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Aggravated inflammation and increased expression of cysteinyl leuko-triene receptors in the brain after focal cerebral ischemia in AQP4-deficient mice

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Neuroscience Bulletin 2012年第6期28卷 680-692页

作者： Wen-Zhen Shi Chun-Zhen zhao bing zhao Qiao-Juan Shi Li-Hui Zhang Yan-Fang Wang San-Hua Fang Yun-Bi Lu Wei-Ping Zhang Er-Qing Wei Institute of Neuroscience and Department of Pharmacology School of MedicineZhejiang University Hangzhou Key Laboratory of Neurobiology and Department of Pharmacology School of Basic MedicineHangzhou Normal University

Objective Aquaporin-4 （AQP4）, the main water channel protein in the brain, plays a critical role in water homeostasis and brain edema. Here, we investigated its role in the inflammatory responses after focal cerebral ischemia. Methods In AQP4-knockout （KO） and wild-type mice, focal cerebral ischemia was induced by 30 rain of middle cerebral arterial occlusion （MCAO）. Ischemic neuronal injury and cellular inflammatory responses, as well as the expression and localization of cysteinyl leukotriene CysLT2 and CysLT~ receptors, were determined at 24 and 72 h after MCAO. Results AQP4-KO mice showed more neuronal loss, more severe microglial activation and neutrophil infiltration, but less astrocyte proliferation in the brain after MCAO than wild-type mice. In addition, the protein levels of both CysLT1 and CysLT2 receptors were up-regulated in the ischemic brain, and the up-regulation was more pronounced in AQP4-KO mice. The CysLT1 and CysLT2 receptors were primarily localized in neurons, microglia and neutrophils; those localized in microglia and neutrophils were enhanced in AQP4-KO mice. Conclusion AQP4 may play an inhibitory role in postischemic inflammation.

关键词： aquaporin 4 gene deficiency inflammation cysteinyl leukotriene receptor microglia astrocyte focal cerebral ischemia

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基于XML技术的Web数据库应用系统设计

移动信息 2024年第5期46卷 318-320页

作者：张成川赵兵重庆移通学院招生处重庆401520 公共大数据安全技术重庆市重点实验室重庆401520

随着互联网的普及与发展,数据库技术已成为支撑各类应用系统的核心。然而,传统的关系型数据库在跨平台的数据交换、异构系统间的信息共享等应用场景中存在诸多局限。在这一背景下,XML技术应运而生,其作为一种数据描述和交换的标准,为We... 详细信息

随着互联网的普及与发展,数据库技术已成为支撑各类应用系统的核心。然而,传统的关系型数据库在跨平台的数据交换、异构系统间的信息共享等应用场景中存在诸多局限。在这一背景下,XML技术应运而生,其作为一种数据描述和交换的标准,为Web数据库应用系统的设计提供了新的思路和解决方案。文中介绍了XML技术的特点、XML结合Web数据库的优势,分析了基于XML技术的Web数据库应用系统的设计与实现,以期为数据的存储、查询和管理提供参考。

关键词： XML技术 Web数据库应用系统数据查询

Discovery of thiosemicarbazone derivatives as effective New Delhi metallo-β-lactamase-1(NDM-1) inhibitors against NDM-1 producing clinical isolates

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Acta Pharmaceutica Sinica B 2021年第1期11卷 203-221页

作者： bing zhao Xinhui Zhang Tingting Yu Ying Liu Xiaoling Zhang Yongfang Yao Xuejian Feng Hongmin Liu Dequan Yu Liying Ma Shangshang Qin State Key Laboratory of Esophageal Cancer Prevention and Treament Key Laboratory of Technology of Drug Preparation(Zhengzhou University)Ministry of Education of ChinaKey Laboratory of Henan Province for Drug Quality and EvaluationInstitute of Pharmaceutical Research and School of Pharmaceutical SciencesZhengzhou UniversityZhengzhou 450001China State Key Laboratory of Bioactive Substance and Function of Natural Medicines Institute of Materia MedicaChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100050China

