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Comparative pluripotency analysis of mouse embryonic stem cells derived from wild-type and infertile hermaphrodite somatic cell nuclear transfer blastocysts

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Chinese science Bulletin 2008年第23期53卷 3648-3655页

作者： fan Yong TONG Man ZHAO ChunLi DING ChenHui HAO Jie LV Zhuo DAI XiangPeng HAI Tang LI XueMei yao RuQiang YU Yang LI ZanDong WANG Liu ALICE Jouneau ZHOU Qi State Key Laboratory of Reproductive Biology Institute of Zoology Chinese Academy of Sciences Beijing 100101 China Department of Biochemistry and Molecular Biology College of Biological Sciences China Agricultural University Beijing 100094 China Joint Laboratory of Biology of Embryonic Cells of Mammalians (LABIOCEM) Institute of Zoology Chinese Academy of Sciences Beijing 100101 China Graduate University of Chinese Academy of sciences Beijing 100049 China INRA UMR 1198 ENVA CNRS FRE 2857 Biologie du Developpement et Reproduction Jouy en Josas F-78350 France

Therapeutic cloning, whereby embryonic stem cells (ESCs) are derived from patient-specific cloned blastocysts via somatic cell nuclear transfer (SCNT), holds great promise for treating many human diseases using regenerative medicine. Teratoma formation and germline transmission have been used to confirm the pluripotency of mouse stem cells, but human embryonic stem cells (hESCs) have not been proven to be fully pluripotent owing to the ethical impossibility of testing for germ line transmission, which would be the strongest evidence for full pluripotency. Therefore, formation of differentiated cells from the three somatic germ layers within a teratoma is taken as the best indicator of pluripotency in hESC lines. The possibility that these lines lack full multi-or pluripotency has not yet been evaluated. In this study, we established 16 mouse ESC lines, including 3 genetically defective nuclear transfer- ESC (ntESC) lines derived from SCNT blastocysts of infertile hermaphrodite F1 mice and 13 ntESC lines derived from SCNT blastocysts of normal F1 mice. We found that the defective ntESCs expressed all in vitro markers of pluripotency and could form teratomas that included derivatives from all three germ layers, but could not be transmitted via the germ line, in contrast with normal ntESCs. Our results indicate that teratoma formation assays with hESCs might be an insufficient standard to assess full pluripotency, although they do define multipotency to some degree. More rigorous standards are required to assess the safety of hESCs for therapeutic cloning.

关键词：体细胞核转移胚胎干细胞生物疗法雌雄同体

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高密度立交出入口区段车流量对驾驶人精神负荷影响

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科学技术与工程 2024年第3期24卷 1224-1233页

作者：易刚杨迪矫成武孔繁星陈正欢徐进重庆交通大学交通运输学院重庆400074 余姚市交通规划设计研究院余姚354001 交通运输部公路科学研究院北京100088 中铁二院工程集团有限责任公司成都610031

要为明确高密度互通立交行驶环境下,主线车流量对出入口区段驾驶人精神负荷间的影响,在重庆市内环快速路高密度互通立交群进行自然驾驶实车试验,使用Physiolab生理检测仪连续采集驾驶人在行驶过程中的心电数据,用于统计各驾驶人的心率... 详细信息

要为明确高密度互通立交行驶环境下,主线车流量对出入口区段驾驶人精神负荷间的影响,在重庆市内环快速路高密度互通立交群进行自然驾驶实车试验,使用Physiolab生理检测仪连续采集驾驶人在行驶过程中的心电数据,用于统计各驾驶人的心率指标变化情况。本次试验基于主成分分析法选择心率变异率指标RMSSD(root mean square of successive differences)、LFnorm(low frequency norm)、HFnorm(high frequency norm)、LF(low frequency)/HF(high frequency)以及心率突变率指标HRMR(heat ratemutation rate)作为驾驶人精神负荷的评价指标,记为主成分F 1和主成分F 2.并建立评价模型。结果表明:驾驶人在小净距立交出入口区段行驶时,立交主线车流量的大小会影响驾驶人的精神负荷;当驾驶人驶入立交主线时,三次模型对入口段车流量与主成分F 2.拟合效果最好,呈开口向上的三次曲线,曲线谷值点出现在2.流量水平处,模型显著;当驾驶人驶出立交主线时,一次线性模型对出口段车流量与主成分F 1的拟合效果最好,模型显著。

关键词：互通式立体交叉高密度立交小净距出入口心率变异率心率突变率精神负荷

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Synthesis of selective PAK4 inhibitors for lung metastasis of lung cancer and melanoma cells

