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Long-term correction of hemorrhagic diathesis in hemophilia A mice by an AAV-delivered hybrid FⅧcomposed of the human heavy chain and the rat light chain

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Frontiers of Medicine 2022年第4期16卷 584-595页

作者： Jianhua Mao Yun Wang Wei Zhang Yan Shen Guowei Zhang Wenda xi Qiang Wang Zheng Ruan Jin Wang xiaodong xi Shanghai Institute of Hematology State Key Laboratory of Medical GenomicsCollaborative Innovation Center of HematologyRuijin Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghai 200025China Shanghai Institute of Hematology State Key Laboratory for Medical Genomics and Department of HematologyCollaborative Innovation Center of Systems BiomedicinePôle SinoFrançais des Sciences du Vivant et GenomiqueRuijin Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghai 200025China Research Center for Experimental Medicine Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghai 200025China The School of Medicine Hangzhou Normal UniversityHangzhou 310036China Shanghai Institute of Hypertension Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghai 200025China

Conventional therapies for hemophilia A(HA)are prophylactic or on-demand intravenous FⅧinfusions.However,they are expensive and inconvenient to perform.Thus,better strategies for HA treatment must be developed.In this study,a recombinant FⅧcDNA encoding a human/rat hybrid FⅧwith an enhanced procoagulant potential for adeno-associated virus(AAV)-delivered gene therapy was developed.Plasmids containing human FⅧheavy chain(hHC),human light chain(hLC),and rat light chain(rLC)were transfected into cells and hydrodynamically injected into HA mice.Purified AAV viruses were intravenously injected into HA mice at two doses.Results showed that the hHC+rLC protein had a higher activity than the hHC+hLC protein at comparable expression levels.The specific activity of hHC+rLC was about 4-to 8-fold higher than that of their counterparts.Hydrodynamic injection experiments obtained consistent results.Notably,the HA mice undergoing the AAV-delivered hHC+rLC treatment exhibited a visibly higher activity than those treated with hHC+hLC,and the therapeutic effects lasted for up to 40 weeks.In conclusion,the application of the hybrid FⅧ(hHC+rLC)via an AAV-delivered gene therapy substantially improved the hemorrhagic diathesis of the HA mice.These data might be of help to the development of optimized FⅧexpression cassette for HA gene therapy.

关键词： hemophilia A adeno-associated virus(AAV) human/rat hybrid factorⅧ gene therapy dual chain strategy

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Recent advances in the understanding of the molecular mechanisms regulating platelet integrin αIIbβ3 activation

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Protein & Cell 2010年第7期1卷 627-637页

作者： Lanlan Tao Yue Zhang xiaodong xi Nelly Kieffer Sino-French Research Center for Life Sciences and Genomics(CNRS/LIA-124) Ruijin HospitalShanghai Jiaotong University School of MedicineShanghai 200025China State Key Laboratory of Medical Genomics and Shanghai Institute of Hematology Ruijin HospitalShanghai Jiaotong University School of MedicineShanghai 200025China

Integrins are allosteric cell adhesion receptors that cycle from a low to a high affinity ligand binding state,a complex process of receptor activation that is of particular importance in blood cells such as platelets or leukocytes.Here we highlight recent progress in the understanding of the molecular pathways that regulate integrin activation in platelets and leukocytes,with a special focus on the structural changes in platelet integrinαIIbβ3 brought about by key intracellular proteins,namely talin and kindlins,that are of crucial importance in the regulation of integrin function.Evidence that the small GTPase Rap1 and its guanine exchange factor CalDAG-GEF1,together with RIAM,a Rap1GTP adaptor protein,promote the interaction of talin with the integrinβsubunit,has greatly contributed to fill the gap in our understanding of the signaling pathway from G-coupled agonist receptors and their phospholipase C-dependant second messengers,to integrin activation.Studies of patients with the rare blood cell disorder LAD-III have contributed to the identification of kindlins as new co-regulators of the talin-dependent integrin activation process in platelets and leukocytes,underlining the relevance for the in-depth investigation of patients with rare genetic blood cell disorders.

