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PCC0208017,a novel small-molecule inhibitor of MARK3/MARK4,suppresses glioma progression in vitro and in vivo

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Acta Pharmaceutica Sinica B 2020年第2期10卷 289-300页

作者： Fangfang Li Zongliang Liu Heyuan Sun Chunmei Li Wenyan Wang Liang Ye Chunhong Yan Jingwei tian hongbo Wang School of Pharmacy Key Laboratory of Molecular Pharmacology and Drug Evaluation(Yantai University)Ministry of EducationCollaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs inUniversities of ShandongYantai UniversityYantai 264005China Department of Clinical Medicine Binzhou Medical CollegeYantai 256603China GRU Cancer Center Augusta UniversityAugustaGA 30912USA

Gliomas are the most common primary intracranial neoplasms among all brain malignancies,and the microtubule affinity regulating kinases(MARKs)have become potential drug targets for ***,we report a novel dual small-molecule inhibitor of MARK3 and MARK4,designated as *** vitro,PCC0208017 strongly inhibited kinase activity against MARK3 and MARK4,and strongly reduced proliferation in three glioma cell *** compound attenuated glioma cell migration,glioma cell invasion,and *** mechanism studies revealed that PCC0208017 decreased the phosphorylation of Tau,disrupted microtubule dynamics,and induced a G2/M phase cell cycle *** an in vivo glioma model,PCC0208017 showed robust anti-tumor activity,blood-brain barrier permeability,and a good oral pharmacokinetic *** docking studies showed that PCC0208017 exhibited high binding affinity to MARK3 and *** together,our study describes for the first time that PCC0208017,a novel MARK3/MARK4 inhibitor,might be a promising lead compound for treatment of glioma.

关键词： Glioma PCC0208017 MARK3 MARK4 Molecular docking

Space advanced technology demonstration satellite

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Science China(Technological Sciences) 2024年第1期67卷 240-258页

作者： ZHANG XiaoFeng CHEN Wen ZHU XiaoCheng MENG Na HE JunWang BI XingZi ZHANG YongHe SHI Qi LI Fei LIU Rui FENG ZhengGong LIU Liu LI JinSong WU HaiChen XU DongXiao LI TaiJie HUANG JiangJiang LIU Shuo LI tianTong YU XianSheng GAO Yang ZHOU Heng BAN HanYu ZHANG YanLi ZHANG YueTing YANG YingQuan HE Tao DUAN XuLiang CHEN Xin WANG YaMin SUN AnTai ZHANG KuoXiang SUN Ying WANG YaoBin FAN ChengCheng XIONG ShaoLin LI XinQiao WEN XiangYang LING ZhiXing SUN XiaoJin ZHANG Chen BAI XianYong WANG ZhanShan DENG YuanYong tian Hui YANG JianFeng XUE hongbo SANG Peng LIU JinGuo ZHENG HuiLong ZHU Xiang HE JianWu LI Hui XU LuXiang XU ShuYan CHEN WenWu LIU ZhenDong WANG ZhaoLi MAO XiangLong GAO Rong LI ZongXuan DING GuoPeng WANG XinYu DOU RunJiang WENG LuBin LUO Hao WANG YaPing LIANG XianFeng FANG ZiRuo Innovation Academy for Microsatellites Chinese Academy of SciencesShanghai 201203China Institute of High Energy Physics Chinese Academy of SciencesBeijing 100049China National Astronomical Observatory of China Beijing 100101China Shanghai Institute of Technical Physics Chinese Academy of SciencesShanghai 200083China Institute of Precision Optical Engineering School of Physics Science and EngineeringTongji UniversityShanghai 200092China School of Earth and Space Sciences Peking UniversityBeijing 100871China Xi’an Institute of Optics and Precision Mechanics Chinese Academy of SciencesXi’an 710119China National Space Science Center Chinese Academy of SciencesBeijing 100190China Shenyang Institute of Automation Chinese Academy of SciencesShenyang 110016China Institute of Engineering Thermophysics Chinese Academy of SciencesBeijing 100190China Institute of Mechanics Chinese Academy of SciencesBeijing 100190China Shanghai Institute of Organic Chemistry Chinese Academy of SciencesShanghai 200032China Hangzhou Institute for Advanced Study University of Chinese Academy of SciencesHangzhou 310024China Nanyang Technological University Singapore 569830Singapore Dalian Institute of Chemical Physics Chinese Academy of SciencesDalian 116023China Technical Institute of Physics and Chemistry Chinese Academy of SciencesBeijing 100049China Changchun Institute of Optics Fine Mechanics and PhysicsChinese Academy of SciencesChangchun 130033China Institute of Semiconductors Chinese Academy of SciencesBeijing 100083China Institute of Automation Chinese Academy of SciencesBeijing 100190China School of Aeronautics and Astronautics Zhejiang UniversityHangzhou 310058China

