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PCK1 attenuates tumor stemness via activating the Hippo signaling pathway in hepatocellular carcinoma

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Genes & Diseases 2024年第4期11卷 340-352页

作者： Rui Liu Yi Liu Wenlu Zhang Guiji Zhang Zhirong Zhang Luyi Huang Ni Tang Kai Wang Key laboratory of Molecular Biology for Infectious Diseases(Ministry of Education) Institute for Viral HepatitisDepartment of Infectious DiseasesThe Second Affiliated HospitalChongqing Medical UniversityChongqing 400016China Department of Clinical laboratory Sichuan Clinical Research Center for CancerSichuan Cancer Hospital&InstituteSichuan Cancer CenterAffiliated Cancer Hospital of University of Electronic Science and Technology of ChinaChengduSichuan 610041China

Liver cancer stem cells were found to rely on glycolysis as the preferred metabolic *** carboxylase 1(PCK1),a gluconeogenic metabolic enzyme,is down-regulated in hepatocellular carcinoma and is closely related to poor *** onco-genesis and progression of tumors are closely related to cancer stem *** is not completely clear whether the PCK1 deficiency increases the stemness of hepatoma cells and promotes the oncogenesis of hepatocellular ***,the results showed that PCK1 inhibited the self-renewal property of hepatoma cells,reduced the mRNA level of cancer stem cell markers,and inhibited ***,PCK1 increased the sensitivity of hepatocellular carci-noma cells to ***,we found that PCK1 activated the Hippo pathway by enhancing the phosphorylation of YAP and inhibiting its nuclear *** reduced the stemness of hepatoma cells and promoted the pro-apoptotic effect of ***,combined treatment with verteporfin and sorafenib may be a potential anti-tumor strat-egy in hepatocellular carcinoma.

关键词： Cancer stem cells Chemoresistance Gluconeogenesis Hepatocellular carcinoma YAP

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

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

Preparation and immunoprotective effects of a virus-like particle candidate vaccine of the dominant epidemic D3 genotype coxsackievirus A6 in China

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Biosafety and Health 2024年第1期6卷 28-34页

作者： Xiaoliang Li Xizhu Xu Jichen Li Huanhuan Lu Congcong Wang Rui Wang Jinbo Xiao Ying Liu Yang Song Jingdong Song Qiang Sun Yong Zhang Department of Public Health and Health Administration Shandong First Medical UniversityJinan 250117China National Key laboratory of Intelligent Tracking and Forecasting for Infectious Diseases(NITFID) National Institute for Viral Disease Control and PreventionChinese Center for Disease Control and PreventionBeijing 102206China National Polio laboratory WHO WPRO Regional Polio Reference LaboratoryNational Health Commission Key Laboratory for BiosafetyNational Health Commission Key Laboratory for Medical VirologyNational Institute for Viral Disease Control and PreventionChinese Center for Disease Control and PreventionBejing 102206China Department of Medical Microbiology Weifang Medical UniversityWeifang 261053China

Coxsackievirus A6 of the D3a genotype(CVA6 D3a)is a primary pathogen causingmainland of China's hand,foot,and mouth disease(HFMD).viral‐like particle(VLP)vaccines represent a potential candidate vaccine to prevent *** study collected Anti‐CVA6 D3a VLPs serum from BALB/c female mice immunized using CVA6 D3a *** neutralizing antibody levels were compared against the representative 14‐JX2018(D3a)and N4‐YN2015(D3b)strains between the antisera of different immune *** immunoprotective effect of anti‐CVA6 D3a VLPs against these strains was monitored using pathological sections and immuno-histochemical results of lung and skeletal muscle tissues in seven‐day‐old Institute of Cancer Research(ICR)*** protection against different branches of viruses was evaluated in 7‐day‐old(serum passive immune protection)and 14‐day‐old(VLPs active immune protection)neonatal ICR mice ***‐neutralizing antibody levels were positively correlated with the number of immunizations and higher against 14‐JX2018 than against N4‐***,these levels were significantly higher with abdominal injection than intramuscular *** immunized serum of 7‐day‐old ICR mice inoculated three times was 100%protected against CVA6 D3a 14‐JX2018(lethal titer:106.25 TCID 50)and CVA6 D3b N4‐YN2015(lethal titer:105.25TCID 50)fatal attacks,*** ICR mice that have completed two active immunizations for 14 days,both CVA6 D3a 14‐JX2015(challenge titer:108.25 TCID 50)and CVA6 D3b N4‐YN2015(challenge titer:107.25 TCID 50)were used for the challenge,and the mice were able to ***,the CVA6 D3a VLPs prepared in this study are a potential vaccine candidate for CVA6,as it has the optimal protective effect against both CVA6 D3a and D3b evolutionary branches viruses.

