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Antibodies elicited by Newcastle disease virus-vectored H7N9 avian influenza vaccine are functional in activating the complement system

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Journal of Integrative Agriculture 2024年第6期23卷 2052-2064页

作者： Zenglei Hu Ya Huang Jiao Hu xiaoquan wang Shunlin Hu Xiufan Liu Joint International Research Laboratory of Agriculture and Agri-Product Safety of the Ministry of Education of China Yangzhou UniversityYangzhou 225009China Animal Infectious Disease Laboratory School of Veterinary MedicineYangzhou UniversityYangzhou 225009China Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses Yangzhou UniversityYangzhou 225009China

H7N9 subtype avian influenza virus poses a great challenge for poultry *** disease virus(NDV)-vectored H7N9 avian influenza vaccines(NDV_(vec)H7N9)are effective in disease control because they are protective and allow mass *** note,these vaccines elicit undetectable H7N9-specific hemagglutination-inhibition(HI)but high IgG antibodies in ***,the molecular basis and protective mechanism underlying this particular antibody immunity remain ***,immunization with an NDV_(vec)H7N9 induced low anti-H7N9 HI and virus neutralization titers but high levels of hemagglutinin(HA)-binding IgG antibodies in *** residues(S150,G151 and S152)in HA of H7N9 virus were identified as the dominant epitopes recognized by the NDV_(vec)H7N9 immune *** transferred NDV_(vec)H7N9 immune serum conferred complete protection against H7N9 virus infection in *** NDV_(vec)H7N9 immune serum can mediate a potent lysis of HA-expressing and H7N9 virus-infected cells and significantly suppress H7N9 virus *** activities of the serum were significantly impaired after heat-inactivation or treatment with complement inhibitor,suggesting the engagement of the complement ***,mutations in the 150-SGS-152 sites in HA resulted in significant reductions in cell lysis and virus neutralization mediated by the NDV_(vec)H7N9 immune serum,indicating the requirement of antibody-antigen binding for complement ***,antibodies induced by the NDV_(vec)H7N9 can activate antibody-dependent complement-mediated lysis of H7N9 virus-infected cells and complement-mediated neutralization of H7N9 *** findings unveiled a novel role of the complement in protection conferred by the NDV_(vec)H7N9,highlighting a potential benefit of engaging the complement system in H7N9 vaccine design.

关键词： H7N9 subtype avian influenza virus NDV vector vaccine antibody immunity complement protection

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Phosphorylation of PB2 at serine 181 restricts viral replication and virulence of the highly pathogenic H5N1 avian influenza virus in mice

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Virologica Sinica 2024年第1期39卷 97-112页

作者： Jiao Hu Zixiong Zeng Xia Chen Manyu Zhang Zenglei Hu Min Gu xiaoquan wang Ruyi Gao Shunlin Hu Yu Chen Xiaowen Liu Daxin Peng Xiufan Liu Animal Infectious Disease Laboratory School of Veterinary MedicineYangzhou UniversityYangzhou225009China Joint International Research Laboratory of Agriculture and Agri-Product Safety The Ministry of Education of ChinaYangzhou University225009China Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonosis Yangzhou UniversityYangzhou225009China Key Laboratory of Prevention and Control of Biological Hazard Factors(Animal Origin)for Agri-food Safety and Quality Ministry of Agriculture of China(26116120)Yangzhou UniversityYangzhou225009China

