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Characteristic roadmap of linker governs the rational design of PROTACs

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Acta Pharmaceutica Sinica B 2024年第10期14卷 4266-4295页

作者： Yawen Dong Tingting Ma Ting Xu zhangyan feng Yonggui Li Lingling Song Xiaojun Yao Charles R.Ashby Jr Ge-Fei Hao School of Pharmaceutical Sciences Guizhou UniversityGuiyang 550025China State Key Laboratory of Green Pesticide Key Laboratory of Green Pesticide and Agricultural BioengineeringMinistry of EducationCenter for R&D of Fine ChemicalsGuizhou UniversityGuiyang 550025China Faculty of Applied Sciences Macao Polytechnic UniversityMacao 999078China Department of Pharmaceutical Sciences St.John’s UniversityNew YorkNY 11439USA

Proteolysis targeting chimera (PROTAC) technology represents a groundbreaking development in drug discovery, leveraging the ubiquitin‒proteasome system to specifically degrade proteins responsible for the disease. PROTAC is characterized by its unique heterobifunctional structure, which comprises two functional domains connected by a linker. The linker plays a pivotal role in determining PROTAC's biodegradative efficacy. Advanced and rationally designed functional linkers for PROTAC are under development. Nonetheless, the correlation between linker characteristics and PROTAC efficacy remains under-investigated. Consequently, this study will present a multidisciplinary analysis of PROTAC linkers and their impact on efficacy, thereby guiding the rational design of linkers. We will primarily discuss the structural types and characteristics of PROTAC linkers, and the optimization strategies used for their rational design. Furthermore, we will discuss how factors like linker length, group type, flexibility, and linkage site affect the biodegradation efficiency of PROTACs. We believe that this work will contribute towards the advancement of rational linker design in the PROTAC research area.

关键词： PROTAC PROTAC linker Linker characteristics Rational design Biodegradation efficiency

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锂离子电池正负极材料研究进展

河南师范大学学报（自然科学版） 2000年第4期28卷 52-59页

作者：杨书廷张焰峰刘立君贾俊华陈红军尹艳红河南师范大学化学与环境科学学院新乡453002

本文首先讨论了锂离子电池用正极材料 Li Co O2 、Li-Mn-O体系的相图 ,结构性质和理论电极容量的关系及最新研究进展 ,其次评述了锂离子电池各种负极材料的性能及应用情况。

关键词：锂离子电池正极材料负极材料锂-锰-氧体系

饮茶与中国男性肺癌发病关系的前瞻性队列研究

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中华预防医学杂志 2018年第5期52卷 511-516页

作者：李鑫李霓王刚苏凯李放昌盛谭锋维吕章艳冯小双魏锣沛陈玉恒陈宏达陈朔华任建松石菊芳崔宏吴寿岭代敏赫捷国家癌症中心、中国医学科学院北京协和医学院肿瘤医院癌症早诊早治办公室北京100021 国家癌症中心、中国医学科学院北京协和医学院肿瘤医院胸外科北京100021 国家癌症中心、中国医学科学院北京协和医学院肿瘤医院防癌科北京100021 开滦总医院肿瘤科开滦员工健康保健中心

目的研究我国男性饮茶与肺癌发病风险之间的关联.方法于2006年以开滦集团≥18岁整体在职及离退休男性职工为研究对象,收集人群资料及饮茶相关信息,建立动态队列,每两年进行一次随访,收集对象肺癌发病结局信息.截至2015年12月31日,共有... 详细信息

