Core Viewpoint - The study reveals that cancer cell-secreted DDAH1 protein accelerates lung aging by promoting the accumulation of citrulline, providing new insights for the treatment and diagnosis of tumors through the inhibition of aging lung fibroblasts [3][6]. Group 1: Research Findings - The research indicates that DDAH1 protein secreted by cancer cells induces the TGF-β1/Smad3 signaling pathway, leading to lung fibrosis and aging [3][6]. - The study identifies that increased levels of citrulline inhibit PAD4-mediated citrullination of TGF-β1, thereby activating the TGF-β1/Smad3 signaling pathway in lung fibroblasts [4][6]. - The use of DDAH1 inhibitors has been shown to effectively reduce lung fibrosis and delay lung aging [5][6]. Group 2: Methodology - The research utilized single-cell sequencing and gene knockout mouse experiments to confirm the mechanisms involved in the accumulation of citrulline and its effects on lung aging [4]. - The study highlights the role of vesicle sorting proteins in packaging DDAH1 into late endosomes [4]. Group 3: Implications - The findings suggest a potential therapeutic approach targeting DDAH1 to mitigate lung aging and fibrosis, which could lead to advancements in cancer treatment strategies [6].

Core Viewpoint - The article highlights the establishment and mission of the Hangzhou Institute of Medicine, which aims to advance precision medicine through innovative research and collaboration in translational medicine [4]. Group 1: Institute Overview - The Hangzhou Institute of Medicine (HIMCAS) was founded in 2019 as a forward-looking medical research institution under the Chinese Academy of Sciences [4]. - HIMCAS focuses on connecting molecular discoveries with clinical solutions to accelerate the development of next-generation therapies addressing global health challenges [4]. Group 2: Recruitment Opportunities - HIMCAS is actively recruiting outstanding scientists globally, offering positions such as Senior PI, Junior PI, Postdoctoral Fellow, and Core Facility Specialists [6][7]. - Senior PI candidates should currently hold associate professor positions or higher at renowned institutions, demonstrating leadership and impactful research [6]. - Junior PI positions are aimed at young scientists with significant research achievements, providing a platform for independent research development [7]. Group 3: Advantages of HIMCAS - HIMCAS benefits from clinical integration with its affiliated hospital, Zhejiang Cancer Hospital, facilitating access to extensive clinical data and patient cohorts [8]. - The institute boasts a distinguished talent ecosystem, with over one-third of core researchers receiving national awards and more than 70% having international research experience [8]. - HIMCAS operates competitive core facilities across five key platforms, enabling seamless interdisciplinary research from molecular discovery to translational application [8][9]. Group 4: Strategic Location and Support - HIMCAS is strategically located in the Qiantang Biomedical Town, surrounded by over 1,000 biotechnology companies, enhancing its research and commercialization capabilities [9]. - The institute offers competitive salaries, substantial startup funding, and comprehensive support for establishing impactful research projects [9]. - Living in Hangzhou provides researchers with a vibrant and livable environment, known for its cultural heritage and innovation ecosystem [9].

该研究设计了一种 基于多肽 接枝聚合物 的纳米机器人 （ peptide-grafted polymer-based nanorobot ） ，它能够在阻断 PD-1/PD-L1 的同时； 通过一个 pH 响应模块原位形成纤维来 破坏癌细胞膜 ，诱导 免疫原性细胞死亡 （ICD） ，释放 损伤相关分子模式 （DAMP） ，招募 T 细胞浸润。从而双管齐下 （解除 刹车+踩下油门） 发挥抗癌作用。 撰文丨王聪 编辑丨王多鱼 排版丨水成文 目前，阻断 PD-1 及其受体 PD-L1 为癌症治疗带来了巨大前景。尽管 PD-1/PD-L1 阻断疗法在临床上对多种类型的癌症的治疗取得了令人振奋的进展，但超过 95% 的 结直肠癌 （CRC） 患者属于错配修复功能正常 （pMMR） 的" 冷肿瘤 "，其对 PD-1/PD-L1 阻断疗法无响应，因为免疫细胞几乎无法浸润到免疫抑制 性的肿瘤微环境 （TME） 中。 诸如化疗、放疗和光热疗法之类的策略有可能通过免疫原性细胞死亡 （ICD） 和损伤相关分子模式 （DAMP） 的释放，将 pMMR 型"冷肿瘤"逆转为"热肿瘤"， 从而重塑肿瘤微环境，使癌细胞对基于 PD-1/PD ...

