研究团队利用 GerNA-Bind 对癌症相关 长链非编码 RNA MALAT1 进行了构象特异性高通量虚拟筛选， 鉴定出了 18 个具有 亚微摩尔级亲和力 的小分子，其中 结合效果最好的小分子经实验验证， 能够特异性靶向 MALAT1 的三螺旋结构，并在细胞实验中展示出抑制癌细胞迁移的能力。这些发现 突显了 GerNA-Bind 在 RNA 靶向的药物发现中的强大潜力，兼具准确性和生物学洞察力。 RNA 靶向药物的挑战与机遇 撰文丨王聪 编辑丨王多鱼 排版丨水成文 RNA 是生命活动中的关键调控分子，与多种疾病的发生发展密切相关。RNA 靶向的小分子药物代表着调控生物学通路和开发疗法的变革性策略。然而，由于 RNA 的结构复杂性和高分辨率数据的缺乏，发现能够选择性结合特定 RNA 构象的小分子，仍然充满挑战。 在药物研发领域， 蛋白质 一直是最主要的药物靶点。 RNA 分子是生物学过程的重要调控因子，也是多种 疾病的有前景的治疗靶点。然而， 由于 RNA 结构复杂 多变，且高分辨率数据有限， 传统方法难以精准预测小分子药物与 RNA 的相互作用，这严重制约了 RNA 靶向药物的开发，因此，RNA 长期被视为 ...

Core Viewpoint - The article discusses the challenge of iron deficiency in crops grown in alkaline soils and highlights a new research study that reveals a mechanism by which a specific bacterial strain can enhance iron absorption in plants, potentially improving crop yields in such conditions [1][2][9]. Group 1: Iron Deficiency in Agriculture - Approximately 30% of global arable land consists of alkaline soils, which negatively affect crop yield and quality due to poor iron bioavailability [1]. - Iron deficiency is a common micronutrient deficiency affecting over 2 billion people worldwide, leading to health issues such as anemia and impaired cognitive development in children [1]. Group 2: Research Findings - The research published in Cell Reports connects the synthesis of bacterial iron carriers with biofilm formation, demonstrating their synergistic effect on plant iron absorption [2][5]. - The bacterial strain Bacillus subtilis SQR9 significantly enhances crop growth in alkaline soils, with field trials showing an average yield increase of over 10% [2][6][7]. Group 3: Mechanism of Action - The study reveals that the biofilm produced by SQR9 accumulates iron at the plant roots, acting as an iron reservoir [7]. - The iron carrier Bacillibactin not only helps in iron accumulation within the biofilm but also activates the plant's iron uptake mechanisms [6][7]. Group 4: Implications for Agriculture - This research provides insights into microbial biofortification strategies aimed at addressing iron deficiency in crops, emphasizing the importance of root-associated bacteria in enhancing plant nutrition [9].

Core Viewpoint - The study highlights that tolerance to ferroptosis enhances lipid metabolism and pathogenic type 2 immunity in allergic airway inflammation, suggesting a potential therapeutic target for asthma through the modulation of antioxidant systems [1][6]. Group 1: Key Findings - Pathogenic ILC2 in allergic airway inflammation relies on cysteine for metabolic adaptation and survival [3]. - Cysteine uptake promotes the synthesis of glutathione (GSH), which works in conjunction with the upregulation of GPX4 and TXNRD1 to enhance resistance to ferroptosis by combating lipid peroxidation and reactive oxygen species (ROS) [3]. - The adaptive changes accelerate lipid acquisition and metabolism, promoting the expansion of ILC2 and Th2 cells [3]. Group 2: Implications - The study indicates that the antioxidant and ferroptosis resistance pathways enable lipid metabolism in ILC2 and Th2 cells [4]. - GPX4 and TXNRD1 are crucial in promoting pathogenic type 2 immune responses [4]. - The redox balance system represents a targetable metabolic vulnerability in airway inflammation [4].

