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32 个结果
  • 简介:AbstractBackground:The new emerging avian influenza A H7N9 virus, causing severe human infection with a mortality rate of around 41%. This study aims to provide a novel treatment option for the prevention and control of H7N9.Methods:H7 hemagglutinin (HA)-specific B cells were isolated from peripheral blood plasma cells of the patients previously infected by H7N9 in Jiangsu Province, China. The human monoclonal antibodies (mAbs) were generated by amplification and cloning of these HA-specific B cells. First, all human mAbs were screened for binding activity by enzyme-linked immunosorbent assay. Then, those mAbs, exhibiting potent affinity to recognize H7 HAs were further evaluated by hemagglutination-inhibiting (HAI) and microneutralization in vitro assays. Finally, the lead mAb candidate was selected and tested against the lethal challenge of the H7N9 virus using murine models.Results:The mAb 6-137 was able to recognize a panel of H7 HAs with high affinity but not HA of other subtypes, including H1N1 and H3N2. The mAb 6-137 can efficiently inhibit the HA activity in the inactivated H7N9 virus and neutralize 100 tissue culture infectious dose 50 (TCID50) of H7N9 virus (influenza A/Nanjing/1/2013) in vitro, with neutralizing activity as low as 78 ng/mL. In addition, the mAb 6-137 protected the mice against the lethal challenge of H7N9 prophylactically and therapeutically.Conclusion:The mAb 6-137 could be an effective antibody as a prophylactic or therapeutic biological treatment for the H7N9 exposure or infection.

  • 标签: Avian influenza H7N9 Monoclonal antibody Neutralizing activity
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  • 简介:摘要:将思维可视化教学运用到具体的阅读语篇教学中,从文本分析、教学活动设计与实施三个步骤探索在阅读教学中如何运用思维可视化策略,更好地发展学生的英语核心素养。

  • 标签:   思维可视化,阅读教学,思维导图
  • 简介:Recentdevelopmentsincomputationalsciencesandcomputermodelinghaveallowedemergencypreparednessexercisestoincludesimulationmodelsassupportingtools.Thesesimulationmodelsaregenerallybuiltforpredictingtemporalandgeographicpatternsofdiseasespread.Howeversoleuseofsimulationmodelsinexercisedesignfallsshortintermsofincorporatingpolicydecisionmakers'preferencesintodecision-makingprocesses.Inthispaper,ageneralframeworkforexercisingpublichealthpreparednessplanswithadecisionsupportsystemispresentedtointegrateestimationofkeyepidemiologicalparameterswithasystemdynamicsmodelofanoutbreak.Amulti-criteriadecisionmakingframework,anAnalyticalHierarchyProcessmodel,isthendevelopedandintegratedwiththesimulationmodeltohelppublichealthpolicymakersprioritizetheirresponsegoalsandevaluatemitigationstrategiesinatable-topexerciseenvironment.

  • 标签: 系统动力学模型 多准则决策 模型评估 公众健康 计算机模拟 流感
  • 简介:AbstractBackground:A new candidate vector vaccine against human brucellosis based on recombinant influenza viral vectors (rIVV) subtypes H5N1 expressing Brucella outer membrane protein (Omp) 16, L7/L12, Omp19 or Cu-Zn SOD proteins has been developed. This paper presents the results of the study of protection of the vaccine using on guinea pigs, including various options of administering, dose and frequency. Provided data of the novel vaccine candidate will contribute to its further movement into the preclinical stage study.Methods:General states of guinea pigs was assessed based on behavior and dynamics of a guinea pig weight-gain test. The effectiveness of the new anti-brucellosis vector vaccine was determined by studying its protective effect after conjunctival, intranasal and sublingual administration in doses 105 EID50, 106 EID50 and 107 EID50 during prime and boost vaccinations of animals, followed by challenge with a virulent strain of B. melitensis 16 M infection. For sake of comparison, the commercial B. melitensis Rev.1 vaccine was used as a control. The protective properties of vaccines were assessed by quantitation of Brucella colonization in organs and tissues of infected animals and compared to the control groups.Results:It was observed a gradual increase in body weight of guinea pigs after prime and booster immunization with the vaccine using conjunctival, intranasal and sublingual routes of administration, as well as after using various doses of vaccine. The most optimal way of using the vaccine has been established: double intranasal immunization of guinea pigs at a dose of 106 EID50, which provides 80% protection of guinea pigs from B. melitensis 16 M infection (P < 0.05), which is comparable to the results of the effectiveness of the commercial B. melitensis Rev.1 vaccine.Conclusions:We developed effective human vaccine candidate against brucellosis and developed its immunization protocol in guinea pig model. We believe that because of these studies, the proposed vaccine has achieved the best level of protection, which in turn provides a basis for its further promotion.

