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Development of Human in vitro Brain-blood Barrier Model from Induced Pluripotent Stem Cell-derived Endothelial Cells to Predict the in vivo Permeability of Drugs

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Neuroscience Bulletin 2019年第6期35卷 996-1010页

作者： Yuan Li Xueying Sun Houfu liu Liang Huang Guofeng Meng Yu Ding Wenji Su Jiaqi Lu Sophie Gong Georg C.Terstappen Ru Zhang wandong Zhang Shanghai Key Laboratory of Signaling and Disease Research Laboratory of Receptor-Based Bio-medicineCollaborative Innovation Center for Brain ScienceSchool of Life Sciences and TechnologyTongji UniversityShanghai 200092China Platform Technology&Sciences GlaxoSmithKline China R&D CentreShanghai 201203China Neurosciences Therapeutic Area Unit GlaxoSmithKline China R&D CentreShanghai 201203China Human Health Therapeutics Research Centre National Research Council of Canada Faculty of Medicine University of OttawaOttawa K1A0R6Canada

An in vitro blood-brain barrier(BBB) model is critical for enabling rapid screening of the BBB permeability of the drugs targeting on the central nervous *** many models have been developed, their reproducibility and renewability remain a challenge. Furthermore, drug transport data from many of the models do not correlate well with the data for in vivo BBB drug ***-pluripotent stem cell(i PSC) technology provides reproducible cell resources for in vitro BBB ***, we generated a human in vitro BBB model by differentiating the human i PSC(hi PSC) line GM25256 into brain endothelial-type cells. The model displayed BBB characteristics including tight junction proteins(ZO-1,claudin-5, and occludin) and endothelial markers(von Willebrand factor and Ulex), as well as high transendothelial electrical resistance(TEER)(1560 ***2±230 ***2) and c-GTPase activity. Co-culture with primary rat astrocytes significantly increased the TEER of the model(2970 ***2 to 4185 ***2). RNAseq analysis confirmed the expression of key BBB-related genes in the hi PSC-derived endothelial cells in comparison with primary human brain microvascular endothelial cells,including P-glycoprotein(Pgp) and breast cancer resistant protein(BCRP). Drug transport assays for nine CNS compounds showed that the permeability of non-Pgp/BCRP and Pgp/BCRP substrates across the model was strongly correlated with rodent in situ brain perfusion data for these compounds(R2= 0.982 and R2= 0.9973,respectively), demonstrating the functionality of the drug transporters in the model. Thus, this model may be used to rapidly screen CNS compounds, to predict the in vivo BBB permeability of these compounds and to study the biology of the BBB.

关键词： Blood-brain barrier Drug transport Induced pluripotent stem cell Cell differentiation Prediction of in vivo permeability

Evaluation of the risk factors for severe complications and surgery of intestinal foreign bodies in adults:a single-center experience with 180 cases

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Gastroenterology Report 2022年第1期10卷 420-429页

作者： Tingting Hu Jie Zhang Yang liu Lifang Chen Wei Cen Wenzhi Wu Qingke Huang Xuecheng Sun Simon Stock Maddalena Zippi Vincent Zimmer Zarrin Basharat wandong Hong Department of Gastroenterology and Hepatology The First Affiliated Hospital of Wenzhou Medical UniversityWenzhouZhejiangP.R.China Department of Otolaryngology The First Affiliated Hospital of Wenzhou Medical UniversityWenzhouZhejiangP.R.China Department of Radiology The First Affiliated Hospital of Wenzhou Medical UniversityWenzhouZhejiangP.R.China The First Clinical College Wenzhou Medical UniversityWenzhouZhejiangP.R.China Department of Surgery World Mate Emergency HospitalBattambangCambodia Unit of Gastroenterology and Digestive Endoscopy Sandro Pertini HospitalRomeItaly Department of Medicine II Saarland University Medical CenterSaarland UniversityHomburgGermany Jamil-ur-Rahman Center for Genome Research Dr.Panjwani Center for Molecular Medicine and Drug ResearchInternational Center for Chemical and Biological SciencesUniversity of KarachiKarachiPakistan