目的研究我国男性饮茶与肺癌发病风险之间的关联.方法于2006年以开滦集团≥18岁整体在职及离退休男性职工为研究对象,收集人群资料及饮茶相关信息,建立动态队列,每两年进行一次随访,收集对象肺癌发病结局信息.截至2015年12月31日,共有103010名男性进入研究.以不饮茶人群为对照组,利用Cox比例风险回归模型分析饮茶状况与男性肺癌发病风险的关联.结果调查对象男性年龄为（51.3±13.4）岁,共随访828810.74人年,中位随访时间为8.91年,收集到肺癌新发病例964例.其中,有59926名（58.17%）调查对象不饮茶,24765名（24.04%）每周饮茶〈4次、18319名（17.78%）每周饮茶≥4次.调整年龄、教育程度、经济收入、吸烟情况、饮酒情况、粉尘暴露、BMI、饮茶类型、肿瘤家族史等潜在的混杂因素后,与不饮茶对象相比,每周饮茶〈4次组（HR=0.80,95%CI：0.63-1.02）和≥4次组（HR=1.02,95%CI：0.80-1.30）与男性肺癌发病差异无统计学意义.根据吸烟状况等进行分层分析及敏感性分析结果未发生明显变化.结论尚未发现饮茶与男性肺癌发病风险存在相关性.

关键词：茶男性肺肿瘤队列研究前瞻性研究

Molecular detection of the powdery mildew resistance genes in winter wheats DH51302 and Shimai 26

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Journal of Integrative Agriculture 2020年第4期19卷 931-940页

作者： QU Yun-feng WU Pei-pei HU Jing-huang CHEN Yong-xing SHI Zhan-liang QIU Dan LI Ya-hui ZHANG Hong-jun ZHOU Yang YANG Li LIU Hong-wei ZHU Tong-quan LIU Zhi-yong zhangyan-ming LI Hong-jie Key Laboratory of Molecular Cytogenetic and Genetic Breeding of Heilongjiang Province/College of Life Science and Technology Harbin Normal UniversityHarbin 150025P.R.China National Engineering Laboratory for Crop Molecular Breeding/Institute of Crop Sciences Chinese Academy of Agricultural SciencesBeijing 100081P.R.China Institute of Genetics and Developmental Biology Chinese Academy of SciencesBeijing 100101P.R.China Shijiazhuang Academy of Agricultural and Forestry Sciences Shijiazhuang 050041P.R.China Wheat Research Institute Zhumadian Academy of Agricultural SciencesZhumadian 463000P.R.China

Resistance to powdery mildew is an important trait of interest in many wheat breeding programs. The information on genes conferring resistance to powdery mildew in wheat cultivars is useful in parental selection. Winter wheat breeding line DH51302 derived from Liangxing 99 and cultivar Shimai 26 derived from Jimai 22 showed identical infection patterns against 13 isolates of Blumeria graminis f. sp. tritici(Bgt) that causes wheat powdery mildew. DH51302 and Shimai 26 were crossed to a powdery mildew susceptible cultivar Zhongzuo 9504 and the F2:3 families were used in molecular localization of the resistance genes. Fourteen polymorphic markers, which were linked to Pm52 from Liangxing 99, were used to establish the genetic linkage maps for the resistance genes Pm DH51302 and Pm SM26 in DH51302 and Shimai 26, respectively. These genes were placed in the same genetic interval where Pm52 resides. Analysis of gene-linked molecular markers indicated that Pm DH51302 and Pm SM26 differed from other powdery mildew resistance genes on chromosome arm 2 BL, such as Pm6, Pm33, Pm51, Ml Zec1, Ml AB10, and Pm64. Based on the results of reaction patterns to different Bgt isolates and molecular marker localization, together with the pedigree information, DH51302 and Shimai 26 carried the same gene, Pm52, which confers their resistance to powdery mildew.

