Core Viewpoint - The study of Maria Branyas Morera, the world's oldest verified living person, provides insights into aging and longevity, highlighting the potential for distinguishing molecular changes due to aging from those related to health conditions [2][4][6]. Group 1: Research Findings - The research team conducted a high-throughput multi-omics study on Maria Branyas Morera, analyzing her genome, transcriptome, metabolome, proteome, microbiome, and epigenome, with results to be published in Cell Reports Medicine [2][11]. - One major finding is the ability to differentiate molecular changes due to aging from those caused by poor health, as evidenced by her unusually short telomeres without associated age-related diseases [6][11]. - Genetic analysis revealed she possesses mutations that are known to prevent cardiovascular diseases, cognitive decline, and diabetes, while lacking mutations linked to increased risks of certain diseases like Alzheimer's [6][11]. Group 2: Health and Lifestyle Factors - Maria Branyas Morera's blood tests showed low levels of "bad" cholesterol and high levels of "good" cholesterol, indicating efficient lipid metabolism and a strong immune system with low inflammation markers [7]. - Her gut microbiome was found to be similar to that of much younger individuals, with a high abundance of beneficial bacteria, potentially linked to her diet of three servings of yogurt daily [7][8]. - Lifestyle factors such as adherence to a Mediterranean diet and regular exercise may also contribute to her longevity [8].

Core Viewpoint - David Baker's team has developed a groundbreaking AI protein design model, RFdiffusion, which allows for the precise control of protein-protein interactions, potentially revolutionizing fields such as cancer treatment and immune regulation [2][3]. Group 1: Research Breakthroughs - The new design method enables precise timing of cytokine signaling, allowing for "remote control" of protein interactions with second-level accuracy [3]. - The research focuses on designing the "excited state" of proteins, which influences the kinetics of protein-protein interactions, rather than just their stable states [7]. - A special "hinge protein" was designed to change conformation in response to external signaling molecules, facilitating rapid dissociation of protein complexes [10]. Group 2: Performance Metrics - The new design method achieves up to a 5700-fold increase in dissociation rates, allowing protein complexes that previously took hours to dissociate to do so in seconds [12]. - Structural analysis confirmed that the designed proteins closely matched theoretical predictions, with a maximum deviation of only 1.3Å [12]. Group 3: Applications - The technology has potential applications in developing rapid biosensors, such as a SARS-CoV-2 sensor with a response time of just 30 seconds, which is 70 times faster than previous sensors [14]. - It can create dynamic control circuits at the protein level, enabling efficient signal transmission and amplification [15]. - The method allows for the rapid shutdown of highly active splitting enzyme systems, providing new tools for metabolic engineering [16]. Group 4: Immunology Insights - The research has significant implications for controlling the interleukin-2 (IL-2) signaling pathway, which is crucial for immune response, allowing for rapid on/off switching of IL-2 analogs [18]. - Different durations of IL-2 stimulation were found to have distinct biological effects, with short stimulation providing anti-apoptotic protection while prolonged stimulation activated metabolic changes and cell division [19][20]. Group 5: Paradigm Shift in Protein Design - This research represents a paradigm shift in protein design, moving from static structure design to dynamic kinetic control, with broad applicability across various protein interactions [22]. - The technology not only serves as a powerful tool for basic biological research but also opens new avenues for therapeutic applications, potentially leading to more precise and controllable biotherapies [22].

Core Viewpoint - The research highlights that Alzheimer's disease (AD) is not solely characterized by the accumulation of amyloid-beta (Aβ) plaques and tau tangles, but also involves a disruption in communication between neurons and glial cells, particularly astrocytes and microglia, which is crucial for disease progression [2][3][5]. Group 1: Research Findings - The study published in Cell provides a comprehensive view of how brain cells interact in Alzheimer's patients, revealing that the disruption of information exchange between neurons and glial cells is closely related to the development of AD [3][5]. - A protein named AHNAK has been identified as a key driver protein in the disrupted protein networks associated with Alzheimer's disease, suggesting a new avenue for innovative treatment strategies [3][9]. - The research team conducted deep proteomic analysis on the parahippocampal gyrus (PHG) of 198 deceased Alzheimer's patients, mild cognitive impairment (MCI) patients, and normal controls to understand molecular dysregulation in AD [6][7]. Group 2: Key Protein Networks - The analysis revealed over 300 key driver proteins (KDPs) that play significant roles in triggering or accelerating Alzheimer's disease, with AHNAK being one of the most prominent proteins found in astrocytes [8][11]. - The study indicates that in Alzheimer's disease, the balance between neurons and glial cells is disrupted, leading to hyperactivity of glial cells and diminished neuronal function, which correlates with increased inflammation [8][11]. - Different biological factors, such as sex and genetic background, can influence the expression of these protein networks, with carriers of the APOE4 gene showing distinct patterns of protein network disruption compared to non-carriers [11].