The Space Advanced Technology demonstration satellite(SATech-01),a mission for low-cost space science and new technology experiments,organized by Chinese Academy of Sciences(CAS),was successfully launched into a Sun-synchronous orbit at an altitude of~500 km on July 27,2022,from the Jiuquan Satellite Launch *** as an experimental platform for space science exploration and the demonstration of advanced common technologies in orbit,SATech-01 is equipped with 16 experimental payloads,including the solar upper transition region imager(SUTRI),the lobster eye imager for astronomy(LEIA),the high energy burst searcher(HEBS),and a High Precision Magnetic Field Measurement System based on a CPT Magnetometer(CPT).It also incorporates an imager with freeform optics,an integrated thermal imaging sensor,and a multi-functional integrated imager,*** paper provides an overview of SATech-01,including a technical description of the satellite and its scientific payloads,along with their on-orbit performance.

关键词： SATech-01 spacecraft design scientific instruments on-orbit performance

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铁矿烧结系统漏风治理技术及评估综述

中国冶金 2024年第1期34卷 1-9,26页

作者：周明顺田勇赵东明蒋益卢兴福赵鸿波贾福智柳明旭海洋装备用金属材料及其应用国家重点实验室辽宁鞍山114009 鞍钢集团钢铁研究院辽宁鞍山114009 鞍钢股份有限公司辽宁鞍山114006 鞍钢股份有限公司鲅鱼圈钢铁分公司炼铁部辽宁营口115014 中冶长天国际工程有限责任公司湖南长沙410205 本钢板材股份有限公司研发院辽宁本溪117000

在“以风为纲”的铁矿烧结过程中,漏风对烧结生产带来严重的不利影响,如增大主抽风机的功耗、降低烧结生产质量和产量、加速设备失效、加大环保治理难度等。从分析烧结机漏风的部位出发,介绍了烧结机漏风率测定方法,指出应将静态流量法... 详细信息

在“以风为纲”的铁矿烧结过程中,漏风对烧结生产带来严重的不利影响,如增大主抽风机的功耗、降低烧结生产质量和产量、加速设备失效、加大环保治理难度等。从分析烧结机漏风的部位出发,介绍了烧结机漏风率测定方法,指出应将静态流量法和烟气成分分析法相结合来综合评估烧结系统的漏风率;综合整理和分析了烧结机漏风治理关键技术,重点分析了以负压吸附式端部密封技术为代表的烧结机综合密封技术;总结归纳了国内外钢铁企业针对烧结机漏风所采取的有效措施及效果,为烧结机漏风治理提供参考和借鉴。

关键词：烧结漏风率漏风治理密封漏风检测

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薄皮甜瓜雪花脆宝的选育

长江蔬菜 2024年第16期 37-39页

作者：田磊李树卿沈爱民邵维仙赵洪波廊坊市农林科学院河北廊坊065000 廊坊市农业农村局

雪花脆宝是以花92为母本、金花90为父本选育的杂交一代薄皮甜瓜新品种。雪花脆宝属于中早熟品种,果实成熟期31~35 d。坐果性强,单果质量0.8~1.5 kg。果实长棒形,果皮绿色覆白色条斑,果肉绿色,果肉厚2.5~2.9 cm,中心可溶性固形物含量13.0... 详细信息

