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Targeting the Warburg effect:A revisited perspective from molecular mechanisms to traditional and innovative therapeutic strategies in cancer

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Acta Pharmaceutica Sinica B 2024年第3期14卷 953-1008页

作者： Minru Liao dahong yao Lifeng Wu Chaodan Luo Zhiwen Wang Jin Zhang Bo Liu Department of Biotherapy Cancer Center and State Key Laboratory of BiotherapyWest China HospitalSichuan UniversityChengdu 610041China School of Pharmaceutical Sciences Shenzhen Technology UniversityShenzhen 518118China School of Pharmacy Shenzhen University Medical SchoolShenzhen UniversityShenzhen 518055China Department of Psychology University of Southern CaliforniaLos AngelesCA 90089USA

Cancer reprogramming is an important facilitator of cancer development and survival,with tumor cells exhibiting a preference for aerobic glycolysis beyond oxidative phosphorylation,even under sufficient oxygen supply *** metabolic alteration,known as the Warburg effect,serves as a significant indicator of malignant tumor *** Warburg effect primarily impacts cancer occurrence by influencing the aerobic glycolysis pathway in cancer *** enzymes involved in this process include glucose transporters(GLUTs),HKs,PFKs,LDHs,and ***,the expression of transcriptional regulatory factors and proteins,such as FOXM1,p53,NF-κB,HIF1a,and c-Myc,can also influence cancer ***,lncRNAs,miRNAs,and circular RNAs play a vital role in directly regulating the Warburg ***,gene mutations,tumor microenvironment remodeling,and immune system interactions are closely associated with the Warburg ***,the development of drugs targeting the Warburg effect has exhibited promising potential in tumor *** comprehensive review presents novel directions and approaches for the early diagnosis and treatment of cancer patients by conducting in-depth research and summarizing the bright prospects of targeting the Warburg effect in cancer.

关键词： Warburg effect Cancer Regulatory factor LncRNAs miRNAs Traditional Chinese medicine Small-molecule drug Drug resistance

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A practical strategy to develop isoform-selective near-infrared fluorescent probes for human cytochrome P450 enzymes

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Acta Pharmaceutica Sinica B 2022年第4期12卷 1976-1986页

作者： Lei Feng Xiangge Tian dahong yao Zhenlong Yu Xiaokui Huo Zhenhao Tian Jing Ning Jingnan Cui Tony D.James Xiaochi Ma Second Affiliated Hospital Dalian Medical UniversityDalian 116023China College of Pharmacy the National&Local Joint Engineering Research Center for Drug Development of Neurodegenerative DiseaseDalian Medical UniversityDalian 116044China School of Pharmaceutical Sciences Shenzhen Technology UniversityShenzhen 518060China State Key Laboratory of Fine Chemicals Dalian University of TechnologyDalian 116024China Department of Chemistry University of BathBath BA27AYUK School of Chemistry and Chemical Engineering Henan Normal UniversityXinxiang 453007China

Currently,the development of selective fluorescent probes toward targeted enzymes is still a great challenge,due to the existence of numerous isoenzymes that share similar catalytic ***,a double-filtering strategy was established to effectively develop isoenzyme-specific fluorescent probe(s)for cytochrome P450(CYP)which are key enzymes involving in metabolism of endogenous substances and *** the first-stage of our filtering approach,near-infrared(NIR)fluorophores with alkoxyl group were prepared for the screening of CYP-activated fluorescent substrates using a CYPs-dependent incubation *** the second stage of our filtering approach,these candidates were further screened using reverse protein-ligand docking to effectively determine CYP isoenzyme-specific probe(s).Using our double-filtering approach,probes S9 and S10 were successfully developed for the real-time and selective detection of CYP2C9 and CYP2J2,respectively,to facilitate high-throughput screening and assessment of CYP2C9-mediated clinical drug interaction risks and CYP2J2-associated disease *** observations suggest that our strategy could be used to develop the isoform-specific probes for CYPs.

