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Seasonal and Genetic Characteristics of Human Metapneumovirus Circulating—Henan Province,China,2017-2023

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China CDC weekly 2024年第20期6卷 450-456,I0001页

作者： Zhibo Xie Zhen Zhu Jin Xu Naiying Mao Aili Cui Wenhui Wang Yage Wang Zhibo Zhang Baicheng Xia Haoran Wang Zhen Sun Yan Zhang National Key laboratory of Intelligent Tracking and Forecasting for Infectious Diseases NHC Key Laboratory of Medical Virology and Viral DiseaseNational Institute for Viral Disease Control and PreventionChinese Center for Disease Control and PreventionBeijingChina Henan Provincial Center for Disease Control and Prevention Luohe CityHenan ProvinceChina Luohe Center for Disease Control and Prevention Luohe CityHenan ProvinceChina Luohe Central Hospital Luohe CityHenan ProvinceChina

Introduction:This study examines the seasonal and genetic characteristics of human metapneumovirus(HMPV)in Henan from 2017 to ***:Samples from patients with acute respiratory infection(ARI)testing positive for HMPV were subjected to real-time reverse transcription polymerase chain reaction The G gene was amplified and sequenced from these samples for epidemiological and phylogenetic ***:We enrolled 2,707 ARI patients from October 2017 to March 2023,finding an HMPV positivity rate of 6.17%(167/2,707).Children under five exhibited the highest infection rate at 7.78%(138/1,774).The 2018 and 2019 HMPV outbreaks predominantly occurred in spring(March to May),with peak positivity rates of 31.11%in May 2018 and 19.57%in May 2019.A notable increase occurred in November 2020,when positivity reached a historic high of 42.11%,continuing until January *** February 2021 through March 2023,no significant seasonal peaks were observed,with rates ranging from 0%to 8.70%.Out of 81 G gene sequences analyzed,46.91%(38/81)were identified as subtype A(A2c:45.67%,37/81;A2b:1.23%,1/81)and 53.09%(43/81)as subtype B(B1:9.88%,8/81;B2:43.21%,35/81).Notably,an AAABBA switch pattern was observed in HMPV *** dominant strains were A2c111nt-dup in subtype A and B2 in subtype ***:Six years of surveillance in Henan Province has detailed the seasonal and genetic dynamics of HMPV,contributing valuable insights for the control and prevention of HMPV infections in *** findings support the development of targeted HMPV vaccines and immunization strategies.

关键词： prevention finding seasonal

A novel engineered IL-21 receptor arms T-cell receptor-engineered T cells(TCR-T cells)against hepatocellular carcinoma

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Signal Transduction and Targeted Therapy 2024年第5期9卷 2215-2230页

作者： Wei Zhu Zhiming Zhang Jinzhang Chen Xiaolan Chen Lei Huang Xiaoyong Zhang Xuan Huang Na Ma Weikang Xu Xuan Yi Xinyu Lu Xin Fu Siwei Li Guoheng Mo Yiyue Wang Guosheng Yuan Mengya Zang Qi Li Xiaotao Jiang Yajing He Sha Wu Yukai He Yongyin Li Jinlin Hou State Key laboratory of Organ Failure Research Guangdong Provincial Key Laboratory of Viral Hepatitis ResearchDepartment of Infectious DiseasesNanfang HospitalSouthern Medical UniversityGuangzhouChina Institute of Cellular Medicine Newcastle University Medical SchoolNewcastleUK Department of Pathology The First People’s Hospital of FoshanFoshanChina Dermatology Hospital Southern Medical UniversityGuangzhouChina Department of Immunology School of Basic Medical SciencesSouthern Medical UniversityGuangzhouChina Microbiome Medicine Center Department of Laboratory MedicineZhujiang HospitalSouthern Medical UniversityGuangzhouChina Key laboratory of Proteomics of Guangdong Province Demonstration Center for Experimental Education of Basic Medical Sciences of ChinaGuangzhouChina Medical College of Georgia Augusta University112015th StreetAugustaGAUSA

