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Overview of epigenetic degraders based on PROTAC, molecular glue, and hydrophobic tagging technologies

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Acta Pharmaceutica Sinica B 2024年第2期14卷 533-578页

作者： xiaopeng Peng Zhihao Hu Limei Zeng Meizhu Zhang Congcong Xu Benyan lu Chengpeng Tao Weiming Chen Wen Hou Kui Cheng Huichang Bi Wanyi Pan Jianjun Chen College of Pharmacy Key Laboratory of Prevention and Treatment of Cardiovascular and Cerebrovascular Diseases of Ministry of EducationGannan Medical UniversityGanzhou 314000China College of Basic Medicine Gannan Medical UniversityGanzhou 314000China Guangdong Provincial Key Laboratory of New Drug Screening NMPA Key Laboratory for Research and Evaluation of Drug MetabolismSchool of Pharmaceutical SciencesSouthern Medical UniversityGuangzhou 510515China

Epigenetic pathways play a critical role in the initiation, progression, and metastasis of cancer. Over the past few decades, significant progress has been made in the development of targeted epigenetic modulators(e.g., inhibitors). However, epigenetic inhibitors have faced multiple challenges,including limited clinical efficacy, toxicities, lack of subtype selectivity, and drug resistance. As a result,the design of new epigenetic modulators(e.g., degraders) such as PROTACs, molecular glue, and hydrophobic tagging(Hy T) degraders has garnered significant attention from both academia and pharmaceutical industry, and numerous epigenetic degraders have been discovered in the past decade. In this review,we aim to provide an in-depth illustration of new degrading strategies(2017-2023) targeting epigenetic proteins for cancer therapy, focusing on the rational design, pharmacodynamics, pharmacokinetics, clinical status, and crystal structure information of these degraders. Importantly, we also provide deep insights into the potential challenges and corresponding remedies of this approach to drug design and development. Overall, we hope this review will offer a better mechanistic understanding and serve as a useful guide for the development of emerging epigenetic-targeting degraders.

关键词： Epigenetic Degrader PROTAC Molecularglue Hydrophobic tagging

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水库岩溶地质条件评价及防渗处理

水利水电技术（中英文） 2023年第S1期54卷 209-213页

作者：卢晓鹏云南省水利水电科学研究院云南昆明650228

针对德厚水库库区岩溶渗漏问题,利用DPM随钻技术、跨孔电阻率CT测试技术,结合钻孔声波波速测试等检测数据,进行岩溶地质条件评价,判断出受灌地层地质特点。根据不同地质条件及岩层的可灌性,工程采用水泥黏土砂混合膏浆可控高压脉动灌浆... 详细信息

针对德厚水库库区岩溶渗漏问题,利用DPM随钻技术、跨孔电阻率CT测试技术,结合钻孔声波波速测试等检测数据,进行岩溶地质条件评价,判断出受灌地层地质特点。根据不同地质条件及岩层的可灌性,工程采用水泥黏土砂混合膏浆可控高压脉动灌浆技术、水泥膨润土膏浆高压挤密灌浆技术相结合的综合灌浆施工技术,进行强岩溶地区防渗处理,所形成的防渗幕体最大深度达152.5 m。水泥黏土砂混合膏浆可控高压脉动灌浆技术用于强透水土石混杂地层防渗属国内首次应用,灌浆施工后岩体透水率小于5lu,防渗效果显著,水库已正常蓄水,为当地经济社会发展提供了水源保障。

关键词：岩溶地质条件评价防渗处理混合膏浆

Influence of incorporating Si_(3)N_(4) particles into the oxide layer produced by plasma electrolytic oxidation on AM50 Mg alloy on coating morphology and corrosion properties

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Journal of Magnesium and Alloys 2013年第4期1卷 267-274页

作者： xiaopeng lu Carsten Blawert Nico Scharnagl Karl Ulrich Kainer Helmholtz-Zentrum Geesthacht Zentrum fu¨r Material-und Kustenforschung GmbH Institute of Materials ResearchMax-Plank-Str.121502 GeesthachtGerma

