撰文丨王聪 编辑丨王多鱼 排版丨水成文 铁死亡 （Ferroptosis） 是 2012 年发现的一种铁依赖性的新型细胞程序性死亡方式，由过度堆积的 过氧化脂质 （peroxidized lipids） 诱导发生，其形态特 征，作用方式以及分子机制与其他程序性死亡方式截然不同。 近年来的研究表明， 铁死亡 在 癌症 等多种疾病发生发展中扮演着重要角色。此外， 免疫治疗或放射治疗可诱导肿瘤细胞铁死亡，且铁死亡在肿瘤免疫治疗及放 疗的疗效发挥中发挥着重要的促进作用。因此， 铁死亡正在成为是一种极具前景的抗癌新策略。 经典铁死亡通常由诱导剂 （例如 erastin 和 RSL-3） 或 GPX-4 缺失所触发，然而，铁死亡在体内的自然发生无需这些触发因素，其中的机制一直不清楚。 2026 年 2 月 19 日， 哥伦比亚大学 顾伟 教授团队联合匹茨堡大学 Valerian E. Kagan 团队 （顾伟实验室博士后 夏章传 为论文第一作者） ，在国际顶尖学术 期刊 Cell 上发 表了题为： A GPX1-OSBPL8 axis mediates noncanonical in vivo ferroptosis a ...

撰文丨王聪 编辑丨王多鱼 排版丨水成文 你的免疫系统自带"预警雷达"？科学家发现HIV患者能否"自愈"的关键开关！ 抗逆转录病毒疗法 （ART） 可以有效地抑制 HIV 病毒在体内的复制，使病毒载量降低到检测不到的水平。然而，ART 无法清除"潜伏病毒库"，这些 潜伏的 HIV 病毒库 主要存在于一类特定的免疫细胞——表达 PD-1 蛋白的 CD4 + T 细胞 中。 抗 PD-1 疗法 ，已广泛应用于癌症治疗，对于同时患有艾滋病的癌症患者，抗 PD-1 疗法显示出降低 HIV 病毒库 的额外效果。然而，并非所有接受抗 PD-1 疗 法的患者都能观察到 HIV 病毒库的减少，因此，尚不清楚哪些患者特征与疗效相关。此外，抗 PD-1 疗法具体是通过什么分子和细胞途径来减少 HIV 病毒库的， 目前仍不清楚。 2026 年 2 月 12 日，埃默里大学的研究人员在国际顶尖医学期刊 Nature Medicine 上发表了 题为： Innate antiviral and immune functions associated with the HIV reservoir decay after anti-PD-1 ...

Core Insights - On February 18, 2026, the journal Nature published 28 research papers, with 8 authored by Chinese scholars, highlighting the significant contributions of Chinese researchers in the field of science [2][4][5][8][10][13][15][17]. Group 1: Research Contributions - Zhang Xieyang from Boston University published a paper on "Stereospecific alkyl–alkyl cross-coupling of boronic esters," focusing on a specific chemical reaction [2]. - A team from Pennsylvania State University, led by Qi Ming Zhang, published a study on "Giant energy storage and dielectric performance in all-polymer nanocomposites," emphasizing advancements in energy storage materials [4]. - Researchers from South China University of Technology and Tianjin University published findings on "Practical lithium–organic batteries enabled by an n-type conducting polymer," which could enhance battery technology [5]. - A study from the University of Science and Technology of China explored the roles of microtubules and LIS1 in dynein transport machinery assembly, contributing to the understanding of cellular transport mechanisms [8]. - A collaborative effort from Shanghai Jiao Tong University and Fudan University focused on "In vivo base editing of Chd3 rescues behavioural abnormalities in mice," showcasing advancements in genetic editing techniques [10]. - A paper from Wuhan University and ShanghaiTech University discussed "RYK is a GPNMB receptor that drives MASH," contributing to the understanding of receptor biology [13]. - A research team from Peking University and Changping Laboratory published on "Integrated photonics enabling ultra-wideband fibre–wireless communication," which could impact communication technologies [15]. - An innovative study from Shanghai Jiao Tong University on "An agentic system for rare disease diagnosis with traceable reasoning" presents a new approach to diagnosing rare diseases using AI [17]. Group 2: Additional Research - On February 16, Zhejiang University published a paper titled "De novo Design of GPCR Exoframe Modulators," focusing on the design of modulators for G protein-coupled receptors, which are crucial in drug development [19].

