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DCLK1 autoinhibition and activation in tumorigenesis

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The Innovation 2022年第1期3卷 46-53页

作者： linna cheng Zejing Yang Wenhao Guo chengyong Wu Shufang Liang Aiping Tong Zhongwei Cao Rick F.Thorne Sheng-Yong Yang Yamei Yu Qiang chen State Key Laboratory of Biotherapy and Cancer Center West China HospitalSichuan Universityand Collaborative Innovation Center of BiotherapyChengdu 610041China Institute of Hematology Henan Key Laboratory of Stem Cell Differentiation and ModificationHenan Provincial People’s HospitalPeople’s Hospital of Zhengzhou UniversityPeople’s Hospital of Henan UniversityZhengzhou 450003China Department of Abdominal Oncology Cancer Center and State Key Laboratory of BiotherapyWest China HospitalWest China Medical SchoolSichuan UniversityChengdu 610041China Translational Research Institute Henan Provincial People’s HospitalAcademy of Medical ScienceZhengzhou UniversityZhengzhou 450003China

Doublecortin-like kinase 1(DCLK1)is upregulated in many tumors and is a marker for tumor stem *** evidence suggests DCLK1 constitutes a promising drug target for cancer ***,the regulation of DCLK1 kinase activity is poorly understood,particularly the function of its autoinhibitory domain(AID),and,moreover,no physiological activators of DCLK1 have presently been *** we determined the first DCLK1 kinase structure in the autoinhibited state and identified the neuronal calcium sensor HPCAL1 as an activator of *** C-terminal AID functions to block the ATP-binding site and is competitive with ***1 binds directly to the AID in a Ca^(2+)-dependent manner,which releases the *** also analyzed cancer-associated mutations occurring in the AID and elucidate how these mutations disrupt DCLK1 autoinhibition to elicit kinase activity *** results present a molecular mechanism for autoinhibition and activation of DCLK1 kinase activity and provide insights into DCLK1-associated tumorigenesis.

关键词： inhibited tumorigenesis DCL

CCGD-ESCC： A Comprehensive Database for Genetic Variants Associated with Esophageal Squamous Cell Carcinoma in Chinese Population

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Genomics, Proteomics & Bioinformatics 2018年第4期16卷 262-268页

作者： linna Peng Sijin cheng Yuan Lin Qionghua Cui Yingying Luo Jiahui Chu Mingming Shao Wenyi Fan Yamei chen Ai Lin Yiyi Xi Yanxia Sun Lei Zhang Chao Zhang Wen Tan Ge Gao chen Wu Dongxin Lin Department of Etiology and Carcinogenesis National Cancer Center/Cancer Hospital Chinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China State Key Laboratory of Protein and Plant Gene Research School of Life Sciences Center for Bioinformatics Peking UniversityBeijing 100871China Beijing Advanced Innovation Center for Genomics (ICG) Peking UniversityBeijing 100871China National Engineering Research Center for Beijing Biochip Technology Beijing 102206China School of Life Sciences Peking UniversityBeijing 100871China

Esophageal squamous-cell carcinoma （ESCC） is one of the most lethal malignancies in the world and occurs at particularly higher frequency in China. While several genome-wide association studies （GWAS） of germline variants and whole-genome or whole-exome sequencing studies of somatic mutations in ESCC have been published, there is no comprehensive database publically available for this cancer. Here, we developed the Chinese Cancer Genomic Database-Esophageal Squamous Cell Carcinoma （CCGD-ESCC） database, which contains the associations of 69,593 single nucleotide polymorphisms （SNPs） with ESCC risk in 2022 cases and 2039 controls, survival time of 1006 ESCC patients （survival GWAS） and gene expression （expression quantitative trait loci,eQTL） in 94 ESCC patients. Moreover, this database also provides the associations between8833 somatic mutations and survival time in 675 ESCC patients. Our user-friendly database is a resource useful for biologists and oncologists not only in identifying the associations of genetic variants or somatic mutations with the development and progression of ESCC but also in studying the underlying mechanisms for tumorigenesis of the cancer. CCGD-ESCC is freely accessible at http：//***/ccgd/ESCCdb.

