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Dysfunction of the adhesion G protein-coupled receptor latrophilin 1(ADGRL1/LPHN1)increases the risk of obesity

Signal Transduction and Targeted Therapy 2024年第5期9卷 2298-2311页

作者： Heba ZabriTorsten Schöneberg AndréNguyen Dietzsch Hadi Al-Hasani Joachim Altschmied Katharina Bottermann Jana Brendler Judith Haendeler Susanne Horn Isabell Kaczmarek Antje Körner Kerstin Krause Kathrin Landgraf Diana Le Duc Laura Lehmann Stefan Lehr Stephanie Pick Albert Ricken Rene Schnorr Angela Schulz Martina Strnadová Akhil Velluva Heba Zabri Torsten Schöneberg Doreen Thor Simone Prömel Rudolf Schönheimer institute of Biochemistry Medical FacultyLeipzig UniversityLeipzigGermany institute for Clinical Biochemistry and Pathobiochemistry Medical FacultyGerman Diabetes CenterLeibniz Center for Diabetes Research at Heinrich Heine University DüsseldorfDüsseldorfGermany German Center for Diabetes Research(DZD e.V.) Munich-NeuherbergGermany Cardiovascular Degeneration Clinical Chemistry and Laboratory DiagnosticsMedical FacultyUniversity Hospital and Heinrich Heine University DüsseldorfDüsseldorfGermany Cardiovascular Research institute(CARID) Medical FacultyUniversity Hospital and Heinrich Heine University DüsseldorfDüsseldorfGermany institute of pharmacology Medical FacultyUniversity Hospital and Heinrich Heine University DüsseldorfDüsseldorfGermany institute of Anatomy Medical FacultyLeipzig UniversityLeipzigGermany Center for Pediatric Research Hospital for Children and AdolescentsMedical FacultyLeipzig UniversityLeipzigGermany Helmholtz institute for Metabolic Obesity and Vascular Research(HI-MAG)of the Helmholtz Zentrum München at the University of Leipzig and University Hospital LeipzigLeipzigGermany Department of Endocrinology NephrologyRheumatologyLeipzig University Medical CenterLeipzigGermany institute of Human Genetics Leipzig University Medical CenterLeipzigGermany institute of Cell Biology Department of BiologyHeinrich Heine University DüsseldorfDüsseldorfGermany School of Medicine University of Global Health EquityKigaliRwanda

Obesity is one of the diseases with severe health consequences and rapidly increasing worldwide *** the complex network of food intake and energy balance regulation is an essential prerequisite for pharmacological intervention with obesity.G protein-coupled receptors(GPCRs)are among the main modulators of metabolism and energy ***,for instance,regulate appetite and satiety in certain hypothalamic neurons,as well as glucose and lipid metabolism and hormone secretion from *** in some GPCRs,such as the melanocortin receptor type 4(MC4R),have been associated with early-onset ***,we identified the adhesion GPCR latrophilin 1(ADGRL1/LPHN1)as a member of the regulating network governing food intake and the maintenance of energy *** of the highly conserved receptor in mice results in increased food consumption and severe obesity,accompanied by dysregulation of glucose ***,we identified a partially inactivating mutation in human ADGRL1/LPHN1 in a patient suffering from ***,we propose that LPHN1 dysfunction is a risk factor for obesity development.

关键词： obesity metabolism intake

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A novel strategy for treating oncogene-mutated tumors by targeting tumor microenvironment and synergistically enhancing anti-PD-1 immunotherapy

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Cancer Communications 2024年第3期44卷 438-442页

作者： Yingqiang Liu Linjiang Tong Mengge Zhang Qi Zhang Qiupei Liu Fang Feng Yan Li Mengzhen Lai Haotian Tang Yi Chen Meiyu Geng Wenhu Duan Jian Ding Hua Xie Division of Antitumor pharmacology&State Key Laboratory of Drug Research Shanghai Institute of Materia MedicaChinese Academy of SciencesShanghaiP.R.China University of Chinese Academy of Sciences BeijingP.R.China Department of Chemical and Environmental Engineering University of Nottingham Ningbo ChinaNingboZhejiangP.R.China Zhongshan institute for Drug Discovery Shanghai Institute of Materia MedicaChinese Academy of SciencesZhongshanGuangdongP.R.China Shandong Laboratory of Yantai Drug Discovery Bohai Rim Advanced Research Institute for Drug DiscoveryYantaiShandongP.R.China Small-Molecule Drug Research Center Shanghai Institute of Materia MedicaChinese Academy of SciencesShanghaiP.R.China

Oncogenes are critical factors in tumorigenesis of diverse cancer types and play essential roles in tumor immune *** in Kirsten rat sarcoma viral oncogene homolog(KRAS)and epidermal growth factor receptor(EGFR)are among the most frequent gain-of-function alterations[1].After many years of in-depth research,inhibitors targeting EGFR or KRAS mutations have been successfully developed,however,their clinical benefit is relatively limited,and they will inevitably encounter the challenge of drug *** emergence of resistance is attributed to secondary mutations in driver genes and other complicated factors.

