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Association of β3 Adrenergic Receptor and Peroxisome Proliferator-activated Receptor Gamma 2 Polymorphisms With Insulin Sensitivity:A Twin Study

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Biomedical and Environmental Sciences 2007年第2期20卷 99-105页

作者： tian-jiao chen chenG-YE JI XIAO-YING ZHENG AND YONG-HUAHU Institute of Child and Adolescent Health Peking University Beijing 100083 China Institute of Population Research Peking University/WHO Collaborating Center on Reproductive Health and Population Science Beijing 100083China Department of Epidemiology and Health Statistics School of Public Health Peking University Beijing 100083 China

Objective To study the effect of β3 adrenergic receptor （β3AR） Trp64Arg and peroxisome proliferator activated receptor gamma 2 （PPAR72） Prol2Ala polymorphisms on insulin resistance. Methods One hundred and eight dizygotic twin pairs were enrolled in this study. Microsatellite polymorphism was used to diagnose zygosity of twins. Insulin sensitivity was estimated with logarithm transformed homeostasis model assessment （HOMA）. PCR-RFLP analysis was performed to detect the variants. As a supplement to the sib-pair method, identity by state （IBS） was used to analyze the association of polymorphisms with insulin sensitivity. Results The genotype frequencies of Trp64Trg, Trp64Arg, and Arg64Arg were 72.3%, 23.8%, and 3.9%, respectively, while the genotype frequencies of Pro12Pro, Pro12Ala, and Ala12Ala were 89.9%, 9.6%, and 0.5%, respectively. For β3AR Trp64Arg the interclass co-twin correlations of Waist-to-hip ratio （WHR）, blood glucose （GLU）, and insulin （INS）, homeostasis model assessment insulin resistance index （HOMA-IR） of the twin pairs sharing 2 alleles of IBS were greater than those sharing 0-1 allele of IBS, and HOMA4R had statistic significance. For PPAR3t2 Prol2Ala most traits of twin pairs sharing 2 alleles of IBS had greater correlations and statistic significance in body mass index （BMI）, WHR, percent of body fat （PBF） and GLU, but there were low correlations of either insulin or HOMA-IR of twin pairs sharing 1 or 2 alleles of IBS. The combined effects of the two variations showed less squared significant twin-pair differences of INS and HOMA-IR among twins sharing 4 alleles of IBS. Condusions β3AR Trp64Arg and PPAR）,2 Pro 12Ala polymorphisms might be associated with insulin resistance and obesity, and there might be slight synergistic effects between this two gene loci, and further studies are necessary to confirm this finding.

关键词： Dizygotic twins Beta-3 adrenergic receptor Peroxisome proliferator activated receptor gamma 2 Polymorphism Insulin resistance.

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Three new aspochalasin derivatives from the marine-derived fungus Spicaria elegans

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Chinese Chemical Letters 2010年第7期21卷 824-826页

作者： Zhen Jian Lin tian jiao Zhu Li chen Qian Qun Gu Key Laboratory of Marine Drugs Chinese Ministry of EducationInstitute of Marine Drugs and FoodOcean University of ChinaQingdao 266003China

Three new aspochalsins（R-T）（1-3） were isolated from the marine-derived fungus Spicaria *** structures were elucidated on the basis of comprehensive spectral analysis including 1D and 2D NMR techniques,and HR-ESI-MS.

