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FGF7 enhances the expression of ACE2 in human islet organoids aggravating SARS-CoV-2 infection

Signal Transduction and Targeted Therapy 2024年第5期9卷 2260-2274页

作者： Hao Meng Zhiying Liao Yanting Ji Dong Wang Yang Han Chaolin Huang Xujuan Hu Jingyi Chen Hengrui Zhang Zonghong Li Changliang Wang Hui Sun Jiaqi Sun Lihua Chen Jiaxiang Yin Jincun Zhao Tao Xu huisheng liu School of Biomedical Engineering Guangzhou Medical UniversityGuangzhou 511495 GuangdongChina Guangzhou National Laboratory Guangzhou 510320 GuangdongChina State Key Laboratory of Respiratory Disease National Clinical Research Center for Respiratory DiseaseGuangzhou Institute of Respiratory HealthThe First Affiliated Hospital of Guangzhou Medical UniversityGuangzhou 510120China Center for Translational Medicine Wuhan Jinyintan HospitalWuhan 430023 HubeiChina School of Biomedical Sciences and Engineering South China University of TechnologyGuangzhou 510006 GuangdongChina

The angiotensin-converting enzyme 2(ACE2)is a primary cell surface viral binding receptor for SARS-CoV-2,so finding new regulatory molecules to modulate ACE2 expression levels is a promising strategy against *** the current study,we utilized islet organoids derived from human embryonic stem cells(hESCs),animal models and COVID-19 patients to discover that fibroblast growth factor 7(FGF7)enhances ACE2 expression within the islets,facilitating SARS-CoV-2 infection and resulting in impaired insulin *** hESC-derived islet organoids,we demonstrated that FGF7 interacts with FGF receptor 2(FGFR2)and FGFR1 to upregulate ACE2 expression predominantly inβ*** upregulation increases both insulin secretion and susceptibility ofβcells to SARS-CoV-2 *** FGFR counteracts the FGF7-induced ACE2 upregulation,subsequently reducing viral infection and replication in the ***,retrospective clinical data revealed that diabetic patients with severe COVID-19 symptoms exhibited elevated serum FGF7 levels compared to those with mild ***,animal experiments indicated that SARS-CoV-2 infection increased pancreatic FGF7 levels,resulting in a reduction of insulin concentrations in *** together,our research offers a potential regulatory strategy for ACE2 by controlling FGF7,thereby protecting islets from SARS-CoV-2 infection and preventing the progression of diabetes in the context of COVID-19.

关键词： ACE2 FGF7 islet

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口蹄疫病毒:一种抑制天然免疫的新机制

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中国兽医科学 2024年第6期54卷 851-851页

作者： huisheng liu Qiao Xue Fan Yang Weijun Cao Pengfei liu Xiangtao liu Zixiang Zhu Haixue Zheng

口蹄疫是由口蹄疫病毒(FMDV)感染猪、牛、绵羊、山羊等偶蹄类动物引起的烈性传染病,对我国及世界畜牧业造成了严重影响,世界动物卫生组织将其列为法定报告疫病,我国将其列为一类动物疫病。疫苗接种是预防口蹄疫的有效措施,但FMDV免疫抑... 详细信息

口蹄疫是由口蹄疫病毒(FMDV)感染猪、牛、绵羊、山羊等偶蹄类动物引起的烈性传染病,对我国及世界畜牧业造成了严重影响,世界动物卫生组织将其列为法定报告疫病,我国将其列为一类动物疫病。疫苗接种是预防口蹄疫的有效措施,但FMDV免疫抑制严重,能迅速突破宿主免疫系统,造成FMDV的高效复制与烈性传播。FMDV包含约8.5kb的基因组,其编码单个多蛋白,该多蛋白在翻译后被切割成成熟的结构蛋白和非结构蛋白,包括Lpro、VP1、VP2、VP3、VP4、2A、2B、2C、3A、3B、3Cpro和3Dpol。

关键词：世界动物卫生组织口蹄疫病毒烈性传染病一类动物疫病疫苗接种非结构蛋白免疫抑制法定报告

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Knittable and washable aerogel fiber inspired by polar bear hair

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Science China Materials 2024年第2期67卷 705-706页

作者： Yue liu huisheng Peng State Key Laboratory of Molecular Engineering of Polymers Department of Macromolecular Scienceand Institute of Fiber Materials and DevicesFudan UniversityShanghai 200438China

The advances in chemistry and materials have boosted the development of smart textiles,which are poised to revolutionize human lifestyles through multifunctional integration,such as heating,cooling,sensing and supplying energy^([1,2]).Among them,thermal insulation is an essential function of textiles to protect humans from complex and extreme environments and realize personal thermal management without energy con-sumption^([3]).

