Core Viewpoint - The article discusses a novel approach to control postoperative tumor recurrence using a stable hydrogel system that releases oncolytic viruses, demonstrating its effectiveness in activating immune responses and preventing tumor regrowth after surgery [3][6]. Group 1: Research Background - Tumors pose a significant threat to human health, and postoperative recurrence is a major challenge for patients who have undergone surgery [2]. - Current treatments like chemotherapy and radiotherapy often have severe side effects, highlighting the need for safer and more effective alternatives [2]. Group 2: Study Findings - The research published in Cell Reports Medicine introduces a hydrogel system (adv@Nap gel) that can continuously release oncolytic viruses post-surgery, effectively controlling tumor recurrence [3][6]. - The study confirms that this hydrogel can activate the type I interferon pathway, inducing both innate and adaptive immunity, thereby controlling postoperative tumor recurrence and extending survival in mice [6]. Group 3: Innovations and Implications - **Local Sustained Release System**: The hydrogel provides continuous release of oncolytic viruses, extending the local immune activation window and aligning with the long-term immune regulation needs post-surgery [7]. - **Synergistic Immune Mechanism**: Oncolytic viruses not only directly lyse tumor cells but also activate immune pathways, transforming "cold tumors" into "hot tumors," enhancing sensitivity to other treatments [7]. - **Multi-Virus Platform Applicability**: The study demonstrates that adenoviruses, herpesviruses, and vaccinia viruses can all be effectively delivered using this hydrogel system, indicating broad applicability across various oncolytic virus types [8]. - **Clinical Translation Potential**: The immediate application of this strategy during surgery addresses both micro-residual disease and immune suppression, offering a low-toxicity, high-efficacy combined treatment approach to reduce tumor recurrence [9].

Core Viewpoint - Atrial Fibrillation (AF) is the most common persistent arrhythmia, leading to significant morbidity and mortality due to heart failure and thromboembolic strokes. There is an urgent need for better understanding of the pathways that trigger AF to develop effective and safe treatments [2]. Group 1: Research Findings - A study published by researchers from Harvard Medical School indicates that B cells promote atrial fibrillation through the production of autoantibodies in mice with typical AF risk factors such as hypertension, obesity, and mitral regurgitation [3]. - The use of anti-CD20 monoclonal antibodies to target and deplete B cells significantly reduced the incidence of AF in the HOMER mouse model, suggesting a new therapeutic avenue for patients with autoantibody-induced AF [6][9]. Group 2: Mechanisms of Action - In the HOMER mouse model, dendritic cells and B cells were found to expand in the left atrium and cardiac draining lymph nodes, with myocardial cell-derived proteins detected in these areas. Systemic expansion of B cells under interferon-α stimulation led to the production of autoantibodies that impaired calcium handling in myocardial cells [6]. - The depletion of B cells or inhibition of plasma cell maturation resulted in a significant reduction in the likelihood of AF being induced, highlighting the role of these immune cells in the pathophysiology of AF [7].

该研究揭示了 父母的 溶酶体 发生的促进长寿的变化是如何传递给后代的 —— 溶酶体代谢信号通过 组蛋白 H3.3 变体 和 H3K79 组蛋白甲基 化修饰 组成的表观遗传调控机制，在不改变 DNA 序列的情况下，实现 溶酶体 驱动的 长寿的 跨代 遗传 。 论文通讯作者 王萌 教授表示， 我们总是认为遗传物质在细胞内的细胞核中，但这项新研究证明了， 组蛋白 可以从一个地方移动到另一个地 方，如果这个组蛋白带有任何修饰，那就意味着它将表观遗传信息从一个细胞 （肠道细胞） 传递到另一个细胞 （生殖细胞） 。这为理解 跨 代遗传 效应提供了一种新机制。 撰文丨王聪 编辑丨王多鱼 排版丨水成文 在一些模式生物 （ 秀丽隐杆线虫、小鼠 ） 中，饥饿会延长寿命，进而延长它们后代的寿命。 贝勒医学院 王萌 团队 此前研究发现， 溶酶体 中的一种脂肪酶 LIPL-4 ，在这一过程中发挥了关键作用—— 饥饿会迅速激活 LIPL-4，而过表达 LIPL-4 能够显著延长线虫寿命， 令人惊讶 的是，这些长寿线虫的后代，即便自身没有这种基因改变 （过表达 LIPL-4 ） ，其寿命也比正常线虫更长。而且，当这些长寿线虫与没有基 因改 ...

