RNA 病毒 是一种极其简单但高效的生命形式。在生命周期中，RNA 病毒利用有限的基因组，编码几个到 十几个蛋白质，即可完成高效扩增，这要求病毒基因组必须能够高效的循环使用。同时，转录形成的新生 RNA 5' 端带有三磷酸基团，一旦释放到宿主细胞中，会迅速激活宿主细胞的先天免疫反应，因此必须立即 对其 5' 端的三磷酸基团进行加工，形成 " 帽 " （Cap） 结构，从而逃逸宿主天然免疫的攻击。 虽然基因组的高效重复使用、RNA 加帽是 RNA 病毒生命过程中最核心、最基础的生物学事件，但自 1 00 多年前发现第一种 RNA 病毒至今，这两个过程协同发生的机制一直是病毒学领域的关键未解之谜。 2025 年 10 月 22 日 ，清华大学 娄智勇 教授 / 饶子和 院士、 中国医学科学院 北京协和医院 朱兰 教授 团队 与广州国家实验室、南开大学等单位合作，在国际顶尖学术期刊 Cell 上发表了题为： Structural basis for the concurrence of template recycling and RNA capping in SARS-CoV-2 的研究论文。 编辑丨王多鱼 排版 ...

该研究表明，二烯酸类似物 326E 通过同时作用于 ACLY 和 PPARα 缓解 代谢功能障碍相关脂肪性肝炎 （MASH） ，并在人体临床试验中证实了其耐受性和治 疗潜力。 该研究发现，正在针对 高胆固醇血症 开展 2a 期临床试验的二烯酸 ATP 柠檬酸裂合酶 （ACLY） 抑制剂—— 326E ，能显著减少小鼠模型中 MASH 的肝脏脂 质堆积，并缓解 MASH 症状。 撰文丨王聪 编辑丨王多鱼 排版丨水成文 代谢功能障碍相关脂肪性肝病 （MASLD） 及其进展形式—— 代谢功能障碍相关脂肪性肝炎 （MASH） ，已成为日益严重的公共卫生负担，且治疗选择有限。 MASH 患病率的上升，在很大程度上归因于 脂质代谢失调 。 2025 年 10 月 22 日，中国科学院上海药物所 李静雅 研究员 、 南发俊 研究员、吉林大学白求恩第一医院 丁艳华 等，在 Cell 子刊 Cell Metabolism 上发表 了 题为： The enedioic acid analog 326E alleviates metabolic dysfunction-associated steatohepatitis via ...

撰文丨王聪 编辑丨王多鱼 排版丨水成文 细胞疗法 为 肝病 的治疗提供了一种很有前景的方法，并且已在临床中得到验证。然而，获取足够数量的 安全且功能正常的肝细胞，是通过细胞移植治疗肝衰竭或遗传性肝功能障碍的主要难题。 如今，人类功能性肝细胞可通过多种途径获得：1）从新鲜供体肝脏组织中分离；2）由人类胚胎干细胞 （hESC） 或人类诱导多能干细胞 （hiPSC） 分化而来；3）由成纤维细胞或其他体细胞重编程而来。对 于临床应用而言，这些细胞来源仍存在着或多或少的挑战 。 制造出足够数量的高质量肝细胞，对于肝病治 疗和药物筛选来说，具有重大意义。 近日，海军军医大学基础医学院 王敏君 、 高俊灵 、 陈费 及上海交通大学医学院附属瑞金医院 宋少华 等，在 Cell Press 旗下期刊 Trends in Biotechnology 上发表了题为： Large-scale manufacturing of human gallbladder epithelial cell products and derived hepatocytes via a chemically defined approach 的研究论 ...

