hLife最新文献

{"title":"ZCF4-dependent suppression of MMP-9 drives virulence in fluconazole-resistant Candida auris","authors":"Yue-Mei Hong,&nbsp;Lu Wang,&nbsp;Zuo-Jing Yin,&nbsp;Yun Zou,&nbsp;Zhi-Wen Wang,&nbsp;Xiu-Li Wang,&nbsp;Di Wu,&nbsp;Xiang-Kang Zeng,&nbsp;Jin-An Zhou,&nbsp;Wan-Xing Xu,&nbsp;Yan-Yan Sun,&nbsp;Tian-Yi Zhang,&nbsp;Jian Guo,&nbsp;Jian Bing,&nbsp;Guang-Hua Huang,&nbsp;Wen-Juan Wu,&nbsp;Lei Pan,&nbsp;Chang-Bin Chen,&nbsp;Hui Wang,&nbsp;Ning-Ning Liu","doi":"10.1016/j.hlife.2026.04.004","DOIUrl":"10.1016/j.hlife.2026.04.004","url":null,"abstract":"<div><div>While multidrug-resistant <em>Candida auris</em> poses a global threat to public health, the impact and mechanism of drug resistance on fungal virulence remain unclear. By employing the same-parent-derived fluconazole-resistant <em>C. auris</em> strains, this study utilized <em>in vitro</em> screening and host–pathogen co-culture models. Labile zinc was visualized using the fluorescent probe Zinpyr and Zinquin. Mechanisms identified <em>via</em> dual RNA sequencing were further validated using genetic mutants and pharmacological inhibitors. For in <em>vivo</em> validation, a fly survival model was employed, followed by an infection model in C57BL/6J mice (total <em>n</em> = 84). Mice were challenged with <em>C. auris via</em> lateral tail vein injection and oral gavage. Efficacy was evaluated through daily survival monitoring, fungal burden <em>via</em> colony-forming unit (CFU) counting, histopathological examination of tissue sections, and cytokine level measurement. We revealed that fluconazole-resistant <em>C. auris</em> exhibits enhanced fitness and resistance to macrophage killing under zinc deficiency by mobilizing intracellular zinc. Mechanistically, the inhibition of gene encoding Zn(II)2Cys6 transcription factor 4 (<em>ZCF4</em>) contributes to <em>C. auris</em> resistance to macrophage killing by suppressing the phosphoinositide 3-kinase (PI3K)-AKT-mammalian target of rapamycin (mTOR) pathway and downstream matrix metalloproteinase-9 (MMP-9) activity under low-zinc conditions. Furthermore, dietary zinc deficiency promotes the virulence of fluconazole-resistant <em>C. auris</em>. These findings highlight a fitness advantage of fluconazole-resistant <em>C. auris</em> under zinc-deficient conditions through host–fungal interactions, offering a potential nutrient intervention strategy against fungal infection.</div></div>","PeriodicalId":100609,"journal":{"name":"hLife","volume":"4 7","pages":"Pages 439-456"},"PeriodicalIF":0.0,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148532066","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":"Cytomics-driven insights for investigating host–pathogen interactions","authors":"Andrea Cossarizza,&nbsp;Cristina Mussini,&nbsp;Diana Boraschi,&nbsp;Aldo Tagliabue","doi":"10.1016/j.hlife.2026.04.003","DOIUrl":"10.1016/j.hlife.2026.04.003","url":null,"abstract":"<div><div>Cytomics, the high-dimensional profiling of immune cells, provides a systems-level view of host responses to infection. Unlike traditional diagnostics focused on pathogen detection or early immune activation, cytomics captures rare and functionally specialized immune subsets linked to disease severity and clinical outcome. In this review, we explore how advances in spectral cytometry, mass cytometry, and multimodal single-cell platforms enable unprecedented resolution of immune complexity during infection by summarizing cytomics evolution, high-dimensional single-cell and multimodal technologies, as well as their roles in defining immune heterogeneity and host–pathogen interactions across infectious diseases. Several single-cell technologies rely on antibodies conjugated to fluorochromes or non-radioactive isotopes, generating high-dimensional datasets processed with advanced computational tools, enabling unprecedented precision in defining cell populations and supporting diagnostic advances. During infections, cytomic approaches map immune architecture, identify dysfunctional or protective cell states, and monitor therapeutic responses. In viral infections, it detects hyperinflammatory monocytes and exhausted T-cell subsets; in bacterial diseases, it reveals immunosuppressive monocytes and disrupted neutrophil networks; in parasitic infections, it clarifies mechanisms of persistence and clearance. Integrated with complementary omics technologies, cytomics informs personalized immunomodulatory strategies and rational vaccine design. This review provides a unified framework for applying cytomics to precision diagnostics, therapeutic decision-making, vaccine development, and population-level preparedness, positioning high-dimensional immune profiling as a cornerstone of modern infectious-disease management.