hLife Pub Date : 2025-05-01 DOI: 10.1016/j.hlife.2025.02.002

Satish Kumar Tiwari , Florent Ginhoux

{"title":"Advancements in 3D models for studying human iPSC-microglia: Insights into neurodevelopment and neurological disorders","authors":"Satish Kumar Tiwari , Florent Ginhoux","doi":"10.1016/j.hlife.2025.02.002","DOIUrl":"10.1016/j.hlife.2025.02.002","url":null,"abstract":"<div><div>Microglia are immune cells of the central nervous system, playing a vital role in brain development, homeostasis, and disease. When these cells become dysfunctional, they can contribute to various psychiatric disorders and neurodegenerative diseases. To enhance our understanding of microglial function, researchers are increasingly employing human cell-based models. This approach significantly improves our investigations into these complex conditions and aids in ongoing drug development efforts. <em>In vitro</em> models of human microglia, derived from disease-specific induced pluripotent stem cells (iPSCs), are essential for examining their roles in neurological disorders. These models provide a controlled environment for studying the cellular and molecular processes involved in microglia-driven neuroinflammation and neurodegeneration. Integrating microglia into three-dimensional (3D) organoid cultures yields a more physiologically relevant model of the human brain, thereby advancing the study of brain development and the pathology of neurological disorders. Currently, brain organoid models are limited by the absence of key components, such as vasculature, which restricts their growth and hinders the optimal modeling of neurodevelopment, as well as the examination of microglial forms and functions. This review explores newly developed 3D models for generating human-induced microglia and investigates the potential of these <em>in vitro</em> systems to improve our understanding of brain development and the disorders that emerge from its disruption.</div></div>","PeriodicalId":100609,"journal":{"name":"hLife","volume":"3 5","pages":"Pages 204-215"},"PeriodicalIF":0.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143948868","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}

引用次数: 0

Harnessing allogeneic CAR-T cell therapy for autoimmune conditions 利用异体 CAR-T 细胞疗法治疗自身免疫疾病

hLife Pub Date : 2025-04-01 DOI: 10.1016/j.hlife.2025.02.003

Qun Yan , Huji Xu

引用次数: 0

Developing next-generation tuberculosis vaccines based on pathogen–host interactions: Towards a holistic perspective 基于病原体-宿主相互作用开发新一代结核病疫苗：迈向整体视角

hLife Pub Date : 2025-04-01 DOI: 10.1016/j.hlife.2024.11.003

Zehui Lei , Jing Wang , Cui Hua Liu

引用次数: 0

Machine learning approach to predict prognosis and immunotherapy responses in colorectal cancer patients 机器学习方法预测结直肠癌患者的预后和免疫治疗反应

hLife Pub Date : 2025-04-01 DOI: 10.1016/j.hlife.2025.02.001

Zhen Liu , Dou Yu , Pengyan Xia , Shuo Wang

{"title":"Machine learning approach to predict prognosis and immunotherapy responses in colorectal cancer patients","authors":"Zhen Liu , Dou Yu , Pengyan Xia , Shuo Wang","doi":"10.1016/j.hlife.2025.02.001","DOIUrl":"10.1016/j.hlife.2025.02.001","url":null,"abstract":"<div><div>The immune-related genes in the colorectal cancer (CRC) microenvironment are closely associated with patient prognosis and the efficacy of immunotherapy. In this study, a CRC risk model was established utilizing the expression profiles of immune-related genes. The risk prediction framework for CRC was created by integrating clinical and transcriptomic data through machine learning techniques. We incorporated 13 core immune-related genes (<em>IL18BP</em>, <em>RSAD2</em>, <em>G0S2</em>, <em>SIGLEC1</em>, <em>SFRP2</em>, <em>IFI44L</em>, <em>ISG20</em>, <em>IFIT1</em>, <em>OLR1</em>, <em>SAMHD1</em>, <em>HK3</em>, <em>PTAFR</em>, and <em>CSF1</em>), constructed a prognostic model and established Immune Response-related Risk Score (IRRS) model in CRC. IRRS strongly correlated with cancer staging, immune cell infiltration, immune cell activation, and the expression of genes associated with immunotherapy targets. Furthermore, this IRRS model outperformed the Tumor Immune Dysfunction and Exclusion (TIDE) tool in predicting immunotherapy response. Therefore, by integrating patient clinical and transcriptomic data and applying machine learning algorithms, we developed a predictive model with enhanced accuracy and clinical utility for risk stratification and immunotherapy response prediction in CRC patients.</div></div>","PeriodicalId":100609,"journal":{"name":"hLife","volume":"3 4","pages":"Pages 172-186"},"PeriodicalIF":0.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143829708","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}

引用次数: 0

Dextran sulfate sodium-induced colitis exacerbates periodontitis via the NADPH oxidase 2/reactive oxygen species axis in M1-like macrophages 葡聚糖硫酸钠诱导的结肠炎通过m1样巨噬细胞NADPH氧化酶2/活性氧轴加重牙周炎

hLife Pub Date : 2025-04-01 DOI: 10.1016/j.hlife.2025.01.006

Tiansong Xu , Liqi Zhang , Murong Li , He Zhu , Ying Ni , Cancan Huang , Peihui Zou , Jie Zhang , Qian Zhang , Zhong Zheng , Chenggang Duan , Feng Chen

