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Global Profiles of Acetylated Proteins in Brains of Scrapie Agents 139A- and ME7-Infected Mice Collected at Mid-Early, Mid-Late, and Terminal Stages

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Biomedical and Environmental Sciences 2022年第8期35卷 722-734页

作者： SHI Qi CHEN dong dong ADALATI Maimaitiming xiao Kang GAO Li ping YANG Xue Hua WU Yue Zhang CHEN Cao DONG xiao ping State Key Laboratory of Infectious Disease Prevention and Control NHC Key Laboratory of Medical Virology and Viral DiseasesNational Institute for Viral Disease Control and PreventionChinese Center for Disease Control and PreventionBejing 102200China Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases Zhejiang UniversityHangzhou 310014ZhejiangChina China Academy of Chinese Medical Sciences Bejing 10000China Center for Biosafety Mega-Science Chinese Academy of SciencesWuhan 43000HubeiChina Shanghai Institute of lnfectious Disease and Biosafety Shanghai 201318China

Objective To describe the global profiles of acetylated proteins in the brains of scrapie agents 139Aand ME7-infected mice collected at mid-early,mid-late,and terminal stages.Methods The acetylated proteins from the cortex regions of scrapie agent(139A-and ME7)-infected mice collected at mid-early(80 days postinfection,dpi),mid-late(120 dpi),and terminal(180 dpi) stages were extracted,and the global profiles of brain acetylated proteins were assayed with proteomic mass spectrometry.The proteins in the infected mice showing 1.5-fold higher or lower levels than that of agematched normal controls were considered as differentially expressed acetylated peptides(DEAPs).Results A total of 118,42,and 51 DEAPs were found in the brains of 139A-80,139A-120,and 139A-180dpi mice,respectively.Meanwhile,390,227,and 75 DEAPs were detected in the brains of ME7-80,ME7-120,and ME7-180 dpi mice,respectively.The overwhelming majority of DEAPs in the mid-early stage were down-regulated,and more portions of DEAPs in the mid-late and late stages were up-regulated.Approximately 22.1%(328/1,485) of acetylated peptides mapped to 74 different proteins were mitochondrial associated.Kyoto Encyclopedia of Genes and Genomes pathway analysis identified 39(80dpi),13(120 dpi),and 10(180 dpi) significantly changed pathways in 139A-infected mice.Meanwhile,55,25,and 18 significantly changed pathways were observed in the 80,120,and 180 dpi samples of139A-and ME7-infected mice(P < 0.05),respectively.Six pathways were commonly involved in all tested samples.Moreover,many steps in the citrate cycle(tricarboxylic acid cycle) were affected,represented by down-regulated acetylation for relevant enzymes in the mid-early stage and upregulated acetylation in the mid-late and late stages.Conclusion Our data here illustrated the changes in the global profiles for brain acetylated proteins during prion infection,showing remarkably inhibited acetylation in the early stage and relatively enhanced acetylation in the late stage.

关键词： Prion Scrapie-infected mouse Acetylation Proteomics Kyoto Encyclopedia of Genes and Genomes pathway

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Preparation of PrP-specific Polyclonal Antibody via Immunization of PRNP-knockout Mice with Recombinant Human PrP Protein

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Biomedical and Environmental Sciences 2020年第7期33卷 493-501页

作者： YANG Xue Hua WU Yue Zhang xiao Kang GAO Li ping CHEN dong dong DONG xiao ping SHI Qi State Key Laboratory for Infectious Disease Prevention and Control Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases(Zhejiang University)National Institute for Viral Disease Control and PreventionChinese Center for Disease Control and PreventionBeijing 102206China Center for Global Public Health Chinese Center for Disease Control and PreventionBeijing 102206China Wuhan Institute of Virology Chinese Academy of ScienceWuhan 430071HubeiChina China Academy of Chinese Medical Sciences Beijing 100700China