Influenza A virus(IAV)continues to pose a pandemic threat to public health,resulting a high mortality rate annually and during pandemic *** modification of viral protein plays a substantial role in regulating IAV ***,based on immunoprecipitation(IP)-based mass spectrometry(MS)and purified virus-coupled MS,a total of 89 phosphorylation sites distributed among 10 encoded viral proteins of IAV were identified,including 60 novel phosphorylation ***,for the first time,we provide evidence that PB2 can also be acetylated at site ***,the PB2 S181 phosphorylation site was consistently identified in both IP-based MS and purified virus-based *** S181 and K187 are exposed on the surface of the PB2 protein and are highly conserved in various IAV strains,suggesting their fundamental importance in the IAV life *** analysis results demonstrated that S181E/A and K187Q/R mimic mutations do not significantly alter the PB2 protein *** continuous phosphorylation mimicked by the PB2 S181E mutation substantially decreases viral fitness in mice,PB2 K187Q mimetic acetylation slightly enhances viral virulence in ***,PB2 S181E substantially impairs viral polymerase activity and viral replication,remarkably dampens protein stability and nuclear accumulation of PB2,and significantly weakens IAV-induced inflammatory ***,our study further enriches the database of phosphorylation and acetylation sites of influenza viral proteins,laying a foundation for subsequent mechanistic ***,the unraveled antiviral effect of PB2 S181E mimetic phosphorylation may provide a new target for the subsequent study of antiviral drugs.

关键词： H5N1 influenza virus PB2 Phosphorylation Acetylation Viral fitness Mice

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微型高速燃油泵空化数值模拟与试验研究

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流体机械 2024年第6期52卷 58-66页

作者：廉佳王维军王晓全王新超邹轶群吴刚海军装备部成都610091 航空工业成都凯天电子股份有限公司成都610091 中国航天科工集团公司第三研究院北京100074

以某型微型高速燃油泵为研究对象,采用SST k-ω湍流模型与ZGB空化模型对不同工况下的空化内部流动进行数值模拟;采集了不同工况、不同高度下的X,Y,Z三个轴向的振动加速度,对有、无空化的振动特性进行了分析。结果表明,流量、转速、高度... 详细信息

以某型微型高速燃油泵为研究对象,采用SST k-ω湍流模型与ZGB空化模型对不同工况下的空化内部流动进行数值模拟;采集了不同工况、不同高度下的X,Y,Z三个轴向的振动加速度,对有、无空化的振动特性进行了分析。结果表明,流量、转速、高度等参数变化对微型高速燃油泵空化特性有显著影响;在额定转速下,随着燃油泵进口压力的减小,空泡首先出现在泵进口弯管内侧及叶轮叶片背面,进一步扩大至整个叶轮流道,基本阻断了流动,叶轮中的含气率也从小于5%增大到了70%左右;仿真与可视化试验均可观察到空泡初生位置在弯管处,接着扩散至吸入弯管并逐渐增大,随后形成明显的气液边界线,最终导致完全断流;空化发生时,每个轴向在2倍叶频出现了明显的振动,依次增大趋势为X,Y,Z;随着高度增加,空化程度加剧,各方向振动频谱发生变化,最大峰值均呈现降低的趋势,但激发了较高频率的振动信号;振动功率谱密度幅值变化规律与空化发展程度相对应,可以作为泵内空化程度的表征。本文为微型高速燃油泵空化判别及空化流动控制提供了理论基础。

关键词：燃油泵数值模拟空化振动

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江汉油区探明未动用储量动用实践及认识

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江汉石油职工大学学报 2024年第1期37卷 26-28页

作者：韩利霞朱玲莉胡婷王孝权中石化江汉油田分公司江汉采油厂湖北潜江433123

江汉油区按照总部2020年未动用储量分类评价方案,深化油藏再认识,创新工艺技术手段,对42个未动用储量区块进行重新清理及分类评价,制定“一块一策”攻关方案,有效推动未动用储量的效益开发。

关键词：江汉油区未动用储量储量动用

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浙西南山区高填方地基边坡压实土长期稳定性研究

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水力发电 2024年第4期50卷 32-37,42页

作者：耿康杨怀钰胡元音王孝权窄佐磊浙江省浙南综合工程勘察测绘院有限公司浙江杭州310012 湖北省地质局第七地质大队湖北宜昌443100 河北地质大学城市地质与工程学院河北石家庄050031

