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Discovery of a series of dimethoxybenzene FGFR inhibitors with 5H-pyrrolo[2,3-b]pyrazine scaffold: structure–activity relationship, crystal structural characterization and in vivo study

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Acta Pharmaceutica Sinica B 2019年第2期9卷 351-368页

作者： Peng Wei Bo Liu Ruifeng Wang Yinglei Gao Lanlan Li Yuchi Ma Zhiwei Qian yuelei chen Maosheng cheng Meiyu Geng Jingkang Shen Dongmei Zhao Jing Ai Bing Xiong Key Laboratory of Structure-Based Drug Design and Discovery of Ministry of Education Shenyang Pharmaceutical University Department of Medicinal Chemistry Shanghai Institute of Materia Medica Chinese Academy of Sciences Division of Anti-tumor Pharmacology State Key Laboratory of Drug Research Shanghai Institute of Materia Medica Chinese Academy of Sciences

Genomic alterations are commonly found in the signaling pathways of fibroblast growth factor receptors(FGFRs). Although there is no selective FGFR inhibitors in market, several promising inhibitors have been investigated in clinical trials, and showed encouraging efficacies in patients. By designing a hybrid between the FGFR-selectivity-enhancing motif dimethoxybenzene group and our previously identified novel scaffold, we discovered a new series of potent FGFR inhibitors, with the best one showing sub-nanomolar enzymatic activity. After several round of optimization and with the solved crystal structure, detailed structure–activity relationship was elaborated. Together with in vitro metabolic stability tests and in vivo pharmacokinetic profiling, a representative compound(35) was selected and tested in xenograft mouse model, and the result demonstrated that inhibitor 35 was effective against tumors with FGFR genetic alterations, exhibiting potential for further development.

关键词： Fibroblast growth factor Tyrosine kinase receptor Structure-based Crystallography Selectivity Hybrid 5-Hydrosulfonyl-5Hpyrrolo[2,3-b]pyrazine Inhibitor

Clinical analysis of 32 aconite poisoning in 4 years

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Clinical analysis of 32 aconite poisoning in 4 years

趣味识字,快乐成长——探小学语文低年级趣味识字教学

2017中国中毒救治宜昌论坛暨第九次全国中毒及危重症救治学术研讨会议

作者： Shufang Feng Jiangang Dong Meng Li yuelei chen Zewu Qiu Department of Poisoning Treatment Affiliated Hospital to Academy of Military Medical Sciences(the 307 Hospital)

Background:Aconite poisoning is a severe,life-threatening poisoning related to the use of traditional Chinese medicine(TCM).The herbal including ’Caowu’(kusnezoff monkshood root),’chuanwu’(Aconitum carmichaeli DEBX root),’fuzi’(Aconitum carmichali debx),which were used to treat Rheumatic joint pain,Acute Lumbar Sprain and can also cause cardiac arrhythmias,gastrointestinal and neurological *** is no specific antidote for aconite ***:The aim of the study was to summarize the clinical features and to clarify the causative and contributory factors leading to aconite ***:This study was implement within the Poisoning Treatment Center of the Army,which have integral toxicology laboratory and toxicology testing center in mainland of *** retrospective study reviewed all confirmed aconite poisoning cases handled by clinical toxicology laboratory from January 2014 to August 2017 *** diagnosis was confirmed by aconitum alkaloids in blood ***,herbal specimens were morphologically ***:Thirty-two cases were examined in this aconite poisoning case series.30(93%)exhibited neurological symptoms,10(31.2%) presented with gastrointestinal symptoms,and 26(81.3%) presented with cardiovascular *** fatality in this case *** boiling of processed aconite roots(paozhi)was listed as a major contributor of aconite poisoning(25 victims)(78%);5(15.6%)victims drank the medicinal liquor;2(6.3%) overdose-prescription than recommended dosage of aconite ***:The risk of aconite poisoning is increased by inappropriate *** reduce the incidence of poisoning,increased efforts must be devoted toward enhance public education,and the quality issues of TCM practice should be critically addressed to minimize this poisoning.