</div></div>","PeriodicalId":100609,"journal":{"name":"hLife","volume":"4 7","pages":"Pages 399-422"},"PeriodicalIF":0.0,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148532065","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":"Spatiotemporal omics: Revolutionizing infectious disease research","authors":"Ziheng Chen,&nbsp;Panyu Zhang,&nbsp;Chao Fang,&nbsp;Xiaofeng Shi,&nbsp;Zhihua Ou","doi":"10.1016/j.hlife.2025.12.001","DOIUrl":"10.1016/j.hlife.2025.12.001","url":null,"abstract":"","PeriodicalId":100609,"journal":{"name":"hLife","volume":"4 7","pages":"Pages 461-462"},"PeriodicalIF":0.0,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148532067","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":"Targeted protein degradation via chimeric antigen receptor (CAR)-mediated antigen endocytosis in T cells","authors":"Youguang Wang,&nbsp;Zihao He,&nbsp;Na Yin,&nbsp;Min Peng","doi":"10.1016/j.hlife.2026.05.003","DOIUrl":"10.1016/j.hlife.2026.05.003","url":null,"abstract":"<div><div>Targeted protein degradation (TPD) holds significant therapeutic potential over conventional biologics. However, existing platforms are constrained by their reliance on host protein degradation machinery and limited durability, rendering them inadequate for chronic diseases requiring sustained treatment. Here, we constructed a chimeric antigen receptor (CAR) incorporating the TNFR1 ectodomain as the antigen-binding domain (TNFR1T cells) and used CRISPR-mediated knockout of BCOR and ZC3H12A to generate persistent TNFR1T_IF cells. TNF binding, endocytosis, and degradation were assessed <em>in vitro</em> by flow cytometry and immunofluorescence. Immunocompetent syngeneic, <em>Tnf</em>^−/−, and hTNF-tg rheumatoid arthritis (RA) mice (<em>n</em> = 4–9) were used <em>in vivo</em> to evaluate engraftment, persistence, and disease severity (clinical scoring and grip strength), with adalimumab (Humira, 1 or 10 mg/kg) as a comparator. Safety was assessed by intravenous <em>Listeria monocytogenes</em> challenge (1 × 10⁴ colony-forming units [CFU], <em>n</em> = 6) and Thy1.1-based depletion (0.25 mg, <em>n</em> = 3). We found that TNFR1T cells specifically bound, endocytosed, and degraded soluble TNF <em>in vitro</em>. Without lymphodepletion preconditioning, TNFR1T_IF cells expanded and persisted for one year in immunocompetent mice. A single infusion into hTNF-tg mice reduced serum hTNF to near wild-type levels, preventing and treating all stages of RA with superior efficacy and durability than the repeated high-dose adalimumab. Antibacterial defense remained uncompromised, and anti-Thy1.1 antibody efficiently eliminated TNFR1T_IF cells <em>in vivo</em>. This approach extends CAR-T cell targeting from cellular antigens to soluble extracellular proteins, establishing a host-machinery-independent, durable cellular-TPD platform for chronic inflammatory diseases.</div></div>","PeriodicalId":100609,"journal":{"name":"hLife","volume":"4 7","pages":"Pages 423-438"},"PeriodicalIF":0.0,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148532062","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":"Etiological and epidemiological investigation of two independent parrot-to-human transmission events of Chlamydia psittaci","authors":"Chunge Zhang ,&nbsp;Han Du ,&nbsp;Zhenzhen Li ,&nbsp;Rahat Ullah Khan ,&nbsp;Mingxiao Ma ,&nbsp;Jingyu Liu ,&nbsp;Rui Song ,&nbsp;Yuhai Bi","doi":"10.1016/j.hlife.2026.02.001","DOIUrl":"10.1016/j.hlife.2026.02.001","url":null,"abstract":"","PeriodicalId":100609,"journal":{"name":"hLife","volume":"4 6","pages":"Pages 389-392"},"PeriodicalIF":0.0,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148141527","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"From outbreak to breakthrough: Scientific and technological advances in control and cure of HIV/AIDS","authors":"Qiangyu Xiang ,&nbsp;Zongzhen Wu ,&nbsp;Lu Zhang ,&nbsp;Siqing Liu ,&nbsp;Huan Liu","doi":"10.1016/j.hlife.2025.10.007","DOIUrl":"10.1016/j.hlife.2025.10.007","url":null,"abstract":"","PeriodicalId":100609,"journal":{"name":"hLife","volume":"4 6","pages":"Pages 327-330"},"PeriodicalIF":0.0,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148141533","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Engineering nasally delivered IgM antibodies for respiratory viral infections","authors":"Ashwin Kumar