Core Viewpoint - The study highlights the role of the oral symbiotic bacterium Veillonella in promoting Clostridioides difficile infection (CDI) in patients with Crohn's disease by inhibiting bile acid transport protein ASBT, leading to abnormal bile acid accumulation in the intestine [3][9]. Group 1: Disease Overview - Crohn's disease is a common inflammatory bowel disease (IBD) characterized by abdominal pain, diarrhea, and intestinal obstruction, affecting the entire digestive tract with a high postoperative recurrence rate of approximately 80% [2]. - The global prevalence of IBD was 0.75% as of 2020, projected to rise to 1.0% by 2030, with 37%-59% of IBD cases being Crohn's disease [2]. Group 2: Research Findings - The research published in Cell Host & Microbe indicates that Veillonella intestinal colonization promotes CDI in Crohn's disease patients [3]. - Veillonella parvula inhibits the expression of the bile acid transport protein ASBT, preventing bile acid reabsorption and causing abnormal bile acid accumulation in the intestine, which triggers CDI [9][12]. - The study found a correlation between the abundance of Veillonella and increased bile acid metabolism in Crohn's disease patients, suggesting that the presence of bile acids can facilitate the germination of C. difficile spores [9][12].

Core Viewpoint - The article discusses the critical role of mitochondrial calcium transporters, particularly NCLX, in regulating cellular calcium signaling and mitochondrial function, highlighting recent research that elucidates its structure and mechanism [2][3][6]. Group 1: Importance of NCLX - NCLX is essential for preventing mitochondrial calcium overload, which can lead to cell death and is protective against conditions like heart failure and neurodegenerative diseases [3][6]. - Dysfunction of NCLX is linked to various diseases, including heart failure and tumor progression, making its structural and functional understanding vital for advancing knowledge in physiology and disease [3][6]. Group 2: Recent Research Findings - A study published in Nature by a team from Stanford University revealed the structure and mechanism of NCLX, providing insights into its assembly, conformational states, and an unexpected transport function as a H+/Ca2+ exchanger rather than a Na+/Ca2+ exchanger [3][6][12]. - The research utilized cryo-electron microscopy to analyze NCLX, uncovering critical details about its architecture and transport mechanisms [6][12]. Group 3: Research Contributions - The first author of the study, Dr. Fan Minrui, has made significant contributions to the field, having published multiple influential papers on related topics in top-tier journals [4][16][18].

Core Viewpoint - The study presents a novel method for real-time diagnosis of cholangiocarcinoma (CCA) by combining optical fiber biosensors based on bile clusterin with digestive endoscopy, addressing the urgent need for improved diagnostic techniques for this aggressive cancer type [2][10]. Summary by Sections Diagnosis Challenges - Cholangiocarcinoma is a highly malignant tumor with a poor prognosis, characterized by late diagnosis due to non-specific early symptoms, resulting in a 5-year survival rate of only 7%-20% [2]. Research Findings - The research team identified clusterin (CLU) as a promising biomarker for CCA through proteomic analysis of bile and cell supernatants, highlighting its overexpression in various cancers [5]. - The optical fiber biosensor technology, particularly surface plasmon resonance (SPR), was utilized for its high sensitivity and stability in detecting biological markers [5]. Methodology - The study involved 583 subjects and two rounds of proteomic analysis to screen and validate biomarkers for CCA, leading to the development of an SPR-based optical fiber biosensor [6]. - The biosensor demonstrated a high correlation coefficient of 0.989 and could accurately detect varying concentrations of CLU, with a detection time of 2 seconds and an area under the curve (AUC) of 0.854 [7]. Clinical Application - The CLU optical fiber biosensor was successfully integrated with digestive endoscopy, allowing for real-time in vivo diagnosis of CCA, with results aligning with postoperative pathology findings in patients [8][10].

