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Identification of two distinct transactivation domains in the pluripotency sustaining factor nanog

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Cell Research 2003年第6期13卷 499-502页

作者： GUANG Jin pan, DUAN QING PEI Institute of Pharmacology, department of {2. {2. and biotechnology and State Key Labora tory of Biomembrane and Membrane biotechnology, tsinghua Institutes of Biomedicine, tsinghua university, 100084 beijing, China. E-mail: duanqing@aol.comdepartment of Pharmacology, university of Minnesota, Minneapolis, MN55455, USA 1Institute of Pharmacology Department of Biological Sciences and Biotechnology and State Key Laboratory of Biomembrane and Membrane Biotechnology Tsinghua Institutes of Biomedicine Tsinghua University 100084 Beijing China. E-mail: duanqing@*** 2.0} of Pharmacology University of Minnesota Minneapolis MN55455 USA

Nanog is a newly identified homeodomain gene that functions to sustain the pluripotency of embryonic stem cells. However, the molecular mechanism through which nanog regulates stem cell pluripotency remains unknown. Mouse nanog encodes a polypeptide of 305 residues with a divergent homeodomain similar to those in the NK-2.family. The rest of nanog contains no apparent homology to any known proteins characterized so far. It is hypothesized that nanog encodes a transcription factor that regulates stem cell pluripotency by switching on or off target genes. To test this hypothesis, we constructed fusion proteins between nanog and DNA binding domains of the yeast transcription factor Gal4 and tested the transactivation potentials of these constructs. Our data demonstrate that both regions N- and C- terminal to the homeodomain have transcription activities. Despite the fact that it contains no apparent transactivation motifs, the C-terminal domain is about 7 times as active as the N-terminal one. This unique

关键词： nanog pluripotency stem cells self renewal transactivation domain homeoprotein homeodomain

Enhanced Thermostability of Protein SshlOb due to Induced Conformational Entropy by the pKa Shifts of the Ionizable Residues in the Native State

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Enhanced Thermostability of Protein SshlOb due to Induced Co...

Stem cell pluripotency and transcription factor Oct4

第九届全国酶学学术讨论会暨邹承鲁诞辰85周年纪念会

作者： Meng Ge Xian-Ming pan The Key Laboratory of Bioinformatics,Ministry of Education,department of {2. {2. and biotechnology,tsinghua university,beijing,100084,China

Although the molecular underpinnings of protein thermostabilization have been the focus of many theoretical and experimental efforts,the properties leading to higher denaturation temperatures of hyperthermophilic prot... 详细信息

关键词： thermostabUity conformational entropy proline isomerization pKa shift unfolding free energy change

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Cell Research 2002年第Z2期 321-329页

作者： GUANG JIN pan, ZENG YI CHANG, HANS R. SCHOLER, DUANQING PEI departments of Pharmacology and {2. {2. & biotechnology, Schools of {2. and Medicine,tsinghua university, beijing 100084, China Center for Animal Transgenesis and Germ Cell Research, School of Veterinary Medicine, department of Animal Biology, university of Pennsylvania, New Bolton Center, 382.West Street Road, Kennett Square, PA 19348, USA,department of Pharmacology, university of Minnesota, Minneapolis, MN 55455, USA

Mammalian cell totipotency is a subject that has fascinated scientists for generations. A long lasting question whether some of the somatic cells retains totipotency was answered by the cloning of Dolly at the end of the 2.th century. The dawn of the 2.st has brought forward great expectations in harnessing the power of totipotentcy in medicine. Through stem cell biology, it is possible to generate any parts of the human body by stem cell engineering. Considerable resources will be devoted to harness the untapped potentials of stem cells in the foreseeable future which may transform medicine as we know today. At the molecular level, totipotency has been linked to a singular transcription factor and its expression appears to define whether a cell should be totipotent. Named Oct4, it can activate or repress the expression of various genes. Curiously, very little is known about Oct4 beyond its ability to regulate gene expression. The mechanism by which Oct4 specifies totipotency remains entirely unresolved.

关键词： Oct4 ES cells pluripotency totipotency stem cells cloning.