The influence of incorporating different sizes of Si_(3)N_(4) particles on the microstructure and corrosion properties of a phosphate-based plasma electrolytic oxidation (PEO) coating on AM50 magnesium alloy was investigated. The experiments for this study were performed in alkaline electrolytes containing 1 g/L KOH, 10 g/L Na_(3)PO_(4) with and without three different sized of Si_(3)N_(4) particles. The corrosion properties of PEO coatings were investigated by potentiodynamic polarization and electrochemical impedance spectroscopy (EIS) in 0.5 wt.% NaCl solution. Microstructure observations by SEM showed that the surface morphology and composition of the PEO coating were affected greatly by particle addition. Si_(3)N_(4) particles can still be found without decomposition in the final coating due to their high melting point.

关键词： Magnesium Plasma electrolytic oxidation Microstructure Corrosion resistance

International Popularization of Beijing Culture: A Cross-cultural Perspective Based on an Investigation of Beijing-based International Students' Identity with Beijing Culture

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Contemporary Social Sciences 2016年第1期1卷 27-41页

作者： lu xiaopeng School of Chinese Language and Literature Beijing Foreign Studies University

To more vigorously promote Beijing culture internationally is bothan essential link in the strategy to turn Beijing into a cultural center and an international exchange center. This promotion would also serve as a critical step to advance the cultural development and internationalization of Beijing. As an important group of foreigners living in Beijing, foreign students can play a unique part in upgrading Beijing culture' s international *** students look at Beijing culture from a cross-cultural standpoint and thus can offer a vital reference for the international promotion effort. Using a combination of questionnaires and interviews, the author surveyed international students in seven Beijing universities that have a relatively high number of foreign students. Based on this firsthand data, this paper analyzes the Beijing-based international students' identity with Beijing culture, reflects on the experiences and inadequacies in the current promotion of Beijing culture, and makes relevant suggestions regarding the inadequacies.

关键词： Beijing culture international students culture identity international popularization

Correlating the crystal structure and facet of indium oxides with their activities for CO_(2)electroreduction

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Fundamental Research 2024年第3期4卷 635-641页

作者： Jiajun Wang Guangjin Wang Han Wu Fei Liu Xixi Ren Yidu Wang Yanhui Cao Qi lu Xuerong Zheng xiaopeng Han Yida Deng Wenbin Hu School of Materials Science and Engineering Key Laboratory of Advanced Ceramics and Machining Technology of Ministry of EducationTianjin UniversityTianjin 300072China School of Materials Science and Energy Engineering Foshan UniversityFoshan 528000China State Key Laboratory of Marine Resource Utilization in South China Sea School of Materials Science and EngineeringHainan UniversityHaikou 570228China Joint School of National University of Singapore and Tianjin University International Campus of Tianjin UniversityBinhai New CityFuzhou 350207China

Constructing structure-function relationships is critical for the rational design and development of efficient catalysts for CO_(2) electroreduction reaction(CO_(2)RR).In_(2)O_(3) is well-known for its specific ability to produce formic ***,how the crystal phase and surface affect the CO_(2)RR activity is still unclear,making it difficult to further improve the intrinsic activity and screen for the most active *** this work,cubic and hexagonal In_(2)O_(3) with different stable surfaces((111)and(110)for cubic,(120)and(104)for hexagonal)are investigated for CO_(2)*** results demonstrate that the adsorption of reactants on cubic In_(2)O_(3) is stronger than that on hexagonal In_(2)O_(3),with the cubic(111)surface being the most active for CO_(2)*** experiments,synthesized cubic In_(2)O_(3) nanosheets with predominantly exposed(111)surfaces exhibited a high HCOO^(-)Faradaic efficiency(87.5%)and HCOO^(–)current density(–16.7 mA cm^(-2))at–0.9 V vs *** addition,an aqueous Zn-CO_(2) battery based on a cubic In2O3 cathode was *** work correlates the phases and surfaces with the CO_(2)RR activity,and provides a fundamental understanding of the structure-function relationship of In_(2)O_(3),thereby contributing to further improvements in its CO_(2)RR ***,the results provide a principle for the directional preparation of materials with optimal phases and surfaces for efficient electrocatalysis.

