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Identification of fangchinoline as a broad-spectrum enterovirus inhibitor through reporter virus based high-content screening

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Virologica Sinica 2024年第2期39卷 301-308页

作者： qiu-yan zhang Jia-Qi Li Qi Li yang zhang Zhe-Rui zhang Xiao-Dan Li Hong-Qing zhang Cheng-Lin Deng Feng-Xia yang Yi Xu Bo zhang The Joint Center of Translational Precision Medicine Department of Infections and DiseasesGuangzhou Institute of PediatricsGuangzhou Women and Children's Medical CenterGuangzhou510623China Key Laboratory of Special Pathogens and Biosafety Wuhan Institute of VirologyCenter for Biosafety Mega-ScienceChinese Academy of SciencesWuhan430071China University of Science and Technology of China Department of Life Sciences and MedicineHefei230026China Hunan Normal University School of MedicineChangsha410081China

Hand,foot,and mouth disease(HFMD)is a common pediatric illness mainly caused by enteroviruses,which are important human pathogens.Currently,there are no available antiviral agents for the therapy of enterovirus infection.In this study,an excellent high-content antiviral screening system utilizing the EV-A71-eGFP reporter virus was developed.Using this screening system,we screened a drug library containing 1042 natural compounds to identify potential EV-A71 inhibitors.Fangchinoline(FAN),a bis-benzylisoquinoline alkaloid,exhibits potential inhibitory effects against various enteroviruses that cause HFMD,such as EV-A71,CV-A10,CV-B3 and CV-A16.Further investigations revealed that FAN targets the early stage of the enterovirus life cycle.Through the selection of FAN-resistant EV-A71 viruses,we demonstrated that the VP1 protein could be a potential target of FAN,as two mutations in VP1(E145G and V258I)resulted in viral resistance to FAN.Our research suggests that FAN is an efficient inhibitor of EV-A71 and has the potential to be a broad-spectrum antiviral drug against human enteroviruses.

关键词： Hand,foot,and mouth disease(HFMD) Enterovirus EV-A71 High-content screening Fangchinoline(FAN)

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The potential epidemic threat of Ebola virus and the development of a preventive vaccine

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Journal of Biosafety and Biosecurity 2023年第2期5卷 67-78页

作者： Hong-Qing zhang qiu-yan zhang Zhi-Ming Yuan Bo zhang Key Laboratory of Special Pathogens and Biosafety Wuhan Institute of VirologyCenter for Biosafety Mega-ScienceChinese Academy of SciencesWuhan 430071China University of Chinese Academy of Sciences Beijing 100049China Hubei Jiangxia Laboratory Wuhan 430200China

Ebola virus(EBOV)is classified as a category A pathogen as it causes viral hemorrhagic fever,one of the most-deadly virus-related diseases.Since its discovery in 1976,EBOV has caused a number of global public health incidents,which have posed a serious threat to both humans and non-human primates.Thus,numerous preventive vaccine studies are underway,including research on inactivated vaccines,DNA vaccines,subunit vaccines,virus-like particles,Venezuelan equine encephalitis virus replicon particles,and several viral vector vaccines.The vesicular stomatitis virus-based vaccine Ervebo was recently approved by the Food and Drug Administration and the European Union,and several other vaccines have also been proven to confer potent protection in non-human primates against EBOV lethal challenge.This review provides a brief background of EBOV,with a focus on the epidemiology,available animal models,and advances in preventive approaches for EBOV infection.

关键词： Ebola virus Epidemiology Animal model Vaccine

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Different pathogenesis of SARS-CoV-2 Omicron variant in wild-type laboratory mice and hamsters

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Signal Transduction and Targeted Therapy 2022年第3期7卷 632-634页

作者： Ya-Nan zhang Zhe-Rui zhang Hong-Qing zhang Na Li qiu-yan zhang Xiao-Dan Li Cheng-Lin Deng Fei Deng Shuo Shen Bing Zhu Bo zhang Virus Laboratory Institute of PediatricsGuangzhou Women and Children's Medical CenterGuangzhou Medical UniversityGuangzhou 510623China Key Laboratory of Special Pathogens and Biosafety Wuhan Institute of VirologyCenter for Biosafety Mega-ScienceChinese Academy of SciencesWuhan 430071China University of Chinese Academy of Sciences Beijing 100049China Hunan Normal University School of MedicineChangsha 410081China Wuhan Institute of Biological Products Co.Ltd Wuhan 420115China

Dear Editor,The COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)continues to disrupt global public health since its first report in December 2019,resulting in more than 380 billi... 详细信息

关键词： acute pathogenesis respiratory

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Observation of spectral lines in the exceptional GRB 221009A

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Science China(Physics,Mechanics & Astronomy) 2024年第8期Mechanics & Astronomy) .卷 191-210页