Core Viewpoint - The research highlights the potential of in vivo base editing as a viable strategy to alleviate symptoms associated with Snijders Blok-Campeau Syndrome (SNIBCPS), a genetic neurodevelopmental disorder caused by mutations in the CHD3 gene [2][10]. Group 1: Disease Overview - Snijders Blok-Campeau Syndrome (SNIBCPS) is an autosomal dominant genetic disorder caused by pathogenic mutations in the CHD3 gene, first described in 2018, with over 100 reported cases [5]. - Key clinical features of SNIBCPS include global developmental delay, language delay, intellectual disability, hypotonia, facial dysmorphism, and brain structural abnormalities, often accompanied by autism spectrum disorder (ASD) [5]. Group 2: Research Findings - The research team developed a humanized mouse model (Chd3 hR1025W/+) that exhibited communication, cognitive, and autism-related behavioral deficits [3][7]. - A base editor, TeABE, was designed to correct the A•T base pair mutation, and intravenous delivery via a dual AAV system restored CHD3 protein levels and improved cognitive and autism-like behaviors in the mouse model [3][8]. - In non-human primates (NHP), intrathecal delivery of AAV9 carrying TeABE achieved widespread brain transduction and base editing, supporting the clinical translational feasibility of this approach [3][8]. Group 3: Implications for Treatment - The findings establish in vivo base editing as a feasible treatment method for CHD3-related neurodevelopmental disorders, demonstrating that precise single-base editing in the brain postnatally can restore protein dosage and function [10].

Core Viewpoint - The research identifies the GPNMB-RYK signaling axis as a novel pathogenic ligand-receptor pathway and a promising therapeutic target for Metabolic Dysfunction-Associated Steatotic Hepatitis (MASH) [5] Group 1: Research Findings - MASH is a critical stage of Metabolic Dysfunction-Associated Fatty Liver Disease (MASLD) with increasing global prevalence and limited treatment options [3] - The study published in Nature reveals that the extracellular domain of GPNMB (G-ECD) drives the progression of MASH by promoting fat accumulation and inflammation in the liver [3][4] - The research team found that knocking out the Gpnmb gene in mice protects them from diet-induced MASH, indicating the gene's significant upregulation in MASH [4] Group 2: Mechanism of Action - The binding of G-ECD to the RYK receptor activates the ERK1/2 signaling pathway, leading to the transcriptional activation of PPARγ-CD36 and SREBP1C pathways, which promote lipid uptake and synthesis in the liver [4] - The study confirmed that various therapeutic strategies targeting the GPNMB-RYK signaling axis, including G-ECD vaccines and AAV-delivered shRNA, effectively prevent and treat MASH in preclinical models [4]

Core Viewpoint - The article discusses advancements in T Cell Receptor (TCR) therapy for solid tumors, highlighting the challenges in developing effective and specific TCRs while addressing the potential for off-target toxicity [3]. Group 1: Research Findings - A study published in the journal Cell introduces a histidine scanning engineering strategy that significantly enhances the activation efficacy of mechanosensory receptors like TCRs [4]. - The research demonstrates that histidine scanning can identify hotspots that form additional catch bonds, allowing for the creation of a TCR library aimed at low-affinity, high-efficacy variants without off-target or on-target toxicity [6]. Group 2: Implications for Therapy - The findings provide a universal engineering method for low-affinity, high-efficacy TCRs, enabling the design of TCR libraries without structural constraints [8]. - The histidine scanning approach has broader applications in other mechanosensory ligand-receptor systems, potentially impacting various immunotherapy strategies [8].

Core Insights - The article discusses a study from Tel Aviv University published in Nature Medicine, which explores the connection between "brain thoughts" and "body immunity," specifically how positive expectations can enhance immune responses to vaccinations [2][3]. Research Design - The study involved 85 healthy volunteers divided into three groups: 1. Experimental group trained to upregulate the brain's reward circuitry [7] 2. Control group trained to activate unrelated brain networks [8] 3. Blank control group with no brain training [9] - Participants used a technique called functional magnetic resonance neurofeedback to visualize and adjust their brain activity [10]. Key Findings - The study found that: 1. The brain can be "trained" to enhance specific activity levels, indicating that individuals can learn to self-regulate brain functions [14]. 2. The ventral tegmental area (VTA) is crucial; higher activity in this region correlates with increased antibody levels post-vaccination [14]. 3. Positive expectations are key; strategies that successfully upregulated VTA activity often involved a forward-looking, optimistic mindset [14]. 4. While the study shows correlation rather than causation, it strengthens the reliability of the link between VTA activity and immune response [15]. Implications of the Research - This research outlines a pathway from conscious positive expectations to enhanced immune responses, providing a new explanation for the placebo effect [17]. - It suggests potential for non-invasive methods, such as neurofeedback training and cognitive behavioral therapy, to harness positive psychological resources to improve vaccine efficacy and regulate immune functions in chronic conditions [17].