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Acta Pharmaceutica Sinica B 2022年第6期12卷 2905-2922页

作者： Peilu Song fan Zhao Dahong Li Jiqiang Qu Miao yao Yuan Su Hanxun Wang Miaomiao Zhou Yujie Wang Yinli Gao Feng Li Dongmei Zhao Fengjiao Zhang Yu Rao Mingyu Xia Haitao Li Jian Wang Maosheng Cheng Key Laboratory of Structure-Based Drug Design&Discovery of Ministry of Education Shenyang Pharmaceutical UniversityShenyang 110016China MOE Key Laboratory of Protein sciences School of Pharmaceutical SciencesMOE Key Laboratory of Bioorganic Phosphorus Chemistry Chemical BiologyTsinghua UniversityBeijing 100084China MOE Key Laboratory of Protein sciences Beijing Advanced Innovation Center for Structural BiologyTsinghua-Peking Joint Center for Life SciencesSchool of Life Sciences and School of MedicineTsinghua UniversityBeijing 100084China School of Traditional Chinese Materia Medica Shenyang Pharmaceutical UniversityShenyang 110016China School of Life science and Biopharmaceutics Shenyang Pharmaceutical UniversityShengyang 110016China Wuya college of Innovation Shenyang Pharmaceutical UniversityShenyang 110016China Department of Cell Biology Key Laboratory of Cell BiologyMinistry of Public Healthand Key Laboratory of Medical Cell BiologyMinistry of EducationChina Medical UniversityShenyang 110001China

The p2. activated kinase 4(PAK4) is serine/threonine protein kinase that is critical for cancer *** by X-ray crystallography and structure-based optimization,we report a novel subseries of C-3-substituted 6-ethynyl-1 H-indole derivatives that display high potential and specificity towards group Ⅱ *** these inhibitors,compound 55 exhibited excellent inhibitory activity and kinase selectivity,displayed superior anti-migratory and anti-invasive properties against the lung cancer cell line A549 and the melanoma cell line *** 55 exhibited potent in vivo antitumor metastatic efficacy,with over 80% and 90% inhibition of lung metastasis in A549 or B16-BL6 lung metastasis models,*** mechanistic studies demonstrated that compound 55 mitigated TGF-β1-induced epithelial-mesenchymal transition(EMT).

关键词： Anti-cancer PAK4 inhibitor Kinase selectivity Cocrystallization Lung metastasis EMT

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PAID study design on the role of PKC activation in immune/inflammation-related depression:a randomised placebo-controlled trial protocol

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General Psychiatry 2021年第2期34卷 104-110页

作者： Xiaoyun Guo Ruizhi Mao Lvchun Cui fan Wang Rubai Zhou Yun Wang Jia Huang Yuncheng Zhu Yamin yao Guoqing Zhao Zezhi Li Jun Chen Jinhui Wang Yiru fang Department of Psychiatry Shanghai Mental Health CenterShanghai Jiao Tong University School of MedicineShanghaiChina Department of Psychology Shandong Provincial Hospital affiliated to Shandong First Medical UniversityJinanShandongChina Department of Neurology Renji HospitalShanghai Jiao Tong University School of MedicineShanghaiChina Clinical Research Center and Division of Mood Disorders Shanghai Mental Health CenterShanghai Jiao Tong University School of MedicineShanghaiChina college of Life sciences Chinese Academy of SciencesBeijingChina CAS Center for Excellence in Brain science and Intelligence Technology Chinese Academy of ScienceShanghaiChina Shanghai Key Laboratory of Psychotic Disorders ShanghaiChina

Background Inflammation that is mediated by microglia activation plays an important role in the pathogenesis of *** activation can lead to an increase in the levels of proinflammatory cytokines,including TNF-α,which leads to neuronal apoptosis in the specific neural circuits of some brain regions,abnormal cognition and treatment-resistant depression(TRD).Protein kinase C(PKC)is a key regulator of the microglia activation *** assume that the abnormality in PKC might result in abnormal microglia activation,neuronal apoptosis,significant changes in emotional and cognitive neural circuits,and *** the current study,we plan to target at the PKC signal pathway to improve the TRD treatment *** and analysis This is a 12.week,ongoing,randomised,placebo-controlled *** with TRD(N=180)were recruited from Shanghai Mental Health Center,Shanghai Jiao Tong *** control volunteers(N=60)were recruited by *** with TRD were randomly assigned to‘escitalopram+golimumab(TNF-αinhibitor)’,‘escitalopram+calcium tablet+vitamin D(PKC activator)’or‘escitalopram+placebo’*** define the primary outcome as changes in the 17-item Hamilton Depression Rating Scale(HAMD-17).The secondary outcome is defined as changes in anti-inflammatory effects,cognitive function and quality of *** This study might be the first randomised,placebo-controlled trial to target at the PKC signal pathway in patients with *** study might help to propose individualised treatment strategies for *** registration number The trial protocol is registered with *** under protocol ID 81930033 and *** ID NCT0415642..

