hLife最新文献

{"title":"Rationally designed common-light-chain anti-EGFR/c-MET bispecific antibody ALK101 demonstrates potent, broad-spectrum antitumor activity","authors":"Linrui Jiang, Xiaonan Han, Hongwang He, Mengfan Peng, Meiyu Yang, Jiajia Pan, Dandan Liu, Hui Feng, Jinghua Yan, Li Li","doi":"10.1016/j.hlife.2026.08.003","DOIUrl":"10.1016/j.hlife.2026.08.003","url":null,"abstract":"","PeriodicalId":100609,"journal":{"name":"hLife","volume":"4 10","pages":"Pages 678-682"},"PeriodicalIF":0.0,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149234250","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":"Integrating new approach methodologies into human-relevant preclinical research","authors":"Le Tong, Huafang Zhao, Lucas Baldran-Groves, Kanghua Wang, Xiaoni Ai, Qionglin Liang, Wei Luo, Bo Wang, Yunping Fan, Haiying Liu, Longlong Si","doi":"10.1016/j.hlife.2026.06.003","DOIUrl":"10.1016/j.hlife.2026.06.003","url":null,"abstract":"","PeriodicalId":100609,"journal":{"name":"hLife","volume":"4 10","pages":"Pages 637-641"},"PeriodicalIF":0.0,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149233899","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":"LARGE: A large language model-based tool that unveils high-resolution temporal dynamics of the antibiotic resistome during human aging","authors":"Hang He,&nbsp;Chenrui Duan,&nbsp;Kui Deng,&nbsp;Chang Su,&nbsp;Zelei Miao,&nbsp;Ke Zhang,&nbsp;Yonghe Xia,&nbsp;Jiahao Hong,&nbsp;Yue Xi,&nbsp;Yimin Zhu,&nbsp;Dan Zhou,&nbsp;Huijun Wang,&nbsp;Yu-Ming Chen,&nbsp;Stan Z. Li,&nbsp;Ju-Sheng Zheng","doi":"10.1016/j.hlife.2026.08.002","DOIUrl":"10.1016/j.hlife.2026.08.002","url":null,"abstract":"<div><div>The gut microbiome undergoes profound changes during aging, including shifts in the microbial antibiotic resistome: the collective repertoire of antibiotic resistance genes (ARGs). We developed a language model-based ARG explorer (LARGE, <span><span>https://large.lab.westlake.edu.cn</span><svg><path></path></svg></span>), which uses frozen ESM-2 and FGeneBERT encoders to embed protein sequences and three independent multilayer perceptron classifiers to predict resistance type, mechanism, and gene name. LARGE was trained on 34,008 ARG and 30,309 non-ARG sequences from the NCRD95 and UniProt databases and benchmarked against DeepARG, Resistance Gene Identifier (RGI), PLM-ARG, and ARGNet using F1-scores on multiple independent test sets. We applied LARGE to a longitudinal cohort (Guangzhou Nutrition and Health Study, <em>n</em> = 1078, mean baseline age 64.6 years) and validated key findings in independent cohorts (China Health and Nutrition Survey, <em>n</em> = 356; Zhejiang Metabolic Syndrome Cohort, <em>n</em> = 1361). Linear mixed-effects models were used to assess age-related ARG trajectories, and logistic regression examined associations with 13 chronic diseases. In benchmark testing, LARGE substantially outperformed all four tools, achieving superior F1-scores. In longitudinal cohorts, LARGE revealed declining ARG burdens in dominant resistance drug classes and identified 31 species with significant ARG changes. The ARGs of these 31 species were closely associated with multiple age-related chronic diseases, such as chronic kidney disease and coronary heart disease; a specific chronic kidney disease ARG score was consistently associated with disease risk in both discovery and validation cohorts. These findings highlight the pivotal role of aging in resistome evolution and potentially provide microbiome-targeted interventions to mitigate antibiotic resistance and promote healthy aging.