关键词： Coxsackievirus A6 D3 genotype Virus‐like particle Immunoprotective effect

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

Assessing risk of Bombali virus spillover to humans by mutagenesis analysis of viral glycoprotein

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hLife 2024年第1期2卷 32-42页

作者： Lincan Li Tianyu Gan Ziyue Ma Yi Huang Jin Zhong Unit of viral hepatitis CAS Key Laboratory of Molecular Virology and ImmunologyShanghai Institute of Immunity and InfectionCenter for Biosafety Mega-ScienceChinese Academy of SciencesShanghaiChina University of Chinese Academy of Sciences BeijingChina ShanghaiTech University ShanghaiChina Wuhan National Biosafety laboratory Center for Biosafety Mega-ScienceChinese Academy of SciencesHubeiChina

Ebolaviruses,such as the highly pathogenic Ebola virus(EBOV),belong to the family Filoviridae and have caused out-breaks of severe and fatal hemorrhagic fever over the past *** virus(BOMV)is a newly discovered ebolavirus from bats with unknown potential to infect *** most ebolaviruses,the interaction between viral glycoprotein(GP)and host receptor Niemann-Pick C1(NPC1)is crucial for viral entry and determines host ***,we analyzed the BOMV GP-mediated virus entry into human cells using our recently developed EBOV transcription-and replication-competent virus-like particle(trVLP)*** demonstrated that while BOMV GP can be efﬁciently incorporated into trVLPs,it is inefﬁcient in mediating trVLP entry into human ***,BOMV GP-mediated virus entry into human cells can be signiﬁcantly enhanced by a few mutations in the NPC1-binding domain of ***,we showed that these mutations increase the binding of BOMV-GP to human *** summary,our results suggested that although wild-type BOMV does not efﬁciently infect human cells,the emergence of mutations in viral GP may boost its ability to spill over to humans,highlighting the importance of monitoring BOMV GP evolution in preventing potential BOMV spillover events.

关键词： Bombali virus glycoprotein entry Ebola virus Niemann-Pick C1

A Non-canonical Excitatory PV RGC–PV SC Visual Pathway for Mediating the Looming-evoked Innate Defensive Response

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Neuroscience Bulletin 2024年第3期40卷 310-324页

作者： Man Yuan Sen Jin Gao Tan Siyuan Song Yizong Liu Huadong Wang Yin Shen Eye Center Renmin Hospital of Wuhan UniversityWuhan UniversityWuhan430060China The Brain Cognition and Brain Disease Institute Shenzhen Key Laboratory of Viral Vectors for BiomedicineShenzhen Institute of Advanced TechnologyChinese Academy of Sciences(CAS)Shenzhen-Hong Kong Institute of Brain Science-Shenzhen Fundamental Research InstitutionsNational Medical Products Administration Key Laboratory for Research and Evaluation of Viral Vector Technology in Cell and Gene Therapy Medicinal ProductsShenzhen Key Laboratory of Quality Control Technology for Virus-Based TherapeuticsGuangdong Provincial Medical Products AdministrationShenzhen518055China Jan and Dan Duncan Neurological Research Institute Baylor College of MedicineHouston77030USA State Key laboratory of Magnetic Resonance and Atomic and Molecular Physics Key Laboratory of Magnetic Resonance in Biological SystemsWuhan Center for Magnetic ResonanceInnovation Academy for Precision Measurement Science and TechnologyCASWuhan430071China Frontier Science Center of Immunology and Metabolism Medical Research InstituteWuhan UniversityWuhan430071China

Parvalbumin-positive retinal ganglion cells(PV+RGCs)are an essential subset of RGCs found in various ***,their role in transmitting visual information remains ***,we characterized PV+RGCs in the retina and explored the functions of the PV+RGC-mediated visual *** applying multiple viral tracing strategies,we investigated the downstream of PV+RGCs across the whole ***,we found that the PV+RGCs provided direct monosynaptic input to PV+excitatory neurons in the superficial layers of the superior colliculus(SC).Ablation or suppression of SC-projecting PV+RGCs abolished or severely impaired the flight response to looming visual stimuli in mice without affecting visual ***,using transcriptome expression profiling of individual cells and immunofluorescence colocalization for RGCs,we found that PV+RGCs are predominant glutamatergic ***,our findings indicate the critical role of PV+RGCs in an innate defensive response and suggest a non-canonical subcortical visual pathway from excitatory PV+RGCs to PV+SC neurons that regulates looming visual *** results provide a potential target for intervening and treating diseases related to this circuit,such as schizophrenia and autism.

关键词： Parvalbumin-positive retinal ganglion cell Innate fear Superior colliculus Excitatory-excitatory neuronal connection Looming-evoked defensive response Subcortical pathway