hLife最新文献

{"title":"Establishing a regulatory framework for phage therapy in China","authors":"Jixin Yang, Haiyan Chen, Xuesong He, Nannan Wu, Shuai Le, Tongyu Zhu","doi":"10.1016/j.hlife.2026.05.001","DOIUrl":"10.1016/j.hlife.2026.05.001","url":null,"abstract":"","PeriodicalId":100609,"journal":{"name":"hLife","volume":"4 9","pages":"Pages 554-557"},"PeriodicalIF":0.0,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149033239","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":"A phage-based luminescent reporter platform for rapid typing of multiple capsular types of Klebsiella pneumoniae","authors":"Yiyao Song,&nbsp;Shisong Jing,&nbsp;Yi Li,&nbsp;Yinglu Guo,&nbsp;Jiangqing Huang,&nbsp;Xianbiao Bi,&nbsp;Dawei Wei,&nbsp;Chao Wang,&nbsp;Gang Zhang,&nbsp;Jiajia Zheng,&nbsp;Zhongrui Ma,&nbsp;Jie Feng","doi":"10.1016/j.hlife.2026.06.001","DOIUrl":"10.1016/j.hlife.2026.06.001","url":null,"abstract":"<div><div><em>Klebsiella pneumoniae</em> is an important opportunistic pathogen, and its capsular polysaccharides are key virulence factors. Capsular typing is important for epidemiological surveillance, clinical diagnosis, and therapy development; however, methods for capsule-targeted detection remain limited. Here, we engineered a modular bioluminescent reporter phage platform leveraging bacteriophage receptor-binding proteins (RBPs) for specific <em>K. pneumoniae</em> capsular typing. Initially, the K2-specific bacteriophage ΦRCIP0109 was engineered with the <em>nluc</em> reporter gene to generate ΦRCIP0109::<em>nluc</em> for K2 detection. Using ΦRCIP0109::<em>nluc</em> as the chassis, we engineered reporter phages by swapping RBPs, thereby expanding the detection range to four additional clinically important K-types (K64, K47, K1, and K57). Reporter phage specificity and sensitivity were evaluated against clinical isolates and in simulated polymicrobial environments. Directed evolution was employed to introduce RBP mutations for enhanced phage adsorption. These five reporter phages achieved 100% specificity against clinical isolates, detecting concentrations as low as 10 colony-forming units/mL within 3.5–5.5 h and successfully differentiating host strains in polymicrobial synthetic urine. Directed evolution of an RBP yielded a 10- to 100-fold increase in luminescence compared to that of the wild-type phage. Together, these advances establish a scalable platform that can be expanded to additional capsular types and the detection of other pathogens, representing a platform with clear potential for integration into point-of-care diagnostics, guiding targeted antimicrobial therapy and precision phage therapy.</div></div>","PeriodicalId":100609,"journal":{"name":"hLife","volume":"4 9","pages":"Pages 581-595"},"PeriodicalIF":0.0,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149033337","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":"Golgi-derived COPI vesicles fuel the biogenesis of coronavirus replication organelles","authors":"Zhaohuan Wang,&nbsp;Xinyue Su,&nbsp;Kaoyi Gong,&nbsp;Zixiao Yang,&nbsp;Shu-Rui Liu,&nbsp;Bi-Rong Zheng,&nbsp;Keda Shi,&nbsp;Yu Ye,&nbsp;Xinrong Zhou,&nbsp;Jian Pan,&nbsp;Deyin Guo,&nbsp;Panpan Hou,&nbsp;Chun-Mei Li","doi":"10.1016/j.hlife.2026.06.004","DOIUrl":"10.1016/j.hlife.2026.06.004","url":null,"abstract":"<div><div>Positive-strand RNA viruses remodel host endomembranes to form replication organelles (ROs). However, the membrane sources for coronavirus double-membrane vesicle (DMV) biogenesis remain unclear. Here, we used proteomic, genetic, pharmacological, and imaging approaches to identify the central membrane supply route for DMV formation. APEX2-based proximity proteomics first identified candidate pathways, followed by functional validation using siRNA knockdown, CRISPR/Cas9 editing, and Golgicide A (GCA) inhibition. DMV formation and viral RNA synthesis were assessed by electron microscopy, immunofluorescence, and qRT-PCR. Golgi–DMV association was analyzed by sucrose gradient fractionation and confocal imaging. <em>In vivo</em> relevance was evaluated in C57BL/6J mice infected with mouse hepatitis