Core Viewpoint - The research highlights the critical role of GPX4 in preventing ferroptosis, a form of cell death linked to neurodegenerative diseases, emphasizing the importance of its membrane localization alongside its enzymatic activity [2][10]. Group 1: Ferroptosis and GPX4 - Ferroptosis is a newly identified iron-dependent form of cell death characterized by the accumulation of lipid peroxides, distinct from other forms of programmed cell death [1]. - GPX4 is recognized as a key regulator of ferroptosis, primarily known for its enzymatic activity in detoxifying lipid peroxides [5]. - The study identifies a specific mutation in the GPX4 gene (GPX4 R152H) that disrupts its membrane localization, impairing its protective function against ferroptosis despite retaining enzymatic activity [5][8]. Group 2: Implications for Neurodegenerative Diseases - The research provides molecular evidence linking ferroptosis to neurodegenerative diseases, particularly through the study of a rare condition known as Sedaghatian type spondyloepiphyseal dysplasia (SSMD) [2][4]. - In mouse models, the absence of GPX4 or expression of the GPX4 R152H mutation leads to neuronal death and neuroinflammation, mirroring the pathological processes observed in SSMD [7]. - The findings suggest that ferroptosis may also play a significant role in more common neurodegenerative diseases, such as Alzheimer's disease, as similar protein expression patterns were observed in both conditions [7][10]. Group 3: Research Findings and Future Directions - The study establishes that the membrane localization of GPX4 is as crucial as its enzymatic activity for neuroprotection against ferroptosis [10]. - It underscores the potential of targeting ferroptosis as a therapeutic strategy for neurodegenerative diseases, providing a strong theoretical basis for future drug development [10]. - The research chain from genetic mutation to animal models and human cell models reinforces the conclusion that ferroptosis is a key driver of neurodegenerative changes [10].

撰文丨王聪 编辑丨王多鱼 排版丨水成文 运动锻炼 已被公认为预防疾病和促进健康的有效策略，包括对大脑结构和功能有益，能够减缓年龄相关认知能力下降。然而，运动量与健康之间的关系呈" 倒 J 型 "曲线，也就是说，适量运动促进健康，过度运动可能会导致不良后果，例如肌肉疲劳和心血管功能障碍。 值得注意的是，多项临床研究已表明，过度运动与认知能力下降之间存在关联，但其潜在机制在很大程度上仍不为人知。 2025 年 12 月 3 日，中南大学湘雅医院 罗湘杭 / 彭慧 团队在 Cell 子刊 Cell Metabolism 上发表了题为： Excessive vigorous exercise impairs cognitive function through a muscle-derived mitochondrial pretender 的研究论文。 该研究表明， 过度剧烈运动，通过 促进肌肉分泌一种 线粒体来源的囊泡—— otMDV ，损害认知功能 ， 提示了保持适度运动强度对于维持大脑健康至关重要。 过度运动会损害认知功能，但其潜在机制尚不清楚。 在这项最新研究中， 研究团队发现， 过度剧烈运动导致的乳酸堆积 ...

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 Viewpoint - The article discusses a revolutionary advancement in soft robotics through the development of high-performance artificial muscles using a novel dielectric elastomer design, which addresses the limitations of electromechanical sensitivity in existing materials [3][4]. Group 1: Research Findings - The research team introduced a heterogeneous crosslinking-induced phase separation strategy to create a semi-separated biphasic bicontinuous dielectric elastomer with high electromechanical sensitivity [4]. - This unique structure, achieved by manipulating the crosslinking mechanisms of two commercial silicone elastomers (Sylgard 170 and Elastosil P7676), resulted in a material with an electromechanical sensitivity of up to 360 MPa⁻¹ [4]. Group 2: Applications - The developed artificial muscles can achieve high energy density, high power density, and ultra-long service life under low driving electric fields [6]. - The artificial muscles have been successfully applied in large-stroke robotic arms and tetherless soft crawling robots with multimodal motion capabilities, showcasing their powerful performance and multifunctionality [6].

