hLife最新文献

{"title":"Nasal mucosal secretory immunoglobulin A but not serum antibodies is resistant to Omicron evasion","authors":"","doi":"10.1016/j.hlife.2024.05.004","DOIUrl":"10.1016/j.hlife.2024.05.004","url":null,"abstract":"","PeriodicalId":100609,"journal":{"name":"hLife","volume":"2 9","pages":"Pages 488-491"},"PeriodicalIF":0.0,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2949928324000439/pdfft?md5=824179bdb442aefbee259064f827f7ce&pid=1-s2.0-S2949928324000439-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141142367","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":"Recent advances in surgical management strategies for hepatocellular carcinoma","authors":"Zhen-Bin Ding ,&nbsp;Ying-Hong Shi ,&nbsp;Jia-Feng Chen ,&nbsp;Jia Fan ,&nbsp;Jian Zhou","doi":"10.1016/j.hlife.2024.06.007","DOIUrl":"10.1016/j.hlife.2024.06.007","url":null,"abstract":"<div><div>Hepatocellular carcinoma (HCC) is a significant global health challenge, requiring innovative methods to improve patient survival. Due to different disease backgrounds, different HCC management guidelines have been developed, especially in the field of surgical treatment, with the aim of reducing the risk of incidence and enhancing the therapeutic effect. Focusing on the progress and challenges in the development of surgical management strategies for HCC in recent years, this article systematically elaborates on the research and clinical application of precision surgical treatment, including improvement of the surgical evaluation system, breakthroughs in surgical techniques, and updates in perioperative treatment concepts. In addition, clinical research on surgical treatment for HCC has received unprecedented attention. The conclusions of innovative clinical trials in surgery will provide important guidance for the development of practice guidelines and the selection of appropriate treatment strategies for HCC patients.</div></div>","PeriodicalId":100609,"journal":{"name":"hLife","volume":"2 9","pages":"Pages 439-453"},"PeriodicalIF":0.0,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2949928324000567/pdfft?md5=a638143a9a99027f8cf5c158251033e9&pid=1-s2.0-S2949928324000567-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142311514","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":"Discovering broader antiviral strategies: Role of interferon-induced transmembrane proteins in virus infection","authors":"Zi-Ying Jiang ,&nbsp;Chu Xie ,&nbsp;Pei-Huang Wu ,&nbsp;Zhi-Xuan Li ,&nbsp;Mu-Sheng Zeng ,&nbsp;Cong Sun","doi":"10.1016/j.hlife.2024.07.002","DOIUrl":"10.1016/j.hlife.2024.07.002","url":null,"abstract":"","PeriodicalId":100609,"journal":{"name":"hLife","volume":"2 8","pages":"Pages 377-379"},"PeriodicalIF":0.0,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2949928324000609/pdfft?md5=7cc92e6f494cccd5ec3d3af92a0239bc&pid=1-s2.0-S2949928324000609-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141713148","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":"BCMA-CD19 bispecific CAR-T therapy in refractory chronic inflammatory demyelinating polyneuropathy","authors":"Wei Zhang ,&nbsp;Dan Liu ,&nbsp;Tao Zhang ,&nbsp;Jiang Cao ,&nbsp;Gang Wang ,&nbsp;Huizhong Li ,&nbsp;Su Zhou ,&nbsp;Ruixue Zhang ,&nbsp;Yuqiao Wang ,&nbsp;Jinyu Li ,&nbsp;Zixuan Zhang ,&nbsp;Hao Chen ,&nbsp;Yong Zhang ,&nbsp;Shenyang Zhang ,&nbsp;Jie Zu ,&nbsp;Xiaopeng Wang ,&nbsp;Chuanying Xu ,&nbsp;Manli Zhou ,&nbsp;Ming Shi ,&nbsp;Guiyun Cui ,&nbsp;Junnian Zheng","doi":"10.1016/j.hlife.2024.05.005","DOIUrl":"10.1016/j.hlife.2024.05.005","url":null,"abstract":"","PeriodicalId":100609,"journal":{"name":"hLife","volume":"2 8","pages":"Pages 434-438"},"PeriodicalIF":0.0,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2949928324000440/pdfft?md5=d9543aa1a74f9f57c9a9b70ace2f809c&pid=1-s2.0-S2949928324000440-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142040021","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 is the Omicron main protease of SARS-CoV-2 less stable than its wild-type counterpart? A crystallographic, biophysical, and theoretical study","authors":"Mohamed Ibrahim ,&nbsp;Xinyuanyuan Sun ,&nbsp;Vinicius Martins de Oliveira ,&nbsp;Ruibin Liu ,&nbsp;Joseph Clayton ,&nbsp;Haifa El Kilani ,&nbsp;Jana Shen ,&nbsp;Rolf Hilgenfeld","doi":"10.1016/j.hlife.2024.06.003","DOIUrl":"10.1016/j.hlife.2024.06.003","url":null,"abstract":"<div><p>During the continuing evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)<strong>,</strong> the Omicron variant of concern emerged in the second half of 2021 and has been dominant since