New Delhi metallo-b-lactamase-1(NDM-1)is capable of hydrolyzing nearly allβ-lactam antibiotics,posing an emerging threat to public health.There are currently less effective treatment options for treating NDM-1 positive"superbug",and no promising NDM-1 inhibitors were used in clinical practice.In this study,structure eactivity relationship based on thiosemicarbazone derivatives wassystematically characterized and their potential activities combined with meropenem(MEM)were evaluated.Compounds 19 bg and 19 bh exhibited excellent activity against 10 NDM-positive isolate clinical isolates in reversing MEM resistance.Further studies demonstrated compounds 19 bg and 19 bh were uncompetitive NDM-1 inhibitors with Ki Z 0.63 and 0.44 mmol/L,respectively.Molecular docking speculated that compounds 19 bg and 19 bh were most likely to bind in the allosteric pocket which would affect the catalytic effect of NDM-1 on the substrate meropenem.Toxicity evaluation experiment showed that no hemolysis activities even at concentrations of 1000 mg/m L against red blood cells.In vivo experimental results showed combination of MEM and compound 19 bh was markedly effective in treating infections caused by NDM-1 positive strain and prolonging the survival time of sepsis mice.Our finding showed that compound 19 bh might be a promising lead in developing new inhibitor to treat NDM-1 producing superbug.

关键词： Thiosemicarbazone derivatives New Delhi metallo-β-lactamase-1 Inhibitor Antibiotic resistance

SlMAPKKK43调控番茄对灰霉病的抗性

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园艺学报 2024年第2期51卷 309-320页

作者：董晓南吕红梅赵立群何秉青张姣姣赵冰郭仰东张娜中国农业大学园艺学院蔬菜系北京市设施蔬菜生长发育调控重点实验室北京100193 中国农业大学三亚研究院海南三亚572025 北京市农业技术推广站北京100029 北京市昌平区农业技术推广站北京102200

促丝裂原活化蛋白激酶(Mitogen-activated protein kinase,MAPK)级联途径在植物的多种发育和生理过程中发挥重要作用,并应对各种生物和非生物胁迫。本研究中利用农杆菌介导的遗传转化方法获得了SlMAPKKK43过表达植株和CRISPR-Cas9介导的... 详细信息

促丝裂原活化蛋白激酶(Mitogen-activated protein kinase,MAPK)级联途径在植物的多种发育和生理过程中发挥重要作用,并应对各种生物和非生物胁迫。本研究中利用农杆菌介导的遗传转化方法获得了SlMAPKKK43过表达植株和CRISPR-Cas9介导的SlMAPKKK43敲除突变体,用灰葡萄孢接种转基因株系的离体叶片和果实,分析发现SlMAPKKK43正调控番茄对灰霉病的抗性。为进一步解析SlMAPKKK43调控番茄灰霉病抗性的分子机制,利用Pulldown-MS技术筛选到已知的灰霉病调控因子SlMKK2和SlMKK4可能作为SlMAPKKK43的底物,利用体外磷酸化试验初步验证SlMAPKKK43可以磷酸化SlMKK2和SlMKK4。

关键词：番茄灰葡萄孢 MAPK级联 SlMAPKKK43

Vitamin C Attenuates Hemorrhagic Shock-induced Dendritic Cell-specific Intercellular Adhesion Molecule 3-grabbing Nonintegrin Expression in Tubular Epithelial Cells and Renal Injury in Rats

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Chinese Medical Journal 2016年第14期129卷 1731-1736页

作者： Li Ma Jian Fei Ying Chen bing zhao Zhi-Tao Yang Lu Wang Hui-Qiu Sheng Er-Zhen Chen En-Qiang Mao Department of Emergency Medicine Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine Shanghai 200025 China Department of General Surgery Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine Shanghai 200025 China

Background： The expression of dendritic cell-specific intercellular adhesion molecule 3-grabbing nonintegrin （DC-SIGN） in renal tubular epithelial cells has been thought to be highly correlated with the occurrence of several kidney diseases, but whether it takes place in renal tissues during hemorrhagic shock （HS） is unknown. The present study airned to investigate this phenomenon and the inhibitory effect of Vitamin C （VitC）. Methods： A Sprague Dawley rat HS model was established in vivo in this study. The expression level and location of DC-SIGN were observed in kidneys. Also, the degree of histological damage, the concentrations of tumor necrosis factor-or and interleukin-6 in the renal tissues, and the serum concentration of blood urea nitrogen and creatinine at different times （2-24 h） alter HS （six rats in each group）, with or without VitC treatment belbre resuscitation, were evaluated. Results： HS induced DC-SIGN expression in rat tubular epithelial cells. The proinflarnmatory cytokine concentration, histological damage scores, and functional injury of kidneys had increased. All these phenornena induced by HS were relieved when the rats were treated with VitC before resuscitation. Conclusions： The results of the present study illustrated that HS could induce tubular epithelial cells expressing DC-SIGN, and the levels of proinflarnmatory cytokines in the kidney tissues improved correspondingly. The results also indicated that VitC could suppress the DC-SIGN expression in the tubular epithelial cells induced by HS and alleviate the inflammation and functional injury in the kidney.