Antitumor effects of a novel photosensitizer-mediated photodynamic therapy and its influence on the cell transcriptome

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Oncology Research 2024年第5期32卷 911-923页

作者： JINGJING CHEN DAN WANG ZEQUN WANG MENGYUAN HAN HOUQING YIN WENTING ZHOU RIBAI YAN YAN pan department of Pharmacology School of PharmacyChangzhi Medical CollegeChangzhiChina2 Department of PharmacologySchool of Basic Medical SciencesHealth Science CenterPeking UniversityBeijingChina3 Beijing Key Laboratory of Tumor Systems BiologyPeking UniversityBeijingChina4 Department of PharmacologyXinjiang Medical UniversityUrumqiChina5 School of Pharmaceutical SciencesPeking UniversityBeijingChina

Photodynamic therapy(PDT)is a promising cancer *** study investigated the antitumor effects and mechanisms of a novel photosensitizer meso-5-[ρ-diethylene triamine pentaacetic acid-aminophenyl]−10,15,2.-triphenyl-porphyrin(DTP)mediated PDT(DTP-PDT).Cell viability,reactive oxygen species(ROS),and apoptosis were measured with a Cell Counting Kit-8 assay,DCFH-DA fluorescent probe,and Hoechst staining,*** apoptosis-and autophagy-related proteins were examined using western *** sequencing was used to screen differentially expressed mRNAs(DERs),and bioinformatic analysis was performed to identify the major biological events after *** results show that DTP-PDT inhibited cell growth and induced ROS generation in MCF-7 and SGC7901 *** ROS scavenger N-acetyl-L-cysteine(NAC)and the P38 MAPK inhibitor SB2.3580 alleviated DTP-PDT-induced ***-PDT induced cell apoptosis together with upregulated Bax and downregulated Bcl-2.which could also be inhibited by NAC or *** level of LC3B-Ⅱ,a marker of autophagy,was increased by DTP-PDT.A total of 3496 DERs were obtained after *** Ontology and Kyoto Encyclopedia of Genes and Genomes analyses indicated that DERs included those involved in cytosolic ribosomes,the nuclear lumen,protein binding,cell cycle,protein targeting to the endoplasmic reticulum,and ribosomal DNA *** Ontology and Reactome enrichment analyses indicated that DERs were associated with a variety of cancers and cell cycle ***-protein interaction results demonstrated that cdk1 and rps2.a ranked in the top 10 interacting ***,DTP-PDT could inhibit cell growth and induce cell apoptosis and autophagy,partly through ROS and the P38 MAPK signaling *** associated with the cell cycle,ribosomes,DNA replication,and protein binding may be the key changes in DTP-PDT-mediated cytotoxicity.

关键词： Photodynamic therapy ROS Apoptosis Autophagy Bioinformatic analysis

A comparison of optimization theories for energy conservation in heat exchanger groups

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Science Bulletin 2011年第Z1期 449-454页

作者： CHEN Qun1,2.WU Jing3,WANG MoRan4,pan Ning2.& GUO ZengYuan1 1 Key Laboratory for Thermal Science and Power Engineering of Ministry of Education,department of Engineering Mechanics,{2. {2.,beijing 100084,China 2.department of biological and Agricultural Engineering,{2. of California,Davis CA 95616,USA 3 College of Energy and Power Engineering,Nanjing {2. of Aeronautics and Astronautics,Nanjing 2.0016,China 4 Earth and Environmental sciences Division,Los Alamos National Laboratory,Los Alamos NM 87545,USA

In general,thermal processes can be classified into two categories: heat-work conversion processes and heat transfer processes. Correspondingly,the optimization of thermal processes has to have two different criteria:the well known entropy generation minimization method and the recently proposed entransy dissipation maximization method. This study analyzes the thermal issues in a heat exchanger group,and optimizes the unit arrangements under different constraints based on a suitable optimization crite-rion. The result indicates that the principle of minimum entropy generation rate is valid for optimizing heat exchangers in a ther-modynamic cycle with given boundary temperatures. In contrast,the entransy dissipation maximization is more suitable in heat exchanger optimizations involving only heat transfer processes. Furthermore,the entropy generation rate induced by dumping used streams into ambient surroundings has to be taken into account,except for that originating from the hot and cold-ends of heat exchangers,when using the entropy generation minimization to optimize heat exchangers undergoing a thermodynamic cycle.