virus (MHV) and treated with GCA (intraperitoneal, 50 mg/kg; <em>n</em> = 4–5 per group). We showed that coronaviruses hijack the host GBF1-ARF1-COPI machinery to redirect Golgi-derived membranes to viral replication sites for DMV formation and expansion. Disruption of this pathway markedly impairs viral RNA synthesis, DMV biogenesis, and replication of multiple coronaviruses, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Pharmacological inhibition of Golgi-specific Brefeldin A-resistance factor 1 (GBF1) suppressed viral replication and pathology <em>in vivo</em>. Together, our findings reveal a previously unrecognized Golgi-derived membrane supply route for coronavirus ROs and highlight the GBF1-ARF1-COPI pathway as a potential host-directed target for broad-spectrum antiviral therapies.</div></div>","PeriodicalId":100609,"journal":{"name":"hLife","volume":"4 8","pages":"Pages 507-524"},"PeriodicalIF":0.0,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148775813","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":"Peptide-based henipavirus entry inhibitors as pandemic countermeasures","authors":"Qian Wang,&nbsp;Yuanzhou Wang,&nbsp;Lu Lu,&nbsp;Shibo Jiang","doi":"10.1016/j.hlife.2026.04.002","DOIUrl":"10.1016/j.hlife.2026.04.002","url":null,"abstract":"","PeriodicalId":100609,"journal":{"name":"hLife","volume":"4 8","pages":"Pages 489-493"},"PeriodicalIF":0.0,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148775817","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":"Ex-Tregs: From controversial artifact to therapeutic target","authors":"Liping Li,&nbsp;Minghui Li,&nbsp;Xuyu Zhou","doi":"10.1016/j.hlife.2026.05.002","DOIUrl":"10.1016/j.hlife.2026.05.002","url":null,"abstract":"<div><div>Regulatory T cell (Treg) instability has evolved from a debated artifact into a central concept in immunology, though the mechanisms driving the transition from a stable suppressor to a pathogenic ex-regulatory T cell (ex-Treg) remain unclear. This review synthesizes findings from fate-mapping, epigenetic, and metabolic studies in mouse models and human systems, tracing the ex-Treg concept through three phases: controversy, epigenetic reconciliation, and current views. The Treg-specific demethylated region (TSDR) distinguishes truly committed Tregs from transient forkhead box P3 (FOXP3) expressers. Three interdependent factors—environmental stress (interleukin-1β [IL-1β], interleukin-6 [IL-6]), epigenetic erasure (ten-eleven translocation 2 [TET2] dysfunction leading to TSDR hypermethylation), and metabolic rewiring (mechanistic target of rapamycin [mTOR]-driven glycolysis)—cooperatively drive ex-Treg conversion. The “self <em>vs</em> non-self” hypothesis frames instability as an evolved checkpoint balancing tolerance with host defense. Ex-Tregs contribute to autoimmunity and aging but also offer therapeutic opportunities in cancer. Key uncertainties persist regarding ex-Treg heterogeneity, epigenetic reversibility, and translation to humans. Future directions should focus on biomarker discovery and engineering epigenetically stable Tregs for therapy. Collectively, these advances position Treg instability as a pivotal regulator of immune homeostasis and highlight the promise of therapeutically targeting this pathway to advance treatments for autoimmunity, aging, and cancer.</div></div>","PeriodicalId":100609,"journal":{"name":"hLife","volume":"4 8","pages":"Pages 467-485"},"PeriodicalIF":0.0,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148775815","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":"Prospects for using mRNA vaccines against fungal infections","authors":"Yeqi Li,&nbsp;Xiaorong Lin","doi":"10.1016/j.hlife.2026.02.002","DOIUrl":"10.1016/j.hlife.2026.02.002","url":null,"abstract":"","PeriodicalId":100609,"journal":{"name":"hLife","volume":"4 8","pages":"Pages 486-488"},"PeriodicalIF":0.0,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148775816","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":"New design for universal respiratory vaccines: A new paradigm on integrated immunity","authors":"Zhen