Core Findings - The study demonstrates that the axolotl can regenerate its thymus completely after surgical removal, a process that occurs without any remaining thymic tissue [3][7]. - Within 7 days post-surgery, thymic structures begin to reappear, and by 35 days, the regenerated thymus is nearly indistinguishable from a normal thymus in morphology, size, and cellular composition [7]. Functional Recovery - Experiments showed that the regenerated thymus can function normally; after transplantation into other axolotls, fluorescently labeled cells from the regenerated thymus migrated to the host's blood, spleen, and limbs within 3 days [9]. - A year later, it was found that only thymic epithelial cells were from the donor, while all mature lymphocytes originated from the host, indicating that the regenerated thymus can recruit host hematopoietic progenitor cells to develop into functional T cells [9]. Molecular Mechanisms - The regeneration process involves complex cellular signaling, with two key signaling pathways identified: Bone Morphogenetic Protein (BMP) and Midkine (MDK) [10]. - MDK plays a crucial role in the early stages of regeneration, with expression beginning 1-3 days post-injury, prior to the reappearance of thymic epithelial cells [10]. Scientific Significance - This research confirms the complete regenerative capability of lymphoid organs in vertebrates, challenging previous scientific beliefs about the limits of organ regeneration in vertebrates [12]. - Understanding the molecular mechanisms of axolotl thymus regeneration may provide insights for developing therapies to promote thymus regeneration in humans, particularly for patients who have undergone thymectomy due to conditions like myasthenia gravis or cancer [13].

撰文丨王聪 编辑丨王多鱼 排版丨水成文 一说到 蘑菇 ，相信大部分人会立即想到鲜美的食物。但并非所有的蘑菇都是无毒可食用的，每年因误食有 毒野生菌菇而入院的人不在少数。不仅如此，有些蘑菇还含有致幻毒素，使人产生缤纷如梦境的幻觉，它 们含有的 裸盖菇素 （Psilocybin，也叫做 赛洛西宾 ） ，会在摄入后几个小时内让人产生视听幻觉，是一 种具有神经致幻作用的神经毒素。除了致幻作用外，近年来的多项临床试验证实， 裸盖菇素还具有快速抗 抑郁作用 ，持续时间远超现有的抗抑郁药物 ，而且没有戒断症状。 康奈尔大学 Alex C. Kwan 团队 （ 博士后 蒋权 为论文第一作者 ） 在国际顶尖学术期刊 Cell 上 发表了题 为： Psilocybin triggers an activity-dependent rewiring of large-scale cortical networks 的研究论 文。 该研究绘制出了 裸盖菇素 如何以及在何处重塑大脑网络连接的图谱，发现裸盖菇素削弱了大脑皮层之间的 反馈回路，这种回路可能会使人陷入消极思维；裸盖菇素还强化了通往皮层下区域的通路，这些区域将感 觉知觉转化为 ...

Core Insights - The article discusses a significant research study on the nucleus basalis of Meynert (nbM), highlighting its role in regulating cortical functions, learning, and memory, and its association with neurodegenerative diseases and developmental disorders [2][3]. Group 1: Research Findings - The research team successfully generated human nucleus basalis organoids (hnbMO) from human pluripotent stem cells (hPSC), which contain functional cholinergic projection neurons [5]. - The study established long-distance cholinergic projection pathways from nbM to the cerebral cortex by co-culturing hnbMO with fetal brain tissue and transplanting it into immunodeficient mice [5]. - The nbM-cortical organoid assembloids demonstrated human-specific cholinergic projection systems, confirming the functional connectivity between hnbMO and human cortical organoids (hCO) [5][6]. Group 2: Application and Implications - The organoid assembloids revealed projection defects in organoids derived from patients with Down syndrome, indicating their potential application in studying nbM-related neural circuits and neurological disorders [6]. - The research underscores the importance of the nbM-cortical cholinergic pathway in understanding the mechanisms underlying various neurological conditions [3][6].