关键词： alterations KRAS sarcoma

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Liver-brain axis with alcohol:Role of fibroblast growth factor 21(FGF21)

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Genes & Diseases 2024年第2期11卷 509-511页

作者： Ke Zhang Elena Blokhina Evgeny Krupitsky Marina Vetrova Ti-Fei Yuan Hua Wang Shanghai Key Laboratory of Psychotic Disorders Brain Health InstituteNational Center for Mental DisordersShanghai Mental Health CenterShanghai Jiao Tong University School of MedicineShanghai 200030China Pavlov University Valdman Institute of PharmacologySt.Petersburg 197022Russia Bekhterev National Medical Research Center for Psychiatry and Neurology St.Petersburg 192019Russia Co-innovation Center of Neuroregeneration Nantong UniversityNantongJiangsu 226007China Department of Oncology The First Affiliated Hospital of Anhui Medical UniversityHefeiAnhui 230032China

Fibroblast growth factor21(FGF21)is a hormone that can balance nutrient fluctuations,control metabolic processes,and maintain energy *** FGF21 is produced by a variety of cell types,including hepatocytes,adipocytes,bone cells,myocardial cells,and pancreas cells,and act on various effector tissues such as brain,adipose tissue,liver,heart,and skeletal muscle.1 The target that FGF21 interacts with is the cell-surface receptor composed of FGF receptors in complex with the single-pass transmembrane proteinβ-*** receptors are abundantly expressed,both in peripheral tissues and some regions of the CNS,such as the hypothalamus and amygdala and the locus coeruleus(LC).2 Physiologically,FGF21 can be induced by various metabolic stresses,including hunger,protein deficiency,monosaccharides,and alcohol,by acting onβ-Klotho receptor in corresponding tissues,ultimately exerting regulatory effects(Fig.1)

关键词： Klotho homeostasis alcohol

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Nuclear receptor coactivator 6 is a critical regulator of NLRP3 inflammasome activation and gouty arthritis

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Cellular & Molecular Immunology 2024年第3期21卷 227-244页

作者： Kang-Gu Lee Bong-Ki Hong Saseong Lee Naeun Lee Seung-Whan Kim Donghyun Kim Wan-Uk Kim Center for Integrative Rheumatoid Transcriptomics and Dynamics The Catholic University of KoreaSeoul 06591Republic of Korea Department of Biomedicine&Health Sciences The Catholic University of KoreaSeoul 06591Republic of Korea Department of pharmacology Asan Medical CenterUniversity of Ulsan College of MedicineSeoul 05505Republic of Korea Bio-Medical institute of Technology University of UlsanSeoul 05505Republic of Korea Department of Microbiology and Immunology Seoul National University College of MedicineSeoul 03080Republic of Korea institute of Infectious Diseases Seoul National University College of MedicineSeoul 03080Republic of Korea Division of Rheumatology Department of Internal MedicineThe Catholic University of KoreaSeoul 06591Republic of Korea

Transcriptional coactivators regulate the rate of gene expression in the *** receptor coactivator 6(NCOA6),a coactivator,has been implicated in embryonic development,metabolism,and cancer pathogenesis,but its role in innate immunity and inflammatory diseases remains ***,we demonstrated that NCOA6 was expressed in monocytes and macrophages and that its level was increased under proinflammatory ***,nuclear NCOA6 was found to translocate to the cytoplasm in activated monocytes and then become incorporated into the inflammasome with NLRP3 and ASC,forming cytoplasmic ***,NCOA6 associated with the ATP hydrolysis motifs in the NACHT domain of NLRP3,promoting the oligomerization of NLRP3 and ASC and thereby instigating the production of IL-1βand active *** note,Ncoa6 deficiency markedly inhibited NLRP3 hyperactivation caused by the Nlrp3^(R258W) gain-of-function mutation in *** ablation of Ncoa6 substantially attenuated the severity of two NLRP3-dependent diseases,folic-induced acute tubular necrosis and crystal-induced arthritis,in *** with these findings,NCOA6 was highly expressed in macrophages derived from gout patients,and NCOA6-positive macrophages were significantly enriched in gout macrophages according to the transcriptome profiling ***,NCOA6 is a critical regulator of NLRP3 inflammasome activation and is therefore a promising target for NLRP3-dependent diseases,including gout.