为研究浙西南山区高填方边坡压实土长期稳定性问题,结合现场取样、室内试验与数值模拟计算方法,对压实土的力学性质、变形特征和稳定性的影响因素进行研究,采用Kelvin模型对Burgers模型的改进模型,得到了压实土的蠕变参数,结合有限元模... 详细信息

为研究浙西南山区高填方边坡压实土长期稳定性问题,结合现场取样、室内试验与数值模拟计算方法,对压实土的力学性质、变形特征和稳定性的影响因素进行研究,采用Kelvin模型对Burgers模型的改进模型,得到了压实土的蠕变参数,结合有限元模拟软件研究高填方边坡的蠕变现象。结果表明,模型参数随着荷载增大逐渐减小,蠕变模型参数与压实度呈现正相关,与含水率呈现负相关。选择填筑材料应尽量选用最优含水率的材料,同时对填筑体进行压实,压实度应在90%以上。对于高填方边坡沉降和位移的控制,需要采取优化设计、加强排水设施、控制施工工艺和实施边坡加固等综合措施。

关键词：高填方地基边坡压实土长期稳定性影响因素室内试验数值模拟工程措施浙西南山区

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MCI老年人群血清维生素D水平与认知功能及抑郁情绪的相关性研究

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中华全科医学 2024年第2期22卷 187-190页

作者：蔡菡张军许慧李世霞王小泉芜湖市第四人民医院精神科安徽芜湖241002 安徽中医药高等专科学校基础教学部安徽芜湖241002

目的探讨轻度认知功能障碍(MCI)老年人群血清维生素D水平与认知功能及抑郁情绪的相关性,为临床干预提供理论基础。方法2023年2—8月对社区老人展开筛查,入组315例MCI受试者,采血测量维生素D水平,其中维生素D缺乏组155人和正常组160人,比... 详细信息

目的探讨轻度认知功能障碍(MCI)老年人群血清维生素D水平与认知功能及抑郁情绪的相关性,为临床干预提供理论基础。方法2023年2—8月对社区老人展开筛查,入组315例MCI受试者,采血测量维生素D水平,其中维生素D缺乏组155人和正常组160人,比较2组一般情况、简易智力状态检查量表(MMSE)、蒙特利尔认知评估量表(MoCA)、老年抑郁量表(GDS)、流调用抑郁自评量表(CES-D)评分差异。结果与正常组比较,维生素D缺乏组MMSE的即刻记忆[(9.01±1.41)分vs.(8.46±2.36)分],计算[(3.64±1.60)分vs.(3.20±1.76)分],回忆[2.00(1.00,3.00)分vs.2.00(1.00,2.00)分],复述[1.00(0.00,1.00)分vs.1.00(0.00,1.00)分],三步命令[(2.59±0.71)分vs.(2.28±0.90)分],总分[(25.10±3.05)分vs.(23.56±3.90)分],MoCA语言、回忆、总分均明显降低(P<0.05)。维生素D缺乏组CES-D总分[(13.10±4.12)分vs.(11.26±4.81)分]明显高于正常组(P<0.01)。维生素D水平与总体认知功能具有正相关关系(P<0.05),与抑郁情绪存在负相关关系(P<0.05)。结论MCI人群维生素D水平与认知功能和抑郁存在相关关系。

关键词：社区轻度认知障碍维生素D 认知功能抑郁

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2019—2021年华东地区6株禽源H3亚型流感病毒的遗传进化分析

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中国动物传染病学报 2024年第2期32卷 208-217页

作者：赵婉宸李扬才天宇葛志闯高如一王晓泉顾敏刘秀梵扬州大学兽医学院农业农村部禽用生物制剂创制重点实验室扬州225009 江苏省人兽共患病学重点实验室扬州225009 江苏高校动物重要疫病与人兽共患病防控协同创新中心扬州225009