Objective The definite diagnosis of human and animal prion diseases depends on the examination of special pathological changes and/or detection of PrPSc in the brain tissues of suspected cases.Thus,developing methods to obtain PrP antibody with good specificity and sensitivity is fundamental for prion identification.Methods We prepared a PrP-specific polyclonal antibody(pAb P54)in a PRNP-knockout mouse model via immunization with recombinant full-length human PrP protein residues 23–231.Thereafter,we verified that pAb in Western blot,immunohistochemistry(IHC),and immunofluorescent(IFA)assays.Results Western blot illustrated that the newly prepared pAb P54 could react with recombinant PrP protein,normal brain PrPC from healthy rodents and humans,and pathological PrPSc in the brains of experimental rodents infected with scrapie and humans infected with different types of prion diseases.The electrophoretic patterns of brain PrPC and PrPSc observed after their reaction with pAb P54 were nearly identical to those produced by commercial PrP monoclonal antibodies.Three glycosylated PrP molecules in the brain homogenates were clearly demonstrated in the reactions of these molecules with pAb P54.IHC assay revealed apparent PrP deposits in the GdnCl-treated brain slices of 139 A-infected mice and 263 K-infected hamsters.IFA tests with pAb P54 also showed clear green signals surrounding blue-stained cell nuclei.Conclusion The newly prepared pAb P54 demonstrated reliable specificity and sensitivity and,thus,may have potential applications not only in studies of prion biology but also in the diagnosis of human and experimental rodent prion diseases.

关键词： Prion disease PrP Antibody PRNP-knockout mouse

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Analyses of the Duration and Dynamics of the COVID-19 Epidemic in 11 Severely Affected Countries

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Biomedical and Environmental Sciences 2021年第9期34卷 739-742页

作者： CHEN Cao SHI Qi DONG xiao ping State Key Laboratory for Infectious Disease Prevention and Control NHC Key Laboratory of Medical Virology and Viral DiseasesCollaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases(Zhejiang University)National Institute for Viral Disease Control and PreventionChinese Center for Disease Control and PreventionBeijing 102206China Chinese Center for Disease Control and Prevention-Wuhan Institute of Virology Chinese Academy of Sciences Joint Research Center for Emerging Infectious Diseases and BiosafetyCenter for Biosafety Mega-ScienceChinese Academy of SciencesWuhan 430071HubeiChina Center for Global Public Health Chinese Center for Disease Control and PreventionBeijing 102206China China Academy of Chinese Medical Sciences Beijing 100700China

The COVID-19 pandemic has affected 220 countries,areas,and territories worldwide,with more than 65 million confirmed cases and 1.5 million deaths[1].By the beginning of May,2020,only a few countries,such as China,South Korea,Australia,and New Zealand,seemed to be close to the epidemic’s late stage with a few daily reported new cases[1].

关键词： fir COV milli

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Assessment of the Sensitivity and Specificity of the Established Real-time Quaking-induced Conversion(RT-QuIC)Technique in Chinese CJD Surveillance

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Biomedical and Environmental Sciences 2020年第8期33卷 620-622页

作者： xiao Kang YANG Xue Hua ZOU Wen Quan DONG xiao ping SHI Qi State Key Laboratory for Infectious Disease Prevention and Control Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases(Zhejiang University)National Institute for Viral Disease Control and PreventionChinese Center for Disease Control and PreventionBeijing 102206China Center for Global Public Health Chinese Center for Disease Control and PreventionBeijing 102206China Wuhan Institute of Virology Chinese Academy of ScienceWuhan 430071Hubei China

Real-time quaking-induced conversion(RT-QuIC)assay is a newly established PrPSc-detecting method.The development of RT-QuIC improves the diagnosis of sporadic Creutzfeldt–Jakob disease(sCJD),showing good sensitivity and specificity in many countries when the method was used in cerebrospinal fluid(CSF)samples.However,in China,the sensitivity and specificity of RT-QuIC has yet to be determined due to the lack of definitive diagnosis samples.

关键词： diagnosis CJD cerebrospinal

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An Efficient Iterative Method for the Formulation of Flow Networks

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Communications in Computational Physics 2022年第5期31卷 1317-1340页

作者： Wei Hu dong Wang xiao-ping Wang Department of Mathematics The Hong Kong University of Science and TechnologyClear Water BayKowloonHong Kong School of Science and Engineering The Chinese University of Hong KongShenzhenGuangdong 518172China.

We propose an efficient iterative convolution thresholding method for the formulation of flow networks where thefluid is modeled by the Darcy–Stokesflow with the presence of volume sources.The method is based on the minimization of the dissipation power in thefluid region with a Darcy term.Theflow network is represented by its characteristic function and the energy is approximated under this representation.The minimization problem can then be approximately solved by alternating:1)solving a Brinkman equation to model the Darcy–Stokesflow and 2)updating the characteristic function by a simple convolution and thresholding step.The proposed method is simple and easy to implement.We prove mathematically that the iterative method has the total energy decaying property.Numerical experiments demonstrate the performance and robustness of the proposed method and interesting structures are observed.