关键词： Aspochalasin Spicaria elegans Marine fungus

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A fungal CYP from Beauveria bassiana with promiscuous steroid hydroxylation capabilities

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Chinese Chemical Letters 2024年第5期35卷 218-222页

作者： Yu Peng Yue Wang tian-jiao chen Jing-Jing chen Jin-Ling Yang Ting Gong Ping Zhu State Key Laboratory of Bioactive Substance and Function of Natural Medicines NHC Key Laboratory of Biosynthesis of Natural ProductsCAMS Key Laboratory of Enzyme and Biocatalysis of Natural DrugsInstitute of Materia MedicaChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100050China

Hydroxylation of steroid core is critical to the synthesis of steroid *** sp^(3) C-H hydroxylation is challenging through chemical catalysis,alternatively,fungal biotransformation offers a possible solution to this ***,mining and metabolic engineering of cytochrome P450 monooxygenases(CYPs)is usually regarded as a more eco-friendly and efficient ***,we report the mining and identification of a new steroid CYP(CYP68BE1)from Beauveria bassiana by transcriptomics,heterologous expression,in vivo and in vitro functional *** catalytic promiscuity of CYP68BE1 was explored,and CYP68BE1 showed promiscuously and catalytically versatile,which is qualified for monohydroxylation on C11α,C1α,C6βand dihydroxylation on C1β,11αand C6β,11αof six steroids,leading to the production of key steroid intermediates required in the industrial synthesis of some indispensable steroid *** dynamics simulations were performed,revealing the molecular basis of different binding orientations of CYP68BE1 with different *** discovery of CYP68BE1 offers a promising biocatalyst for enriching the steroid structural and functional diversity,which also can be applied to biosynthesize valuable steroid drug intermediates.

关键词： Fungal CYPs Steroid hydroxylase Beauveria bassiana Promiscuous biocatalyst Molecular dynamics

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Construction of acetyl-CoA and DBAT hybrid metabolic pathway for acetylation of 10-deacetylbaccatin Ⅲ to baccatin Ⅲ

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Acta Pharmaceutica Sinica B 2021年第10期11卷 3322-3334页

作者： Hao Wang Bo-Yong Zhang Ting Gong tian-jiao chen Jing-Jing chen Jin-Ling Yang Ping Zhu State Key Laboratory of Bioactive Substance and Function of Natural Medicines NHC Key Laboratory of Biosynthesis of Natural ProductsCAMS Key Laboratory of Enzyme and Biocatalysis of Natural DrugsInstitute of Materia MedicaChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100050China

10-DeacetylbaccatinⅢ(10-DAB)C10 acetylation is an indispensable procedure for Taxol semi-synthesis,which often requires harsh conditions.10-DeacetylbaccatinⅢ-10-β-O-acetyltransferase(DBAT)catalyzes the acetylation but acetyl-CoA supply remains a key limiting *** we refactored the innate biosynthetic pathway of acetyl-CoA in Escherichia coli and obtained a chassis with acetyl-CoA productivity over three times higher than that of the host ***,we constructed a microbial cell factory by introducing DBAT gene into this chassis for efficiently converting 10-DAB into baccatinⅢ.We found that baccatinⅢcould be efficiently deacetylated into 10-DAB by DBAT with CoASH and K+under alkaline ***,we fed acetic acid to the engineered strain both for serving as a substrate of acetyl-CoA biosynthesis and for alleviating the deacetylation of baccatinⅢ.The fermentation conditions were optimized and the baccatinⅢtiters reached 2,3 and 4.6 g/L,respectively,in a 3-L bioreactor culture when 2,3 and 6 g/L of 10-DAB were *** study provides an environmentfriendly approach for the large scale 10-DAB acetylation without addition of acetyl-CoA in the industrial Taxol *** finding of DBAT deacetylase activity may broaden its application in the structural modification of pharmaceutically important lead compounds.

