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Discovery of a potent and highly selective inhibitor of SIRT6 against pancreatic cancer metastasis in vivo

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Acta Pharmaceutica Sinica B 2024年第3期14卷 1302-1316页

作者： Xinyuan Xu Qian Zhang Xufeng Wang Jing Jin Chengwei Wu Li Feng Xiuyan Yang Mingzhu Zhao Yingyi Chen Shaoyong Lu Zhen Zheng Xiaobing Lan Yi Wang Yan Zheng Xuefeng Lu Qiufen Zhang jian Zhang State Key Laboratory of Medical Genomics National Research Center for Translational Medicine at ShanghaiRuijin HospitalShanghai Jiao Tong University School of MedicineShanghai 200025China Medicinal Chemistry and BioinformaticsCenter Shanghai Jiao Tong University School of MedicineShanghai 200025China Department of General Surgery Huashan HospitalCancer Metastasis InstituteFudan UniversityShanghai 200040China Institute of Immunology and the CAS Key Laboratory of Innate Immunity and Chronic Disease School of Basic Medicine and Medical CenterUniversity of Science and Technology of ChinaHefei 230026China Department of Assisted Reproduction Shanghai Ninth People’s HospitalShanghai Jiao Tong University School of MedicineShanghai 200011China College of Pharmacy Ningxia Medical UniversityYinchuan 750004China Department of Pancreatic Surgery Shanghai General HospitalShanghai Key Laboratory of Pancreatic DiseaseInstitute of Pancreatic DiseaseShanghai Jiao Tong University School of MedicineShanghai 200080China

Pancreatic cancer,one of the most aggressive malignancies,has no effective treatment due to the lack of targets and drugs related to tumour ***6 can promote the migration of pancreatic cancer and could be a potential target for antimetastasis of pancreatic ***,highly selective and potency SIRT6 inhibitor that can be used in vivo is yet to be ***,we developed a noveSIRT6 allosteric inhibitor,compound 11e,with maximal inhibitory potency and an IC_(50) value of 0.98±0.13μmol/***,compound 11e exhibited significant selectivity against other histone deacetylases(HADC1-11 and SIRT1-3)at concentrations up to 100μmol/*** allosteric site and the molecular mechanism of inhibition were extensively elucidated by cocrystal complex structure and dynamic structural ***,we confirmed the antimetastatic function of such inhibitors in four pancreatic cancer cell lines as well as in two mouse models of pancreatic cancer liver *** our knowledge,this is the first study to reveal the in vivo effects of SIRT6 inhibitors on liver metastatic pancreatic *** not only provides a promising lead compound for subsequent inhibitor developmentargeting SIRT6 but also provides a potential approach to address the challenge of metastasis in pancreatic cancer.

关键词： SIRT6 Inhibitor Allosteric Selectivity Cocrystal Pancreatic cancer metastasis

原核表达的褐黄血蜱唾液腺蛋白和铁蛋白1的免疫保护效果评价

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畜牧兽医学报 2024年第2期55卷 688-697页

作者：陈玲陈浩岳婵娟马锐范雪阳刘颂蕊杨光友成都大熊猫繁育研究基地四川省濒危野生动物保护生物学重点实验室成都610081 四川农业大学动物医学院成都611130

旨在获得褐黄血蜱重组蛋白(rHfFer1和rHfAV422)并评价其作为抗蜱疫苗的免疫保护效果。通过原核表达获得rHfFer1和rHfAV422,然后将22只新西兰兔随机分为3组(皂素对照组和两个免疫组),其中皂素对照组6只,两个免疫组各8只,所有兔均免疫两次... 详细信息

旨在获得褐黄血蜱重组蛋白(rHfFer1和rHfAV422)并评价其作为抗蜱疫苗的免疫保护效果。通过原核表达获得rHfFer1和rHfAV422,然后将22只新西兰兔随机分为3组(皂素对照组和两个免疫组),其中皂素对照组6只,两个免疫组各8只,所有兔均免疫两次,首免14 d后同等剂量进行二免,二免后一周感染幼蜱,根据蜱的饱血率和蜕皮率为指标评估抗蜱效果。结果显示,rHfFer1和rHfAV422免疫组的饱血率和蜕皮率与对照组均存在显著差异(P<0.05),计算得出rHfFer1和rHfAV422的抗蜱效果分别为68.06%和50.00%。研究结果表明,rHfFer1和rHfAV422可以作为抗蜱疫苗研发的候选抗原。

