撰文丨王聪 编辑丨王多鱼 排版丨水成文 该研究对 跨越整个脊椎动物类群 （ 包括灵长类、食肉类、偶蹄类、有袋类和啮齿类在内的最大范围的哺乳动物） 进行的大规模研究 发现， 抑制生殖，能够显 著延长寿命。 具体来说，持续的激素避孕和永久性手术绝育与预期寿命延长相关，这种效应在雄性和雌性动物中均存在，但两性受到保护免于特定死因的方式不同。雄性生存 改善的证据仅限于去势手术 （阉割） ，且在青春期前实施手术效果更显著。对已发表数据的荟萃分析表明，绝育能提高脊椎动物的生存率，并延长去势啮齿动物 的健康寿命。这种生存改善在实验室和野生环境中均存在，且无论雌性绝育方式是否切除卵巢都有体现。而在历史上，被去势男性 （古代太监） 的生存率提高与 其他物种情况相似，而女性在永久性手术绝育后生存率略有下降 （1%） 。 总的来说，这项研究表明，激素驱动的生殖会限制脊椎动物成年期的生存，这与动物所处的环境无关。 生物体的能量和资源是有限的，如果大量资源被投入到 生殖活动 （求偶、交配、怀孕、育幼） 中，那么用于 身体维护和修复 的资源就会减少，这可能会导致更 快的衰老和更短的寿命。因此， 生殖被认为会限制寿命，而雄性和雌性在生殖活 ...

Core Viewpoint - The article discusses a systematic evaluation of computational tools for detecting multiple types of RNA modifications using Nanopore Direct RNA Sequencing (DRS), highlighting the performance differences and limitations of existing algorithms [1][2]. Group 1: Research Findings - A high-quality, single-base resolution benchmark dataset was constructed as a "gold standard" to evaluate 86 RNA modification detection algorithms based on DRS technology across four dimensions: accuracy, biological relevance, cross-sample generalization ability, and computational efficiency [2]. - The model retraining strategy significantly improved detection performance, with combined training on in vitro transcribed (IVT) RNA and real biological samples enhancing prediction accuracy and generalization, particularly for Ψ, m5C, and A-to-I modifications [4]. - m6A detection tools performed well overall, with models like Dorado and SingleMod excelling in qualitative and quantitative analysis, while most non-m6A modification detection tools struggled with quantitative accuracy and cross-sample generalization [5]. - Biological relevance is a crucial criterion, as ideal detection tools should not only have high accuracy but also align with known biological patterns; some tools showed discrepancies in predicted modification site distributions [5]. - Current tools face challenges in reliably distinguishing different modifications occurring on the same base, leading to "fuzzy predictions," which is a key area for future algorithm optimization [4]. - The retrained models can adapt to the iterative advancements in DRS technology, effectively addressing the challenges posed by changes in signal characteristics with the upgrade from RNA002 to RNA004 [6]. Group 2: Resource Development - To promote field development, the research team launched NaRMBench, an online resource platform that consolidates 12 key performance indicators of each tool into an interactive radar chart, aiding users in selecting and comparing analysis tools [8].

Core Viewpoint - The article discusses the potential of fasting to enhance the efficacy of endocrine therapy in HR+ breast cancer patients, highlighting a recent study that identifies glucocorticoid activation as a key mechanism behind this effect [2][4][11]. Group 1: Fasting and Endocrine Therapy - HR+ breast cancer, which includes estrogen receptor-positive (ER+) and progesterone receptor-positive (PR+) types, accounts for 75% of all breast cancer diagnoses, with endocrine therapy being the primary treatment method [2][6]. - Standard endocrine therapy often faces limitations due to primary or acquired resistance, leading to tumor recurrence and progression after several years of treatment [6][7]. - Periodic fasting has been shown to enhance the effects of standard endocrine therapy and delay the onset of acquired resistance, although the underlying mechanisms were previously unclear [7][9]. Group 2: Recent Research Findings - A study published in Nature by researchers from the Netherlands Cancer Institute and the University of Genoa on December 10, 2025, demonstrates that fasting enhances breast cancer treatment efficacy through glucocorticoid activation [3][4]. - The research indicates that fasting induces extensive epigenetic reprogramming in ER+ breast cancer models, activating glucocorticoid receptors (GR) and progesterone receptors (PR), while reducing the activity of AP-1 family members [7][9]. - In human patients undergoing periodic simulated fasting diets, increased levels of progesterone and cortisol were observed, correlating with the activation of GR and negative correlation with proliferation markers in tumor samples [9][11]. Group 3: Implications for Treatment - The study suggests that the activation of glucocorticoid receptors plays a critical role in enhancing the activity of endocrine therapy during fasting, indicating the potential for evaluating corticosteroids as adjuncts to endocrine treatment [11].