雪花脆宝是以花92为母本、金花90为父本选育的杂交一代薄皮甜瓜新品种。雪花脆宝属于中早熟品种,果实成熟期31~35 d。坐果性强,单果质量0.8~1.5 kg。果实长棒形,果皮绿色覆白色条斑,果肉绿色,果肉厚2.5~2.9 cm,中心可溶性固形物含量13.0%~14.1%。中抗白粉病和霜霉病,吊蔓栽培667 m2平均产量3260 kg左右。适合我国华北地区保护地栽培。2019年10月通过农业农村部非主要农作物品种登记。

关键词：甜瓜新品种雪花脆宝杂交一代

高碳铬轴承钢全流程夹杂物演变机理及关键控制工艺

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中国冶金 2024年第2期34卷 117-125页

作者：刘洪波刘颖谢荣圆张彩东车晓锐李民高鹏田志强张杰河钢材料院河北石家庄050023 河钢数字技术股份有限公司河北石家庄050100 河钢集团石钢公司河北石家庄050199 北京科技大学冶金与生态工程学院北京100083

为研究GCr15轴承钢中夹杂物演变规律,利用Zeiss Ultra55型场发射扫描电镜配置的Aztec-Feature夹杂物自动分析系统对GCr15轴承钢EAF-LF-RH-CC全流程中各工序试样进行大范围(大于200 mm^(2))定量扫描分析,研究各工序夹杂物形貌、成分、数... 详细信息

为研究GCr15轴承钢中夹杂物演变规律,利用Zeiss Ultra55型场发射扫描电镜配置的Aztec-Feature夹杂物自动分析系统对GCr15轴承钢EAF-LF-RH-CC全流程中各工序试样进行大范围(大于200 mm^(2))定量扫描分析,研究各工序夹杂物形貌、成分、数量、尺寸、分布等演变规律。结果表明,GCr15轴承钢EAF出站时夹杂物主要为纯Al_(2)O_(3)夹杂;LF精炼过程中夹杂物转变为MgO-Al_(2)O_(3)及含有少量CaO的Al_(2)O_(3)-MgO-CaO复合夹杂;RH进站后夹杂物中CaO含量升高,逐渐形成Al_(2)O_(3)-CaO-MgO夹杂;最终GCr15轴承钢中间包内夹杂物平均成分为56Al_(2)O_(3)-22CaO-7MgO-8CaS。同时,LF-RH精炼阶段及软吹前期对GCr15轴承钢中夹杂物具有显著去除效果,去除率达95.6%;但随着RH软吹时间的增加,对钢中T[O]、[N]含量的进一步去除影响不大,甚至还会发生大型夹杂物的卷入,导致T[O]含量升高、夹杂物平均尺寸增大等问题。由FactSage平衡热力学计算分析可知,在轴承钢w(T[O])=7×10^(-6)条件下,钢中w([Mg])和w([Ca])分别超过0.4×10^(-6)和0.16×10^(-6)时,钢液中可分别生成镁铝尖晶石和钙铝酸盐夹杂物。研究结果为轴承钢中该类夹杂物控制提供了参考和理论指导。

关键词：轴承钢夹杂物演变规律氧化铝氧化镁

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342例重症手足口病患儿的临床特征分析

癫痫与神经电生理学杂志 2024年第3期33卷 160-166页

作者：王庆圆徐洪波田茂强马一翔幸黔鲁陈艳遵义医科大学第一临床学院儿科学贵州遵义563000 遵义医科大学附属医院小儿内科贵州遵义563000 遵义医科大学第二附属医院小儿内科贵州遵义563000

目的探讨重症手足口病(HFMD)患儿的临床特征并对其高危因素进行分析。方法回顾性分析2018年6月至2022年6月在遵义医科大学附属医院住院治疗的342例重症HFMD患儿的临床资料、病原学相关指标及治疗情况,根据患儿神经系统受累后是否发生心... 详细信息