撰文丨王聪 编辑丨王多鱼 酶的从头设计，旨在构建含有理想活性位点的蛋白质，这些位点周围的催化氨基酸残基能够稳定目标化学 反应的过渡态。此前已有研究利用蛋白质从头设计来生成新的 金属水解酶 （ Metallohydrolase ） ， 但这 些酶的活性和效率相对较低， 需要经过大量的定向进化才能达到天然酶的活性和效率水平。 排版丨水成文 David Baker 教授 David Baker 团队之前开发的用于蛋白质从头设计的生成式 AI 工具—— RFdiffusion，可以解决上述难 题，但其需要为每个催化氨基酸残基指定序列位置和主链坐标，这限制了 设计空间范围。 2025 年 12 月 3 日，诺奖得主、蛋白质设计先驱 David Baker 教授团队在国际顶尖学术期刊 Nature 上发 表了题为 ： Computational design of metallohydrolases 的研究论文。 该研究利用新一代 AI 蛋白质设计工具—— RFdiffusion2 ， 成功设计了活性极高的锌金属水解酶，其催化 效率比之前设计的金属水解酶高出上千倍 。更令人惊叹的是，这些高性能酶完全"从头开始"设计，且无 ...

Core Viewpoint - The article discusses the significant role of neuroinflammation in the development and progression of dementia, suggesting that neurotropic viruses, particularly herpes simplex virus, may contribute to or accelerate the course of dementia [1] Group 1: Research Findings - A recent study published in the journal Cell indicates that shingles vaccination can prevent or delay mild cognitive impairment and dementia in the elderly, as well as slow the progression of dementia in diagnosed patients, reducing the risk of dementia-related mortality [2] - The study utilized a natural experiment design based on the UK's vaccination policy, which created a unique opportunity to compare two groups with similar conditions but different vaccination eligibility based on birth dates [5] Group 2: Study Methodology - The research employed a rigorous regression discontinuity design, comparing over 300,000 participants, including more than 280,000 without cognitive impairment and over 14,000 diagnosed with dementia, tracked over nine years [7] - Results showed that vaccination reduced the risk of mild cognitive impairment by 3.1 percentage points in cognitively normal individuals, meaning that for every 100 vaccinated individuals, 3 avoided cognitive decline [7] Group 3: Gender Differences - The protective effect of the shingles vaccine was more pronounced in women, with a 5.1 percentage point reduction in mild cognitive impairment risk and a 52.3 percentage point reduction in dementia-related mortality risk, while the effects in men were not statistically significant [10] Group 4: Mechanisms of Action - The study proposes that the shingles vaccine may protect brain health by reducing the reactivation of the varicella-zoster virus, which can cause neuroinflammation, a key factor in the development of dementia [12] - Additionally, the vaccine may help combat immune aging, maintaining a more youthful immune response that better protects the nervous system [12] Group 5: Implications for Public Health - The study's methodology offers a strong basis for causal inference, suggesting that shingles vaccination could be a cost-effective strategy for preventing or delaying dementia, especially in the context of an aging population [16][18] - The findings highlight the potential for vaccines to provide multiple health benefits beyond immediate infection prevention, opening new perspectives on public health strategies [16]

以下文章来源于赛业生物订阅号 ，作者小赛 赛业生物订阅号 . 分享生命科学领域的前沿资讯、解读行业动态、讲解实用的学科知识、实验方法和技巧。 师姐 你的flox鼠和Cre鼠是同一个品系吗？实验后期很容易出现好几代交配完，才发现背 景不纯、Cre还泄露了的情况。 类似的对话，也许时常出现在你的身边，从课题启动到获得可靠数据，基因敲入模型的构建之路往往布满荆 棘： ❓ 传统ES打靶结合多代育种流程漫长，如何将模型交付周期缩短一半以上？ 如此种种，让宝贵的科研时间在反复验证中悄然流逝。 新一期线上课程 「基因敲入（KI）模型构建策略及应用案例分析」 将深入剖析。 课程时间： 12月9日（周二）晚7点 讲师： 赛业生物生产中心ES部经理李晓亮、生产中心分子部门经理王康 师妹 完蛋，我的敲入小鼠和预期的表型对不上，但我明明是按Protocol做的…… 通过这节课你可以学到什么？ ❓ 如何避免Cre工具鼠的泄露表达、重组效率低等问题对表型数据造成干扰？ ❓ 面对复杂条件性模型，如何在保证高成功率的同时，有效控制项目成本？ 1 KI、CKI模型分别对应的设计逻辑、适用场景及其在基因功能研究中的价值 2 新一代ES打靶技术如 ...