关键词： textiles insulation extreme

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Flexible electrochemical fiber sensor for intracranial nitric oxide monitoring

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Science China Chemistry 2024年第8期67卷 2431-2433页

作者： Ziwei liu huisheng Peng State Key Laboratory of Molecular Engineering of Polymers Department of Macromolecular ScienceInstitute of Fiber Materials and Devicesand Laboratory of Advanced MaterialsFudan UniversityShanghai 200438China

Real-time and accurate monitoring of vital biomarkers in vivo forms a crucial foundation for health assessment,early intervention,and disease ***,continuous monitoring of intracranial nitric oxide(NO)levels plays a pivotal role in promptly assessing immune responses,neurovirulence,and cerebrovascular diseases[1].Differing from non-real-time monitoring methods like chemiluminescence[2]and fluorescent probes[3],implantable electrochemical sensors excel in simultaneously high temporal resolution,sensitivity,and cost-effectiveness[4].

关键词： prompt electrochemical monitoring

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FoxJ1 inhibits African swine fever virus replication and viral S273R protein decreases the expression of FoxJ1 to impair its antiviral effect

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Virologica Sinica 2022年第3期37卷 445-454页

作者： Caina Ma Shasha Li Fan Yang Weijun Cao huisheng liu Tao Feng Keshan Zhang Zixiang Zhu Xiangtao liu Yonghao Hu Haixue Zheng College of Veterinary Medicine Gansu Agricultural UniversityLanzhou730070China State Key Laboratory of Veterinary Etiological Biology National Foot and Mouth Diseases Reference LaboratoryKey Laboratory of Animal Virology of Ministry of AgricultureLanzhou Veterinary Research InstituteChinese Academy of Agricultural SciencesLanzhou730046China

African swine fever(ASF)is a highly pathogenic swine infectious disease that affects domestic pigs and wild boar,which is caused by the African swine fever virus(ASFV).ASF has caused huge economic losses to the pig industry and seriously threatens global food security and livestock *** date,there is no safe and effective commercial vaccine against *** the underlying mechanisms of ASFV-host interplay is critical for developing effective vaccines and drugs against *** the present study,RNA-sequencing,RT-qPCR and Western blotting analysis revealed that the transcriptional and protein levels of the host factor FoxJ1 were significantly down-regulated in primary porcine alveolar macrophages(PAMs)infected by ***-qPCR analysis showed that overexpression of FoxJ1 upregulated the transcription of type I interferon and interferon stimulating genes(ISGs)induced by poly(dA:dT).FoxJ1 revealed a function to positively regulate innate immune response,therefore,suppressing the replication of *** addition,Western blotting analysis indicated that FoxJ1 degraded ASFV MGF505-2R and E165R proteins through autophagy ***,RT-qPCR and Western blotting analysis showed that ASFV S273R inhibited the expression of ***,we determined that FoxJ1 plays an antiviral role against ASFV replication,and ASFV protein impairs FoxJ1-mediated antiviral effect by degradation of *** findings provide new insights into the antiviral function of FoxJ1,which might help design antiviral drugs or vaccines against ASFV infection.

关键词： African swine fever virus(ASFV) FoxJ1 ISGs MGF505-2R E165R S273R

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The single-sample network module biomarkers(sNMB)method reveals the pre-deterioration stage of disease progression

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Journal of Molecular Cell Biology 2022年第8期14卷 17-28页

作者： Jiayuan Zhong huisheng liu Pei Chen School of Mathematics and Big Data Foshan UniversityFoshan 528000China School of Mathematics South China University of TechnologyGuangzhou 510640China Pazhou Lab Guangzhou 510330China School of Life Sciences and Technology Tongji UniversityShanghai 200092China

