撰文丨王聪 编辑丨王多鱼 排版丨水成文 在全世界范围内， 结直肠癌 （CRC） 是发病人数第三的癌症 （仅次于肺癌和乳腺癌） ，是死亡人数第二的癌症 （仅次于肺癌） 。约 15% 的结直肠癌患者被 发现存在 微卫星高度不稳定/错配修复缺陷 （MSI-H/dMMR） ，这已被认为是结肠癌的一个独特亚型，具有独特的生物学和临床特征。这些肿瘤表现出高突变 负荷，导致产生大量新抗原和免疫响应性肿瘤微环境，使其特别容易受到免疫治疗的影响。 新辅助治疗 （Neoadjuvant therapy） 是指在手术前进行的系统性治疗 （例如化疗、放疗或免疫治疗） ，目的是缩小肿瘤、降低手术难度、减少术后复发风险， 或提前评估治疗效果。当联合免疫治疗 （例如抗 PD-1 单抗、抗 CTLA-4 单抗） 时，称为 新辅助免疫治疗 （ Neoadjuvant immunotherapy ） ， 其在 MSI- H/dMMR 结肠癌中显示出良好的治疗效果，但 双免疫检查点抑制（ 抗 PD-1 单抗 + 抗 CTLA-4 单抗 ） 是否比抗 PD-1 单抗的单药治疗带来更多益处，目前 仍不清楚。 2025 年 10 月 13 日， 一项来 ...

Core Insights - The article discusses the development of a new framework called DIAL (Dynamically Editable Artificial Loci) that allows for unprecedented precision in controlling transgene expression, addressing a long-standing challenge in synthetic biology [4][5]. Group 1: Gene Expression Control - Small changes in gene expression can lead to significant shifts in cell states, necessitating tools that can precisely regulate expression levels [7]. - DIAL utilizes a synthetic zinc finger transcription factor whose activity increases as spacer sequences are removed, allowing for fine-tuned control of transgene expression [7][9]. - The framework introduces a modular and scalable approach to constructing editable promoters, setting new standards for transcriptional controllability [7][9]. Group 2: Applications and Benefits - DIAL enables user-guided, time-defined transgene expression control, which is crucial for applications requiring staged developmental signals or gradual activation of therapeutic genes [9][10]. - The technology is compatible with lentiviral delivery systems, demonstrating its versatility in generating various expression levels in primary cells and induced pluripotent stem cells (iPSCs) [9][10]. - One of DIAL's most attractive features is its ability to produce stable and heritable expression states, facilitating long-term lineage tracing and phenotypic mapping [10]. Group 3: Implications for Research and Medicine - The ability to finely tune gene dosage is expected to significantly enhance cell fate engineering strategies, potentially improving regenerative medicine approaches for neurodegenerative diseases [10]. - DIAL aims to increase the precision and predictability of synthetic gene circuits, which is critical for the safety and efficacy of gene therapy applications [10].

Core Insights - Tumor-infiltrating bacteria, particularly Fusobacterium nucleatum, are increasingly recognized as key components of the tumor microenvironment (TME) and are linked to cancer recurrence and treatment resistance [2][5] - The recent study published in Cancer Cell highlights a new mechanism by which these bacteria disrupt interactions between cancer epithelial cells and induce cell-cycle arrest, leading to resistance against chemotherapy drug 5-fluorouracil (5-FU) [3][10] Summary by Sections Tumor-Infiltrating Bacteria and Cancer - Tumor-infiltrating bacteria, especially in mucosal sites, are being viewed as critical elements of TME [2] - Specific bacteria have been associated with cancer progression and poor prognosis, such as the enrichment of Fusobacterium nucleatum in colorectal cancer (CRC) tissues [2] Mechanism of Action - The study describes how extracellular bacteria, including Fusobacterium nucleatum, regulate the behavior of cancer epithelial cells [6] - These bacteria are primarily found in the extracellular regions of the TME in colorectal and oral cancers, where cell density, transcriptional activity, and proliferation are reduced [6] Experimental Findings - In vitro experiments show that Fusobacterium nucleatum disrupts epithelial cell contact, causing cells to enter a G0-G1 phase and inhibiting transcriptional activity [6] - This state confers resistance to the chemotherapy drug 5-FU and remodels the tumor microenvironment [6] - The findings were validated through live-cell imaging, spatial analysis, mouse models, and a cohort of 52 colorectal cancer patients [6] Clinical Implications - High loads of Fusobacterium nucleatum in tumors correlate with reduced treatment response [8] - The study emphasizes the potential of targeting microbial-tumor interactions as a therapeutic strategy [10]