关键词： Aconite Poisoning retrospective study cardiovascular symptoms

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当代家庭教育 2022年第21期 117-119页

作者：陈玥蕾江苏省苏州市昆山高新区紫竹小学

识字写字是小学语文低年级教学的主要目标,语文课标中提出明确要求:“要让低年级的学生喜欢识字,并产生主动识字和写字的愿望。”然而,低年级学生普遍有着好玩、好动的天性,学习时注意力难以集中,容易在识字学习中遇到挫折和困难。对此... 详细信息

识字写字是小学语文低年级教学的主要目标,语文课标中提出明确要求:“要让低年级的学生喜欢识字,并产生主动识字和写字的愿望。”然而,低年级学生普遍有着好玩、好动的天性,学习时注意力难以集中,容易在识字学习中遇到挫折和困难。对此,教师在开展语文识字教学时,应根据低年级学生的思维特点和兴趣爱好,设计趣味化的教学内容,激发学生的识字兴趣,提高他们的识字积极性,为学生日后的语文学习打下坚实基础。

关键词：小学语文低年级趣味识字教学策略

Innovations in 3D bioprinting and biomaterials for liver tissue engineering:Paving the way for tissue-engineered liver

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iLIVER 2024年第1期3卷 67-81页

作者： Qi Wang Yutian Feng Anqi Wang yuelei Hu Yannan Cao Jingjing Zheng Yinpeng Le Juan Liu Hepato-Pancreato-Biliary Center Beijing Tsinghua Changgung HospitalBeijing 102218China School of Clinical Medicine Tsinghua UniversityBeijing 100084China Department of Hepatobiliary and Pancreatic Surgery The First Hospital of Jilin UniversityChangchun 130021China Key Laboratory of Digital Intelligence Hepatology(Tsinghua University) Ministry of EducationBeijing 102218China Shenzhen International Graduate School Tsinghua UniversityShenzhen 518055China Institute of Smart Biomedical Materials School of Materials Science and EngineeringZhejiang Sci-Tech UniversityHangzhou 310018China

The liver is a pivotal organ that maintains internal homeostasis and actively participates in multiple physiological *** tissue engineering(LTE),by which in vitro biomimetic liver models are constructed,serves as a platform for disease research,drug screening,and cell replacement therapies.3D bioprinting is used in tissue engineering to create microenvironments that closely mimic authentic tissues with carefully selected functional *** functional biomaterials exhibit characteristics such as high biocompatibility,mechanical strength,flexibility,processability,and tunable *** can be categorized into natural and synthetic biomaterials,each with its own advantages and limitations,and their combinations serve as a primary source of 3D bioprinting *** is noteworthy that the liver decellularized extracellular matrix(dECM),obtained by removing cellular components from tissues,possesses traits such as bioactivity,biocompatibility,and non-immunogenicity,making it a common choice among functional ***,crosslinking of biomaterials significantly impacts the mechanical strength,physicochemical properties,and cellular behavior of the printed *** review covers the current utilization of biomaterials in LTE,focusing on natural and synthetic biomaterials as well as the selection and application of crosslinking *** aim is to enhance the fidelity of in vitro liver tissue models by providing a comprehensive coverage of functional biomaterials,thereby establishing a versatile platform for tissue-engineered livers.

关键词： Tissue engineered liver Natural biomaterials Synthetic biomaterials Crosslinking 3D bioprinting

Current Status of Brazil’s New Energy and Green Low-carbon Practices in Deep-water Oil Fields

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China Oil & Gas 2024年第4期31卷 10-19页

作者： Qiu Zhaojun Zhang yuelei Zhao Jian Feng Jian Yang Yihan CNPC Brazil PetroChina Research Institute of Petroleum Exploration and Development

Brazil possesses abundant new energy resources such as solar energy,wind energy,and biomass energy,and is at the forefront of the world in the development and utilization of new energy,becoming a pioneer in energy transition and low-carbon *** energy accounts for nearly half of Brazil’s primary energy consumption,with the share in the power sector exceeding 75%.Brazil has achieved its carbon peak and is still actively promoting carbon and emission further reduction and the development of new energy.

关键词： Brazil exceeding becoming

弱纹理环境下融合点线特征的双目视觉同步定位与建图

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光学精密工程 2024年第5期32卷 752-763页

作者：龚坤徐鑫陈小庆许悦雷张兆祥西北工业大学无人系统技术研究院陕西西安710072 中国人民解放军军事科学院国防科技创新研究院北京100850

针对室内弱纹理环境下基于点特征的视觉同步定位与建图(Simultaneous Localization and Mapping,SLAM)存在的轨迹漂移等问题,提出了一种融合点线特征的双目视觉SLAM系统,并对线特征的提取与匹配问题展开研究。为了提高线特征的质量,通... 详细信息

针对室内弱纹理环境下基于点特征的视觉同步定位与建图(Simultaneous Localization and Mapping,SLAM)存在的轨迹漂移等问题,提出了一种融合点线特征的双目视觉SLAM系统,并对线特征的提取与匹配问题展开研究。为了提高线特征的质量,通过长度与梯度抑制、短线合并等方法,进一步改进LSD(Line Segment Detector)线特征提取方法。同时,通过将匹配问题转换为优化问题,并利用几何约束构建代价函数,提出了一种基于几何约束的快速线段三角化方法。实验结果表明,本文所提方法在多个数据集上的表现都优于基于描述子的传统方法,尤其在室内弱纹理场景下,其平均匹配精度达到91.67%,平均匹配时间仅需7.4 ms。基于此方法,双目视觉SLAM系统在弱纹理数据集上与已有算法ORBSLAM2,PL-SLAM的定位误差分别为1.24,7.49,3.67 m,定位精度优于现有算法。

