编辑丨王多鱼 排版丨水成文 时间永不停歇地前进……但这对于免疫系统意味着什么？ 近期， Immunity 期刊 特邀来自中国科学院 （ 刘光慧 、 田烨 ） 、斯坦福大学、剑桥大学等机构的一组知名学者， 围绕衰老如何影响免疫反应、免疫细胞如何 参与衰老进程等关键问题展开了深入探讨。这些讨论为 通过调控免疫力以延长健康寿命 提供了新的科学视角。 Christoph A. Thaiss ， Arc 研究所，斯坦福大学， 感知免疫变化 在其 1956 年前瞻性讲座《 心灵与物质 》的开篇，物理学家 埃尔温 · 薛定谔 指出： " 世界是我们感觉、知觉与记忆的建构产物。 " 这一建构基于两大感觉系 统：外感受负责感知外部物理与化学环境，内感受则负责感知机体内在环境。免疫细胞发出的信号极大地拓展了内感受的疆界 —— 例如，响应微生物识别而释放 的细胞因子可激活感觉神经元上的受体，进而将信号传递至大脑，协调适应性反应。 尽管外感受功能随年龄增长而衰退 （日常生活中常通过眼镜或助听器等设备进行补偿） ，但关于内感受如何衰老，我们仍知之甚少。免疫细胞功能在整个生命周 期中发生深刻变化：骨髓造血输出呈现髓系偏倚，记忆性 T 细 ...

撰文丨王聪 编辑丨王多鱼 排版丨水成文 肺癌 是一种极为常见的恶性肿瘤，是全球癌症相关死亡的主要原因。其中， 非小细胞肺癌 （NSCLC） 约 占所有肺癌病例的 85%， 其预后通常不佳。 免疫治疗领域的最新进展，尤其是 PD-1/PD-L1 单克隆抗体的应用，为 NSCLC 患者带来了新希望。临床 上，关键免疫检查点 PD-L1 表达情况常被评估以选择合适的免疫治疗药物，阻断 PD-1/PD-L1 通路能够 使耗竭的 CD8 + T 细胞重新活跃并恢复其肿瘤杀伤功能。 然而，PD-L1 并非理想的预测性生物标志物，因为一些 PD-L1 低表达的患者仍能从免疫治疗中获益。尽 管免疫治疗在晚期 NSCLC 患者中取得了令人鼓舞的 5 年生存率，但仍有部分患者出现复发或远端转移。 因此，寻找更有效的免疫治疗预测性生物标志物，对于 NSCLC 患者而言 至关重要。 近日，山东第一医科大学附属肿瘤医院 （山东省肿瘤防治研究院、山东省肿瘤医院） 陈大卫 团队在 Therapeutic Advances in Medical Oncology 期刊发表了 题为： Neutrophil extracellular trap ...

撰文丨王聪 编辑丨王多鱼 排版丨水成文 卵巢癌 （ Ovarian cancer ） 是全球最致命的妇科恶性肿瘤。这种癌症相对罕见，但在患有 子宫内膜异位 症 （ Endometriosis ） 的女性中更为常见，尤其是 透明细胞卵巢癌 。 子宫内膜异位症相关卵巢癌 （EAOC） 在子宫内膜异位症患者中的发生率高达 4.5%，其主要由卵巢病变 （子宫内膜异位囊肿） 恶变所致。在过去的几十年里，子宫内膜异位症的发病率有所上升，与此同时，在 子宫内膜异位症患者中卵巢肿瘤的检出率也有所增加。 与其它卵巢癌相比，EAOC 存在一些尚未解决的问 题，包括化疗耐药性、预后较差以及发病年龄更小。 然而，子宫内膜异位症与卵巢癌之间的因果关系仍有待确定。因此，阐明这种恶性肿瘤的发病机制对于防 止诊断延误以及降低其长期发病率至关重要。 2025 年 11 月 20 日，暨南大学医学院 李平 、香港中文大学（深圳）第二附属医院 王明华 、暨南大学附 属第一医院 周宏 等人 ， 在 Cell 子刊 Cell Reports Medicine 上发表了题为： Therapeutic targeting of interleukin-1 ...