  • 标签: Human brucellosis Influenza viral vectors Vaccine candidate Protection Guinea pigs Immunization route Vaccination dose
  • 简介:AbstractBird infections with highly pathogenic avian influenza A(H5N6) viruses have been identified since 2014. With very limited occasion, the virus could sporadically spilled over to infect humans. It has been recognized that all human infections were within southern region of Mainland China until the case reported here in Beijing in Aug. 2019. This was the first human case infected with highly pathogenic avian influenza A(H5N6) virus in northern China. The infection was confirmed by real-time RT-PCR assay. The whole genome sequences were obtained from clinical sample. Genetic characteristics of the virus were identified similar to those of previous avian influenza A(H5N6) viruses, retaining the main features of the avian influenza virus.

  • 标签: Highly pathogenic avian influenza H5N6 Human infection
  • 简介:AbstractInfluenza A (H3N2) virus has a faster evolution rate than other types of influenza viruses. In this study, whole genome sequencing was performed to better understand the molecular evolution of influenza H3N2 and the protective effect of influenza virus vaccine in Qinghai Province, China, in 2017. Complete sequences of eight gene segments of two seasonal influenza H3N2 isolates were sequenced and analyzed using DNASTAR and MEGA 6.06 software. Additionally, the three-dimensional structure of the HA protein was predicted using the SWISS-MODEL server. Phylogenetic and amino acid sequence analysis revealed that two Qinghai H3N2 isolates were typical low-pathogenic influenza viruses, and were relatively closely related to the 2016-2017 vaccine strain, 3C.2a-A/Hong Kong/4801/2014. The presence of several antigenic site substitutions (T131K, G/R142K, K160T and R261Q in the HA protein) were specific for the two Qinghai H3N2 virus strains. In addition, amino acid substitution of K160T at the glycosylation site of HA and H75P in PB1-F2 in Qinghai isolates might affect the antibody binding ability and virulence of the influenza virus. The presence of several antigenic site mutations in the Qinghai H3N2 isolates confirmed the evolution of circulating H3N2 strains.

  • 标签: Influenza virus Subtype H3N2 Influenza virus vaccines Whole genome sequencing
  • 简介:高度病原的鸟的流行性感冒H5N1流行病是重要公共健康危险。有哺乳动物的传播活动的遗传上设计的H5N1病毒加亮人的流行性感冒H5N1的潜在的风险流行。响应流行性感冒H5N1病毒理解天生的免疫系统的内在的原则将导致这些潜在地致命的病毒的改进预防和控制。γ;δ;当第一对微生物引起的感染防卫排队并且帮助在病毒的感染的早阶段期间开始适应有免疫力的回答,T房间行动。在这研究,我们调查了γ的分子的机制;δ;响应流行性感冒H5N1病毒的感染的T房间。我们发现从流行性感冒H5N1病毒的三不同紧张导出的recombinant红血球凝聚素(rHA)得到了γ的激活;δ;在外部血mononuclear房间(PBMC)有教养的T房间。两CD69的房间表面表示,γ上的一个早激活标记;δ;interferon-γ的T房间,和生产;(IFN-γ;)显著地被增加。尤其是,rHA导致蛋白质的γ;δ;T房间激活没被TCRγ调停;δ;,NKG2D或模式识别受体(PRR)或NKp46受体。有sialic酸受体的rHA蛋白质的相互作用可以在γ起一个关键作用;δ;T房间激活。我们的数据可以提供卓见进位于γ下面的机制;δ;响应有H5N1病毒的感染的T房间激活。

  • 标签: 高致病性禽流感 H5N1病毒 T细胞活化 受体介导 相互作用 唾液酸
  • 简介:AbstractWe conducted environmental surveillance to detect avian influenza viruses circulating at live poultry markets (LPMs) and poultry farms in Guangxi Autonomous Region, China, where near the China-Vietnam border. From November through April 2017-2018 and 2018-2019, we collected environmental samples from 14 LPMs, 4 poultry farms, and 5 households with backyard poultry in two counties of Guangxi and tested for avian influenza A, H5, H7, and H9 by real-time reverse transcription-polymerase chain reaction (rRT-PCR). In addition, we conducted four cross-sectional questionnaire surveys among stall owners on biosecurity practices in LPMs of two study sites. Among 16,713 environmental specimens collected and tested, the median weekly positive rate for avian influenza A was 53.6% (range = 33.5% - 66.0%), including 25.2% for H9, 4.9% for H5, and 21.2% for other avian influenza viruses A subtypes, whereas a total of two H7 positive samples were detected. Among the 189 LPM stalls investigated, most stall owners (73.0%) sold chickens and ducks. Therefore, continued surveillance of the avian influenza virus is necessary for detecting and responding to emerging trends in avian influenza virus epidemiology.

