撰文丨王聪 编辑丨王多鱼 排版丨水成文 新陈代谢是生物学的一个重要组成部分，通过 RNA 的转录和翻译过程实现快速且广泛的重编程。代谢还控制着负责可逆 RNA 修饰 （例如 m 6 A） 的酶的活 性。 m 6 A 是高等真核生物中 mRNA 上最常见的内部修饰。m 6 A 具有广泛的影响，已被证明参与 RNA 稳定性、剪接和翻译的调控，而 m 6 A 的失调则与多种发育 疾病以及癌症的发展密切相关。m 6 A 修饰由 METTL3–METTL14 复合物催化，这是一种 S-腺苷甲硫氨酸 （SAM） 依赖的 RNA 甲基转移酶。FTO 作为首个 RNA 去甲基化酶的发现，则突显了 m 6 A 修饰的可逆性和动态性。 代谢在影响表观遗传学和细胞命运决定方面发挥着重要作用。然而，代谢酶和代谢物以及它们在 RNA 表观遗传学中的调控机制，目前仍不清楚。 然而，甲硫氨酸代谢是否涉及独立于 S-腺苷甲硫氨酸 （SAM） 的表观遗传机制，以及此类机制在肿瘤发生中发挥何种作用，目前仍不清楚。 在这项最新研究中，研究团队发现， 腺苷高半胱氨酸酶 （Adenosylhomocysteinase，AHCY） - 腺苷 （ADO） ...

Core Viewpoint - The study indicates that vegetarian diets, particularly strict vegan diets, are negatively correlated with the likelihood of becoming centenarians among Chinese adults aged 80 and older, with vegetarians having a 19% lower chance and vegans a 29% lower chance compared to omnivores [2][6]. Study Design and Methodology - The research is a nested case-control study involving 5,203 participants aged 80 and above from a nationwide survey initiated in 1998, categorizing them into omnivores and vegetarians, with further subdivisions into pescatarians, lacto-ovo vegetarians, and strict vegans [4]. - The primary outcome measured was the likelihood of reaching 100 years of age by the end of the follow-up in 2018, using multivariable unconditional logistic regression for association analysis [4]. Key Findings - A total of 1,459 centenarians were identified and matched with 3,744 non-centenarians, revealing that vegetarians had a lower likelihood of becoming centenarians (OR=0.81), with strict vegans showing an even lower likelihood (OR=0.71) [5]. - No significant association was found for pescatarians (OR=0.84) and lacto-ovo vegetarians (OR=0.86) regarding centenarian status [5]. - Significant associations were observed in individuals with a BMI < 18.5 kg/m² (OR=0.72), while no significant association was noted in those with a BMI ≥ 18.5 kg/m² (OR=0.92) [5]. Implications - The results suggest that a vegetarian diet, especially a strict vegan diet, is associated with a reduced likelihood of reaching 100 years of age, emphasizing the importance of a balanced and high-quality diet that includes both animal and plant-based food components for longevity, particularly in underweight elderly individuals [6]. - It is recommended that vegetarians consider incorporating fish, eggs, and dairy products to prevent nutritional imbalances and the negative impacts of low body weight on long-term survival [6].

为应对上述挑战，溶瘤病毒的全身给药，已成为改善难以触及的癌症临床疗效的主要研究方向；然而，此 前的研究报告指出，溶瘤病毒全身给药存在一些问题，包括被预先存在的抗病毒中和抗体迅速清除以及潜 在的全身毒性。 尽管提高溶瘤病毒的剂量能够提升其向肿瘤的递送效率，但这也带来了潜在的全身毒性风 险，可能导致严重的副作用甚至患者死亡。 因此，迫切需要开发一种能够增强 溶瘤病毒向肿瘤的递送能力的同时 降低给药剂量的平衡方法。 撰文丨王聪 编辑丨王多鱼 排版丨水成文 溶瘤病毒 （ Oncolytic Viruse， OV） 是癌症治疗中一种很有前景的疗法。这些具有复制能力的病毒既能 感染正常细胞也能感染肿瘤细胞，但它们在肿瘤细胞中选择性复制，从而引发抗肿瘤反应。基于单纯疱疹 病毒 （HSV） 的首个获美国 FDA 批准的溶瘤病毒疗法 Imlygic 瘤内注射治疗黑色素瘤取得了成功，但其 在深部或转移性肿瘤中的治疗效果仍有限。 在这项最新研究中，研究团队开发了基因工程改造的、免疫兼容的细胞膜，其表达 嵌合抗原受体 （CAR） 以被 溶瘤病毒 （OV） ，从而构建了一种肿瘤靶向的溶瘤病毒递送平台—— iNV-GOV ，该平台既能保 ...

