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Mechanism of action of the bile acid receptor TGR5 in obesity

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

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Dcalycinumines A-E,Alkaloids with Cytotoxic Activities of Nasopharyngeal Carcinoma Cells from Daphniphyllum calycinum

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Chinese Journal of Chemistry 2024年第1期42卷 35-42页

作者： Qing Tang Xiao-Yong Dai Qiang Lin Zhi-Peng Ling Yi-Kun Hao Tian-Xi Zhu Ji-Hui Zhang Yi-Bo Hou Yao-Lan Li Lai-Qiang Huang Jing-Hao Wang Guo-Cai Wang Yu-Bo Zhang guangdong Clinical Translational centerfor Targeted Drug Department of PharmacologySchoolof MedicineJinan University GuangzhouGuangdong 510632China Institute of Traditional Chinese Medicine&natural products Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs ResearchCollegeof PharmacyJinan UniversityGuangzhouGuangdong511443China Institute of Biopharmaceutical and Health engineering Shenzhen Key Laboratory of Gene and Antibody TherapyState Key Laboratory of Chemical OncogenomicsShenzhen International Graduate SchoolTsinghua UniversityShenzhenGuangdong 518055China The Guangzhou Key Laboratoryof Basic and Translational research on Chronic Disease Department of PharmacyThe First Affiliated HospitalJinan UniversityGuangzhouGuangdong 510630China

Fivenovel Daphniphyllum alkaloids,named dcalycinumines A-E(1-4,6),andeight previously described Daphniphyllum alkaloids(5,7-13)were isolated from Daphniphyllum *** 1 is the first Daphniphyllum alkaloid possessing a highly rearranged 6/6/6/7/5/6 hexacyclic architecture with a unique 3-methyl-1-azabicyclo[4,4,0]decane ring *** 2 represents a rare diamino Daphniphyllum alkaloid with an unprecedented 6/5/5/6/6/5 carbon skeleton featuring a unique 1-aza-6-azaspiro[4,5]decane unit,whereas 3 also represents a rare diamino Daphniphyllum alkaloid as a possible precursor of *** 4 is the second example of c-22-nor yuzurimine-type *** structures and absolute configurations were elucidated by HRESIMS,NMR spectroscopic analyses,EcD calculations,and single-crystal X-ray ***,compound 1 showed remarkable antitumor activities,which could inhibit the proliferation,migration and invasion of nasopharyngeal carcinoma cells,and promoted nasopharyngeal carcinoma cells apoptosis.

关键词： Daphniphyllum calycinum natural products Daphniphyllum alkaloid Structural elucidation Biological activity Apoptosis Nasopharyngealcarcinoma

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Encouraging Solution to the Problem of Synthesizing Protein α-Thioester

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Chinese Journal of Chemistry 2024年第10期42卷 1114-1120页

作者： Xinliang Liu Zijun Gao Jie Zhao Farong Ye Ping Huang Ping Wang center for Chemical Glycobiology Shanghai Key Laboratory for Molecular Engineering of Chiral DrugsFrontiers Science Center for Transformative MoleculesSchool of Chemistry and Chemical EngineeringZhangjiang Institute for Advanced StudyShanghai JiaoTongUniversityShanghai 200240China Shenzhen research Institute of Shanghai Jiao Tong University ShenzhenGuangdong 518057China

Expressed protein ligation(EPL)provides a powerful tool to access large-size proteins with precise *** methods for constructing the critical protein thioester for EPL have predominantly relied on the recombinant intein fusion expressed in Escherichia coli(***).Despite its powerful applications,the expression of thioester derived from eukaryotic protein in *** inherently suffers from its limited solubility,the inactivity of intein,premature hydrolysis and low *** overcome these obstacles,we present herein the facile one-flask synthesis of inaccessible proteinα-thioester via a SUMO-protein-intein(SPI)sandwich *** utility of SUMO enhances the protein fusion yield and solubility,prevents premature hydrolysis and simplifies the purification *** inaccessible protein thioester with internal Cys residues can be readily produced and is compatible with the EPL-desulfurization protocol used to prepare complex proteins,which is otherwise difficult to obtain using traditional *** utility has been highlighted through the synthesis of human granulocyte colony-stimulating factor(G-CSF).