Core Viewpoint - The research highlights the significant role of the ABCA7 gene in Alzheimer's disease risk, particularly through its rare functional loss mutations and their impact on phosphatidylcholine metabolism and mitochondrial function in neurons [3][4][10]. Group 1: Genetic Risk Factors - APOE4 is identified as the strongest genetic risk factor for Alzheimer's disease, increasing the risk by 3 times with one copy and 8-12 times with two copies [3]. - ABCA7 gene mutations, particularly those causing functional loss, double the risk of developing Alzheimer's compared to non-carriers [3]. Group 2: Mechanisms of ABCA7 - ABCA7 protein is crucial for lipid transport and maintaining membrane asymmetry in the brain, with its dysfunction linked to amyloid protein deposition and increased neuroinflammation [6]. - The study utilized brain tissue samples from the ROSMAP study, focusing on 12 patients with ABCA7 functional loss mutations to explore the genetic impact on Alzheimer's risk [6][7]. Group 3: Cellular Impact and Interventions - Single-nucleus RNA sequencing revealed extensive gene expression changes in various neuronal cell types associated with ABCA7 mutations, affecting lipid metabolism and mitochondrial function [7]. - Supplementation with cytidine diphosphate-choline (CDP-choline) was shown to reverse the negative effects of ABCA7 mutations on neurons, restoring mitochondrial function and reducing oxidative stress [8][10].

Core Points - The Lasker Awards are prestigious biomedical awards in the U.S., established in 1946, recognizing significant contributions in the medical field, often seen as a precursor to the Nobel Prize [2][3] - The 2025 Lasker Award winners include six scientists recognized for their groundbreaking work in basic and clinical medicine [3] Group 1: Lasker Basic Medical Award - Winners: Dirk Görlich and Steven L. McKnight for their discoveries regarding the structure and function of low-complexity domains (LCDs) in proteins, which elucidate new principles of intracellular transport and organization [7][26] - Their research challenges traditional views that LCDs, composed of a limited number of amino acids, are insignificant, revealing that approximately 15%-20% of eukaryotic proteins contain such domains that play crucial roles in various physiological functions [7][26] Group 2: Lasker Clinical Medical Award - Winners: Michael J. Welsh, Jesús González, and Paul A. Negulescu for their pivotal role in developing a three-drug combination therapy for cystic fibrosis, transforming it into a manageable condition [29] Group 3: Lasker Special Achievement Award - Winner: Lucy Shapiro for her 55 years of contributions in bacterial cell biology and national leadership, including the establishment of Stanford University's developmental biology department and her advisory role on issues like antibiotic resistance [30]

撰文丨王聪 编辑丨王多鱼 排版丨水成文 野火 （ wildfire ） 影响全球碳循环、生态系统、空气质量以及人类健康。在这些影响中，近年来野火对全 球 PM2.5 污染的贡献一直在稳步上升，其中北美地区的增幅最大。2023 年 5 月至 9 月期间，加拿大发生 了严重的森林火灾，过火面积总计达 1500 万公顷 （约占加拿大森林总面积的 4%，是 1983 年至 2022 年年均过火面积的 7 倍多） ，并导致大量碳排放。此外，加拿大野火产生的烟雾不仅飘过北美大陆，导致 美国多地发布空气质量警报，还飘过北大西洋，抵达欧洲和亚洲，这凸显出严重的野火并非只造成局部影 响。 尽管此前已从不同角度对野火产生的 PM2.5 暴露情况进行了研究，并且在以往的研究中也已识别出跨境火 灾污染事件，但此类极端野火对全球空气质量及人类健康的影响仍鲜有探索。 鉴于未来野火预计增多可能带来的持续影响，对这种空气污染的暴露程度以及在全球范围内对健康的影响 程度进行量化，有助于制定应对措施，包括野火监测和预报、灭火、土地管理和大规模景观燃料处理，以 及更广泛的气候缓解措施。 2025 年 9 月 10 日，清华大学 地球系统科学系 张 ...

撰文丨王聪 编辑丨王多鱼 排版丨水成文 尽管多不饱和磷脂对细胞功能至关重要，但其过度积累会使细胞易受 铁死亡 （ ferroptosis ） 的影响。细胞暴露于过量 多不饱和脂肪酸 （PUFA） 时如何防止 其过度掺入磷脂，目前仍不清楚。 2025 年 9 月 10 日，德克萨斯大学西南医学中心 Jin Ye 团队 （ 邓亚琴 为第一作者） 在 Cell 子刊 Molecular Cell 上发表了题为： Protection against ferroptosis through maintaining homeostasis of docosahexaenoate-containing phospholipids 的研究论文。 该研究揭示了一种脂肪酸感应机制 ，通过维持 含二十二碳六烯酸的磷脂 （DHA-PL） 的稳态来抵御 铁死亡 。 这一发现也为 ω-3 多不饱和脂肪酸的健康益处提 供了分子层面的解释。 在这项研究中，研究团队发现了一种机制—— 脂肪酸 （FA） 相互作用蛋白 UBXD8 可防止 二十二碳六烯酸 （DHA） 含量过高的磷脂过度积累，DHA 是哺乳动 物细胞中含量最丰富的多不饱和脂肪酸 ...

