hLife最新文献

{"title":"Evolutionary history and biological adaptation of Han Chinese people on the Mongolian Plateau","authors":"Xiangping Li ,&nbsp;Mengge Wang ,&nbsp;Haoran Su ,&nbsp;Shuhan Duan ,&nbsp;Yuntao Sun ,&nbsp;Hongyu Chen ,&nbsp;Zhiyong Wang ,&nbsp;Qiuxia Sun ,&nbsp;Qingxin Yang ,&nbsp;Jing Chen ,&nbsp;Ting Yang ,&nbsp;Yuguo Huang ,&nbsp;Jie Zhong ,&nbsp;Xiucheng Jiang ,&nbsp;Jinyue Ma ,&nbsp;Shijia Chen ,&nbsp;Yunhui Liu ,&nbsp;Lintao Luo ,&nbsp;Xinyu Lin ,&nbsp;Shengjie Nie ,&nbsp;Guanglin He","doi":"10.1016/j.hlife.2024.04.005","DOIUrl":"10.1016/j.hlife.2024.04.005","url":null,"abstract":"<div><p>Complex demographic processes and natural selection pressures are critical to resolving patterns of the molecular genetic basis of adaptive traits or complex diseases. Recent ancient genome data allow us to trace how key traits evolved in different human populations over time, connecting ancient population history with disease susceptibility in western Eurasians. To fill this gap in eastern Eurasians and provide deep insights into the evolutionary history of the population-specific genetic basis of complex biological traits, we explored the evolutionary basis of adaptive traits in one integrative modern and ancient genomic database, including 225 out of 5583 genomes first reported here. We comprehensively characterized the demographic history and biological adaptation of Han Chinese individuals on the Mongolian Plateau based on the allele frequency spectrum and haplotype-resolved fragments. We found strong genetic homogeneity among geographically different Han populations from Inner Mongolia (IMH). We reconstructed their admixture models and demographic events, revealing that IMH had a close genetic relationship with ancient millet farmers and obtained additional gene flow from Altaic-speaking populations. The enrichment of selected candidate genes suggested that essential metabolism-related genes promoted the rapid adaptation of eastern Eurasians to ancient environmental shifts and dietary changes during agricultural innovations. Evolutionary trajectory reconstruction of metabolism-related genes of methylenetetrahydrofolate reductase (<em>MTHFR</em>) and fatty acid desaturase 1 (<em>FADS1</em>) suggested that ancient dietary shifts during the Neolithic transition period promoted the differentiated metabolic rate of folate and fatty acid. We revealed the polygenicity of biological adaptation traits and the pleiotropy of adaptive genes, indicating that complex recent polygenic adaptations, genetic interactions, and genotype–phenotype correlations have contributed to the genetic architecture of complex traits in eastern Eurasians.</p></div>","PeriodicalId":100609,"journal":{"name":"hLife","volume":"2 6","pages":"Pages 296-313"},"PeriodicalIF":0.0,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2949928324000336/pdfft?md5=3b7d10b130d6794db4c4add576489a53&pid=1-s2.0-S2949928324000336-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140776865","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Heterogeneity and clinical genomics of blaKPC-2-producing, carbapenem-resistant Pseudomonas aeruginosa","authors":"Man Huang ,&nbsp;Lizhang Liu ,&nbsp;Xiaoxia Li ,&nbsp;Yu Shi ,&nbsp;Huimin Zhang ,&nbsp;Ting Lu ,&nbsp;Youjun Feng","doi":"10.1016/j.hlife.2024.04.001","DOIUrl":"10.1016/j.hlife.2024.04.001","url":null,"abstract":"","PeriodicalId":100609,"journal":{"name":"hLife","volume":"2 6","pages":"Pages 314-319"},"PeriodicalIF":0.0,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2949928324000257/pdfft?md5=c3eed14be3de14f0a2f7f3dc24ae0b6d&pid=1-s2.0-S2949928324000257-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140786281","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reconciling host-microbiota metabolic incompatibility safeguards male fertility","authors":"Qing Shang ,&nbsp;Zhuoyang Li ,&nbsp;Na Yin ,&nbsp;Min