关键词： heat exchangers optimization criterion entransy dissipation maximization entropy generation minimization

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

Recent advances in chemical protein synthesis:method developments and biological applications

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Science China Chemistry 2024年第4期67卷 1060-1096页

作者： Suwei Dong Ji-Shen Zheng Yiming Li Huan Wang Gong Chen Yongxiang Chen Gemin Fang Jun Guo Chunmao He Honggang Hu Xuechen Li Yanmei Li Zigang Li Man pan Shan Tang Changlin Tian Ping Wang Bian Wu Chuanliu Wu Junfeng Zhao Lei Liu State Key Laboratory of Natural and Biomimetic Drugs and School of Pharmaceutical SciencesPeking UniversityBeijing 100191China Division of Life sciences and Medicine University of Science and Technology of ChinaHefei 230027China School of Food and biological Engineering Engineering Research Center of Bio-processMinistry of EducationHefei University of TechnologyHefei 230009China School of Chemistry and Chemical Engineering Nanjing UniversityNanjing 210023China State Key Laboratory of Elemento-Organic Chemistry Nankai UniversityTianjin 300071China department of Chemistry Tsinghua UniversityBeijing 100084China Institute of Health sciences Anhui UniversityHefei 230601China College of Chemistry Central China Normal UniversityWuhan 430079China School of Chemistry and Chemical Engineering South China University of TechnologyGuangzhou 510640China School of Medicine or Institute of Translational Medicine Shanghai UniversityShanghai 200444China department of Chemistry The University of Hong KongHong Kong 999077China Shenzhen Graduate School Peking UniversityShenzhen 518055China School of Chemistry and Chemical Engineering Shanghai Jiao Tong UniversityShanghai 200240China School of Life sciences University of Science and Technology of ChinaHefei 230026China department of Chemical Biology Shanghai Jiao Tong UniversityShanghai 200240China Institute of Microbiology Chinese Academy of SciencesBeijing 100101China department of Chemistry Xiamen UniversityXiamen 361005China School of Pharmaceutical Science Guangzhou Medical UniversityGuangzhou 511436China

The central dogma of modern biology underscores the pivotal roles proteins play in diverse biological processes,the study of which necessitates advanced methods to produce proteins with precision and *** protein synthesis,a powerful approach utilizing chemical reactions for the de novo construction of structurally accurate proteins,has emerged as a transformative tool for studying proteins and generating protein derivatives/mimics inaccessible by natural biological machinery,including post-translationally modified proteins,proteins comprised of unnatural amino acids,as well as mirror-image *** review summarizes recent strides in synthetic method developments for chemical protein synthesis,including innovative techniques in solid-phase peptide synthesis,the challenges presented by difficult sequences in either synthesis or folding and the exploration of novel ligation reactions using both chemical and enzymatic ***,the review also delves into newly developed protocols for site-selective protein modifications and the generation of stapled or macrocyclized peptides/miniproteins,highlighting the power of chemical methods to make structurally diverse *** applications of synthetic proteins in investigating post-translational modifications(phosphorylation,lipidation,glycosylation,ubiquitination,etc.),mirror-image biological processes and drug development are further ***,these topics provide a comprehensive overview of the current landscape of chemical protein synthesis.

