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 - The article discusses the revolutionary impact of Smart Spatial Omics (S2-omics) technology in biomedical research, which optimizes region selection for spatial omics experiments, enhancing molecular analysis while preserving tissue structure [2][19]. Group 1: Challenges in Spatial Omics - Spatial omics platforms like Xenium, Visium HD, and CosMx provide single-cell gene expression data but are costly, with sample costs reaching up to $7,000, and have limited tissue capture areas [6]. - Traditional region selection relies heavily on pathologists' subjective experience, leading to labor-intensive processes and variability in results across different laboratories [6][5]. Group 2: S2-omics Overview - S2-omics utilizes AI models to extract features from H&E stained images, simulating molecular heterogeneity to guide experimental design [8]. - The workflow consists of three steps: 1. Feature extraction from tissue images, segmenting them into 8μm×8μm superpixels to capture cellular morphology and tissue architecture [8]. 2. Automatic selection of regions of interest (ROI) based on a scoring system that balances coverage and diversity, allowing user-defined parameters [8]. 3. Prediction of molecular information for unmeasured areas based on selected regions, providing a comprehensive "virtual preview" of the tissue [9][11]. Group 3: Practical Applications - In a gastric cancer sample experiment, S2-omics selected a region covering 7 key tissue clusters, achieving prediction accuracies of 73.8% for cell types and 72.8% for community labels [13]. - In a colon cancer study, S2-omics covered 89.3% of the cells selected by experts while reducing blank areas, thus capturing critical structures more effectively [14]. - For kidney samples, S2-omics optimized the layout of views, successfully capturing glomeruli structures and enhancing data continuity and interpretability [15]. Group 4: Flexibility and Efficiency - S2-omics allows users to specify "positive priors" (e.g., focusing on tumor clusters) or "negative priors" (e.g., ignoring muscle areas), adjusting selection strategies accordingly [16]. - The system can automatically determine the optimal number of regions needed, as demonstrated in breast cancer samples where it identified two 2mm×2mm regions sufficient for capturing heterogeneity [17]. Group 5: Implications for Research - The introduction of S2-omics marks a significant step towards standardization and reproducibility in spatial omics experiments, reducing costs and subjective bias while empowering subsequent experimental designs through virtual predictions [19].

Core Insights - The research from Harvard University reveals a dual mechanism by which stress leads to hair loss, providing new insights into autoimmune diseases [1] Group 1: Mechanism of Hair Loss - The first mechanism identified is "immediate hair loss," triggered by the sympathetic nervous system's response to stress, resulting in the release of high levels of norepinephrine, which can kill rapidly proliferating cells in hair follicles [1] - The second mechanism involves the destruction of hair follicles by norepinephrine, which leads the body to perceive the damaged tissue as foreign, triggering an immune response that activates CD8+ T cells to attack hair follicles, potentially causing recurrent hair loss with lasting effects [1] Group 2: Implications for Autoimmune Diseases - This discovery is significant for understanding autoimmune diseases, as conditions like type 1 diabetes, lupus, and multiple sclerosis often require external triggers, with stress potentially being one of them [1]

Core Insights - The research team from the Swiss Federal Institute of Technology in Lausanne has developed a new three-dimensional organoid called "Budoid," which exhibits key features of developing limbs, including symmetry breaking and early cartilage formation [1][2] Group 1: Research and Development - The study published in the journal "Science Advances" highlights the importance of chemical signaling between different cell types during the early stages of embryonic development, particularly in limb formation [1] - Previous organoid models focused mainly on mesodermal cells, neglecting the role of the Apical Ectodermal Ridge (AER) and other ectodermal cells in guiding limb formation [2] - The "Budoid" was created using mixed cell populations derived from mouse embryonic stem cells, which naturally formed structures resembling AER, superficial ectoderm, and mesoderm cells, covering all major cell types involved in limb development [2] Group 2: Applications and Implications - "Budoid" provides a novel platform for exploring difficult-to-study areas in embryonic development, such as how cells coordinate behavior, how early structures develop, and how cartilage forms [2] - The implications of this research extend beyond basic science, potentially aiding in congenital disease modeling, testing chemicals that may impair limb development, and advancing regenerative medicine applications [2] - The new stem cell-based approach offers a more ethical alternative to traditional animal experiments in biomedical research, allowing for the reproduction of key embryonic tissue features without the need for large numbers of embryos [3]