Background Foreign bodies(FBs)lodged in the intestine or causing intestinal complications are uncommon in clinical practice but may pose diagnostic difficulties and prove *** study aimed to evaluate the risk factors for severe complications and surgery to aid clinicians in the diagnosis and management of intestinal *** We performed a retrospective analysis of patients in whom FBs were lodged in the intestine or caused complications from 2010 to 2020 in the First Affiliated Hospital of Wenzhou Medical University(Zhejiang,China).The characteristics of the patients and FBs,symptoms,imaging findings,diagnostics,treatment strategies,and clinical outcomes were ***,the risk factors for complications and surgery were *** In total,180 patients were included in our *** patients(76.1%)were unable to provide a history of *** were the most common FBs(35.6%).The FBs were mainly located in the duodenum(32.8%)and the ileum(27.8%).Surgical removal of FBs was successful in 89(49.4%)patients and endoscopic removal in 54(30.0%)*** with perforations were treated *** located in the jejunum or ileum were more likely to cause severe complications than those located in the *** located in the jejunum,ileum,or sigmoid colon were more likely to undergo surgery,and severe complications were an independent risk factor for *** Intestinal FBs,often localized in angulation,are likely to be misdiagnosed because most patients do not provide a history of FB *** and endoscopic therapy are the most commonly used treatment *** is not mandatory in clinically stable patients with small and contained *** located in the jejunum or ileum are risk factors for both complications and surgery.

关键词： complication foreign body intestine risk factor surgery

Mechanism studies of Xinfeng capsule on improving cardiovascular function though toll-like receptor 4/nuclear factor kappa B pathway in a rat model of adjuvant arthritis

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Journal of Traditional Chinese Medicine 2017年第1期37卷 116-123页

作者： Wang Yuan liu Jian Huang Chuanbing Sun Yue Zhang wandong Wan Lei Zong Ruikai Wang Yali Department of Rheumatology First Affiliated HospitalAnhui University of Traditional Chinese MedicineHefei 230038China Graduate Faculty Anhui University of Traditional Chinese MedicineHefei 230038China

OBJECTIVE: To observe the impact of Xinfeng capsule(XFC) on cardiovascular function in adjuvant arthritis(AA) model rats and investigate the mechanism though toll-like receptor 4(TLR4)/nuclear factor kappa B(NF-κB) signaling ***: Seventy rats were randomly divided into seven groups: normal control(NC), model control(MC), tripterygium glycosides tablet(TPT),methotrexate(MTX), high, moderate and low dose XFC group. The administration began from day 19 after modeling for 30 day. Paw swelling, arthritic in-dex(AI), cardiac function indexes and myocardial pathological pattern were detected. The expression of TLR4, myeloid differentiation factor(My D) 88, interleukin-1 receptor-associated kinase(IRAK) 1, tumor necrosis factor receptor associated factor(TRAF) 6, NF-κB, tumor necrosis factor-alpha(TNF-α) proteins in myocardial tissue were determined by western blot ***: Paw swelling and AI in MC group increased in MC group(P 0.05). Left ventricular systolic pressure(LVSP),left ventricular end-diastolic pressure(LVEDP),heart rate(HR) were elevated in MC group(P <0.01), and ± dp/dtmax and CI were reduced(P <0.01); while LVSP, LVEDP and HR declined and ±dp/dtmax, CI improved in high dose XFC group(P <0.05 or P < 0.01). LVSP in high dose XFC group were reduced more than other treatment groups(P <0.05 or P < 0.01). The improvements on LVEDP, dp/dt-max were superior to MTX and low dose XFC group, and the improvement on CI was better than low dose XFC group(P < 0.05 or P < 0.01). Myocardial fibers arranged irregular in MC group with intracellular edema and mitochondria damage. The modifications on myocardial structural were shown in each treatment group, but more prominent in TPT, high and moderate dose XFC group. The proteins of TLR4, My D88, IRAK1, TRAF6, NF-κB, TNF-αwere highly expressed in MC group, and those proteins declined in high and moderate dose XFC group(P < 0.05 or P < 0

关键词： Arthritis experimental Cardiovascular diseases Toll-like receptor 4 NF-kappa B Signal transduction Xinfeng capsule

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长输供热管道经济比摩阻的影响因素分析

区域供热 2024年第2期 103-110页

作者：赵江栋臧洪泉李亚男陈向荣贺凯刘禹郑万冬万志豪中铁三局集团投资有限公司山西太原030001 中国市政工程华北设计研究总院有限公司第六设计研究院天津300381 呼和浩特市长输供热有限公司内蒙古呼和浩特010030 天津大学环境科学与工程学院天津300350

为推动大面积清洁供暖,分布式燃煤、燃气锅炉房逐步被热电联产所取代。与热电联产配套的长输供热管道成为常见的一种供热设备。长输供热管道比摩阻的选取,在项目建设运行经济性上起到重要的作用。以呼和浩特市某一长输供热管道工程项目... 详细信息