招聘职位 编辑丨王多鱼 排版丨水成文 国际衰老与癌症研究中心 （International Center for Aging and Cancer， ICAC ） 由海南医科大学 、 上 海交通大学医学院附属瑞金医院和 Samuel Waxman 癌症研究基金会共同建立的非营利性科研机构，位于 中国海南省海口市。该研究中心旨在通过创新的实验室、转化和临床研究，增进对衰老与癌症的理解，并 减轻作为衰老疾病癌症在全球范围内日益加重的负担。 ICAC 正在招募杰出的首席研究员 （PI） ，以开展生命科学领域的前沿研究以及衰老和癌症的转化研究。 新入职 PI 将获得具有国际竞争力的薪资和启动资金。此外，ICAC 还提供由专业科学家领导的先进核心设 施以及专门的行政服务。 更多信息：https://www.muhn.edu.cn/icac/index.htm 一）教职 研究重点 ：关键学科包括但不限于：肿瘤学、衰老生物学、血液学、生物信息学、细胞生物学、生物化学 与分子生物学、再生生物医学、基础医学、免疫学、药学、人工智能及相关领域。 职位要求 ：候选人须拥有博士学位或医学博士/哲学博士学位，并且具有数年的博士后培训经 ...

Core Viewpoint - The research highlights the role of tumor-produced ammonia in enhancing regulatory T cells (Treg cells), which impedes anti-tumor immunity, suggesting ammonia generation as a potential target for cancer immunotherapy [2][5]. Group 1: Research Findings - The study published in Cell reveals that ammonia produced by tumors is metabolized by Treg cells, leading to their enhancement and further obstruction of anti-tumor immune responses [2][5]. - The research team identified metabolic heterogeneity in human hepatocellular carcinoma (HCC), characterized by high levels of glutamine breakdown and ammonia, where Treg cells are prevalent while CD8+ and CD4+ effector T cells are diminished [3]. - Treg cells utilize the urea cycle to detoxify ammonia by upregulating argininosuccinate lyase (ASL), and ammonia is converted into spermidine under the regulation of the FOXP3 transcription factor [3][8]. Group 2: Clinical Implications - The study indicates that tumor cells undergoing anti-PD-1 treatment release ammonia through deamination, which enhances Treg cell function and leads to resistance to immunotherapy [4][8]. - The findings suggest that targeting ammonia production could inhibit Treg cells, providing a novel strategy for enhancing anti-tumor immunity [5][8].

生殖能力 对于物种延续至关重要，然而全球范围内 不育症 的发病率不断上升，已成为一个严重的公共卫 生问题，带来了深远的社会和心理影响。 基因突变和精子生成缺陷是 弱畸精子症 （ Asthenoteratozoospermia ） 的主要诱因。 弱畸精子症 是一 种复杂病症，表现为精子前向运动活力严重降低 （弱精子症） 以及形态异常精子比例过高 （ 畸精子症 ） 。这些功能和结构上的缺陷共同作用，削弱了精子到达并受精卵子的能力，因此，即便借助辅助生殖技 术，也会导致受孕失败。 撰文丨王聪 编辑丨王多鱼 排版丨水成文 弱畸精子症的遗传病因，目前仍不完全清楚。迄今仅有少量致病突变被报道，而这些变异破坏精子活力和 形态的潜在分子机制，目前仍不清楚。 2025 年 12 月 24 日，浙江大学医学院/复旦大学附属妇产科医院 黄荷凤 院士 、 复旦大学附属妇产科医 院 张晨 研究员、浙江大学医学院附属邵逸夫医院 高玉珍 等，在 期刊发表了题为 ： Targeting SKAP2 restores sperm motility and morphology through modulating mitochondrial ...