撰文丨王聪 编辑丨王多鱼 排版丨水成文 乳酸 （ Lactate ） 是糖酵解过程中的核心代谢产物，在作为主要能量来源的同时，还参与三羧酸 （TCA） 循环。近期的研究阐明了其在免疫微环境调控和细胞信号转导中的关键作用，这些作用有助于肿 瘤进展和对治疗产生抗性。 经典的" Warburg 效应"模型认为，癌细胞是通过有氧糖酵解产生乳酸的主要 细胞。然而，最近的研究强调，包括癌相关成纤维细胞 （CAF） 、免疫细胞和内皮细胞在内的基质细胞也 在肿瘤微环境 （TME） 中对乳酸的生成做出了重要贡献。因此，研究微环境中不同来源的乳酸的作用，可 能有助于重新定义其在细胞稳态和疾病发病机制中的功能。 2026 年 1 月 16 日， 中山大学肿瘤防治中心 王骏 、 李永红 及湖南师范大学附属第一医院（ 湖南省人民 医院） 李震 等， 在 Science 子刊 Science Advances 上发表了题为： Lactate derived from cancer- associated fibroblasts promotes alternative splicing and castration resistance ...

Core Viewpoint - Recent research indicates that crotonate, a short-chain fatty acid, has potential as a candidate drug for inhibiting breast cancer growth and metastasis by inducing specific modifications in the EZH2 protein, enhancing responses to immunotherapy [4][9]. Group 1: Research Findings - Crotonate suppresses breast cancer metastasis and promotes immunotherapy response through ACSS2-mediated EZH2-K348 crotonylation [3][4]. - The study reveals a new pathway where crotonate leads to the degradation of EZH2 protein via crotonylation at the K348 site, resulting in decreased levels of H3K27me3 [6][8]. - Compared to the EZH2 inhibitor tazemetostat, crotonate shows superior efficacy in inhibiting breast cancer metastasis [8]. Group 2: Mechanism of Action - Crotonate is metabolized to crotonyl-CoA, which then induces the crotonylation of EZH2, leading to its ubiquitin-mediated degradation [6][9]. - The mechanism involves the action of acetyltransferase p300, which catalyzes the formation of EZH2-K348cr, promoting the degradation of the modified EZH2 protein [6][8].

Core Viewpoint - The research published by Francis Crick Institute in Nature highlights the role of antibodies against endogenous retroviruses (ERVs) in enhancing lung cancer immunotherapy, suggesting a potential therapeutic strategy combining CXCL13 with immune checkpoint blockade (ICB) therapy [4][5]. Group 1 - The study reveals that tertiary lymphoid structures (TLS) improve the efficacy of lung cancer immunotherapy by enabling B cells to produce antibodies targeting activated ERVs within tumor cells [4][5]. - Immune checkpoint blockade (ICB) therapy enhances the B cell response against ERVs, and the resulting antibodies exhibit anti-tumor effects and can predict treatment efficacy [4][5]. - The formation of TLS is dependent on the cytokine CXCL13, and utilizing CXCL13 in treatment could synergize with existing ICB therapies for better anti-cancer outcomes [4][5]. Group 2 - The paper was retracted on January 14, 2026, due to issues found in the data presented in the figures, which were critical to the study's conclusions [6][8]. - Specific problems included irreproducible data in figure 5c, potential data manipulation in figures 5d and 5e, and unverifiable source data integrity for B cell and antibody quantification in figures 3c and extended data figure 5c [8][9]. - The investigation indicated that the first author, Kevin W. Ng, was responsible for the data manipulation issues, and the authors issued an apology to the scientific community for any confusion caused [12].

Core Viewpoint - The article discusses a recent study revealing the mechanism by which chromatin fragments are released from the nucleus during aging, highlighting the potential of targeting this process to inhibit age-related inflammation [3][6]. Group 1: Research Findings - The study published by a team from Harvard Medical School/Massachusetts General Hospital identifies "Nuclear Egress" as a mechanism for the export of chromatin fragments from the nucleus, which is crucial for understanding chronic inflammation in aging [3][6]. - The research demonstrates that inhibiting key nuclear egress proteins, such as the ESCRT-III complex, can prevent chromatin fragments from activating the cGAS-STING pathway, thereby reducing age-related inflammation [6]. - Metformin treatment was shown to significantly lower ALIX expression in intestinal tissues of aged mice, leading to decreased levels of chromatin fragments and reduced cGAS-mediated inflammatory responses [6]. Group 2: Implications for Treatment - The findings suggest a novel therapeutic strategy targeting the nuclear release of chromatin fragments to mitigate age-related inflammation, linking metabolic interventions with inflammatory responses [6]. - The study indicates that both glucose restriction and metformin can inhibit the formation of chromatin fragments through AMPK-dependent phosphorylation and autophagic degradation pathways [6].