Ramesh,&nbsp;Zhiqiang An","doi":"10.1016/j.hlife.2026.03.004","DOIUrl":"10.1016/j.hlife.2026.03.004","url":null,"abstract":"<div><div>Respiratory viral infections remain a significant global health burden, requiring interventions that establish robust defense directly at the portal of entry. Intranasal delivery of engineered IgM antibodies represents a highly potent platform for achieving mucosal protection. In this review, we evaluate the structural and functional rationale for prioritizing engineered IgM antibodies for mucosal immunity, provide preclinical evidence of their efficacy against respiratory viruses, and critically analyze the biomanufacturing and formulation strategies necessary for clinical translation. While bivalent antibodies are highly susceptible to viral mutational escape, the avidity-driven affinity enhancement provided by IgM scaffolds enables superior cross-linking of virions. This effectively immobilizes antigenically drifted variants and facilitates rapid mucociliary clearance, demonstrating superior efficacy against respiratory pathogens compared to their parental IgG isotypes. Concurrently, emerging biomanufacturing, purification, and formulation strategies are successfully overcoming historical stability and production hurdles to enable clinical translation. By addressing these translational challenges, this review provides a comprehensive roadmap for developing engineered IgM into a robust, variant-agnostic mucosal defense strategy against emerging and reemerging respiratory threats.</div></div>","PeriodicalId":100609,"journal":{"name":"hLife","volume":"4 6","pages":"Pages 331-351"},"PeriodicalIF":0.0,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148141534","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Placental endothelial ferroptosis induced by neutrophil NETosis leads to intrauterine growth restriction in dengue virus infection","authors":"Ziyang Sheng ,&nbsp;Jiaying Cao ,&nbsp;Hao Zhang ,&nbsp;Yuetong Li ,&nbsp;Yingying Zhang ,&nbsp;Han Wang ,&nbsp;Feiyang Xue ,&nbsp;Shiqi He ,&nbsp;Na Gao ,&nbsp;Dongying Fan ,&nbsp;Peigang Wang ,&nbsp;Jing An","doi":"10.1016/j.hlife.2026.03.003","DOIUrl":"10.1016/j.hlife.2026.03.003","url":null,"abstract":"<div><div>Studies on dengue virus (DENV) infection during pregnancy show that symptomatic dengue is associated with adverse fetal outcomes, but the mechanisms remain unclear. Our previous research indicated that neutrophils contribute to intrauterine growth restriction (IUGR) by damaging placental vasculature, yet the molecular mechanisms underlying this microvascular injury remain poorly defined. To address this, this study examined placental microvascular ferroptosis by bulk and single-cell transcriptomic reanalyses, immunofluorescence staining, and Western blotting in DENV-2-infected E18.5 placentas from pregnant <em>Ifnar1</em>^−/− C57BL/6J mice (<em>n</em> = 5 per group). Causality was investigated by assessing fetal weight and microvascular damage assessment following administration of ferroptosis inhibitor, neutrophil extracellular trap formation (NETosis) inhibitor, or glutathione supplementation. We observed that ferroptosis in placental vascular endothelial cells was accompanied by vascular disruption and NETosis in our IUGR mouse model. Pharmacological inhibition of ferroptosis alleviated placental injury and restored fetal weight, directly linking ferroptosis to DENV-2-induced IUGR. Moreover, increased 4-hydroxynonenal (4-HNE) levels and decreased glutathione peroxidase 4 (GPX4) levels were detected in the placenta, indicating oxidative stress–driven lipid peroxidation. Glutathione supplementation attenuated ferroptosis and IUGR. Finally, NETosis inhibition reduced placental lipid peroxidation and vascular injury, suggesting that excessive NETosis initially triggers oxidative stress. Taken together, our data suggest that ferroptosis in vascular endothelial cells induced by neutrophil NETosis is the driving cause of IUGR in DENV infections. This study reveals the mechanism underlying DENV-associated adverse pregnancy outcomes and provides potential therapeutic insights.