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Elimination of GGTA1,CmAH,β4GalNT2 and CIITA genes in pigs compromises human versus pig xenogeneic immune reactions

Animal models and Experimental medicine 2024年第4期7卷 584-590页

作者： Jing Xu Jilong Ren kai Xu minghui Fang meina ka Fei Xu Xin Wang Jing Wang Zhiqiang Han Guihai Feng Ying Zhang Tang Hai Wei Li Zheng Hu State Key Laboratory of Stem Cell and Reproductive Biology Institute of ZoologyChinese Academy of SciencesBeijingChina Key Laboratory of Organ Regeneration and Reconstruction Chinese Academy of SciencesBeijingChina University of Chinese Academy of Sciences BeijingChina Beijing Institute for Stem Cell and Regenerative medicine BeijingChina Key Laboratory of Organ Regeneration and Transplantation of the ministry of Education The First HospitalJilin UniversityChangchunChina Beijing Farm Animal Research Center Institute of ZoologyChinese Academy of SciencesBeijingChina

Background:Pig organ xenotransplantation is a potential solution for the severe organ shortage in clinic,while immunogenic genes need to be eliminated to im-prove the immune compatibility between humans and *** knockout strat-egies are mainly aimed at the genes causing hyperacute immune rejection(HAR)that occurs in the first few hours while adaptive immune reactions orchestrated by CD4 T cell thereafter also cause graft failure,in which process the mHC II molecule plays critical ***:Thus,we generate a 4-gene(GGTA1,CmAH,β4GalNT2,and CIITA)knockout pig by CRISPR/Cas9 and somatic cell nuclear transfer to compromise HAR and CD4 T cell reactions ***:We successfully obtained 4KO piglets with deficiency in all alleles of genes,and at cellular and tissue ***,the safety of our animals after gene editing was verified by using whole-genome sequencing and *** have survived for more than one year in the barrier,and also survived for more than 3 months in the conventional environment,suggesting that the piglets without mHC II can be raised in the barrier and then gradually mated in the conventional ***:4KO piglets have lower immunogenicity,are safe in genomic level,and are easier to breed than the model with both mHC I and II deletion.

关键词： CD4 T cell genetically edited pig immune rejection major histocompatibility complex II xenotransplantation

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Results of the influenza virus surveillance in wild birds in Western part of mongolia

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Asian Pacific Journal of Tropical medicine 2010年第2期3卷 90-93页

作者： marchenko V Yu Alekseev A Yu Tserennorov D Yurlov AK Susloparov im Sharshov ka Ilyinykh FA Zolotykh SI Abmed D Otgonbaatar D Shestopalov Am Federal State Research Institution State Research Center of Virology and Biotechnology VectorKoltsovoNovosibirsk RegionRussia National Centre for Diseases with Natural Foci UlaanbaatarMongolia Institute of Systematic and Ecology of Animals Siberian BranchRussian Academy of ScienceNovosibirskRussia National Centre for Infectious Diseases UlaanbaatarMongolia

Objective:To present results of virological study of wild birds inhabiting Western mongolia. methods:Over a period of 2003-2008,we isolated 13 influenza A viruses:H1N1,H3N6, H13N8 and H4N6 *** did not isolate any H5N1 subtype,that still cause epizooty in wild birds and ***:We revealed taxonomic and ecological heterogeneity of the birds involved in maintenance of circulation of influenza viruses in the given *** viruses were isolated from birds of 6 orders;among them there are species preferring water and semi-aquatic biotopes,one species preferring dry plain region,and also one species which can inhabit both dry and water ***:Representatives of all main orders of Western mongolia avifauna are involved in support of influenza A virus circulation,highly pathogenic H5N1 influenza viruses were registered in mongolia thus it’s necessary to continue permanent influenza virus surveillance in wild birds’ populations.