撰文丨王聪 编辑丨王多鱼 排版丨水成文 环境、社会和遗传因素促使人们暴饮暴食并减少身体运动，从而导致体重增加。随着时间的推移，体重增加通常与高血压、血脂异常和心血管疾病的发展有关。 肥胖相关的血脂异常的特征是血清甘油三酯 （TG） 水平升高、低密度脂蛋白 （LDL） 胆固醇水平升高以及高密度脂蛋白 （HDL） 胆固醇水平低，这种血脂谱 型具有促动脉粥样硬化作用。然而，肥胖导致血脂水平变化的机制尚不清楚。 2025 年 10 月 16 日，剑桥大学的研究人员在国际顶尖医学期刊 Nature Medicine 上发表了题为： Obesity due to MC4R deficiency is associated with reduced cholesterol, triglycerides and cardiovascular disease risk 的研究论文。 肥胖 通常与 低密度脂蛋白 胆固醇 水平升高以及 心血管疾病 风险增加有关。而这项研究带来一项矛盾的发现——携带 MC4R 基因突变的人会 严重肥胖 ，但他 们 低密度脂蛋白胆固醇 水平较低，且 心脏病 患病风险也低于体重指数 （BMI） 相似的同 ...

撰文丨王聪 编辑丨王多鱼 排版丨水成文 人工智能 （AI） 和 机器人 在向精准农业转型方面提供了巨大机遇，有助于提高农作物产量、降低成本并 促进可持续发展。然而，许多农作物的特性阻碍了基于人工智能的机器人技术的应用 。其中 一个瓶颈在于 花朵形态，其柱头凹陷，这妨碍了杂交育种过程的去雄和授粉。 2025 年 10 月 16 日，一项来自中国团队的研究登上了最新一期的 Cell 期刊的封面。该论文题为： Engineering crop flower morphology facilitates robotization of cross-pollination and speed breeding ， 中国科学院遗传与发育生物学研究所 许操 研究员为论文通讯作者 ， 中国科学院遗传与发育生物学研究 该研究将 生物技术 + 人工智能 （ BT + AI ） 深度融合，首次提出 作物-机器人协同设计 （Crop-robot co-design） 理念，通过基因编辑重新设计作物花型，快速精准创制"机器人友好"的结构型雄性不育系， 运用深度学习和人工智能成功研制 世界首台可自动巡航杂交授粉的智能育种机器人 ——" ...

Core Viewpoint - The article discusses the potential of Budigalimab, an anti-PD-1 monoclonal antibody developed by AbbVie, as a treatment for HIV infection, highlighting its safety and efficacy in a Phase 1b clinical trial, which may lead to a paradigm shift in HIV treatment by enabling "ART-free" control of the virus [2][3][8]. Group 1: Background on HIV and Current Treatments - Approximately 40 million people worldwide are infected with HIV, making it a significant public health threat [2]. - Antiretroviral therapy (ART) is the standard treatment that suppresses HIV replication but does not cure the infection, requiring daily medication which poses adherence challenges [2]. Group 2: Budigalimab Clinical Trial Overview - Budigalimab is a humanized anti-PD-1 monoclonal antibody designed to reverse immune exhaustion in chronic HIV-1 infection [6]. - The Phase 1b clinical trial involved 41 HIV-infected participants, assessing safety, tolerability, and pharmacokinetics through multiple low-dose intravenous injections [6][7]. Group 3: Trial Results and Efficacy - The trial demonstrated good tolerability of Budigalimab, with 29 out of 41 participants experiencing adverse events, mostly mild and unrelated to the treatment [7]. - In a 12-week exploratory efficacy analysis, 6 out of 11 participants showed delayed HIV viral rebound after treatment interruption, indicating potential for sustained viral control without ART [7][8]. Group 4: Implications for Future Research - The successful outcomes of the Phase 1b trial support further Phase 2 clinical trials, aiming to explore the feasibility of "ART-free" HIV control through immune modulation [8].