关键词： Desulfurization Glycoproteins Glycopeptides Protein expression Peptide thioester

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A novel marine-derived anti-acute kidney injury agent targeting peroxiredoxin 1 and its nanodelivery strategy based on ADME optimization

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Acta Pharmaceutica Sinica B 2024年第7期14卷 3232-3250页

作者： Ping Yu Tanwei Gu Yueyang Rao Weimin Liang Xi Zhang Huanguo Jiang Jindi Lu Jianglian She Jianmin Guo Wei Yang Yonghong Liu Yingfeng Tu Lan Tang Xuefeng Zhou guangdong Provincial Key Laboratory of new Drug Screening Guangdong-Hong Kong-Macao Joint Laboratory for New Drug ScreeningSchool of Pharmaceutical SciencesSouthern Medical UniversityGuangzhou 510515China CAS Key Laboratory of Tropical Marine Bio-Resources and Ecology Guangdong Key Laboratory of Marine Materia MedicaSouth China Sea Institute of OceanologyChinese Academy of SciencesGuangzhou 510301China NMPA Key Laboratory for research and Evaluation of Drug Metabolism School of Pharmaceutical SciencesSouthern Medical UniversityGuangzhou 510515China guangdong Lewwin Pharmaceutical research Institute Co. Ltd.Guangdong Provincial Key Laboratory of Drug Non-Clinical Evaluation and ResearchGuangdong Engineering Research Center for Innovative Drug Evaluation and ResearchGuangzhou 510990China

Insufficient therapeutic strategies for acute kidney injury(AKI)necessitate precision therapy targeting its *** study reveals the new mechanism of the marine-derived anti-AKI agent,piericidin glycoside S14,targeting peroxiredoxin 1(PRDX1).By binding to Cys83 of PRDX1 and augmenting its peroxidase activity,S14 alleviates kidney injury efficiently in Prdx1-overexpression(Prdx1-OE)***,S14 also increases PRDX1 nuclear translocation and directly activates the Nrf2/HO-1/NQO1 pathway to inhibit ROS *** to the limited druggability of S14 with low bioavailability(2.6%)and poor renal distribution,a pH-sensitive kidney-targeting dodecanaminechitosan nanoparticle system is constructed to load S14 for precise treatment of AKI.L-Serine conjugation to chitosan imparts specificity to kidney injury molecule-1(Kim-1)-overexpressed *** developed S14-nanodrug exhibits higher therapeutic efficiency by improving the in vivo behavior of S14 *** encapsulation with micelles,the AUC_(0-t),half-life time,and renal distribution of S14 increase 2.5-,1.8-,and 3.1-fold,*** main factors contributing to the improved druggability of S14 nanodrugs include the lower metabolic elimination rate and UDPglycosyltransferase(UGT)-mediated *** summary,this study identifies a new therapeutic target for the marine-derived anti-AKI agent while enhancing its ADME properties and druggability through nanotechnology,thereby driving advancements in marine drug development for AKI.

关键词： Acute kidney injury Piericidin glycoside Peroxiredoxin 1 Nanodrug Kim-1 targeted ADME Marine drug Druggability

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Antibacterial mechanism of kojic acid and tea polyphenols against Escherichia coli O157:H7 through transcriptomic analysis

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Food Science and Human Wellness 2024年第2期13卷 736-747页

作者： Yilin Lin Ruifei Wang Xiaoqing Li Keren Agyekumwaa Addo Meimei Fang Yehui Zhang Yigang Yu School of Food Sciences and engineering South China University of TechnologyGuangzhou 510640China Sericulture&Agri-food research Institute guangdong Academy of Agricultural Sciences Key Laboratory of Functional FoodsMinistry of Agriculture and Rural AffairsGuangdong Key Laboratory of Agricultural Products ProcessingGuangzhou 510610China research center of Food Safety and Detection College of Food Science and EngineeringSouth China University of TechnologyGuangzhou 510640China