Core Viewpoint - The article discusses the significant role of respiratory viruses, particularly coronaviruses and influenza viruses, in global pandemics and their impact on public health, emphasizing the importance of understanding immune responses and potential antiviral strategies [1][2]. Group 1: Immune Response and Interferon - The innate immune response, including interferons (IFN) and interferon-stimulated genes (ISG), serves as the first line of defense against viral attacks [2]. - Delayed or impaired type I interferon (IFN-I) responses are notable characteristics of severe COVID-19 and influenza infections, with 3.5% of life-threatening COVID-19 patients exhibiting harmful mutations in interferon system genes [2]. - In critical COVID-19 patients, nearly 15% have been found to possess neutralizing antibodies against their own interferons, indicating a significant immune response issue [2]. Group 2: GALNT2 and Antiviral Mechanism - A recent study published in Nature Microbiology identifies GALNT2 as an ISG with broad antiviral activity, establishing it as a crucial defense factor against respiratory virus infections [3][9]. - GALNT2 inhibits the replication of various coronaviruses and influenza viruses, promoting viral clearance and reducing disease severity through O-glycosylation of viral proteins [6][9]. - The mechanism involves GALNT2 modifying the spike protein of SARS-CoV-2, preventing its cleavage by proteases, thus blocking virus-host cell fusion [6][7]. Group 3: Genetic Insights and Implications - Analysis of human genetic data reveals that individuals with GALNT2 gene mutations that impair antiviral function have a significantly higher risk of hospitalization after SARS-CoV-2 infection [8]. - The findings deepen the understanding of host-virus interactions and provide new targets for developing broad-spectrum antiviral strategies against respiratory pathogens [10].

撰文丨王聪 编辑丨王多鱼 排版丨水成文 近日， 军事医学研究院 的一项新研究登上了 Cell Press 头条。 该论文以： Computational modeling reveals cognitive processes in simple rodent depression tests 为题，于 2025 年 12 月 2 日在线发表于 Cell 子刊 Cell Reports Methods 上， 军事医学研究院 李至涵 为论文第一作者兼共同通讯作者， 李云峰 为论文通讯作者。该 研究通过结合自动化行为追踪和计算建 模，首次系统揭示了简单抑郁行为测试中隐藏的复杂认知过程，为理解抑郁样行为的认知机制提供了新视 角 总的来说，这项研究通过结合自动化行为追踪和计算建模，首次系统揭示了简单抑郁行为测试中隐藏的复 杂认知过程，为理解抑郁样行为的认知机制提供了新视角，并强调了分析完整行为轨迹的重要性。 这些发现挑战了当前对抑郁行为测试的传统理解，为未来开发更精确的动物行为分析方法和抗抑郁治疗策 略提供了重要理论基础。 论文链接 ： https://www.cell.com /cell-reports-metho ...

Core Viewpoint - CAR-T cell therapy shows strong efficacy in hematological cancers and autoimmune diseases, but struggles with solid tumors due to antigen heterogeneity and immunosuppressive tumor microenvironment (TME) [2] Group 1: Research Findings - The study published on December 11, 2025, in Cancer Cell demonstrates that IL-36γ armored CAR-T cells can reprogram neutrophils to induce endogenous antitumor immunity, effectively clearing solid tumors and overcoming key obstacles faced by adoptive cell therapy for solid tumors [2][5] - IL-36γ is a pro-inflammatory cytokine that enhances CAR-T cell persistence and positively modulates the TME, leading to an endogenous antitumor immune response [5] - The research indicates that IL-36γ armored CAR-T cells can eradicate primary solid tumors without prior lymphocyte depletion and can activate cancer immune cycles by reprogramming neutrophils [6][8] Group 2: Mechanism of Action - The reprogrammed neutrophils exhibit tumor-killing capabilities and antigen-presenting functions, which are crucial for recognizing tumor antigens beyond the CAR-targeted antigens [5][6] - The combination of CAR-T cells and neutrophils is identified as a key step in establishing cancer immune cycles, introducing a broadly applicable method to address the challenges of solid tumor therapies [8]

撰文丨王聪 编辑丨王多鱼 排版丨水成文 环境光能够调控诸如摄食等非成像功能， 强光疗法 更是展现出抗肥胖潜力，但其神经基础尚不明确。 核心发现：光感通路的"三级跳" 研究团队发现，明亮光线通过一条名为" 视网膜-vLGN-LHA "的三级神经通路抑制食欲。这条通路如同一 个精密的光控开关： 2025 年 12 月 12 日，暨南大学粤港澳中枢神经再生研究院 黄鲁 研究员、 任超然 研究员 、 陶倩 教授以 及 林嵩 副教授作为共同通讯作者 （ 李文、黄晓丹、吴冀津、胡峥芳为论文共同第一作者 ） 在 Nature Neuroscience 期刊发 表了题为： Bright light exposure suppresses feeding and weight gain via a visual circuit linked to the lateral hypothalamus 研究论文。 该研究 首次揭示了一条从 眼睛到大脑的神经通路，解释了为什么明亮光线能够抑制食欲并控制体重。 该研究阐明了 亮光对摄食和体重增长的抑制作用依赖于" 视网膜 → vLGN → LHA "神经 通路的激活。这 项研究为 饮食障 ...