作者： yan-qiu zhang Shao-Lin Xiong Ji-Rong Mao Shuang-Nan zhang Wang-Chen Xue Chao Zheng Jia-Cong Liu Zhen zhang Xi-Lu Wang Ming-Yu Ge Shu-Xu Yi Li-Ming Song Zheng-Hua An Ce Cai Xin-Qiao Li Wen-Xi Peng Wen-Jun Tan Chen-Wei Wang Xiang-yang Wen Yue Wang Shuo Xiao Fan zhang Peng zhang Shi-Jie Zheng Key Laboratory of Particle Astrophysics Institute of High Energy PhysicsChinese Academy of Sciences University of Chinese Academy of Sciences Yunnan Observatories Chinese Academy of Sciences Center for Astronomical Mega-Science Chinese Academy of Sciences Key Laboratory for the Structure and Evolution of Celestial Objects Chinese Academy of Sciences College of Physics and Hebei Key Laboratory of Photophysics Research and Application Hebei Normal University Guizhou Provincial Key Laboratory of Radio Astronomy and Data Processing Guizhou Normal University College of Electronic and Information Engineering Tongji University

As the brightest gamma-ray burst ever observed, GRB 221009A provided a precious opportunity to explore spectral line features. In this article, we performed a comprehensive spectroscopy analysis of GRB 221009A jointly with GECAM-C and Fermi/GBM data to search for emission and absorption lines. For the first time we investigated the line feature throughout this GRB including the most bright part where many instruments suffered problems, and identified prominent emission lines in multiple time intervals. The central energy of the Gaussian emission line evolves from about 37 to 6 MeV, with a nearly constant ratio（about 10%） between the line width and central energy. Particularly, we find that both the central energy and the energy flux of the emission line evolve with time as a power law decay with power law index of –1 and –2, respectively. We suggest that the observed emission lines most likely origin from the blue-shifted electron positron pair annihilation 511 ke V line. We find that a standard high latitude emission scenario cannot fully interpret the observation, thus we propose that the emission line comes from some dense clumps with electron positron pairs traveling together with the jet. In this scenario, we can use the emission line to directly, for the first time, measure the bulk Lorentz factor of the jet（Γ） and reveal its time evolution(i.e., Γ～ t-1) during the prompt emission. Interestingly, we find that the flux of the annihilation line in the co-moving frame keeps constant. These discoveries of the spectral line features shed new and important lights on the physics of GRB and relativistic jet.

关键词： GRB GRB 221009A emission line

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Intranasal delivery of replicating mRNA encoding neutralizing antibody against SARS-CoV-2 infection in mice

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Signal Transduction and Targeted Therapy 2021年第11期6卷 3333-3340页

作者： Jia-Qi Li Zhe-Rui zhang Hong-Qing zhang Ya-Nan zhang Xiang-Yue Zeng qiu-yan zhang Cheng-Lin Deng Xiao-Dan Li Bo zhang Han-Qing Ye Key Laboratory of Special Pathogens and Biosafety Wuhan Institute of VirologyCenter for Biosafety Mega-ScienceChinese Academy of SciencesWuhanChina University of Chinese Academy of Sciences 100049BeijingChina School of Medicine Hunan Normal University410081ChangshaChina

The lung is the prophylaxis target against SARS-CoV-2 infection,and neutralizing antibodies are a leading class of biological products against various infectious viral pathogen.In this study,we develop a safe and cost-effective platform to express neutralizing antibody in the lung with replicating mRNA basing on alphavirus replicon particle(VRP)delivery system,to prevent SARS-CoV-2 infections.First,a modified VEEV replicon with two subgenomic(sg)promoters was engineered to translate the light and heavy chains of antibody simultaneously,for expression and assembly of neutralizing anti-SARS-CoV-2 antibody CB6.Second,the feasibility and protective efficacy of replicating mRNA against SARS-CoV-2 infection were demonstrated through both in vitro and in vivo assays.The lung target delivery with the help of VRP system resulted in efficiently block SARS-CoV-2 infection with reducing viral titer and less tissue damage in the lung of mice.Overall,our data suggests that expressing neutralizing antibodies in the lungs with the help of self-replicating mRNA could potentially be a promising prophylaxis approach against SARS-CoV-2 infection.

