Cell Chemical Biology最新文献_第7页

Commensal-derived tryptophan metabolites fortify the skin barrier: Insights from a 50-species gnotobiotic model of human skin microbiome 评论衍生色氨酸代谢物强化皮肤屏障：来自人类皮肤微生物组的50种非生物模型的见解

IF 6.6 1区生物学

Cell Chemical Biology Pub Date : 2025-01-16 DOI: 10.1016/j.chembiol.2024.12.007

Aayushi Uberoi , Sofía M. Murga-Garrido , Preeti Bhanap , Amy E. Campbell , Simon A.B. Knight , Monica Wei , Anya Chan , Taylor Senay , Saba Tegegne , Ellen K. White , Carrie Hayes Sutter , Clementina Mesaros , Thomas R. Sutter , Elizabeth A. Grice

{"title":"Commensal-derived tryptophan metabolites fortify the skin barrier: Insights from a 50-species gnotobiotic model of human skin microbiome","authors":"Aayushi Uberoi , Sofía M. Murga-Garrido , Preeti Bhanap , Amy E. Campbell , Simon A.B. Knight , Monica Wei , Anya Chan , Taylor Senay , Saba Tegegne , Ellen K. White , Carrie Hayes Sutter , Clementina Mesaros , Thomas R. Sutter , Elizabeth A. Grice","doi":"10.1016/j.chembiol.2024.12.007","DOIUrl":"10.1016/j.chembiol.2024.12.007","url":null,"abstract":"<div><div>The epidermal barrier defends the body against dehydration and harmful substances. The commensal microbiota is essential for proper differentiation and repair of the epidermal barrier, an effect mediated by the aryl hydrocarbon receptor (AHR). However, the microbial mechanisms of AHR activation in skin are less understood. Tryptophan metabolites are AHR ligands that can be products of microbial metabolism. To identify microbially regulated tryptophan metabolites <em>in vivo</em>, we established a gnotobiotic model colonized with fifty human skin commensals and performed targeted mass spectrometry on murine skin. Indole-related metabolites were enriched in colonized skin compared to germ-free skin. In reconstructed human epidermis and in murine models of atopic-like barrier damage, these metabolites improved barrier repair and function individually and as a cocktail. These results provide a framework for the identification of microbial metabolites that mediate specific host functions, which can guide the development of microbe-based therapies for skin disorders.</div></div>","PeriodicalId":265,"journal":{"name":"Cell Chemical Biology","volume":"32 1","pages":"Pages 111-125.e6"},"PeriodicalIF":6.6,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142986933","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

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Yeast paves the way for cancer immunotherapy 酵母为癌症免疫治疗铺平了道路

IF 6.6 1区生物学

Cell Chemical Biology Pub Date : 2025-01-16 DOI: 10.1016/j.chembiol.2024.12.011

Dingjiacheng Jia , Shujie Chen

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Calcineurin: An essential regulator of sleep revealed by biochemical, chemical biological, and genetic approaches 钙调磷酸酶：通过生物化学、生物化学和遗传方法揭示睡眠的重要调节因子

IF 6.6 1区生物学

Cell Chemical Biology Pub Date : 2025-01-16 DOI: 10.1016/j.chembiol.2024.12.003

Jianjun Yu (余建军) , Huijie Liu (刘慧洁) , Rui Gao (高瑞) , Tao V. Wang (王涛) , Chenggang Li (李成钢) , Yuxiang Liu (刘玉祥) , Lu Yang (杨璐) , Ying Xu (徐颖) , Yunfeng Cui (崔云凤) , Chenxi Jia (贾辰熙) , Juan Huang (黄娟) , Peng R. Chen (陈鹏) , Yi Rao (饶毅)