H3亚型流感病毒在自然界广泛存在,可感染人、猪、马、犬、禽等众多宿主并能发生跨种间传播,危害不容忽视。本研究于2019—2021年在华东地区活禽市场采集表观健康的家禽喉头与泄殖腔棉拭,通过血清学试验鉴定、筛选出6株代表性水禽源H3亚... 详细信息

H3亚型流感病毒在自然界广泛存在,可感染人、猪、马、犬、禽等众多宿主并能发生跨种间传播,危害不容忽视。本研究于2019—2021年在华东地区活禽市场采集表观健康的家禽喉头与泄殖腔棉拭,通过血清学试验鉴定、筛选出6株代表性水禽源H3亚型流感病毒,并经RT-PCR试验确定5株为H3N2亚型、1株为H3N1亚型。进一步对6株分离株进行全基因组测序、同源性比对和遗传进化分析,结果显示:HA蛋白裂解位点处均为PEKQTR/GLF,不存在连续碱性氨基酸,符合低致病性禽流感病毒的分子特征;受体结合位点处均为禽源特征性的226Q和228S,提示其跨种传播至哺乳动物的潜能较低;内部基因片段来源多样化,与H3N8、H4N6、H5N8、H6N1、H7N7、H0N3等众多亚型禽流感病毒的亲缘关系密切;除JS1018/19和JS1094/19的NS基因属于北美谱系以外,其余均属于欧亚谱系的禽源分支,与犬、马、猪、人等哺乳动物源毒株的亲缘关系较远,提示虽然可能存在不同进化谱系间的基因重组但并未发生从禽到哺乳动物宿主的基因交换。该研究结果丰富了H3亚型禽流感病毒的流行病学数据,为进一步了解我国低致病性禽流感病毒的分布特征提供了参考依据。

关键词：禽流感病毒 H3N1 H3N2 基因组分析遗传进化

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Enhanced pathogenicity and transmissibility of H9N2 avian influenza virus in mammals by hemagglutinin mutations combined with PB2-627K

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Virologica Sinica 2023年第1期38卷 47-55页

作者： Kaituo Liu Yaqian Guo Huafen Zheng Zhuxing Ji Miao Cai Ruyi Gao Pinghu Zhang Xiaowen Liu Xiulong Xu xiaoquan wang Xiufan Liu Joint International Research Laboratory of Agriculture and Agri-Product Safety The Ministry of Education of ChinaYangzhou UniversityYangzhou225009China Animal Infectious Disease Laboratory College of Veterinary MedicineYangzhou UniversityYangzhou225009China Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonosis Yangzhou UniversityYangzhou225009China Jiangsu Key Laboratory of Zoonosis Yangzhou225009China Institute of Translational Medicine Key Laboratory of Geriatric Disease Prevention and Control of Jiangsu ProvinceMedical CollegeYangzhou UniversityYangzhou225009China

H9N2 avian influenza viruses(AIVs)circulate globally in poultry and have become the dominant AIV subtype in China in recent ***,we demonstrated that the H9N2 virus(A/chicken/Eastern China/SDKD1/2015)naturally harbors a mammalian-adaptive molecular factor(627K)in the PB2 protein and is weakly pathogenic in ***,we focused on new markers for virulence in mammals.A mouse-adapted H9N2 virus was serially passaged in mice by infecting their *** expected,infected mice showed clinical symptoms and died at passage six.A comparison between the wild-type and mouse-adapted virus sequences identified amino acid substitutions in the hemagglutinin(HA)protein.H9N2 viruses with the T187P t M227L double mutation exhibited an increased affinity to human-type(SAα2,6Gal)receptors and significantly enhanced viral attachment to mouse lung tissues,which contributed to enhancing viral replication and virulence in ***,HA with the T187P t M227L mutation enabled H9N2 viral transmission in guinea pigs via direct *** pathogenicity in mice is a polygenic *** results demonstrated that these HA mutations might be combined with PB2-627K to significantly increase H9N2 virulence in mice,and this enhanced virulence was achieved in other H9N2 AIVs by generating the same combination of *** summary,our study identified novel key elements in the HA protein that are required for H9N2 pathogenicity in mice and provided valuable insights into pandemic preparedness against emerging H_(9)N_(2)strains.