关键词：双目视觉线特征提取视觉同步定位与建图特征匹配

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微生物与细胞资源的保存与发掘利用

中国科学院院刊 2019年第12期34卷 1379-1388页

作者：杨蕾蕾李婷邓菲郝捷逄少军宋立荣陈跃磊周宇光中国科学院微生物研究所北京100101 中国科学院广州生物医药与健康研究院广州510530 中国科学院武汉病毒研究所武汉430071 中国科学院动物研究所北京100101 中国科学院海洋研究所青岛266071 中国科学院水生生物研究所武汉430072 中国科学院上海生命科学研究院上海200031

1995年中国科学院典型培养物保藏委员会成立,旨在统一指导、协调中国科学院生物培养物资源工作,以加强对全院生命科学和生物技术研究的支撑。2015年,该委员会更名为中国科学院生物遗传资源库工作委员会,包括隶属于中国科学院11个科研机... 详细信息

1995年中国科学院典型培养物保藏委员会成立,旨在统一指导、协调中国科学院生物培养物资源工作,以加强对全院生命科学和生物技术研究的支撑。2015年,该委员会更名为中国科学院生物遗传资源库工作委员会,包括隶属于中国科学院11个科研机构的12个资源库。中国科学院生物遗传资源库保藏的生物资源类型涵盖了植物种子和离体材料、人及动物的细胞株和干细胞、微生物菌毒种、淡水藻种、海藻等,以其基础性、权威性和前瞻性区别于产业部门和大学所属的资源库,代表了我国生物资源设施保藏的水平;每年面向国家的科学研究、技术开发、环境治理、重大疫病防控、医药健康、生物能源开发、农作物育种等,提供各类生物资源4万—5万株/份。文章介绍了中国科学院生物遗传资源库的基本定位、组成、生物资源规模,及其在科学研究、国家重大需求、经济发展和社会进步中发挥的重要支撑作用,并根据生物遗传资源保护和可持续利用的发展趋势,提出了生物资源收集保藏和共享利用的重点工作建议。

关键词：微生物资源细胞资源生物遗传资源库

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膜分离技术在工业水处理中的应用

山西化工 2024年第4期44卷 184-185,246页

作者：顾跃雷上海中核八所科技有限公司上海201800

随着经济社会的发展,工业建设的规模不断扩大,对于低耗能高环保的技术的需求也在增大,而膜分离技术的出现能更好的满足这种需求。基于此,本文着重对膜分离技术在工业水处理中的应用进行研究,重点分析了膜分离技术的特点及工作原理,并在... 详细信息

随着经济社会的发展,工业建设的规模不断扩大,对于低耗能高环保的技术的需求也在增大,而膜分离技术的出现能更好的满足这种需求。基于此,本文着重对膜分离技术在工业水处理中的应用进行研究,重点分析了膜分离技术的特点及工作原理,并在此基础上的分析了其在含酚废水和染料废水等的应用、在轻工废水中的应用、在含重金属废水的应用、在化学及石油工业废水中的处理,,希望对以后工业水处理中的膜分离技术应用能有所帮助。

关键词：膜分离技术工业水处理含酚废水

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认知友好社区建设研究进展

科技导报 2024年第17期42卷 53-64页

作者：董慰赵月镭董禹蔡佳淇哈尔滨工业大学建筑与设计学院哈尔滨150006 自然资源部寒地国土空间规划与生态保护修复重点实验室哈尔滨150006

梳理了认知友好社区的理念与意义,挖掘了认知障碍群体的群体属性、行为特征与环境需求,探讨了认知友好社区在物质环境(安全寻路、环境刺激、需求满足)与社会环境(社会资本、社会认同)方面的建设要点,提出了挖掘认知障碍群体需求与偏好... 详细信息

梳理了认知友好社区的理念与意义,挖掘了认知障碍群体的群体属性、行为特征与环境需求,探讨了认知友好社区在物质环境(安全寻路、环境刺激、需求满足)与社会环境(社会资本、社会认同)方面的建设要点,提出了挖掘认知障碍群体需求与偏好、探索环境因素刺激类别与作用机制、量化分析环境影响效用、构建认知友好社区评估体系等建议。

关键词：认知障碍群体认知友好社区物质环境社会环境