目的探讨重症手足口病(HFMD)患儿的临床特征并对其高危因素进行分析。方法回顾性分析2018年6月至2022年6月在遵义医科大学附属医院住院治疗的342例重症HFMD患儿的临床资料、病原学相关指标及治疗情况,根据患儿神经系统受累后是否发生心肺功能衰竭分为Ⅰ组(HFMD并神经系统损害,有心肺功能衰竭)和Ⅱ组(HFMD并神经系统损害,无心肺功能衰竭),两组间进行基线资料比较。结果纳入342例重症HFMD患儿,其中男性214例,女性128例。中位年龄为17(12,24)个月。中位住院时间为5(5,6)d。发病具有明显季节性,高峰期为5~9月。其中Ⅰ组13例,Ⅱ组329例,Ⅰ组患儿年龄更小,住院时间更长(P<0.05)。重症HFMD患儿的临床表现以发热、皮疹常见,同时伴神经系统症状,部分患儿伴有呼吸系统及循环系统受累。重症HFMD患儿的病原学以其他肠道病毒感染常见,两组患儿病原学资料比较,EV71与其他病原学差异有统计学意义(P<0.001)。重症HFMD患儿的治疗以降低颅内压、免疫调节及营养支持等综合治疗为主,累及心肺功能的患儿可联合血管活性药物及呼吸机治疗。结论重症HFMD以男性患儿多见,年龄≤3岁,发病高峰季节为5~9月。临床表现多样,危重症更易导致患儿脑干损伤及出现气促、心动过速及肺出血等。应加强对重症HFMD患儿病原学的检测,尤其EV71感染后可导致严重并发症。重症HFMD患儿早期应用糖皮质激素联合静脉用人免疫球蛋白治疗十分重要。

关键词：手足口病重症神经系统心肺衰竭儿童临床特征病原学

Ecosystem service valuation of bays in East China Sea and its response to sea reclamation activities

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Journal of Geographical Sciences 2020年第7期30卷 1095-1116页

作者： LIU Ruiqing XU Hao LI Jialin PU Ruiliang SUN Chao CAO Luodan JIANG Yimei tian Peng WANG Lijia GONG hongbo Donghai Institute Ningbo UniversityNingbo 315211ZhejiangChina Department of Geography&Spatial Information Techniques Ningbo UniversityNingbo 315211ZhejiangChina School of Geosciences University of South FloridaTampaFL 33620-5250USA

Ecosystem service values(ESVs)of bays and their response to sea reclamation are of great practical importance for forming bay eco-compensation policy and extension of blue economic *** on land use information of bays collected during the period of 1990–2015,the spatiotemporal evolution of ESVs of 12 main bays in East China Sea and their response to sea reclamation activities over the past 25 years were quantitatively *** analysis results indicate that ESVs of bays in East China Sea showed a continuous downward trend and the whole ecosystem was continuously degraded,in which the degradation degree of ESV in the southern bays was higher than that in the northern *** zoning of ESVs of bays in East China Sea was remarkable,showing a continuous downward trend from low-value to high-value *** variation of ESVs of each bay was also significant,expanding from a city and from inland to the coast,which suggests that human activities,mainly reclamation,have become main agents for ESV evolution of bays in East China *** of bays have a significant response to sea reclamation,manifested as a significant negative correlation between ESV and reclamation *** correlation in the southern bays was stronger than that in the northern bays,which was caused by different effects of sea reclamation modes on ESV evolution of muddy and bedrock bays.A negative effect of sea reclamation activities on bay ecosystem was ***,an attention should be paid to dynamic monitoring and early warning of development status in offshore areas,ecosystem-level reclamation control policy,and coastal wetland reserves ***,the spatial coupling mechanism study between bay ecosystem service demand and its service supply capacity should be strengthened to realize systematic regulation of bay ecological security pattern.