细菌性肺炎 是全球重大的健康负担，具有高发病率和高死亡率，尤其在免疫缺陷或有既往健康问题的人群中。它是由肺实质和肺泡腔内严重的炎症所定义的，这 种炎症是由细菌病原体引发的，这些病原体与宿主的免疫防御系统复杂地相互作用。 目前，细菌性肺炎的一线治疗主要依赖经验性使用 抗生素 ，包括氟喹诺酮类、β-内酰胺类和大环内酯类。尽管这些抗生素对敏感细菌仍有效，但其临床疗效正逐 渐受到 多重耐药 （MDR） 细菌日益增多的影响，这类细菌如今在超过 25% 的肺炎病例中出现，并且与死亡率上升密切相关。 细菌清除功能缺陷会导致过度炎症，损害组织的恢复能力，并削弱宿主维持有效免疫防御的能力。这种不断加剧的炎症循环会加速疾病的发展进程，给治疗干预 带来了巨大的障碍。因此，迫切需要开发出能够同时根除多重耐药菌并减轻炎症引起的肺部损伤的创新治疗策略。 近日，西奈山伊坎医学院 董一洲 教授团队 （ 薛涌尔 、 侯续成 、 王思雨 为论文共同第一作者 ） 在 Nature 子刊 Nature Biotechnology 上发表了题为 ： Antimicrobial peptide delivery to lung as peptibody ...

Core Viewpoint - Cancer immunotherapy has revolutionized cancer treatment by activating the immune system to attack tumors, but many patients still face tumor recurrence, with underlying mechanisms not fully understood [1][4]. Group 1: Tumor-Initiating Stem Cells (tSC) - Tumor-initiating stem cells (tSC) are considered a key cell population responsible for tumor recurrence, yet their role in regulating the immune microenvironment remains largely unknown [1][5]. - Recent research indicates that tSC can survive during strong anti-tumor immune responses induced by immunotherapy, contributing to cancer recurrence post-treatment [5][10]. Group 2: Neutrophils in Tumor Microenvironment - Neutrophils, as one of the most abundant immune cells in the tumor microenvironment (TME), have a close relationship with the effectiveness of immunotherapy [1][4]. - Tumor-associated neutrophils (TAN) have been traditionally viewed as having immunosuppressive roles, but recent studies suggest they can enhance anti-tumor immune responses by presenting new antigens through MHCII molecules [1][6]. Group 3: Research Findings - A study published in Cancer Cell reveals that tSC regulate the plasticity of neutrophils through metabolic reprogramming, creating a protective niche that allows them to survive during cancer immunotherapy, leading to recurrence [2][10]. - The study identifies a specific signaling axis (SOX2-FADS1-PGE2) that could serve as a novel combination therapy strategy to prevent immunotherapy resistance and tumor recurrence [2][10]. Group 4: Implications of Findings - The research highlights the dynamic interactions between tSC and TAN, showing that effective immunotherapy can induce different responses in various TAN subpopulations [8][10]. - The findings suggest that targeting the PGE2 signaling pathway can restore the anti-tumor functions of neutrophils, enhancing the effectiveness of immunotherapy and significantly reducing tumor recurrence rates [7][12].

Core Viewpoint - The research identifies GNE-6468 as a novel STING agonist that effectively activates STING-mediated innate immune responses and shows potential applications in antiviral and antitumor immunotherapy [2][6]. Group 1: Mechanism of Action - The study reveals the mechanism by which PI4P and the chemical agonist GNE-6468 activate STING, demonstrating that GNE-6468 binds to a specific pocket in the transmembrane domain of STING, causing outward displacement of the TM3 helix without altering the conformation of the ligand-binding domain [3][4]. - The structural analysis shows that both PI4P and GNE-6468 induce STING oligomerization and immune response, confirming the critical role of their interaction in STING activation [3][4]. Group 2: Functional Implications - GNE-6468 mediates a strong antiviral and antitumor immune response in a STING-dependent manner, indicating its potential as a therapeutic agent [4][6]. - The combination of GNE-6468 with PD-1 antibodies exhibits significant synergistic antitumor effects, highlighting its promising application in immunotherapy [3][4].

Core Viewpoint - The article discusses a significant breakthrough in plant stem cell regulation, revealing the decisive role of cell wall microstructure in maintaining stem cell homeostasis and decoding the "cell wall code" that determines plant cell fate [3][10]. Group 1: Research Findings - The research team from the Chinese Academy of Sciences published a study in *Science*, highlighting the importance of pectin's methylation modification in the mechanical properties of the cell wall, which influences stem cell dynamics [3][10]. - A unique "binary distribution" pattern of pectin was identified, where highly methylated pectin is found in mature cell walls, while demethylated pectin is enriched in the new cell plate, creating mechanical heterogeneity that supports stem cell proliferation [5][10]. - The study also uncovered a sophisticated "timed release system" for PME5 mRNA, which is crucial for regulating pectin demethylation during cell division, linking stem cell proliferation with cell wall remodeling [6][10]. Group 2: Implications for Agriculture - The newly discovered mechanism of mRNA nuclear retention and its role in stem cell activity is conserved across various crops, including maize, soybean, and tomato, suggesting its potential impact on agricultural traits such as plant height, tiller number, and fruit size [10]. - The findings provide a theoretical basis and technical pathway for enhancing stem cell activity in crops, which could lead to improved yield and quality in agricultural breeding, aligning with carbon neutrality goals [10].

