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Large-scale loss-of-function perturbations reveal a comprehensive epigenetic regulatory network in breast cancer

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Cancer Biology & Medicine 2024年第1期21卷 83-103页

作者： yumei Wang Haiyan Wang Wei Shao yuhui Chen yu gui Chao Hu Xiaohong Yi Lijun Huang Shasha Li Dong Wang School of Basic Medical Sciences State Key Laboratory of Southwestern Chinese Medicine ResourcesChengdu University of Traditional Chinese MedicineChengdu 611137China Department of Pathology School of MedicineQinghai UniversityXining 810001China Omics Biosciences Inc Beijing 100871China Laboratory of Integrative Medicine Clinical Research Center for BreastState Key Laboratory of BiotherapyWest China HospitalSichuan University and Collaborative Innovation CenterChengdu 610041China State Key Laboratory of Southwestern Chinese Medicine Resources School of PharmacyChengdu University of Traditional Chinese MedicineChengdu 611137China Department of Endocrinology and Metabolism Guangdong Provincial Key Laboratory of Diabetology&Guangzhou Municipal Key Laboratory of Mechanistic and Translational Obesity ResearchMedical Center for Comprehensive Weight ControlThe Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhou 510630China

Objective:Epigenetic abnormalities have a critical role in breast cancer by regulating gene expression;however,the intricate interrelationships and key roles of approximately 400 epigenetic regulators in breast cancer remain *** is important to decipher the comprehensive epigenetic regulatory network in breast cancer cells to identify master epigenetic regulators and potential therapeutic ***:We employed high-throughput sequencing-based high-throughput screening(HTS^(2))to effectively detect changes in the expression of 2,986 genes following the knockdown of 400 epigenetic ***,bioinformatics analysis tools were used for the resulting gene expression signatures to investigate the epigenetic regulations in breast ***:Utilizing these gene expression signatures,we classified the epigenetic regulators into five distinct clusters,each characterized by specific *** discovered functional similarities between BAZ2B and SETMAR,as well as CLOCK and ***,we observed that CLOCK functions in a manner opposite to that of HDAC8 in downstream gene ***,we constructed an epigenetic regulatory network based on the gene expression signatures,which revealed 8 distinct modules and identified 10 master epigenetic regulators in breast ***:Our work deciphered the extensive regulation among hundreds of epigenetic *** identification of 10 master epigenetic regulators offers promising therapeutic targets for breast cancer treatment.

关键词： Epigenetic regulators breast cancer regulatory network HTS^(2)

Efficacy comparison of fruquintinib,regorafenib monotherapy or plus programmed death-1 inhibitors for microsatellite stable metastatic colorectal cancer

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World Journal of Gastrointestinal Oncology 2024年第6期16卷 2449-2462页

作者： Tian-Qi An Hui Qiu Quan-Bo Zhou Hong Zong Shuang Hu yu-gui Lian Rui-Hua Zhao Department of Oncology The First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450000Henan ProvinceChina Department of Hepato-Pancreato-Biliary Surgery Peking University Cancer Hospital and InstituteBeijing 100000China Department of Colorectal Surgery The First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450000Henan ProvinceChina

BACKGROUND Regorafenib(R)and fruquintinib(F)are the standard third-line regimens for colorectal cancer(CRC)according to the National Comprehensive Cancer Network guidelines,but both have limited *** phase 2 trials have indicated that R or F combined with immune checkpoint inhibitors can reverse immunosuppression and achieve promising efficacy for microsatellite stable or proficient mismatch repair(MSS/pMMR)*** to the lack of studies comparing the efficacy between F,R,F plus programmed death-1(PD-1)inhibitor,and R plus PD-1 inhibitors(RP),it is still unclear whether the combination therapy is more effective than *** To provide critical evidence for selecting the appropriate drugs for MSS/pMMR metastatic CRC(mCRC)patients in clinical *** A total of 2639 CRC patients were enrolled from January 2018 to September 2022 in our hospital,and 313 MSS/pMMR mCRC patients were finally *** A total of 313 eligible patients were divided into F(n=70),R(n=67),F plus PD-1 inhibitor(FP)(n=95)and RP(n=81)*** key clinical characteristics were well balanced among the *** median progression-free survival(PFS)of the F,R,FP,and RP groups was 3.5 months,3.6 months,4.9 months,and 3.0 months,*** median overall survival(OS)was 14.6 months,15.7 months,16.7 months,and 14.1 *** FP regimen had an improved disease control rate(DCR)(P=0.044)and 6-month PFS(P=0.014)and exhibited a better trend in PFS(P=0.057)compared with F,and it was also significantly better in PFS than RP(P=0.030).RP did not confer a significant survival benefit;instead,the R group had a trend toward greater benefit with OS(P=0.080)compared with *** significant differences were observed between the R and F groups in PFS or OS(P>0.05).CONCLUSION FP is superior to F in achieving 6-month PFS and DCR,while RP is not better than *** has an improved PFS and 6-month PFS compared with RP,but F and R had similar clinical ***,FP may be a