编辑丨王多鱼 排版丨水成文 2025 年 12 月 10 日，北京生命科学研究所/清华大学生物医学交叉研究院 邵峰 实验室 （ 田笑影 博士、 博士研究生 刘佳琪 为论文第一作者 ） 在 Nature 期刊 发表了题为： Agonists for cytosolic bacterial receptor ALPK1 induce antitumour immunity 的研究成果。 19 世纪， 美国外科医生 威廉·科利 （William Coley） 观察到部分癌症患者在发生细菌感染后肿瘤 会 缩 小 甚至消退， 基于此，他尝试使用灭活的细菌混合物 （即"科利毒素"） 来激发患者的免疫系统以 治疗 肿瘤，这 是肿瘤 免疫治疗 的早期尝试。 20 世纪中期， F. Macfarlane Burnet 和 Lewis Thoma s 提 出"免疫监视"理论，为免疫系统识别并清除肿瘤提供理论基础。随后，IL-2、IFN-α 等细胞因子疗法在 1980-1990 年代获批， 拉开了现代免疫治疗的序幕。 这项研究 首次阐明了 ALPK1 激动剂 作为一种 新型癌症免疫疗法 的巨大潜力 。 ADP-Hep 衍生物 UD ...

撰文丨王聪 编辑丨王多鱼 排版丨水成文 近日， Nature 期刊撤回了一篇仅发表了一年多的高影响力论文。 这篇论文题为： The economic commitment of climate change （气候变化的经济代价） ，来自德国 波 茨坦气 候影响研究所，于 2024 年 4 月 17 日发表于 Nature 期刊。 该论文 探讨了气温和降水等气候变化如何影响全球经济增长，该论文一经发表就受到广泛关注，仅一年多 时间，论文访问量就超过了 310000 次 ，谷歌学术显示，该论文被引用次数高达 441 次 。 关于气候变化对全世界造成的宏观经济损害的预测，通常只考虑长期时间尺度上的年平均温度和国家级温 度的影响。在这项研究中，研究团队利用过去 40 年间全世界 1600 多个地区的近期实证研究结果，来预测 温度和降水对次国家级地区造成的损害。 该研究显示，即便从现在开始大幅削减二氧化碳排放，由于气候变化，世界经济到 2050 年仍将面临 19% 的收入损失，也就是每年损失高达 38 万亿美元，这些损失主要源于气温上升，以及 降雨量和气温波动的 变化，如果 将风暴、野火等极端天气因素考虑在内，经济损 ...

Core Viewpoint - The article discusses the effectiveness and safety of Tegileridine, a new analgesic developed by Heng Rui Medicine, in managing moderate-to-severe acute pain following abdominal surgery, highlighting its advantages over traditional opioids like morphine [4][6][10]. Group 1: Clinical Trial Results - A randomized, double-blind, phase 3 clinical trial involving 528 patients demonstrated that Tegileridine provided effective pain relief, significantly outperforming a placebo and showing comparable efficacy to morphine [4][6][7]. - The primary endpoint, SPID24 (Sum of Pain Intensity Difference over 24 hours), showed Tegileridine 1.0 mg group at -68.98, morphine group at -71.16, and placebo group at -49.63, indicating similar effectiveness between Tegileridine and morphine [7]. Group 2: Safety and Side Effects - Tegileridine exhibited a lower incidence of gastrointestinal reactions, with moderate to severe vomiting occurring 3.8% less frequently than in the morphine group, and a 6.7% lower need for additional antiemetic medication [8]. - Only one case of transient respiratory depression was reported in the Tegileridine group, contrasting with the higher risks associated with traditional opioids [8]. - Other common opioid side effects, such as dizziness and itching, were reported at lower rates in the Tegileridine group, with all events being mild to moderate [8]. Group 3: Broader Implications - Tegileridine represents a new approach to pain management, balancing effective analgesia with reduced side effects, which could be beneficial for various pain management scenarios, including chronic pain patients and the elderly [10].