关键词： H9N2 Hemagglutinin(HA) PB2-627K Mammalian adaptation Pathogenicity Transmissibility

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Analysis of the Impact of the Space Guide Vane Wrap Angle on the Performance of a Submersible Well Pump

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Fluid Dynamics & Materials Processing 2019年第3期15卷 271-284页

作者： Xiaorui Cheng Hongxing Chen xiaoquan wang Lanzhou University of Technology College of Energy and Power EngineeringLanzhou730050China Key Laboratory of Fluid machinery and Systems of Gansu Province Lanzhou730050China

In order to study the influence of the wrap angle relating to the space guide vane of a submersible well pump(250QJ125)on the flow field and pump performance,seven possible configurations have been considered(obtained by changing the blade wrap angle while keeping unchanged all the other parameters).Such configurations have been numerically simulated in the framework of a computational model based on the Reynolds time-averaged N-S equations,the RNG k-εturbulence approach and the SIMPLE *** impact exerted by different wrap angles of the guide vane on the performance of the pump,the internal losses of the guide vane and the flow field distribution in the bladeless area at the guide vane outlet has been assessed via cross-comparison of all these *** results show that the wrap angle has a significant influence:the wrap angle with the highest head is different from that with the highest efficiency,and changes in this angle have a more significant effect on the head than efficiency.A moderate raise of the wrap angle can improve the properties of the flow,reduce turbulence losses and enhance the energy conversion rate inside the guide *** wrap angles can also lead to different fluid circulation modes in the bladeless area from guide vane outlet to impeller inlet,while they have a weak influence on the absolute value of the velocity of the fluid entering the impeller.

关键词： Submersible well pump space guide vane wrap angle internal flow

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Emergence of a novel reassortant avian influenza virus(H10N3) in Eastern China with high pathogenicity and respiratory droplet transmissibility to mammals

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Science China(Life Sciences) 2022年第5期65卷 1024-1035页

作者： Kaituo Liu Pingyun Ding Yuru Pei Ruyi Gao Wenwen Han Huafen Zheng Zhuxing Ji Miao Cai Jinyuan Gu Xiuli Li Min Gu Jiao Hu Xiaowen Liu Shunlin Hu Pinghu Zhang Xiaobo wang xiaoquan wang Xiufan Liu College of Veterinary Medicine Yangzhou UniversityYangzhou 225009China Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonosis Yangzhou UniversityYangzhou 225009China Jiangsu Key Laboratory of Zoonosis Yangzhou 225009China Institute of Translational Medicine Key Laboratory of Geriatric Disease Prevention and Control of Jiangsu ProvinceMedical CollegeYangzhou UniversityYangzhou 225009China

Decades have passed since the first discovery of H10-subtype avian influenza virus(AIV) in chickens in 1949,and it has been detected in many species including mammals such as minks,pigs,seals and *** of human infections with H10N8viruses identified in China in 2013 have raised widespread *** novel reassortant H10N3 viruses were isolated from chickens in December 2019 in eastern China during routine surveillance for *** internal genes of these viruses were derived from genotype S(G57) H9N2 and were consistent with H5N6,H7N9 and H10N8,which cause fatal infections in *** viral pathogenicity and transmissibility were further studied in different animal *** two H10N3 isolates had low pathogenicity in chickens and were transmitted between chickens via direct *** viruses were highly pathogenic in mice and could be transmitted between guinea pigs via direct contact and respiratory *** importantly,these viruses can bind to both human-type SAα-2,6-Gal receptors and avian-type SAα-2,3-Gal *** shedding in chickens and good adaptability to mammals of these H10N3 isolates would make it easier to transmit to humans and pose a threat to public health.

关键词： H10N3 H9N2 receptor binding pathogenicity respiratory droplet transmissibility

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