  • 标签: Avian influenza virus Environmental surveillance Live-poultry-market
  • 简介:流行性感冒A病毒(IAV)感染是一个主要全球公共的健康问题。然而,因素在调停包含了煽动性的反应到这感染和他们糟糕理解的关系遗体。这里,我们证明IAV感染刺激可溶的IL-6受体(sIL-6R)的表示,涉及IL-6发信号的多功能的蛋白质。有趣地,sIL-6R表示upregulated它的自己的ligand,支持inflammatorycytokineIL-32的IL-6和那些的层次。调停shRNAsIL-6R击倒压制的IL-6和IL-32,显示这条规定在IAV感染期间依赖于sIL-6R。而且,我们的结果证明IL-32参予禁止sIL-6R的一个否定反馈环当时upregulatingIL-6表示在IAV感染期间。因此,我们证明sIL-6R是涉及对病毒的感染的尖锐煽动性的反应的一个关键细胞的因素。

  • 标签: A型流感病毒 病毒感染 IL-6 RNA介导 细胞因子 炎症反应
  • 简介:AbstractBackground:Endothelial cells play a key role in the cytokine storm caused by influenza A virus. MicroRNA-155 (miR-155) is an important regulator in inflammation. Its role in the inflammatory response to influenza A infection, however, has yet to be elucidated. In this study, we explored the role as well as the underlying mechanism of miR-155 in the cytokine production in influenza A-infected endothelial cells.Methods:Human pulmonary microvascular endothelial cells (HPMECs) were infected with the influenza A virus strain H1N1. The efficiency of H1N1 infection was confirmed by immunofluorescence. The expression levels of proinflammatory cytokines and miR-155 were determined using real-time polymerase chain reaction. A dual-luciferase reporter assay characterized the interaction between miR-155 and sphingosine-1-phosphate receptor 1 (S1PR1). Changes in the target protein levels were determined using Western blot analysis.Results:MiR-155 was elevated in response to the H1N1 infection in HPMECs (24 h post-infection vs. 0 h post-infection, 3.875 ± 0.062 vs. 1.043 ± 0.013, P = 0.001). Over-expression of miR-155 enhanced inflammatory cytokine production (miR-155 mimic vs. negative control, all P < 0.05 in regard of cytokine levels) and activation of nuclear factor kappa B in infected HPMECs (miR-155 mimic vs. negative control, P = 0.004), and down-regulation of miR-155 had the opposite effect. In addition, S1PR1 was a direct target of miR-155 in the HPMECs. Inhibition of miR-155 enhanced the expression of the S1PR1 protein. Down-regulation of S1PR1 decreased the inhibitory effect of the miR-155 blockade on H1N1-induced cytokine production and nuclear factor kappa B activation in HPMECs.Conclusion:MiR-155 maybe modulate influenza A-induced inflammatory response by targeting S1PR1.

  • 标签: MicroRNA-155 Sphingosine 1-phosphate receptor 1 Influenza A virus Endothelial cells
  • 简介:流行性感冒病毒红血球凝聚素的梗区域很好相对与球状的头领域相比被保存,它对流行性感冒用作一支通用疫苗使它成为一个潜在的目标。然而,在红血球凝聚素的CD4T房间的角色梗特定的有免疫力的反应不是清楚的。这里,我们识别了在流行性感冒的尚不致命的感染以后从红血球凝聚素梗领域包含残余HA2113-131的老鼠CD4T房间epitope。响应有识别epitope的刺激,从感染的老鼠导出的splenocytes显示出象degranulation一样由IL-2,TNF-和IFN-生产出现的重要polyfunctionality。而且,与相应于这CD4T房间epitope的肽使免疫的老鼠展出了CD4T房间受体分享的interindividual序列,和他们有更高的幸存率与流行H1N1流行性感冒的致命的剂量跟随挑战病毒。因此,我们的数据表明了红血球凝聚素的一个关键角色在对流行性感冒病毒感染的主机免疫者反应的梗特定的CD4T房间。

  • 标签: BALB/c小鼠 T细胞表位 流感病毒 抗原表位 CD4 血凝素