Core Viewpoint - A recent study from Central South University Xiangya Hospital highlights that excessive vigorous exercise can impair cognitive function through a muscle-derived mitochondrial vesicle called otMDV, emphasizing the importance of maintaining moderate exercise intensity for brain health [4][7]. Group 1: Relationship Between Exercise and Cognitive Function - The relationship between exercise and health follows an "inverted J-shaped" curve, indicating that moderate exercise promotes health, while excessive exercise can lead to adverse effects such as muscle fatigue and cardiovascular dysfunction [6]. - The study analyzed data from over 300,000 participants in the UK Biobank, revealing a "J-shaped" relationship between exercise and cognitive function, where moderate exercise is beneficial, but exceeding a certain threshold leads to cognitive decline [9]. - The optimal "dose" of vigorous exercise is approximately 1216 MET-min per week; exceeding this threshold results in a decline in cognitive function, a pattern validated across different age and gender groups [9]. Group 2: Mechanisms of Cognitive Impairment Due to Excessive Exercise - Excessive vigorous exercise leads to lactate accumulation in muscles, stimulating the secretion of otMDV, which can cross the blood-brain barrier and interfere with mitochondrial function in hippocampal neurons, crucial for learning and memory [11]. - OtMDV disrupts synaptic function through two mechanisms: first, it binds to the mitochondrial anchoring protein Syntaphilin, preventing normal mitochondria from anchoring at synapses; second, the mtDNA carried by otMDV activates the cGAS-STING signaling pathway, inhibiting the transport of the neuron’s own mitochondria to energy-demanding synaptic sites [13][14]. - These mechanisms collectively lead to a synaptic energy crisis, resulting in synaptic loss and cognitive decline [15]. Group 3: Human Study and Implications - A clinical trial involving 40 regular exercisers divided into moderate and excessive exercise groups showed that the excessive exercise group had significantly higher levels of PAF+ MDV in their blood, with decreased neural activity in the hippocampus and poorer performance in fluid intelligence and digit memory tests [18]. - The level of PAF+ MDV was directly correlated with the degree of cognitive decline, indicating the real risks of excessive exercise in humans [18]. Group 4: Potential Strategies for Prevention and Treatment - The research team developed neutralizing antibodies targeting the PAF protein, which effectively blocked the cognitive impairment caused by otMDV in animal experiments, suggesting a new avenue for treating cognitive disorders related to excessive exercise [20]. - Key factors include controlling the duration of intense exercise, with short bursts (15-45 minutes) causing only temporary lactate elevation, while prolonged intense exercise (over 60 minutes) leads to sustained high lactate levels and otMDV secretion [20]. - The study emphasizes the importance of moderation in exercise, listening to bodily feedback, diversifying exercise routines, and ensuring adequate rest and recovery [20].

以下文章来源于赛业生物订阅号 ，作者西米 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。 慢性肾脏病 （CKD） 是全球范围内的重大公共卫生挑战，影响着约10%的成年人口，其发病率与死亡率持 续攀升，给患者家庭及医疗卫生系统带来沉重负担。其核心病理特征之一是 肾小管间质纤维化 （TIF） ， TIF以肾小管萎缩、间质成纤维细胞活化、细胞外基质过度沉积与炎症浸润为特征，其严重程度与肾功能下降 速度和预后密切相关 。然而，目前针对TIF的治疗手段有限，开发特异性高、作用明确的新型抗纤维化药 物，已成为打破CKD治疗瓶颈、改善患者预后的迫切需求。 近期， 北京大学聂静教授团队 在 Kidney International 发表的研究论文发现，天然化合物水仙环素 （Narciclasine，Ncls） 能够显著逆转TIF相关基因表达。在多种CKD动物模型中，Ncls不仅减轻了纤维 化和炎症，还改善了肾功能。这一研究成果为CKD的治疗提供了潜在的新策略 [1] 。 新一期 「大咖来了，赛业有约」 系列课程，我们有幸邀请到通讯作者 北京大学聂静教授 ，于12月16日 （ ...

