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Mechanism of action of the bile acid receptor TGR5 in obesity

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Acta Pharmaceutica Sinica B 2024年第2期14卷 468-491页

作者： Weijun Lun Qihao Yan Xinghua guo Minchuan Zhou Yan Bai Jincan He hua Cao Qishi Che Jiao guo Zhengquan Su Guangdong Engineering Research Center of Natural Products and New Drugs Guangdong Provincial University Engineering Technology Research Center of Natural Products and DrugsGuangdong Pharmaceutical UniversityGuangzhou 510006China Guangdong Metabolic Disease Research Center of Integrated Chinese and Western Medicine Key Laboratory of Glucolipid Metabolic DisorderMinistry of Education of ChinaGuangdong TCM Key Laboratory for Metabolic DiseasesGuangdong Pharmaceutical UniversityGuangzhou 510006China School of Public Health Guangdong Pharmaceutical UniversityGuangzhou 510310China School of Chemistry and Chemical Engineering Guangdong Pharmaceutical UniversityZhongshan 528458China Guangzhou Rainhome Pharm&Tech Co. Ltd.Science CityGuangzhou 510663China

G protein-coupled receptors(GPCRs)are a large family of membrane protein receptors,and Takeda G protein-coupled receptor 5(TGR5)is a member of this *** a membrane receptor,TGR5 is widely distributed in different parts of the human body and plays a vital role in regulating metabolism,including the processes of energy consumption,weight loss and blood glucose *** studies have shown that TGR5 plays an important role in glucose and lipid metabolism disorders such as fatty liver,obesity and *** the global obesity situation becoming more and more serious,a comprehensive explanation of the mechanism of TGR5 and filling the gaps in knowledge concerning clinical ligand drugs are urgently *** this review,we mainly explain the anti-obesity mechanism of TGR5 to promote the further study of this target,and show the electron microscope structure of TGR5 and review recent studies on TGR5 ligands to illustrate the specific binding between TGR5 receptor binding sites and ligands,which can effectively provide new ideas for ligand research and promote drug research.

关键词： Obesity TGR5 Bile acids Ligand Appetite Metabolism GLP-1 Inflammation

Regioselective C-C bond cleavage/aminocarbonylation cascade under copper catalysis

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Science China Chemistry 2024年第11期67卷 3798-3806页

作者： Qi-Chao Shan Yan Zhao Yong Wu Hong-Fei Liu Xin-hua Duan Li-Na guo Department of Chemistry School of Chemistry Energy Research Center of Energy Storage Materials and Devices Ministry of EducationXi'an Jiaotong University State Key Laboratory of Applied Organic Chemistry Lanzhou University

A regioselective C-C bond cleavage/aminocarbonylation cascade is presented. In recent years, tremendous progress has been made in the alkoxyl radical-mediated C-C bond cleavage of unstrained monocarbocycles. In contrast, the deconstruction and functionalization of bicyclic skeletons has been less developed and has mainly focused on the ring expansion process. Inspired by the aromatization-driven C-C bond cleavage, here we demonstrate a ring-opening/aminocarbonylation cascade under copper catalysis, in which the formation of a stable γ-lactam or succinimide skeleton reverses the selectivity of C-C cleavage. Remarkably, the photo and thermal assistance is not required when the succinimide skeleton is formed during the ring opening process. DFT calculations revealed that this unexpected ring-opening process is thermodynamically and kinetically favourable.

关键词： C-C bond cleavage controllable regioselectivity aminocarbonylation bicyclic alkoxy radical

Simulation and test on the operation process of an intermittent filmpicking component on full-film mulched double ditches

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International Journal of Agricultural and Biological Engineering 2024年第1期17卷 99-108页

作者： Fei dai Feng Wang Wenjuan guo Ruijie Shi Shanglong Xin Xiaolong Liu Wuyun Zhao College of Mechanical and Electrical Engineering Gansu Agricultural UniversityLanzhou 730070China School of Cyber Security Gansu University of Political Science and LawLanzhou 730070China

In view of the problems in operation process of fixed rake-type residual recycling component,such as poor individual profiling effect in film picking,easy clogging of the compound of films,soil and corn stubbles,high power consumption in film picking,and strong disturbance to seedbed soil,in this study,an operation model of intermittent filmpicking on full-film mulched double ditches was proposed and an intermittent film picking component was *** DEMMBD coupled algorithm was adopted for numerical simulation on the operation process of the intermittent film-picking component on full-film mulched double ditches,and a comparative analysis was carried out on the seedbed disturbance effect and resistance variation characteristics in film-picking by fixed and intermittent film-picking *** taking the forward speed in film-picking,cam arrangement angle of the film-picking component and rotating speed of the cam shaft as independent variables,film-picking rate as the response value,a mathematical model between test factors and the film-picking rate was established,to explore the influence order of the factors on film-picking rate,and the optimal working parameters of the intermittent film-picking component were obtained as follows:the forward speed in film-picking was 2 km/h,cam arrangement angle was 180°,rotating speed of the cam shaft was 120 r/*** the optimal parameter combination,the average film-picking rate of the simulation test was 96.1%.Field test showed that,the average film-picking rate of the intermittent film-picking component was 95.6%,and 0.5%higher than that of the simulation *** working condition of the sample machine was basically consistent with the simulation process,and can accurately represent the operation mechanism of intermittent film-picking on full-film mulched double ditches,showing that the established discrete element simulation model and its parameters were accurate and reasonable.