{"title":"Calcineurin: An essential regulator of sleep revealed by biochemical, chemical biological, and genetic approaches","authors":"Jianjun Yu (余建军) , Huijie Liu (刘慧洁) , Rui Gao (高瑞) , Tao V. Wang (王涛) , Chenggang Li (李成钢) , Yuxiang Liu (刘玉祥) , Lu Yang (杨璐) , Ying Xu (徐颖) , Yunfeng Cui (崔云凤) , Chenxi Jia (贾辰熙) , Juan Huang (黄娟) , Peng R. Chen (陈鹏) , Yi Rao (饶毅)","doi":"10.1016/j.chembiol.2024.12.003","DOIUrl":"10.1016/j.chembiol.2024.12.003","url":null,"abstract":"<div><div>Research into mechanisms underlying sleep traditionally relies on electrophysiology and genetics. Because sleep can only be measured on whole animals by behavioral observations and physical means, no sleep research was initiated by biochemical and chemical biological approaches. We used phosphorylation sites of kinases important for sleep as targets for biochemical and chemical biological approaches. Sleep was increased in mice carrying a threonine-to-alanine substitution at residue T469 of salt-inducible kinase 3 (SIK3). Our biochemical purification and photo-crosslinking revealed calcineurin (CaN) dephosphorylation, both <em>in vitro</em> and <em>in vivo</em>, of SIK3 at T469 and S551, but not T221. Knocking down CaN regulatory subunit reduced daily sleep by more than 5 h, exceeding all known mouse mutants. Our work uncovered a critical physiological role for CaN in sleep and pioneered biochemical purification and chemical biology as effective approaches to study sleep.</div></div>","PeriodicalId":265,"journal":{"name":"Cell Chemical Biology","volume":"32 1","pages":"Pages 157-173.e7"},"PeriodicalIF":6.6,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142902000","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Chemical interplay between gut microbiota and epigenetics: Implications in circadian biology 肠道微生物群与表观遗传学之间的化学相互作用：对昼夜节律生物学的影响

IF 6.6 1区生物学

Cell Chemical Biology Pub Date : 2025-01-16 DOI: 10.1016/j.chembiol.2024.04.016

Samskrathi Aravinda Sharma , Sarah Olanrewaju Oladejo , Zheng Kuang

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Meet the authors: Aayushi Uberoi and Elizabeth A. Grice 来认识一下这篇文章的作者：银井青史和伊丽莎白·a·格赖斯

IF 6.6 1区生物学

Cell Chemical Biology Pub Date : 2025-01-16 DOI: 10.1016/j.chembiol.2024.12.010

Aayushi Uberoi, Elizabeth A. Grice

引用次数: 0

β-hydroxybutyrate is a metabolic regulator of proteostasis in the aged and Alzheimer disease brain β-羟基丁酸盐是老年人和阿尔茨海默病患者大脑中蛋白质平衡的代谢调节剂

IF 6.6 1区生物学

Cell Chemical Biology Pub Date : 2025-01-16 DOI: 10.1016/j.chembiol.2024.11.001

Sidharth S. Madhavan , Stephanie Roa Diaz , Sawyer Peralta , Mitsunori Nomura , Christina D. King , Kaya E. Ceyhan , Anwen Lin , Dipa Bhaumik , Anna C. Foulger , Samah Shah , Thanh Blade , Wyatt Gray , Manish Chamoli , Brenda Eap , Oishika Panda , Diego Diaz , Thelma Y. Garcia , Brianna J. Stubbs , Scott M. Ulrich , Gordon J. Lithgow , John C. Newman

{"title":"β-hydroxybutyrate is a metabolic regulator of proteostasis in the aged and Alzheimer disease brain","authors":"Sidharth S. Madhavan , Stephanie Roa Diaz , Sawyer Peralta , Mitsunori Nomura , Christina D. King , Kaya E. Ceyhan , Anwen Lin , Dipa Bhaumik , Anna C. Foulger , Samah Shah , Thanh Blade , Wyatt Gray , Manish Chamoli , Brenda Eap , Oishika Panda , Diego Diaz , Thelma Y. Garcia , Brianna J. Stubbs , Scott M. Ulrich , Gordon J. Lithgow , John C. Newman","doi":"10.1016/j.chembiol.2024.11.001","DOIUrl":"10.1016/j.chembiol.2024.11.001","url":null,"abstract":"<div><div>Loss of proteostasis is a hallmark of aging and Alzheimer disease (AD). We identify β-hydroxybutyrate (βHB), a ketone body, as a regulator of protein solubility. βHB primarily provides ATP substrate during periods of reduced glucose availability, and regulates other cellular processes through protein interactions. We demonstrate βHB-induced protein insolubility is not dependent on covalent protein modification, pH, or solute load, and is observable in mouse brain <em>in vivo</em> after delivery of a ketone ester. This mechanism is selective for pathological proteins such as amyloid-β, and exogenous βHB ameliorates pathology in nematode models of amyloid-β aggregation toxicity. We generate libraries of the βHB-induced protein insolublome using mass spectrometry proteomics, and identify common protein domains and upstream regulators. We show enrichment of neurodegeneration-related proteins among βHB targets and the clearance of these targets from mouse brain. These data indicate a metabolically regulated mechanism of proteostasis relevant to aging and AD.</div></div>","PeriodicalId":265,"journal":{"name":"Cell Chemical Biology","volume":"32 1","pages":"Pages 174-191.e8"},"PeriodicalIF":6.6,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142758618","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