关键词： activation β3 rare

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城市轨道交通多系统耦合仿真实现方法研究

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智慧轨道交通 2024年第2期61卷 56-62页

作者：奚笑冬上海地铁维护保障有限公司上海201100

随着城市地铁线路运营规模的增加和运行时间的增长,节能降耗、运营维护、改造升级等一系列问题越来越不可被忽视。仿真技术一直是轨道交通行业研发生产过程中的重要手段,是实现大型复杂产品数字化的重要基础,在优化系统参数、缩短开发... 详细信息

随着城市地铁线路运营规模的增加和运行时间的增长,节能降耗、运营维护、改造升级等一系列问题越来越不可被忽视。仿真技术一直是轨道交通行业研发生产过程中的重要手段,是实现大型复杂产品数字化的重要基础,在优化系统参数、缩短开发周期、节约设计及验证成本等方面发挥重要作用。在过去的研发生产过程中,各专业往往更关注于本专业、本系统的功能仿真分析,将其他相关专业做理想化的简化处理,很少有统一考虑列车、牵引供电、信号、运行调度等系统相互耦合特性的综合仿真平台。文章针对上海地铁运维中面临的实际问题,从线路运营角度出发,基于目前主流的仿真技术,并考虑未来平台的可扩展性,搭建一种综合仿真平台,实现城轨“多专业、多系统”集成层面,车辆、信号、供电三大专业多个核心子系统的耦合仿真。通过上海地铁某线路耦合仿真计算结果和实际运行数据的对比,证明了所提出的多系统耦合仿真方法的正确性。

关键词：城市轨道交通多系统耦合仿真数字化模型数字化测试

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基于改进YOLOv8模型的弓网燃弧视觉检测

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机械设计与制造工程 2024年第3期53卷 102-106页

作者：奚笑冬上海地铁维护保障有限公司上海200025

针对燃弧视觉检测中遮挡下目标尺寸过小的问题,设计了一种基于BiFormer注意力机制的非接触式弓网燃弧视觉检测算法,增强了识别燃弧小目标的表征学习能力。首先,基于目标检测,引入了经典目标检测算法YOLOv8,搭建了一种用于检测弓网燃弧... 详细信息

针对燃弧视觉检测中遮挡下目标尺寸过小的问题,设计了一种基于BiFormer注意力机制的非接触式弓网燃弧视觉检测算法,增强了识别燃弧小目标的表征学习能力。首先,基于目标检测,引入了经典目标检测算法YOLOv8,搭建了一种用于检测弓网燃弧的视觉检测平台;其次,为了提高计算效率,将BiFormer注意力机制引入到YOLOv8模型中,并将Focal-EIoU应用到损失函数中,以增强系统对燃弧小目标的检测能力,提升对燃弧特征的判别性能;最后,在不同地铁工况下对该方法的有效性进行了实验验证。

关键词：地铁弓网燃弧小目标检测 BiFormer注意力机制 YOLOv8

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基于目标检测和三维重建的弓网燃弧检测方法

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城市轨道交通研究 2024年第S1期27卷 1-6,17页

作者：奚笑冬吴丽李世江上海地铁维护保障有限公司上海200235 中国科学院上海微系统与信息技术研究所上海200050

[目的]为提高弓网燃弧检测准确率,针对背景噪声和亮度变化的鲁棒性较弱,以及受到隧道光源、日光、接触线反光及其他异物干扰等问题,提出了一种基于目标检测和三维重建的弓网燃弧检测方法。[方法]首先,采用双目相机的图像获取模块对受电... 详细信息