关键词： Triticum aestivum Blumeria graminis f.sp.tritici Pm52 molecular mapping

Cohort profile: design and methods of the Chinese colorectal, breast, lung, liver, and stomach cancer screening trial(C-BLAST)

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Cancer Biology & Medicine 2023年第10期20卷 713-720页

作者： Yubei Huang zhangyan Lyu Yu Zhang Xiaomin Liu Yacong Zhang Ya Liu Chao Sheng Hongyuan Duan Zeyu Fani Chenyang Li Xiao Lin Zhuowei feng Lu Zheng Zhaoxiang Ye Hong Lu Ying Zhu Dejun Zhou Xi Wei Li Ren Bin Meng Fangfang Song fengju Song Kexin Chen Department of Cancer Epidemiology and Biostatistics Key Laboratory of Molecular Cancer Epidemiology(Tianjin)Key Laboratory of Cancer Prevention and TherapyTianjin's Clinical Research Center for CancerTianjin 300060China Department of Radiology Key Laboratory of Cancer Prevention and TherapyTianjin's Clinical Research Center for CancerTianjin 300060China Department of Breast Imaging Diagnosis Key Laboratory of Cancer Prevention and TherapyTianjin's Clinical Research Center for CancerTianjin 300060China Department of Endoscopy Key Laboratory of Cancer Prevention and TherapyTianjin's Clinical Research Center for CancerTianjin 300060China Department of Ultrasound Imaging Diagnosis Key Laboratory of Cancer Prevention and TherapyTianjin's Clinical Research Center for CancerTianjin 300060China Department of Clinical Laboratory Key Laboratory of Cancer Prevention and TherapyTianjin's Clinical Research Center for CancerTianjin 300060China Department of Pathology Tianjin Medical University Cancer Institute&HospitalNational Clinical Research Center for CancerKey Laboratory of Cancer Prevention and TherapyTianjin's Clinical Research Center for CancerTianjin 300060China

Given the rapid changes in social structure(urbanization),economic structure(industrialization),and demographic structure(population aging)in China,cancer has become a major public health *** evidence has indicated that screening can decrease cancer mortality,particularly among high-risk groups,and several representative national and regional cancer screening programs have been launched in China to cope with the increasing burden of cancer.

关键词： stomach cancer mortality

基于结构方程模型的陕西果业跨境电商发展路径研究

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北方园艺 2020年第11期 145-152页

作者：毛凤霞胡章艳冯青云西安邮电大学经济与管理学院陕西西安710000

发展果业跨境电商是农村经济在陕西自贸区背景下转型的重要途径,而研究其发展路径是推进果业跨境电商进程的关键任务。首先,该研究在调研和果业产业链的基础上,将影响因素总结为果业生产因素、外部环境因素、专业配备因素、贸易环节因素... 详细信息

发展果业跨境电商是农村经济在陕西自贸区背景下转型的重要途径,而研究其发展路径是推进果业跨境电商进程的关键任务。首先,该研究在调研和果业产业链的基础上,将影响因素总结为果业生产因素、外部环境因素、专业配备因素、贸易环节因素;其次,提出假设,将上述影响因素作为潜变量,设置可观察变量,从而建立结构方程模型;再次,选取陕西省8个市为样本,检验所选样本数据的信度以及效度,拟合、修正模型的结果;最后,计算出优化模型及路径系数。在此基础上,提出了陕西果业跨境电商发展路径及"水果基地-果业企业-跨境电商平台-物流企业-政府"五位一体的提升策略。

关键词：跨境电商果业产业链结构方程模型

A de novo Genome of a Chinese Radish Cultivar

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Horticultural Plant Journal 2015年第3期1卷 155-164页

作者： ZHANG Xiaohui YUE Zhen MEI Shiyong QIU Yang YANG Xinhua CHEN Xiaohua CHENG feng WU zhangyan SUN Yuyan JING Yi LIU Bo SHEN Di WANG Haiping CUI Na DUAN Yundan WU Jian WANG Jinglei GAN Caixia WANG Jun WANG Xiaowu LI Xixiang Institute of Vegetables and Flowers Chinese Academy of Agricultural Sciences Key Laboratory of Biology and Genetic Improvement of Horticultural Crops of Ministry of Agriculture The Beijing Genomics Institute Institute of Economic Crop Hubei Academy of Agricultural Sciences