关键词： Topology optimization convolution thresholding Darcy-Stokes flow

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Analysis of the Electrophoretic Profiles of Prion Protein in Carcinous and Pericarcinous Lysates of Six Different Types of Cancers

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Biomedical and Environmental Sciences 2021年第9期34卷 683-692页

作者： WEI Wei WU Yue Zhang xiao Kang XU Guo Hui SONG Yun Tao SHI Qi DONG xiao ping Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education) Head and Neck Surgery DepartmentPeking University Cancer Hospital&InstituteBeijing 100142China State Key Laboratory for Infectious Disease Prevention and Control Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases(Zhejiang University)National Institute for Viral Disease Control and PreventionChinese Center for Disease Control and PreventionBeijing 102206China Center for Global Public Health Chinese Center for Disease Control and PreventionBeijing 102206China Wuhan Institute of Virology Chinese Academy of ScienceWuhan 430071Hubei China China Academy of Chinese Medical Sciences Beijing 100700China

Objective To find the different electrophoretic profiles of prion protein in carcinous and individual pericarcinous tissues in lysates of gastric,colon,liver,lung,thyroid,and laryngeal cancers.Methods Sodium dodecyl sulfate polyacrylamide gel electrophoresis(SDS-PAGE)and Western blot were used to test the amounts and electrophoretic patterns of total Pr P and the tolerance of PK(protease K)digestion among six various cancer tissue types.Results A mass of Pr P signals with a large molecular weight were identified in the homogenates of peripheral tissues.The amounts and electrophoretic patterns of total Pr P did not differ significantly between carcinous and pericarcinous tissues.Pr Ps in all types of the tested cancer samples were PK sensitive but showed diversity in the tolerance of PK digestion among various tissue types.Conclusions The study revealed that the included electrophoretic patterns of carcinous and pericarcinous tissues were almost similar.Unlike Pr P-specific immunohistochemical assay,evaluation of Pr P electrophoretic patterns in the peripheral organs and tissues by Western blot does not reflect tumor malignancy.

关键词： Prion protein Cancer Electrophoretic profiles

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Ginkgo Biloba Extract Ameliorates Scopolamine-induced Memory Deficits via Rescuing Synaptic Damage

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Current Medical Science 2022年第3期42卷 474-482页

作者： Gui-jiao ZHANG dong ZHENG Huan YU xiao-ping LUO Wei WU Department of Pediatrics Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030China Department of Orthopedics Union HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430022China

Objective Alzheimer’s disease(AD)is the most common age-related neurodegenerative disorder.Emerging evidence suggests that synaptic dysfunction is associated with the onset and progression of AD.Interestingly,Ginkgo biloba extract(EGb)is one of the most frequently investigated herbal medicines for enhancing cognition and alleviating neurodegenerative dementia.This study aimed to investigate the effect and the mechanism of EGb on AD-like synaptic disorders.Methods Scopolamine(SCO)-induced rats were used to mimic AD-like memory deficits.Morris water maze test and fear conditioning test were conducted to evaluate the memory status of rats in response to different treatments.Then,the synapse alterations were assessed by Golgi staining,and Western blotting was conducted to assess the protein expression of PSD95,GluN2B,synapsin-1,and synaptophysin.Reverse transcription quantitative polymerase chain reaction was applied to detect the mRNA expression of PSD95 and the levels of miR-1-3p/miR-206-3p.Results EGb supplement alleviated the learning and memory deficits induced by SCO in behavioral experiments.Moreover,EGb treatment attenuated synaptic damage elicited by SCO,manifested as increased dendritic spine density and the proportion of mushroom-type spines in hippocampal neurons.Further investigation indicated that EGb rescued the expression of synaptic-related proteins,especially PSD95,and decreased the levels of miR-1-3p/miR-206-3p in the rat hippocampus.Conclusion The application of EGb effectively treats SCO-induced memory impairments probably by suppressing miR-1-3p/miR-206-3p and elevating the expression of PSD95.

关键词： Ginkgo biloba extract Alzheimer’s disease synapse PSD95 MiR-1 MiR-206

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均匀化处理对GH141高温合金热变形行为的影响

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材料热处理学报 2022年第4期43卷 107-115页

作者：肖东平成都先进金属材料产业技术研究院股份有限公司四川成都610000 海洋装备用金属材料及其应用国家重点实验室辽宁鞍山114009

采用热模拟试验机对铸态和不同程度均匀化处理后的GH141合金进行压缩和拉伸变形,研究了合金的热变形行为以及热变形后的再结晶程度。结果表明:铸态GH141合金热变形过程中开始再结晶温度为1050℃,随着变形温度升高,再结晶越充分,变形抗... 详细信息