关键词： placebo inflammation vitamin

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Positive Rate of Different Hepatitis B Virus Serological Markers in Peking Union Medical college Hospital,a General Tertiary Hospital in beijing

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Chinese Medical sciences Journal 2016年第1期31卷 17-22页

作者： Yue-qiu Zhang Sai-nan Bian Xiao-qing Liu Shao-xia Xu Li-fan Zhang Bao-tong Zhou Wei-hong Zhang yao Zhang Ying-chun Xu Guo-hua Deng Department of Infectious Diseases Peking Union Medical College HospitalChinese Academy of Medical Sciences & Peking Union Medical College Clinical Epidemiology Unit Peking Union Medical College HospitalChinese Academy of Medical Sciences & Peking Union Medical College Department of Clinical Laboratory Peking Union Medical College HospitalChinese Academy of Medical Sciences & Peking Union Medical College

Objectives To investigate the positive rate of different hepatitis B virus （HBV） serological markers, and the demographic factors related to HBV infection. Methods We enrolled all patients tested for HBV serological markers, such as HBV surface antigen （HBsAg）, HBV surface antibody （HBsAb）, hepatitis B e antigen （HBeAg）, hepatitis B e antibody （HBeAb）, HBV core antibody （HBcAb）, and HBV-DNA from July 2.08 to July 2.09 in Peking Union Medical college Hospital. The positive rate of each HBV serological marker was calculated according to gender, age, and department, respectively. The positive rates of HBV-DNA among patients with positive HBsAg were also analyzed. Results Among 2. 409 samples included, 2.81 （9.8%） were HBsAg positive. When patients were divided into 9 age groups, the age-specific positive rate of HBsAg was 1.2., 9.6%, 12.3%, 10.9%, 10.3%, 9.7%, 8.0%, 5.8%, and 4.3%, respectively. The positive rate of HBsAg in non-surgical department, surgical department, and health examination center was 16.2., 5.8%, and 4.7%, respectively. The positive rate of HBsAg of males （13.3%） was higher than that of females （7.3%, P=0.000）. Among the 2.81 HBsAg （＋） patients, 12.0 （45.9%） had HBV-DNA test, of whom 564 （45.9%） were positive. Patients with HBsAg （＋）, HBeAg （＋）, and HBcAg （＋） result usually had high positive rate of HBV-DNA results （71.8%, P=0.000）. Conclusions Among this group of patients in our hospital, the positive rate of HBsAg was relatively high. Age group of 2.-2., males, and patients in non-surgical departments were factors associated with high positive rate of HBsAg.

关键词： hepatitis B virus infection positive rate hepatitis B virus serological markers demographic factors

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Stretchable polymer composites with ultrahigh piezoelectric performance

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National science Review 2023年第8期10卷 203-210页

作者： Tongxiang Tang Zhonghui Shen Jian Wang Shiqi Xu Jiaxi Jiang Jiahui Chang Mengfan Guo Youjun fan {2. Xiao Zhihao Dong Houbing Huang Xiaoyan Li Yihui Zhang Danyang Wang Long-Qing Chen Ke Wang Shujun Zhang Ce-Wen Nan Yang Shen State Key Lab of New Ceramics and Fine Processing School of Materials Science and Engineering Tsinghua University State Key Laboratory of Advanced Technology for Materials Synthesis and Processing Center of Smart Materials and Devices Wuhan University of Technology Advanced Research Institute of Multidisciplinary science Beijing Institute of Technology applied Mechanics Laboratory Department of Engineering Mechanics Tsinghua University Center for Flexible Electronics Technology Tsinghua University School of Materials science and Engineering University of New South Wales Department of Materials science and Engineering The Pennsylvania State University State College Institute for Superconducting and Electronic Materials Australian Institute for Innovative MaterialsUniversity of Wollongong

Flexible piezoelectric materials capable of withstanding large deformation play key roles in flexible electronics. Ferroelectric ceramics with a high piezoelectric coefficient are inherently brittle, whereas polar polymers exhibit a low piezoelectric coefficient. Here we report a highly stretchable/compressible piezoelectric composite composed of ferroelectric ceramic skeleton, elastomer matrix and relaxor ferroelectric-based hybrid at the ceramic/matrix interface as dielectric transition layers, exhibiting a giant piezoelectric coefficient of 2.0 picometers per volt, high electromechanical coupling factor keff of 65%,ultralow acoustic impedance of 3MRyl and high cyclic stability under 50% compression strain. The superior flexibility and piezoelectric properties are attributed to the electric polarization and mechanical load transfer paths formed by the ceramic skeleton, and dielectric mismatch mitigation between ceramic fillers and elastomer matrix by the dielectric transition layer. The synergistic fusion of ultrahigh piezoelectric properties and superior flexibility in these polymer composites is expected to drive emerging applications in flexible smart electronics.