Core Viewpoint - The article discusses a significant advancement in the field of neuroscience, specifically the successful creation of human sympathetic ganglia organoids (hSGO) from human pluripotent stem cells (hPSC), which can be integrated with human heart organoids (hHFO) to form a human sympathetically innervated heart organoid (hSHO) [1][6]. Group 1: Research Background - The sympathetic ganglia are a crucial component of the peripheral nervous system (PNS) and play an essential role in maintaining homeostasis [4]. - Previous attempts to create organoids representing the peripheral nervous system have been limited, particularly in mimicking the self-organizing development of sympathetic ganglia [5]. Group 2: Research Methodology - The research team utilized directed 3D differentiation techniques from human pluripotent stem cells to develop a method for generating human sympathetic ganglia organoids (hSGO), which exhibit directed and self-organizing sympathetic neuronal differentiation [5]. - The hSGO produced sympathetic neurons and glial cells, demonstrating functional development over long-term culture [5]. Group 3: Key Findings - By fusing hSGO with hHFO, the researchers successfully recreated the functional sympathetic innervation of the human heart, resulting in the formation of hSHO [6]. - The hSHO model allows for the evaluation of factors regulating sympathetic innervation of the heart, such as nerve growth factor signaling, and reveals that inter-tissue interactions influence the development of both sympathetic nerves and the heart [6].

撰文丨王聪 编辑丨王多鱼 排版丨水成文 近日，南京农业大学植物保护学院 顾沁 教授、 高学文 教授、 熊武 教授团队合作 （ 博士研究生 徐钰姣 、 汪志远 为论文第一作者 ） ， 在 Cell 子刊 Cell Host & Microbe 上发表了题为 ： Keystone Pseudomonas species in the wheat phyllosphere microbiome mitigate Fusarium head blight by altering host pH 的研究论文，该研究还被选为当期 封面论文 。 小麦赤霉病 是威胁全球农业生物安全的重大真菌病害，该研究发现， 禾谷镰孢菌 侵染小麦时，会通过诱导寄主碱化来增强自身致病力。与此同时，小麦穗部的 天然微生物群落中潜藏着一类能够"以酸制碱"的守护者—— 寄主酸化型假单胞菌 。这些细菌在赤霉病菌侵入时被招募至麦穗，分泌有机酸降低病原菌诱导的寄主 碱化效应，从而有效抑制赤霉病发展。 这项研究揭示了寄主、病原体与有益微生物间围绕 pH 的精妙博弈，并展示了通过调控寄主微环境实现作物绿色防控的新思路。 该封面图片描绘了小麦穗部的微环境，其中 ...

撰文丨王聪 编辑丨王多鱼 排版丨水成文 性别决定是雄花和雌花形成的基础，在植物育种方面具有特别重要的意义。早在上世纪五十年代，就观察到了 生长素促进雌花产生的现象，这也成为了一直以来 植物生理学领域的 " 未解之谜 " ，此外， 生长素和乙烯是如何协同调控植物单性花发育 的遗传 机制，目前 仍 模糊不清。 2025 年 12 月 11 日，中国农业大学 张小兰 、 周朝阳 团队 （ 韩立杰 博士 为论文第一作者 ） 在国际顶尖学术期刊 Science 上发表题为： ARF3-mediated auxin signaling is essential for sex determination in cucumber 的研究论文。 该研究破解了"生长素促进雌花产生"这一长期谜题，鉴定到其中发挥作用的关键调控因子 CsARF3 （Auxin Response Factor 3） ，阐释了生长素和乙烯在性别 决定上的互惠关系，为植物性别决定的调控网络提供了全新认识 ，也为作物育种和农业生产中的 性别调控提供了精准的分子靶点。 该研究阐明了黄瓜中由激素调控的性别决定机制，鉴定了一个关键基因—— CsARF3 （ Au ...