Here, we report a high-quality draft genome of a Chinese radish(Raphanus sativus) cultivar. This draft contains 387.73 Mb of assembled scaffolds, 83.93% of the scaffolds were anchored onto nine pseudochromosomes and 95.09% of 43 240 protein-coding genes were functionally annotated. 184.75 Mb(47.65%) of repeat sequences was identified in the assembled genome. By comparative analyses of the radish genome against 10 other plant genomes, 2 275 genes in 780 gene families were found unique to R. sativus. This genome is a good reference for genomic study and of great value for genetic improvement of radish.

关键词： Raphanus sativus genome sequencing

代谢综合征与女性乳腺癌发病风险的前瞻性队列研究

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中华预防医学杂志 2021年第3期55卷 359-364页

作者：于欣阳李鑫温艳杨卓煜郑亚迪冯小双吕章艳李霓赫捷国家癌症中心国家肿瘤临床医学研究中心中国医学科学院北京协和医学院肿瘤医院癌症早诊早治办公室北京100021 河南省人民医院病案科郑州大学人民医院郑州450003 国家癌症中心国家肿瘤临床医学研究中心中国医学科学院北京协和医学院肿瘤医院胸外科北京100021

目的研究代谢综合征(MS)与女性乳腺癌发病风险关联。方法基于“开滦女性动态队列”,于2006年5月至2015年12月,纳入25618名开滦集团在职及离退休女性职工为研究对象,并进行随访。采用问卷调查、身体测量和实验室检测的方法收集基线社会... 详细信息

目的研究代谢综合征(MS)与女性乳腺癌发病风险关联。方法基于“开滦女性动态队列”,于2006年5月至2015年12月,纳入25618名开滦集团在职及离退休女性职工为研究对象,并进行随访。采用问卷调查、身体测量和实验室检测的方法收集基线社会人口学特征、身高、体重、血糖、血脂、血压及肿瘤发病结局信息。采用Cox比例风险回归模型分析MS及其组分(体重指数、血压、血糖、血脂)与女性乳腺癌发病风险的关系。结果25618名研究对象年龄为(47.65±12.02)岁,中位随访时间为8.78年;乳腺癌新发病例为235例,发病密度为113.19/10万人年。调整年龄、教育程度、经济收入、吸烟状态、饮酒状态等因素后,与体重指数正常者相比,超重或肥胖者的乳腺癌发病风险较高,HR(95%CI)值为1.47(1.12~1.93);与无MS异常组分相比,具有2个MS异常组分的女性乳腺癌发病风险增加(HR=1.70,95%CI:1.16~2.50);随着MS异常组分个数的增加,乳腺癌发病风险逐渐增加(P趋势<0.05)。结论超重/肥胖、MS异常组分的个数均可增加女性乳腺癌发病风险。

关键词：乳腺肿瘤队列研究女(雌)性代谢综合征

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基于疫情防控的门诊电子病历系统优化策略

中国数字医学 2020年第5期15卷 40-41,69页

作者：张艳华包国峰王永杰山东第一医科大学附属省立医院信息网络管理办公室山东省济南市250021

目的:在新冠肺炎疫情下优化门诊就医流程,采集预检发热信息,降低交叉感染风险。方法:从多角度优化改造门诊电子病历系统功能。结果:优化了门诊电子病历系统功能,建立疑似新冠肺炎患者的处理机制。结论:门诊电子病历系统的优化改造为疫... 详细信息

目的:在新冠肺炎疫情下优化门诊就医流程,采集预检发热信息,降低交叉感染风险。方法:从多角度优化改造门诊电子病历系统功能。结果:优化了门诊电子病历系统功能,建立疑似新冠肺炎患者的处理机制。结论:门诊电子病历系统的优化改造为疫情防控提供强有力的技术支撑。

关键词：门诊电子病历预检分诊新冠肺炎信息共享