关键词： Dendritic Cell-specific Intercellular Adhesion Molecule 3-grabbing Nonintegrin Hemorrhagic Shock Renal Injury Tubular Epithelial Cells Vitamin C

“五彩”党建创建品质公交——郑州公交车队“五彩”党建品牌记述

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城市公共交通 2024年第4期310卷 11-12页

作者：赵冰张昕嫣郑州市公共交通集团有限公司第四运营公司

郑州公交集团第四运营公司四车队以党建促发展,围绕运营生产全力打造“五彩党建·品质公交”党建品牌,使党建工作与运营生产深度融合,有力地推动了企业高质量发展。“五彩党建”的“五彩”是“红橙黄绿蓝”五种颜色,寓意为党建“红色旗... 详细信息

郑州公交集团第四运营公司四车队以党建促发展,围绕运营生产全力打造“五彩党建·品质公交”党建品牌,使党建工作与运营生产深度融合,有力地推动了企业高质量发展。“五彩党建”的“五彩”是“红橙黄绿蓝”五种颜色,寓意为党建“红色旗帜、橙色温暖、黄色徽记、绿色发展、紫烟红日”,以党建引领线路改革,优化乘客乘车环境,为广大市民群众提供优质高效便捷的出行服务。

关键词：党建品牌党建引领党建工作出行服务运营公司公交集团乘车环境深度融合

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银纳米线导电纺织品制备及应用研究进展

针织工业 2024年第3期 89-94页

作者：周燕王晓雨王文侠赵兵苏州经贸职业技术学院江苏苏州215009 昆山华阳新材料股份有限公司江苏苏州215331

银纳米线具有优异的长径比、导电、透光、柔性、抗菌等特性,是制备导电纺织品最有前途的纳米材料之一。介绍银纳米线导电纺织品的常用制备方法,即共混纺丝法、后整理法,综述银纳米线导电纺织品在空气过滤、饮用水过滤、电磁屏蔽、个人... 详细信息

银纳米线具有优异的长径比、导电、透光、柔性、抗菌等特性,是制备导电纺织品最有前途的纳米材料之一。介绍银纳米线导电纺织品的常用制备方法,即共混纺丝法、后整理法,综述银纳米线导电纺织品在空气过滤、饮用水过滤、电磁屏蔽、个人热管理、柔性压力传感器等领域的应用进展。最后对银纳米线导电纺织品的未来发展趋势进行展望,为下一代智能纺织品的研发提供思路。

关键词：银纳米线纳米材料共混纺丝法后整理法导电纺织品可穿戴智能纺织品

Thrombin is a therapeutic target for non-small-cell lung cancer to inhibit vasculogenic mimicry formation

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Signal Transduction and Targeted Therapy 2020年第1期5卷 1407-1418页

作者： bing zhao Mengfang Wu Zhihuang Hu Yixin Ma Wang Qi Yanling Zhang Yaran Li Min Yu Huijie Wang Wei Mo Key Laboratory of Metabolism and Molecular Medicine Ministry of EducationFudan UniversityShanghaiChina The Department of Biochemistry and Molecular Biology School of Basic Medical SciencesFudan UniversityShanghaiChina Department of Oncology Shanghai Medical CollegeFudan UniversityShanghaiChina Department of Medical Oncology Shanghai Cancer CenterFudan UniversityShanghaiChina Collaborative Innovation Center for Biotherapy Sichuan UniversityChengduChina