关键词： Colorectal cancer Fruquintinib Regorafenib Programmed death-1 inhibitor Real-world

Heteroatom Structural Engineering Enables Ethenylene-Bridged Bisisoindigo-Based Copolymers to Exhibit Unique n-Type Transistor Performance

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CCS Chemistry 2024年第2期6卷 473-486页

作者： yuchai Pan Weifeng Zhang Yankai Zhou Xuyang Wei Hao Luo Jinbei Wei Liping Wang gui yu Beijing National Laboratory for Molecular Sciences CAS Research/Education Center for Excellence in Molecular SciencesInstitute of ChemistryChinese Academy of SciencesBeijing 100190 School of Chemical Sciences University of Chinese Academy of SciencesBeijing 100049 School of Material Science and Engineering University of Science and Technology BeijingBeijing 100083

Herein,we report three novel electron-deficient aromatics,ethenylene-bridged bisisoindigos 3,3′-((3E,3′E)-((E)-ethene-1,2-diyl)bis(1-(4-decyltetradecyl)-2-oxoind-oline-6-yl-3-ylidene))bis(1-(4-decyltetradecyl)-1,3-dihydro-2H-pyrrolo[2,3-b]pyridin-2-one)(NCCN),3,3′-((3E,3′E)-((E)-ethene-1,2-diyl)bis(1-(4-decyltetradecyl)-7-fluoro-2-oxoindoline-6-yl-3-ylidene))bis(1-(4-decyltetradecyl)-1,3-dihydro-2H-pyrrolo[2,3-b]pyridin-2-one)(NFFN),and(3E,3″E)-6,6″-((E)-ethene-1,2-diyl)bis(1,1′-bis(4-decyltetradecyl)-[3,3′-bipyrrolo[2,3-b]pyridinylidene]-2,2′(1H,1′H)-dione)(NNNN),and their derived donor–acceptor(D–A)copolymers,namely poly[3,3′-((3E,3′E)-((E)-ethene-1,2-diyl)bis(1-(4-decyltetradecyl)-2-oxoindoline-6-yl-3-ylidene))bis(1-(4-decyltetradecyl)-1,3-dihydro-2H-pyrrolo[2,3-b]pyridin-2-one-6-yl)]-alt-[5,6-difluoro-4,7-di[(thiophen-2-yl)-5-yl)]benzo[c][1,2,5]thiadiazole](PNCCN-FBT),poly[3,3′-((3E,3′E)-((E)-ethene-1,2-diyl)bis(1-(4-decyltetradecyl)-7-fluoro-2-oxoindoline-6-yl-3-ylidene))bis(1-(4-decyltetradecyl)-1,3-dihydro-2H-pyrrolo[2,3-b]pyridin-2-one-6-yl)]-alt-[5,6-difluoro-4,7-di[(thiophen-2-yl)-5-yl)]benzo[c][1,2,5]thiadiazole](PNFFNFBT),and poly[(3E,3″E)-6′,6‴-((E)-ethene-1,2-diyl)bis(1,1′-bis(4-decyltetradecyl)-[3,3′-bipyrrolo[2,3-b]pyridinylidene]-2,2′(1H,1′H)-dione-6-yl)]-alt-[5,6-difluoro-4,7-di[(thiophen-2-yl)-5-yl)]benzo[c][1,2,5]thiadiazole](PNNNN-FBT),in which 5,6-difluoro-4,7-di(thiophen-2-yl)benzo[c][1,2,5]thiadiazole(FBT)acts as the electron-donating *** ethenylene-bridging unit reduces the steric hindrance of the three *** of heteroatoms,such as fluorine and sp2-nitrogen atoms,endows them with multiple CH···F,CH···N,and N···S intramolecular hydrogen bonds/nonbinding interactions,resulting in increasing backbone planarity from NCCN,NFFN,to NNNN,and thus from PNCCN-FBT,PNFFN-FBT,to *** found that all copolymers formed an improved molecular packing in the 1-chloronaphthalene(CN)-processed thin film compared with the 1,2-d

关键词： D-A copolymers bisisoindigos heteroatom structural engineering n-type field-effect transistors electron mobilities