编辑丨王多鱼 排版丨水成文 2018 年 1 月， 孙强 、 刘真 团队 在 Cell 期刊发表论文 【1】 ， 在全世界范围内首次利用体细胞核移植 技术成功培育出了 克隆猴 。 2023 年 11 月， 刘真 、 孙强 团队 在 Cell 期刊 发表论文论文 【2】 ， 在全世界范围内 首次成功构建了 高比例胚胎干细胞贡献的出生存活的 嵌合体猴 ，并证实了猴胚胎干细胞可以高效的贡献到胚外胎盘组织和 生殖细胞，该论文还被选为封面论文。 2025 年 1 月， 刘真 团队等 在 Cell 期刊 发表论文 【3】 ， 该研究绘制 了人类和小鼠 着床前胚胎的深度 蛋白质组景观图谱 ，结合跨物种比较和多组学整合分析， 系统性解读了哺乳动物早期胚胎发育过程 ， 阐 明了人类着床前胚胎发育及失败的机制。 2025 年 12 月 3 日， 中国科学院脑科学与智能技术卓越创新中心 刘真 研究员、 孙强 研究员及西班牙庞 培法布拉大学 Alfonso Martinez-Arias 教授、西北农林科技大学 王小龙 教授合作 （ 李杰 、 李杰 、 曹 静 、 尚申申 为该论文共同第一作者 ） ，在国际顶尖学术期刊 Nature ...

Core Viewpoint - The article discusses the significance of long non-coding RNAs (lncRNAs) in human genetics, emphasizing their essential roles in cancer and development, despite being previously considered non-functional or "junk" DNA [2][4]. Group 1: Research Development - A new CRISPR-Cas13 based screening technology was developed to target RNA at a transcriptome scale, allowing for the identification of 778 essential lncRNAs across five human cell types [4]. - This research indicates that many lncRNAs play crucial roles in human biology, challenging the notion that they are merely non-functional sequences [4]. Group 2: Research Withdrawal - The authors of the study announced the retraction of their paper due to the discovery of unfiltered off-target sequences in their CRISPR library, which could have led to inaccurate results [6][8]. - Following the identification of potential off-targets, the authors conducted a re-analysis of their data and updated their experiments, which resulted in changes to the identified essential lncRNAs [9].

Core Insights - The study demonstrates that large language models (LLMs) can significantly assist physicians in overcoming technical barriers in medical AI research, with project completion rates increasing from 25% to 87% when using LLMs [11][12] - Despite the benefits, the research highlights potential risks associated with LLMs, including the possibility of dependency and the phenomenon of "hallucination" where AI may generate incorrect information [8][12] Study Overview - The research titled "The effectiveness of large language models in medical AI research for physicians: A randomized controlled trial" was published on November 26, 2025, in Cell Reports Medicine [4] - Conducted by a team from Sun Yat-sen University, the study involved a randomized controlled trial with 64 primary ophthalmologists, assessing the effectiveness of LLMs in an "automated cataract identification" project [6][7] Results - The intervention group using ChatGPT-3.5 had a total project completion rate of 87.5%, compared to 25.0% in the control group, and a non-assisted completion rate of 68.7% versus 3.1% [7] - After a washout period, 41.2% of successful intervention participants were able to complete new projects independently without LLM support [7] - Concerns were raised among participants, with 42.6% worried about mindlessly repeating AI-generated information and 40.4% fearing that AI could foster lazy thinking [7] Conclusion - The study concludes that while LLMs can democratize medical AI research and help physicians navigate technical challenges, the long-term risks associated with their use, such as dependency, require further investigation [8][12]