关键词： Influenza A virus mongolia Wild birds

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Optimal Design of Splitters Attached to Turbo Blower impeller by RSm

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Journal of Thermal Science 2012年第3期21卷 215-222页

作者： Choon-man Jang ka-Ram Choi Environmental Engineering Research Division Korea Institute of Construction Technology

This paper describes the optimization of the impeller having splitters for a turbo *** design variables,chord of splitter and pitch of splitter,are introduced to enhance the blower *** pressure and ef-ficiency are selected as an object function,and the optimization of the blower impeller is performed by a response surface method (RSm).Three-dimensional Navier-Stokes equations are introduced to analyze the internal flow of the blower and to find the value of the object function for each *** the shape optimization of the splitters attached to the impeller in the turbo blower,pressure and efficiency at the design flow condition are suc-cessively increased by 5.9 percent and 17.9 percent respectively based on the reference *** higher blower efficiency obtained by optimization of impeller having splitters is mainly caused by reducing the number of im-peller blades and optimal design of splitters in the blade passage while pressure increase keeps almost the same with the reference *** the object function of pressure,pressure increase is obtained at the design and off-design conditions while efficiency keeps higher compared to the reference *** enhancement of blow-er performance is due to the reduction of reverse and circulation flows in the blade passage.

关键词： Turbo Blower Splitter Numerical Simulation Optimal Design Pressure Response Surface method

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A murine model for human immune thrombocytopenic purpura and comparative analysis of multiple gene expression in bone marrow and spleen

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Journal of Genetics and Genomics 2008年第11期35卷 665-671页

作者： Hong Wei Xinchun Ding Jiangong Ren ka Liu Pingping Tan Daquan Li Runlin Z. ma College of Animal Science and Technology Shihezi University Shihezi 832003 China Institute of Genetics and Developmental Biology Chinese Academy of Sciences Beijing 100101 China Graduate University of Chinese Academy of Sciences Beijing 100101 China

Homeostasis of platelet number in human and other mammals is well maintained for prevention of minor bleeding and for other im- munological functions, but the exact molecular mechanism responsible for immune thrombocytopenic purpura （ITP） has not been fully understood. In an effort to identify genetic factors involved in initiation of platelet production in response to bleeding injury or platelet destruction, we have successfully generated an animal model of human ITP via intraperitoneal injection of anti-platelet antibody into the Balb/c mouse. Platelet counts were dropped dramatically in animals that received antibody injection within 4 h, maintained at the mini- mum level for a period of 44 h, started to rebound after 48 h, and reached to the maximum at 144 h （6 days）. Final homeostasis reached at approximately 408 h （17 days）, following a minor cycle of platelet number fluctuation. Using semi-quantitative RT-PCR, we assessed and compared mRNA level of CD41, c-myb, c-mpl, caspase-3, caspase-9, GATA-1, and Bcl-xl in bone marrow and spleen. Alteration of mRNA expression was correlated with the change of platelet level, and an inverse relationship was found for expression of the genes be- tween bone marrow and spleen. No transcription was detectable for any of the seven genes in bone marrow at the time when platelet number reached the maximum （144 h）. In contrast, mRNA transcripts of the seven genes were found to be at the highest level in spleen tissue. This is the first study of simultaneous detection of multiple platelet related genes in a highly reproducible ITP animal model. Our results provided the supportive evidence that expression of the above seven genes are more related to negative regulation of platelet number in spleen tissue, at least in the model animals.

关键词： immune thrombocytopenic purpura murine model semi-quantative RT-PCR

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Osteoarthritis:toward a comprehensive understanding of pathological mechanism

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Bone Research 2017年第1期5卷 1-13页

作者： Di Chen Jie Shen Weiwei Zhao Tingyu Wang Lin Han John L Hamilton Hee-Jeong im Department of Biochemistry Rush University Medical Center Department of Orthopaedic Surgery Washington University Department of Orthopaedics & Traumatology Li Ka Shing Faculty of MedicineThe University of Hong Kong Department of Pharmacy Shanghai Ninth People’s HospitalShanghai Jiao Tong University School of Medicine School of Biomedical Engineering Scienceand Health SystemsDrexel University

Osteoarthritis （OA） is the most common degenerative joint disease and a major cause of pain and disability in adult individuals. The etiology of OA includes joint injury, obesity, aging, and heredity. However, the detailed molecular mechanisms of OA initiation and progression remain poorly understood and, currently, there are no interventions available to restore degraded cartilage or decelerate disease progression. The diathrodial joint is a complicated organ and its function is to bear weight, perform physical activity and exhibit a joint-specific range of motion during movement. During OA development, the entire joint organ is affected, including articular cartilage, subchondral bone, synovial tissue and meniscus. A full understanding of the pathological mechanism of OA development relies on the discovery of the interplaying mechanisms among different OA symptoms, including articular cartilage degradation, osteophyte formation, subchondral sclerosis and synovial hyperplasia, and the signaling pathway（s） controlling these pathological processes.