Escherichia coli O157:H7 is one of the major foodborne pathogenic bacterial that cause infectious diseases in *** previous found that a combination of kojic acid and tea polyphenols exhibited better activity against *** O157:H7 than using either *** study aimed to explore responses underlying the antibacterial mechanisms of kojic acid and tea polyphenols from the gene *** functional enrichment analysis by comparing kojic acid and tea polyphenols individually or synergistically against *** O157:H7 found that acid resistance systems in kojic acid were activated,and the cell membrane and genomic DNA were destructed in the cells,resulting in“oxygen starvation”.The oxidative stress response triggered by tea polyphenols inhibited both sulfur uptake and the synthesis of ATP,which affected the bacteria's life metabolic ***,we found that kojic acid combined with tea polyphenols hindered the uptake of iron that played an essential role in the synthesis of DNA,respiration,tricarboxylic acid *** results suggested that the iron uptake pathways may represent a novel approach for kojic acid and tea polyphenols synergistically against *** O157:H7 and provided a theoretical basis for bacterial pathogen control in the food industry.

关键词： Kojic acid Tea polyphenols Antibacterial mechanism Escherichia coli O157:H7 RNA-seq

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Photodegradation of xylene isomers:Kinetics,mechanism,secondary pollutant formation potential and health risk evaluation

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Journal of Environmental Sciences 2024年第2期136卷 658-669页

作者： Xiaoyan Chen Weikun Zhu Sufen Feng Jiangyao Chen guangdong Key Laboratory of Environmental Catalysis and Health Risk Control Guangdong Technology Research Center for Photocatalytic Technology Integration and Equipment EngineeringInstitute of Environmental Health and Pollution ControlGuangdong University of TechnologyGuangzhou 510006China Guangzhou Key Laboratory of Environmental Catalysis and Pollution Control Guangdong-Hong Kong-Macao Joint Laboratory for Contaminants Exposure and HealthSchool of Environmental Science and EngineeringGuangdong University of TechnologyGuangzhou 510006China

Photodegradation technology has been widely applied in the purification of industrial aromatic ***,whether this technology efficiently removes the pollutants to prevent secondary pollution and health risk is still ***,the photodegradation processes of three xylenes were compared under designed reaction atmospheres and light *** lamp showed poor photodegradation ability toward xylenes,no matter in N_(2) or N_(2)+O_(2)system,while much higher photodegradation performance of xylenes were obtained under ultraviolet(UV)and vacuum ultraviolet(VUV)irradiation,especially in N_(2)+O_(2)+VUV system,where 97.9%of m-xylene,99.0%of o-xylene or 87.5%of p-xylene with the initial concentration of 860 mg/m^(3) was removed within 240 *** xylenes underwent three processes of photo-isomerization,photodecomposition and photo-oxidation to produce intermediates of aromatics,alkanes and *** them,the photo-isomerization products showed the highest concentration percentage(e.g.,≥50%in o-xylene system),confirming that photo-isomerization reaction was the dominated photodegradation process of ***,these isomerized products not only contributed about 97%and91%to the formation potential of O3(OFP)and secondary organic aerosols(SOAFP),but also displayed obvious non-carcinogenic risk,although one of photodecomposition product—benzene showed the highest occupational exposure ***,the secondary pollution and health risks of photodegradation products of xylenes were non-ignorable,although the OFP,SOAFP and health risks of the generated products reduced at least 4.5 times in comparison with that of the degraded *** findings are helpful for the appropriate application of this technology in the purification of industrial organic waste gas.

关键词： Isomer aromatics Photodegradation Ozone formation Secondary organic aerosols Health risk

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Cobalt phthalocyanine promoted copper catalysts toward enhanced electro reduction of CO_(2)to C_(2):Synergistic catalysis or tandem catalysis?

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Journal of Energy Chemistry 2024年第5期92卷 499-507页

作者： Yan Luo Jun Yang Jundi Qin Kanghua Miao Dong Xiang Aidar Kuchkaev Dmitry Yakhvarov Chuansheng Hu Xiongwu Kang new Energy research Institute School of Environment and EnergySouth China University of TechnologyHigher Education Mega CenterGuangzhou 510006GuangdongChina guangdong University of Petrochemical Technology School of Chemical EngineeringMaoming 525000GuangdongChina Arbuzov Institute of Organic and Physical Chemistry FRC Kazan Scientific Center of RASArbuzov Street 8Kazan 420088Russian Federation National Synchrotron Radiation Laboratory University of Science and Technology of ChinaHefei 230029AnhuiChina