The progression of complex diseases generally involves a pre-deterioration stage that occurs during the transition from a healthy state to disease deterioration,at which a drastic and qualitative shift *** development of an effective approach is urgently needed to identify such a pre-deterioration stage or critical state just before disease deterioration,which allows the timely implementation of appropriate measures to prevent a catastrophic ***,identifying the pre-deterioration stage is a challenging task in clinical medicine,especially when only a single sample is available for most patients,which is responsible for the failure of most statistical *** this study,a novel computational method,called single-sample network module biomarkers(sNMB),is presented to predict the pre-deterioration stage or critical point using only a single ***,the proposed single-sample index effectively quantifies the disturbance caused by a single sample against a group of given reference *** method successfully detected the early warning signal of the critical transitions when applied to both a numerical simulation and four real datasets,including acute lung injury,stomach adenocarcinoma,esophageal carcinoma,and rectum *** addition,it provides signaling biomarkers for further practical application,which helps to discover prognostic indicators and reveal the underlying molecular mechanisms of disease progression.

关键词： critical point pre-deterioration stage critical transition dynamic network biomarker(DNB) single-sample network module biomarkers(sNMB)

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Heterogenous glucose-stimulated insulin secretion at single islet level

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Engineered Regeneration 2023年第4期4卷 387-395页

作者： Jiaxiang Yin Hao Meng Haopeng Lin Meijun Mo Jingfang Lin Jingyi Chen Lihua Chen Xiaojun Xu Zonghong Li Wei Ji Tao Xu huisheng liu School of Biomedical Engineering Guangzhou Medical UniversityGuangzhouChina Guangzhou National Laboratory GuangzhouGuangdongChina Bioland Laboratory GuangzhouGuangdongChina National Laboratory of Biomacromolecules CAS Center for Excellence in BiomacromoleculesInstitute of BiophysicsChinese Academy of SciencesBeijingChina School of Biomedical Sciences and Engineering South China University of TechnologyGuangzhou International CampusGuangzhouChina

Insulin secretion by pancreatic islets plays a vital role in regulating blood glucose ***,the mech-anism responsible for this dynamic insulin secretion has not been completely understood,particularly at the single islet *** this study,we have successfully developed an easy microfluidic platform that allows for the exploration of dynamic glucose-stimulated insulin secretion(GSIS)at the single islet *** the utilization of this platform,we evaluated dynamic GSIS from single islets isolated from both normal and diabetic *** results demonstrate that islets can be categorized into three types based on their dynamic GSIS:Type Ⅰ exhibits a biphasic GSIS profile with a fast first phase and flat second phase;Type Ⅱ also has a biphasic GSIS profile with a fast first phase but a slow increased second phase;Type Ⅲ displays only a slowly increased second phase and lacks a fast first *** sequencing analysis demonstrated that the cell type and exocytosis-specific genes are consistent with the proportion of cells and insulin release kinetics among the three types of islets,***,our findings suggest that high expression of Atp5pb is anti-correlated with the first phase of insulin ***,we revealed that diabetic islets exhibit only the type Ⅰ GSIS response,indicating a deliberate impairment of the second phase of insulin ***,this device serves as a crucial tool in the research field of islets and diabetes,allowing researchers to investigate islet functional heterogeneity and identity at the single islet level.

关键词： Islet-on-a-chip Single islet Glucose-stimulated insulin secretion Heterogeneity Diabetes

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Foot-and-Mouth Disease Virus Inhibits RIP2 Protein Expression to Promote Viral Replication

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Virologica Sinica 2021年第4期36卷 608-622页

作者： huisheng liu Qiao Xue Zixiang Zhu Fan Yang Weijun Cao Xiangtao liu Haixue Zheng State Key Laboratory of Veterinary Etiological Biology National Foot and Mouth Diseases Reference LaboratoryKey Laboratory of Animal Virology of Ministry of AgricultureLanzhou Veterinary Research InstituteChinese Academy of Agricultural SciencesLanzhou 730046China

