Core Viewpoint - Oncolytic viruses (OV) represent a promising therapy for cancer treatment, selectively replicating in tumor cells to trigger anti-tumor responses, but systemic delivery remains a challenge due to pre-existing neutralizing antibodies and potential systemic toxicity [3][4]. Group 1 - The research team from Zhejiang University developed a systemically injectable oncolytic virus delivery platform called iNV-GOV, which protects viral particles from immune recognition and directs them to tumor sites, accelerating cancer cell pyroptosis and eliciting a strong anti-tumor immune response [4][5]. - The iNV-GOV platform integrates cancer virotherapy, cell membrane coating technology, CAR targeting, and controlled cell pyroptosis, addressing issues of low viral delivery efficiency and safety while significantly enhancing anti-tumor immune effects [5][7]. Group 2 - The engineered immune-compatible cell membrane expresses chimeric antigen receptors (CAR) to construct the tumor-targeting oncolytic virus delivery platform, functioning as an "invisibility cloak" to protect viral particles and as a "navigation" system to guide them to tumor sites [7]. - The viral load is controlled by a heat shock promoter, allowing ultrasound-induced mild hyperthermia to trigger tumor-specific cell pyroptosis, enhancing tumor lysis and promoting rapid release of oncolytic viruses from lysed tumor cells, thereby increasing infection of adjacent tumor cell populations [7][9]. Group 3 - Overall, this systemically injectable, tumor-targeting oncolytic virus platform enables rapid and sustained proliferation of viruses within tumors, providing a promising new strategy for treating various cancers [9].

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].

Core Viewpoint - The study demonstrates that CD19-targeted CAR-T cell therapy shows promising efficacy in treating refractory autoimmune hemolytic anemia (AIHA), with all 11 patients achieving complete response, marking a significant breakthrough in this field [3][6]. Group 1: Study Overview - The research involved 11 patients with refractory AIHA who had previously undergone at least three lines of treatment without success [6]. - The therapy utilized autologous CD19 CAR-T cells developed by Healion Biotech, which has been approved for treating relapsed/refractory B-cell acute lymphoblastic leukemia and large B-cell lymphoma [6]. - The primary aim of the study was to assess safety characteristics, including the incidence and severity of adverse events such as cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome [6]. Group 2: Efficacy Results - All 11 patients achieved complete response, with a median time to complete response of 45 days (range 21-153 days) [7]. - The median duration of drug-free remission was 11.5 months (range 6.8-21.0 months) [7]. - The study provides the first global evidence of the efficacy of CD19 CAR-T cell therapy in the AIHA domain, offering new hope for patients with recurrent or refractory AIHA [3]. Group 3: Safety Profile - Nine patients experienced grade 1-2 cytokine release syndrome, and one patient had grade 1 immune effector cell-associated neurotoxicity syndrome [9]. - A total of 15 infection events occurred among seven patients, with no grade 4 or higher infections reported [9]. - The study identified a specific B cell microenvironment associated with relapse, characterized by initial B cells and interactions with HLA-DRB5+ B cells and CD4+ T cells [9]. Group 4: Conclusion - Overall, the clinical study indicates that CD19 CAR-T cell therapy produces expected toxic effects while providing sustained remission in patients with multi-drug refractory AIHA [11].

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 ...

撰文丨王聪 编辑丨王多鱼 排版丨水成文 糖尿病性勃起功能障碍 （ diabetes mellitus-induced erectile dysfunction， DMED） 是由糖尿病引发或加重的男性勃起困难， 在 男性糖尿病患者中高发，是 糖尿病最常见和令人困扰的并发症之一，且现有疗法效果有限，这迫切需要更深入的机制研究。 2026 年 1 月 16 日，中南大学湘雅二医院 金鑫 、 吴水清 等在 Nature 子刊 Nature Communications 上发表了题为： Improving erectile function in diabetic male mice by rescuing depalmitoylated FBP1 to reduce cavernosal lactate 的研究论文。 该研究揭示了 海绵体乳酸堆积 是 糖尿病性勃起功能障碍 （ DMED） 的核心病理机制，并阐明了 其分子调控机制，通过 mRNA-LNP 疗法恢复去棕榈酰化修饰 的 FBP1 以降低海绵体乳酸水平，成功改善了糖尿病雄性小鼠的勃起功能。 https://www.nature.com/articles/s ...

撰文丨王聪 编辑丨王多鱼 排版丨水成文 骨骼肌 占人体体重的 40% - 50%，是人体最大的组织之一，在日常活动和运动功能中发挥着至关重要的 作用。虽然肌肉具有固有的自我修复机制，但在 大体积肌肉缺失 （VML） 后，这些修复机制往往无法完 全恢复肌肉组织。VML 不仅会导致肌肉力量下降和活动受限，还常常造成持续的功能缺陷和长期残疾。传 统的 VML 治疗方法，例如自体肌肉移植和物理治疗，虽然常用，但存在诸多局限性，包括供体部位短缺、 供体与受体不匹配以及恢复时间长等问题。 近年来， 电刺激 （ES） 作为一种促进组织再生的有前景的方法受到了关注。作为一种外源性治疗技术， 电刺激模拟生物电，已被证明通过调节细胞膜上的钙离子通道来促进组织修复和伤口愈合，从而改善愈合 过程。然而，传统的电刺激方法 （例如那些涉及植入针和电极的方法） ，仍面临着一些挑战，包括依赖体 积庞大的外部电源、使用便捷性以及患者舒适度等问题。 2026 年 1 月 16 日，中国科学院过程工程研究所 白硕 / 李琦 团队联合云南大学 孙韬 团队，在 Cell 子刊 Cell Biomaterials 上发表了题为 ： Fully biod ...