关键词： infection lung protective

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Simple Ultrasonic-Assisted Clean Graphene Transfer

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Journal of Electronic Science and Technology 2022年第3期20卷 237-245页

作者： Zhuo-Cheng zhang Xiao-qiu-yan zhang Min Hu the Terahertz Research Center School of Electronic Science and EngineeringUniversity of Electronic Science and Technology of ChinaChengdu610054China the Key Laboratory of Terahertz Technology(Ministry of Education) University of Electronic Science and Technology of ChinaChengdu610054China

Clean graphene transfer has received widespread research attention, where most methods are focused on cleaning the upper surface of graphene to improve the transfer technique. However, the residue formation on the bottom surface of graphene is also inevitable;therefore, cleaning the bottom surface is crucial. In this study, we proposed an improved graphene wet transfer method using an ultrasonic processing(UP) step for etching copper(Cu). Using this method, the bottom surface can be cleaned efficiently. The results of atomic force microscopy(AFM)and Raman spectroscopy mapping revealed that the graphene films transferred with UP had smoother and cleaner surfaces, less contamination, and higher quality than those transferred without UP.

关键词： Chemical vapor deposition(CVD) clean graphene transfer ultrasonic processing

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β-escin reverses multidrug resistance through inhibition of the GSK3β/β-catenin pathway in cholangiocarcinoma

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World Journal of Gastroenterology 2015年第4期21卷 1148-1157页

作者： Gui-Li Huang Dong-yan Shen Cheng-Fu Cai qiu-yan zhang Hong-Yue Ren Qing-Xi Chen State Key Laboratory of Cellular Stress Biology Key Laboratory of the Ministry of Education for Coastal and Wetland EcosystemsSchool of Life SciencesXiamen University Biobank the First Affiliated Hospital of Xiamen University Department of Otorhinolaryngology Head and Neck Surgerythe First Affiliated Hospital of Xiamen University

AIM: To develop a safe and effective agent for cholangiocarcinoma(CCA) chemotherapy. METHODS: A drug combination experiment was conducted to determine the effects of β-escin in c o m b i n a t i o n w i t h c h e m o t h e ra p y o n C C A c e l l s. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay was performed to determine the effects of β-escin and common chemotherapeutics on the proliferation of human CCA cells(QBC939, Sk-Ch A-1, and MZ-Ch A-1). Immunocytochemistry was used to detect the expression of P-glycoprotein(P-gp) protein. Luciferase reporter assay was used to detect the activation of the Wnt/β-catenin pathway. The protein levels of P-gp, p S9-GSK3β, p T216-GSK3β, GSK3β, β-catenin, and p-β-catenin were further confirmed by western blotting.RESULTS: The drug sensitivity of QBC939 and QBC939/5-fluorouracil(5-FU) cells to 5-FU, vincristine sulfate(VCR), or mitomycin C was significantly enhanced by β-escin compared with either agent alone(P < 0.05). In addition, the combination of β-escin(20 μmol/L) with 5-FU and VCR was synergic with a combination index < 1. Further investigation found that the m RNA and protein expression of P-gp was downregulated by β-escin. Moreover, β-escin induced GSK3β phosphorylation at Tyr-216 and dephosphorylation at Ser-9, resulting in phosphorylation and degradation of β-catenin. Interestingly, activation of the GSK3β/β-catenin pathway induced by Wnt3 a resulted in upregulation of P-gp, which was effectively abolished by β-escin, indicating that β-escin down-regulated P-gp expression in a GSK3β-dependent manner.CONCLUSION: β-escin was a potent reverser of P-gpdependent multidrug resistance, with said effect likely being achieved via inhibition of the GSK3β/β-catenin pathway and thus suggesting a promising strategy of developing combination drugs for CCA.

关键词： β-escin Multi-drug resistance P-glycoprotein GSK3β

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Clustering for Bivariate Functional Data

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Acta Mathematicae Applicatae Sinica 2024年第3期40卷 613-629页

作者： Shi-yun CAO yan-qiu ZHOU yan-ling WAN Tao zhang School of Science Guangxi University of Science and TechnologyLiuzhou 545006China School of Marxism Guangxi University of Science and TechnologyLiuzhou 545006China Key Laboratory of Intelligent Information Processing and Graph Processing Guangxi University of Science and TechnologyLiuzhou 545006China

In this paper,we consider the clustering of bivariate functional data where each random surface consists of a set of curves recorded repeatedly for each subject.The k-centres surface clustering method based on marginal functional principal component analysis is proposed for the bivariate functional data,and a novel clustering criterion is presented where both the random surface and its partial derivative function in two directions are considered.In addition,we also consider two other clustering methods,k-centres surface clustering methods based on product functional principal component analysis or double functional principal component analysis.Simulation results indicate that the proposed methods have a nice performance in terms of both the correct classification rate and the adjusted rand index.The approaches are further illustrated through empirical analysis of human mortality data.