关键词：褐黄血蜱铁蛋白1 Fer1 唾液腺蛋白 AV422 重组蛋白抗蜱效果

Viewing Chinese modernization and Its Requirements for Human Rights Protection from the Perspective of Human Development

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The Journal of Human Rights 2024年第1期23卷 42-75页

作者：常健 QIAN Chuijun the Centre for the Study of Human Rights at Nankai University the Zhou Enlai School of Government at Nankai University 不详

Modernization,as a specific stage in the historical development of human society,possesses a multi-layered composite structure,with each layer playing both a promoting and inhibiting role in human development and dignity *** modernization is a strategic choice made based on lessons learned from various experiences of modernization processes in other countries,reflecting judgments on the benefits and choices on the values of human development and dignity in *** values the promotion of the free and well-rounded development of all individuals as its standard,demanding the full realization of the positive effects of modernization on human development and the overcoming of its negative *** rights,aiming to promote the free and well-rounded development of every person as the ultimate value goal,are not only an intrinsic structural element of the modernization stage but also a social normative tool that restrains the direction of modernization development,aligning closely with the values pursued by Chinese *** modernization poses dual requirements for human rights protection:on the one hand,it demands the affirmation and promotion of the positive effects of modernization on human development and dignity through human rights standards,and on the other hand,it requires the prevention and mitigation of the negative effects of modernization on human development and dignity through human rights *** exists a certain tension between these two dimensions,necessitating an appropriate balance and thereby presenting corresponding requirements for China’s approach to human rights protection.

关键词： Chinese modernization human development and dignity human rights standards

Effect of Tanshinone IIA on High Glucose-induced Apoptosis and Oxidative Stress Damage in Vascular Endothelial Cells

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Chinese Journal of Biomedical Engineering(English Edition) 2024年第2期33卷 62-68页

作者： QIU Shui-lin HUANG Rong HUANG jian-qing QIU Rong-shui Longyan First Affiliated Hospital of Fujian Medical University Longyan Fujian 364000China Xiamen Medical College Affiliated Haicang Hospital Xiamen Fujian 361003China

Objective:The primary cause of microvascular disease in diabetic complications is long-term hyperglycemia,wherein the damage and apoptosis of vascular endothelial cells play a significant *** tanshinone IIA sulfonate(STS)has been found to have beneficial effects on cardiovascular *** study aimed to investigate the impact of STS on high glucose-induced apoptosis and oxidative stress damage in vascular endothelial cells,as well as its potential protective ***:Human umbilical vein endothelial cells(HUVECs)were divided into five groups:low-glucose group,high-glucose group,and three STS groups(STS-a,STS-b,and STS-c).The low-glucose group was incubated with DMEM low-sugar medium containing 5.5 mmol·L-1glucose,while the high-glucose group was treated with 33.3mmol·*** STS groups were exposed to 10,30,and 50μg·m L-1of STS,*** group was cultured for 72 h,and the MTT method was utilized to assess cell ***,flow cytometry was employed to monitor changes in cell apoptosis and cellular oxidative stress indicators at 24,48,and 72 h of cell culture in each ***:As time went on,the cell proliferation ability and apoptosis rate of each group gradually *** high-glucose group exhibited lower proliferation ability compared to the other *** STS-c group demonstrated the highest OD value for proliferation ability(24 h:1.19±0.12;48 h:1.20±0.13;72 h:1.25±0.12),but it was still lower than that of the low-sugar ***,the high-glucose group had the highest cell apoptosis rate,while the low-glucose group had the *** apoptosis rate of the STS-c group(24 h:8.02±0.13;48 h:10.10±0.12;72 h:13.18±0.11)%was between that of the low-glucose group and the high-glucose group,and lower than the STS-a and STS-b ***,the high-glucose group exhibited the highest malondialdehyde and nitric oxide synthase activities,as well as superoxide dismutase activity and nitric oxide levels,