关键词： Microbial cell factory Biosynthetic pathway of acetyl-CoA Bioconversion of 10-deacetylbaccatinⅢto baccatinⅢ 10-DeacetylbaccatinⅢ-10-β-Oacetyltransferase Deacetylation of baccatinⅢ High-cell-density fermentation Taxol semi-synthesis

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Waist Circumference Distribution of Chinese School-age Children and Adolescents

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Biomedical and Environmental Sciences 2010年第1期23卷 12-20页

作者： chenG-YE JI RITA YT SUNG GUAN-SHENG MA JUN MA ZHONG-HU HE tian-jiao chen Institute of ChiM and Adolescent Health Peking University Health Science Center Beijing 100191 China Department of Paediatrics The Chinese University of Hong Kong Hong Kong Special Administrative Region China National Institute for Nutrition and Food Safety Chinese Center for Disease Control and Prevention Beijing 100021 China

Background Waist circumference （WC）, a proxy measure of central body fat, is a better predictor than overall body fat for cardiovascular risk factors in both adults and children. WC cutoffs have been established in many countries, but the national WC reference has not been developed in China. Objective To study the distribution of WC in a representative group of Chinese children for establishing Chinese WC cutoff points. Methods Cross-sectional data obtained from 15 mainland provinces and Hong Kong were collected. There were 160 225 children and adolescents aged 7-18 years old in total. The subjects were divided into five regional groups namely costal city, other city, noah rural, south rural, and Hong Kong, for analyzing the distribution of WC. Results A large variation in WC distribution was found among the five groups for both sexes. Coastal city group had the highest P85 WC values consistently from the early school ages to 18-year-old compared with other groups. In contrast, south rural group had P85 values consistently lagged behind not only the city groups but also the north rural group. Hong Kong group had a high P85 WC at early ages, but because of the smaller increments of WC during adolescence, the P85 curve was gradually exceeded by the north rural groups. Catch-up trend was found in the two rural groups since the peak of puberty. These disparities were caused by not only socioeconomic and urban-rural factors but also north-south differences. Because of the regional variation of WC, a ＂gradient＂ prevalence of central obesity was prospected among these groups. Comparisons of WC distributions between the Chinese and the U.S.A or Netherlands demonstrated the necessary of setting up China＇s own WC cutoffs. Sex and age-specific percentiles were obtained and smoothed by using LMS method. Conclusion The data obtained from this study could be used to develop national WC cutoff points for Chinese children and adolescents.

关键词： Overweight and obesity Central obesity Waist circumference Chinese youth School-age children and adolescents

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Matching actions to needs: shifting policy responses to the changing health needs of Chinese children and adolescents

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四川生理科学杂志 2024年第4期46卷 866-866页

作者： tian-jiao chen Institute of Child and Adolescent Health School of Public Health Peking University Beijing China National Health Commission Key Laboratory of Reproductive Health Peking University Beijing China National Center for Occupational Safety and Health Beijing China China National Health Development Research Center Beijing China Health Commission of Hainan Province Haikou China Beijing Anding Hospital Capital Medical University Beijing China National Center for Women and Children's Health China Center for Disease Control and Prevention Beijing China Department of Maternal Child and Adolescent Health School of Public Health Anhui Medical University Hefei China MOE Key Laboratory of Population Health Across Life Cycle Anhui Medical University Hefei China Department of Education Economics and Management Graduate School of Education Peking University Beijing China Department of Plastic Surgery Peking University Third Hospital Beijing China Chongqing Municipal Health Care Center for Primary and Secondary Schools Chongqing China Centre for Adolescent Health Royal Children's Hospital Parkville VIC Australia Department of Paediatrics Faculty of Medicine Dentistry and Health Sciences The University of Melbourne Parkville VIC Australia Murdoch Children's Research Institute Parkville VIC Australia Child Health and Development UNICEF China Beijing China

China is home to the second largest population of children and adolescents in the *** demographic shifts mean that the government must manage the challenge of fewer children with the needs of an ageing population,while considering the delicate tension between economic growth and environmental *** mapped the health problems and risks of contemporary school-aged children and adolescents in China against current national health *** involved multidisciplinary experts,including young people,with the aim of identifying actionable strategies and specific recommendations to promote child and adolescent health and *** major improvements in their health over the past few decades,contemporary Chinese children and adolescents face distinct social challenges,including high academic pressures and youth unemployment,and new health concerns including obesity,mental health issues,and sexually transmitted *** by gender,geography,and ethnicity remains a feature of health risks and *** identified a mismatch between current health determinants,risks and outcomes,and government policies.