[目的]为提高弓网燃弧检测准确率,针对背景噪声和亮度变化的鲁棒性较弱,以及受到隧道光源、日光、接触线反光及其他异物干扰等问题,提出了一种基于目标检测和三维重建的弓网燃弧检测方法。[方法]首先,采用双目相机的图像获取模块对受电弓和接触网进行拍摄,获取微秒级实时同步的两幅受电弓与接触网图像;其次,将经过预处理后的图像送入第一检测模块,即进行受电弓与接触网的接触区域以及受电弓与接触网接触点的目标检测;再次,将图像送入燃弧第二检测模块,实现双目图像中的燃弧目标检测;最后,对检测出双目图像中的燃弧进行三维重建,得到燃弧空间三维坐标,用于计算燃弧和受电弓与接触网的接触点的距离,并根据距离滤除错误结果。通过构建YOLOv5-3DR算法模型,对所研制双目立体视觉模块进行试验验证。[结果及结论]所提出的检测方法对复杂应用场景有更好的适应力,能够精准识别燃弧。采用所提出的方法能够极大提高弓网燃弧检测准确率。

关键词：城市轨道交通接触网受电弓燃弧检测目标检测三维重建

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Roles of integrin β3 cytoplasmic tail in bidirectional signal transduction in a trans-dominant inhibition model

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Frontiers of Medicine 2016年第3期10卷 311-319页

作者： Jiansong Huang Yulan Zhou xiaoyu Su Yuanjing Lyu Lanlan Tao xiaofeng Shi Ping Liu Zhangbiao Long Zheng Ruan Bing xiao Wenda xi Quansheng Zhou Jianhua Mao xiaodong xi State Key Laboratory of Medical Genomics Shanghai Institute of Hematology Collaborative Innovation Center of Hematology Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine Shanghai 200025 China Institute of Hematology The First Affiliated Hospital School of Medicine Zhejiang University Hangzhou 310003 China Department of Hematology The First Affiliated Hospital of Nanchang University Nanchang 330006 China Department of Hematology Affiliated Hospital of Jiangsu University Zhenjiang 212001 China Department of Pediatrics Renji Hospital Shanghai Jiao Tong University School of Medicine Shanghai 200001 China Department of Hematology Peking Union Medical College Hospital Chinese Academy of Medical Sciences & Peking Union Medical College Beijing 100073 China Shanghai Institute of Hypertension Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine Shanghai 200025 China Cyrus Tang Hematology Center Jiangsu Institute of Hematology 2011 Collaborative Innovation Center of Hematology Soochow University Suzhou 215123 China Sino-French Research Centre for Life Sciences and Genomics Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine Shanghai 200025 China

We evaluated the roles of calpain cleavage-related mutations of the integrin β3 cytoplasmic tail in integrin αIIbβ3 bidirectional signaling using a trans-dominant inhibition model. Chimeric Tac-β3 proteins （i.e., Tac-β3, Tac-β3△741, Tac-β3△747, Tac-β3△754, Tac-β3△759, and Tac-β3ANITY） consisting of the extracellular and transmembrane domains of human IL-2 receptor （Tac） and the human integrin β3 cytoplasmic domain were stably expressed in the 123 CHO cells harboring human glycoprotein Ib-IX and wild-type integrin uIIbβ3. The different cells were assayed for stable adhesion and spreading on immobilized fibrinogen, and for binding soluble fibrinogen representing outside-in and inside-out signaling events, respectively. The chimeric protein Tac-β3 inhibited, and Tac-β3△NITY partially attenuated stable adhesion and spreading. Tac-β3, Tac-β3△759, Tac-β3ANITY, and Tac-β3△754, but not Tac-β3△747 or Tac-β3△741, impaired the soluble fibrinogen binding. Results indicated that the bidirectional signaling was significantly inhibited by Tac-β3△ and Tac-β3ANITY, albeit to a much lesser extent. Moreover, only inside-out signaling was impaired in the 123/Tac-β3△759 and 123/Tac-β3△754 cells in contrast to an intact bidirectional signaling in the 123/Tac-β3△747 and 123/Tac-β3△741 cells. In conclusion, the calpain cleavage of integrin β3 resulted in the regulatory effects on signaling by interrupting its interaction with cytoplasmic proteins rather than altering its conformation, and may thus regulate platelet function.