关键词： tanshinone IIA diabetes vascular endothelial cells oxidative stress apoptosis

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地理学视角下中国农业功能研究进展与展望

热带地理 2024年第1期44卷 56-67页

作者：谭雪兰李印齐安悦周舟刘悦朱晶晶湖南农业大学资源学院长沙410128

伴随中国城镇化、工业化、市场化的快速推进及乡村振兴战略的深入实施,中国农业发展迈入转型升级的新时期。国内学者高度重视农业发展及农业产业为全社会所提供的服务,地理学者充分发挥学科优势,逐步融合多学科理论与方法针对农业功能... 详细信息

伴随中国城镇化、工业化、市场化的快速推进及乡村振兴战略的深入实施,中国农业发展迈入转型升级的新时期。国内学者高度重视农业发展及农业产业为全社会所提供的服务,地理学者充分发挥学科优势,逐步融合多学科理论与方法针对农业功能的概念内涵、理论基础、分类体系、测度评价、时空过程、影响因素及优化路径等开展了诸多研究。文章通过梳理中国知网平台上近10年核心期刊中关于农业功能的学术论文,选取了151篇高质量文献进行研究,得到以下几点结果:1)地理学者聚焦于农业的生产功能、经济功能、及生态功能等方面研究,更加关注农业功能空间分布、地理特征及其与环境的关系;2)人地关系地域系统理论、农业多功能理论、农业区位理论和农业功能阶段论等是农业功能研究的基础,地理学者正不断完善和丰富农业功能相关理论;3)基于GIS和RS技术以及地理数学模型,地理学者进一步研究了农业功能的空间变化与地域特征;4)地理学者科学诊断了不同地理环境下各因子的作用方式、方向与强度,并针对地区地理环境与影响因子进行功能区划与优化;5)未来地理学视角下的农业功能研究需要进一步完善理论框架体系,推动多要素、多尺度、多目标的体系研究;聚焦农业功能转型,强化多学科、大数据、新技术手段的集成研究。

关键词：地理学农业功能农业可持续发展乡村振兴中国

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双循环新发展格局研究综述

新疆师范大学学报（哲学社会科学版） 2024年第5期45卷 91-101页

作者：高伟李岳洋中央财经大学经济学院北京100081

进入“十四五”时期,构建双循环新发展格局是促使我国迈向高质量发展的必经之路,新发展格局及其构建问题成为理论界探讨的一个焦点。文本着眼新发展格局的理论内涵与实施方略,对阐释新发展格局构建问题的现有文献进行全面梳理和评述,并... 详细信息

进入“十四五”时期,构建双循环新发展格局是促使我国迈向高质量发展的必经之路,新发展格局及其构建问题成为理论界探讨的一个焦点。文本着眼新发展格局的理论内涵与实施方略,对阐释新发展格局构建问题的现有文献进行全面梳理和评述,并论述相关实证研究:基于国内循环和国际循环间的关系对双循环新发展格局的科学内涵进行阐释,利用政治经济学理论、大国经济发展理论、经济增长理论、国际贸易理论和“阶段—模式—动力”三维理论对双循环新发展格局展开逻辑说明,并探讨新发展格局的历史逻辑;在实施方略方面,从国际环境、我国国内条件和需要应对的突出矛盾角度探讨双循环新发展格局的实践背景,从产业升级、收入分配、资源分配、现代物流能力改善、扩大内需、数字经济、经济社会基础等角度探讨双循环新发展格局的构建方略;在实证研究方面,论述全球产业链和区域融合发展对产业升级的影响以及双循环新发展格局能否对全要素生产率发挥促进作用。最后,文本对新发展格局构建问题的现有研究作出评价,对未来研究进行展望。

关键词：双循环新发展格局内涵实践实证分析

基于可解释机器学习模型的南宁市野火灾害易发性研究

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科学技术与工程 2024年第2期24卷 858-870页

