hLife最新文献

{"title":"Personalized bacteriophage therapy for chronic biliary tract Pseudomonas aeruginosa infections","authors":"Na Li ,&nbsp;Linlin Li ,&nbsp;Bo He ,&nbsp;Dandan Li ,&nbsp;Wenting Jin ,&nbsp;Yuan Wu ,&nbsp;Beidi Zhu ,&nbsp;Mengjun Cheng ,&nbsp;Nannan Wu ,&nbsp;Demeng Tan ,&nbsp;Jue Pan ,&nbsp;Chunmei Zhou ,&nbsp;Rong Bao ,&nbsp;Hao Wu ,&nbsp;Wen Zhang ,&nbsp;Ming Li ,&nbsp;Zhuojun Zhong ,&nbsp;Jiazhen Liu ,&nbsp;Jianglin Liao ,&nbsp;Tongyu Zhu ,&nbsp;Shuai Le","doi":"10.1016/j.hlife.2025.03.004","DOIUrl":"10.1016/j.hlife.2025.03.004","url":null,"abstract":"<div><div>Biliary tract infections (BTIs) present a significant therapeutic challenge, particularly in the face of increasing antimicrobial resistance. Bacteriophages, viruses that target and destroy bacteria, offer the potential for treating severe bacterial infections, although their use in BTIs has been limited. We describe an 88-year-old female with a complex and recurrent BTI caused by multiple bacteria, including multidrug-resistant <em>Pseudomonas aeruginosa</em>. Despite treatment with various antibiotics and percutaneous transhepatic cholangiodrainage (PTCD), her condition did not improve. As a final measure, we implemented personalized phage therapy in combination with antibiotics. An initial 9-day antibiotic treatment combined with a <em>P. aeruginosa</em> phage cocktail administered <em>via</em> PTCD fluid resulted in significant symptom relief. However, phage-resistant pathogens emerged, exhibiting resistance to all 100 double-stranded DNA (dsDNA) phages in our library due to genetic mutations affecting lipopolysaccharides biosynthesis. A second round of therapy with a double-stranded RNA (dsRNA) phage, phiYY, which targets O-antigen deficient mutants, was subsequently administered. Although complete eradication of <em>P. aeruginosa</em> was not achieved, the patient's clinical symptoms were markedly improved. This case demonstrated the safety and efficacy of phage therapy in the treatment of BTIs and showcased the feasibility of employing dsRNA phages to combat the emergence of O-antigen-deficient bacterial mutants. However, it also underscores the considerable challenges in completely eradicating persistent <em>P. aeruginosa</em> infections, which may be attributed to bacterial heterogeneity, biofilm formation, and phage-resistant genetic mutations.</div></div>","PeriodicalId":100609,"journal":{"name":"hLife","volume":"3 6","pages":"Pages 275-283"},"PeriodicalIF":0.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144204302","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":"Comparison of innate immune responses against arboviruses in mammalian hosts and mosquito vectors","authors":"Liming Zhang ,&nbsp;Yibin Zhu ,&nbsp;Gong Cheng","doi":"10.1016/j.hlife.2025.02.007","DOIUrl":"10.1016/j.hlife.2025.02.007","url":null,"abstract":"<div><div>Mosquito-borne arboviruses significantly threaten global health, affecting millions of people worldwide. The innate immune system is the primary line of defense against arboviruses in both mammalian hosts and mosquito vectors, although the innate immune responses of these organisms involve distinct mechanisms. This review compares the innate immune responses of mammals with those of mosquitoes, focusing on their shared reliance on pattern recognition receptors (PRRs), immune signaling pathways, and cellular innate immunity. While mosquitoes utilize RNA interference (RNAi) and melanization to control arboviral replication without inflammation, mammals depend on complement systems, complex interferon (IFN) responses, and cytokine production to rapidly clear arboviral infections. This review provides a comparative analysis of the innate immune responses of mammalian hosts and mosquito vectors, highlighting key differences in the strategies by which these organisms manage arboviral infections. Understanding these distinctions may inform the development of novel interventions to disrupt arboviral transmission and improve disease control.</div></div>","PeriodicalId":100609,"journal":{"name":"hLife","volume":"3 6","pages":"Pages 258-274"},"PeriodicalIF":0.