中国城市产业结构与服务功能协同升级的时空演化研究

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数学的实践与认识 2024年第7期54卷 84-99页

作者：卢玉桂广西职业师范学院经济与贸易学院广西南宁530007

实现城市产业结构与服务功能协同升级是推动以人为核心的新型城镇化的迫切要求和关键举措.文章综合运用熵权法、耦合协调度模型、Kernel密度估计法、马尔科夫链模型、Dagum基尼系数及分解等方法展开实证分析,以揭示2010-2021年中国284... 详细信息

实现城市产业结构与服务功能协同升级是推动以人为核心的新型城镇化的迫切要求和关键举措.文章综合运用熵权法、耦合协调度模型、Kernel密度估计法、马尔科夫链模型、Dagum基尼系数及分解等方法展开实证分析,以揭示2010-2021年中国284个城市产业结构与服务功能协同升级的时空演化特征.结果显示:全国及四大区域城市产业结构与服务功能协同水平均呈现稳步上升趋势,但区域异质性明显;中国城市产业结构与服务功能协同升级呈现出“整体水平提升、离散趋势多样、梯度形态不一”的分布特征,层级稳定性和“俱乐部趋同”现象明显,空间溢出效应是影响其演变趋势的重要因素;中国城市产业结构与服务功能协同升级的总体空间差异呈现下滑态势,超变密度、区域间差异、区域内差异的年均贡献率依次降低.

关键词：产业结构优化升级城市服务功能时空演化区域差异

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高频交易:现状、理论与监管

保险研究 2024年第7期 3-17页

作者：李路章玉贵贺宇倩上海外国语大学国际金融贸易学院上海外国语大学国际金融贸易学院党委上海师范大学商学院

经过二十余年发展,高频交易已经成为海外市场主流的交易模式,学术界对其的认识也从初期的一致赞誉演变成如今的众说纷纭。首先,从理论研究而言,高频交易的复杂性在于如何处理信息与价格的关系、信息的构成结构、信息效率与做市效率的权... 详细信息

经过二十余年发展,高频交易已经成为海外市场主流的交易模式,学术界对其的认识也从初期的一致赞誉演变成如今的众说纷纭。首先,从理论研究而言,高频交易的复杂性在于如何处理信息与价格的关系、信息的构成结构、信息效率与做市效率的权衡这三个关键性问题。其次,从实证研究而言,检验的核心始终是高频交易与市场流动性、市场稳定性和市场效率的关系,争论之处在于上述关系在区分正常与极端市场、真实与虚幻流动性、信息与做市效率之后的结论大相径庭。最后,当高频交易的交易量占比过大之后,其与散户投资者、机构投资者、分析师之间甚至是高频交易内部产生了诸多利益冲突。本文旨在梳理高频交易的发展脉络和人类对于高频交易的认知过程,为学术研究和监管政策提供参考。

关键词：高频交易与市场效率价格与信息的关系信息效率与做市效率

乡村振兴视域下清水江林业契约文书中的生态法治理念之价值

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贵州民族研究 2024年第1期45卷 61-66页

作者：王敏余贵忠杨再忠贵州大学法学院贵州贵阳550025 贵州财经大学法学院贵州贵阳550025

清水江林业契约文书中的生态法治理念是古代中国生态法治文化之精髓,亦是该流域本土生态法治文化的集体印记与智慧结晶,其与当下的生态法治理念同根同源,价值不可估量。文章在现有研究基础上扩展其契约自由、主体平等之生态法治理念的... 详细信息

清水江林业契约文书中的生态法治理念是古代中国生态法治文化之精髓,亦是该流域本土生态法治文化的集体印记与智慧结晶,其与当下的生态法治理念同根同源,价值不可估量。文章在现有研究基础上扩展其契约自由、主体平等之生态法治理念的法治特征,并将其纳入法治之中,以探索出其在乡村振兴场域下理论之生态伦理、实践之生态本位、制度之生态法治及信仰之精神支撑等价值,使其成为支撑乡村生态振兴的中流砥柱,彰显对清水江流域的乡村振兴建设有着重要的现实意义。

关键词：乡村振兴林业契约文书生态法治理念

一个新PHEX基因变异导致X连锁遗传性低血磷性佝偻病的家系遗传学分析

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中华骨质疏松和骨矿盐疾病杂志 2024年第3期17卷 213-220页

作者：康可张玉薇张闻宇侯巧芳娄桂予郑州颐和医院关节与运动医学科郑州450018 河南省人民医院医学遗传研究所郑州450002 郑州人民医院内分泌与代谢科郑州450002