作者：岳韦霆任超梁月吉郭玥张胜国桂林理工大学测绘地理信息学院桂林541006 广西空间信息与测绘重点实验室桂林541006

野火易发性评价对野火灾害的前期预防以及灾害管理决策的制定至关重要。目前野火易发性的研究主要集中于提高模型的预测精度,而往往忽略对模型的内部决策机制进行解释分析。为此,构建了一种基于可解释机器学习的野火易发性模型,并详细... 详细信息

野火易发性评价对野火灾害的前期预防以及灾害管理决策的制定至关重要。目前野火易发性的研究主要集中于提高模型的预测精度,而往往忽略对模型的内部决策机制进行解释分析。为此,构建了一种基于可解释机器学习的野火易发性模型,并详细分析了各因子对野火易发性预测结果的影响。以南宁市历史野火样本为基础,综合考虑样本的空间分布特征,选取高程、归一化植被指数(normalized difference vegetation index, NDVI)、年均降雨和平均气温等18项评价因子,利用分类和回归树(calssification and regression tree, CART)、随机森林(random forest, RF)、轻量的梯度提升机(light gradient boosting machine, LGBM)和极致梯度提升(extreme gradient boosting, XGBoost)4种机器学习模型构建野火易发性预测模型。基于性能最优的易发性模型,运用沙普利加和解释(shapley additive explanations, SHAP)方法完成特征全局性解释、依赖性分析和典型样本的局部性分析。结果表明:XGBoost较其他模型拥有更优的预测性能,其极高易发区位于南宁市西北部、东部及南部,占全域面积的39.113%;野火灾害易发性主要受NDVI、年均降雨、土壤类型等9项因子的影响;对典型历史野火样本的局部性解释结果可为南宁市指定区域的野火灾害的治理提供针对性参考和指导。

关键词：野火灾害野火易发性评价机器学习模型 SHAP 模型解释

环状RNA对神经血管单元的调控作用及其应用进展

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中国药学杂志 2024年第11期59卷 970-973页

作者：沈灵姚红红东南大学医学院南京210009

环状RNA(circular RNA,circRNA)是一类具有共价闭合环状结构的单链RNA分子,在疾病发生发展中具有重要作用。神经血管单元是指脑微血管细胞、胶质细胞、神经元和细胞外基质等组成的脑功能的基本结构单元,对维持大脑稳态具有重要意义,近... 详细信息

环状RNA(circular RNA,circRNA)是一类具有共价闭合环状结构的单链RNA分子,在疾病发生发展中具有重要作用。神经血管单元是指脑微血管细胞、胶质细胞、神经元和细胞外基质等组成的脑功能的基本结构单元,对维持大脑稳态具有重要意义,近年来已成为多种复杂脑疾病的研究热点。然而circRNA对于神经血管单元的调控作用目前尚未明确,本文就circRNA对神经血管单元的调控作用及其应用的研究进展进行综述,以期为相关疾病提供治疗新靶点和新策略。

关键词：环状RNA 神经血管单元缺血性脑卒中抑郁症

High-efficiency gene editing in Anopheles sinensis using ReMOT control

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Insect Science 2024年第1期31卷 307-312页

作者： Xiao-lin Yang Xia ling Quan Sun Pin-pin Qiu Kai Xiang Jun-feng Hong Shu-lin He Jie Chen Xin Ding Hai Hu Zheng-bo He Cao Zhou Bin Chen Liang Qiao Chongqing Key Laboratory of Vector Insects Institute of Entomology and Molecular BiologyCollege of Life SciencesChongqing Normal UniversityChongqingChina Xunjian Life Science&Technology Co.Ltd. ChongqingChina State Key Laboratory of Resource Insects Southwest UniversityChongqingChina

Dear editor,Functional genomics studies of mosquito vectors are crucial for understanding their physiological behavior,pathogen transmission,and evolution,and for providing essential molecular targets for genetic control(Severson&Behura,201l;Alphey,2014;Ruzzante et al.,2019;Hong et al.,2022).The main methods involve clustered regularly interspaced palindromic repeats(CRISPR)/CRISPR-associated protein 9(Cas9)gene editing via embryo microinjection(Criscione et al.,2015;Kistler et al.,2015).

关键词： editor editing injection