Strategies to improve T cell therapy efficacy in solid tumors such as hepatocellular carcinoma(HCC)are urgently *** common cytokine receptorγchain(γc)family cytokines such as IL-2,IL-7,IL-15 and IL-21 play fundamental roles in T cell development,differentiation and effector *** study aims to determine the combination effects of IL-21 in T cell therapy against HCC and investigate optimized strategies to utilize the effect of IL-21 signal in T cell *** antitumor function of AFP-specific T cell receptor-engineered T cells(TCR-T)was augmented by exogenous IL-21 in vitro and in ***-21 enhanced proliferation capacity,promoted memory differentiation,downregulated PD-1 expression and alleviated apoptosis in TCR-T after activation.A novel engineered IL-21 receptor was established,and TCR-T armed with the novel engineered IL-21 receptors(IL-21R-TCR-T)showed upregulated phosphorylated STAT3 expression without exogenous IL-21 ***-21R-TCR-T showed better proliferation upon activation and superior antitumor function in vitro and in ***-21R-TCR-T exhibited a less differentiated,exhausted and apoptotic phenotype than conventional TCR-T upon repetitive tumor antigen *** novel IL-21 receptor in our study programs powerful TCR-T and can avoid side effects induced by IL-21 systemic *** novel IL-21 receptor creates new opportunities for next-generation TCR-T against HCC.

关键词： hepatocellular TCR utilize

Establishment of a Multiplex Detection Method for Common Bacteria in Blood Based on Human Mannan-Binding Lectin Protein-Conjugated Magnetic Bead Enrichment Combined with Recombinase-Aided PCR Technology

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Biomedical and Environmental Sciences 2024年第4期37卷 387-398页

作者： ZHAO Zi Jin CHEN Xiao Ping HUA Shao Wei LI Feng Yu ZHAO Meng XING Chen Hao WANG Jie TIAN Feng Yu ZHANG Rui Qing LYU Xiao Na HAN Zhi Qiang WANG Yu Xin LI Hong Yi SHEN Xin Xin MA Xue Jun TIE Yan Qing Graduate School Hebei North UniversityZhangjiakou 075000HebeiChina Department of Clinical laboratory Hebei General HospitalShijiazhuang 050051HebeiChina National Key laboratory of Intelligent Tracking and Forecasting for Infectious Diseases NHC Key Laboratory of Medical Virology and Viral DiseasesNational Institute for Viral Disease Control and PreventionChinese Center for Disease Control and PreventionBeijing 102206China National Institute for Communicable Disease Control and Prevention Chinese Center for Disease Control and PreventionBeijing 102206China Department of Clinical laboratory Pathology Diagnostic Center Shiyan General HospitalShiyan 442000HubeiChina Graduate School Hebei Medical University Shijiazhuang 050031HebeiChina

Objective Recombinase-aided polymerase chain reaction(RAP)is a sensitive,single-tube,two-stage nucleic acid amplification *** study aimed to develop an assay that can be used for the early diagnosis of three types of bacteremia caused by Staphylococcus aureus(SA),Pseudomonas aeruginosa(PA),and Acinetobacter baumannii(AB)in the bloodstream based on recombinant human mannanbinding lectin protein(M1 protein)-conjugated magnetic bead(M1 bead)enrichment of pathogens combined with *** Recombinant plasmids were used to evaluate the assay *** blood influenza bacteria were used for the specific *** and clinical plasma samples were enriched with M1 beads and then subjected to multiple recombinase-aided PCR(M-RAP)and quantitative PCR(qPCR)*** analysis was used to evaluate the consistency between the two *** The M-RAP method had sensitivity rates of 1,10,and 1 copies/μL for the detection of SA,PA,and AB plasmids,respectively,without cross-reaction to other bacterial *** M-RAP assay obtained results for<10 CFU/mL pathogens in the blood within 4 h,with higher sensitivity than qPCR.M-RAP and qPCR for SA,PA,and AB yielded Kappa values of 0.839,0.815,and 0.856,respectively(P<0.05).Conclusion An M-RAP assay for SA,PA,and AB in blood samples utilizing M1 bead enrichment has been developed and can be potentially used for the early detection of bacteremia.