</div></div>","PeriodicalId":100609,"journal":{"name":"hLife","volume":"4 6","pages":"Pages 352-368"},"PeriodicalIF":0.0,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148141543","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"hMPV M2-2 protein modulates host mRNA alternative splicing to favor virus replication","authors":"Jiayin Guo ,&nbsp;Yiman Huang ,&nbsp;Pengtao Jiao ,&nbsp;Dongqi Xie ,&nbsp;Gang Pang ,&nbsp;Jiaxu Ying ,&nbsp;Qianru Yang ,&nbsp;Ying Wu ,&nbsp;Siqi Wang ,&nbsp;Xiaojuan Jia ,&nbsp;Miaowei Mao ,&nbsp;Lishu Zheng ,&nbsp;Ke Zhang","doi":"10.1016/j.hlife.2026.03.005","DOIUrl":"10.1016/j.hlife.2026.03.005","url":null,"abstract":"<div><div>Human metapneumovirus (hMPV) is a widespread and prevalent respiratory pathogen, yet the mechanisms by which hMPV modulates host gene expression to facilitate replication remain incompletely characterized. Here, we systematically profiled hMPV–host protein–protein interactions by affinity purification-mass spectrometry and assessed their impact on host messenger RNA (mRNA) splicing using RNA sequencing, complemented by genetic perturbation, protein interaction assays, and fluorescence microscopy–based subcellular localization and colocalization analyses. Among the viral proteins analyzed, the regulatory protein M2-2 was found to directly interact with multiple splicing factors. Transcriptomic analysis revealed that M2-2 triggers extensive changes in alternative splicing across host genes, notably affecting genes encoding serine-threonine kinase receptor-associated protein (<em>STRAP</em>) and tetratricopeptide repeat, ankyrin repeat and coiled-coil containing 2 (<em>TANC2</em>), both of which exhibit distinct splicing patterns during hMPV infection. Knockdown of M2-2 using short hairpin RNA (shRNA) during hMPV infection reversed M2-2–driven changes in the splicing patterns of <em>STRAP</em> and <em>TANC2</em>, confirming its regulatory role. Functional knockout of <em>STRAP</em> or <em>TANC2</em> significantly impaired viral replication, indicating that the M2-2–favored isoforms are required for efficient viral propagation. Collectively, our findings demonstrate a novel mechanism by which hMPV M2-2 hijacks the host splicing machinery to reprogram key factors that facilitate viral replication. This extends the functional repertoire of M2-2 and highlights the virus-spliceosome interface as a potential therapeutic target for anti-hMPV intervention.</div></div>","PeriodicalId":100609,"journal":{"name":"hLife","volume":"4 6","pages":"Pages 369-388"},"PeriodicalIF":0.0,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148141532","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Porphyromonas gingivalis links Alzheimer’s disease and periodontal disease: Neuroinflammatory mechanisms and therapeutic implications","authors":"Siyu Jin ,&nbsp;Xing Wu ,&nbsp;Yulong Zhang ,&nbsp;Fei Xu ,&nbsp;Wenyu Zhen ,&nbsp;Yuqiang Sun ,&nbsp;Yufei Pan ,&nbsp;Yutong Lu ,&nbsp;Ying Yang ,&nbsp;Wansu Sun ,&nbsp;Haitao Wang ,&nbsp;Hengguo Zhang","doi":"10.1016/j.hlife.2026.03.001","DOIUrl":"10.1016/j.hlife.2026.03.001","url":null,"abstract":"<div><div>The global increase in the aging population has significantly increased the prevalence of Alzheimer’s disease (AD), placing substantial burdens on healthcare systems. Emerging evidence highlights a potential link between AD and periodontal disease (PD), implicating <em>Porphyromonas gingivalis</em> (Pg) as a key microbial driver. In this review, we explore the bidirectional relationship between AD and PD through epidemiological evidence, Pg dissemination along the oral–brain axis, virulence factor-driven neuroinflammation and blood–brain barrier dysfunction, as well as aging-mediated susceptibility and therapeutic implications. Available data suggest that Pg and its virulence factors reach the central nervous system through hematogenous dissemination and neural pathways. Once in the brain, these agents trigger microglial and astrocytic activation, fostering chronic neuroinflammation and accelerating amyloid-β deposition and tau hyperphosphorylation, two hallmark pathologies of AD. Aging may further amplify host susceptibility and inflammatory responses. Although gingipain inhibitors have demonstrated neuroprotective potential in preclinical models, their clinical applications remain limited. Importantly, most existing evidence is based on preclinical and epidemiological studies and remains to be validated in well-designed human studies. Future studies integrating multi-omics approaches and precision medicine strategies are warranted to identify individuals at high risk and develop targeted interventions aimed at mitigating Pg-associated neurodegenerative processes and reducing the AD burden.</div></div>","PeriodicalId":100609,"journal":{"name":"hLife","volume":"4 5","pages":"Pages 267-288"},"PeriodicalIF":0.0,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147872115","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}