关键词： bivariate functional data -centres surface clustering functional principal component analysis partial derivative function

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Mitophagy in neurodegenerative disease pathogenesis

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Neural Regeneration Research 2024年第5期19卷 998-1005页

作者： Kan yang Yuqing yan Anni Yu Ru zhang Yuefang zhang Zilong qiu Zhengyi Li Qianlong zhang Shihao Wu Fei Li Department of Developmental and Behavioural Pediatric&Child Primary Care Brain and Behavioural Research Unit of Shanghai Institute for Pediatric Research and MOE-Shanghai Key Laboratory for Children’s Environmental HealthXinhua HospitalShanghai Jiao Tong University School of MedicineShanghaiChina Center for Excellence in Brain Science and Intelligence Technology Institute of NeuroscienceState Key Laboratory of NeuroscienceCAS Key Laboratory of Primate NeurobiologyChinese Academy of SciencesShanghaiChina College of Materials and Chemical Engineering Hunan Institute of EngineeringXiangtanHunan ProvinceChina School of Medicine Yunnan UniversityKunmingYunnan ProvinceChina Songjiang Research Institute Shanghai Jiao Tong University School of MedicineShanghaiChina Neurosurgery Department Kunming Yenan HospitalKunmingYunnan ProvinceChina

Mitochondria are critical cellular energy resources and are central to the life of the neuron.Mitophagy selectively clears damaged or dysfunctional mitochondria through autophagic machinery to maintain mitochondrial quality control and homeostasis.Mature neurons are postmitotic and consume substantial energy,thus require highly efficient mitophagy pathways to turn over damaged or dysfunctional mitochondria.Recent evidence indicates that mitophagy is pivotal to the pathogenesis of neurological diseases.However,more work is needed to study mitophagy pathway components as potential therapeutic targets.In this review,we briefly discuss the characteristics of nonselective autophagy and selective autophagy,including ERphagy,aggrephagy,and mitophagy.We then introduce the mechanisms of Parkin-dependent and Parkin-independent mitophagy pathways under physiological conditions.Next,we summarize the diverse repertoire of mitochondrial membrane receptors and phospholipids that mediate mitophagy.Importantly,we review the critical role of mitophagy in the pathogenesis of neurodegenerative diseases including Alzheimer’s disease,Parkinson’s disease,and amyotrophic lateral sclerosis.Last,we discuss recent studies considering mitophagy as a potential therapeutic target for treating neurodegenerative diseases.Together,our review may provide novel views to better understand the roles of mitophagy in neurodegenerative disease pathogenesis.

关键词： Alzheimer’s disease amyotrophic lateral sclerosis autophagy mitochondria mitophagy mitophagy receptor Parkin Parkinson’s disease PINK1

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Thermally Conductive,Healable Glass Fiber Cloth Reinforced Polymer Composite based onβ-Hydroxyester Bonds Crosslinked Epoxy with Improved Heat Resistance

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Chinese Journal of Polymer Science 2024年第5期42卷 643-654,I0009页

作者： Fang Chen Xiao-yan Pang Ze-Ping zhang Min-Zhi Rong Ming-qiu zhang Key Laboratory for Polymeric Composite and Functional Materials of Ministry of Education GD HPPC LabIGCMESchool of ChemistrySun Yat-sen UniversityGuangzhou510275China Guangdong Provincial Laboratory of Chemistry and Fine Chemical Engineering Jieyang Center Jieyang515200China

To simultaneously endow thermal conductivity,high glass transition temperature(Tg)and healing capability to glass fiber/epoxy(GFREP)composite,dynamic crosslinked epoxy resin bearing reversibleβ-hydroxyl ester bonds was reinforced with boron nitride nanosheets modified glass fiber cloth(GFC@BNNSs).The in-plane heat conduction paths were constructed by electrostatic self-assembly of polyacrylic acid treated GFC and polyethyleneimine decorated BNNSs.Then,the GFC@BNNSs were impregnated with the mixture of lower concentration(3-glycidyloxypropyl)trimethoxysilane grafted BN micron sheets,3,4-epoxycyclohexylmethyl 3,4-epoxycyclohexanecarboxylate and hexahydro-4-methylphthalic anhydride,which accounted for establishing the through-plane heat transport pathways and avoiding serious deterioration of mechanical performances.The resultant GFREP composite containing less boron nitride particles(17.6 wt%)exhibited superior in-plane(3.29 W·m^(-1)·K^(-1))and through-plane(1.16 W·m^(-1)·K^(-1))thermal conductivities,as well as high Tg of 204℃(Tg of the unfilled epoxy=177℃).The reversible transesterification reaction enabled closure of interlaminar cracks within the composite,achieving decent healing efficiencies estimated by means of tensile strength(71.2%),electrical breakdown strength(83.6%)and thermal conductivity(69.1%).The present work overcame the disadvantages of conventional thermally conductive composites,and provided an efficient approach to prolong the life span of thermally conductive GFREP laminate for high-temperature resistant integrated circuit application.

关键词： Thermally conductive composites Boron nitride High-temperature resistance β-Hydroxyl ester bond Healing

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