RNA infrastructure profiling illuminates transcriptome structure in crowded spaces RNA 基础结构剖析揭示拥挤空间中的转录组结构

IF 6.6 1区生物学

Cell Chemical Biology Pub Date : 2024-12-19 DOI: 10.1016/j.chembiol.2024.09.009

Lu Xiao , Linglan Fang , Wenrui Zhong , Eric T. Kool

{"title":"RNA infrastructure profiling illuminates transcriptome structure in crowded spaces","authors":"Lu Xiao , Linglan Fang , Wenrui Zhong , Eric T. Kool","doi":"10.1016/j.chembiol.2024.09.009","DOIUrl":"10.1016/j.chembiol.2024.09.009","url":null,"abstract":"<div><div>RNAs fold into compact structures and undergo protein interactions in cells. These occluded environments can block reagents that probe the underlying RNAs. Probes that can analyze structure in crowded settings can shed light on RNA biology. Here, we employ 2′-OH-reactive probes that are small enough to access folded RNA structure underlying close molecular contacts within cells, providing considerably broader coverage for intracellular RNA structural analysis. The data are analyzed first with well-characterized human ribosomal RNAs and then applied transcriptome-wide to polyadenylated transcripts. The smallest probe acetylimidazole (AcIm) yields 80% greater structural coverage than larger conventional reagent NAIN3, providing enhanced structural information in hundreds of transcripts. The acetyl probe also provides superior signals for identifying m<sup>6</sup>A modification sites in transcripts, particularly in sites that are inaccessible to a standard probe. Our strategy enables profiling RNA infrastructure, enhancing analysis of transcriptome structure, modification, and intracellular interactions, especially in spatially crowded settings.</div></div>","PeriodicalId":265,"journal":{"name":"Cell Chemical Biology","volume":"31 12","pages":"Pages 2156-2167.e5"},"PeriodicalIF":6.6,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142487423","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

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Host specific sphingomyelin is critical for replication of diverse RNA viruses 宿主特异性鞘磷脂对多种 RNA 病毒的复制至关重要

IF 6.6 1区生物学

Cell Chemical Biology Pub Date : 2024-12-19 DOI: 10.1016/j.chembiol.2024.10.009

Shuo Han , Xiaolei Ye , Jintong Yang , Xuefang Peng , Xiaming Jiang , Jin Li , Xiaojie Zheng , Xinchen Zhang , Yumin Zhang , Lingyu Zhang , Wei Wang , Jiaxin Li , Wenwen Xin , Xiaoai Zhang , Gengfu Xiao , Ke Peng , Leike Zhang , Xuguang Du , Lu Zhou , Wei Liu , Hao Li