关键词： polymer composites piezoelectric materials structure design flexible electronics

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Partial liquid ventilation decreases tissue and serum tumor necrosis factor-~ concentrations in acute lung injury model of immature piglet induced by oleic acid

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Chinese Medical Journal 2012年第1期125卷 123-128页

作者： ZHU yao-bin fan Xiang-ming LI Xiao-feng LI Zhi-qiang WANG Qiang SUN Li-zhong LIU Ying-long Pediatric Heart Center Beijing Anzhen HospitalCapital Medical University Beijing 100029 China Pediatric Cardiac Surgery Center Fuwai Hospital Chinese Academy of Medical Sciences and Peking Union Medical College Beijing 100037 China Cardiovascular Center Beijing Anzhen HospitalCapital Medical University Beijing 100029 China

Background Pediatric patients are susceptible to lung *** lung injury in children often results in high *** liquid ventilation （PLV） has been shown to markedly improve oxygenation and reduce histologic evidence of injury in a number of lung injury *** study was designed to examine the hypothesis that PLV would attenuate the production of local and systemic tumor necrosis factor （TNF）-α in an immature piglet model of acute lung injury induced by oleic acid （OA）.Methods Twelve Chinese immature piglets were induced acute lung injury by *** animals were randomly assigned to two groups of six animals,（1） conventional mechanical ventilation （MV） group and （2. PLV with 10 ml/kg FC-77 *** Compared with MV group,the PLV group had better cardiopulmonary variables （P 〈0.05）.These variables included heart rate,mean blood pressure,blood pH,partial pressure of arterial oxygen （PaO2.,PaO2.inspired O2.fraction （FiO2. and partial pressure of arterial carbon dioxide （PaCO2..PLV reduced TNF-α levels both in plasma and tissue compared with MV group （P 〈0.05）.Conclusion PLV provides protective effects against TNF-a response in OA-induced acute lung injury in immature piglets.

关键词： acute lung injury animal models partial liquid ventilation

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Immunogenicity of Whole Mycobacterium intracellulare Proteins and Fingding on the Cross-Reactive Proteins between *** and ***

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Biomedical and Environmental sciences 2021年第7期34卷 528-539页

作者： XIAO Shi Qi XU Da DUAN Hong Yang fan Xue Ting LI Gui Lian ZHANG Wen LI Ma Chao HAN Na LI Xin yao LI Na ZHAO Li lan ZHAO Xiu Qin WAN Kang Lin LIU Hai Can FENG Wen Hai State Key Laboratory of Agrobiotechnology Department of Microbiology and ImmunologyCollege of Biological SciencesChina Agricultural UniversityBeijing 100193China State Key Laboratory for Infectious Disease Prevention and Control National Institute for Communicable Disease Control and PreventionChinese Center for Disease Control and PreventionBeijing 102206China Department of Stomatology The Second Xiangya Hospital of Central South UniversityChangsha 410000HunanChina

Objectives To evaluate the immunogenicity of Mycobacterium intracellulare proteins and determine the cross-reactive proteins between *** and *** Protein extracts from *** were used to immunize BALB/c *** antigens were evaluated using cellular and humoral *** common genes between *** and *** were identified using genome-wide comparative analysis,and cross-reactive proteins were screened using immunoproteome *** Immunization with *** proteins induced significantly higher levels of the cytokines interferon-γ(IFN-γ),interleukin-2.IL-2.,interleukin-12.IL-12.,interleukin-6(IL-6)and immunoglobulins IgG,IgG1,IgM,and IgG2. in mouse *** marrow-derived macrophages isolated from mice immunized with *** antigens displayed significantly lower bacillary loads than those isolated from mice immunized with ***-genome sequence analysis revealed 396 common genes between *** and *** hybridization with *** proteins revealed the presence of 478 proteins in the serum of mice immunized with *** protein *** common antigens were found using both microchip and genomic comparative *** This is the advanced study to investigate the immunogenicity of *** proteins and the cross-reactive proteins between *** and *** results revealed the presence of a number of cross-reactive proteins between *** and ***,this study provides a new way of identifying immunogenic proteins for use in tuberculosis vaccines against both *** and *** in future.