The activity and selectivity of electrocatalytic CO_(2)reduction reaction(CO_(2)RR)to C_(2)products on metal catalysts can be regulated by molecular ***,the mechanism behind it remains elusive and ***,copper nanowires(Cu NWs)were fabricated and decorated with cobalt phthalocyanine(CoPc).The electronic interaction between the Cu NWs,CoPc,CO_(2) and CO_(2)RR intermediates were explored by density functional theory(DFT)*** was found that the selectivity and activity of CO_(2)RR towards C_(2)products on Cu NWs were considerably enhanced from 35.2%to 69.9%by surface decoration of *** calculations revealed that CO_(2)RR can proceed in the interphase between Cu substrate and CoPc,and the CO_(2)RR intermediates could synergistically bond with both Cu and Co metal centre in CuNWs-CoPc,which favours the adsorption of CO_(2),CO and CO_(2)RR intermediates,thus reducing the free energy for CO-COcoupling towards C_(2)*** synergistic interaction was further extended to phthalocyanine(Pc)and other metal phthalocyanine derivatives(MPc),where a relatively weaker synergistic interaction of COintermediates with MPc and Cu substrate and only a slight enhancement of CO_(2)RR towards C_(2) products were *** study demonstrates a synergistic catalysis pathway for CO_(2)RR,a novel perspective in interpreting the role of CoPc in enhancing the activity and selectivity of CO_(2)RR on Cu NWs,in contrast to the conventional tandem catalysis mechanism.

关键词： CO_(2)reduction reaction Raman spectroscopy Synergistic catalysis DFT calculation

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Efficient Photolytic Halogenation and Oxidation of Unactivated Alkyl sp^(3) C—H Bonds with Iodine(III)

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Chinese Journal of Chemistry 2024年第5期42卷 505-510页

作者： Hao Jia Nan Li Chunmei Tang Yajuan Wang Yonghao Xi Rongbao Liao Wei Xu Fufang Wu Xiaobao Shen Hongbin Zhai Biomass Oligosaccharides engineering Technology research center of Anhui Province Engineering Research Center of Biomass Conversion and Pollution Prevention of Anhui Educational InstitutionsFuyang Normal UniversityFuyangAnhui236037 China Institute of Marine Biomedicine Shenzhen PolytechnicShenzhenGuangdong518055 China State Key Laboratory of Chemical Oncogenomics Shenzhen Engineering Laboratory of Nano Drug Slow-ReleasePeking University Shenzhen Graduate SchoolShenzhenGuangdong518055 China

A metal-free,green,and sustainable functionalization of unactivated alkyl sp^(3) C—H bonds is reported using iodine(III)as a feasible dehydrogenation agent under visible light or KBr,and alkyl chlorides,bromides,alcohols,and ketones could be constructed by addition of different coupling *** and safe iodobenzene diacetate was used to form a radical to activate the alkyl sp^(3) C—H bond in a highly efficient manner,which can construct different alkylation products by adding corresponding coupling reagents.

关键词： Alkyl sp^(3)C—H bonds Chlorination Bromination Oxidation Iodine(III) C—H activation Radical Photocatalysis

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Energetic,bio-oil,biochar,and ash performances of co-pyrolysis-gasification of textile dyeing sludge and Chinese medicine residues in response to K_(2)CO_(3),atmosphere type,blend ratio,and temperature

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Journal of Environmental Sciences 2024年第2期136卷 133-150页

作者： Gang Zhang Zhiyun Chen Tao Chen Shaojun Jiang Fatih Evrendilek Shengzheng Huang Xiaojie Tang Ziyi Ding Yao He Wuming Xie Jingyong Liu engineering research center of None-food Biomass Efficient Pyrolysis and Utilization Technology of guangdong Higher Education Institutes Dongguan University of TechnologyDongguan 523808China School of Environmental Science and engineering Guangdong University of TechnologyGuangzhou 510006China School of Environment The Environmental Research InstituteMOE Key Laboratory of Theoretical Chemistry of EnvironmentSouth China Normal UniversityGuangzhou 510006China Department of Environmental engineering Bolu Abant Izzet Baysal UniversityBolu 14052Turkey