关键词： Nuclear receptor coactivator 6 Nuclear-to-cytoplasmic translocation NLRP3 inflammasome NACHT domain Gouty arthritis

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A Novel Approach to Breast Tumor Detection: Enhanced Speckle Reduction and Hybrid Classification in Ultrasound Imaging

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Computers, Materials & Continua 2024年第5期79卷 1875-1901页

作者： K.Umapathi S.Shobana Anand Nayyar Judith Justin R.Vanithamani Miguel Villagómez Galindo Mushtaq Ahmad Ansari Hitesh Panchal Department of Biomedical Engineering KIT-Kalaignarkarunanidhi Institute of TechnologyCoimbatore641402India Graduate School Faculty of Information TechnologyDuy Tan UniversityDa Nang550000Viet Nam Department of Biomedical and Instrumentation Engineering Avinashilingam Institute for Home Science and Higher Education forWomenCoimbatore641043India UniversidadMichoacana de SanNicolás de HidalgoAvenida Francisco J.Múgica S/N Ciudad Universitaria MoreliaCP58030Mexico Department of pharmacology and Toxicology College of PharmacyKing Saud UniversityRiyadh11451Saudi Arabia Department of Mechanical Engineering Gujarat Technological UniveristyNigam NagarChandkhedaAhmedabadGujarat382424India

Breast cancer detection heavily relies on medical imaging, particularly ultrasound, for early diagnosis and effectivetreatment. This research addresses the challenges associated with computer-aided diagnosis (CAD) of breastcancer fromultrasound images. The primary challenge is accurately distinguishing between malignant and benigntumors, complicated by factors such as speckle noise, variable image quality, and the need for precise segmentationand classification. The main objective of the research paper is to develop an advanced methodology for breastultrasound image classification, focusing on speckle noise reduction, precise segmentation, feature extraction, andmachine learning-based classification. A unique approach is introduced that combines Enhanced Speckle ReducedAnisotropic Diffusion (SRAD) filters for speckle noise reduction, U-NET-based segmentation, Genetic Algorithm(GA)-based feature selection, and Random Forest and Bagging Tree classifiers, resulting in a novel and efficientmodel. To test and validate the hybrid model, rigorous experimentations were performed and results state thatthe proposed hybrid model achieved accuracy rate of 99.9%, outperforming other existing techniques, and alsosignificantly reducing computational time. This enhanced accuracy, along with improved sensitivity and specificity,makes the proposed hybrid model a valuable addition to CAD systems in breast cancer diagnosis, ultimatelyenhancing diagnostic accuracy in clinical applications.

关键词： Ultrasound images breast cancer tumor classification segmentation deep learning lesion detection

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Insights into optimizing exosome therapies for acute skin wound healing and other tissue repair

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Frontiers of Medicine 2024年第2期18卷 258-284页

作者： Tianjing Sun Mo Li Qi Liu Anyong Yu Kun Cheng Jianxing Ma Sean Murphy Patrick Michael McNutt Yuanyuan Zhang Department of Emergency Affiliated Hospital of Zunyi Medical UniversityZunyi563003China Department of Nephrology Affiliated Hospital of Zunyi Medical UniversityZunyi563003China Division of pharmacology and Pharmaceutical Sciences School of PharmacyUniversity of Missouri-Kansas CityKansas CityMO64108USA Department of Biochemistry Wake Forest University School of MedicineWinston-SalemNC27157USA Wake Forest institute of Regenerative Medicine Wake Forest School of MedicineWinston-SalemNC27109USA

Exosome therapy holds great promise as a novel approach to improve acute skin wound *** review provides a comprehensive overview of the current understanding of exosome biology and its potential applications in acute skin wound healing and ***,small extracellular vesicles secreted by various stem cells,have emerged as potent mediators of intercellular communication and tissue *** advantage of exosome therapy is its ability to avoid potential risks associated with stem cell therapy,such as immune rejection or stem cells differentiating into unwanted cell ***,further research is necessary to optimize exosome therapy,not only in the areas of exosome isolation,characterization,and engineering,but also in determining the optimal dose,timing,administration,and frequency of exosome ***,optimization of exosome therapy is critical for the development of more effective and safer exosome-based therapies for acute skin wound healing and other diseases induced by cancer,ischemia,or *** review provides valuable insights into the potential of exosome therapy and highlights the need for further research to optimize exosome therapy for clinical use.