Core Insights - The study published by Yale University reveals a significant association between the consumption of sweetened beverages (both sugary and artificially sweetened) and adverse liver health outcomes, indicating that daily intake of these beverages increases the risk of metabolic dysfunction-related fatty liver disease (MASLD), severe liver disease, and chronic liver disease mortality [2][4]. Group 1: Study Overview - The research utilized data from the UK Biobank, involving 173,840 participants aged 40-69, and applied Cox proportional hazards regression models to analyze the relationship between sweetened beverage consumption and liver health outcomes [3]. - At baseline, 14.2% of participants consumed at least one sugary drink daily, while 10.8% consumed at least one artificially sweetened drink daily, with one serving defined as 250mL [3]. Group 2: Findings on Beverage Consumption - Each additional serving of sugary beverages per day was associated with a 10% increase in MASLD risk, a 21% increase in cirrhosis risk, an 18% increase in severe liver disease risk, and a 37% increase in chronic liver disease mortality risk [4]. - For artificially sweetened beverages, each additional serving per day correlated with a 15% increase in MASLD risk, a 14% increase in severe liver disease risk, and a 41% increase in chronic liver disease mortality risk [4]. Group 3: Health Improvement Potential - Reducing sweetened beverage intake may significantly improve liver health; substituting one serving of sugary drinks with tea or coffee is linked to a 10%-32% reduction in risks associated with MASLD, cirrhosis, severe liver disease, and chronic liver disease mortality [5]. - Similarly, replacing one serving of artificially sweetened beverages with tea or coffee is associated with a 14%-34% reduction in the same health risks [5]. Group 4: Protein Signatures and Health Risks - The study identified specific proteomic signatures associated with sweetened beverage consumption that correlate with increased risks of MASLD, cirrhosis, severe liver disease, and chronic liver disease mortality [5]. - For sugary beverages, each standard deviation increase in related proteomic features was linked to a 65% increase in MASLD risk, a 52% increase in cirrhosis risk, a 111% increase in severe liver disease risk, and a 53% increase in chronic liver disease mortality risk [5]. - For artificially sweetened beverages, the corresponding increases were 96% for MASLD, 71% for cirrhosis, 114% for severe liver disease, and 442% for chronic liver disease mortality [5]. Group 5: Implications for Dietary Recommendations - The findings underscore the importance of understanding how sweetened beverages impact liver health and suggest the need for personalized dietary recommendations to reduce the intake of these beverages to improve liver health and lower the risk of severe complications related to liver disease [6].

编辑丨王多鱼 排版丨水成文 | 序号 | 申请人 | 車位 | 院系 | | --- | --- | --- | --- | | 1 | 李德柜 | 澳门大学 | 工商管理学院 | | 2 | 祝梦华 | 澳门科技大学 | 月球与行星科学全国重点实验室 | | 3 | 陈琦 | 北京大学 | 环境科学与工程学院 | | 4 | 宫继成 | 北京大学 | 环境科学与工程学院 | | 5 | 刘思彤 | 北京大学 | 环境科学与工程学院 | | 6 | 陈克终 | 北京大学 | 人民医院胸外科 | | 7 | 法文哲 | 北京大学 | 地球与空间科学学院 | | 8 | 王昌 | 北京大学 | 药学院 | | 9 | 张艳席 | 北京大学 | 物理学院 | | 10 | 杨学林 | 北京大学 | 物理学院 | | 44 | 大山 | 六十十二 | 四六十六 | | דד | 子训 | 北京人子 | 儿干倒子沉 | | --- | --- | --- | --- | | 12 | 钟超 | 北京大学 | 基础医学院 | | J3 | 段小洁 | 北京大学 | 未来技术学院 | | 14 | 陈亮 | 北京大学 | ...