关键词： OA Osteoarthritis:toward a comprehensive understanding of pathological mechanism ADAmTS NGF

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Tierexperimentelle Untersuchung zur Effektivit tder transarteriellen Chemoembolisation unter Einsatz von Poly-Laktide-co-Glykolide-mikrosph ren

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Journal of Huazhong University of Science and Technology(medical Sciences) 2002年第4期22卷 346-349页

作者：钱骏 Rntgenabteilung

Evaluierung der Effektivit t von Poly- L aktide- co- Glykolide (PL CG ) - mikrosph ren als Em bolisationsm aterial in der transarteriellen Chem oem bolisation(TACE) im tierexperimentellen *** m nnlichen ACI- Ratten(n=11) erfolgte die im plantation eines soliden morris Hepatomas(1m m3) subkapsul r in den linken L eberlappen. 13Tage nach implan- tation wurden die Tumorvolumina kernspintom ographisch bestim *** Tiere wurden in Thera- piegruppe (n =4 ) und Kontrollgruppe (n=7) geteilt. Nach L aparotomie und retrograder ka- theterisierung der Arteria gastroduodenalis wurden 4 0 mg PL CG- mikrosph ren und 0 ,0 5 m g mit- omycin in Therapiegruppe,1,5 ml 0 ,9% Kochsalzl sung in Kontrollgruppe zum Vergleich *** Effektivit tsbeurteilung der beiden methoden erfolgte14 Tage nach katheter- isierung eine erneute kernspintomographische Volumenbestimm ung der Tum *** deutliche Tumorvolumenzunahme von2 7,12 fache in Kontrollgruppe wurde im Beobachtungszeitraum gese- *** Vergleich zur Kontrollgruppe zeigte die Therapiegruppe eine sehr geringere Tumorvolu- menzunahme von 2 ,87fache im Beobachtungszeitraum . Die Tum orvolumenzunahm e zwischen der beiden Gruppen zeigten beim T- Test einen signifikanten U nterschied (Pm des L ebertum ors wurde unter Einsatz von PL CG- mikrosph ren in der TACE im tierexperi- mentellen modell deutlich gehemmt.

关键词： L eber Tumor TACE PL CG mikrosph ren

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考虑初稳心高摄动的船舶旋回性能分析

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中国航海 2019年第4期42卷 33-37页

作者：张强吕蒙蒙 im Nankyun 山东交通学院航海学院山东威海264209 木浦国立海事大学航海学院韩国木浦530729

针对船舶的初稳心高度(metacentric Height,Gm)摄动后船舶旋回性能改变引发的船舶操纵安全问题,提出一种利用自航模进行h Gm摄动下的船舶旋回性能分析方法。通过调整自航模重心高度改变Gm值,对7组不同h Gm摄动下的自航模进行旋回试验,... 详细信息

针对船舶的初稳心高度(metacentric Height,Gm)摄动后船舶旋回性能改变引发的船舶操纵安全问题,提出一种利用自航模进行h Gm摄动下的船舶旋回性能分析方法。通过调整自航模重心高度改变Gm值,对7组不同h Gm摄动下的自航模进行旋回试验,利用差分全球定位系统(Differential Global Positioning System,DGPS)采集船舶旋回运动轨迹的试验数据,再利用mATLAB工具箱将其中5组试验数据拟合出h Gm与旋回性能的关系曲线,并得出h Gm摄动与旋回性能中的进距(Advance Diameter,D A)和旋回初径(Tactical Diameter,D T)的回归公式。通过剩余2组试验数据验证该方法的有效性。试验结果表明:该分析方法误差较小,回归公式的符合度较高。本研究可根据船舶实时稳性参数预测船舶旋回性能,为船舶安全营运和智能船舶研究提供参考。

关键词：稳性参数摄动旋回性能自航模

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美国结合医学临床在全科医学领域的发展

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中国中西医结合杂志 2015年第4期35卷 394-400页

作者：张卫军许家杰洛杉矶加州大学东西医学中心美国90024

近20年来,美国结合医学临床、科研和教学均得到迅猛发展。民众的热情要求西医师能够了解互补替代医学(complementary and alternative medicine,CAm)的安全性和有效性,并能够提供临床咨询。美国的全科医学,尤其是家庭科,是最早接纳结合... 详细信息