关键词： exosomes stem cells therapeutic impact skin wound healing

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DNA G-Quadruplexes as Targets for Natural Product Drug Discovery

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Engineering 2024年第7期38卷 39-51页

作者： Kai-Bo Wang Yingying Wang Jonathan Dickerhoff Danzhou Yang Borch Department of Medicinal Chemistry and Molecular pharmacology College of PharmacyPurdue UniversityWest LafayetteIN 47907USA Purdue Center for Cancer Research Purdue UniversityWest LafayetteIN 47907USA Department of Chemistry Purdue UniversityWest LafayetteIN 47907USA Purdue institute for Drug Discovery Purdue UniversityWest LafayetteIN 47907USA Jiangsu Key Laboratory of Bioactive Natural Product Research&State Key Laboratory of Natural Medicines China Pharmaceutical UniversityNanjing 210009China

DNA guanine(G)-quadruplexes(G4s)are unique secondary structures formed by two or more stacked Gtetrads in G-rich DNA *** structures have been found to play a crucial role in highly transcribed genes,especially in cancer-related oncogenes,making them attractive targets for cancer ***,targeting oncogene promoter G4 structures has emerged as a promising strategy to address the challenge of undruggable and drug-resistant proteins,such as MYC,BCL2,KRAS,and *** products have long been an important source of drug discovery,particularly in the fields of cancer and infectious *** progress has recently been made in the discovery of naturally occurring DNA G4-targeting *** DNA G4s,such as MYC-G4,BCL2-G4,KRAS-G4,PDGFR-b-G4,VEGF-G4,and telomeric-G4,have been identified as potential targets of natural products,including berberine,telomestatin,quindoline,sanguinarine,isaindigotone,and many ***,we summarize and evaluate recent advancements in natural and nature-derived DNA G4 binders,focusing on understanding the structural recognition of DNA G4s by small molecules derived from *** also discuss the challenges and opportunities associated with developing drugs that target DNA G4s.

关键词： G-quadruplex Natural products Alkaloids Cancer Promoter

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Fundamentals and application in phytoremediation of an efficient arsenate reducing bacterium Pseudomonas putida ARS1

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Journal of Environmental Sciences 2024年第3期137卷 237-244页

作者： Ze-Wen Wang Guang Yang Jian Chen Yaoyu Zhou Avelino Nunez Delgado Hui-Ling Cui Gui-Lan Duan Barry P.Rosen Yong-Guan Zhu Henan institute of Advanced Technology Zhengzhou UniversityZhengzhou 450052China State Key Lab of Urban and Regional Ecology Research Center for Eco-Environmental SciencesChinese Academy of SciencesBeijing 100085China Department of Cellular Biology and pharmacology Florida International UniversityHerbert Wertheim College of MedicineMiamiFL33199USA University of Chinese Academy of Sciences Beijing 100049China Key Laboratory of Urban Environment and Health Institute of Urban EnvironmentChinese Academy of SciencesXiamen 361021China College of Resources and Environment Hunan Agricultural UniversityChangsha 410128China Department of Soil Science and Agricultura Chemistry Engineering Polytechnic SchoolUniversity of Santiago de CompostelaCampus Univ.s/n27002LugoSpain

Arsenic is a ubiquitous environmental ***-mediated arsenic biotransformations significantly infuence arsenic mobility and *** transformations by soil and aquatic organisms have been well documented,while little is known regarding effects due to endophytic *** endophyte Pseudomonas putida ARS1 was isolated from rice grown in arsenic contaminated *** ARS1 shows high tolerance to arsenite(As(Ⅲ))and arsenate(As(V)),and exhibits efficient As(V)reduction and As(Ⅲ)effux *** exposed to 0.6 mg/L As(V),As(V)in the medium was completely converted to As(Ⅲ)by *** ARS1 within 4 *** sequencing showed that *** ARS1 has two chromosomal arsenic resistance gene clusters(arsRCBH)that contribute to efficient As(V)reduction and As(Ⅲ)effux,and result in high resistance to *** globosa is a strong arsenic accumulator with high potential for arsenic phytoremediation,which takes up As(Ⅲ)more efficiently than As(V).Co-culture of *** ARS1 and *** enhanced arsenic accumulation in *** by 69%,and resulted in 91%removal of arsenic(at initial concentration of 0.6 mg/L As(V))from water within 3 *** study provides a promising strategy for in situ arsenic phytoremediation through the cooperation of plant and endophytic bacterium.