关键词： Structure-function relationship CO_(2)electroreduction Indium oxide Reactionmechanism Catalyst design

Valproic acid therapy decreases serum 25-hydroxyvitamin D level in female infants and toddlers with epilepsy-a pilot longitudinal study

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The Journal of Biomedical Research 2021年第1期35卷 61-67页

作者： Jinchun Qiu Hongli Guo Ling Li Zeyue Xu Zejun Xu Xia Jing Yahui Hu Xiaoyi Wen Feng Chen xiaopeng lu Department of Pharmacy Children's Hospital of Nanjing Medical UniversityNanjingJiangsu 210008China School of Basic Medicine and Clinical Pharmacy China Pharmaceutical UniversityNanjingJiangsu 211198China Department of Neurology Children's Hospital of Nanjing Medical UniversityNanjingJiangsu 210008China.

To evaluate if valproic acid(VPA)therapy is associated with vitamin D deficiency among infants and toddlers with epilepsy,a cross-sectional clinical study was conducted in 25 children with epilepsy taking *** levels of calcium,phosphorus,alkaline phosphatase,and 25-hydroxy vitamin D[25(OH)D]and plasma VPA level were measured at 1-to 3-month *** the initial and final measurements,vitamin D deficiency or insufficiency was recognized in 8(32%)and 12(42%),*** girls,a decreasing trend in serum25(OH)D levels(Plusion,our study indicates that a high proportion of girls after VPA therapy had hypovitaminosis D.

关键词： valproic acid vitamin D hypovitaminosis D epilepsy infants and toddlers

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扬州市初中生体力活动与睡眠焦虑的关系

中国学校卫生 2022年第8期43卷 1185-1188页

作者：卢晓鹏谭长青谭业麒江苏省扬州市第一中学 225100 扬州大学体育学院南京邮电大学通达学院

目的探讨初中生体力活动现状及其与睡眠、焦虑的关系,为改善身体素质、调节心理健康提供切实有效的证据。方法采取分层随机抽样方法,于2021年3—7月选取扬州市4个县区12所初中的11 436名初中生为调查对象。利用匹兹堡睡眠质量指数量表... 详细信息

目的探讨初中生体力活动现状及其与睡眠、焦虑的关系,为改善身体素质、调节心理健康提供切实有效的证据。方法采取分层随机抽样方法,于2021年3—7月选取扬州市4个县区12所初中的11 436名初中生为调查对象。利用匹兹堡睡眠质量指数量表(PSQI)、体力活动等级量表(PARS-3)以及广泛性焦虑量表(GAD-7)采集受试者体力活动等级、睡眠得分以及焦虑得分。采用单因素方差分析、χ^(2)检验分析初中生各项指标之间的差异及相关性,采用线性回归分析体力活动与睡眠质量、焦虑的关系。结果有34.30%的初中生为低体力活动水平;初中男生的体力活动得分(32.01±13.02)高于女生(24.73±12.30)(t=30.73,P<0.01);不同体力活动水平学生焦虑、睡眠质量差异均有统计学意义(F值分别为260.20,1 570.20,P值均<0.01);体力活动水平与性别(χ^(2)=918.11)、父母运动支持(χ^(2)=100.04)、睡眠质量(χ^(2)=2 903.64)、焦虑(χ^(2)=521.38)均相关(P值均<0.01)。线性回归分析结果显示,中体力活动与睡眠质量呈负相关(B=-3.61,P<0.05);中、高体力活动水平与焦虑呈负相关(B值分别为-0.98,-0.91,P值均<0.05)。结论扬州市初中生体力活动水平不理想,同时存在睡眠障碍、焦虑等问题,适当的体力活动能有效改善睡眠障碍、焦虑问题。

关键词：运动活动睡眠焦虑精神卫生回归分析学生

Small-molecule agents for cancer immunotherapy

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Acta Pharmaceutica Sinica B 2024年第3期14卷 905-952页