关键词： Esophageal cancer Germline variants Somatic mutations Association databaseChinese population

cFos-ANAB:A cFos-based Web Tool for Exploring Activated Neurons and Associated Behaviors

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Neuroscience Bulletin 2021年第10期37卷 1441-1453页

作者： Fan Wang Wenjie Sun Lei Chang Kefang Sun Leying Hou linna Qian Chaoyin Jin Jiandong chen Jiali Pu Panmeng Ye Shuang Qiu Jianhong Luo Shumin Duan Baorong Zhang Zhihua Gao Xiaojun Hu Center for Neuroscience and Department of Neurology Second Affiliated HospitalZhejiang University School of MedicineHangzhou 310058China Medical Information Center Zhejiang University School of MedicineHangzhou 310058China Department of Neurology Second Affiliated HospitalZhejiang University School of MedicineHangzhou 310003China Hangzhou Hikvision Digital Technology Co. LtdHangzhou 310053China

cFos is one of the most widely-studied genes in the field of ***,there is no systematic database focusing on cFos in *** developed a curated database-cFos-ANAB-a cFos-based web tool for exploring activated neurons and associated behaviors in rats and mice,comprising 398 brain nuclei and sub-nuclei,and five associated behaviors:pain,fear,feeding,aggression,and sexual *** relationships among behaviors and nuclei(even cell types)under specific stimulating conditions were constructed based on cFos expression profiles extracted from original ***,overlapping nuclei and sub-nuclei with potentially complex functions among different associated behaviors were emphasized,leading to results serving as important clues to the development of valid hypotheses for exploring as yet unknown *** the analysis function of cFos-ANAB,multi-layered pictures of networks and their relationships can quickly be explored depending on users’*** features provide a useful tool and good reference for early exploration in *** cFos-ANAB database is available at ***.

关键词： cFos expression Curated database Brain nucleus Behavior Stimulus Visualization tools

华南上奥陶统观音桥层的空间分布和古地理重建

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科学通报 2016年第18期61卷 2053-2063页

作者：张琳娜樊隽轩陈清中国科学院南京地质古生物研究所现代古生物学和地层学国家重点实验室南京210008 中国科学院大学北京100049 中国科学院南京地质古生物研究所中国科学院资源地层学与古地理学重点实验室南京210008

观音桥层是晚奥陶世赫南特期在华南上扬子区广泛发育的一套介壳相泥质灰岩地层,位于五峰组和龙马溪组两套页岩气产出层位之间.恢复观音桥层的地理分布,分析其空间分布型式和规律,将有利于重建华南奥陶纪末期的古地理,更好地理解华南奥... 详细信息

观音桥层是晚奥陶世赫南特期在华南上扬子区广泛发育的一套介壳相泥质灰岩地层,位于五峰组和龙马溪组两套页岩气产出层位之间.恢复观音桥层的地理分布,分析其空间分布型式和规律,将有利于重建华南奥陶纪末期的古地理,更好地理解华南奥陶纪末生物大灭绝的环境背景,以及五峰组和龙马溪组黑色页岩形成的古地理背景.本研究基于GBDB数据库收集、整理和厘定了342条剖面的综合数据,利用地理信息系统的Arc GIS软件进行空间模拟,重建了华南上扬子区观音桥层的空间展布.重建结果显示,观音桥层广泛分布于上扬子台地的大部分地区,集中出露于滇东北、黔北、川东南、重庆、鄂西等地,其中厚度最大的区域呈东西向分布于滇黔桂古陆的北缘,形成了一个完整的沉积中心区;而同期的其他岩石地层单元则主要分布于上扬子台地的边缘地区.同时,利用各剖面的沉积学与古生物学、古生态学特征推测该时期各地点具体的古水深值,从而恢复了上扬子区观音桥层沉积期的古地形.结果表明,上扬子区在赫南特中期呈现出"一隆三坳"的古地理格局,"一隆"为湘鄂西水下高地,"三坳"为川东南坳陷、湘中坳陷和鄂北坳陷.这一三面为古陆环绕、局限滞留的古地理环境,是五峰组和龙马溪组富有机质页岩富集的控制因素之一.