Core Viewpoint - A novel gene therapy has shown significant potential in slowing the progression of Huntington's disease, marking a possible breakthrough in treatment options for this rare genetic neurodegenerative disorder [4][5]. Group 1: Disease Overview - Huntington's disease is a rare hereditary neurodegenerative disorder characterized by the gradual degeneration of nerve cells in the brain, leading to motor, cognitive, and psychiatric impairments [3]. - The disease is caused by an expansion of the CAG repeat sequence in the HTT gene, resulting in a toxic protein that progressively damages the brain [5]. - Patients typically begin to exhibit symptoms between the ages of 35 and 55, with initial symptoms including mild coordination loss and memory issues, which can escalate to involuntary movements and severe emotional disturbances [4]. Group 2: Gene Therapy Development - The gene therapy developed by uniQure, known as AMT-130, utilizes adeno-associated virus type 5 (AAV5) to deliver miRNA designed to silence the mutated HTT gene, thereby blocking the production of the toxic protein [6][8]. - In a clinical trial involving 29 early-stage Huntington's disease patients, those receiving the high-dose gene therapy experienced a 75% reduction in disease progression over three years compared to the control group [4]. - uniQure plans to apply for regulatory approval for this therapy next year based on significant clinical indicators, including reduced levels of toxic proteins in the cerebrospinal fluid of treated patients [4][6]. Group 3: Future Research Directions - CRISPR gene editing technology shows promise for potentially providing a permanent cure by targeting and editing the mutated HTT gene [9]. - Recent studies have developed new gene editing delivery tools, such as RIDE, which successfully knocked out CAG repeat sequences in mouse models, leading to a reduction in toxic protein expression and improvement in disease symptoms [10]. - Base editing techniques have also demonstrated potential in interrupting repeat expansions associated with Huntington's disease, offering new strategies for treatment [12].

Core Viewpoint - The research highlights the identification of two distinct subtypes of antigen-presenting cancer-associated fibroblasts (apCAF) that play significant roles in tumor progression and metastasis, emphasizing the complexity of the tumor microenvironment and the potential for targeted therapies [4][8]. Group 1: Identification of apCAF Subtypes - The study identifies two different subtypes of apCAF: mesothelial apCAF (M-apCAF) and fibroblast-like apCAF (F-apCAF) [6][10]. - M-apCAF is located near cancer cells, while F-apCAF is associated with lymphocyte-rich niches [7][10]. - Both apCAF subtypes express high levels of SPP1, which contributes to tumor progression and metastasis [8][10]. Group 2: Research Methodology and Findings - The research utilized single-cell resolution spatial analysis to characterize the spatial niches of the two apCAF subtypes [4][7]. - A comprehensive molecular atlas of fibroblasts across 15 tissue types and solid tumors was constructed to understand the origin and function of apCAF [6][10]. - The findings significantly advance the understanding of apCAF, suggesting future studies should incorporate genetic lineage tracing tools to clarify the developmental trajectories of these subtypes [10].

近日，首都医科大学宣武医院 郝峻巍 教授团队 在 Nature 子刊 Nature Metabolism 上发表了题为： Cholesterol metabolic reprogramming mediates microglia-induced chronic neuroinflammation and hinders neurorestoration following stroke 的研究论文。 该研究表明， 胆固醇代谢重编程 介导了小胶质细胞诱导的慢性神经炎症，并阻碍中风后的神经修复 。这一发现 为通过靶向胆固醇代谢来减轻长期脑损伤和促进 神经修复提供了新的治疗策略，有望改善中风相关的残疾结局。 撰文丨王聪 编辑丨王多鱼 排版丨水成文 大多数缺血性中风患者未能接受重组组织型纤溶酶原激活剂的溶栓治疗，原因是其治疗时间窗狭窄，仅限于发病后 4.5 小时内。相比之下，在慢性期可能存在更 宽的治疗时间窗，这为促进晚期恢复、减少中风相关残疾和复发提供了机会。因此，在慢性期针对神经修复机制进行治疗是一种很有前景的方法，有助于增强中 风幸存者的恢复能力并改善其预后。 慢性神经炎症 是中风后恢复的主要障碍，但其潜在机 ...