Hazardous waste stream needs to be managed so as not to exceed stock-and rate-limited properties of its recipient *** co-pyrolysis of Chinese medicine residue(CMR)and textile dyeing sludge(TDS)and its bio-oil,biochar,and ash quality and quantity were characterized as a function of the immersion of K_(2)CO_(3),atmosphere type,blend ratio,and *** to the mono-pyrolysis of TDS,its co-pyrolysis performance with CMR(the comprehensive performance index(CPI))significantly improved by 33.9%in the N_(2)atmosphere and 33.2%in the CO_(2)*** impregnation catalyzed the co-pyrolysis at 370℃,reduced its activation energy by 77.3 kJ/mol in the N_(2)atmosphere and 134.6 kJ/mol in the CO_(2)atmosphere,and enriched the degree of coke gasification by 44.25%in the CO_(2)*** impregnation increased the decomposition rate of the co-pyrolysis by weakening the bond energy of fatty side chains and bridge bonds,its catalytic and secondary products,and its bio-oil yield by 66.19%.Its bio-oils mainly contained olefins,aromatic structural substances,and *** immersion of K_(2)CO_(3)improved the aromaticity of the copyrolytic biochars and reduced the contact between K and Si which made it convenient for Mg to react with SiO_(2)to form *** co-pyrolytic biochar surfaces mainly included-OH,-CH_(2),C=C,and *** main phases in the co-pyrolytic ash included Ca_(5)(PO_(4))_(3)(OH),Al_(2)O_(3),and magnesium-silicate.

关键词： Chemical impregnation Catalytic pyrolysis Chinese medicine residue Textile dyeing sludge Co-pyrolysis

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Aqueous-phase formation of N-containing secondary organic compounds affected by the ionic strength

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Journal of Environmental Sciences 2024年第4期138卷 88-101页

作者： Yuqi Gan Xiaohui Lu Shaodong Chen Xinghua Jiang Shanye Yang Xiewen Ma Mei Li Fan Yang Yewen Shi Xiaofei Wang Shanghai Key Laboratory of Atmospheric Particle Pollution and Prevention Department of Environmental Science and EngineeringFudan UniversityShanghai 200433China Shanghai Institute of Pollution Control and Ecological Security Shanghai 200092China guangdong Provincial Observation and research Station for Coastal Atmosphere and Climate of the Great Bay Area Southern University of Science and TechnologyShenzhen 518055China Institute of Mass Spectrometry and Atmospheric Environment Guangdong Provincial Engineering Research Center for On-line Source Apportionment System of Air PollutionJinan UniversityGuangzhouChina Environmental Monitoring Station of Pudong new District Shanghai 201200China Shanghai Municipal center for Disease Control&Prevention Shanghai 200336China

The reaction of carbonyl-to-imine/hemiaminal conversion in the atmospheric aqueous phase is a critical pathway to produce the light-absorbing N-containing secondary organic compounds(SOC).The formation mechanism of these compounds has been wildly investigated in bulk solutions with a low ionic ***,the ionic strength in the aqueous phase of the polluted atmosphere may be *** is still unclear whether and to what extent the inorganic ions can affect the SOC *** we prepared the bulk solution with certain ionic strength,in which glyoxal and ammonium were mixed to mimic the aqueous-phase *** characterization by High-resolution Mass Spectrometry was performed to identify the N-containing products,and the light absorption of the mixtures was measured by ultraviolet-visible ***-nine N-containing compounds were identified and divided into four categories(N-heterocyclic chromophores,high-molecular-weight compounds with N-heterocycle,aliphatic imines/hemiaminals,and the unclassified).It was observed that the longer reaction time and higher ionic strength led to the formation of more N-heterocyclic chromophores and the increasing of the lightabsorbance of the *** added inorganic ions were proposed to make the aqueous phase somewhat viscous so that the molecules were prone to undergo consecutive and intramolecular reactions to form the *** general,this study revealed that the enhanced ionic strength and prolonged reaction time had the promotion effect on the lightabsorbing SOC *** implies that the aldehyde-derived aqueous-phase SOC would contribute more light-absorbing particulate matter in the industrial or populated area where inorganic ions are abundant.

关键词： Ionic strength Carbonyl-to-imine/hemiaminal Heterocyclic Brown carbon Mass spectrometry Aqueous-phase reaction

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