Liu,&nbsp;Shuo Wang","doi":"10.1016/j.hlife.2026.05.005","DOIUrl":"10.1016/j.hlife.2026.05.005","url":null,"abstract":"","PeriodicalId":100609,"journal":{"name":"hLife","volume":"4 8","pages":"Pages 463-466"},"PeriodicalIF":0.0,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148775814","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":"Genetic tool for specific tracking of mature neutrophils","authors":"Jiayu Cao,&nbsp;Hui Ping Yaw,&nbsp;Shilin Yi,&nbsp;Yanxi Zhou,&nbsp;Shifan Qin,&nbsp;Yuanyuan Wang,&nbsp;Raul da Costa,&nbsp;Lei Zhang,&nbsp;Dandan Wu,&nbsp;Changbin Chen,&nbsp;Melissa Ng,&nbsp;Immanuel Kwok,&nbsp;Oliver Soehnlein,&nbsp;Xiaoxiang Chen,&nbsp;Jieqing Wan,&nbsp;Lai Guan Ng","doi":"10.1016/j.hlife.2026.05.007","DOIUrl":"10.1016/j.hlife.2026.05.007","url":null,"abstract":"<div><div>Tracking mature neutrophils remains challenging due to the lack of reliable cell surface markers. Although CD101 is a promising candidate as a marker for mature neutrophils, its stability under pathological conditions is unclear. Here, we developed a novel CD101-tdTomato reporter mouse model to specifically identify mature neutrophils. CD101 expression, tdTomato fluorescence, and neutrophil physiology were characterized by flow cytometry across peripheral tissues under homeostasis and by a transwell migration assay, in parallel with morphological features assessed by Wright-Giemsa staining. To assess marker stability, CD101-tdTomato and wild-type (WT) mice were treated with lipopolysaccharide (LPS) (200 ng, intraperitoneally, 2 h, <em>n</em> = 8), influenza virus (5 × 10³ PFU/mL, intratracheally, days 1 and 5, <em>n</em> = 6), or granulocyte colony-stimulating factor (G-CSF) (2.5 μg, intravenously, 2–6 h, <em>n</em> = 5), followed by flow cytometry analyses. CD101-tdTomato mice were crossed with Lysozyme-GFP mice to validate reporter specificity across myeloid subsets. We confirmed that CD101⁺ and tdTomato⁺ neutrophils display identical characteristics of mature neutrophils, including poly-segmented nuclei, cell size, and key functional properties under homeostasis. Under pathological challenges, the decrease in CD101 expression was not attributed to shedding or degradation of the protein, supporting its robustness under inflammatory conditions. Using CD101-tdTomato × Lysozyme-GFP mice, we established a dual-reporter system that enables precise distinction of mature neutrophils from total myeloid cells. Collectively, our findings support CD101 as a robust and reliable marker of neutrophil maturity, providing a foundation for its future applications in spatial transcriptomics and lineage tracing studies of the heterogeneity and functions of neutrophils.</div></div>","PeriodicalId":100609,"journal":{"name":"hLife","volume":"4 8","pages":"Pages 494-506"},"PeriodicalIF":0.0,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148775818","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":"A collective roadmap for spatiotemporal omics in combating infections","authors":"Zhihua Ou,&nbsp;George Fu Gao,&nbsp;Andrea Cossarizza,&nbsp;Wenhong Zhang,&nbsp;Aldo Tagliabue,&nbsp;Ziqing Deng","doi":"10.1016/j.hlife.2025.12.005","DOIUrl":"10.1016/j.hlife.2025.12.005","url":null,"abstract":"","PeriodicalId":100609,"journal":{"name":"hLife","volume":"4 7","pages":"Pages 393-398"},"PeriodicalIF":0.0,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148532063","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":"Polyfunctional varicella-zoster virus–reactive memory CD4+ T cells reside in human bone marrow","authors":"Zixu Wang,&nbsp;Simon Reinke,&nbsp;Yu Shen,&nbsp;Xiangyi Deng,&nbsp;Tobias Alexander,&nbsp;Anne Claußnitzer,&nbsp;Sebastian Hardt,&nbsp;Luis Becker,&nbsp;Koji Tokoyoda,&nbsp;Carsten Perka,&nbsp;Andreas Radbruch,&nbsp;Jun Dong","doi":"10.1016/j.hlife.2026.04.001","DOIUrl":"10.1016/j.hlife.2026.04.001","url":null,"abstract":"","PeriodicalId":100609,"journal":{"name":"hLife","volume":"4 7","pages":"Pages 457-460"},"PeriodicalIF":0.0,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148532064","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}