关键词： integrin β3 signal transduction tmns-dominant inhibition model

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基于YOLOv8模型和LSD算法的列车接触网腕臂识别

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机械设计与制造工程 2024年第2期53卷 125-129页

作者：奚笑冬顾正隆上海地铁维护保障有限公司上海200025

针对列车接触网腕臂视觉检测中存在识别精度低、速度慢及腕臂图像易模糊的问题,设计了一种基于YOLOv8模型与LSD算法的接触网腕臂检测系统。首先,引入了YOLOv8目标检测模型,搭建了一种用于检测列车腕臂位置的视觉检测平台;其次,基于HIS... 详细信息

针对列车接触网腕臂视觉检测中存在识别精度低、速度慢及腕臂图像易模糊的问题,设计了一种基于YOLOv8模型与LSD算法的接触网腕臂检测系统。首先,引入了YOLOv8目标检测模型,搭建了一种用于检测列车腕臂位置的视觉检测平台;其次,基于HIS颜色空间和图像滤波技术,对图像进行了增强处理,提升了腕臂识别的准确度;然后,基于LSD算法,完成了对接触网腕臂线段信息的提取;最后,根据现场采集的列车接触网图像,对算法的有效性进行了腕臂正反架识别实验验证。

关键词：接触网腕臂 YOLOv8 运动模糊图像增强 LSD算法

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A rare case of B-lymphoproliferative disorder with villous lymphocytes harboring t（8;14）（q24;q32） translocation

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Frontiers of Medicine 2018年第3期12卷 324-329页

作者： xiaofeng Shi Rong Ba Haiyan You Qian Jiang Jiansong Huang Jianhua Mao Lanxiu Han Shuo Zhang Qin Zhuang xianqiu Yu Lixia Wang Yun Wang Dongya Li Wei Zhu Yong Zhang Yan Zhu xiaodong xi Department of Hematology Affiliated Hospital of Jiangsu University Zhenjiang 212001 China The Center of Thrombosis Affiliated Hospital of Jiangsu University Zhenjiang 212001 China State Key Laboratory of Medical Genomics Shanghai Institute of Hematology Collaborative Innovation Center of Hematology Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine Shanghai 200025 China Institute of Hematology The First Affiliated Hospital School of Medicine Zhejiang University Hangzhou 310003 China School of Medicine Jiangsu University Zhenjiang 212013 China Blood Cell Development and Function Program Fox Chase Cancer Center 333 Cottman Avenue Room 364 Philadelphia PA 19111-2497 USA

Splenic lymphoma with villous lymphocytes （SLVL） or splenic marginal zone lymphoma with circulating villous lymphocytes is rare, and prolymphocytic transformation of SLVL is rarer. At present, only one case of SLVL with t（8;14）（q24;q32） translocation has been reported. In this study, we report a case of B- lymphoproliferative disorder with villous lymphocytes harboring t（8;14）（q24;q32） chromosome translocation that we inclined to SLVL with a prolymphocytic transformation. A 73-year-old female showed marked hepatosplenomegaly and high lymphocytosis （lymphocytes 〉 200 × 10^9/L）. The abnormal lymphocytes had short coarse villi and round nuclei with prominent nucleoli. The immunophenotypes showed CD19^＋, CD20^＋, HLA- DR^＋, CD22^＋, CD5^＋, Kappa^＋, CD25^dim, CD71^dim, Lambda, CD7, CD10-, CD23 , CD34, CD33, CD13 , CD14, CDll7, CD64, CD103, and CD11c-. The karyotype showed complex abnormality： 46XX,＋ 3,-10, t（8;14）（q24; q32）lll]/46XX[9]. The cytoplasmic projection, immunological characteristics, and trisomy 3 chromosome abnormality supported the diagnosis of SLVL. However, the presence of prominent nucleoli and high lymphocytosis suggested prolymphocytic transformation, probably as a result of t（8,14） chromosome translocation. In this report, we described an unusual case of B-lymphoproliferative disorder with villous lymphocytes harboring t（8;14）（q24;q32） translocation, which could provide help in the diagnosis and differential diagnosis of B-lymphocytic proliferative diseases.