Core Viewpoint - The research presents a novel strategy for developing high energy density and high safety solid-state lithium batteries by utilizing a "rich anion solvation structure" in polymer electrolytes, achieving an energy density of 604 Wh·kg⁻¹ [3][5]. Group 1: Research Findings - The research team developed an integrated fluorinated polyether electrolyte that combines strong solvating polyether segments with weakly solvating fluorinated hydrocarbon side chains, creating a "rich anion solvation structure" [4]. - This electrolyte enhances the redox reversibility of the LRMO cathode and significantly reduces side reactions at the oxygen interface, leading to improved performance [4]. - The quasi-solid polymer electrolyte, with 30wt% of trimethyl phosphate, achieved a reversible high surface capacity of over 8 mAh·cm⁻² in pouch cells and demonstrated over 500 cycles of long-term stability at 25°C in button cells [4]. Group 2: Comparative Analysis - The pouch battery reached an energy density of 604 Wh·kg⁻¹, which is significantly higher than the current commercial lithium iron phosphate energy density of approximately 150-190 Wh·kg⁻¹ and nickel-cobalt-manganese energy density of about 240-320 Wh·kg⁻¹ [4]. - The developed battery exhibited excellent safety performance during puncture and thermal tests at 120°C, with no incidents of combustion or explosion [4].

编译丨王聪 编辑丨王多鱼 排版丨水成文 医疗 AI 智能体 （ medical AI agent ）代表了医疗保健领域的变革性范式，其 自主性 、 适应性 和对复杂任务的 决策能力 使其区别于传统的人工智能。 2025 年 9 月 26 日，澳门科技大学 张康 、 霍文逊 、澳门城市大学 印赟 、解放军总医院第一医学中心 陈香美 院士、中山大学肿瘤防治中心 骆卉妍 等在 Cell 子刊 Cell Reports Medicine 上发表了题为： A foundational architecture for AI agents in healthcare 的综述论文。 该综述提出了一个基于四大核心组件—— 规划 、 行动 、 反思 与 记忆 的 医疗 AI 智能体 概念框架，重点考察该框架在关键临床领域的应用——从提升诊断准确 率、个性化治疗方案，到指导机器人手术和实现实时患者监测。研究深入分析了实施过程中面临的多重挑战，包括技术集成、临床医生接受度、法规适应性，以 及数据隐私和算法偏见等伦理问题。未来发展方向包括向主动式多智能体协作系统的转型，以及具有前瞻性的" AI 智能体医院 "概念。尽管这些智能体系统 ...

撰文丨王聪 编辑丨王多鱼 排版丨水成文 肾脏的 缺血再灌注损伤 （IRI） 是临床上急性肾损伤 （AKI） 的主要诱因，通常发生在肾血供中断一段时 间后恢复之时。在临床上，肾脏 IRI 是部分肾切除术、肾移植、创伤和心脏搭桥手术等常见的几乎不可避免 的病理生理后果，影响患者的预后和生活质量。遗憾的是，目前临床上预防和治疗肾脏 IRI 的有效方法寥寥 无几。 肾脏近端小管上皮细胞 （PTEC） 是肾脏 IRI 的主要靶细胞。肾脏 IRI 的病理生理机制复杂，包括能量代谢 异常、线粒体功能障碍、氧化应激以及包括细胞凋亡、铁死亡和坏死性凋亡在内的异常细胞死亡，目前尚 未完全明了。因此，揭示这些机制以探究预防和治疗肾脏 IRI 的有效策略迫在眉睫。 2025 年 9 月 25 日， 南方医科大学 吴芃 、 赵洁 、 邹志鹏 等人 在 Cell 子刊 Cell Reports Medicine 上 发表了题为： Gut symbiont-derived ursodeoxycholic acid promotes fatty acid oxidation to protect against renal ischemia ...

撰文丨王聪 编辑丨王多鱼 排版丨水成文 本周 （9 月 22 日- 9 月 28 日） ，国际顶尖学术期刊 Cell 共上线了 7 篇研究论文，其中 4 篇来自 华人学 者，这些研究分别是 —— 时间分辨荧光蛋白 、 阿 尔茨海默病发病新机制 、 泛癌免疫疗法 、 单细胞新生转录组测序 。 时间分辨荧光蛋白，拓展荧光显微镜应用范围 9 月 22 日， 西湖大学 张鑫 教授团队 （ 谈自主 、 熊家亨 、 冯嘉辉 为共同第一作者 ） 在 Cell 期刊发表了题为： Time-resolved fluorescent proteins expand fluorescent microscopy in temporal and spectral domains 的研究论文。 该研究首次提出并发展了 时间分辨荧光蛋白 （t ime-resolved fluorescent protein， tr-FP ） 这一变革性工具集， 在时间和光谱域上拓展了荧光显微镜的应用 范围， 为生物学研究提供了整合系统复杂性和定量准确性的全新解决方案。 阿尔茨海默病发病新机制 9 月 25 日，西奈山 伊坎 医学院 张斌 、 蔡东明 、 ...