关键词： full-film mulched double ditches residual film recovery intermittent film-picking component DEM-MBD parameter optimization

Mechanisms of tumor immunosuppressive microenvironment formation in esophageal cancer

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World Journal of Gastroenterology 2024年第16期30卷 2195-2208页

作者： Xiao-Jun Zhang Yan Yu He-Ping Zhao Lei guo Kun dai Jing Lv Department of Clinical Laboratory Honghui HospitalXi’an Jiaotong UniversityXi’an 710054Shaanxi ProvinceChina Department of Spinal Surgery Honghui HospitalXi’an Jiaotong UniversityXi’an 710054Shaanxi ProvinceChina Department of Clinical Laboratory Yanliang Railway Hospital of Xi’anXi’an 710089Shaanxi ProvinceChina

As a highly invasive malignancy,esophageal cancer(EC)is a global health issue,and was the eighth most prevalent cancer and the sixth leading cause of cancerrelated death worldwide in *** to its highly immunogenic nature,emerging immunotherapy approaches,such as immune checkpoint blockade,have demonstrated promising efficacy in treating EC;however,certain limitations and challenges still *** addition,tumors may exhibit primary or acquired resistance to immunotherapy in the tumor immune microenvironment(TIME);thus,understanding the TIME is urgent and crucial,especially given the importance of an immunosuppressive microenvironment in tumor *** aim of this review was to better elucidate the mechanisms of the suppressive TIME,including cell infiltration,immune cell subsets,cytokines and signaling pathways in the tumor microenvironment of EC patients,as well as the downregulated expression of major histocompatibility complex molecules in tumor cells,to obtain a better understanding of the differences in EC patient responses to immunotherapeutic strategies and accurately predict the efficacy of ***,personalized treatments could be developed to maximize the advantages of immunotherapy.

关键词： Esophageal cancer Esophageal squamous cell carcinoma Esophageal adenocarcinoma Tumor immune microenvironment Immunosuppression Immunotherapy

Construction of Prediction Model of Foodborne Disease Outbreaks and Its Trend Prediction—Guizhou Province,China,2023-2025

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China CDC weekly 2024年第18期6卷 408-408,I0009,409-412,I0010-I0015页

作者： Li Zhang Sufang Xiong Shu Zhu Jigui Tian Qingyuan Chen Xiaobo Luo hua guo Institute of Public Health Surveillance and Evaluation Guizhou Center for Disease Control and PreventionGuiyang CityGuizhou ProvinceChina School of Public Health Guizhou Medical University.Guiyang CityGuizhou ProvinceChina

Objective:Foodborne diseases pose a significant public health concern *** study aims to analyze the correlation between disease prevalence and climatic conditions,forecast the pattern of foodborne disease outbreaks,and offer insights for effective prevention and control strategies and optimizing health resource allocation policies in Guizhou ***:This study utilized theχ^(2) test and four comprehensive prediction models to analyze foodborne disease outbreaks recorded in the Guizhou Foodborne Disease Outbreak system between 2012 and *** best-performing model was chosen to forecast the trend of foodborne disease outbreaks in Guizhou Province,***:Significant variations were observed in the incidence of foodborne disease outbreaks in Guizhou Province concerning various meteorological factors(all P≤0.05).Among all models,the SARIMA-ARIMAX combined model demonstrated the most accurate predictive performance(RMSE:Prophet model=67.645,SARIMA model=3.953,ARIMAX model=26.544,SARIMA-ARIMAX model=26.196;MAPE:Prophet model=42.357%,SARIMA model=37.740%,ARIMAX model=15.289%,SARIMA-ARIMAX model=13.961%).Conclusion:The analysis indicates that foodborne disease outbreaks in Guizhou Province demonstrate distinct seasonal *** is recommended to concentrate prevention efforts during peak *** SARIMA-ARIMAX hybrid model enhances the precision of monthly forecasts for foodborne disease outbreaks,offering valuable insights for future prevention and control strategies.

关键词： Guizhou prevention offering

2:17-type SmCo permanent magnets with controllable remanence temperature coefficients via substitution of heavy rare earth elements

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Rare Metals 2024年第8期43卷 3990-3996页

作者： Jia-Yi huang Shu-Lan Zuo Qi Zhang Hong-Yang dai Lei Yang Jing-hua Liu Cheng-Bao Jiang Key Laboratory of Aerospace Materials and Performance(Ministry of Education) School of Materials Science and EngineeringBeihang UniversityBeijing 100191China

Permanent magnets that can maintain a constant magnetic flux over a wide temperature range are highly desirable in certain applications such as precision instruments.2:17-type SmCo permanent magnets are promising for such instruments owing to their excellent high-temperature magnetic properties that can be further manipulated byadding heavy rare earth elements (HREs).