Peng","doi":"10.1016/j.hlife.2024.04.006","DOIUrl":"10.1016/j.hlife.2024.04.006","url":null,"abstract":"<div><p>The symbiotic relationship between the host and microbiota is widely acknowledged as mutually beneficial. However, due to significant differences in metabolic substrates and products between prokaryotic bacteria and mammalian cells, mechanisms must exist to reconcile the metabolic incompatibility between the host and microbiota. We report that host enzymes are required to detoxify gut microbiota-derived acetate to maintain male fertility in mice. The combined deletion of acetyl-CoA synthetase short-chain family member 1 and 2 (ACSS1 and ACSS2), two enzymes consuming acetate in mammals, leads to excessive accumulation of acetate in circulation. This accumulation causes metabolic acidosis, blocking spermatogenesis and rendering male mice infertile. ACSS1/2-deficient germ cells exhibit comprehensive metabolic alterations with nicotinamide adenine dinucleotide (NAD⁺) deficiency that impairs betaine production. Supplementation with betaine restores spermatogenesis and fertility in ACSS1/2-deficient mice. Thus, the inevitable production of acetate by gut bacteria and its reproductive toxicity to the host represents an unappreciated metabolic incompatibility between the host and microbiota, which is reconciled by ACSS1/2.</p></div>","PeriodicalId":100609,"journal":{"name":"hLife","volume":"2 6","pages":"Pages 284-295"},"PeriodicalIF":0.0,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2949928324000348/pdfft?md5=bee3bae047fbba868d44e6bf17de35e3&pid=1-s2.0-S2949928324000348-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140789767","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of COVID-19-related nonpharmaceutical interventions on diarrheal diseases and zoonotic Salmonella","authors":"Linlin Huang ,&nbsp;Haiyang Zhou ,&nbsp;Jiaqi Chen ,&nbsp;Chenghao Jia ,&nbsp;Abubakar Siddique ,&nbsp;Beibei Wu ,&nbsp;Haoqiu Wang ,&nbsp;Biao Tang ,&nbsp;Fang He ,&nbsp;Guoping Zhao ,&nbsp;Min Yue","doi":"10.1016/j.hlife.2024.03.005","DOIUrl":"10.1016/j.hlife.2024.03.005","url":null,"abstract":"<div><p>Non-pharmaceutical interventions (NPIs) have been proven effective in reducing the spread of the coronavirus disease 2019 (COVID-19), but their broader impact on gastrointestinal disorders remains poorly studied. Here, we report an observational analysis and retrospective study that compares the incidence of acute diarrheal diseases in Hangzhou, Zhejiang, China, between 2019 and 2020, with an examination of the antimicrobial resistance and genetic spectrum of non-typhoidal <em>Salmonella</em> (NTS) from 2015 to 2022, before and during the COVID-19 pandemic. Our findings underscore that NPIs related to COVID-19 effectively reduced the incidence of acute diarrhea, with a substantial decrease in most enteric pathogens. Notably, NTS exhibited an unexpected surge. Further genomic investigations of NTS isolates revealed an overall reduction in antimicrobial-resistant (AMR), disinfection-tolerant, and virulent capabilities, but with marked variations detected between human and animal isolates. Additional genome-based analysis confirmed a decrease in the scale of zoonotic transmission in response to NPIs, suggesting particular NTS types may contribute to human infections <em>via</em> alternative pathways. The collective findings manifested that COVID-19-related NPIs had a mixed impact on NTS infections, which may inform AMR NTS mitigation policy.