</div></div>","PeriodicalId":100609,"journal":{"name":"hLife","volume":"4 10","pages":"Pages 658-677"},"PeriodicalIF":0.0,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149234248","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":"Efficacy and safety of XKH004, a novel dual interleukin-17A/F inhibitory monoclonal antibody, in active ankylosing spondylitis: A 52-week phase 3 randomized study","authors":"Ling Zhou,&nbsp;Ran Yan,&nbsp;Songying Ye,&nbsp;Juan Zhao,&nbsp;Xiaofei Shi,&nbsp;Guixiu Shi,&nbsp;Shujie Li,&nbsp;Yanfei Chen,&nbsp;Hui Luo,&nbsp;Yongtao Chen,&nbsp;Rui Wu,&nbsp;Jinying Lin,&nbsp;Zhenyu Jiang,&nbsp;Lingyun Sun,&nbsp;Jiankang Hu,&nbsp;Xiaomei Li,&nbsp;Zhenchun Zhang,&nbsp;Yi Zhao,&nbsp;Jian Xu,&nbsp;Xiaoping Hong,&nbsp;Huji Xu","doi":"10.1016/j.hlife.2026.07.005","DOIUrl":"10.1016/j.hlife.2026.07.005","url":null,"abstract":"<div><div>Ankylosing spondylitis (AS) is an immune-mediated spondyloarthropathy with unmet clinical needs. We conducted a superiority, phase 3, multicenter, randomized, double-blind, placebo-controlled trial to evaluate the efficacy and safety of XKH004, a humanized monoclonal antibody targeting interleukin-17A/F in active AS. Of 489 screened patients with inadequate response to conventional therapy, 166 were excluded based on predefined criteria. The remaining 323 eligible patients were randomized 1:1 <em>via</em> a centralized interactive web-response system to receive subcutaneous XKH004 160 mg every 4 weeks or placebo until week 16. All patients completed a 52-week follow-up period, comprising 44 weeks of open-label XKH004 treatment followed by an 8-week safety follow-up. Participants and investigators were blinded to treatment allocation. Efficacy analyses utilized the Cochran–Mantel–Haenszel test. The primary endpoint was the proportion of patients achieving an Assessment of SpondyloArthritis international Society ≥ 40% improvement (ASAS40) response at week 16; secondary endpoints included ASAS20/50, Bath Ankylosing Spondylitis Disease Activity Index, Bath Ankylosing Spondylitis Functional Index, Ankylosing Spondylitis Quality of Life, and Ankylosing Spondylitis Disease Activity Score. At week 16, ASAS40 response was achieved by 45.4% with XKH004 (<em>n</em> = 161) <em>vs</em> 19.4% with placebo (<em>n</em> = 162; absolute difference, 95% confidence interval, 15.47–35.02; <em>P</em> &lt; 0.001), with efficacy in the XKH004 group sustaining and further improving to 66.2% by week 52. Serious adverse events occurred in 1.2% and 2.5% of patients in the XKH004 and placebo groups, respectively. Overall, XKH004 was well tolerated and induced rapid, sustained improvements, supporting its potential as a novel therapeutic option for active AS. The trial was registered in the China Drug Experiment database (CTR20232310) and ClinicalTrials.gov (NCT07498634) and supported by the National Natural Science Foundation of China, National Key Research and Development Project, Shanghai Municipal Key Clinical Specialty, and Shanghai Science and Technology Development Funds.</div></div>","PeriodicalId":100609,"journal":{"name":"hLife","volume":"4 10","pages":"Pages 642-657"},"PeriodicalIF":0.0,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149234249","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":"Why do promising preclinical drugs fail in clinical trials? From a trade-off framework to higher-fidelity models","authors":"Bo-Wen Zhou,&nbsp;Ding-Jun Jin,&nbsp;Ya-Ping Zhang","doi":"10.1016/j.hlife.2026.06.005","DOIUrl":"10.1016/j.hlife.2026.06.005","url":null,"abstract":"","PeriodicalId":100609,"journal":{"name":"hLife","volume":"4 10","pages":"Pages 633-636"},"PeriodicalIF":0.0,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149233898","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":"Pseudomonas aeruginosa: From acute virulence to chronic persistence—mechanisms and therapeutic implications","authors":"Haoyun Zhu,&nbsp;Haolang Zhao,&nbsp;Jing Li,&nbsp;Xikun Zhou","doi":"10.1016/j.hlife.2026.07.001","DOIUrl":"10.1016/j.hlife.2026.07.001","url":null,"abstract":"<div><div><em>Pseudomonas