撰文丨王聪 编辑丨王多鱼 排版丨水成文 哺乳动物的大脑是一个错综复杂的神经元回路网络，由数十亿个神经元通过数以万亿计的突触相互连接而 成。在这个复杂的结构中，单个神经元在形态、转录身份和功能作用方面表现出显著的异质性。揭开大脑 的组织原则和功能连接性需要具备单细胞分辨率的方法学，以捕捉这种多样性。 基因标记、高分辨率成像和计算分析方面的最新进展，极大地促进了在哺乳动物系统中对整个大脑神经元 形态的重建工作。这些进展为了解介观尺度 （即细胞水平） 的连接性和支撑大脑功能的结构模式提供了关 键见解。然而，要想生成具有单神经元分辨率的全面大规模脑图谱，仍需在 标记准确度和成像效率方面取 得进一步创新。 近日，北京生命科学研究所/清华大学生物医学交叉研究院 林睿 实验室与北京脑科学与类脑研究所 罗敏敏 实验室合作，在 Cell 子刊 Neuron 上发表了题为： Ultrabright Chemical Labeling Enables Rapid Neural Connectivity Profiling in Large Tissue Samples 的研究论文，该论文还被选为当期 封面论文 。 该研究提出了一种 ...

Core Insights - The article discusses a recent study revealing the neuroimmune mechanisms behind social withdrawal during illness, suggesting that this behavior is an active choice driven by specific neurons in the brain rather than a passive response to physical discomfort [2][20]. Group 1: Research Background - Traditional views suggest that social withdrawal during illness is a passive reaction due to discomfort, but evolutionary biologists propose it may serve adaptive purposes, such as preventing disease spread and conserving energy [6]. - The research team from MIT and Harvard Medical School conducted experiments to explore the neural mechanisms underlying this behavior, focusing on cytokines as messengers between the immune and nervous systems [6]. Group 2: Key Molecule - IL-1β - In a large-scale behavioral screening, the study found that among 21 cytokines tested, only IL-1β uniquely induced social withdrawal in mice [8]. - The experimental design allowed mice to explore a runway, showing that those treated with IL-1β exhibited significant social withdrawal compared to normal mice [8]. Group 3: Identifying the "Loneliness Switch" - The study identified that IL-1β's main receptor, IL-1R1, is highly expressed in the dorsal raphe nucleus (DRN), a key source of serotonin neurons that regulate social behavior [12]. - Over 90% of IL-1R1-expressing neurons in the DRN are serotonin neurons, challenging the traditional view that serotonin primarily promotes social behavior [12]. Group 4: Causal Relationship Verification - The research confirmed that activating IL-1R1 neurons led to social withdrawal even without immune challenges, while inhibiting these neurons prevented social withdrawal induced by IL-1β [14][15]. - Gene knockout experiments showed that specifically knocking out IL-1R1 in DRN neurons completely blocked IL-1β-induced social withdrawal without affecting motor suppression [16]. Group 5: Real-World Implications - The study's findings were validated in a natural social environment, where IL-1β-treated mice actively isolated themselves from companions, demonstrating that social withdrawal is a conscious choice during illness [18]. - Both peripheral and central IL-1β contribute to this process, creating a self-reinforcing cycle that prolongs social withdrawal, with microglia playing a crucial role [18]. Group 6: Broader Implications - This research provides insights into the neuroimmune interactions that may help understand social withdrawal in certain mental disorders, such as depression, which often accompanies inflammatory states [20]. - The findings highlight the complexity of the dialogue between the brain and immune system, suggesting that the desire for solitude during illness is a biologically sophisticated self-protection strategy shaped by natural selection [20].