Receptors interaction protein 2(RIP2)is a specific adaptor molecule in the downstream of *** role of RIP2 during foot-and-mouth disease virus(FMDV)infection remains ***,our results showed that RIP2 inhibited FMDV replication and played an important role in the activation of IFN-βand NF-κB signal pathways during FMDV *** infection triggered RIP2 transcription,while it reduced the expression of RIP2 *** analysis showed that FMDV 2B,2C,3C^(pro),and L^(pro) proteins were responsible for inducing the reduction of RIP2 protein.3C^(pro) and L^(pro) are viral proteinases that can induce the cleavage or reduction of many host proteins and block host protein *** carboxyl terminal 105-C114 and 135-C144 regions of 2B were essential for reduction of *** results also showed that the N terminal 1-61 region of 2C were essential for the reduction of *** 2C-induced reduction of RIP2 was dependent on inducing the reduction of poly(A)-binding protein 1(PABPC1).The interaction between RIP2 and 2C was observed in the context of viral infection,and the residues 1-61 were required for the *** data clarify novel mechanisms of reduction of RIP2 mediated by FMDV.

关键词： Foot-and-mouth disease virus(FMDV) Receptors interaction protein 2(RIP2) PABPC1 2C Immune evasion

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Role of FGF-2/FGFR signaling pathway in cancer and its signification in breast cancer

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Chinese Science Bulletin 2003年第15期48卷 1539-1547页

作者： FANG Jianwu HUANG Siluo liu huisheng M. Crepin XU Tao liu Jianfeng Instiute of Biophyscis & Biochemnistry of Huazhong University of Science & Technology Wuhan 430074China CNRS-UPR 9023 Mecanismes Moleculaires des Communications CellulairesCCIPE 34090 France Laboratoire de Recherche Oncologie MoleAculaire Humaine (EA445) UFR LeAonard de Vinci UniversiteA Paris-nord 74 rue Marcel Cachin 93012BobignyFrance

Fibroblast growth factor-2 (FGF-2) is a member of a large family of proteins that bind heparin and heparan sulfate and modulate the function of a wide range of cell types. It has been proved that FGF-2 stimulates the growth and development of new blood vessels (angiogenesis) that contribute to the pathogenesis of several diseases (i.e. cancer, atherosclerosis). However, many of the biological activities of FGF-2 have been found to depend on its receptor抯 intrinsic tyrosine kinase activity and second messengers such as the mitogen activated protein kinases. This review will focus on the mechanism of FGF-2/FGFR induced signaling pathway in tumor and human breast cancer.

关键词：乳腺癌蛋白质肝磷脂硫酸乙酰肝素血管生成

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The DEAD-Box RNA Helicase DDX1 Interacts with the Viral Protein 3D and Inhibits Foot-and-Mouth Disease Virus Replication

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Virologica Sinica 2019年第6期34卷 610-617页

作者： Qiao Xue huisheng liu Qiaoying Zeng Haixue Zheng Qinghong Xue Xuepeng Cai Laboratory of Veterinary Microbiology College of Veterinary MedicineGansu Agricultural UniversityLanzhou 730070China State Key Laboratory of Veterinary Etiological Biology National Foot and Mouth Diseases Reference LaboratoryKey Laboratory of Animal Virology of Ministry of AgricultureLanzhou Veterinary Research InstituteChinese Academy of Agricultural SciencesLanzhou 730046China China Institute of Veterinary Drug Control Beijing 100081China

Foot-and-mouth disease virus(FMDV)can infect domestic and wild cloven-hoofed *** non-structural protein 3D plays an important role in FMDV replication and ***,the interaction partners of 3D,and the effects of those interactions on FMDV replication,remain incompletely *** the present study,using the yeast two-hybrid system,we identified a porcine cell protein,DEAD-box RNA helicase 1(DDX1),which interacted with FMDV *** DDX1-3D interaction was further confirmed by co-immunoprecipitation experiments and an indirect immunofluorescence assay(IFA)in porcine kidney 15(PK-15)***1 was reported to either inhibit or facilitate viral replication and regulate host innate immune ***,the roles of DDX1 during FMDV infection remain *** results revealed that DDX1 inhibited FMDV replication in an ATPase/helicase activity-dependent *** addition,DDX1 stimulated IFN-p activation in FMDV-infected ***,our results expand the body of knowledge regarding the role of DDX1 in FMDV infection.

关键词： Foot-and-mouth disease virus(FMDV) Interaction DEAD-box RNA helicase 1(DDX1) Antiviral function Interferon

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