hLife Pub Date : 2025-02-01 DOI: 10.1016/j.hlife.2024.12.003

Yuchen Kang , Ping Gao , Xiaotong Chen , Xiaoyu Zhai , Xi Wang , Xiaojuan Han , Baoqian Jia , Baidong Hou , Xuyu Zhou , Jian Song , Fuping Zhang

{"title":"Lrrk2 promotes M1 macrophage polarization via regulating cytokine (IFN-γ) and TLR4 (LPS)-mediated responses","authors":"Yuchen Kang , Ping Gao , Xiaotong Chen , Xiaoyu Zhai , Xi Wang , Xiaojuan Han , Baoqian Jia , Baidong Hou , Xuyu Zhou , Jian Song , Fuping Zhang","doi":"10.1016/j.hlife.2024.12.003","DOIUrl":"10.1016/j.hlife.2024.12.003","url":null,"abstract":"<div><div>Leucine-rich repeat kinase 2 (<em>Lrrk2</em>) has received widespread attention as a risk gene associated with Parkinson's disease. As the immune response attributes of Parkinson's disease have been gradually revealed, the link between <em>Lrrk2</em> and the immune system has emerged. Here, we demonstrated that <em>Lrrk2</em> regulates macrophage function by promoting M1 polarization. Transcriptome and immunological analyses revealed that deletion of <em>Lrrk2</em> in macrophages leads to blunted interferon (IFN)-γ and lipopolysaccharide (LPS)-stimulated M1 macrophage-associated gene expression and function. Mechanistically, <em>Lrrk2</em> supports M1-associated immune effector signatures, including chemokines and inducible nitric oxide synthase (iNOS) expression, by enhancing signal transducer and activator of transcription 1 (STAT1) transcription factor signaling. The effect of <em>Lrrk2</em> on macrophages is dependent on its kinase activity. These results revealed a previously uncharacterized role of <em>Lrrk2</em> in M1 macrophage polarization by modulating cellular responses to cytokines and toll-like receptors (TLRs), such as IFN-γ and LPS.</div></div>","PeriodicalId":100609,"journal":{"name":"hLife","volume":"3 2","pages":"Pages 98-111"},"PeriodicalIF":0.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143402792","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

Diversity of reverse-transcriptase-containing viruses through global metagenomics 通过全球宏基因组分析含逆转录酶病毒的多样性

hLife Pub Date : 2025-01-01 DOI: 10.1016/j.hlife.2024.10.002

Kaiyang Zheng , Yantao Liang , Yan Zhang , David Páez-Espino , Hongbing Shao , Yeong Yik Sung , Wen Jye Mok , Li Lian Wong , Shi Wang , Andrew McMinn , Min Wang

引用次数: 0

Altitude adaptation: The unseen work of gut microbiota 海拔适应：肠道微生物群的隐形工作

hLife Pub Date : 2025-01-01 DOI: 10.1016/j.hlife.2024.11.004

Jingling Guo , Runzhou Zhao , Kun Li , Yafang Tan , Likun Wang , Hui Ling , Huan Zhang , Guha Dharmarajan , Yujing Bi , Ruifu Yang

{"title":"Altitude adaptation: The unseen work of gut microbiota","authors":"Jingling Guo , Runzhou Zhao , Kun Li , Yafang Tan , Likun Wang , Hui Ling , Huan Zhang , Guha Dharmarajan , Yujing Bi , Ruifu Yang","doi":"10.1016/j.hlife.2024.11.004","DOIUrl":"10.1016/j.hlife.2024.11.004","url":null,"abstract":"<div><div>High altitudes are one type of extreme environment characterized by hypobaric hypoxia, extreme cold, strong ultraviolet radiation, and low energy availabilty that present tremendous challenges to human and wildlife inhabiting these environs. These extreme environments serve as a unique natural laboratory for delving into the impact of selective pressures on species variation and adaptation. This narrative review compiles the latest research on high-altitude adaptation, with a specific focus on the crucial role of gut microbiota in this process. Evidence indicates that gut microbiota significantly impacts an organism's ability to adapt to high-altitude conditions by adjusting its composition, and hence impacting its function and ability to release microbial metabolites. We explore the link between gut microbiota and high-altitude environments, the microbial signatures, and their effects on adaptation, as well as the potential for targeted modulation of gut microbiota to enhance acclimatization to high altitudes. By examining the interaction between microbiota and host adaptation, this review aims to promote further mechanistic studies and support strategies for improving high-altitude acclimatization through gut microbiota modulation.</div></div>","PeriodicalId":100609,"journal":{"name":"hLife","volume":"3 1","pages":"Pages 5-20"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143137025","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

