hLife Pub Date : 2024-05-01 DOI: 10.1016/j.hlife.2024.03.006

Kaichun Jin , Xiaolu Tang , Zhaohui Qian , Zhiqiang Wu , Zifeng Yang , Tao Qian , Chitin Hon , Jian Lu

{"title":"Modeling viral evolution: A novel SIRSVIDE framework with application to SARS-CoV-2 dynamics","authors":"Kaichun Jin , Xiaolu Tang , Zhaohui Qian , Zhiqiang Wu , Zifeng Yang , Tao Qian , Chitin Hon , Jian Lu","doi":"10.1016/j.hlife.2024.03.006","DOIUrl":"10.1016/j.hlife.2024.03.006","url":null,"abstract":"<div>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.</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}

引用次数: 0

International cooperation in science, technology, and health, challenges and perspectives 科学、技术和卫生领域的国际合作、挑战和前景

hLife Pub Date : 2024-05-01 DOI: 10.1016/j.hlife.2023.12.003

André Costa Lobato , Carlos Medicis Morel , Yi Shen

引用次数: 0

Innovating medicine: The path forward 创新医学：前进之路

hLife Pub Date : 2024-04-01 DOI: 10.1016/j.hlife.2024.02.003

Chen Dong

引用次数: 0

Structural basis for the regulatory mechanism of mammalian mitochondrial respiratory chain megacomplex-I2III2IV2 哺乳动物线粒体呼吸链巨型复合体-I2III2IV2调控机制的结构基础

hLife Pub Date : 2024-04-01 DOI: 10.1016/j.hlife.2024.03.003

Laixing Zhang , Runyu Guo , Chun Xiao , Jiaqi Li , Jinke Gu , Maojun Yang

{"title":"Structural basis for the regulatory mechanism of mammalian mitochondrial respiratory chain megacomplex-I2III2IV2","authors":"Laixing Zhang , Runyu Guo , Chun Xiao , Jiaqi Li , Jinke Gu , Maojun Yang","doi":"10.1016/j.hlife.2024.03.003","DOIUrl":"10.1016/j.hlife.2024.03.003","url":null,"abstract":"<div>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.</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}

引用次数: 0

Aldo-keto reductase 1B: Much learned, much more to do 醛酮还原酶 1B：获益良多，任重道远

hLife Pub Date : 2024-04-01 DOI: 10.1016/j.hlife.2023.12.002

Yaya Zhao , Miaomiao Zhang , Huaping Li , Yiwen Yang , Xiaofu Lu , Junjing Yu , Lei Pan

{"title":"Aldo-keto reductase 1B: Much learned, much more to do","authors":"Yaya Zhao , Miaomiao Zhang , Huaping Li , Yiwen Yang , Xiaofu Lu , Junjing Yu , Lei Pan","doi":"10.1016/j.hlife.2023.12.002","DOIUrl":"10.1016/j.hlife.2023.12.002","url":null,"abstract":"<div>The aldo-keto reductase 1B (AKR1B) subfamily was initially known for its association with the pathogenesis of secondary diabetic complications such as retinopathy, neuropathy, nephropathy, and cataracts. Unfortunately, over the past few decades, all drug development efforts targeting this family have failed for one reason or another. Recently, a growing body of evidence showing the deep involvement of AKR1B in metabolic reprogramming and production of signaling metabolites has led to a re-evaluation of their role in the pathogenesis of several immunometabolism-related diseases, such as gastrointestinal diseases, psoriasis, congenital disorders of glycosylation, carcinogenesis, even progression, and acquired chemoresistance. Therefore, in this review, we will summarize the current knowledge of AKR1B, highlighting their potential function in regulating immune cell function and then inflammatory complications. We will also explore how discovering this new insight into this old enzyme is essential for envisioning potential therapeutic strategies to prevent or treat inflammatory diseases.</div>","PeriodicalId":100609,"journal":{"name":"hLife","volume":"2 4","pages":"Pages 154-178"},"PeriodicalIF":0.0,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2949928323000342/pdfft?md5=1a8e2e16aea9b7c181cb209667184497&pid=1-s2.0-S2949928323000342-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139026334","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}

引用次数: 0

Medical journals: The past, present, and future 医学期刊：过去、现在和未来

hLife Pub Date : 2024-04-01 DOI: 10.1016/j.hlife.2024.02.002

Chen Dong , Eric Rubin , Rui-Ping Xiao

引用次数: 0

Optimized pretreatment increases the susceptibility of hepatitis B virus infection by enhancing actomyosin-driven cell spreading 优化预处理可通过增强肌动蛋白驱动的细胞扩散提高乙型肝炎病毒感染的易感性

hLife Pub Date : 2024-04-01 DOI: 10.1016/j.hlife.2023.12.006

Shuzhi Cui , Wei Gao , Zonghong Li , Yi Xu , Yaming Jiu

引用次数: 0

Mitochondrial flashes are interlinked with adaptive thermogenesis in brown adipocytes 线粒体闪烁与棕色脂肪细胞的适应性产热相互关联

hLife Pub Date : 2024-04-01 DOI: 10.1016/j.hlife.2024.02.004

Xinyu Chen , Huwatibieke Bahetiyaer , Xuejiao Song , Zuzhi Jiang , Wenfeng Qi , Weizheng Gao , Lin Zhang , Jue Zhang , Heping Cheng , Xianhua Wang