</p></div>","PeriodicalId":100609,"journal":{"name":"hLife","volume":"2 5","pages":"Pages 246-256"},"PeriodicalIF":0.0,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S294992832400021X/pdfft?md5=ef4692c24d1eaa5a8c17e9096447be89&pid=1-s2.0-S294992832400021X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140400966","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring structure-based drug discovery of GPCRs beyond the orthosteric binding site","authors":"Zhao Chen ,&nbsp;Xintong Ren ,&nbsp;Yu Zhou ,&nbsp;Niu Huang","doi":"10.1016/j.hlife.2024.01.002","DOIUrl":"10.1016/j.hlife.2024.01.002","url":null,"abstract":"<div><p>G-protein coupled receptors (GPCRs) are the largest family of druggable targets. In recent years, GPCR structural biology has made great advances, revealing the three-dimensional structures of many GPCRs and their interactions with ligands, proteins, and membrane components, which also have inspired a surge of structure-based drug discovery campaigns. This article provides a comprehensive summary of the currently available structural insights into the allosteric pockets of GPCRs and their regulatory mechanisms governing GPCR conformational changes. Furthermore, this article also presents several structure-inspired studies that utilize both orthosteric and allosteric modulation to discover small molecular modulators targeting GPCRs. The article emphasizes the promising potential of drug discovery targeting GPCR allosteric sites, while acknowledging the challenges arising from the limited structural information regarding the lipids and cholesterols in the membrane. Finally, the article discusses the future prospects of using large-scale or focused compound libraries to discover novel chemotypes, as well as the application of artificial intelligence (AI) in structure-based virtual screening (SBVS) against GPCRs.</p></div>","PeriodicalId":100609,"journal":{"name":"hLife","volume":"2 5","pages":"Pages 211-226"},"PeriodicalIF":0.0,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S294992832400004X/pdfft?md5=f8438112b4a1d7b8661feb4e1f40b1ec&pid=1-s2.0-S294992832400004X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139537270","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Safety and immunogenicity of COVID-19 vaccine ZF2001 in Chinese aged 60 years and older","authors":"Lidong Gao ,&nbsp;Huijie Yang ,&nbsp;Peng He ,&nbsp;Shilong Yang ,&nbsp;Wanjun Li ,&nbsp;Fangjun Li ,&nbsp;Wei Xia ,&nbsp;Shangxiao Zhang ,&nbsp;Xilu Wang ,&nbsp;Lingfeng Yuan ,&nbsp;Ruyue Wang ,&nbsp;Liangliang Xiao ,&nbsp;Lianpan Dai ,&nbsp;George Fu Gao ,&nbsp;Zhongyu Hu ,&nbsp;Zaixin Zhong ,&nbsp;Fan Ding ,&nbsp;Yan Li","doi":"10.1016/j.hlife.2024.03.001","DOIUrl":"10.1016/j.hlife.2024.03.001","url":null,"abstract":"","PeriodicalId":100609,"journal":{"name":"hLife","volume":"2 5","pages":"Pages 257-261"},"PeriodicalIF":0.0,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2949928324000166/pdfft?md5=4c422165768088012a6ad5e26845cc74&pid=1-s2.0-S2949928324000166-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140271976","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Modeling viral evolution: A novel SIRSVIDE framework with application to SARS-CoV-2 dynamics","authors":"Kaichun Jin ,&nbsp;Xiaolu Tang ,&nbsp;Zhaohui Qian ,&nbsp;Zhiqiang Wu ,&nbsp;Zifeng Yang ,&nbsp;Tao Qian ,&nbsp;Chitin Hon ,&nbsp;Jian Lu","doi":"10.1016/j.hlife.2024.03.006","DOIUrl":"10.1016/j.hlife.2024.03.006","url":null,"abstract":"<div><p>Understanding evolutionary trends in emerging viruses, such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is crucial for effective public health management and response. Nonetheless, extensive debates have arisen concerning viral evolutionary trends, particularly the interplay between transmissibility, pathogenicity, and immune escape. In this context, we have developed a novel computational model named SIRSVIDE (Susceptible-Infected-Recovered-Susceptible-Variation-Immune Decay-Immune Escape) to simulate the transmission and evolutionary dynamics of viral populations. Our simulation results indicate that under conditions of high mutation rates, elevated transmission rates, and larger susceptible host populations, viral populations exhibit prolonged increases in transmissibility and immune escape, accompanied by reductions in pathogenicity and noticeable short-term fluctuations. However, when the total susceptible population size and mutation rate decrease, substantial uncertainty in the evolutionary trends of viral populations becomes apparent. In summary, the SIRSVIDE model establishes a comprehensive framework for generating both short- and long-term viral epidemiological and evolutionary dynamics. The simulation outcomes align with existing evidence indicating that SARS-CoV-2 is undergoing selection for heightened transmissibility, decreased pathogenicity, and enhanced immune escape. Furthermore, the model sheds light on the possible evolutionary dynamics of other viruses.