关键词： policy children shifting

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Combinatorial mutation on the β-glycosidase specific to 7-β-xylosyltaxanes and increasing the mutated enzyme production by engineering the recombinant yeast

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Acta Pharmaceutica Sinica B 2019年第3期9卷 626-638页

作者： Jing-Jing chen Xiao Liang Fen Wang Yan-Hua Wen tian-jiao chen Wan-Cang Liu Ting Gong Jin-Ling Yang Ping Zhu State Key Laboratory of Bioactive Substance and Function of Natural Medicines & NHC Key Laboratory of Biosynthesis of Natural Products Institute of Materia Medica Chinese Academy of Medical Sciences & Peking Union Medical College

Taxol is a 'blockbuster' antitumor drug produced by Taxus species with extremely low amount, while its analogue 7-β-xylosyl-10-deacetyltaxol is generally much higher in the plants. Both the fungal enzymes LXYL-P1à1 and LXYL-P1à2 can convert 7-β-xylosyl-10-deacetyltaxol into10-deacetyltaxol for Taxol semi-synthesis. Of them, LXYL-P1à2 is twice more active than LXYLP1à1, but there are only 11 significantly different amino acids in terms of the polarity and acidic-basic properties between them. In this study, single and multiple site-directed mutations at the 11 sites from LXYL-P1à1 to LXYL-P1à2 were performed to define the amino acids with upward bias in activities and to acquire variants with improved catalytic properties. Among all the 17 mutants, E12(A72 T/V91 S) was the most active and even displayed 2.8-and 3-fold higher than LXYL-P1à2 on β-xylosidase andβ-glucosidase activities. The possible mechanism for such improvement was proposed by homology modeling and molecular docking between E12 and 7-β-xylosyl-10-deacetyltaxol. The recombinant yeast GS115-P1 E12-7 was constructed by introducing variant E12, the molecular chaperone gene pdi and the bacterial hemoglobin gene vhb. This engineered yeast rendered 4 times higher biomass enzyme activity than GS115-3.5 K-P1à2 that had been used for demo-scale fermentation. Thus, GS115-P1 E12-7 becomes a promising candidate to replace GS115-3.5 K-P1à2 for industrial purpose.

关键词： β-Glycosidases Combinatorial mutation Improved catalytic property Molecular docking Engineered yeast Taxol

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Advances in the Development of Gradient Scaffolds Made of Nano‑Micromaterials for Musculoskeletal Tissue Regeneration

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Nano-Micro Letters 2025年第3期17卷 455-500页

作者： Lei Fang Xiaoqi Lin Ruian Xu Lu Liu Yu Zhang Feng tian jiao jiao Li Jiajia Xue Beijing Laboratory of Biomedical Materials Beijing University of Chemical TechnologyBeijing 100029People’s Republic of China State Key Laboratory of Organic‑Inorganic Composites Beijing University of Chemical TechnologyBeijing 100029People’s Republic of China School of Biomedical Engineering Faculty of Engineering and ITUniversity of Technology SydneySydneyNSW 2007Australia

The intricate hierarchical structure of musculoskeletal tissues,including bone and interface tissues,necessitates the use of complex scaffold designs and material structures to serve as tissue-engineered *** has led to growing interest in the development of gradient bone scaffolds with hierarchical structures mimicking the extracellular matrix of native tissues to achieve improved therapeutic *** on the anatomical characteristics of bone and interfacial tissues,this review provides a summary of current strategies used to design and fabricate biomimetic gradient scaffolds for repairing musculoskeletal tissues,specifically focusing on methods used to construct compositional and structural gradients within the *** latest applications of gradient scaffolds for the regeneration of bone,osteochondral,and tendon-to-bone interfaces are ***,the current progress of testing gradient scaffolds in physiologically relevant animal models of skeletal repair is discussed,as well as the challenges and prospects of moving these scaffolds into clinical application for treating musculoskeletal injuries.