关键词： Staphylococcus aureus Pseudomonas aeruginosa Acinetobacter baumannii Human Mannan-binding lectin protein Bloodstream infection Recombinase-aided PCR assay Multiple detection

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Molecular Evolution of Protein Sequences and Codon Usage in Monkeypox Viruses

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Genomics, Proteomics & Bioinformatics 2024年第1期22卷 89-97页

作者： Ke-Jia Shan Changcheng Wu Xiaolu Tang Roujian Lu Yaling Hu Wenjie Tan Jian Lu State Key laboratory of Protein and Plant Gene Research Center for BioinformaticsSchool of Life SciencesPeking UniversityBeijing 100871China Sinovac Biotech Ltd. Beijing 100085China NHC Key laboratory of Biosafety National Institute for Viral Disease Control and PreventionChinese Center for Disease Control and PreventionBeijing 100052China

The monkeypox virus(mpox virus,MPXV)epidemic in 2022 has posed a significant public health ***,the evolutionary principles of MPXV remain largely ***,we examined the evolutionary patterns of protein sequences and codon usage in *** first demonstrated the signal of positive selection in OPG027,specifically in the CladeⅠlineage of ***,we discovered accelerated protein sequence evolution over time in the variants responsible for the 2022 ***,we showed strong epistasis between amino acid substitutions located in different *** codon adaptation index(CAI)analysis revealed that MPXV genes tended to use more non-preferred codons compared to human genes,and the CAI decreased over time and diverged between clades,with CladeⅠ>Ⅱa andⅡb-A>Ⅱ*** the decrease in fatality rate among the three groups aligned with the CAI pattern,it remains unclear whether this correlation was coincidental or if the deoptimization of codon usage in MPXV led to a reduction in fatality *** study sheds new light on the mechanisms that govern the evolution of MPXV in human populations.

关键词： Mpox virus Positive selection OPG027 Accelerated evolution Codon usage bias

TEA domain transcription factor 1(TEAD1)induces cardiac fibroblasts cells remodeling through BRD4/Wnt4 pathway

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Signal Transduction and Targeted Therapy 2024年第3期9卷 1209-1220页

作者： Shuai Song Xiaokai Zhang Zihang Huang Yongchao Zhao Shuyang Lu Linqi Zeng Fengze Cai Tongyao Wang Zhiqiang Pei Xinyu Weng Wei Luo Hao Lu Zilun Wei Jian Wu Peng Yu Li Shen Xiaochun Zhang Aijun Sun Junbo Ge Department of Cardiology Zhongshan HospitalFudan UniversityShanghai Institute of Cardiovascular DiseasesShanghaiChina State Key laboratory of Cardiology Zhongshan HospitalFudan UniversityShanghaiChina Key laboratory of viral Heart Diseases National Health CommissionShanghaiChina Key laboratory of viral Heart Diseases Chinese Academy of Medical SciencesShanghaiChina National Clinical Research Center for Interventional Medicine ShanghaiChina Department of cardiac surgery Zhongshan HospitalFudan UniversityShanghaiChina Institutes of Biomedical Sciences Fudan UniversityShanghaiChina Shanghai Institute of Hypertension Ruijin HospitalShanghai Jiao Tong University School of MedicineShanghaiChina

Cardiac fibroblasts(CFs)are the primary cells tasked with depositing and remodeling collagen and significantly associated with heart failure(HF).TEAD1 has been shown to be essential for heart development and ***,fibroblast endogenous TEAD1 in cardiac remodeling remains incompletely *** analyses revealed consistently upregulated cardiac TEAD1 expression in mice 4 weeks after transverse aortic constriction(TAC)and Ang-l *** investigation revealed that CFs were the primary cell type expressing elevated TEAD1 levels in response to pressure *** TEAD1 knockout was achieved by crossing TEAD1-floxed mice with CFs-and myofibroblasts-specific Cre *** and histological analyses demonstrated that CFs-and myofibroblasts-specific TEAD1 deficiency and treatment with TEAD1 inhibitor,VT103,ameliorated TAC-induced cardiac ***,RNA-seq and ChiP-seq analysis identified Wnt4 as a novel TEAD1 ***1 has been shown to promote the fibroblast-to-myofibroblast transition through the Wnt signalling pathway,and genetic Wnt4 knockdown inhibited the pro-transformation phenotype in CFs with TEAD1 ***,coimmunoprecipitation combined with mass spectrometry,chromatin immunoprecipitation,and luciferase assays demonstrated interaction between TEAD1 and BET protein BRD4,leading to the binding and activation of the Wnt4 *** conclusion,TEAD1 is an essential regulator of the pro-fibrotic CFs phenotype associated with pathological cardiac remodeling via the BRD4/Wnt4 signallingpathway.