撰文丨王聪 编辑丨王多鱼 排版丨水成文 内皮细胞 （ Endothelial Cell， EC） 是脊椎动物中最基本的细胞类型之一。这种特化的细胞群位于循环系 统的内侧，对于营养物质的运输、免疫监视以及器官的发育至关重要。大量研究工作揭示了血管生成的常 见分子机制，但对于器官特异性血管发育以及多器官胚胎内皮细胞的比较，相关知识仍处于很大程度上的 未开发状态。 过去， 血管内皮细胞 根据相应的分子标记被分为动脉内皮细胞、静脉内皮细胞和毛细血管内皮细胞。近期 的研究揭示了不同器官内皮细胞中此前未知的器官特异性异质性。例如，在成年小鼠中，单细胞 RNA 测序 （scRNA-seq） 显示，不同器官中的内皮细胞在转录组水平上表现出独特的器官特异性特征。然而，目前 仍不清楚这是一个快速的发育过程，还是一个需要内皮细胞与组织驻留细胞之间长期相互作用的耗 时事 件。 控制器官特异性内皮细胞分化的关键调控因子，在很大程度上仍不清楚，而且内皮细胞失去器官特异性特 征是否会影响相应器官的发育和再生，也尚未得到研究。 在中国马年春节到来之际， 中 国科学院广州生物医药与健康研究院 陈奇 研究员、 陈捷凯 研究员、 彭广 敦 研究员 ...

Core Viewpoint - The article discusses a groundbreaking study on GPCR (G-protein-coupled receptor) modulation through the introduction of a novel concept called "GPCR Exoframe Modulators" (GEM), which utilizes deep learning for the design of proteins that target GPCR transmembrane domains, offering new therapeutic avenues for GPCR-related diseases [2][3][4]. Group 1 - GPCR is the largest membrane protein family in the human body, responsible for transducing various extracellular signals and regulating a wide range of physiological processes, making it a primary drug target [2]. - The research team from Zhejiang University published their findings in Nature, introducing the concept of GEM, which can specifically bind to the transmembrane surface of GPCRs and stabilize specific receptor conformations [3][4]. - The study highlights the potential of deep learning methods in designing function-oriented membrane proteins, marking a significant advancement in GPCR allosteric modulation [8]. Group 2 - The research focused on the dopamine D1 receptor (D1R) as a prototype model, investigating four types of GEM: GEM anchor, GEM BAM, GEM NAM, and GEM ago-PAM, which exhibit various allosteric modulation functions [6]. - Among these, GEM ago-PAM has shown the ability to restore the activity of multiple D1R loss-of-function mutants, providing a new potential target for the treatment of GPCR-related diseases [6][8]. - The study emphasizes that targeting transmembrane domains with GEM can serve as an effective tool for GPCR allosteric modulation, showcasing the innovative approach to drug design [8].

Core Viewpoint - The research conducted by Professor Wang Geng's team at Xiamen University reveals that mitochondrial double-stranded RNA (mt-dsRNA) plays a significant role in aging-associated cognitive decline, with SEC61A1 being a key regulator of mt-dsRNA homeostasis [2][4]. Group 1 - The study published in Cell Research identifies SEC61A1 as a crucial factor that is specifically upregulated in the aging brain, enhancing endoplasmic reticulum-mitochondria contact (ERMCS) and promoting mitochondrial transcription [2][4]. - The activation of the cytoplasmic MDA5/RIG-I-MAVS innate immune pathway due to the accumulation of mt-dsRNA drives cognitive decline associated with aging [2][4]. - The research demonstrates that overexpression of Sec61a1 in the cortex of mice can induce cognitive decline without affecting motor abilities, while knockdown of Sec61a1 or Mavs can alleviate mt-dsRNA-mediated innate immune signaling and cognitive decline in aging mice [4]. Group 2 - The findings provide insights into the molecular mechanisms underlying cognitive decline related to aging and diseases, suggesting potential therapeutic targets for intervention [4].