Core Viewpoint - The article discusses a novel approach to overcoming tumor resistance to traditional therapies through a CRISPR-based nano-vaccine (AVAX) that targets the HO-1 gene, enhancing the efficacy of photodynamic therapy and activating anti-tumor immunity [3][4]. Group 1: Research Findings - The study published in Nature Biomedical Engineering presents a CRISPR-Cas9 based nano-vaccine (AVAX) that effectively knocks out the HO-1 gene, reversing tumor cell resistance to reactive oxygen species (ROS) and significantly improving photodynamic therapy outcomes [3][4]. - AVAX demonstrated a 20.15% gene editing efficiency for HO-1 in B16F10 melanoma and LL/2 lung cancer models, leading to enhanced photodynamic therapy efficacy and the induction of an autologous vaccine effect [6][8]. - The combination of AVAX and photodynamic therapy achieved a tumor suppression rate of 93%, with edited ROS-sensitive phenotypes being heritable in progeny tumor cells [8]. Group 2: Mechanism and Efficacy - The AVAX platform utilizes a core-shell self-assembly structure for efficient delivery of the CRISPR-Cas9 system, targeting the ROS resistance gene HO-1 [6]. - When combined with PD-L1 antibodies, 50% of tumor-bearing mice exhibited complete tumor regression, with survival extending beyond 50 days [8]. - The treatment led to a significant increase in CD8 T and CD4 T cell infiltration in tumors, while reducing immunosuppressive myeloid cells [9]. Group 3: Safety and Implications - Safety assessments indicated that the nano-vaccine did not exhibit significant toxicity to major organs, and no off-target editing was detected in immune cells [9]. - This research integrates gene editing with immune activation, achieving a strategy of "enhanced sensitivity and reversal of resistance" in tumor treatment [9].

Core Viewpoint - Baichuan Intelligent has launched the Baichuan-M2 Plus, an evidence-enhanced medical large model, which significantly reduces the hallucination rate compared to general models, achieving credibility comparable to experienced clinical doctors [3][15]. Group 1: Product Launch and Features - Baichuan-M2 Plus is an upgrade from the previously open-sourced Baichuan-M2, featuring a significant reduction in hallucination rates, outperforming both DeepSeek and OpenEvidence [3][4]. - The model introduces a six-source evidence reasoning (EAR) paradigm, making it suitable for clinical decision support in various healthcare environments, including China, the US, Japan, and the UK [4][22]. - The model's architecture is designed to ensure that it only uses authoritative medical evidence, avoiding non-professional information from the internet [6][9]. Group 2: Evidence Framework - The six-source evidence framework consists of layers that evolve from original research to real-world feedback, ensuring a comprehensive knowledge system [5][8]. - The layers include original research, evidence reviews, guidelines, practical knowledge, public health education, and regulatory information, creating a robust evidence chain [8][9]. Group 3: Retrieval and Reasoning Mechanisms - M2 Plus employs a PICO framework for structured medical queries, enhancing the precision of evidence retrieval [11][12]. - The model incorporates a "evidence-enhanced training" mechanism that prioritizes citation over speculation, fundamentally changing its response logic [13][15]. - The model's ability to evaluate evidence quality ensures that it prioritizes high-trust information, embedding it seamlessly into its reasoning process [13][15]. Group 4: Performance Metrics - M2 Plus achieved a score of 97 in the USMLE, surpassing the average human score and matching GPT-5, demonstrating its clinical problem-solving capabilities [19][21]. - In the Chinese medical licensing exam, M2 Plus scored 568, significantly higher than the average passing score, showcasing its mastery of clinical guidelines and practices [21]. - The model also performed well in various international medical qualification exams, achieving over 85% accuracy [20][21]. Group 5: Market Position and Applications - Baichuan-M2 Plus is positioned as a "doctor's version of ChatGPT," enhancing the usability of AI in serious medical scenarios [22][23]. - The model is integrated into the Baixiao app, providing a tool for doctors to counteract the challenges posed by general models like DeepSeek [23][24]. - The company aims to continuously improve the applicability of AI in real clinical settings through open-source initiatives and API offerings [24].

Core Insights - Lung cancer is the most prevalent cancer globally, with 2.48 million new cases and 1.8 million deaths annually, primarily due to non-small cell lung cancer (NSCLC) which accounts for over 85% of cases [2] - The recent study published by a team from Sun Yat-sen University identifies LIC1 as a new therapeutic target for NSCLC and highlights the potential of DAA as an autophagy-inducing agent for treatment [3][7] Group 1: Research Findings - The research isolated a small molecule, DAA, from endophytic fungi of Euphorbiaceae plants, which effectively induces autophagic cell death in NSCLC cells [3][5] - DAA shows significant anti-tumor efficacy in NSCLC and enhances sensitivity to anti-PD-1 immunotherapy while exhibiting low toxicity to normal lung fibroblasts [5] - LIC1 was identified as the direct target of DAA, which is overexpressed in NSCLC tumors and associated with poor prognosis [5] Group 2: Mechanism of Action - DAA disrupts the interaction between LIC1 and the stress response effector RuvBL1, enhancing the integrated stress response mediated by the GCN2-eIF2α-ATF4 signaling axis, ultimately promoting autophagic cell death [5]