{"title":"Mitochondrial flashes are interlinked with adaptive thermogenesis in brown adipocytes","authors":"Xinyu Chen , Huwatibieke Bahetiyaer , Xuejiao Song , Zuzhi Jiang , Wenfeng Qi , Weizheng Gao , Lin Zhang , Jue Zhang , Heping Cheng , Xianhua Wang","doi":"10.1016/j.hlife.2024.02.004","DOIUrl":"10.1016/j.hlife.2024.02.004","url":null,"abstract":"<div>Mitochondrial flash (mitoflash) is the electrochemical excitation of a single mitochondrion and plays diverse signaling roles in a variety of cells. From the viewpoint of bioenergetics, it represents the transient uncoupling of mitochondrial respiration from ATP synthesis. Brown adipose tissue (BAT) produces heat, primarily via mitochondrial uncoupled respiration. Here, we aim to illustrate the mitoflash activity in BAT thermogenesis. We show that BAT mitochondria undergo stochastic and intermittent mitoflashes at the levels of isolated mitochondria, cultured brown adipocytes, and even intact BAT. A BAT mitoflash contains multiple signals, including transient depolarization of mitochondrial membrane potential, transient matrix alkalization, and bursting production of reactive oxygen species. Importantly, thermogenic activation by β3-adrenergic stimulation dramatically augments mitoflash incidence, with mild effects on its unitary characteristics. Ablation of the thermogenic uncoupling protein 1 (UCP1) showed little effect on mitoflash biogenesis during heat production. Collectively, our results suggest that mitoflash might constitute an elemental signaling activity of mitochondria to regulate BAT thermogenesis.</div>","PeriodicalId":100609,"journal":{"name":"hLife","volume":"2 4","pages":"Pages 179-188"},"PeriodicalIF":0.0,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2949928324000154/pdfft?md5=b7cf3e1348bb8eed376769a98e594328&pid=1-s2.0-S2949928324000154-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140088732","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}

引用次数: 0

A human monoclonal antibody neutralizes SARS-CoV-2 Omicron variants by targeting the upstream region of spike protein HR2 motif 一种人类单克隆抗体通过靶向尖峰蛋白 HR2 Motif 的上游区域中和 SARS-CoV-2 Omicron 变体

hLife Pub Date : 2024-03-01 DOI: 10.1016/j.hlife.2024.02.001

Hang Su , Jun Zhang , Zhenfei Yi , Sajid Khan , Mian Peng , Liang Ye , Alan Bao , Han Zhang , Guangli Suo , Qian Li , Housheng Zheng , Dandan Wu , Thomas J. Kipps , Lanfeng Wang , Zhenghong Lin , Suping Zhang

{"title":"A human monoclonal antibody neutralizes SARS-CoV-2 Omicron variants by targeting the upstream region of spike protein HR2 motif","authors":"Hang Su , Jun Zhang , Zhenfei Yi , Sajid Khan , Mian Peng , Liang Ye , Alan Bao , Han Zhang , Guangli Suo , Qian Li , Housheng Zheng , Dandan Wu , Thomas J. Kipps , Lanfeng Wang , Zhenghong Lin , Suping Zhang","doi":"10.1016/j.hlife.2024.02.001","DOIUrl":"10.1016/j.hlife.2024.02.001","url":null,"abstract":"<div>The continuous emergence of new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants means there is a need to explore additional strategies to develop broad-spectrum vaccines or therapeutics for individuals remaining at risk of coronavirus disease 2019 (COVID-19). Neutralizing monoclonal antibody (mAb) that binds to the conserved S2 subunit of the SARS-CoV-2 spike (S) protein alone, or in combination with mAb that binds to the receptor-binding domain (RBD) of S protein, might be effective in eliciting protection from infection by a variety of SARS-CoV-2 variants. Using high-throughput single-cell immunoglobulin sequencing of B cells from COVID-19-convalescent donors, we identified a high-affinity S2-specific mAb-39, that could inhibit original SARS-CoV-2 strain, Omicron BA.1, BA.2.86, BA.4, BA.5, and EG.5.1 S protein-mediated membrane fusion, leading to the neutralization of these pseudoviral infections. Moreover, mAb-39 could also improve the neutralizing activity of anti-RBD antibody against the highly neutralization-resistant Omicron variants. Molecular docking and point mutation analyses revealed that mAb-39 recognized epitopes within the conserved upstream region of the heptad repeat 2 (HR2) motif of the S2 subunit. Collectively, these findings demonstrate that targeting the conserved upstream region of the HR2 motif (e.g., using mAbs) provides a novel strategy for preventing the infection of SARS-CoV-2 and its variants.</div>","PeriodicalId":100609,"journal":{"name":"hLife","volume":"2 3","pages":"Pages 126-140"},"PeriodicalIF":0.0,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2949928324000099/pdfft?md5=11653956591dc457ecdf3cd236c53ddd&pid=1-s2.0-S2949928324000099-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139815165","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}

引用次数: 0

Medicine has no borders, health unites us all: Henry Norman Bethune as a pioneer, medical scientist, and internationalist 医学无国界，健康心连心：亨利-诺尔曼-白求恩--医术精湛的先驱专家和伟大的国际斗士

hLife Pub Date : 2024-03-01 DOI: 10.1016/j.hlife.2023.11.002

Huan Liu , Xue Gong , Zhaoqi Liu , Kunlan Zuo , Hao Cheng

引用次数: 0

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