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144204301","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":"Metagenomic mining reveals novel viral histones in dsDNA viruses","authors":"Yang Liu ,&nbsp;Zhuru Hou ,&nbsp;Wanshan Hao ,&nbsp;Shaoqing Cui ,&nbsp;Haibo Wang ,&nbsp;Yue Liu","doi":"10.1016/j.hlife.2025.02.005","DOIUrl":"10.1016/j.hlife.2025.02.005","url":null,"abstract":"<div><div>The compaction of genomic DNA into nucleosomes with the help of histones has long been considered a fundamental feature exclusive to eukaryotic cells. However, it was recently shown that archaea and bacteria also encode histones. A complex picture has emerged with more recent discoveries of eukaryotic-like histones within one phylum of double-stranded DNA (dsDNA) viruses. Nevertheless, the extent to which other dsDNA viruses encode histones remains largely unexplored. Here, we conducted a metagenomic survey of viral histones that were further clustered based on sequence and predicted structural similarities. We identified over 1500 viral histones and histone-fold proteins, including previously undescribed proteins found in the viral class Caudoviricetes. Structural predictions and <em>in vitro</em> assays demonstrated that histone triplets (where three histone folds are fused) and singlets co-occurring in the same viral genome are capable of forming nucleosome-like particles. Beyond nucleosomal histone functions, our analysis revealed six types of structurally and functionally diverse viral histone-fold proteins, some of which do not have known structural or functional homologs. Altogether, our findings reveal a previously unrecognized diversity of viral histones in dsDNA viruses, expanding the known repertoire, structural diversity, and functional versatility of viral histones beyond nucleocytoplasmic large DNA viruses.</div></div>","PeriodicalId":100609,"journal":{"name":"hLife","volume":"3 6","pages":"Pages 284-296"},"PeriodicalIF":0.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144204303","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":"Global health visionaries, Professors Peter Piot and Heidi Larson, join hLife editorial board","authors":"Qun Yan","doi":"10.1016/j.hlife.2025.04.001","DOIUrl":"10.1016/j.hlife.2025.04.001","url":null,"abstract":"","PeriodicalId":100609,"journal":{"name":"hLife","volume":"3 6","pages":"Pages 301-302"},"PeriodicalIF":0.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144204379","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 NF-κB to cGAS: An interview with Prof. Zhijian James Chen on unraveling innate immunity","authors":"Wenwen Zeng ,&nbsp;Lai Guan Ng ,&nbsp;Zhijian James Chen ,&nbsp;Qun Yan","doi":"10.1016/j.hlife.2025.03.002","DOIUrl":"10.1016/j.hlife.2025.03.002","url":null,"abstract":"","PeriodicalId":100609,"journal":{"name":"hLife","volume":"3 6","pages":"Pages 253-257"},"PeriodicalIF":0.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144204300","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":"Modeling the pathogenic infection of mpox virus clade IIb in type I and II interferon pathway double deficient mice","authors":"Qinghong Fan ,&nbsp;Mengling Jiang ,&nbsp;Tianxing Lv ,&nbsp;Meifang Pan ,&nbsp;Jun Dai ,&nbsp;Peng Qian ,&nbsp;Fengyu Hu ,&nbsp;Haisheng Yu ,&nbsp;Yun Ling ,&nbsp;Xiaoping Tang ,&nbsp;Feng Li","doi":"10.1016/j.hlife.2025.03.003","DOIUrl":"10.1016/j.hlife.2025.03.003","url":null,"abstract":"","PeriodicalId":100609,"journal":{"name":"hLife","volume":"3 6","pages":"Pages 297-300"},"PeriodicalIF":0.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144204304","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 of highly active gene targeting RNase P ribozyme against human cytomegalovirus infection","authors":"Yujun Liu ,&nbsp;Bin Yan ,&nbsp;Isadora Zhang ,&nbsp;Fenyong Liu","doi":"10.1016/j.hlife.2025.02.006","DOIUrl":"10.1016/j.hlife.2025.02.006","url":null,"abstract":"<div><div>Sequence-specific ribonuclease (RNase) P ribozymes can be engineered <em>in vitro</em> and are promising gene-targeting agents to knock down gene expression. In this study, we applied an RNase P ribozyme variant to hydrolyze the mRNA of human cytomegalovirus (HCMV) major capsid protein (MCP), which is