采用热模拟试验机对铸态和不同程度均匀化处理后的GH141合金进行压缩和拉伸变形,研究了合金的热变形行为以及热变形后的再结晶程度。结果表明:铸态GH141合金热变形过程中开始再结晶温度为1050℃,随着变形温度升高,再结晶越充分,变形抗力越低。不同程度均匀化处理后,合金再结晶程度相比未均匀化处理的合金更低,但均匀化处理后,合金的热塑性显著提高。均匀化程度较低时,合金的变形抗力大,塑性仍较差;随着均匀化程度增加,合金的变形抗力逐渐降低,塑性增加;当均匀化时间过长,合金的再结晶程度降低,合金的变形抗力反而增加,塑性降低。

关键词： GH141合金均匀化热变形再结晶

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Genetic Prion Disease:Insight from the Features and Experience of China National Surveillance for Creutzfeldt-Jakob Disease

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Neuroscience Bulletin 2021年第11期37卷 1570-1582页

作者： Qi Shi Cao Chen Kang xiao Wei Zhou Li-ping Gao dong-dong Chen Yue-Zhang Wu Yuan Wang Chao Hu Chen Gao xiao-ping dong State Key Laboratory for Infectious Disease Prevention and Control Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases(Zhejiang University)National Institute for Viral Disease Control and PreventionChinese Center for Disease Control and PreventionBeijing102206China Center for Global Public Health Chinese Center for Disease Control and PreventionBeijing102206China Center for Biosafety Mega-Science Chinese Academy of SciencesWuhan430064China China Academy of Chinese Medical Sciences Beijing100700China

Human genetic prion diseases(gPrDs)are directly associated with mutations and insertions in the PRNP(Prion Protein)gene.We collected and analyzed the data of 218 Chinese gPrD patients identified between Jan 2006 and June 2020.Nineteen different subtypes were identified and gPrDs accounted for 10.9%of all diagnosed PrDs within the same period.Some subtypes of gPrDs showed a degree of geographic association.The age at onset of Chinese gPrDs peaked in the 50–59 year group.Gerstmann–Sträussler–Scheinker syndrome(GSS)and fatal familial insomnia(FFI)cases usually displayed clinical symptoms earlier than genetic Creutzfeldt–Jakob disease(gCJD)patients with point mutations.A family history was more frequently recalled in P105L GSS and D178N FFI patients than T188K and E200K patients.None of the E196A gCJD patients reported a family history.The gCJD cases with point mutations always developed clinical manifestations typical of sporadic CJD(sCJD).EEG examination was not sensitive for gPrDs.sCJD-associated abnormalities on MRI were found in high proportions of GSS and gCJD patients.CSF 14-3-3 positivity was frequently detected in gCJD patients.Increased CSF tau was found in more than half of FFI and T188K gCJD cases,and an even higher proportion of E196A and E200K gCJD patients.63.6%of P105L GSS cases showed a positive reaction in cerebrospinal fluid RT-QuIC.GSS and FFI cases had longer durations than most subtypes of gCJD.This is one of the largest studies of gPrDs in East Asians,and the illness profile of Chinese gPrDs is clearly distinct.Extremely high proportions of T188K and E196A occur among Chinese gPrDs;these mutations are rarely reported in Caucasians and Japanese.

关键词： Genetic prion disease Mutation Surveillance Creutzfeldt-Jakob disease Gerstmann-Sträussler-Scheinker syndrome Fatal familial insomnia

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Cerebrospinal Fluids from Patients with Five Common Genetic Prion Diseases in China Display Distinct Reactivities in the RT-QuIC Assays

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Biomedical and Environmental Sciences 2021年第10期34卷 830-833页

作者： HU Chao CHEN Cao CHEN Jia xiao Kang ZHOU Wei XIA Ying YANG Wei WANG Lin SHI Qi DONG xiao ping State Key Laboratory for Infectious Disease Prevention and Control Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases(Zhejiang University)National Institute for Viral Disease Control and PreventionChinese Center for Disease Control and PreventionBeijing 102206China Center for Biosafety Mega-Science Chinese Academy of SciencesWuhan 420115HubeiChina College of Life Science and Technology Heilongjiang Bayi Agricultural UniversityDaqing 163711HeilongjiangChina China Academy of Chinese Medical Sciences Beijing 100700China Center for Global Public Health Chinese Center for Disease Control and PreventionBeijing 102206China

Prion diseases(PrDs)are fatal neurodegenerative conditions that affect humans and other mammals,which consist of sporadic,genetic,and acquired forms in human PrDs[1].The genetic form accounts for approximately 5%–15%... 详细信息

关键词： diseases Patients Assay

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