November of that year. Along with its sublineages, it has maintained a prominent role ever since. The Nsp5 main protease (M^pro) of the Omicron virus is characterized by a single dominant mutation, P132H. Here we determined the X-ray crystal structures of the P132H mutant (or O-M^pro) as a free enzyme and in complex with the M^pro inhibitor, the alpha-ketoamide 13b-K, and we conducted enzymological, biophysical, as well as theoretical studies to characterize the O-M^pro. We found that O-M^pro has a similar overall structure and binding with 13b-K; however, it displays lower enzymatic activity and lower thermal stability compared to the WT-M^pro (with “WT” referring to the prototype strain). Intriguingly, the imidazole ring of His132 and the carboxylate plane of Glu240 are in a stacked configuration in the X-ray structures determined here. Empirical folding free energy calculations suggest that the O-M^pro dimer is destabilized relative to the WT-M^pro due to less favorable van der Waals interactions and backbone conformations in the individual protomers. All-atom continuous constant-pH molecular dynamics (MD) simulations reveal that His132 and Glu240 display coupled titration. At pH 7, His132 is predominantly neutral and in a stacked configuration with respect to Glu240 which is charged. In order to examine whether the Omicron mutation eases the emergence of further M^pro mutations, we also analyzed the P132H+T169S double mutant, which is characteristic of the BA.1.1.2 lineage. However, we found little evidence of a correlation between the two mutation sites.</p></div>","PeriodicalId":100609,"journal":{"name":"hLife","volume":"2 8","pages":"Pages 419-433"},"PeriodicalIF":0.0,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S294992832400049X/pdfft?md5=46f4a86fab2e946cbb89c2ad34803747&pid=1-s2.0-S294992832400049X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142040020","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":"Boosting CAR-T cell therapy with CRISPR technology","authors":"","doi":"10.1016/j.hlife.2024.06.002","DOIUrl":"10.1016/j.hlife.2024.06.002","url":null,"abstract":"<div><p>Chimeric antigen receptor (CAR)-T cell therapy has made remarkable breakthroughs in treating cancers, especially hematologic malignancies, yet its broader application in cancer treatment is hindered by multiple challenges. Meanwhile, the development of clustered regularly interspaced short palindromic repeats (CRISPR) and its derived technologies has provided unprecedentedly efficient tools for genomic and cellular reprogramming, offering potential advantages for developing CAR-T cell therapy. There is hence a rapidly increasing interest in applying CRISPR to engineer CAR-T cells. Here, we present a review of recent research utilizing CRISPR to boost CAR-T cell therapy by enhancing its safety or effectiveness. We first provide an overview of CAR-T cell therapy and CRISPR technology, followed by discussions on how CRISPR and its related technologies can be adopted to tackle various issues associated with CAR-T cell therapy, either <em>via</em> knockout/knockin of specific genes or CRISPR-based screening. We also summarize clinical trials involving CRISPR-edited CAR-T cells. Lastly, we address the potential risks of applying CRISPR in CAR-T cell engineering.</p></div>","PeriodicalId":100609,"journal":{"name":"hLife","volume":"2 8","pages":"Pages 380-396"},"PeriodicalIF":0.0,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2949928324000488/pdfft?md5=12ca53e31dd76cdfb4baa2c88fbf98f0&pid=1-s2.0-S2949928324000488-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141393989","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":"Dysregulated STAT1 gain-of-function: Pathogen-free autoimmunity and fungal infection","authors":"","doi":"10.1016/j.hlife.2024.03.002","DOIUrl":"10.1016/j.hlife.2024.03.002","url":null,"abstract":"<div><p>Inborn errors of the signal transducer and activator of transcription 1 (STAT1) result in four types of immunodeficiency disease with varying degrees of impaired STAT1 function: autosomal recessive (AR) complete STAT1 deficiency, AR partial STAT1 deficiency, autosomal dominant (AD) STAT1 deficiency, and AD STAT1 gain-of-function (STAT1-GOF). Of which, the STAT1-GOF mutations promote a clinical syndrome of immune dysregulation characterized by recurrent infections, especially chronic mucocutaneous candidiasis (CMC) and <em>Talaromyces marneffei</em> infection and predisposition to humoral autoimmunity. STAT1-GOF mutations lead to enhanced phosphorylation of STAT1 (pSTAT1), delayed