Core Insights - The article discusses the significant impact of rotavirus infections on neonates, particularly highlighting the severe symptoms and systemic infections that can arise, which are not effectively prevented by existing vaccines [2][5] - A recent study reveals that dysregulation of the hepcidin-iron axis plays a critical role in impairing antiviral immunity and causing liver damage in neonates infected with rotavirus, providing new therapeutic targets for related diseases such as biliary atresia [3][11] Summary by Sections Rotavirus and Its Impact - Rotavirus is a major cause of life-threatening gastroenteritis in children under five, leading to severe symptoms in neonates, including blood in stool and unstable vital signs, with current vaccination strategies offering no protection [2][5] - The prevalence of biliary atresia (BA) is noted, affecting 1 in every 5,000 to 18,000 newborns, with its etiology linked to infections, immune dysregulation, and genetic susceptibility [5] Research Findings - The study published in the journal Immunity identifies iron metabolism dysregulation as a key mechanism in rotavirus-related systemic infections in neonates, suggesting new treatment avenues [3][11] - Single-cell RNA sequencing revealed that iron dysregulation is a driving factor for liver damage in rotavirus infections, with elevated hepcidin levels inhibiting iron export and leading to cellular damage [6][9] Clinical Implications - An open-label clinical trial demonstrated that preoperative folic acid supplementation significantly reduced the incidence of cholangitis from 74% to 21% and liver transplantation rates from 41.1% to 11.1% in biliary atresia patients [8] - The study emphasizes the importance of targeting the hepcidin-iron signaling pathway to mitigate liver damage and improve outcomes in neonates with rotavirus infections [9][11]

Core Viewpoint - A research team from Zhejiang University has developed a novel cancer immunotherapy platform by repurposing mast cells, traditionally involved in allergic reactions, to deliver anti-cancer drugs directly to tumor sites, enhancing the immune response against cancer [2][5]. Group 1: Research Background and Methodology - The study published in the journal Cell describes a targeted therapy platform using engineered mast cells that act as "couriers" to deliver anti-tumor drugs by utilizing tumor-associated antigens as "allergens" [2][5]. - The engineered mast cells, sensitized with IgE antibodies specific to tumor markers, can migrate to tumor sites and trigger a rapid immune response, transforming "cold tumors" into "hot tumors" that are more susceptible to immune attack [5][11]. Group 2: Drug Delivery Mechanism - The engineered IgE-MC platform can carry various therapeutic agents, including oncolytic viruses, chemotherapy drugs, immune checkpoint inhibitors, and mRNA vaccines, with a focus on delivering oncolytic viruses [7][9]. - The oncolytic viruses can selectively infect and lyse tumor cells, and the IgE-MC protects these viruses from being cleared by the immune system during intravenous administration [9][10]. Group 3: Efficacy and Safety - In mouse models, treatment with OV@IgE-MC showed significant efficacy, with 60% of mice surviving beyond 25 days in the B16F10-OVA melanoma model, compared to a control group that all died within 15 days [11][12]. - Safety assessments indicated that injected IgE-MC are cleared within two weeks without disrupting mast cell homeostasis or inducing systemic allergic reactions, and they reduced liver toxicity compared to free oncolytic viruses [16][15]. Group 4: Future Prospects - The technology allows for personalized cancer treatment by matching specific IgE antibodies to patient tumor markers, simplifying the preparation process compared to traditional CAR-T cell therapies [18][19]. - The research team plans to establish a screening process for patient-specific IgE and explore combinations with existing immunotherapies, aiming to bring this innovative "tumor allergy" therapy from the lab to clinical application [19][18].