关键词： Enzyme activity bioimaging Cytochrome P450 Drugedrug interactions Biomarker analysis Fluorescent probe

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LED光质影响微藻生长和代谢产物积累的研究进展

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食品与发酵工业 2024年第2期50卷 321-328页

作者：孙建瑞姚琳琳李菁岚尤芳芳原江锋王大红河南科技大学食品与生物工程学院、河南省食品微生物工程技术研究中心河南洛阳471000 洛阳海关河南洛阳471000

光质是影响微藻生理代谢的重要环境因子之一,它会影响微藻的生长发育、光合作用及代谢产物的积累等。发光二极管(light emitting diode,LED)作为一种新型冷光源,因具有能耗低、稳定性强、颜色多变、安全环保等优点而被广泛应用,且能按... 详细信息

光质是影响微藻生理代谢的重要环境因子之一,它会影响微藻的生长发育、光合作用及代谢产物的积累等。发光二极管(light emitting diode,LED)作为一种新型冷光源,因具有能耗低、稳定性强、颜色多变、安全环保等优点而被广泛应用,且能按需求获得单色光与复合光谱,是一种非常适合于微藻培养的人工光源。已经有越来越多的研究者和企业关注LED光质在调节微藻生长和代谢产物积累方面的优势。该文对现有文献进行整理,重点综述了LED不同光质对微藻生长及代谢产物积累的影响。在LED单色光(红光、蓝光、绿光、黄光和橙光)中以红光和蓝光对不同类群微藻生物量和代谢产物积累的提升最为显著;而LED混合光,特别是红蓝光往往比单色光更能增加微藻生物量和代谢产物的积累。然而,微藻的光合作用、生长及代谢产物积累的最佳光质在不同类群和同一物种的不同藻株中通常有很大差异。未来,LED光质在微藻生产中的应用应该着重从光质影响微藻代谢产物积累的分子机制、开发新型高效LED光源、开发基于LED光质调节的高效光生物反应器、LED光质应用于微藻大规模培养等几个方面开展。

关键词：微藻光质发光二极管脂质蛋白质碳水化合物类胡萝卜素

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利用DELPHI开发ASP应用程序

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重庆工业高等专科学校学报 2001年第2期16卷 74-76页

作者：张峰姚大红解放军后勤工程学院重庆400016

通过比较纯脚本语言开发和调用DELPHI开发的定制ASP对象的两种方法。

关键词： DELPHI ASP程序定制ASP对象程序设计

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构建现代物流信息标准化体系研究

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商品储运与养护 2007年第1期29卷 37-39,36页

作者：李敏姚大红曹彬后勤工程学院后勤信息实验中心现代物流研究所重庆400016

随着物流信息系统建设步伐的加快,一个十分紧迫的问题摆在我们面前,这就是现代物流信息标准化体系在“十一五”期间具体制定和修订标准的问题。文中首先论述政府在构建现代物流信息化标准化体系所发挥的协调功能作用,接着重点研究了现... 详细信息

随着物流信息系统建设步伐的加快,一个十分紧迫的问题摆在我们面前,这就是现代物流信息标准化体系在“十一五”期间具体制定和修订标准的问题。文中首先论述政府在构建现代物流信息化标准化体系所发挥的协调功能作用,接着重点研究了现代物流信息标准化体系的三个标准,即基础标准、业务标准、相关标准,并对它们各自标准的制定进行了研究。最后论述了信息标准化体系的构建应与国际相接轨,以此来推进现代物流国际标准化进程。总之只有通过构建现代物流信息标准化体系,才能更好、更快地推进现代物流业迅速发展。

关键词：现代物流信息标准化体系

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Molecular glues modulate protein functions by inducing protein aggregation:A promising therapeutic strategy of small molecules for disease treatment

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Acta Pharmaceutica Sinica B 2022年第9期12卷 3548-3566页

作者： Hongyu Wu Hong yao Chen He Yilin Jia Zheying Zhu Shengtao Xu dahong Li Jinyi Xu State Key Laboratory of Natural Medicines Department of Medicinal ChemistryChina Pharmaceutical UniversityNanjing 210009China Division of Molecular Therapeutics&Formulation School of Pharmacythe University of NottinghamUniversity Park CampusNottingham NG72RDUK Key Laboratory of Structure-Based Drug Design&Discovery Ministry of EducationSchool of Traditional Chinese Materia MedicaShenyang Pharmaceutical UniversityShenyang 110016China