关键词： chemical protein synthesis solid-phase peptide synthesis ligation reactions post-translational modifications mirror-image proteins peptide drugs

Andrographolide Attenuates Noise-Induced Hearing Loss by Ameliorating Cochlear Inflammation

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World Journal of Traditional Chinese Medicine 2024年第2期10卷 204-212页

作者： Meng-Hua Li Wan-Qi Wang Li-Ting Zheng Meng Bing Chen Yang Chu Miao Qiao Zuo-Li Zhang Konduru Naveena Yong pan Yun-Shi Zhang He Sun Xiao-Hui Ma Xi Shi Artificial Auditory Laboratory of Jiangsu Province Xuzhou Medical UniversityXuzhouChina Key Laboratory of Tropical biological Resources of Ministry of Education School of Pharmaceutical SciencesHainan UniversityHaikouChina department of ENT Beijing Friendship HospitalCapital Medical UniversityBeijingChina National Key Laboratory of Chinese Medicine Modernization Tasly AcademyTasly Pharmaceutical Group Co.Ltd.TianjinChina Endoscopy Center Ankang People's HospitalAnkangChina department of Respiratory Medicine Xuzhou Infectious Diseases HospitalAffiliated Hospital of Xuzhou Medical UniversityXuzhouChina department of ENT The People's Hospital of Rongchang DistrictChongqingChina

Objective:This study aimed to explore andrographolide's mechanism of action and its protective effect on noise-induced hearing loss(NIHL).Materials and Methods:A mice animal model for NIHL was established through exposure to broadband noise at 12. d B sound pressure level for 4 *** analysis and pharmacodynamic experiments were carried ***:Andrographolide enters the inner ear and effectively prevents hearing damage following noise exposure in the mice model for permanent hearing ***,treatment with andrographolide inhibited the excessive activation of inflammatory factors in the cochleae of noise-exposed ***:Andrographolide might be a promising candidate for auditory protective drug investigation.

关键词： Andrographolide anti-inflammatory auditory protection noise-induced hearing loss traditional Chinese medicine compound

Genetic variation in a heat shock transcription factor modulates cold tolerance in maize

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Molecular Plant 2024年第9期17卷 1423-1438页

作者： Lei Gao Lingling pan Yiting Shi Rong Zeng Minze Li Zhuoyang Li Xuan Zhang Xiaoming Zhao Xinru Gong Wei Huang Xiaohong Yang Jinsheng Lai Jianru Zuo Zhizhong Gong Xiqing Wang Weiwei Jin Zhaobin Dong Shuhua Yang State Key Laboratory of Plant Environmental Resilience Frontiers Science Center for Molecular Design BreedingCollege of Biological SciencesCenter for Crop Functional Genomics and Molecular BreedingChina Agricultural UniversityBeijing 100193China State Key Laboratory of Maize Bio-breeding National Maize Improvement CenterFrontiers Science Center for Molecular Design BreedingDepartment of Plant Geneticsand BreedingChinaAgricultural UniversityBeijingChina State Key Laboratory of Plant Genomics and National Plant Gene Research Center Institute of Genetics and Developmental BiologyChinese Academy of SciencesBeijing100101China

Understanding how maize(Zea mays)responds to cold stress is crucial for facilitating breeding programs of cold-tolerant *** extensive utilization of the genome-wide association study(GWAs)approach for exploring favorable natural alleles associated with maize cold tolerance,few studies have successfully identified candidate genes that contribute to maize cold *** this study,we used a diverse panel of inbred maize lines collected from different germplasm sources to perform a GWAS on var-iations in the relative injured area of maize true leaves during cold stress-a trait very closely correlated with maize cold *** identified HsF2.,which encodes a B-class heat shock transcription factor(HSF)that positively regulates cold tolerance at both the seedling and germination *** varia-tions in the promoter of the cold-tolerant HSF2.Hap1 allele led to increased HSF2. expression under cold stress by inhibiting binding of the basic leucine zipper bziP68 transcription factor,a negative regulator of cold *** integrating transcriptome deep sequencing,DNA affinity purification sequencing,and targeted lipidomic analysis,we revealed the function of HsF2. in regulating lipid metabolism homeo-stasis to modulate cold tolerance in *** addition,we found that HsF2. confers maize cold tolerance without incurring yield ***,this study establishes HsF2. as a key regulator that en-hances cold tolerance in maize,providing valuable genetic resources for breeding of cold-tolerant maize varieties.

关键词： heat shock factor HSF2. cold tolerance natural variation bZiP68 lipid metabolism maize