目的以一个临床表型为低血磷性佝偻病(hypophosphatemic rickets,HR)的家系为研究对象,通过全外显子组测序寻找该家系的致病变异基因,并分析变异的致病性。方法收集HR家系临床资料,进行生化检测。提取先证者DNA,进行临床全外显子组测序... 详细信息

目的以一个临床表型为低血磷性佝偻病(hypophosphatemic rickets,HR)的家系为研究对象,通过全外显子组测序寻找该家系的致病变异基因,并分析变异的致病性。方法收集HR家系临床资料,进行生化检测。提取先证者DNA,进行临床全外显子组测序,并针对可疑致病变异对家系所有成员进行PCR扩增,Sanger测序验证。预测变异的致病性及对蛋白质空间结构的影响。结果该家系共3代,先证者是一位26岁女性,先证者母亲、先证者及其儿子和女儿为患者,临床表现为O型腿、鸡胸、低磷血症,骨骼X线检查、生化检测、成纤维细胞生长因子23(fibroblast growth factor 23,FGF23)检测结果提示低血磷性佝偻病。临床全外显子组测序发现PHEX(NM_000444)c.2193dupT的插入移码杂合变异,该变异可导致编码第732位的天冬酰胺变异为终止密码子(p.N732*),从而出现了蛋白质截短。先证者的母亲、儿子及女儿PHEX基因均存在该变异。根据美国医学遗传学与基因组学学会(American College of Medical Genetics and Genomics,ACMG)对变异的分类标准,分级为可能致病性变异。经查阅文献及查找人类基因突变数据库,该变异均未被报道或收录。结论本研究发现了一个PHEX新致病变异,为该家系的临床诊断和治疗及遗传咨询提供了实验依据。

关键词： X连锁遗传性低血磷性佝偻病 PHEX基因基因变异

基于标准化红外热成像检测选穴电针治疗肩周炎的效果观察

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中国标准化 2024年第14期 280-283页

作者：于成贵山东省济南市长清区张夏卫生院

目的:探究基于标准化红外热成像检测选穴电针治疗肩周炎的临床效果。方法:选择2023年1月至2023年12月山东省济南市长清区张夏卫生院84例肩周炎患者,随机分成对照组与观察组各42例。对照组采用体外冲击波+双氯芬酸钠治疗,观察组在对照组... 详细信息

目的:探究基于标准化红外热成像检测选穴电针治疗肩周炎的临床效果。方法:选择2023年1月至2023年12月山东省济南市长清区张夏卫生院84例肩周炎患者,随机分成对照组与观察组各42例。对照组采用体外冲击波+双氯芬酸钠治疗,观察组在对照组的基础上基于标准化红外热成像检测选穴进行电针治疗,治疗5天,比较两组的治疗总有效率、治疗前后疼痛评分、肩关节功能评分变化。结果:观察组治疗总有效率95.24%,较对照组80.95%高(P<0.05)。观察组治疗后的疼痛VAS评分明显低于对照组,肩关节功能分值明显高于对照组(P<0.05)。结论:基于标准化红外热成像检测选穴电针治疗肩周炎效果良好,能够更有效减轻患者疼痛感,促进肩关节功能恢复。

关键词：肩周炎标准化红外热成像检测电针治疗选穴

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新型研发机构功能定位的实现机制研究——以北京为例

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科学学研究 2024年第3期42卷 563-570页

作者：于贵芳胡贝贝王海芸北京市科学技术研究院北京100089 中国科学院科技战略咨询研究院北京100190

新型研发机构作为一种新的研发组织形式,正逐步成为创新驱动发展的新生力量。文章从知识协同视角构建了包括机制层、目标层、功能层三方面的新型研发机构功能定位实现机制理论模型,并以北京为例,从中选取北京智源人工智能研究院等3个代... 详细信息

新型研发机构作为一种新的研发组织形式,正逐步成为创新驱动发展的新生力量。文章从知识协同视角构建了包括机制层、目标层、功能层三方面的新型研发机构功能定位实现机制理论模型,并以北京为例,从中选取北京智源人工智能研究院等3个代表性新型研发机构,对其功能定位的实现机制进行了多案例分析,研究发现:新型研发机构通过一系列内部治理机制创新,突破创新协同中的知识流动障碍,支撑其基础研究、应用研究到成果转化集成功能的实现。基于此提出应进一步促进多元主体参与新型研发机构创新,进一步创新管理机制保障新型研发机构成果转化应用等政策启示。

关键词：新型研发机构功能定位实现机制