Core Viewpoint - The study highlights the role of interferon-induced CD8+ T cell senescence as a driving factor for immune therapy resistance in early triple-negative breast cancer (TNBC), suggesting that nicotinamide mononucleotide (NMN) treatment may restore T cell function and enhance the benefits of immune checkpoint blockade therapy [4][5][8]. Group 1: TNBC Characteristics and Treatment Challenges - TNBC is defined by the absence or low expression of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2), characterized by higher recurrence rates and shorter overall survival in patients [3]. - Chemotherapy remains the primary systemic treatment for TNBC due to the lack of specific therapeutic targets, but its efficacy is limited to a subset of patients [3]. Group 2: Research Findings on T Cell Senescence - A study published in Science Translational Medicine found that interferon (IFN)-induced CD8+ T cells reduce the efficacy of anti-PD-1 immunotherapy in early TNBC patients and preclinical models [4][5]. - The research identified a group of enriched IFN-induced CD8+ T cells in early TNBC samples that predict non-responsiveness to immunotherapy, driven by HLA-DR+ monocyte-derived IFN leading to T cell senescence [6]. Group 3: Potential Therapeutic Strategies - Treatment with NMN, a precursor of NAD+, was shown to restore the function of senescent CD8+ T cells and enhance the effects of immunotherapy in both patient-derived organoid-T cell co-cultures and mouse models [5][6][8]. - The findings suggest that targeting T cell senescence could be a promising strategy to improve immunotherapy outcomes in early TNBC [8].

Core Viewpoint - The article discusses the recent changes in leadership at the Chinese Academy of Medical Sciences and Peking Union Medical College, highlighting the appointment of Professor Ji Xunming as the new president and the removal of Wang Chen from his position as vice president of the Chinese Academy of Engineering [2][4]. Group 1: Leadership Changes - Wang Chen has been removed from his position as vice president of the Chinese Academy of Engineering and as the president of Peking Union Medical College [2]. - Professor Ji Xunming has been appointed as the new president of Peking Union Medical College, effective from August 15, 2023 [2][4]. - Ji Xunming is a newly elected academician of the Chinese Academy of Engineering and has a strong background in stroke prevention and translational medicine research [4]. Group 2: Institutional Background - The Chinese Academy of Medical Sciences was established in 1956, and Peking Union Medical College was founded in 1917, operating under a unified management system since 1957 [7]. - The institution comprises 21 research institutes, 6 affiliated hospitals, and 10 colleges, making it a comprehensive national medical research and education organization [7]. - The institution currently has 24 academicians, 56 National Outstanding Youth Scholars, and over 2,200 graduate advisors, with several key national research facilities [7].

Core Insights - The article discusses the emerging technology of proximity labeling, which allows for precise and controllable chemical reactions in complex biological systems, addressing a significant challenge in chemical biology [2] - A recent study published in Nature introduces a novel approach to tumor immunotherapy using proximity labeling to construct artificial antigens, enhancing immune responses against tumors [3][9] Group 1: Proximity Labeling Technology - Proximity labeling has been widely adopted in laboratories over the past decade as a tool to reveal biological processes, but its potential applications beyond biotin substrates remain underexplored [2] - The study proposes the concept of using proximity labeling reactions to construct artificial antigens specifically in tumor tissues, aiming to improve immunotherapy outcomes [7] Group 2: PATCH Technology - The research team developed a technique called Proximity Amplification and Tagging of Cytotoxic Haptens (PATCH), which utilizes engineered nanoenzymes activated by red light or ultrasound to catalyze reactions on tumor cell surfaces [3][7] - This method allows for the rapid and covalent attachment of artificial antigens to nearby proteins on cancer cells, creating high-density antigen clusters that serve as "super beacons" for immune cells [9] Group 3: Efficacy and Safety - In multiple mouse tumor models, PATCH therapy demonstrated the ability to quickly and safely eliminate existing tumors while also inducing systemic immune activation and long-term immune memory [9][10] - The technology addresses two major challenges in current CAR-T and antibody therapies: the heterogeneity of tumor antigens and the potential toxicity to healthy tissues, by ensuring that reactions occur selectively at the tumor site [6][10] Group 4: Future Directions - The research team plans to explore the translational applications of this technology further, including testing its potential in recruiting other types of immune cells and expanding its use in various diseases such as organ aging and autoimmune disorders [10]