这一技术的核心创新在于将组织中的蛋白质先锚定、再膨胀、再扫描：第一步，锚定蛋白质，即用锚定 试剂将蛋白质锚定在水凝胶网络中，避免蛋白质扩散并去除干扰物质；第二步，使组织线性膨胀3至7倍 且保持结构完整；第三步，给蛋白"拍高清照"，即原位酶解与质谱成像；第四步，通过自主开发的计算 流程解析数据，自动识别组织结构与特异性蛋白。 为验证iPEX的性能与应用价值，研究团队在多种组织、类器官及疾病模型中开展实验。邹贻龙介绍， 在小鼠视网膜研究中，iPEX仅凭蛋白质表达谱就重构出清晰的组织分层，识别出不同细胞层的特异性 蛋白质，这是传统技术无法实现的。此外，研究团队还在小鼠小脑、小鼠肠道、人源脑类器官、小鼠肝 脏组织等样本中展开测试，验证了iPEX的通用性。 "未来，iPEX技术有望在基础研究中助力科学家直接观察蛋白质在精细组织中的分布规律，在临床转化 层面有望为阿尔茨海默病等疾病的早期诊断与治疗提供新路径，为生命科学研究开辟更广阔的视 野。"邹贻龙表示。（记者刘园园，西湖大学供图） 记者11月13日获悉，西湖大学生命科学学院特聘研究员邹贻龙团队与基里尔·皮亚特克维奇（Kiryl D. Piatkevich）团队合作研发 ...

Core Insights - Researchers at Ben-Gurion University of the Negev have discovered a type of immune cell that may help delay aging and provide new approaches for diagnosing and treating age-related diseases [1][2] Group 1: Research Findings - Aging cells in the human body are defined as cells that irreversibly stop dividing due to chromosomal damage under stress, accumulating with age and leading to various age-related diseases [1] - A previously underappreciated subset of CD4 helper T cells accumulates with age, which was initially overlooked by researchers [1] - A study in Japan on centenarians revealed that their immune systems are rich in this subset of helper T cells [1] Group 2: Mechanism and Implications - CD4 helper T cells have the ability to "clean up" aging cells, as confirmed by experiments on mice [1] - Reducing the number of these helper T cells in mice leads to accelerated aging and shorter lifespan, while increasing their numbers helps delay aging [1] - The research suggests that rather than needing an "overactive immune system," a properly functioning immune system aligned with life stages is essential for combating aging [1]

Core Insights - The Changping Laboratory in Beijing, celebrating its 5th anniversary, has gathered top scientists from China, the US, Japan, and Europe to discuss the latest advancements and future trends in "immunology and oncology" for the benefit of global biomedical development and human health [1][2] Group 1: Laboratory's Role and Achievements - The Changping Laboratory is a key national life sciences research institution focused on strategic, forward-looking, and fundamental scientific research, aiming to build a world-class innovation hub in life sciences [2] - Over the past five years, the laboratory has achieved several internationally influential research results [2] - The laboratory provides a broad research platform for young scientists, with ongoing projects utilizing artificial intelligence, big data, and algorithms for antibody drug design [2] Group 2: International Collaboration and Recognition - International experts recognize China's significant emphasis on basic research, which benefits both the nation and global scientific exploration [2] - Clinical research and translational outcomes from China have impressed international scholars, highlighting the potential for direct benefits to patients and improvements in human health [2] - There is a strong desire among international scientists to collaborate with Chinese researchers to explore scientific frontiers together [2][4]

Core Viewpoint - The 5th anniversary of Changping Laboratory highlights its contributions to the field of immunology and oncology, emphasizing the importance of tumor immunotherapy in addressing global health challenges such as aging populations and rising cancer rates [1][2]. Group 1: Scientific Contributions - The laboratory has made significant advancements in cancer treatment, particularly in tumor immunotherapy, positioning China as a key player in the transition to precision immunotherapy [1]. - Notable research achievements include the identification of broad-spectrum neutralizing antibodies, the discovery of tumor memory cells responsive to PD-1 therapy, and the application of stem cell reprogramming in liver disease treatment [3]. Group 2: Collaborative Efforts - The forum featured participation from top scientists from China, the US, Japan, and Europe, fostering international collaboration in life sciences and cancer research [1][2]. - Emphasis was placed on the need for interdisciplinary and cross-national cooperation to enhance basic and applied research in life sciences, leveraging emerging technologies like artificial intelligence and big data [2]. Group 3: Future Directions - Changping Laboratory aims to continue its focus on strategic and foundational scientific research, aspiring to become a world-class center for life science innovation [2]. - The laboratory is encouraged to lead in exploring new ideas and methods for cancer prevention and treatment, contributing significantly to global health initiatives [2][3].