Tumor cells transform into endothelial cells by epithelial-to-mesenchymal transition,which is characterized by vasculogenic mimicry(VM).VM not only accelerates tumor progression but also increases drug-induced resistance.However,very little is currently known about the molecular determinants that enable VM.Targeting VM might bring a new breakthrough in cancer treatment.Thrombin is the key enzyme of the blood coagulation system and could contribute to tumor progression.Nevertheless,the association between thrombin and VM formation remains largely unknown.We found that VM was associated with the overall survival of non-small-cell lung cancer(NSCLC)patients,and that thrombin expression was closely related to VM formation.This research revealed that thrombin induced VM formation via PAR-1-mediated NF-κB signaling cascades.The novel thrombin inhibitors r-hirudin and DTIP inhibited VM formation and spontaneous metastases in subcutaneous tumors.Clinical pathological analysis confirmed that NSCLC patients with thrombin-positive/PAR-1-high expression had the poorest prognosis and were the most likely to form VM.The promotional activity of thrombin in VM formation and tumor metastasis was abolished in PAR-1-deficient NSCLC cells.The EGFR inhibitor gefitinib had no effect on VM and increased VEGF expression in tumors.The combination therapy of DTIP and gefitinib achieved a better therapeutic effect than either agent alone.This study is the first to illustrate that thrombin substantially contributes,together with PAR-1,to VM formation and to illustrate that VM might be a target of r-hirudin and DTIP to suppress tumor progression.The anticoagulants r-hirudin and DTIP could be employed for antitumor therapy.Combination therapy with DTIP with an EGFR inhibitor might achieve superior therapeutic effects.

关键词： therapeutic cancer inhibited

血清PAI-1、Flk-1与深部浸润型子宫内膜异位症及其腹腔镜保守治疗效果的关系研究

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临床和实验医学杂志 2024年第11期23卷 1188-1192页

作者：赵冰赵萌黄丹青淄博市妇幼保健院妇科山东淄博255000

目的分析血清纤溶酶原激活物抑制物(PAI)-1、胎肝激酶-1(Flk-1)与深部浸润型子宫内膜异位症(DIE)及其腹腔镜保守治疗效果的关系。方法回顾性选择自2020年1月至2022年11月在淄博市妇幼保健院行腹腔镜保守治疗的120例子宫内膜异位症患... 详细信息

目的分析血清纤溶酶原激活物抑制物(PAI)-1、胎肝激酶-1(Flk-1)与深部浸润型子宫内膜异位症(DIE)及其腹腔镜保守治疗效果的关系。方法回顾性选择自2020年1月至2022年11月在淄博市妇幼保健院行腹腔镜保守治疗的120例子宫内膜异位症患者作为研究对象。根据是否为DIE分为DIE组(n=48)和非DIE组(n=72)。比较DIE组与非DIE组的年龄、病程、癌抗原125(CA125)、美国生育学会修正分期法(r-AFS)评分、血清PAI-1及Flk-1表达水平;分析DIE患者血清PAI-1、Flk-1表达水平与病程、CA125、r-AFS评分的关系;采用受试者工作特征(ROC)曲线评价血清PAI-1、Flk-1对腹腔镜保守治疗后病情复发的预测效能。结果 DIE组病程为(7.42±4.56)年,长于非DIE组[(5.12±2.18)年],CA125水平、r-AFS评分及PAI-1、Flk-1表达水平分别为(61.42±8.75) kU/L、(47.57±6.08)分、(231.47±46.87) mg/L、(52.42±10.17) ng/mL,均高于非DIE组[(43.08±4.67) kU/L、(34.25±4.26)分、(156.24±16.93) mg/L、(21.65±4.53) ng/mL],差异均有统计学意义(P<0.05)。经多因素Logistic回归分析,病程、CA125、r-AFS评分、PAI-1、Flk-1均是DIE的独立危险因素(P<0.05)。经Pearson相关性分析,DIE患者血清PAI-1、Flk-1表达水平均与病程、CA125水平、r-AFS评分呈正相关(P<0.05)。在48例DIE患者中,腹腔镜保守治疗无效6例,占12.50%;无效患者血清PAI-1、Flk-1表达水平均高于有效患者,差异均有统计学意义(P<0.05)。经ROC曲线分析结果显示,血清PAI-1联合Flk-1预测DIE患者腹腔镜保守治疗后病情复发的曲线下面积(AUC)为0.931。结论血清PAI-1、Flk-1与DIE严重程度密切相关,联合应用可提高对腹腔镜保守治疗后病情复发的预测效能。

关键词：子宫内膜异位症纤溶酶原激活物抑制物-1 腹腔镜深部浸润型胎肝激酶-1