近20年来,美国结合医学临床、科研和教学均得到迅猛发展。民众的热情要求西医师能够了解互补替代医学(complementary and alternative medicine,CAm)的安全性和有效性,并能够提供临床咨询。美国的全科医学,尤其是家庭科,是最早接纳结合医学的专业学科,因为两者诊治的疾病谱存在交叉和重叠,也强调基本相同的核心价值,如以患者为中心、循证医疗、治疗的主动性及连续性。随着结合医学全科医师项目的发展,全科医学的教育人员试图通过加入结合医学的核心要素来提高全科医学的学科能力和建设,如发展出培训课程设计指南和需掌握结合医学核心的可测量的能力指标。当前全美有超过40个全科医学项目宣称其加入CAm和结合医学的内容,同时各结合医学中心根据自己的特点也发展了具有不同特色的全科医师项目。这种以西医师为主体的结合医学从业人员结构与中国的中西医结合医学初创时相似。时值中国在强调基层西医学习中医项目之际,希望本文能提供一定的借鉴。

关键词：全科医学结合医学互补替代医学中医医疗改革

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基于船舶旋回试验的Gm摄动下横摇安全性能分析

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大连海事大学学报 2019年第4期45卷 9-13页

作者：张强葛晓芳林南均山东交通学院航海学院山东威海264209 大连海事大学交通运输工程学院辽宁大连116026 木浦国立海事大学航海学院韩国木浦530729

为提高船舶在旋回过程中的操纵安全,以旋回过程中横倾角变化趋势为研究对象,搭建自航模实验平台,进行旋回横摇实验,并配备高精度DGPS设备以获取船舶旋回运动轨迹数据.基于mATLAB软件标绘出的实验中具有横倾角变化的运动轨迹点,以及拟合... 详细信息

为提高船舶在旋回过程中的操纵安全,以旋回过程中横倾角变化趋势为研究对象,搭建自航模实验平台,进行旋回横摇实验,并配备高精度DGPS设备以获取船舶旋回运动轨迹数据.基于mATLAB软件标绘出的实验中具有横倾角变化的运动轨迹点,以及拟合出的Gm与横倾角之间的关系曲线,得出横倾角的变化规律,给出回归公式并验证其可靠性,从而可以根据船舶Gm摄动预测船舶操纵安全,为海上航行船舶操纵及海上交通运输提供了参考依据.

关键词：船舶初稳性高度(Gm) 横倾角旋回自航模

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The relation between ductility at high temperature and solid solution in mg alloys

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Journal of magnesium and Alloys 2022年第1期10卷 241-256页

作者： D.F.Shi C.m.Cepeda-Jiménez m.T.Pérez-Prado im DEA materials Institute C/Eric Ka ridel228906 GetafeMadridSpain Department of materials Science Polytechnic University of Madrid/Universidad Politecnica de MadridE.T.S.de Ingenieros de Caminos28040MadridSpain Department of Physical metallurgy CENIMCSICAv.Gregorio del Amo 828040 MadridSpain

This work investigates the effect of solid solution on ductility and on the activation of individual deformation mechanisms at moderate temperatures and at quasi-static strain rates in mg-Zn and mg-Al alloys. With that aim, four solid solution mg-Zn and mg-Al binary alloy ingots containing 1 and 2 wt.% solute atoms were subjected to hot rolling and subsequent annealing to generate polycrystals with similar average grain size and basal-type texture for each composition. The activity of the different slip systems after tensile testing at 150°C and at 250°C was evaluated in pure mg and in the alloys by EBSD-assisted slip trace analysis. In addition, segregation of Zn and Al atoms at grain boundaries during the thermo-mechanical processing was characterized by HAADF-STEm and EDX. It was found that while the addition of Al and Zn atoms to pure mg does not lead to major changes in the mechanical strength at the investigated temperatures, it does enhance ductility significantly, especially at 250℃. Our results show that this increase in ductility cannot be attributed to a higher activation of non-basal systems in the alloys, as reported earlier, as the incidence of non-basal systems is indeed considerably higher in pure mg. This work suggests, on the contrary, that the ductility increase may be attributed to the presence of a more homogenous basal activity in the alloys due to a lower degree of orientation clustering, to grain boundary solute segregation, and to a higher slip diffusivity at grain interiors.

关键词： magnesium Solute segregation Slip trace analysis Ductility Deformation mechanisms

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