dephosphorylation, and impaired nuclear dephosphorylation. As a result, the development of T helper (Th) 17 cells is impaired, limiting the production of interleukin (IL)-17, which plays an important role in antifungal immunity. Additionally, mutations can also cause a decrease in the proportion of CD4⁺, CD8⁺, and natural killer (NK) cells. Recent research demonstrated that in the absence of overt infection, STAT-GOF mice can disrupt naïve CD4⁺ T cell homeostasis and promote expansion and differentiation of abnormal T-follicular helper/T-helper 1-like (Tfh/Th1-like) T cells and germinal center-like (GC-like) B cells, and thus reminds us of the complex molecular mechanism of autoimmune disease with/without fungal infection, which may further involve specific clinical treatment including antifungal and anti-autoimmunity therapies. In addition, sex and location of mutation were also associated with the clinical phenotype. Individuals with DNA binding domain (DBD) mutations had a higher prevalence of autoimmunity and aberrant B cell activation. Disrupted CD4⁺ T cell homeostasis occurred sooner and more robustly in females, highlighting the importance of specific treatment to normalize STAT1 expression and restore immune tolerance in patients with STAT1-GOF syndrome. Herein, we provide a comprehensive review of STAT1-GOF aiming to further clarify the regulatory mechanism of cellular and humoral immune deficiency in patients with fungal infection with or without autoimmunity.</p></div>","PeriodicalId":100609,"journal":{"name":"hLife","volume":"2 8","pages":"Pages 397-418"},"PeriodicalIF":0.0,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2949928324000178/pdfft?md5=9c1ec4c7cd2786b686915cab4a6055cf&pid=1-s2.0-S2949928324000178-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140091823","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":"Ism1 deficiency in mice exacerbates bleomycin-induced pulmonary fibrosis with enhanced cellular senescence and delayed fibrosis resolution","authors":"Mahalakshmi Shanmugasundaram,&nbsp;Simin Xu,&nbsp;Yujie Yang,&nbsp;Jong Huat Tee,&nbsp;Terence Yin Weng Lam,&nbsp;Ruowen Ge","doi":"10.1016/j.hlife.2024.05.006","DOIUrl":"10.1016/j.hlife.2024.05.006","url":null,"abstract":"<div><p>Idiopathic pulmonary fibrosis (IPF) is a progressive fibrosing interstitial lung disease with high morbidity and mortality but unclear etiology and incomplete pathophysiological understandings, making the discovery of effective therapeutics arduous. Currently, two drugs, nintedanib and pirfenidone, are available for IPF treatment which can slow down the fibrotic scarring in the lung but are unable to provide disease resolution. Hence, further revelation of the molecular mechanisms of IPF is critical for the development of novel therapeutics. Isthmin-1 (ISM1) is a secreted anti-inflammatory protein highly expressed in the mouse and human lung. <em>Ism1</em>^{<em>−/−</em>} mice presented spontaneous and progressive lung emphysema, as well as heightened acute lung injury (ALI) upon lipopolysaccharide (LPS) treatment with an accompanied increase of post-LPS-ALI pulmonary fibrosis. ISM1 is important for lung homeostasis with airway-delivered recombinant ISM1 (rISM1) suppressing cigarette smoke-induced emphysema, LPS-ALI, and house-dust mites (HDM)-induced asthma-like symptoms in mice. However, the role of ISM1 in pulmonary fibrosis is yet to be clearly understood. In this work, we show that <em>Ism1</em>^{<em>−/−</em>} mice presented heightened bleomycin-induced pulmonary fibrosis (BIPF), with enhanced immune cell infiltration, myofibroblast accumulation, and collagen deposition. ISM1 deficiency also led to increased cellular senescence in mouse lungs, isolated primary alveolar type II epithelial cells, and primary lung fibroblasts upon bleomycin treatment. <em>Ism1</em>^{<em>−/−</em>} mice also showed delayed resolution of pulmonary fibrosis with reduced lipofibroblasts and downregulation of lipid synthesis-related genes. These results are in congruence with the RNA-seq data which demonstrated gene expression alterations in <em>Ism1</em>^{<em>−/−</em>} lung that are linked to predisposition to pulmonary fibrosis and dysregulation of lipid metabolism pathways. Gene expression analyses showed that <em>Ism1</em> is similarly dysregulated in the lungs of BIPF and human IPF patients. These findings reveal an anti-fibrotic role of ISM1 in mouse lungs and provide the foundation to further investigate possible therapeutic applications of ISM1 for pulmonary fibrosis in the future.