关键词：观音桥层赫南特阶上扬子区 GBDB数据库地理信息系统古地理重建

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基于知识协同的产学研协同创新稳定性研究

科学学与科学技术管理 2023年第9期44卷 67-81页

作者：石琳娜陈劲清华大学经济管理学院清华大学技术创新研究中心四川省科学技术发展战略研究院

结合产学研创新主体的知识属性与特征，根据产、学研双方投入的知识协同成本、获得的知识协同收益、知识协同保障机制等一系列因素为基础，运用演化博弈理论探究创新主体的知识协同演化行为及其稳定性问题。构建产学研演化博弈模型，并... 详细信息

结合产学研创新主体的知识属性与特征，根据产、学研双方投入的知识协同成本、获得的知识协同收益、知识协同保障机制等一系列因素为基础，运用演化博弈理论探究创新主体的知识协同演化行为及其稳定性问题。构建产学研演化博弈模型，并通过理论推导和仿真模拟分析产学研协同创新个体及整体利益最大化的帕累托最优状态。研究发现：在产学研协同创新过程中，知识协同存在知识供需关系，双方投入的知识协同成本（知识贡献成本、知识溢出风险、知识加工成本）过高会抑制创新主体的协同意愿，不利于系统帕累托改进；资金收益与学术收益的增加会提高双方的协同积极性，而背叛收益与协同积极性呈负相关；合理的知识协同成本投入与知识协同收益分配、完善的知识资源共享机制、有效的知识协同激励与惩罚机制以及健全的法律措施是产学研协同创新稳定运行的关键。

关键词：产学研协同创新知识协同稳定性演化博弈

Intestinal dysbiosis exacerbates the pathogenesis of psoriasis-like phenotype through changes in fatty acid metabolism

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Signal Transduction and Targeted Therapy 2023年第2期8卷 851-868页

作者： Qixiang Zhao Jiadong Yu Hong Zhou Xiaoyan Wang chen Zhang Jing Hu Yawen Hu Huaping Zheng Fanlian Zeng chengcheng Yue linna Gu Zhen Wang Fulei Zhao Pei Zhou Haozhou Zhang Nongyu Huang Wenling Wu Yifan Zhou Jiong Li State Key Laboratory of Biotherapy and Cancer Center West China HospitalWest China Medical SchoolSichuan Universityand Collaborative Innovation Center for BiotherapyChengduChina

The intestinal microbiota has been associated with host immunity as well as psoriasis;however,the mechanism of intestinal microbiota regulating psoriasis needs to be demonstrated ***,we sought to examine its role and mechanism of action in the pathogenesis of *** found that the severity of psoriasis-like skin phenotype was accompanied by changes in the composition of the intestinal *** performed co-housing and fecal microbial transplantation(FMT)experiments using the K14-VEGF transgenic mouse model of psoriasis and demonstrated that the transfer of intestinal microbiota from mice with severe psoriasis-like skin phenotype exacerbated psoriasiform skin inflammation in mice with mild symptoms,including increasing the infiltration and differentiation of Th17,and increased the abundance of Prevotella,while decreasing that of Parabacteroides distasonis,in the *** alterations affected fatty acid metabolism,increasing the abundance of oleic and stearic ***,gentamicin treatment significantly reduced the abundance of Prevotella and alleviated the psoriasis-like symptoms in both K14-VEGF mice and imiquimod(IMQ)-induced psoriasis-like ***,administration of oleic and stearic acids exacerbated psoriasis-like symptoms and increased Th17 and monocyte-derived dendritic cell infiltration in the skin lesion areas in vivo,as well as increased the secretion of IL-23 by stimulating DCs in *** last,we found that,treatment of PDE-4 inhibitor alleviated psoriasis-like phenotype of K14-VEGF mice accompanied by the recovery of intestinal microbiota,including the decrease of Prevotella and increase of Parabacteroides ***,our findings reveal that the intestinal microbiota modulates host metabolism and psoriasis-like skin inflammation in mice,suggesting a new target for the clinical diagnosis and treatment of psoriasis.