</p></div>","PeriodicalId":100609,"journal":{"name":"hLife","volume":"2 5","pages":"Pages 227-245"},"PeriodicalIF":0.0,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2949928324000221/pdfft?md5=7cf15c596cb5dd9fdf96fa3518689590&pid=1-s2.0-S2949928324000221-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140407931","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"International cooperation in science, technology, and health, challenges and perspectives","authors":"André Costa Lobato ,&nbsp;Carlos Medicis Morel ,&nbsp;Yi Shen","doi":"10.1016/j.hlife.2023.12.003","DOIUrl":"10.1016/j.hlife.2023.12.003","url":null,"abstract":"","PeriodicalId":100609,"journal":{"name":"hLife","volume":"2 5","pages":"Pages 207-210"},"PeriodicalIF":0.0,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2949928323000354/pdfft?md5=59f5d992bc04851f41ff1e7b4d0f992b&pid=1-s2.0-S2949928323000354-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139023475","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Innovating medicine: The path forward","authors":"Chen Dong","doi":"10.1016/j.hlife.2024.02.003","DOIUrl":"10.1016/j.hlife.2024.02.003","url":null,"abstract":"","PeriodicalId":100609,"journal":{"name":"hLife","volume":"2 4","pages":"Page 147"},"PeriodicalIF":0.0,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2949928324000142/pdfft?md5=dbd7d4e18981d5e3d78fa6a852e55952&pid=1-s2.0-S2949928324000142-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140088826","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Structural basis for the regulatory mechanism of mammalian mitochondrial respiratory chain megacomplex-I2III2IV2","authors":"Laixing Zhang ,&nbsp;Runyu Guo ,&nbsp;Chun Xiao ,&nbsp;Jiaqi Li ,&nbsp;Jinke Gu ,&nbsp;Maojun Yang","doi":"10.1016/j.hlife.2024.03.003","DOIUrl":"10.1016/j.hlife.2024.03.003","url":null,"abstract":"<div><p>Mammalian mitochondrial electron transport chain complexes are the most important and complicated protein machinery in mitochondria. Although this system has been studied for more than a century, its composition and molecular mechanism are still largely unknown. Here we report the high-resolution cryo-electron microscopy (Cryo-EM) structures of porcine respiratory chain megacomplex-I₂III₂IV₂ (MCI₂III₂IV₂) in five different conformations, including State 1, State 2, Mid 1, Mid 2, and Mid 3. High-resolution Cryo-EM imaging, combined with super-resolution gated stimulated emission depletion microscopy (gSTED), strongly supports the formation of MCI₂III₂IV₂ in live cells. Each MCI₂III₂IV₂ structure contains 141 subunits (70 different kinds of peptides, 2.9 MDa) in total with 240 transmembrane helices. The mutual influence among CI, CIII, and CIV shown in the MCI₂III₂IV₂ structure suggests this megacomplex could act as an integral unit in electron transfer and proton pumping. The conformational changes from different states suggest a plausible regulatory mechanism for the MCI₂III₂IV₂ activation/deactivation process.</p></div>","PeriodicalId":100609,"journal":{"name":"hLife","volume":"2 4","pages":"Pages 189-200"},"PeriodicalIF":0.0,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S294992832400018X/pdfft?md5=0af226589712f8a816daf8ee52975c5b&pid=1-s2.0-S294992832400018X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140276342","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}