Drosophila Cul3 contributes to Diap2-mediated innate immune signaling for antimicrobial defense 果蝇Cul3参与diap2介导的抗微生物防御的先天免疫信号

hLife Pub Date : 2025-01-01 DOI: 10.1016/j.hlife.2024.10.001

Fanrui Kong , Zixuan Wang , Chuchu Zhang , Yihua Xiao , Muhammad Abdul Rehman Saeed , Weini Li , Akira Goto , Qingshuang Cai , Shanming Ji

{"title":"Drosophila Cul3 contributes to Diap2-mediated innate immune signaling for antimicrobial defense","authors":"Fanrui Kong , Zixuan Wang , Chuchu Zhang , Yihua Xiao , Muhammad Abdul Rehman Saeed , Weini Li , Akira Goto , Qingshuang Cai , Shanming Ji","doi":"10.1016/j.hlife.2024.10.001","DOIUrl":"10.1016/j.hlife.2024.10.001","url":null,"abstract":"<div><div>The host antimicrobial immune response relies on a complex interplay of molecular mechanisms to effectively combat microbial infections. Herein, we investigate the functional role of Cullin-3 (Cul3), one critical constituent of Cullin-RING ubiquitin ligases, in the <em>Drosophila melanogaster</em> (fruit fly) antimicrobial immune defense. We show that silencing of <em>Cul3</em> leads to a decreased induction of antimicrobial peptides and high mortality in adult flies after bacterial infection. Through biochemical approaches, we demonstrate that Cul3 predominantly relies on its BTB-binding domain and neddylation domain to physically associate with death-associated inhibitor of apoptosis 2 (Diap2). Importantly, Cul3 ameliorates the Diap2-mediated ubiquitination of death-related ced-3/Nedd2-like caspase (Dredd), a process essential for robust immune deficiency signaling upon bacterial infection. Taken together, our findings highlight a previously unrecognized regulatory axis of Cul3/Diap2/Dredd in the fly antimicrobial immune defense, providing potential insights into therapeutic strategies for combating bacterial infections in humans.</div></div>","PeriodicalId":100609,"journal":{"name":"hLife","volume":"3 1","pages":"Pages 38-51"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143137023","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

Induction of translation-suppressive G3BP1+ stress granules and interferon-signaling cGAS condensates by transfected plasmid DNA 转染质粒DNA诱导翻译抑制G3BP1+应激颗粒和干扰素信号传导cGAS凝析物