关键词： TEAD1 expression Wnt4

Serological Investigation into the Infected Genotypes of Patients with Japanese Encephalitis in the Coastal Provinces of China

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Biomedical and Environmental Sciences 2024年第7期37卷 716-725页

作者： Weijia Zhang Jierong Zhao Qikai Yin Shenghui Liu Ruichen Wang Shihong Fu Fan Li Ying He Kai Nie Guodong Liang Songtao Xu Guang Yang Huanyu Wang National Key laboratory of Intelligent Tracking and Forecasting for Infectious Diseases National Institute for Viral Disease Control and PreventionChinese Center for Disease Control and PreventionBeijing 102206China School of Basic Medicine and Public Health Jinan UniversityGuangzhou 510000GuangdongChina

Objective Genotypes(G)1,3,and 5 of the Japanese encephalitis virus(JEV)have been isolated in China,but the dominant genotype circulating in Chinese coastal areas remains *** searched for G5 JEV-infected cases and attempted to elucidate which JEV genotype was most closely related to human Japanese encephalitis(JE)in the coastal provinces of *** In this study,we collected serum specimens from patients with JE in three coastal provinces of China(Guangdong,Zhejiang,and Shandong)from 2018 to 2020 and conducted JEV cross-neutralization tests against G1,G3,and *** Acute serum specimens from clinically reported JE cases were obtained for laboratory confirmation from hospitals in Shandong(92 patients),Zhejiang(192 patients),and Guangdong(77 patients),China,from 2018 to *** of the 361 serum specimens were laboratory-confirmed to be infected with *** cases were confirmed to be infected with G1 JEV,32 with G3 JEV,and two with G5 *** G3 was the primary infection genotype among JE cases with a definite infection genotype,and the infection caused by G5 JEV was confirmed serologically in China.

关键词： Japanese encephalitis virus Serological investigation Plaque reduction neutralization test Cross-neutralization test Genotype

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Thirty Years of Experience of Acute Flaccid Paralysis Surveillance for Polio — China, 1993–2022

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China CDC weekly 2024年第16期6卷 344-349页

作者： Hong Yang Ning Wen Chunxiang Fan Fuzhen Wang Yong Zhang Lei Cao Shuangli Zhu Lixin Hao Dongmei Yan Lei Wang Quanwei Song Miao Wang Yifan Song Chao Ma Zhijie An Lance ERodewald Huaqing Wang Zundong Yin National Key laboratory of Intelligent Tracking and Forecasting for Infectious Diseases(NITFID) BeijingChina National Immunization Program Chinese Center for Disease Control and PreventionBeijingChina Institute for viral Disease Control and Prevention Chinese Center for Disease Control and PreventionBeijingChina

Introduction:Detecting poliovirus infections proves to be highly challenging due to their asymptomatic nature and infectious potential,highlighting the crucial importance of effective detection methods in the context of polio eradication *** many countries,including China,the primary approach for identifying polio outbreaks has been through acute flaccid paralysis(AFP)*** this study,we conducted an evaluation spanning three decades(1993–2022)to assess the effectiveness of AFP surveillance in ***:Data on all AFP cases identified since 1993 and national-level AFP surveillance system quality indicators aligned with the World Health Organization(WHO)standards were collected for *** quality indicators assess surveillance sensitivity,completeness,timeliness of detection notification,case investigation,and laboratory *** sensitivity is determined by the non-polio AFP(NPAFP)detection rate among children under 15 years of ***:Between 1993 and 2022,a total of 150,779 AFP cases were identified and *** this pool,surveillance identified 95 cases of wild poliovirus(WPV)and 24 cases due to vaccinederived *** 1995 onwards,the detection rate of NPAFP cases consistently adhered to the WHO and national standards of≥1 case per 100,000,falling between 1.38 and *** in 1997,all timeliness indicators consistently achieved the criteria of 80%,apart from the consistency in meeting standards set for the rate of positive specimens sent to the national ***:AFP surveillance has been instrumental in China’s accomplishment of maintaining a polio-free *** ongoing adherence to key performance indicators,ensuring sensitivity and prompt specimen collection,demonstrates that AFP surveillance is proficient in detecting poliovirus in *** we move into the post-eradication phase,AFP surveillance remains crucial for the sustained absence of polioviruses in the long term.