{"title":"Host specific sphingomyelin is critical for replication of diverse RNA viruses","authors":"Shuo Han , Xiaolei Ye , Jintong Yang , Xuefang Peng , Xiaming Jiang , Jin Li , Xiaojie Zheng , Xinchen Zhang , Yumin Zhang , Lingyu Zhang , Wei Wang , Jiaxin Li , Wenwen Xin , Xiaoai Zhang , Gengfu Xiao , Ke Peng , Leike Zhang , Xuguang Du , Lu Zhou , Wei Liu , Hao Li","doi":"10.1016/j.chembiol.2024.10.009","DOIUrl":"10.1016/j.chembiol.2024.10.009","url":null,"abstract":"<div><div>Lipids and lipid metabolism play an important role in RNA virus replication, which typically occurs on host cell endomembrane structures in the cytoplasm through mechanisms that are not yet fully identified. We conducted genome-scale CRISPR screening and identified sphingomyelin synthase 1 (SMS1; encoded by SGMS1) as a critical host factor for infection by severe fever with thrombocytopenia syndrome virus (SFTSV). <em>SGMS1</em> knockout reduced sphingomyelin (SM) (d18:1/16:1) levels, inhibiting SFTSV replication. A helix-turn-helix motif in SFTSV RNA-dependent RNA polymerase (RdRp) directly binds to SM(d18:1/16:1) in Golgi apparatus, which was also observed in SARS-CoV-2 and lymphocytic choriomeningitis virus (LCMV), both showing inhibited replication in <em>SGMS1</em>-KO cells. SM metabolic disturbance is associated with disease severity of viral infections. We designed a novel SMS1 inhibitor that protects mice against lethal SFTSV infection and reduce SARS-CoV-2 replication and pathogenesis. These findings highlight the critical role of SMS1 and SM(d18:1/16:1) in RNA virus replication, suggesting a broad-spectrum antiviral strategy.</div></div>","PeriodicalId":265,"journal":{"name":"Cell Chemical Biology","volume":"31 12","pages":"Pages 2052-2068.e11"},"PeriodicalIF":6.6,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142670993","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

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Macrophages make “sense” of obesity-driven acidity in the TME 巨噬细胞“理解”肥胖导致的TME酸性

IF 6.6 1区生物学

Cell Chemical Biology Pub Date : 2024-12-19 DOI: 10.1016/j.chembiol.2024.11.008

Spenser H. Stone , Jeffrey C. Rathmell , Jackie E. Bader

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Quinoline-based compounds can inhibit diverse enzymes that act on DNA 喹啉类化合物可抑制作用于 DNA 的各种酶

IF 6.6 1区生物学

Cell Chemical Biology Pub Date : 2024-12-19 DOI: 10.1016/j.chembiol.2024.09.007

Jujun Zhou , Qin Chen , Ren Ren , Jie Yang , Bigang Liu , John R. Horton , Caleb Chang , Chuxuan Li , Leora Maksoud , Yifei Yang , Dante Rotili , Abhinav K. Jain , Xing Zhang , Robert M. Blumenthal , Taiping Chen , Yang Gao , Sergio Valente , Antonello Mai , Xiaodong Cheng

{"title":"Quinoline-based compounds can inhibit diverse enzymes that act on DNA","authors":"Jujun Zhou , Qin Chen , Ren Ren , Jie Yang , Bigang Liu , John R. Horton , Caleb Chang , Chuxuan Li , Leora Maksoud , Yifei Yang , Dante Rotili , Abhinav K. Jain , Xing Zhang , Robert M. Blumenthal , Taiping Chen , Yang Gao , Sergio Valente , Antonello Mai , Xiaodong Cheng","doi":"10.1016/j.chembiol.2024.09.007","DOIUrl":"10.1016/j.chembiol.2024.09.007","url":null,"abstract":"<div><div>DNA methylation, as exemplified by cytosine-C5 methylation in mammals and adenine-N6 methylation in bacteria, is a key epigenetic process. Developing non-nucleoside inhibitors to cause DNA hypomethylation is crucial for treating various conditions without the toxicities associated with existing cytidine-based hypomethylating agents. This study characterized fifteen quinoline-based analogs, particularly compounds with additions like a methylamine (<strong>9</strong>) or methylpiperazine (<strong>11</strong>), which demonstrate similar low micromolar inhibitory potency against human DNMT1 and <em>Clostridioides difficile</em> CamA. These compounds (<strong>9</strong> and <strong>11</strong>) intercalate into CamA-bound DNA via the minor groove, causing a conformational shift that moves the catalytic domain away from the DNA. This study adds to the limited examples of DNA methyltransferases being inhibited by non-nucleotide compounds through DNA intercalation. Additionally, some quinoline-based analogs inhibit other DNA-interacting enzymes, such as polymerases and base excision repair glycosylases. Finally, compound <strong>11</strong> elicits DNA damage response via p53 activation in cancer cells.</div></div>","PeriodicalId":265,"journal":{"name":"Cell Chemical Biology","volume":"31 12","pages":"Pages 2112-2127.e6"},"PeriodicalIF":6.6,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142452302","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0