necessary for viral capsid formation and growth. Functional variant R668-F was about 100 times more efficient in slicing the MCP mRNA <em>in vitro</em> than M1-F, the ribozyme with a natural RNase P ribozyme sequence. In R668-F-expressing cells, a decrease of about 98%–99% in the expression of MCP was detected, and the virus production was reduced by 70,000 folds. However, the expression of inactive control ribozymes in cells resulted in a less than 10% decrease in MCP expression and no apparent decrease in HCMV growth. In cells observed with the ribozyme-mediated reduction of MCP expression, HCMV capsid formation and virus growth were inhibited and the expressions of other viral genes were unaffected. These findings provide the first direct evidence that ribozyme R668-F specifically inhibits MCP expression and blocks HCMV growth. Our results further suggest that the engineered RNase P ribozymes, including R668-F, may act as a novel general gene-targeting strategy to treat infections of viruses, including HCMV.</div></div>","PeriodicalId":100609,"journal":{"name":"hLife","volume":"3 5","pages":"Pages 243-252"},"PeriodicalIF":0.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143948722","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":"Learning from life, enabling artificial intelligence: Scientific historical insights from the Nobel Prize in Physics","authors":"Zongzhen Wu ,&nbsp;Lu Zhang ,&nbsp;Qiangyu Xiang ,&nbsp;Xiaobo Zhao ,&nbsp;Huan Liu","doi":"10.1016/j.hlife.2025.03.005","DOIUrl":"10.1016/j.hlife.2025.03.005","url":null,"abstract":"","PeriodicalId":100609,"journal":{"name":"hLife","volume":"3 5","pages":"Pages 201-203"},"PeriodicalIF":0.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143948859","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":"Advancing virology research with a human brain organoid platform","authors":"Juntong Liu,&nbsp;Na Zhu,&nbsp;Weibang Huo,&nbsp;Wenjie Tan","doi":"10.1016/j.hlife.2024.09.003","DOIUrl":"10.1016/j.hlife.2024.09.003","url":null,"abstract":"","PeriodicalId":100609,"journal":{"name":"hLife","volume":"3 5","pages":"Pages 237-242"},"PeriodicalIF":0.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143948879","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":"Cancer research revolutionized: Unveiling the power of organoids and their therapeutic potential in oncology","authors":"Yingxin Zhang ,&nbsp;Ming Liu ,&nbsp;Na Xie ,&nbsp;Zhoufeng Wang ,&nbsp;Chuanjiang Yu ,&nbsp;Jing Li ,&nbsp;Xikun Zhou","doi":"10.1016/j.hlife.2024.05.002","DOIUrl":"10.1016/j.hlife.2024.05.002","url":null,"abstract":"<div><div>Organoids are <em>in vitro</em> microstructures similar to the source tissue formed by the self-organizing construction of stem cells from various sources. It is now widely recognized as a powerful <em>in vitro</em> model to facilitate cancer research and personalized precision therapy. Since the successful establishment of the first organoid model in 2009, there has been a global upsurge in organoid research. At present, organoids have been widely used in research on the mechanism of cancer occurrence and development, the study of cell interactions in the tumor microenvironment, the development and screening of new drugs, and the individualized precision treatment of cancer. In addition, the development of organoid chip technology and the establishment of organoid biobanks are expected to further promote the irreplaceable role of organoids in precision medical treatment. In this review, we offer a comprehensive outline of the historical development of organoids and their advantages, focusing on the latest progress and application of organoids in cancer research. We also discuss the problems that need to be solved and the potential applications of organoids. This review summarizes the impact and potential of organoids in cancer research and treatment, and we also provide a comprehensive view of organoid applications in cancer.</div></div>","PeriodicalId":100609,"journal":{"name":"hLife","volume":"3 5","pages":"Pages 216-236"},"PeriodicalIF":0.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141041995","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}