Core Insights - The article discusses a significant research study on esophageal squamous cell carcinoma (ESCC), highlighting the discovery of a GPR116⁺ pericyte subpopulation that plays an immunosuppressive role in cancer metastasis [2][3][5]. Group 1: Research Findings - The study utilized single-cell multi-omics and spatial transcriptomics techniques, analyzing 16 samples with 117,169 cells and 5 samples with 195,366 cells, respectively, to reveal the cellular and spatial characteristics of ESCC [5]. - A pericyte subpopulation driven by the transcription factor PRRX1 was identified, which promotes tumor metastasis and immune evasion [3][5][6]. - GPR116⁺ pericytes secrete EGFL6, which binds to integrin β1 on cancer cells, activating the NF-κB signaling pathway and facilitating tumor progression [6]. Group 2: Clinical Implications - The study suggests that serum levels of EGFL6 could serve as a non-invasive biomarker for the diagnosis and prognosis of various tumors [6]. - Blocking integrin β1 in ESCC animal models effectively inhibited tumor metastasis and significantly improved responses to immunotherapy [6]. - The research provides a spatially resolved map of the tumor microenvironment in ESCC, revealing the biological and clinical significance of GPR116⁺ pericytes, which may lead to innovative treatment strategies for metastatic cancer [6][7].

撰文丨王聪 编辑丨王多鱼 排版丨水成文 肝细胞癌 （HCC，肝癌的主要类型） 是全球第四大常见癌症，也是癌症相关死亡的第二大原因。临床上，肝细胞癌常在晚期才被诊断出来，这使得患者可选择的 治疗方案十分有限。近来，使用靶向 PD-1、PD-L1 或 CTLA-4 的单克隆抗体进行免疫检查点阻断 （ICB） 治疗，已成为肝细胞癌的一种有前景的治疗方法。 然而，独特的肝脏环境显著降低了 肝细胞癌 对 ICB 治疗的响应，且经常出现耐药性，患者的总体受益率仅为 15%- 20%。 联合疗法是克服 PD-1/PD-L1 耐药性并提高治疗响应率的一种有前景的策略。然而，没有强机制依据的抗 PD-1/PD-L1 与其他抗肿瘤药物的联合临床试验并未 显示出协同效应。因此，迫切需要创新的联合疗法，这种疗法不仅要包含抗 PD-1/PD-L1 免疫检查点抑制剂，还要纳入可预测疗效的标志物。 2025 年 10 月 10 日，华中科技大学同济医学院附 属同济医院 张必翔 、 朱鹏 、 张占国 等人 ，在 Nature 子刊 Nature Communications 上发表了题为： VRK2 targeting potentiate ...

Core Viewpoint - Guided Bone Regeneration (GBR) is a crucial technique in dental and maxillofacial surgery for repairing bone defects caused by periodontal disease, trauma, or implant surgery, utilizing barrier membranes to promote bone regeneration while preventing faster migrating connective tissue from entering the defect area [2]. Group 1: GBR Membrane Development - Numerous GBR membranes have been developed, with collagen-based membranes like Bio-Gide favored for their biocompatibility and biodegradability, yet they face challenges such as rapid degradation and insufficient mechanical properties [2]. - The need for natural polymer-based materials with superior mechanical properties for GBR membranes is emphasized due to issues like membrane displacement and loss of bone grafts during the healing process [2]. Group 2: Research Findings - A study published in Cell Biomaterials by researchers from Tianjin University and Shandong University developed strong and tough natural protein hydrogels as GBR membranes regulated by tea polyphenols [3][4]. - The tea polyphenol-treated hydrogels exhibited excellent mechanical properties, including a tensile strength of 2.64 ± 0.20 MPa, a Young's modulus of 60.37 ± 2.71 MPa, and toughness of 1.83 ± 0.13 MJ/m³, surpassing most pure natural protein-based hydrogels [6]. - The asymmetric porous natural protein-based hydrogels serve as a physical barrier to prevent soft tissue infiltration while providing ample space for new bone growth, demonstrating significant effectiveness in promoting periodontal bone regeneration over a 12-week in vivo study [6][8].