aeruginosa</em> (PA) is a gram-negative opportunistic bacterium that frequently causes nosocomial infections. Its capacity to evolve from an acute infection characterized by rapid tissue damage to a persistent chronic infection that is difficult to eradicate leads to reduced antibiotic efficacy, disease deterioration, and poor prognosis. This review dissects two major driving forces—intrinsic regulatory networks and adaptive evolution under selective pressures underlying this transition—defines the central role of biofilms, and explores therapeutic implications. Under pressures such as the immune system and antibiotics, PA undergoes lifestyle transition, metabolic reprogramming, and immune evasion through the quorum-sensing (QS), Gac-Rsm, and c-di-GMP networks. Based on these mechanisms, therapeutic approaches targeting the acute-to-chronic infection transition have been developed, including anti-virulence therapy, anti-biofilm strategies, anti-persister strategies, immunomodulatory therapy, and phage therapy. Although these novel therapeutic strategies have demonstrated substantial potential in preclinical models of chronic persistent infections, their clinical applications remain limited. Future studies should further elucidate the dynamic crosstalk among the core regulatory systems within the host microenvironment and develop intervention strategies targeting key nodes in the acute-to-chronic transition. Such advances hold considerable promise for eradicating chronic persistent infections and ultimately improving clinical outcomes for patients.</div></div>","PeriodicalId":100609,"journal":{"name":"hLife","volume":"4 10","pages":"Pages 601-632"},"PeriodicalIF":0.0,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149233897","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":"Conserved nucleocapsid epitopes induce cross-reactive CD4+ T-cell responses with selective protection against human coronaviruses in mice","authors":"Xiaomin Lai,&nbsp;Zhao Chen,&nbsp;Suoqun Zhao,&nbsp;Airu Zhu,&nbsp;Jian Zheng,&nbsp;Zhaoyong Zhang,&nbsp;Junxiang Wang,&nbsp;Yanqun Wang,&nbsp;Jing Sun,&nbsp;Fang Li,&nbsp;Yihao Li,&nbsp;Jiamin Liu,&nbsp;Stanley Perlman,&nbsp;Jingxian Zhao,&nbsp;Jincun Zhao,&nbsp;Zhen Zhuang","doi":"10.1016/j.hlife.2026.07.004","DOIUrl":"10.1016/j.hlife.2026.07.004","url":null,"abstract":"","PeriodicalId":100609,"journal":{"name":"hLife","volume":"4 9","pages":"Pages 596-600"},"PeriodicalIF":0.0,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149033336","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":"Engineering organoids toward implantable living therapeutics","authors":"Zhicheng Shi,&nbsp;Qianrong Yang,&nbsp;Xiaoyan You,&nbsp;Hui Wang,&nbsp;Hanjie Wang,&nbsp;Guoping Zhao","doi":"10.1016/j.hlife.2026.06.002","DOIUrl":"10.1016/j.hlife.2026.06.002","url":null,"abstract":"<div><div>Stem cell-derived organoids are emerging as living therapeutics for repairing or replacing damaged tissues and organs, offering new opportunities for regenerative medicine. However, their clinical translation remains limited by immune rejection, insufficient functional integration, and low manufacturing throughput. In this review, we summarize recent advances in engineering organoids toward implantable living therapeutics by examining how hydrogel engineering, microfluidic chips, three-dimensional bioprinting, and synthetic biology overcome key translational barriers and facilitate the <em>in vivo</em> application of organoids. We further discuss the existing regulatory frameworks supporting the clinical translation of organoid-based therapies. Current evidence indicates that these bioengineering strategies enhance graft survival, tissue integration, and therapeutic efficacy through complementary mechanisms, including immunomodulatory signals, biomimetic microenvironments, hierarchical tissue