hLife Pub Date : 2025-01-01 DOI: 10.1016/j.hlife.2024.11.005

Vladimir Majerciak, Zhi-Ming Zheng

{"title":"Induction of translation-suppressive G3BP1+ stress granules and interferon-signaling cGAS condensates by transfected plasmid DNA","authors":"Vladimir Majerciak, Zhi-Ming Zheng","doi":"10.1016/j.hlife.2024.11.005","DOIUrl":"10.1016/j.hlife.2024.11.005","url":null,"abstract":"<div><div>Plasmid DNA transfection is one of the fundamental tools of biomedical research. Here, we found that plasmid DNA transfection mediated by liposomes activates multiple innate immune responses in several widely used cell lines. Their activations were visible by the detection of stress granules (SG) and cyclic guanosine monophosphate-adenosine monophosphate synthase (cGAS)-DNA condensates (cGC) in the transfected cells in a plasmid DNA dose-dependent manner. The elevated levels of phosphorylated eukaryotic translation initiation factor 2 subunit alpha (eIF2α), interferon regulatory factor 3 (IRF3), and signal transducer and activator of transcription 1 (STAT1) were induced in plasmid DNA-transfected cells. The formation of SG but not cGC required active transcription and the formation of double-stranded RNA in transfected cells. Plasmid DNA-induced SG or cGC were mutually exclusive because they triggered two distinct pathways. Knockdown (KD) of protein kinase R (PKR) before plasmid DNA transfection led to abolishing SG without affecting cGC formation. Conversely, cGAS KD could prevent cGC without affecting SG formation. In addition, plasmid DNA-induced SG and cGC formation could be prevented, respectively, by co-expression of Kaposi's sarcoma-associated herpesvirus proteins ORF57 (PKR inhibitor) and ORF52 (cGAS inhibitor). Inhibition of SG formation mediated by PKR KD, but not cGC KD, also led to increased expression of transgenes, indicating that PKR activation represents a major roadblock to gene expression. Together, these data indicate that plasmid DNA triggers innate immune responses in the transfected cells and causes a significant cellular perturbation that should be considered during experiment design and data interpretation.</div></div>","PeriodicalId":100609,"journal":{"name":"hLife","volume":"3 1","pages":"Pages 21-37"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143137024","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

MicroRNAs unveiled: Nobel recognition of a revolutionary gene regulation mechanism MicroRNAs揭秘：革命性基因调控机制获诺贝尔奖

hLife Pub Date : 2025-01-01 DOI: 10.1016/j.hlife.2024.11.002

Junchao Xue , Gangming Zhang , Enzhi Shen

引用次数: 0

Comparison of antigen-specific B cell responses reveals disparity in immunogenicity and memory B cell formation across COVID-19 vaccine platforms 抗原特异性B细胞反应的比较揭示了不同疫苗平台在免疫原性和记忆性B细胞形成方面的差异

hLife Pub Date : 2024-12-01 DOI: 10.1016/j.hlife.2024.09.002

Chang Guo , Xin Chai , Maidaiti Baerlike , Yingping Liu , Yao Wang , Fei Shao , Qingrui Huang , Weiguo Zhang , Shan Cen , Yijie Dong , Yunlong Cao , Jinghua Yan , Xuyu Zhou , Zhaolin Hua , Baidong Hou

{"title":"Comparison of antigen-specific B cell responses reveals disparity in immunogenicity and memory B cell formation across COVID-19 vaccine platforms","authors":"Chang Guo , Xin Chai , Maidaiti Baerlike , Yingping Liu , Yao Wang , Fei Shao , Qingrui Huang , Weiguo Zhang , Shan Cen , Yijie Dong , Yunlong Cao , Jinghua Yan , Xuyu Zhou , Zhaolin Hua , Baidong Hou","doi":"10.1016/j.hlife.2024.09.002","DOIUrl":"10.1016/j.hlife.2024.09.002","url":null,"abstract":"<div><div>Various vaccine technologies have been employed in the coronavirus disease 2019 (COVID-19) vaccines, including whole inactivated virus (WIV), recombinant protein, mRNA, and nanoparticle vaccines. To elucidate the cellular mechanisms underlying the immune responses elicited by different vaccines, we examined and compared antigen-specific B cell responses targeting the receptor-binding domain (RBD) of the viral spike protein. We found that the nanoparticle vaccine pathogen-like antigens-RBD (PLA-RBD) and the mRNA vaccine demonstrated superior immunogenicity compared with the WIV vaccine and the RBD-dimer, a recombinant protein vaccine. Interestingly, the WIV vaccine contains toll-like receptor ligands that enhance IgG2a/c class-switching. For the mRNA vaccine, although it induces robust germinal center responses and T follicular helper (Tfh) cells, it has limited ability to induce memory B cells and long-lived plasma cells. These results indicate that vaccine formats significantly influence both the quantity and quality of immune responses, providing valuable insights for the future development of vaccines.</div></div>","PeriodicalId":100609,"journal":{"name":"hLife","volume":"2 12","pages":"Pages 625-640"},"PeriodicalIF":0.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143180725","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