撰文丨王聪 编辑丨王多鱼 排版丨水成文 自身免疫性溶血性贫血 （ Autoimmune Hemolytic Anemia， AIHA ） ，是由自身抗体介导的红细胞破坏性的自身免疫疾病，其发病机制是自身反应性 B 细胞和 浆细胞产生的抗红细胞抗体持续攻击红细胞，导致患者反复发生溶血和贫血。 难治性 AIHA 是该疾病的更晚期阶段，其被定义为对至少三种治疗方案均无反应。CD19 靶向的 CAR-T 细胞疗法 ，能够导致 B 细胞大量减少，除了治疗血液类 癌症，已在多种自身免疫疾病中展现了有希望的治疗效果，因此，可能是实现难治性 AIHA 无药物缓解的有效方法。 2026 年 1 月 14 日， 中国医学科学院血液病医院 （中国医学科学院血液学研究所） 施均 教授领衔的研究团队，在国际顶尖医学期刊《 新英格兰医学杂志 》 （NEJM） 上发表了题为 ： CD19 CAR T-Cell Therapy for Autoimmune Hemolytic Anemia 的研究论文， 中国医学科学院血液病医院 施均 教授、 熊海清 研 究员为论文共同通讯作者； 李若难 、 潘虹 、 张乐乐 和 马佳秀 为论文共同第一作者 ...

Core Insights - The article discusses the development of a generative foundation model for continuous glucose monitoring (CGM) data called GluFormer, which has significant predictive capabilities for both short-term glucose parameters and long-term disease risk stratification, particularly for diabetes and cardiovascular mortality [4][6]. Group 1: Model Development - The GluFormer model was trained using over 10 million glucose measurements from 10,812 adults, primarily non-diabetic, and employs self-supervised learning [5]. - The model's representations can be transferred across 19 external cohorts, covering five countries and various CGM devices, demonstrating continuous improvement in predicting glucose parameters compared to baseline glucose and HbA1c levels [5]. Group 2: Risk Stratification - In individuals with prediabetes, GluFormer effectively stratified risk for those likely to experience clinically significant HbA1c increases within two years, outperforming baseline HbA1c and common CGM metrics [6]. - In a cohort of 580 adults with a median follow-up of 11 years, GluFormer identified 66% of new diabetes cases and 69% of cardiovascular mortality cases in the highest risk quartile, compared to only 7% and 0% in the lowest risk quartile [6]. Group 3: Multimodal Integration - The research team also developed a multimodal extension of GluFormer that integrates dietary data, allowing for the generation of reasonable glucose trajectories and predictions of individual glucose responses to food [7]. - Overall, GluFormer provides a scalable framework for encoding glucose patterns, enhancing both short-term glucose predictions and long-term disease risk stratification, thus offering a powerful tool for precision medicine and metabolic health management [7].

撰文丨王聪 编辑丨王多鱼 排版丨水成文 众所周知，生命在于运动。当我们谈及运动时，很多人脑海中浮现的是健身房中的汗流浃背，或是户外几公里的跑步。实际上，在当下快节奏的生活中，大多数 人很难抽出大段时间，也很难有恒心坚持进行运动锻炼。 除了运动不足，久坐也是健康的隐形杀手。该研究显示， 每天减少 30 分钟 久坐时间，可在高危人群 （他们平均每天久坐 12 小时） 中预防 3.0% 的死亡，在 大多数人群 （他们平均每天久坐 10 小时） 中预防 7.3% 的死亡。 2026 年 1 月 13 日， 挪威体育科学学院领衔的国际科研团队在国际顶尖医学期刊《 柳叶刀 》 （The Lancet） 发表了题为： Deaths potentially averted by small changes in physical activity and sedentary time: an individual participant data meta-analysis of prospective cohort studies 的研究论文。 这项大型研究汇集了来自挪威、瑞典和美国的 13.5 万名参与者数据，平均跟踪时 ...