为推动大面积清洁供暖,分布式燃煤、燃气锅炉房逐步被热电联产所取代。与热电联产配套的长输供热管道成为常见的一种供热设备。长输供热管道比摩阻的选取,在项目建设运行经济性上起到重要的作用。以呼和浩特市某一长输供热管道工程项目为例,采用单因素分析法,探究了不同工程参数对经济比摩阻的影响。计算结果显示该工程的实际最佳经济比摩阻为22.8 Pa/m。以实际工程为例,详细分析了经济比摩阻的优化过程,同时分析了各因素对经济比摩阻的影响程度,供热温差对经济比摩阻的影响最大,供热负荷次之,供热年限最小。因此在设计经济比摩阻时,应着重考虑工程项目的供热温差。

关键词：长输管道经济比摩阻供热温差

Biochemical and behavioral characterization of the double transgenic mouse model (APPswe/PS1dE9) of Alzheimer’s disease

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Neuroscience Bulletin 2011年第4期27卷 221-232页

作者： Huaqi XIONG Debbie Callaghan Jolanta Wodzinska Jiejing XU Maryna Premyslova Qing-Yan liu John Con- nelly wandong ZHANG 加拿大国家科学院生物科学研究所神经生物学系渥太华安大略省加拿大 ApoPharma公司多伦多安大略省加拿大

Objective The double transgenic mouse model （APPswe/PSldE9） of Alzheimer＇s disease （AD） has been widely used in experimental studies. β-Amyloid （Aβ） peptide is excessively produced in AD mouse brain, which affects synaptic function and the development of central nervous system. However, little has been reported on characterization of this model. The present study aimed to characterize this mouse AD model and its wild-type counterparts by biochemical and functional approaches. Methods Blood samples were collected from the transgenic and the wild-type mice, and radial arm water maze behavioral test was conducted at the ages of 6 and 12 months. The mice were sacrificed at 12-month age. One hemisphere of the brain was frozen-sectioned for immunohistochemistry and the other hemisphere was dissected into 7 regions. The levels ofAβ1-40, Aβ1-42 and 8-hydroxydeoxyguanosine （8-OHdG） in blood or/and brain samples were analyzed by ELISA. Secretase activities in brain regions were analyzed by in vitro assays. Results The pre-mature death rate of transgenic mice was approximately 35% before 6-month age, and high levels of Aβ1-40 and Aβ1-42 were detected in these dead mice brains with a ratio of 1 ： 1 0. The level of blood-borne Aβ at 6-month age was similar with that at 12-month age. Besides, Aβ1-40 level in the blood was significantly higher than Aβ1-42 level at the ages of 6 and 12 months （ratio 2.37：1）. In contrast, the level of Aβ1-42 in the brain （160.6 ng/mg protein） was higher than that of Aβ1-40 （74 ng/mg protein）（ratio 2.17：1）. In addition, the levels of Aβ1-40 and Aβ1-42 varied markedly among different brain regions. Aβ1-42 level was significantly higher than Aβ1-40 level in cerebellum, frontal and posterior cortex, and hippocampus. Secretase activity assays did not reveal major differences among different brain regions or between wild-type and transgenic mice, suggesting that the transgene PS1 did not lead to higher 7-secretase activity but was more efficient in produ

关键词： mouse model Alzheimer's disease β-amyloid peptides secretase activities DNA oxidative damage behavioral test

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采用并行遗传算法的文本分割研究

西安交通大学学报 2009年第12期43卷 40-44页

作者：赵煜蔡皖东樊娜刘念西北工业大学计算机学院西安710072 西安建筑科技大学图书馆西安710055

针对短篇幅文本数据稀疏的特性,提出了一种利用外部语料库知识提高短篇幅文本分割准确率的方法.该方法分2个步骤完成:①利用Gibbs采样方法估计语料库对应的潜在狄利克雷分配(LDA)模型,并利用该模型推断目标文本的潜在语义结构信息;②通... 详细信息

针对短篇幅文本数据稀疏的特性,提出了一种利用外部语料库知识提高短篇幅文本分割准确率的方法.该方法分2个步骤完成:①利用Gibbs采样方法估计语料库对应的潜在狄利克雷分配(LDA)模型,并利用该模型推断目标文本的潜在语义结构信息;②通过定义语义段落内凝聚性和语义段落间发散性2个目标函数,将文本分割问题转化为多目标优化问题.采用一种针对文本分割的并行遗传算法,获得全局最优解.通过实验,在文本数据稀疏的情况下,该算法在准确率方面优于多元判别分析(MDA)方法和基于LDA的文本分割方法,对于提高文本分割的准确率是可行和有效的.