{"title":"Dextran sulfate sodium-induced colitis exacerbates periodontitis via the NADPH oxidase 2/reactive oxygen species axis in M1-like macrophages","authors":"Tiansong Xu , Liqi Zhang , Murong Li , He Zhu , Ying Ni , Cancan Huang , Peihui Zou , Jie Zhang , Qian Zhang , Zhong Zheng , Chenggang Duan , Feng Chen","doi":"10.1016/j.hlife.2025.01.006","DOIUrl":"10.1016/j.hlife.2025.01.006","url":null,"abstract":"<div><div>Periodontitis is associated with various systemic diseases, among the most important of which is inflammatory bowel disease (IBD). However, the mechanisms by which IBD exacerbates periodontitis remain unclear. Activation of the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 2 (NOX2)/reactive oxygen species (ROS) axis in macrophages can worsen intestinal inflammation and periodontitis. Nonetheless, whether IBD aggravates periodontitis by activating the NOX2/ROS axis, specifically in oral macrophages is unknown. In this study, we established animal models and analyzed single-cell RNA data to investigate these pathogenic pathways. Periodontal inflammation was exacerbated <em>via</em> the NOX2/ROS pathway in tumor necrosis factor M1-like macrophages during colitis. Notably, when a NOX2 inhibitor was administered, resulting in reduced ROS expression in periodontal tissue, both periodontal and intestinal inflammation were significantly alleviated, and disruption of the periodontal and intestinal microbiota was reduced. By uncovering the pathogenic pathways linking these two diseases, this study provides insight into potential treatments for periodontitis and related systemic conditions.</div></div>","PeriodicalId":100609,"journal":{"name":"hLife","volume":"3 4","pages":"Pages 187-200"},"PeriodicalIF":0.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143829709","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}

引用次数: 0

Artificial intelligence is transforming the study of proteins: Structures and beyond 人工智能正在改变蛋白质的研究：结构及其他

hLife Pub Date : 2025-04-01 DOI: 10.1016/j.hlife.2025.01.002

Haiyan Liu , Quan Chen , Yufeng Liu

引用次数: 0

Time is now: Preparing for the next pandemic 时不我待：为下一次大流行做好准备

hLife Pub Date : 2025-03-01 DOI: 10.1016/j.hlife.2024.12.008

Jun Liu , George Fu Gao , Kwok-Yung Yuen , Lit Man Leo Poon , Nan Song

引用次数: 0

Enabling the immune escaped etesevimab fully-armed against SARS-CoV-2 Omicron subvariants including KP.2 使免疫逃逸的 etesevimab 能够完全对抗 SARS-CoV-2 Omicron 亚变种，包括 KP.2

hLife Pub Date : 2025-03-01 DOI: 10.1016/j.hlife.2024.12.006

Chao Su , Juanhua He , Yufeng Xie , Yu Hu , Xin Li , Shitong Qiao , Peipei Liu , Min Huang , Rong Zhang , Liang Wang , Zhen Chang , Wenqiao Sun , Ke Xu , Jing Zhang , Longxing Cao , Pengcheng Han , Xin Zhao , Jianxun Qi , Qihui Wang , Mengsu Yang , George Fu Gao

{"title":"Enabling the immune escaped etesevimab fully-armed against SARS-CoV-2 Omicron subvariants including KP.2","authors":"Chao Su , Juanhua He , Yufeng Xie , Yu Hu , Xin Li , Shitong Qiao , Peipei Liu , Min Huang , Rong Zhang , Liang Wang , Zhen Chang , Wenqiao Sun , Ke Xu , Jing Zhang , Longxing Cao , Pengcheng Han , Xin Zhao , Jianxun Qi , Qihui Wang , Mengsu Yang , George Fu Gao","doi":"10.1016/j.hlife.2024.12.006","DOIUrl":"10.1016/j.hlife.2024.12.006","url":null,"abstract":"<div><div>Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is continuously evolving since 2019. Some monoclonal antibodies (mAbs) have been developed and widely used, such as etesevimab (CB6) developed by Eli-Lilly/Junshi. However, the mAb escaped from the variant of concern (VOC) ever since the emergence of Beta VOC, with a complete loss of efficacy against the Omicron subvariants. Here, we developed a broad-spectrum and affinity-mature antibody design (BAADesign) procedure to design CB6, enabling it to bind to the receptor-binding domains (RBDs) of multiple important Omicron subvariants, including the recent variant KP.2. Structural analysis confirmed the desired CB6-RBD interactions. Additionally, identical mutations in the complementarity determining regions (CDR)1 and CDR2 of the CB6 mutants also restored neutralizing potency for some RBD-1 group antibodies. Overall, the enhanced CB6 neutralizing capacity makes it a promising candidate against SARS-CoV-2 infection, and the BAADesign method has implications for the design of other antibodies.</div></div>","PeriodicalId":100609,"journal":{"name":"hLife","volume":"3 3","pages":"Pages 132-145"},"PeriodicalIF":0.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143628449","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}