</p></div>","PeriodicalId":100609,"journal":{"name":"hLife","volume":"2 7","pages":"Pages 342-359"},"PeriodicalIF":0.0,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2949928324000464/pdfft?md5=48d5f0032627380503802dc826f87517&pid=1-s2.0-S2949928324000464-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141637294","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":"Single-cell omics in tracing cellular heterogeneity of drug-induced liver injury: Technological landscape and prospective application","authors":"","doi":"10.1016/j.hlife.2024.01.004","DOIUrl":"10.1016/j.hlife.2024.01.004","url":null,"abstract":"<div><p>Drug-induced liver injury (DILI) remains a serious problem in clinics for both diagnoses and treatment decisions. It is a result of accumulated drugs in human bodies metabolized into toxic constituents generating reactive metabolites, and then arise initial consequences of oxidative stress, organelle stress responses, and lethal consequences (liver necrosis or apoptosis). However, the idiosyncratic nature of DILI complexes its mechanistic studies and still little is known of its potential etiopathogenesis for certain. Single-cell omics technology and approaches serve as powerful tools for investigating cellular heterogeneity and relationships from measurements of up to millions of individual cells at an unprecedented resolution, which are achieved by advances in genome, epigenome, transcriptome, proteome, and metabolism technologies. As liver contains heterogeneous cell types of distinct spatial, molecular, and functional properties, they interact with each other to precede cell type-specific omics reprogramming and play an irreplaceable role in liver cells with heterogeneous properties upon encountering toxic insults. Single-cell omics, especially single-cell transcriptomics and single-cell proteomics, have been utilized for exploring the mechanisms of DILI and prediction for risk factors. In this review, we discuss the recent development and future perspectives of single-cell omics-based technologies for DILI-related research.</p></div>","PeriodicalId":100609,"journal":{"name":"hLife","volume":"2 7","pages":"Pages 325-341"},"PeriodicalIF":0.0,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2949928324000063/pdfft?md5=0ecc03b8c92ab1d50723fb86a717c8ed&pid=1-s2.0-S2949928324000063-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139638066","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 cholangiocyte organoid system for Cryptosporidium parvum cultivation and transcriptomic studies of biliary cryptosporidiosis","authors":"","doi":"10.1016/j.hlife.2024.05.001","DOIUrl":"10.1016/j.hlife.2024.05.001","url":null,"abstract":"<div><p>Biliary cryptosporidiosis caused by <em>Cryptosporidium</em> is life-threatening in immunocompromised individuals, particularly those with acquired immune deficiency syndrome (AIDS), resulting in AIDS cholangiopathy. However, studies of biliary cryptosporidiosis have lagged due to the lack of <em>in vitro</em> models that allow complete pathogen development. Here we describe procedures for the generation of mouse cholangiocyte organoids (Chol-orgs). The Chol-orgs, which expressed stem and biliary cell markers, could be clonally expanded for three months and stored in liquid nitrogen for more than one year. Combined with cell differentiation using the air-liquid interface (ALI) approach, we established a culture system for <em>C. parvum</em>. ALI cultures using Chol-orgs have supported ∼50-fold amplification of the pathogen and generated viable oocysts <em>in vitro</em>. In addition, we analyzed the transcriptome of Chol-ALI cultures infected with the IId subtype of <em>C. parvum</em> to characterize host cell responses. RNA-seq analysis revealed that <em>C. parvum</em> upregulated immune and inflammatory responses and downregulated metabolic and cell proliferation signaling pathways in Chol-orgs. A similar system using bovine cholangiocytes also supported the complete development of <em>C. parvum in vitro</em>. These <em>in vitro</em> models provide convenient methods to study biliary cryptosporidiosis and other hepatic infections and to develop effective therapies for AIDS cholangiopathy.</p></div>","PeriodicalId":100609,"journal":{"name":"hLife","volume":"2 7","pages":"Pages 360-370"},"PeriodicalIF":0.0,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2949928324000373/pdfft?md5=729af4d98153157e4a39c0983b556dde&pid=1-s2.0-S2949928324000373-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141033250","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}