作者： Fang Wang Kai Fu Yujue Wang Can Pan Xueping Wang Zeyu Liu Chuan Yang Ying Zheng xiaopeng Li Yu lu Kenneth Kin Wah To Chenglai Xia Jianye Zhang Zhi Shi Zeping Hu Min Huang Liwu Fu State Key Laboratory of Oncology in South China Collaborative Innovation Center for Cancer MedicineGuangdong Esophageal Cancer InstituteGuangdong Provincial Clinical Research Center for CancerSun Yat-sen University Cancer CenterGuangzhou 510060China School of Pharmaceutical Sciences Tsinghua-Peking Center for Life SciencesBeijing Frontier Research Center for Biological StructureTsinghua UniversityBeijing 100084China State Key Laboratory of Drug Research Shanghai Institute of Materia MedicaChinese Academy of SciencesShanghai 201203China Department of Cell Biology&Institute of Biomedicine National Engineering Research Center of Genetic MedicineMOE Key Laboratory of Tumor Molecular BiologyGuangdong Provincial Key Laboratory of Bioengineering MedicineCollege of Life Science and TechnologyJinan UniversityGuangzhou 510632China Guangzhou Municipal and Guangdong Provincial Key Laboratory of Molecular Target&Clinical Pharmacology NMPA and State Key Laboratory of Respiratory DiseaseSchool of Pharmaceutical Sciences and the Fifth Affiliated HospitalGuangzhou Medical UniversityGuangzhou 511436China School of Pharmacy The Chinese University of Hong KongHong Kong 999077China Affiliated Foshan Maternity and Child Healthcare Hospital Southern Medical UniversityFoshan 528000China

Cancer immunotherapy,exemplified by the remarkable clinical benefits of the immune checkpoint blockade and chimeric antigen receptor T-cell therapy,is revolutionizing cancer *** induce long-term tumor regression and overall survival benefit in many types of *** the advances in our knowledge about the tumor immune microenvironment,remarkable progress has been made in the development of small-molecule drugs for *** molecules targeting PRR-associated pathways,immune checkpoints,oncogenic signaling,metabolic pathways,cytokine/chemokine signaling,and immune-related kinases have been extensively *** of smallmolecule immunotherapeutic drugs and their combinations with other antitumor modalities are under active clinical investigations to overcome immune tolerance and circumvent immune checkpoint inhibitor ***,we review the latest development of small-molecule agents for cancer immunotherapy by targeting defined pathways and highlighting their progress in recent clinical investigations.

关键词： Cancer immunotherapy Small-molecule agents Immune checkpoints Oncogenic signaling Metabolic pathways Cytokine/chemokine signaling Antitumor immunity Tumor immune microenvironment

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草莓和蓝莓镉积累特征分析

分子植物育种 2022年第19期20卷 6532-6540页

作者：张子木谢深喜卢晓鹏湖南农业大学园艺学院长沙410128 国家柑橘改良中心长沙分中心长沙410128

通过改变基质镉含量和灌溉水pH值的方法研究镉污染对草莓和蓝莓的影响,以期为土壤镉超标区域草莓与蓝莓安全栽培提供理论依据。研究结果表明,不同种类的果树镉富集特征不同,相同条件下蓝莓地上部分镉含量、富集系数和转运系数低于草莓... 详细信息

通过改变基质镉含量和灌溉水pH值的方法研究镉污染对草莓和蓝莓的影响,以期为土壤镉超标区域草莓与蓝莓安全栽培提供理论依据。研究结果表明,不同种类的果树镉富集特征不同,相同条件下蓝莓地上部分镉含量、富集系数和转运系数低于草莓。草莓与蓝莓各部位镉含量随基质中镉含量的上升而上升,不同镉浓度处理下体内镉含量均以根部最高,茎叶部分次之,果实最低。随处理pH值升高各组织部位镉含量先降后升,草莓中镉含量最低的处理是pH 5.5和pH 7.0,蓝莓中镉含量最低的是pH 4.0和pH 5.5。因此,草莓和蓝莓对基质镉含量敏感,较容易富集土壤镉而导致果实镉含量超标,蓝莓作为木本果树其根茎叶对镉富集能力较强;草莓和蓝莓富集基质镉的能力对pH敏感,较低的pH值更有利于作物镉富集。本研究结果为进一步比较研究草本和木本植物镉积累规律提供了科学依据,也为草莓蓝莓的安全栽培提供了参考。

关键词：镉草莓蓝莓镉积累特征