关键词： reclamation ecosystem service value correlation analysis bay East China Sea

基于中医传承辅助系统探讨中药方剂治疗癫痫的用药规律

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中国中医药现代远程教育 2023年第22期21卷 34-36页

作者：车萍黄海量任正肖李紫薇陈子超张振韩涛田洪波山东中医药大学实验中心山东济南250355 山东中医药大学康复医学院山东济南250355 山东中医药大学中医药创新研究院山东济南250355 山东中医药大学研究生处山东济南250355 济南市中医医院骨科山东济南250355

目的分析《中医方剂大辞典》中治疗癫痫的方剂的组方用药规律。方法检索并提取《中医方剂大辞典》中治疗癫痫的方剂,共得到有效方剂110首。运用中医传承辅助系统,对该110首方剂进行用药的频次、用药规则分析、用药模式分析以及聚类分析... 详细信息

目的分析《中医方剂大辞典》中治疗癫痫的方剂的组方用药规律。方法检索并提取《中医方剂大辞典》中治疗癫痫的方剂,共得到有效方剂110首。运用中医传承辅助系统,对该110首方剂进行用药的频次、用药规则分析、用药模式分析以及聚类分析等统计。结果用药频率在15次以上的中药有15味;支持度个数为12,置信度为0.6时,得到6对药物组合;支持度个数为12,置信度为8时,得到6对常用的用药组合;相关度为2,惩罚度为2时,得到关联系数大于0.0778的药对12对,以及潜在的新方组合2个。结论中医药是现代医家治疗癫痫的重要手段,其中安神药、补虚药为治疗癫痫的核心药物,其剂型多为丸剂和散剂。中医药中沿承的古方对于癫痫的治疗具有良好的效果,其中许多方剂被现代医家应用与研究,值得进一步推广。

关键词：中医传承辅助系统痫病癫痫中医方剂大辞典用药规律

Lx2-32c,a novel semi-synthetic taxane,exerts antitumor activity against prostate cancer cells in vitro and in vivo

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Acta Pharmaceutica Sinica B 2017年第1期7卷 52-58页

作者： Guangyao Lv Dengjun Sun Jingwen Zhang Xiaoxia Xie Xiaoqiong Wu Weishuo Fang Jingwei tian Chunhong Yan hongbo Wang Fenghua Fu School of Pharmacy Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University)Ministry of EducationYantai University Departments of Medical Oncology Affiliated Yuhuangding HospitalMedical College of Qingdao University The Military Affiliated General Hospital of Beijing PLA State Key Laboratory of Bioactive Substances and Functions of Natural Medicines Institute of Materia MedicaChinese Academy of Medical Sciences and Peking Union Medical College GRU Cancer Center Georgia Regents University

Tubulin has been shown to be an effective target for the development of cytotoxic agents against prostate cancer. Previously, we reported that Lx2-32 c is an anti-tubulin agent with high binding affinity to tubulin. In this study, we investigated the potential of Lx2-32 c to act as an effective cytotoxic agent in the treatment of prostate cancer. MTT assays showed that Lx2-32 c was cytotoxic to all tested prostate cancer cell lines. The Lx2-32c-treated cells typically exhibited a rounded morphology associated with the onset of apoptosis, as evidenced by immunocytochemical staining. Human prostate cancer cell lines treated with Lx2-32 c arrest in the G2/M phase of the cell cycle and the treatment is associated with an increased ratio of cells in the sub-G0/G1 phase as determined by flow cytometry. Furthermore, expression of the cleaved form of poly(ADP-ribose) polymerase in prostate cancer cell lines treated with Lx2-32 c was shown by Western blotting assay. Xenograft implants of LNCa P and PC3-derived tumors in nude mice showed that Lx2-32 c treatment significant inhibited tumor growth with effects equivalent to those of docetaxel. These findings demonstrate the potential of Lx2-32 c as a candidate antitumor agent for the treatment of prostate cancer.

关键词： Lx2-32c Cephalomannine Prostate cancer Microtubule Cell cycle arrest Apoptosis