关键词： sustained prompt surveillance

To Analyze the Sensitivity of RT-PCR Assays Employing S Gene Target Failure with Whole Genome Sequencing Data during Third Wave by SARS-CoV-2 Omicron Variant

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Advances in Microbiology 2024年第5期14卷 247-255页

作者： Pooja Patel Yogita Mistry Monika Patel Summaiya Mullan viral Research and Diagnostic laboratory Department of Microbiology Government Medical college Surat India

Introduction: Omicron is a highly divergent variant of concern (VOCs) of a severe acute respiratory syndrome SARS-CoV-2. It carries a high number of mutations in its spike protein hence;it is more transmissible in the community by immune evasion mechanisms. Due to mutation within S gene, most Omicron variants have reported S gene target failure (SGTF) with some commercially available PCR kits. Such diagnostic features can be used as markers to screen Omicron. However, Whole Genome Sequencing (WGS) is the only gold standard approach to confirm novel microorganisms at genetically level as similar mutations can also be found in other variants that are circulating at low frequencies worldwide. This Retrospective study is aimed to assess RT-PCR sensitivity in the detection of S gene target failure in comparison with whole genome sequencing to detect variants of Omicron. Methods: We have analysed retrospective data of SARS-CoV-2 positive RT-PCR samples for S gene target failure (SGTF) with TaqPath COVID-19 RT-PCR Combo Kit (ThermoFisher) and combined with sequencing technologies to study the emerged pattern of SARS-CoV-2 variants during third wave at the tertiary care centre, Surat. Results: From the first day of December 2021 till the end of February 2022, a total of 321,803 diagnostic RT-PCR tests for SARS-CoV-2 were performed, of which 20,566 positive cases were reported at our tertiary care centre with an average cumulative positivity of 6.39% over a period of three months. In the month of December 21 samples characterized by the SGTF (70/129) were suggestive of being infected by the Omicron variant and identified as Omicron (B.1.1.529 lineage) when sequence. In the month of January, we analysed a subset of samples (n = 618) with SGTF (24%) and without SGTF (76%) with Ct values Conclusions: During the COVID-19 pandemic, it took almost more than 15 days to diagnose infection and identify pathogen by sequencing technology. In contrast to that molecular assay provided qu

关键词： SARS-CoV-2 S Gene Target Failure Whole Genome Sequencing Omicron

Establishment of a humanized ST6GAL1 mouse model for influenza research

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Animal Models and Experimental Medicine 2024年第3期7卷 337-346页

作者： Lyu Chao Han Feng Gao Qian Lv Limin Lu Ziwei Lu Shuangshuang Li Xiaoyan Hu Yuechao Yang Mengjie Zhao Yingze Liu Jun Lu Xuancheng Duo Shuguang National Key laboratory of Intelligent Tracking and Forecasting for Infectious Diseases Chinese Center for Disease Control and PreventionBeijingChina Institute of Zoology Chinese Academy of SciencesBeijingChina NHC Key laboratory of Biosafety National Key Laboratory of Intelligent Tracking and Forecasting for Infectious DiseasesNational Institute for Viral Disease Control and PreventionChinese Center for Disease Control and PreventionBeijingChina Zhejiang Provincial Key laboratory of Medical Genetics Key Laboratory of Laboratory MedicineMinistry of EducationSchool of Laboratory Medicine and Life SciencesWenzhou Medical UniversityWenzhouChina

Background:This study aimed to construct and characterize a humanized influenza mouse model expressing ***:Humanized fragments,consisting of the endothelial cell-specific K18 promoter,human ST6GAL1-encoding gene,and luciferase gene,were microinjected into the fertilized eggs of *** manipulated embryos were transferred into the oviducts of pseudopregnant female *** offspring were identified using *** exhibiting elevated expression of the hST6GAL1 gene were selectively bred for propagation,and in vivo analysis was performed for *** of the humanized gene was tested by performing immunohistochemical(IHC)*** and biochemical analyses using the whole blood and serum of humanized hST6GAL1 mice were ***:Successful integration of the human ST6GAL1 gene into the mouse genome led to the overexpression of human SiaT *** mice were identified as carrying copies of the humanized gene,and the in vivo analysis indicated that hST6GAL1gene expression in positive mice mirrored influenza virus infection *** IHC results revealed that hST6GAL1 was expressed in the lungs of humanized ***,the hematologic and biochemical parameters of the positive mice were within the normal ***:A humanized influenza mouse model expressing the hST6GAL1 gene was successfully established and characterized.

关键词： hST6GAL1 humanized mice influenza animal model

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