关键词：中文信息处理文本分割遗传算法

基于双容错编码的DP-RAID数据布局研究

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西北工业大学学报 2006年第2期24卷 219-223页

作者：刘卫平蔡皖东任建奇西北工业大学计算机学院陕西西安710072

基于单容错编码的数据布局已经不能满足存储系统对可靠性越来越高的要求,而现有的基于多容错编码的数据布局普遍存在编码解码复杂,计算负载大等缺点。文中设计了一种基于双奇偶校验的双容错数据布局DP-RA ID。该布局只需要在磁盘数量为... 详细信息

基于单容错编码的数据布局已经不能满足存储系统对可靠性越来越高的要求,而现有的基于多容错编码的数据布局普遍存在编码解码复杂,计算负载大等缺点。文中设计了一种基于双奇偶校验的双容错数据布局DP-RA ID。该布局只需要在磁盘数量为素数的RA ID 5阵列系统中增加1个校验磁盘,通过水平和对角方向的双重奇偶校验实现双容错。该布局的双重校验条纹长度相同,结构简单,易于实现。而且该布局的编码解码算法简单,计算负载小。研究表明该布局与RA ID 5相比,写操作性能会有少许的下降,读操作性能不变,而可靠性大幅度提高。

关键词： RAID 奇偶校验双容错编码可靠性

Viral receptor profiles of masked palm civet revealed by single-cell transcriptomics

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Journal of Genetics and Genomics 2022年第11期49卷 1072-1075页

作者： Peiwen Ding Haoyu Wang Jiacheng Zhu Fuyu An Jinqian Xu Xiangning Ding Lihua Luo Weiying Wu Qiuyu Qin Yanan Wei wandong Zhao Zhiyuan Lv Haimeng Li Yixin Zhu Meiling Li Wensheng Zhang Yanan Zhang Zhihua Ou Huan liu Yan Hua College of Life Sciences University of Chinese Academy of SciencesBeijing 100049China BGI-Shenzhen ShenzhenGuangdong 518083China Guangdong Provincial Key Laboratory of Silviculture Protection and UtilizationGuangdong Academy of ForestryGuangzhouGuangdong 510520China Department of Neurobiology NHC and CAMS Key Laboratory of Medical NeurobiologySchool of Brain Science and Brian Medicineand the MOE Frontier Science Center for Brain Research and Brain–Machine IntegrationZhejiang University School of MedicineHangzhouZhejiang 310012China School of Basic Medicine Qingdao UniversityQingdaoShandong 266071China School of Basic Medical Sciences Binzhou Medical UniversityYantaiShandong 264003China Tsinghua-Berkeley Shenzhen Institute Tsinghua UniversityShenzhenGuangdong 518000China Shenzhen Key Laboratory of Unknown Pathogen Identification BGI-ShenzhenShenzhenGuangdong 518083China

Civets are small mammals belonging to the family *** masked palm civets(Paguma larvata)served as an intermediate host in the bat-to-human transmission of severe acute respiratory syndrome coronavirus(SARS-Co V)in 2003(Guan et al.,2003).Because of their unique role in the SARS outbreak,civets were suspected as a potential intermediate host of SARS-Co V-2.

关键词： Vive mask intermediate

一种基于iSCSI的网络RAID设计与实现

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计算机工程与应用 2006年第14期42卷 162-164,168页

作者：刘卫平蔡皖东西北工业大学计算机学院西安710072

RAID是存储系统的基础和关键部件,它通过数据分布存储、并行访问以及信息冗余等技术,极大地扩大了存储容量、增强了I/O请求处理能力、提高了数据可靠性。论文将RAID的思想扩展到了分布的存储网络环境之中,设计了一种基于iSCSI的网络RAI... 详细信息

RAID是存储系统的基础和关键部件,它通过数据分布存储、并行访问以及信息冗余等技术,极大地扩大了存储容量、增强了I/O请求处理能力、提高了数据可靠性。论文将RAID的思想扩展到了分布的存储网络环境之中,设计了一种基于iSCSI的网络RAID系统,实现了系统原型,并对该系统进行了性能测试和分析。结果表明,该系统可以通过并行数据读写提高存取速度,通过奇偶校验技术提高数据的可靠性。

关键词： iSCSI 存储网络 RAID