撰文丨王聪 编辑丨王多鱼 排版丨水成文 近日，哈尔滨医科大学附属第一医院、 扬州大学附属医院 、 佳木斯大学附属第一医院等单位合作的 一篇研究论文登上了 登上了 Cell Press 官网头条。 该论文以： Multi-omic underpinnings of heterogeneous aging across multiple organ systems （ 多组学视角下多器官系统异质性衰老的基础 ） 为题，于 2025 年 10 月 2 日发表在 Cell 子刊 Cell Genomics 上， 哈尔滨医科大学附属第一医院 涂应锋 主任医师、 扬州大学附属医院 Li Zhaoyue 博士为共同通讯作 者， 哈尔滨医科大学附属第一医院 熊杰 医生为论文第一作者。 鉴于延缓生物学衰老具有巨大的临床潜力，阐明介导表观遗传衰老和器官特异性衰老的相互作用网络，以及确定能够调控这些异质性衰老过程的分子靶点，将极 大地促进年龄相关疾病管理策略从" 分而治之 "向" 合而防之 "的范式转变。 衰老 （Aging） 是一种复杂的生物学过程，其特征是身体各系统和器官逐渐退化，是大多数常见慢性疾病和死亡的主要决定因素。从历 ...

Core Viewpoint - The study published in Nature Biomedical Engineering highlights the role of LARP4 in regulating the quiescence exit of naive CD4+ T cells, suggesting that inhibiting LARP4 could improve autoimmune and allergic diseases [2][3][6]. Group 1: Research Findings - Naive T cells are in a resting state and exit this state upon antigen stimulation, with LARP4 identified as a critical regulatory factor for this process [6]. - Conditional knockout of LARP4 in naive CD4+ T cells enhances their resting state and impedes quiescence exit, affecting the stability of several mRNAs crucial for T cell activation [6]. - The differentiation of naive CD4+ T cells into helper T cell subsets is impaired following LARP4 knockout, leading to improvements in autoimmune and allergic responses [6][8]. Group 2: Therapeutic Implications - The research team developed a LARP4 peptide inhibitor, LIPEP, which mimics the effects of LARP4 deficiency and alleviates the severity of autoimmune diseases and allergies in mouse models [6][8]. - The findings establish a link between RNA stability and the homeostasis/adaptive activation of CD4+ T cells, indicating that LARP4 could be a new target for preventing and treating autoimmune and allergic diseases [8].

随着干旱持续时间延长且强度加大，预计对陆地初级生产力的影响将逐渐加剧。然而，一些生态系统似乎能够适应多年干旱，其生产力的下降幅度在干旱 持续时间增加时保持不变或逐渐减小。 编辑丨王多鱼 排版丨水成文 气候变化正使全球许多地区遭遇更严重、持续时间更长的干旱。一些生态系统对日益加剧的干旱表现出了一定的适应能力，但随着干旱程度的加重， 这种情况可能会发生变化。 2025 年 10 月 17 日，北京林业大学 庾强 教授团队联合全球 28 个国家 126 家单位的 177 位科研人员，在国际顶尖学术期刊 Science 发表了题为： Drought intensity and duration interact to magnify losses in primary productivity （ 干旱强度和持续时间互作加剧初级生产力的损失 ） 的研究论文。 该研究发现，随着干旱强度增加和持续时间延长，草原和灌丛生态系统会从逐步适应转向生产力急速衰退。 论文链接 ： https://www.science.org/doi/10.1126/science.ads8144 https://www.nature.com/a ...

大脑功能的实现，依赖于神经元之间高效而精准的 突触传递 。当动作电位到达突触前终端时，突触囊泡释 放神经递质实现信号的跨神经元传递。 20 世纪 50 年代，伯纳德·卡茨 （Bernard Katz） 提出了突触传递过程中神经递质的 量子化释放 假说，奠 定了神经信息传递的细胞机制基础。至 1970 年代初，学界逐渐形成两种对立的突触囊泡释放模型： 全融 合 （Full-collapse） 和 亲吻-逃逸 （Kiss-and-run） 。 然而，由于囊泡释放过程发生在毫秒时间尺度、结构变化处于纳米空间尺度，技术手段的局限，使得关于这 两种模型的争议长期悬而未决，成为困扰神经科学领域半个世纪的难题。 2025 年 10 月 17 日，中国科学技术大学 /中国科学院深圳先进技术研究院 脑认知与脑疾病研究所/深港脑 科学创新研究院 毕国强 、 刘北明 、 陶长路 团队，联合加州大学洛杉矶分校 周正洪 团队，在国际顶尖学 术期刊 Science 上发表了题为： "Kiss-shrink-run" unifies mechanisms for synaptic vesicle exocytosis and hyperf ...