Molecular glues can specifically induce aggregation between two or more proteins to modulate biological *** recent years,molecular glues have been widely used as protein *** addition,however,molecular glues play a variety of vital roles,such as complex stabilization,interactome modulation and transporter inhibition,enabling challenging therapeutic targets to be druggable and offering an exciting novel approach for drug *** most molecular glues are identified serendipitously,exploration of their systematic discovery and rational design are *** this review,representative examples of molecular glues with various physiological functions are divided into those mediating homo-dimerization,homo-polymerization and hetero-dimerization according to their aggregation modes,and we attempt to elucidate their mechanisms of *** particular,we aim to highlight some biochemical techniques typically exploited within these representative studies and classify them in terms of three stages of molecular glue development:starting point,optimization and identification.

关键词： Small molecule Molecular glue Dimerization Polymerization Protein–protein interaction

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现代物流信息化建设评估研究

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商品储运与养护 2007年第2期29卷 5-7页

作者：李敏姚大红王开勇曹彬后勤工程学院后勤信息实验中心现代物流研究所重庆400016

随着现代信息技术的发展,信息技术已被广泛应用到物流业各个领域,现代物流信息化建设也日益得到广泛关注。文中主要论述了现代物流信息化建设到一定阶段,借助可靠的评估手段和方法,建立科学、合理、完善的信息化建设评估指标体系,通过... 详细信息

随着现代信息技术的发展,信息技术已被广泛应用到物流业各个领域,现代物流信息化建设也日益得到广泛关注。文中主要论述了现代物流信息化建设到一定阶段,借助可靠的评估手段和方法,建立科学、合理、完善的信息化建设评估指标体系,通过构建定性与定量相结合的三级模糊综合评价模型来对信息化建设所处状态、水平、绩效等做出合理、有效的评估,从而实现现代物流信息化建设的良性发展。

关键词：现代物流信息化建设评估指标体系

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Synthesis of selective PAK4 inhibitors for lung metastasis of lung cancer and melanoma cells

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Acta Pharmaceutica Sinica B 2022年第6期12卷 2905-2922页

作者： Peilu Song Fan Zhao dahong Li Jiqiang Qu Miao yao Yuan Su Hanxun Wang Miaomiao Zhou Yujie Wang Yinli Gao Feng Li Dongmei Zhao Fengjiao Zhang Yu Rao Mingyu Xia Haitao Li Jian Wang Maosheng Cheng Key Laboratory of Structure-Based Drug Design&Discovery of Ministry of Education Shenyang Pharmaceutical UniversityShenyang 110016China MOE Key Laboratory of Protein Sciences School of Pharmaceutical SciencesMOE Key Laboratory of Bioorganic Phosphorus Chemistry Chemical BiologyTsinghua UniversityBeijing 100084China MOE Key Laboratory of Protein Sciences Beijing Advanced Innovation Center for Structural BiologyTsinghua-Peking Joint Center for Life SciencesSchool of Life Sciences and School of MedicineTsinghua UniversityBeijing 100084China School of Traditional Chinese Materia Medica Shenyang Pharmaceutical UniversityShenyang 110016China School of Life Science and Biopharmaceutics Shenyang Pharmaceutical UniversityShengyang 110016China Wuya College of Innovation Shenyang Pharmaceutical UniversityShenyang 110016China Department of Cell Biology Key Laboratory of Cell BiologyMinistry of Public Healthand Key Laboratory of Medical Cell BiologyMinistry of EducationChina Medical UniversityShenyang 110001China

The p21 activated kinase 4(PAK4) is serine/threonine protein kinase that is critical for cancer *** by X-ray crystallography and structure-based optimization,we report a novel subseries of C-3-substituted 6-ethynyl-1 H-indole derivatives that display high potential and specificity towards group Ⅱ *** these inhibitors,compound 55 exhibited excellent inhibitory activity and kinase selectivity,displayed superior anti-migratory and anti-invasive properties against the lung cancer cell line A549 and the melanoma cell line *** 55 exhibited potent in vivo antitumor metastatic efficacy,with over 80% and 90% inhibition of lung metastasis in A549 or B16-BL6 lung metastasis models,*** mechanistic studies demonstrated that compound 55 mitigated TGF-β1-induced epithelial-mesenchymal transition(EMT).