Myeloid cell diversity: From fundamental biology to disease states 骨髓细胞多样性：从基础生物学到疾病状态

hLife Pub Date : 2024-12-01 DOI: 10.1016/j.hlife.2024.11.001

Iván Ballesteros , Lai Guan Ng , Daniela F. Quail , Andrés Hidalgo

引用次数: 0

WHO revised bacterial priority pathogens list to encourage global actions to combat AMR 世卫组织修订细菌重点病原体清单以鼓励全球采取行动抗击抗生素耐药性

hLife Pub Date : 2024-12-01 DOI: 10.1016/j.hlife.2024.10.003

Yingying Ma , Pan Chen , Yin Mo , Yonghong Xiao

引用次数: 0

Understanding carbapenem-resistant hypervirulent Klebsiella pneumoniae: Key virulence factors and evolutionary convergence 了解耐碳青霉烯高致病性肺炎克雷伯菌：关键毒力因素和进化趋同

hLife Pub Date : 2024-12-01 DOI: 10.1016/j.hlife.2024.06.005

Tao Chen , Liya Ying , Luying Xiong , Xueting Wang , Ping Lu , Yuan Wang , Ping Shen , Yonghong Xiao

{"title":"Understanding carbapenem-resistant hypervirulent Klebsiella pneumoniae: Key virulence factors and evolutionary convergence","authors":"Tao Chen , Liya Ying , Luying Xiong , Xueting Wang , Ping Lu , Yuan Wang , Ping Shen , Yonghong Xiao","doi":"10.1016/j.hlife.2024.06.005","DOIUrl":"10.1016/j.hlife.2024.06.005","url":null,"abstract":"<div><div>The emergence of hypervirulence (hv) and carbapenem resistance (CR) as distinct evolutionary directions for <em>Klebsiella pneumoniae</em> presents a significant threat in clinical settings. However, in recent years, there has been a growing identification of <em>K. pneumoniae</em> strains that integrate both phenotypes, resulting in severe clinical outcomes. Carbapenem-resistant hypervirulent <em>K. pneumoniae</em> (CRhvKP) typically emerges through the acquisition of plasmids carrying either virulence or CR-encoded genes by carbapenem-resistant <em>K. pneumoniae</em> or hypervirulent <em>K. pneumoniae</em>. Furthermore, the acquisition of a hybrid plasmid can confer a combination of CR and hv. CRhvKP can cause a variety of infections, including pneumonia, urinary tract infections, bloodstream infections, liver abscesses, and other related conditions. While the sequence type 11 (ST11) dominates the majority of CRhvKP strains in China, the molecular factors responsible for the success of ST11 CRhvKP largely remain unknown. Here, we provide an overview of the current understanding of the variation and distribution of crucial virulence determinants, the mechanisms driving the merging of hv and CR, and the potential molecular factors influencing the epidemiological success of ST11 CRhvKP. This research aims to contribute to a comprehensive understanding of the complexities surrounding CRhvKP. It is imperative to underscore the development of combination therapies, precision medicine, and vaccine strategies as pivotal approaches in effectively combating CRhvKP. Considering the widespread prevalence of CRhvKP, a prioritized, multifaceted approach encompassing infection control, active surveillance, and the development of innovative therapeutics is essential.</div></div>","PeriodicalId":100609,"journal":{"name":"hLife","volume":"2 12","pages":"Pages 611-624"},"PeriodicalIF":0.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143180724","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

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