architectures, and programmable cellular functions. Importantly, engineered organoids have been successfully applied to restore hair-bearing skin, repair colonic epithelial continuity, bridge critical-size bone defects, and correct metabolic disorders. Despite these advances, significant challenges remain in quality-control standardization, scalable manufacturing, regulatory harmonization, and long-term safety assessment. Future studies integrating artificial intelligence (AI) and intelligent living devices are warranted to facilitate high-fidelity manufacturing, quality inspection, real-time monitoring, and closed-loop therapeutic regulation in clinical practice. Collectively, engineered organoids represent a promising frontier for new-generation transplantation and regenerative medicine.</div></div>","PeriodicalId":100609,"journal":{"name":"hLife","volume":"4 9","pages":"Pages 529-553"},"PeriodicalIF":0.0,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149033238","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":"Intranasal gold nanoparticle-antigen induces mucosal and systemic immunity against β-coronaviruses","authors":"Muzhuo Wang,&nbsp;Weijie Wang,&nbsp;Wei Xu,&nbsp;Zhikai Chen,&nbsp;Junlan Zhang,&nbsp;Zeya Li,&nbsp;Jiadong Li,&nbsp;Shibo Jiang,&nbsp;Lu Lu,&nbsp;Zezhong Liu","doi":"10.1016/j.hlife.2026.07.002","DOIUrl":"10.1016/j.hlife.2026.07.002","url":null,"abstract":"<div><div>The continued emergence of diverse beta-coronaviruses (β-CoVs) from animal reservoirs underscores the urgent need for broad-spectrum mucosal vaccines, yet their development is hindered by physiological barriers, rapid antigen clearance, and suboptimal multivalent display strategies. To address this, we intranasally immunized BALB/c mice (<em>n</em> = 3 or 4 per group) with 5 or 15 nm gold nanoparticles (AuNPs) displaying the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) receptor-binding domain (RBD, 5 μg per mouse) and adjuvanted with the STING agonist cGAMP (20 μg per mouse). Guided by the serotyping of STING agonist-elicited neutralizing responses, we generated AuNP-Mix co-displaying six representative β-CoV RBDs for comparative immunological evaluation against single-RBD AuNP formulations. Antigen delivery, pulmonary retention, mucosal and systemic immune responses were evaluated <em>via in vivo</em> imaging, enzyme-linked immunosorbent assays, pseudovirus neutralization assays, flow cytometry, immunofluorescence, and challenge studies. We demonstrated that 5 nm AuNP-RBD adjuvanted with cGAMP exhibited superior mucosal penetration and lung retention, induced robust local and systemic immunity, and elicited cross-neutralizing antibodies against SARS-CoV-2 variants, SARS-CoV, and SARS-related coronaviruses. Intranasal immunization with AuNP-Mix elicited broader mucosal/systemic immune responses than those achieved with simple RBD mixtures, as demonstrated by its potent neutralizing activity against SARS-CoV-2 variants, SARS-CoV, Middle East respiratory syndrome coronavirus (MERS-CoV), and divergent MERS-like viruses. These findings establish AuNP-based mosaic display as a versatile platform for next-generation mucosal vaccines.</div></div>","PeriodicalId":100609,"journal":{"name":"hLife","volume":"4 9","pages":"Pages 558-580"},"PeriodicalIF":0.0,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149033240","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":"Recollections of an open U.S.–China anti-hantaviral clinical trial in the 1980s","authors":"Zhi-Ming Zheng","doi":"10.1016/j.hlife.2026.05.006","DOIUrl":"10.1016/j.hlife.2026.05.006","url":null,"abstract":"","PeriodicalId":100609,"journal":{"name":"hLife","volume":"4 9","pages":"Pages 525-528"},"PeriodicalIF":0.0,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149033338","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}