jeong Duk-Hwan Kim Kyun-Hwan Kim Eunyoung Chun Ki-Young Lee Department of Immunology Samsung Biomedical Research InstituteSungkyunkwan University School of MedicineSuwonRepublic of Korea research and Development center CHA Vaccine InstituteSeongnam-siRepublic of Korea Department of Molecular Cell Biology Sungkyunkwan University School of MedicineSuwonRepublic of Korea Department of Precision Medicine Sungkyunkwan University School of MedicineSuwonRepublic of Korea Department of Health Sciences and Technology Samsung Advanced Institute for Health Sciences&TechnologySamsung Medical CenterSungkyunkwan UniversitySeoulRepublic of Korea

Dear editor,Severe acute respiratory syndrome coronavirus2(SARS-CoV-2)infection can lead to severe outcomes in patients with cancer[1].It has been reported that patients with lung cancers disproportionately manifest severe COVID-19 with a high rate of hospitalization and death[2].Notably,the SARS-CoV-2 Spike(S)protein can induce hyper-inflammation in both epithelial cells and macrophages through toll-like receptor(TLR)1/TLR2 or TLR2/6-dependent nuclear factor-kappaB(NF-κB)path-way[3].However,molecular and cellular evidence on whether the SARS-CoV-2 virus affects the severity of lung cancer patients through TLR1/2 or TLR2/6 signaling remains unclear.

关键词： lung TLR2 invasion

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Mechanism of Mingjing Granules in Treating Wet Age-Related Macular Degeneration Based on Network Pharmacology and Experimental Verification

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World Journal of Traditional Chinese Medicine 2024年第1期10卷 22-32页

作者： Xiao-Yu Li Li-Na Liang Wei-Jun Zhang Yun Gao Qiang Chen Eye Function Laboratory Eye HospitalChina Academy of Chinese Medical SciencesBeijingChina China Evidence-Based Medicine center for Traditional Chinese Medicine BeijingChina center for East-West Medicine UCLA David Geffen School of MedicineLos AngelesCAUSA

Objective:To analyze the potential mechanism of Mingjing granules in the treatment of wet age-related macular degeneration(wAMD)based on the research methods of network pharmacology and molecular docking approach and to provide a new reference for the currently limited treatment of *** and Methods:We searched TCMSP,GeneCards,OMIM,PharmGkb,TTD,and DrugBank database to screen the main active ingredients of Mingjing granules and their therapeutic targets of *** network of active components and targets was constructed using Cytoscape3.6.1 software,which was also used for the topological analysis of target *** network of Protein-Protein Interactions(PPI)was mapped using the String *** also used R language to do the Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway for additional *** docking studies were finished by Chemoffice,Autodock,and ***,the efficacy of the Mingjing granules was examined in animal experiments,in which we used enzyme-linked immunosorbent assay to the contents of vascular endothelial growth factor(VEGF)and matrix metalloproteinase-9(MMP-9)levels in peripheral ***:Active compounds,including quercetin,lignocaine,and kaempferol,were *** network analysis showed that tumor necrosis factor(TNF),MMP-9,epidermal growth factor(EGF),prostaglandin-endoperoxide synthase 2(PTGS2),and caspase-3(CASP3)were related to both Mingjing granules and *** and KEGG pathway analysis showed that these targets were mainly involving lipids and atherosclerosis,TNF,and interleukin-17(IL-17)signaling *** studies suggested that quercetin and luteolin can fit in the binding pocket of four target proteins(CASP3,EGF,PTGS2,and TNF).In the vivo experiment,the Mingjing granules were found to be effective on the expression of VEGF and MMP-9 in peripheral ***:This study initially reveals the multi-constituent,multi-target,and multi-pathway mechanism of action of Ming

关键词： Experimental verification Mingjing granules molecular docking network pharmacology wet age-related macular degeneration

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3'-Sialyllactose regulates glucose and lipid metabolic disorders via the gut–liver axis in mice fed a high-fat die

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Food Science and Human Wellness 2024年

作者： Wei Zhang Meizhen Zhu Kelsang Dekyi Linxi Zheng Yichen Zhang Youping Lv Dongbei Guo Xiaoxuan Chen Lili Pan Xinyue Wang Hongwei Li State Key Laboratory of vaccines for Infectious Diseases Xiang An Biomedicine Laboratory School of Public Health Xiamen University State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics National Innovation Platform for Industry-Education Integration in vaccine research Xiamen University Department of Nutrition Zhongshan Hospital (Xiamen) Fudan University Xiamen Clinical research center for Cancer Therapy

Recent research has indicated that sialic acid， such as free sialic acid (N-acetylneuraminic acid， Neu5Ac) and bound sialic acid (3'-sialyllactose， 3'-SL)， can ameliorate disorders associated with glycolipid metabolism， although the underlying mechanisms have yet to be determined. We examined the effects of 3'-SL on glycolipid metabolism in mice fed a high-fat diet. Male C57BL/6J mice were divided into six groups: two model control groups (normal and high-fat diets) and four intervention groups [Neu5Ac， and low-，moderate-， and high-dose 3'-SL]. After 8 weeks of continuous gavage intervention， mice in the 3'-SL intervention groups had lower body weight and total fat content; reduced fasting blood glucose， triglycerides， low-density lipoproteins and oxidized-low-density lipoproteins; and increased high-density lipoproteins，but no dosage-dependent of 3'-SL intervention was found， 3’-SL＿M intervention as optimal for further exploration. 3'-SL intervention could increase respiratory exchange ratio， energy expenditure， and amount of exercise performed. 3'-SL increased the colonic abundances of Akkermansia， Lactobacillus， and Bacteroides， and reduced those of Erysipelatoclostridium， Faecalibaculum， and Aldercreutzia. Changes were also observed in colonic metabolites， and liver gene transcript and metabolites， which were mainly enriched in bile secretion， taurine and hypotaurine metabolism， and insulin resistance. Additionally， 3'-SL was observed to regulate genes associated with physiological rhythms， including clock， per2， cry1， and bhihe41. Collectively， our findings indicate that 3'-SL can contribute to the prevention and control of disorders associated with glucose and lipid metabolism caused by high-fat diets. Compared with Neu5Ac， 3'-SL intervention can ameliorate intestinal flora disorders， enhance bile acid circulation， increase tissue energy expenditure， and reduce lipid synthesis， thereby promoting lipid-lowering effects mediated via the liver–gut axis， and can a

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