引用次数: 0

H3N2 influenza virus characteristics in China (2019–2022): Genetic, antigenic, and infection dynamics during the COVID-19 pandemic 中国H3N2流感病毒特征（2019-2022年）：COVID-19大流行期间的遗传、抗原和感染动态

hLife Pub Date : 2025-03-01 DOI: 10.1016/j.hlife.2025.01.004

Jiaming Li , Yu Huan , Qianfeng Xia , Yan Li , Rahat Ullah Khan , Qingzhi Liu , Chuanran Dou , Marina Gulyaeva , Alexander Shestopalov , Ning Zhang , Xuefeng Duan , Jing Yang , Hongchun Zhang , Yuhai Bi

{"title":"H3N2 influenza virus characteristics in China (2019–2022): Genetic, antigenic, and infection dynamics during the COVID-19 pandemic","authors":"Jiaming Li , Yu Huan , Qianfeng Xia , Yan Li , Rahat Ullah Khan , Qingzhi Liu , Chuanran Dou , Marina Gulyaeva , Alexander Shestopalov , Ning Zhang , Xuefeng Duan , Jing Yang , Hongchun Zhang , Yuhai Bi","doi":"10.1016/j.hlife.2025.01.004","DOIUrl":"10.1016/j.hlife.2025.01.004","url":null,"abstract":"<div><div>Seasonal influenza activity significantly decreased in China during the coronavirus disease 2019 (COVID-19) pandemic, yet the H3N2 virus led to three epidemic waves. Understanding the characteristics of H3N2 epidemic viruses is essential for recognizing influenza during COVID-19 and for updating vaccines. In this study, we analyzed 579 respiratory samples from patients exhibiting influenza-like symptoms, collected in 2019–2022, leading to the successful sequencing of 36 complete H3N2 genomes. Genomic analysis indicated that the epidemic strains from these periods belonged to different hemagglutinin (<em>HA</em>) clades and exhibited phylogenetic divergence from the concurrently used vaccine strains. Significant antigenic differences were identified through cross-hemagglutination inhibition (HI) and cross-microneutralization (MN) assays. Furthermore, pathogenicity studies showed that representative strains replicated in Madin-Darby canine kidney‌ (MDCK) cells, with varying abilities, and all replicated more effectively at 37 °C compared to 33 °C. These strains also replicated well in the respiratory tracts of mice and guinea pigs. The findings indicate a mismatch between circulating H3N2 viruses and recommended vaccine strains, highlighting the need for improved international cooperation and epidemiological surveillance of influenza viruses post-COVID-19. Optimizing effective vaccine strain update strategy and developing a universal influenza vaccine are crucial for future preparedness.</div></div>","PeriodicalId":100609,"journal":{"name":"hLife","volume":"3 3","pages":"Pages 146-158"},"PeriodicalIF":0.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143628450","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}

引用次数: 0

Neutrophils: Key players in the metabolic syndrome puzzle 中性粒细胞：代谢综合征之谜中的关键角色

hLife Pub Date : 2025-03-01 DOI: 10.1016/j.hlife.2025.01.003

Hui Ping Yaw , Sapna Devi , Lai Guan Ng

{"title":"Neutrophils: Key players in the metabolic syndrome puzzle","authors":"Hui Ping Yaw , Sapna Devi , Lai Guan Ng","doi":"10.1016/j.hlife.2025.01.003","DOIUrl":"10.1016/j.hlife.2025.01.003","url":null,"abstract":"<div><div>Metabolic syndrome (MetS) is a group of metabolic abnormalities associated with an increased risk of getting type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD). For many years, MetS has been viewed solely as a metabolic disease. In recent decades, MetS development has been associated with chronic inflammation related to nutrient excess, especially in the adipose tissues (AT). Metabolic stress, arising from the significant metabolic changes in MetS, is known to impact the balance of immune homeostasis. Although multiple immune cells have been investigated in this context, neutrophils, the first responder to inflammation, have only gained increased attention in recent years. Hence, this review aims to summarize the current evidence for the effects of MetS-induced systemic and AT-specific metabolic changes on neutrophils and their functions. We first provide an overview of the metabolic pathways used by neutrophils, with a specific focus on their recently discovered metabolic plasticity. This is followed by a discussion on the impact of MetS-induced alterations on the systemic metabolism and in the AT environment, how these changes may affect neutrophil effector functions, and the main mechanisms involved. Finally, we will examine the roles of neutrophils and their functions in T2DM and CVD that develop due to MetS. We will also provide perspectives on how a deeper understanding of the effects of systemic and site-specific metabolic changes in neutrophils and their effector functions could unlock the therapeutic potential of targeting neutrophils, as the arbiters of innate immunity in the context of MetS.</div></div>","PeriodicalId":100609,"journal":{"name":"hLife","volume":"3 3","pages":"Pages 121-131"},"PeriodicalIF":0.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143628451","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}

引用次数: 0

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