这一关乎 " 同一性 " 与 " 异质性 " 的辩证矛盾，是困扰生物学界数十年的 " 生命同源异质 " 之问。其核心便隐藏在每 个细胞不尽相同的转录活动中，一种被称为 " 基因表达噪声 " 的微观波动，是探索生命复杂性的关键入口。 长期以来，相关研究多聚焦于基因表达的平均水平，而将这种噪声波动视为技术误差。然而，它恰恰蕴藏着细胞命运决 策、机体衰老与疾病发生的关键线索。为什么在高度一致的条件下，细胞仍表现出如此丰富的转录异质性？这些波动又 如何在生理与病理过程中发挥作用？解析 基因表达噪声 的遗传基础，不仅有望填补 " 遗失的遗传力 " ，更将为复杂疾 病的机制研究开辟全新视角，具有重要的科学价值与临床意义。 202 5 年 11 月 23 日，中国医学科学院基础医学研究所 龙尔平 / 倪晓琳 团队与美国国家癌症研究所 张同武 团队合 作，在 Cell Reports 期刊 在线发表了题为： Genetic determinants of gene expression noise and its role in complex trait variation 的研究论文 。 该研究建立了基于百万级单细胞数据 ...

排版丨水成文 代谢功能障碍相关脂肪性肝病 （MASLD） ，此前被称为非酒精性脂肪肝病 （NAFLD） ，正日益受到关注，成为全球 性的健康危机。它涵盖了从单纯脂肪变性到代谢功能障碍相关脂肪性肝炎 （MASH） 的范围，病情可能会发展为肝纤 维化、肝硬化，甚至肝细胞癌。 尽管 MASLD 的负担沉重且其病理生理学复杂，但目前仅有 1 种药物 （瑞美替罗） 获批专门用于 MASH 的治疗，这 凸显了迫切需要更多替代策略，其中 益生元 已崭露头角，成为颇具前景的候选方案。 2025 年 11 月 2 0 日， 上海交通大学医学院附属第六人民医院 李华婷 教授、上海交通大学数学科学学院 / 人工智能 学院 陈洛南 教授、上海交通大学医学院附属第六人民医院 倪岳琼 研究员、上海科技大学 / 上海临床研究中心 曾嵘 教 授及上海交通大学医学院附属第六人民医院 贾伟平 教授等， 在 Cell 子刊 Cell Metabolism 上 发表了题为： Interindividual variability in gut microbiome mediates the efficacy of resistant starch ...

Core Viewpoint - The study published by Professor Wu Baojian's team from Guangzhou University of Chinese Medicine in Cell Metabolism highlights the role of the intestinal clock in regulating the sleep-wake cycle through maintaining glutamine homeostasis, suggesting potential new targets for enhancing sleep rhythms and treating sleep disorders [2][7]. Summary by Sections Research Findings - The integrity of the intestinal epithelial cells (IEC) is essential for maintaining the circadian sleep-wake cycle [4]. - BMAL1 in the intestinal epithelial cells drives the circadian expression of SLC6A19, promoting glutamine absorption during active periods, which enhances the activity of glutamatergic neurons in the hypothalamus, thereby increasing wakefulness and reducing sleep [4][5]. - A lack of REV-ERBα in intestinal epithelial cells leads to elevated glutamine levels during rest phases, which is causally linked to sleep abnormalities characterized by reduced sleep [4][5]. Implications - The intestinal clock regulates glutamine homeostasis temporally, shaping the circadian sleep-wake cycle, and may serve as a potential target for enhancing sleep rhythms and treating sleep disorders [7].