Core Viewpoint - Coffee consumption is associated with potential health benefits, particularly in reducing biological aging in individuals with severe mental disorders, with a recommended intake of up to 4 cups per day showing the most significant positive effects [2][11]. Group 1: Research Findings - A study published in BMJ Mental Health found that daily consumption of up to 4 cups of coffee is linked to longer telomere length, which corresponds to a biological age reduction of approximately 5 years [2][11]. - The research involved 436 patients with severe mental disorders, including schizophrenia and mood disorders, and measured their telomere lengths in relation to their coffee intake [7][11]. - The relationship between coffee consumption and telomere length displayed a "reverse J-shaped" curve, indicating that moderate consumption is beneficial, while excessive intake (5 cups or more) does not provide additional benefits and may even be harmful [8][9]. Group 2: Mechanisms of Action - Coffee contains various bioactive compounds that exhibit strong antioxidant and anti-inflammatory properties, which may help protect telomeres from oxidative stress and chronic inflammation, common in individuals with severe mental disorders [13]. - Key components in coffee, such as caffeine, may activate telomerase, an enzyme that can repair and extend telomeres, thus contributing to the maintenance of telomere length [13]. Group 3: Implications for Public Health - The study emphasizes the importance of moderation in dietary habits, suggesting that even beneficial foods can have adverse effects when consumed excessively [14]. - It encourages further exploration into how diet and lifestyle factors influence biological aging processes in populations with mental health issues [15].

Core Viewpoint - Caloric restriction (CR) has been shown to improve health and potentially extend lifespan in mammals, with a newly identified mechanism involving tumor-infiltrating neutrophils (TIN) and the IGF-1/HIF-1α/HILPDA signaling axis as a target for cancer treatment [3][5][7]. Group 1: Mechanism of Action - CR alters the proportion and gene expression profile of TIN, indicating their critical role in the anti-tumor effects of CR [4]. - The gene expression changes in TIN due to CR are primarily related to lipid processes, particularly downregulating HILPDA, which reduces lipid accumulation in TIN [4][5]. - The reduction of HILPDA expression limits lipid transfer to tumor cells and immune effector cells, thereby inhibiting tumor growth and enhancing anti-tumor immunity [4][5]. Group 2: Signaling Pathway - CR decreases circulating IGF-1 levels, which in turn reduces HIF-1α mRNA expression in neutrophils, leading to lower HILPDA expression in TIN [4][5]. - Patients with low baseline HIF-1α mRNA levels in neutrophils show better responses to combined immunotherapy [4]. Group 3: Implications for Cancer Treatment - The findings establish a new mechanism centered on neutrophils and lipids that explains the tumor-suppressive effects of CR [7]. - The IGF-1/HIF-1α/HILPDA signaling axis is proposed as a novel target for cancer therapy [7].

撰文丨王聪 编辑丨王多鱼 排版丨水成文 在 结直肠癌 周围的正常癌旁组织中， 结肠上皮细胞 （CEC） 是最丰富的细胞成分之一，然而，其与肿瘤细胞之间的相互作用，目前仍知之甚少。 2025 年 12 月 3 日，复旦大学附属肿瘤医院 赵森林 医师、 上海交通大学医学院附属第一人民医院 严东旺 教授、复旦大学附属肿瘤医院 李大卫 主任医师作为 共同通讯作者 （管 冰杰 、周满堂 、谢博文 、戴卫星 、张静 、 密玉帅 为本文共同第一作者） ，在 Nature 子刊 Nature Aging 上发表了题为： Peritumoral colonic epithelial cell-derived GDF15 sustains colorectal cancer via regulation of glycolysis and histone lactylation 的研究论文。 该研究发现， 癌旁结直肠上皮细胞 高表达 GDF15 以获得 衰老表型 ，通过调控 糖酵解和组蛋白乳酸化修饰， 重塑肠道 促癌生态位 （ pro-carcinogenic niche ） ，维持结直肠癌。 在这项最新研究中，研究团队发现，癌 ...