关键词： Anti-cancer PAK4 inhibitor Kinase selectivity Cocrystallization Lung metastasis EMT

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两种天竺葵的精油成分和矿物元素的研究

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香料香精化妆品 2004年第1期 8-11页

作者：李大红姚雷黄健上海交通大学农业与生物学院上海201101 上海爱普香料有限公司上海200072

本研究是对两种天竺葵 (香叶天竺葵 ,Pelargoniumgraveolens;肉豆蔻天竺葵 ,Pelargoniumfragrans)在开花初期时叶中的精油成分和矿物元素进行研究。研究表明 :两种天竺葵在开花初期叶的精油成分和含量有很大的不同 ,香叶天竺葵的精油中... 详细信息

本研究是对两种天竺葵 (香叶天竺葵 ,Pelargoniumgraveolens;肉豆蔻天竺葵 ,Pelargoniumfragrans)在开花初期时叶中的精油成分和矿物元素进行研究。研究表明 :两种天竺葵在开花初期叶的精油成分和含量有很大的不同 ,香叶天竺葵的精油中β -香茅醇 (β -citronellol)、甲酸香茅酯 (citronellylformate)、环己酮 (cyclohexanone)的百分含量最高 ,共占精油组成的 6 5 .82 % ,而肉豆蔻天竺葵中 β -香茅醇 (β -citronellol)、α -崖柏烯 (α -thujene)、葑酮 (fenchone)的百分含量最高 ,共占其精油组成的 33.71%。在矿物元素中 ,10 0克干物质中香叶天竺葵Ca、Na、Mg的百分含量比肉豆蔻天竺葵中多 ;肉豆蔻天竺葵中的S、P的百分含量比香叶天竺葵中多 ;10 0克干物质中微量元素Fe、B、Zn、Mn、Si的百分含量在香叶天竺葵的含量高于肉豆蔻天竺葵。

关键词：精油成分矿物元素分析香叶天竺葵肉豆蔻天竺葵成分分析

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Glacier changes in the Qaidam Basin from 1977 to 2018

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Research in Cold and Arid Regions 2020年第6期12卷 491-502页

作者： SuGang Zhou XiaoJun yao Yuan Zhang dahong Zhang Juan Liu HongYu Duan College of Geography and Environmental Science Northwest Normal UniversityLanzhouGansu 730070China

Based on Landsat MSS/TM/OLI remote sensing images,glaciers vector data in the Qaidam Basin were extracted for 1977,2002,and 2018,and their spatial-temporal variations were *** show that there were 2,050 glaciers covering an area of 1,693.54±40.96 km2 and having an ice volume of 108.65±2.43 km^3 in the Qaidam Basin in *** with areas<1.0 km2 accounted for the largest number,while glaciers with areas of 1.0−5.0 km2 accounted for the most glacierized *** the past 50 years,the number of glaciers decreased by 177,and the glacier area and volume reduced by 338.08 km2(−8.12 km^2/a)and 19.92 km3(−0.48 km^3/a),*** altitudes of glaciers were concentrated at 4,900−5,600 m,4,700−5,200 m,and 5,000−5,600 m and reduced areas accounted for 95.53%,77.80%,and 69.19%in the Kunlun,Qilian,and Altun mountains,*** area of north-oriented glaciers decreased the most(−125.43 km^2),but the west-and east-oriented glaciers retreated at the fastest rate(i.e.,−27.11%and−27.10%).All glaciers showed a decreasing trend in sub-regions of the Qaidam Basin from 1977 to *** decreasing trend was accelerated gradually from northwest to southeast in the northern part of the basin,while glacier change was the smallest in the middle section and gradually accelerated towards both ends of the basin's southern *** temperature had continued to rise,and the precipitation had increased slowly in the Qaidam Basin during the past 50 *** continuous rise in air temperature was the main reason for the retreat of glaciers.

关键词： glacier change climate change Landsat Qaidam Basin

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