Core Insights - The article discusses the transformative impact of machine learning-based AI tools on protein structure research, highlighting advancements in computational tools for predicting protein structures and properties, and their applications in protein design [1][2][3]. Group 1: Advances in Protein Modeling - Machine learning tools are addressing challenges in understanding macromolecular dynamics and functions, moving beyond single structure limitations [2]. - AlphaFold has revolutionized protein structure biology, making it a common perspective in experimental design [2]. - Recent advancements, particularly AlphaFold3 and RoseTTAFold All-Atom, have significantly improved the accuracy and scope of protein structure and interaction predictions [3]. Group 2: Challenges in Predicting Complex Structures - While tools like AlphaFold-Multimer can accurately predict many tightly interacting complexes, challenges remain in simulating large, dynamic, or transient complexes [4]. - Membrane proteins and intrinsically disordered proteins present significant challenges due to the lack of high-resolution experimental data [4][5]. - The main obstacles to improving predictions for these complex structures include the scarcity of high-resolution experimental data and the need for new deep learning methods [4][5]. Group 3: Dynamic Structures and Environmental Conditions - Current tools do not predict folding pathways and have limitations in considering different solution conditions or temperatures [6][9]. - Integrating multiple data sources into machine learning models is crucial for describing dynamic structures and predicting conformational changes in response to environmental variations [8][10]. Group 4: Tools for Designing Functional Proteins - Current tools struggle to capture the dynamic characteristics of protein functions, which depend on various interactions and require quantitative predictions of conformational changes [10][11]. - Progress has been made in designing tools for properties beyond structure, but challenges remain in accurately predicting binding affinities and controlling dynamic properties [11][12]. Group 5: Integration of Machine Learning with Other Methods - Significant progress has been made in integrating machine learning with molecular dynamics and other computational methods to enhance protein design [17][18]. - AI 2 BMD exemplifies a hybrid system that combines machine learning with quantum mechanics to simulate large biomolecules with high accuracy [18]. Group 6: Future Directions and Data Needs - Expanding datasets to include functional and biophysical measurements is essential for improving model predictions [15][16]. - The development of databases for dynamic and polymorphic conformations is critical for simulating proteins that rely on structural dynamics for functionality [15][16]. Group 7: Responsible Use of AI in Protein Design - Concerns about the responsible use of AI in protein design include the potential for creating harmful proteins and the energy consumption of AI models [19][20]. - Continuous improvement of detection algorithms and collaboration between academia and industry are necessary to ensure safety while promoting scientific advancement [20][21].

Core Viewpoint - The study reveals a novel immune evasion mechanism in melanoma, where melanoma cells release melanosomes that mimic tumor antigens, leading to T cell exhaustion and impaired immune response [2][3]. Group 1: Immune Evasion Mechanism - Melanoma cells secrete melanosomes that are decorated with MHC molecules, which stimulate CD8+ T cells, causing their exhaustion and apoptosis [2][3]. - The presence of melanosomes allows melanoma cells to effectively evade immune detection by misleading T cells [3]. Group 2: Research Findings - Analysis of 69 melanoma patient samples showed that non-responders to immunotherapy had significantly more T cells with pigment deposits, indicating a state of exhaustion [6]. - Melanosomes, previously thought to only transport skin pigment, were found to be rich in immune-related proteins, including MHC molecules loaded with tumor-associated antigens [9]. Group 3: Mechanism of T Cell Exhaustion - T cells that mistakenly recognize melanosomes as tumor cells undergo incomplete activation, leading to mitochondrial dysfunction and eventual apoptosis [10][11]. - This mechanism results in T cells being unable to fully activate or rest, creating a state of cognitive confusion [10][11]. Group 4: Therapeutic Implications - Inhibition of melanosome secretion using a known tyrosinase inhibitor, such as kojic acid, significantly increased CD8+ T cell infiltration and suppressed tumor growth in melanoma models [12]. - The study suggests that targeting melanosome biogenesis or secretion pathways could enhance the efficacy of existing immune checkpoint inhibitors [14][16]. Group 5: Future Directions - Combining melanosome secretion inhibitors with anti-PD-1 antibodies may provide new hope for patients unresponsive to current immunotherapies [16]. - The findings could also influence CAR-T cell therapies by removing T cell clones sensitive to melanosomes before reinfusion, potentially improving treatment outcomes [17].