关键词： Gradient scaffolds Musculoskeletal tissues Advanced manufacturing Biomaterials Tissue regeneration

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Coordinated Control Strategy of New Energy Power Generation System with Hybrid Energy Storage Unit

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Energy Engineering 2025年第1期122卷 167-184页

作者： Yun Zhang ZifenHan Biao tian Ning chen Yi Fan School of Mechano-Electronic Engineering Xidian UniversityXi’an710071China Electric Power Control Center State Grid Gansu Electric Power CompanyLanzhou730030China Electric Power Control Center State Grid Gansu Electric Power Company Zhangye Power Supply BranchZhangye734000China

The new energy power generation is becoming increasingly important in the power *** as photovoltaic power generation has become a research hotspot,however,due to the characteristics of light radiation changes,photovoltaic power generation is unstable and random,resulting in a low utilization rate and directly affecting the stability of the power *** solve this problem,this paper proposes a coordinated control strategy for a newenergy power generation system with a hybrid energy storage unit based on the lithium iron phosphate-supercapacitor hybrid energy storage ***,the variational mode decomposition algorithm is used to separate the high and low frequencies of the power signal,which is conducive to the rapid and accurate suppression of the power fluctuation of the energy storage ***,the fuzzy control algorithm is introduced to balance the power between energy *** this paper,the actual data is used for simulation,and the simulation results show that the strategy realizes the effective suppression of the bus voltage fluctuation and the accurate control of the internal state of the energy storage unit,effectively avoiding problems such as overshoot and over-discharge,and can significantly improve the stability of the photovoltaic power generation systemand the stability of the Direct Current *** is of great significance to promote the development of collaborative control technology for photovoltaic hybrid energy storage units.

关键词： Photovoltaic power suppression hybrid energy storage unit variationalmodal decomposition fuzzy control power distribution control

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Lipid droplets in the nervous system:involvement in cell metabolic homeostasis

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Neural Regeneration Research 2025年第3期20卷 740-750页

作者： Yuchen Zhang Yiqing chen cheng Zhuang Jingxuan Qi Robert Chunhua Zhao jiao Wang School of Life Sciences Shanghai UniversityShanghaiChina School of Medicine Shanghai UniversityShanghaiChina Institute of Basic Medical Sciences Chinese Academy of Medical Sciences School of Basic MedicinePeking Union Medical CollegeBeijingChina Center of Excellence in Tissue Engineering Chinese Academy of Medical SciencesBeijingChina Beijing Key Laboratory of New Drug Development and Clinical Trial of Stem Cell Therapy BeijingChina

Lipid droplets serve as primary storage organelles for neutral lipids in neurons,glial cells,and other cells in the nervous *** droplet formation begins with the synthesis of neutral lipids in the endoplasmic ***,lipid droplets were recognized for their role in maintaining lipid metabolism and energy homeostasis;however,recent research has shown that lipid droplets are highly adaptive organelles with diverse functions in the nervous *** addition to their role in regulating cell metabolism,lipid droplets play a protective role in various cellular stress ***,lipid droplets exhibit specific functions in neurons and glial *** of lipid droplet formation leads to cellular dysfunction,metabolic abnormalities,and nervous system *** review aims to provide an overview of the role of lipid droplets in the nervous system,covering topics such as biogenesis,cellular specificity,and ***,it will explore the association between lipid droplets and neurodegenerative *** the involvement of lipid droplets in cell metabolic homeostasis related to the nervous system is crucial to determine the underlying causes and in exploring potential therapeutic approaches for these diseases.

关键词： Alzheimer's disease lipid droplet biogenesis lipid droplets lipid metabolism nervous system neurodegenerative disorders oxidative stress Parkinson's disease

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