关键词： splenic lymphoma with villous lymphocytes splenic marginal zone lymphoma transformation chromosometranslocation

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Preparation,characterization and catalytic behavior of hierachically porous CuO/α-Fe_2O_3/SiO_2 composite material for CO and o-DCB oxidation

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Journal of Natural Gas Chemistry 2011年第6期20卷 618-622页

作者： xiaodong Ma xi Feng Xuan He Hongwen Guo Lu Lu Key Laboratory of Environmental Pollution Process and Standard Ministry of Education Tianjin Key Laboratory of Environmental Remediation and Pollution Control College of Environmental Science and Engineering Nankai University Tianjin 300071 China

Hierachically porous （HP） CuO/α-Fe2O3/SiO2 composite material was fabricated by sol-gel method and multi-hydrothermal processes using HP-SiO2 as support.The resulting material was characterized by N2 adsorption-desorption,X-ray diffraction and scanning electron microscopy.The as-prepared CuO/Fe2O3/HP-SiO2 sample,with α-Fe2O3 and CuO nanocrystals,possessed a co-continuous skeleton,through-macroporous and mesoporous structure.Its catalytic behavior for CO and o-DCB oxidation was investigated.The result showed that CuO/Fe2O3/HP-SiO2 catalyst exhibited high catalytic activity for both CO and o-DCB oxidation,indicating its potential application in combined abatement of CO and chlorinated volatile organic compounds.

关键词： CO and o-DCB oxidation hierachically porous CuO/α-Fe2O3/HP-SiO2 monolith

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Effects of acid deposition control in China:a review based on responses of subtropical forests

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Frontiers of Environmental Science & Engineering 2024年第6期18卷 115-126页

作者： Danni xie xiaodong Ge Lei Duan Jan Mulder School of Land Engineering Chang’an UniversityXi’an 710064China State Key Laboratory of Environmental Simulation and Pollution Control School of EnvironmentTsinghua UniversityBeijing 100084China State Environmental Protection Key Laboratory of Sources and Control of Air Pollution Complex Beijing 100084China Faculty of Environmental Sciences and Natural Resource Management Norwegian University of Life SciencesBox 5003NO-1432ÅsNorway

For many decades,acid deposition used to pose a significant regional air pollution challenge in China.After substantial emission control of anthropogenically derived sulfur and nitrogen containing gasses,both sulfur and nitrogen deposition,as well as the acid rain-affected area,have significantly decreased compared to their peak levels.Forests,particularly in the humid subtropics,are sensitive to acid deposition,as evidenced by soil acidification,sulfate and nitrate leaching in stream water,and elevated soil nitrous oxide emission.Reduction in the total deposition of sulfur and nitrogen,caused a significant decline in sulfate and nitrate leaching from subtropical forest and subsequently in sulfate and nitrate concentrations in stream water,although there was about a 5-year delay.This delay may be attributed to the desorption of accumulated sulfate and continued elevated mineralization of accumulated nitrogen pools.Emissions of nitrous oxide,a potent greenhouse gas,also declined in nitrogen-saturated subtropical forest soils,as soil water nitrate concentration decreased.Therefore,subtropical forests in China suffering from elevated acid deposition have begun to recover.Yet,the current levels of sulfur and nitrogen deposition continue to exceed the critical loads,i.e.,the assigned threshold levels in accordance with emission control policies,in more than 10%of the country’s land area,respectively,indicating remaining risks of acidification and eutrophication.Thus,further emission reductions are urgently needed,also because they will help achieving goals related to air quality and nitrous oxide emissions.

关键词： Acidification Critical load Nitrous oxide Surface water chemistry Recovery

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