关键词： Mycobacterium intracellulare Mycobacterium tuberculosis Cross-reactive immune response Vaccine Antigen

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A New Species of the Extinct Genus Schizolepis from the Jurassic Daohugou Flora,Inner Mongolia,china with Special Reference to the Fossil Diversity and Evolutionary Implications

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Acta Geologica Sinica(English Edition) 2011年第2期85卷 471-481页

作者： ZHANG Jianwei Ashalata D＇ROZARIO yao Jianxin WU Zhenjie WANG Lijun Institute of Geology Chinese Academy of Geological Science Beijing 100037 China Department of Botany Narasinha Dutt College 129 Bellilious Road Howrah 711 101 India college of Ethnology and Sociology South Central University for Nationalities Wuhan 430074 Hubei China

Schizolepis daohugouensis sp. nov. is described from the Jurassic sediments of Daohugou flora, from Ningcheng County, Inner Mongolia Autonomous Region, china. The female cone is slender, cylindrical in shape, seed scale complexes are loosely and helically arranged on the cone axis at intervals of 3-5 mm. The seed scales are bilobed and divided almost from the base; the scales have no evident petiole but an articulation at the region of attachment to the cone axis. Each lobe of the seed scales is oval in shape, widest at the lower middle part; lobes are obtusely pointed with entire margins. Bract scale is fan shaped. Based on the records of Schizolepis, this is the first report of the occurrence of female cone of Schizolepis with the seed scales, the winged seeds and vegetative branches preserved together in the Jurassic deposits. The new discovery provides evidence that confirms the phylogenetic position of Schizolepis to the extant Pinaceae.

关键词： Daohugou Jurassic Pinaceae Schizolepis china

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Renin--angiotensin system inhibitor is associated with the reduced risk of all-cause mortality in COVID-19 among patients with/without hypertension

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Frontiers of Medicine 2022年第1期16卷 102-110页

作者： Huai-yu Wang Suyuan Peng Zhanghui Ye Pengfei Li Qing Li Xuanyu Shi Rui Zeng Ying yao fan He Junhua Li Liu Liu Shuwang Ge Xianjun Ke Zhibin Zhou Gang Xu Ming-hui Zhao Haibo Wang Luxia Zhang Erdan Dong National Institute of Health Data science at Peking University Beijing 100191China Peking University Advanced Institute of Information Technology Hangzhou 311215China Department of Nephrology Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030China Department of Clinical Nutrition Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030China Taikang Tongji(Wuhan)Hospital Wuhan 430050China First Affiliated Hospital of Sun Yat-sen University Guangzhou 510080China Renal Division Department of MedicinePeking University First HospitalPeking University Institute of NephrologyBeijing 100034China Peking-Tsinghua Center for Life sciences Beijing 100871China Department of Cardiology and Institute of Vascular Medicine Peking University Third HospitalKey Laboratory of Cardiovascular Molecular Biology and Regulatory PeptidesMinistry of HealthKey Laboratory of Molecular Cardiovascular SciencesMinistry of EducationBeijing Key Laboratory of Cardiovascular Receptors ResearchBeijing 100191China

Consecutively hospitalized patients with confirmed coronavirus disease 2.19(COVID-19)in Wuhan,china were retrospectively enrolled from January 2.2. to March 2.2. to investigate the association between the use of renin–angiotensin system inhibitor(RAS-I)and the outcome of this *** between the use of RAS-I(angiotensin-converting enzyme inhibitor(ACEI)or angiotensin receptor blocker(ARB)),ACEI,and ARB and in-hospital mortality were analyzed using multivariate Cox proportional hazards regression models in overall and subgroup of hypertension status.A total of 2.71 patients with COVID-19 were included,with moderate and severe cases accounting for 45.0%and 36.5%,respectively.A total of 195(7.0%)patients ***-I(hazard ratio(HR)=0.499,95%confidence interval(CI)0.32.–0.767)and ARB(HR=0.410,95%CI 0.2.0–0.700)use was associated with a reduced risk of all-cause mortality among patients with *** patients with hypertension,RAS-I and ARB applications were also associated with a reduced risk of mortality with HR of 0.352.95%CI 0.162.0.764)and 0.2.9(95%CI 0.115–0.677),***-I exhibited protective effects on the survival outcome of *** use was associated with a reduced risk of all-cause mortality among patients with COVID-19.

关键词： COVID-19 RAS inhibitor hypertension all-cause mortality

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