关键词： magnets permanent earth

Updates of developments in interventional therapy for elderly patients with cardiovascular diseases

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Journal of Geriatric Cardiology 2024年第1期21卷 1-3页

作者： hua SHEN Xun-Xun FENG Qian-Yun guo Yu-Jie ZHOU Beijing Key Laboratory of Precision Medicine of Coronary Atherosclerotic Disease Beijing Institute of Heart Lung and Blood Vessel DiseaseClinical Center for Coronary Heart DiseaseDepartment of CardiologyBeijing Anzhen HospitalCapital Medical UniversityBeijingChina

Cardiovascular diseases(CVD)are the leading cause of death in the world and one of the most common diseases in the elderly,with high prevalence and poor prognosis,which seriously affect the health of the elder *** report showed that global deaths from CVD increased from 12.4 million in 1990 to 19.8 million in 2022,reflecting the global population growth and aging,as well as the impact of metabolic,environmental,and behavioral risks.[1]With the progress of aging population,the burden of CVD in the elderly in China has increased year by year,and factors including multiple complications,organ function decline,and high complication rate have made the interventional treatment of CVD in the elderly one of the difficulties and focuses in the field of cardiology in China.

关键词： diseases patients prognosis

Molecular Mechanisms of Intracellular Delivery of Nanoparticles Monitored by an Enzyme‑Induced Proximity Labeling

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Nano-Micro Letters 2024年第6期16卷 14-37页

作者： Junji Ren Zibin Zhang Shuo Geng Yuxi Cheng Huize Han Zhipu Fan Wenbing dai hua Zhang Xueqing Wang Qiang Zhang Bing He Department of Pharmaceutics School of Pharmaceutical Sciences Peking University38 Xueyuan RdHaidian DistrictBeijing 100191People’s Republic of China

Achieving increasingly finely targeted drug delivery to organs,tissues,cells,and even to intracellular biomacromolecules is one of the core goals of *** the delivery destination is refined to cellular and subcellular targets,it is essential to explore the delivery of nanomedicines at the molecular ***,due to the lack of technical methods,the molecular mechanism of the intracellular delivery of nanomedicines remains unclear to ***,we develop an enzyme-induced proximity labeling technology in nanoparticles(nano-EPL)for the real-time monitoring of proteins that interact with intracellular ***(lactic-co-glycolic acid)nanoparticles coupled with horseradish peroxidase(HRP)were fabricated as a model(HRP(+)-PNPs)to evaluate the molecular mechanism of nano delivery in *** adding the labeling probe biotin-phenol and the catalytic substrate H_(2)O_(2)at different time points in cellular delivery,nano-EPL technology was validated for the real-time in situ labeling of proteins interacting with ***-EPL achieves the dynamic molecular profiling of 740 proteins to map the intracellular delivery of HRP(+)-PNPs in macrophages over *** on dynamic clustering analysis of these proteins,we further discovered that different organelles,including endosomes,lysosomes,the endoplasmic reticulum,and the Golgi apparatus,are involved in delivery with distinct participation *** importantly,the engagement of these organelles differentially affects the drug delivery efficiency,reflecting the spatial–temporal heterogeneity of nano delivery in *** summary,these findings highlight a significant methodological advance toward understanding the molecular mechanisms involved in the intracellular delivery of nanomedicines.

关键词： Enzyme-induced proximity labeling Intracellular delivery Nano-protein interaction Dynamic molecule profiling Macrophages

Rational design of superior catalysts from topological semimetals with nontrivial energy window

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Rare Metals 2024年第5期43卷 1956-1964页

作者： Min Zhao Li-Rong Wang Wei Liu Ming-Hang Li Ying Liu Xue-Fang dai guo-Dong Liu Xiao-Ming Zhang Key Laboratory of Reliability and Intelligence of Electrical Equipment School of Materials Science and Engineering ManufacturingHebei University of TechnologyTianjin 300130China

Materials featuring topological energy bands and nontrivial surface states hold significant promise in unlocking unprecedented opportunities for innovating electrocatalytic ***,it remains a challenge to realize superior topological catalysts which can carry both high catalytic activity and excellent catalytic ***,we propose that a family of Ni-based binary materials hosting fantasying topological conjunct-nodalpoint state and a large nontrivial energy window(NEWD)represents an ideal choice for such superior topological catalysts in hydrogen evolution *** presence of conjunct-nodal-points ensures long Fermi arcs on the surface,thereby enabling an extremely high catalytic *** NEWD plays a crucial role in stabilizing the high catalytic activity against external perturbations,such as strain and electron/hole *** roles for conjunctnodal-points and NEWD are substantiated by the observable weakening of catalytic performance during topological phase transitions,which result in the removal of the conjunct-nodal-points,NEWD and their corresponding long Fermi *** work unveils a hidden mechanism and opens a feasible route for developing superior quantum catalysts from novel topology point of view.

关键词： First-principles modeling Topological semimetal Nontrivial surface states Hydrogen evolution reaction