编译丨王聪 编辑丨王多鱼 排版丨水成文 当 清华大学 今年的新生打开录取通知书时，迎接他们的第一位"校园代表"并非真人，而是一个 人工智能 助手 ，这个 AI 智能体被设计用于解答关于课程、社团和校园生活的各种问题。 与此同时，美国俄亥俄州立大学将 AI 课程设为必修课，确保所有毕业生具备"AI 素养"；而悉尼大学则采取 传统线下考试方式，以验证学生真正掌握了知识而非依赖 AI 完成学习任务。 2025 年 10 月 21 日，国际顶尖学术期刊 Nature 在其官网 头条发表了一年题为： Universities are embracing AI: will students get smarter or stop thinking? 的文章，当大学开始拥抱 AI，大学生们会在 AI 的帮助下变得更聪明，还是开始变得停止思考？ 校园 AI 浪潮，学生已成"重度用户" 根据 2024 年的一项全球调查，86% 的大学生在学业中经常使用 AI。一些调查显示这一比例甚至更高。 科学类专业的学生似乎是 AI 的重度使用者。AI 公司 Anthropic 对大学生与其 AI 工具 Claude 的 100 万次 匿名 ...

撰文丨王聪 编辑丨王多鱼 排版丨水成文 搞笑诺贝尔奖 （Ig Nobel Prize ） 旨在表彰那些 " 先让人发笑，然后引人深思 "的科学研究。 2024 年 10 月 29 日， 搞笑诺贝尔生理学奖 （Ig Nobel Prize in Physiology） 授予了一项神奇的研究——来自东京理科大学的 武部贵则 （Takanori Takebe） 发现 ，包括小鼠、大鼠和猪在内的哺乳动物可以绕过呼吸系统、通过肛门呼吸。 一年后的 2025 年 10 月 20 日，该团队进行了 首次人体试验，验证了这种肛门呼吸方式在人类中的安全性、耐受性和可行性。 武部贵则 （左一）团队获得 2024 年搞笑诺贝尔生理学奖 这项研究始于新冠疫情期间，当时疫情导致呼吸机严重短缺，从而危及患者生命。 泥鳅 等水生生物进化出了一种独特的肠道呼吸机制，从而得以在长期缺氧的环境中生存。受此启发， 武部贵则 在哺乳动物中验证了 经肛门肠内通气 （EVA） 技 术，该研究以 ： Mammalian enteral ventilation ameliorates respiratory failure 为题，于 2021 年 6 月 ...

Core Viewpoint - The research reveals a novel metabolic interaction between tumor-associated macrophages (TAM) and hepatocellular carcinoma (HCC) cells, identifying TAM as a source of acetate that drives HCC metastasis through the synthesis of acetyl-CoA [2][3][4]. Group 1: Research Findings - TAM secretes acetate, which is then taken up by HCC cells to support their acetate accumulation [3]. - Lactate produced by HCC cells activates lipid peroxidation-ALDH2 pathways in TAM, promoting the secretion of acetate [3]. - In a mouse model of HCC, knocking out the ALDH2 gene in TAM reduces acetate levels in HCC cells and decreases lung metastasis of HCC [3][4]. Group 2: Implications - The study positions TAM as a critical acetate supply source that drives HCC metastasis, suggesting potential intervention targets in the tumor microenvironment [2][4].

撰文丨王聪 编辑丨王多鱼 排版丨水成文 FSTL1 是一种调节外周组织能量代谢的信号分子，也在大脑中表达。然而，下丘脑 FSTL1 是否调节碳水化合物/脂质代谢和能量平衡尚不清楚。 卵泡抑素样蛋白-1 （FSTL1） 是一种参与炎症和组织稳态的分泌因子，最近还被发现与代谢疾病有关。在代谢应激或运动条件下，血清 FSTL1 被认为主要来源 于骨骼肌和脂肪组织。已有报道显示，2 型糖尿病患者的血清 FSTL1 水平升高。 有趣的是，虽然 FSTL1 水平在轻度肥胖时似乎会增加，但在重度肥胖时则会降低。这种模式表明，FSTL1 可能在调节胰岛素抵抗和肥胖方面发挥潜在作用。然 而，FSTL1 是否以及如何在肥胖发展中发挥作用，目前仍不清楚。 2025 年 10 月 21 日，重庆医科大学 杨梦柳 副研究员、 李伶 教授、 杨刚毅 教授及 陆军军医大学第一附属医院（西南医院） 李旻典 教授等，在 Cell 子刊 Neuron 上发表了题为： Reversal of diet-induced obesity by central insulin sensitizer FSTL1 的研究论文。 这项研究表明，下丘脑 FST ...