关键词： Arsenic Pseudomonas putida Arsenate reduction Endophyte Wolffia globosa Phytoremediation

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Isoimperatorin alleviates acetic acid-induced colitis in rats

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Asian Pacific Journal of Tropical Biomedicine 2024年第4期14卷 147-153页

作者： Saied Goodarzi Amir Hossein Abdolghaffari Behnaz Najafi Mostafa Pirali Hamedani Saeed Tavakoli Mahshad Marvi Maryam Baeeri Narguess Yassa Abbas Hadjiakhoondi Mohammad Abdollahi Zahra Tofighi Medicinal Plants Research Center Faculty of PharmacyTehran University of Medical SciencesTehranIran Department of Toxicology and pharmacology Faculty of PharmacyTehran Medical SciencesIslamic Azad UniversityTehranIran Department of Pharmacognosy Faculty of PharmacyTehran University of Medical SciencesTehranIran Medicinal Plants Research Center Institute of Medicinal PlantsACECRKarajIran International Campus School of Pharmacy Tehran University of Medical SciencesTehranIran Toxicology and Diseases group The Pharmaceutical Sciences Research CenterTehran University of Medical SciencesTehranIran Department of Toxicology and pharmacology Faculty of PharmacyTehran University of Medical SciencesTehranIran

Objective:To investigate the effect of isoimperatorin on histopathological and biochemical changes in acetic acid-induced colitis ***:Colitis was induced by intracolonic administration of acetic acid solution(4%v/v)in *** were divided into six groups including the sham group,the negative control group,the dexamethasone-treated group,and the groups treated with isoimperatorin(0.1,1,and 10 mg/kg/d by gavage).The treatments were administered for three days and then colonic status was assessed by macroscopic,histopathological,and biochemical ***:Isoimperatorin significantly alleviated colonic damage in a dose-dependent manner and improved histological changes in rats with acetic acid-induced *** also significantly reduced myeloperoxidase,TNF-α,IL-1β,and malodialdehyde ***:Isoimperatorin alleviates acetic acid-induced colitis in rats and may be a potential therapeutic agent for the treatment of colitis.

关键词： Isoimperatorin Inflammatory bowel disease Acetic acid Colitis TNF-α IL-1β

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Acceptor-engineering tailored type-Ⅰ photosensitizer with aggregation-induced NIR-II emission for cancer multimodal phototheranostics

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Science China Chemistry 2024年第8期67卷 2647-2660页

作者： Jiangao Li Niu Niu Deliang Wang Xue Liu Yi Qin Lei Wang Ben Zhong Tang Dong Wang Center for AIE Research Shenzhen Key Laboratory of Polymer Science and TechnologyGuangdong Research Center for Interfacial Engineering of Functional MaterialsCollege of Materials Science and EngineeringShenzhen UniversityShenzhen 518060China Guangzhou Municipal and Guangdong Provincial Key Laboratory of Molecular Target Clinical Pharmacologythe State Key Laboratory of Respiratory DiseaseSchool of Pharmaceutical Sciences and the Fifth Affiliated HospitalGuangzhou Medical UniversityGuangzhou 511436China School of Science and Engineering Shenzhen Institute of Aggregate Science and TechnologyThe Chinese University of Hong KongShenzhen(CUHK-Shenzhen)Shenzhen 518172China

Exploration of single molecular species synchronously featured by long excitation/emission wavelength, accurate diagnosis, and effective therapy, remains supremely appealing to implement high-performance cancer phototheranostics. However, those previously established phototheranostic agents are undiversified and stereotyped in terms of structural skeleton, and generally exhibit insufficient phototheranostic outcomes. Herein, we innovatively utilized indanone-condensed thiadiazolo[3,4-g]quinoxaline(ITQ) as electron acceptor to construct novel photosensitizer with second near-infrared(NIR-II) emission. Experimental study and theoretical calculation demonstrated that comparing with the counterparts constituting by widely employed NIR-II building block benzobisthiadiazole(BBTD) and 6,7-diphenylthiadiazoloquinoxaline(DPTQ), ITQ-based photosensitizer(TITQ) showed superior aggregation-induced emission(AIE) characteristics, much stronger type-I reactive oxygen species(ROS) production, and prominent photothermal conversion capacity. Furthermore, TITQ nanoparticles with excellent biocompatibility were capable of effectively accumulating in the tumor site and visualizing tumor through fluorescence-photoacoustic-photothermal trimodal imaging with highly spatiotemporal resolution, and completely eliminating tumor by type-I photodynamic-photothermal therapy.

关键词： phototheranostics aggregation-induced emission NIR-Ⅱfluorescence acceptor engineering photodynamic-photothermal therapy

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