Core Viewpoint - Jiangsu Runhe Software Co., Ltd. has signed a strategic cooperation agreement with the Guangzhou Institute of Biomedicine and Health, focusing on enhancing biological research processes through digital technologies [1] Group 1: Strategic Cooperation - The partnership will concentrate on the human cell lineage big science research facility [1] - Collaboration will involve domestic operating systems, smart IoT, big data analysis, and artificial intelligence [1] Group 2: Technological Enhancement - The aim is to improve the standardization, intelligence, and visualization of biological research processes through digital technology [1]

Core Viewpoint - The article discusses the significance of Total Neoadjuvant Therapy (TNT) in the treatment of locally advanced rectal cancer (LARC) and highlights the need for a deeper understanding of the immune remodeling mechanisms involved in its efficacy [3][6]. Group 1: Treatment Strategies and Mechanisms - LARC accounts for over one-third of both incidence and mortality in colorectal cancer, which is the third most common and the second deadliest cancer globally [3]. - Recommended treatment strategies for LARC include TNT or neoadjuvant chemotherapy (nCT), with additional options like radiotherapy for cases with poor response [3]. - The immune remodeling mechanisms behind the efficacy of TNT remain unclear, necessitating further research into the tumor microenvironment (TME) changes induced by this therapy [6]. Group 2: Research Findings - A study published in Cancer Cell reveals that TNT significantly remodels the immune microenvironment in LARC, with CD8+ T cells and endothelial cells interacting as a potential key factor for clinical efficacy [4][10]. - The research utilized single-cell RNA sequencing and spatial transcriptomics to analyze pre- and post-treatment samples, showing that TNT is associated with a reduction in regulatory T cells (Treg) and an increase in IFNG+ CD8+ effector memory T cells, which may enhance complete response rates [6][7]. - The abundance of tumor-infiltrating CD8+ T cells post-TNT correlates with the enrichment of ACKR1+ endothelial cell subpopulations, which are activated by IFNγ released from CD8+ T cells, enhancing their antigen-presenting capabilities [6][7][10]. Group 3: Implications for Clinical Practice - The study provides new insights into optimizing clinical treatment strategies for rectal cancer by elucidating the complex mechanisms of immune response during neoadjuvant therapy [4][10]. - The findings suggest that the quantity of IFNG+ CD8+ T cells and peripheral blood IFNG signaling could serve as markers for response to TNT [8].

Core Viewpoint - The research published by the Beijing Brain Science and Brain-like Research Institute highlights the significant role of adenosine signaling in the rapid antidepressant effects of ketamine and electroconvulsive therapy (ECT), proposing a new intermittent hypoxia intervention to safely induce adenosine release in the brain for effective depression treatment [1] Group 1: Research Findings - The study identifies adenosine as a key signaling molecule that mediates the rapid antidepressant actions of ketamine and ECT [1] - The research confirms that the adenosine signaling pathway is a common mechanism underlying the rapid antidepressant effects of both treatments [1] - The findings provide a solid theoretical basis and clear targets for developing new generation antidepressant strategies that are based on adenosine signaling modulation, potentially leading to smaller side effects [1] Group 2: Implications for Treatment - The proposed intermittent hypoxia intervention (aIH) aims to safely and controllably induce adenosine release in the brain, achieving significant antidepressant effects [1] - This research deepens the understanding of the mechanisms behind rapid antidepressant effects, which could lead to innovative treatment options [1] - The study opens avenues for the development of small molecule drugs and non-drug interventions targeting adenosine signaling for depression treatment [1]

Core Insights - The study identifies Mesothelin (MSLN) as a biomarker and potential therapeutic target for bone destruction in rheumatoid arthritis (RA) [4][8] - MSLN levels are significantly elevated in RA patients and collagen-induced arthritis (CIA) animal models, indicating its role in disease pathology [6][9] Group 1: Research Findings - MSLN is involved in various biological processes, particularly in regulating immune responses, but its role in osteoclastogenesis is not well understood [6] - Inhibition of MSLN through pharmacological and genetic methods significantly impairs osteoclast differentiation and bone resorption [6] - Downregulation of MSLN in animal models effectively reduces bone destruction [6] Group 2: Mechanism of Action - MSLN interacts directly with PI3K, leading to the activation of the PI3K/AKT signaling pathway, which promotes the expression and translocation of NFATc1, thereby facilitating osteoclast differentiation [6][9] - MSLN is upregulated in the synovial tissue and plasma of RA patients, driving osteoclast differentiation and mediating pathological bone destruction [9] Group 3: Implications for Treatment - Targeting MSLN may represent a novel therapeutic strategy for addressing bone destruction associated with rheumatoid arthritis [8][9]