关键词： metabolism psoriasis pathogenesis

Comparison of percutaneous ultrasound(guided 18(gauge or 20(gauge TruCut needle biopsy in patients with suspected pancreatic carcinoma

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Comparison of percutaneous ultrasound(guided 18(gauge or 20(...

中国超声医学工程学会第五届全国介入超声医学学术交流大会

作者： linna Su Tao Li Yiming Lei Hui chen Jianhong Wang Ultrasonic center & Xijing Hospital of Digestive Diseases the Fourth Military Medical University

Background and study aims:Ultrasound guided percutaneous trucut needle biopsy(US(TNB) is an important method for diagnosing pancreatic mass ***,it is uncertainty about which needle size is more suitable for percutaneous US(TNB of pancreatic mass *** aimed to evaluate the performance of the 18(gauge and 20(gauge types of needle in obtaining histopathological diagnosis of pancreatic mass ***:A total of 285(70:18 G

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数字经济推动实现共同富裕的机理与路径研究

科技进步与对策 2023年第21期40卷 1-11页

作者：石琳娜陈劲清华大学经济管理学院清华大学技术创新研究中心北京100084 四川省科学技术发展战略研究院四川成都610041

系统阐述共同富裕和数字经济内涵并分别构建研究框架,解析数字经济推动实现共同富裕的作用机理和理论逻辑,总结数字经济推动实现共同富裕的5个优势,即数字经济溢出效应能够创造社会财富,夯实共同富裕的物质基础;数字经济普惠效应能够缩... 详细信息

系统阐述共同富裕和数字经济内涵并分别构建研究框架,解析数字经济推动实现共同富裕的作用机理和理论逻辑,总结数字经济推动实现共同富裕的5个优势,即数字经济溢出效应能够创造社会财富,夯实共同富裕的物质基础;数字经济普惠效应能够缩小发展差距,提供共富平台;数字经济融通效应能够畅通双循环,促进资源优化配置;数字经济替代效应能够变革生产方式,加速新旧动能转换;数字经济创新效应能够构建国家竞争新优势,助力国强民富。最后,从改善民生、加快数字基础设施建设、助力乡村振兴、促进数字技术与实体经济深度融合、把握数字经济发展自主权等方面提炼推动实现共同富裕的路径安排和政策措施,对于促进数字经济发展、丰富共同富裕理论、探寻新发展路径具有重要意义。

关键词：数字经济共同富裕作用机理实现路径

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核动力厂火灾自动报警系统设备鉴定研究

化学工程 2024年第5期52卷 91-94页

作者：张晨张琳娜陈琳中国核电工程有限公司北京100840

对核动力厂火灾自动报警系统设备鉴定进行介绍,对设备鉴定适用的标准体系进行分析。首先从主体标准、配套标准、通用标准3个层次对设备鉴定适用标准进行分析。后续基于核动力厂火灾自动报警系统设计及设备设计的特殊性,整合不同堆型电... 详细信息

对核动力厂火灾自动报警系统设备鉴定进行介绍,对设备鉴定适用的标准体系进行分析。首先从主体标准、配套标准、通用标准3个层次对设备鉴定适用标准进行分析。后续基于核动力厂火灾自动报警系统设计及设备设计的特殊性,整合不同堆型电厂需求并进行融合,同时结合实际的核动力厂工程经验和研究成果,提出核动力厂火灾自动报警系统设备鉴定要求。主要包括一般性能鉴定要求、特殊鉴定要求及非标设备鉴定要求。在一般性能鉴定试验通过后,进行特殊鉴定试验,在特殊鉴定试验后进行抗震鉴定、耐压试验等偏重机械安装结构的鉴定试验以及软件鉴定试验,最后开展火灾自动报警系统非标设备鉴定试验。通过实现鉴定程序和准则的标准化,提升我国核动力火灾自动报警系统设备的成熟性和先进性,从而提高核动力厂整体防火安全性。

关键词：核动力厂火灾自动报警系统设备鉴定鉴定要求