编辑丨王多鱼 排版丨水成文 近年来， 以 肥 胖 和 2 型糖尿病 为代表的 内分泌代谢系统疾病已成为严重威胁 人类 健康的重大公共卫生 问题。《 柳叶刀 》的一项研究指出， 2022 年全球肥胖人口已突破 10 亿，占全球总人口的八分之一，且 这一趋势仍在持续上升。肥胖不仅显著增加个体罹患心血管疾病、癌症等多种重大疾病的风险，也给公共 卫生体系带来了沉重负担。 2 型糖尿病在全球范围内 也 呈持续攀升趋势。国际糖尿病联盟 （ IDF ） 数据 显示， 2021 年全球 20–79 岁的成年人中约有 5.89 亿人患糖尿病，占全球成人总数约 10.5% ，预计到 2045 年患者将增至约 7.8 亿人，占比超过 12% ，这意味着几乎每 9 名成年人中就有 1 人受累，其中大 部分为 2 型糖尿病。 随着全球老龄化、城市化、久坐生活方式以及高热量饮食的普及，未来几十年， 2 型糖尿病的患病率还将 持续上升，并将带来更大的心血管、肾脏、神经及眼底疾病负担 。 内分泌代谢系统疾病迫切需要依托大规 模人群遗传学获取高质量证据，识别可用于预防、早筛与精准干预的新分子靶点。 2025 年 10 月 10 日 ，昌平实验 ...

Core Insights - The article discusses a study revealing that both gender (male) and smoking are significant risk factors for bladder cancer, influencing the selection and accumulation of specific somatic mutations in normal bladder tissue long before cancer develops [3][9]. Group 1: Molecular Basis of Gender Differences - The study found that male bladder tissue accumulates significantly more driver mutations in key genes (RBM10, CDKN1A, ARID1A) compared to females, indicating a stronger survival or proliferation advantage for cells with these harmful mutations [7]. - This accumulation of "latent" harmful cell clones in males explains the higher risk of bladder cancer in men [7]. Group 2: Impact of Smoking and Aging - The research identified that TERT promoter mutations, common drivers of bladder cancer, can promote the expansion of clones in normal bladder tissue, showing a strong positive correlation with age and smoking history [7]. - Smoking and aging processes directly enhance the growth of potentially carcinogenic clones in normal tissue, significantly increasing cancer risk [7]. Group 3: Research Methodology - The study utilized ultra-deep double-strand DNA sequencing (approximately 5000× depth) to analyze 79 normal bladder samples from 45 individuals, identifying thousands of clone-driving mutations across 16 genes [8]. - This "Natural Saturation Mutagenesis" approach allows for a more accurate reflection of human biology compared to traditional cell line or animal model experiments, providing insights into precancerous lesions in various tissues [8]. Group 4: Implications for Cancer Risk and Prevention - The findings challenge the traditional dichotomy of "health" and "disease," showing that cancer risk factors like male gender and smoking begin shaping normal tissue cell clone landscapes years before cancer onset [9]. - The study offers new molecular targets and theoretical foundations for high-risk population screening and early intervention for bladder cancer [9].

Core Insights - The 2025 Nobel Prize in Physiology or Medicine was awarded to Mary Brunkow, Fred Ramsdell, and Shimon Sakaguchi for their discovery and definition of regulatory T cells (Treg cells), highlighting their role in preventing the immune system from attacking its own tissues, thus establishing a new field of Treg-mediated peripheral immune tolerance [2] Group 1: Research Findings on Treg Cells - A recent study published in Nature Immunology by researchers from Yale University and the Memorial Sloan Kettering Cancer Center revealed the context-dependent requirements for the transcription factor Foxp3 in Treg cells, indicating that Foxp3 is essential for newly generated Treg cells but less critical for mature Treg cells, except in stressful environments like severe inflammation or tumors [3][6] - The study utilized a technique called "chemical genetic induction of protein degradation" to precisely degrade Foxp3 in live animals, allowing for a better understanding of its role at specific stages and in specific environments [7] Group 2: Key Roles of Foxp3 - Foxp3 acts as a "training instructor" for newly generated Treg cells, as its removal prevents the establishment of the unique gene expression program and suppressive function characteristic of Treg cells, confirming its foundational role [8] - Mature Treg cells exhibit remarkable resilience; even in the absence of Foxp3 under steady-state conditions, their gene expression and suppressive functions show only minor changes, indicating that their immune suppressive capabilities become largely independent of Foxp3 once fully matured [9] - In stressful environments, such as severe inflammation, the loss of Foxp3 in mature Treg cells leads to significant disruptions in gene expression and cellular fitness, highlighting the renewed dependence on Foxp3 under immune stress [9] Group 3: Implications for Cancer Immunotherapy - Treg cells within tumors are particularly sensitive to Foxp3 degradation; its removal significantly weakens their suppressive function, leading to tumor shrinkage without causing severe autoimmune side effects, suggesting a promising avenue for cancer immunotherapy [10] - The study emphasizes that the role of Foxp3 is not static but varies with the life stage of Treg cells and the external immune environment, providing mechanistic insights into why Treg cells may become "ineffective" in autoimmune diseases and severe infections [10]

Core Viewpoint - The recent research reveals that Mycobacterium tuberculosis actively secretes linoleic acid to manipulate host immune responses, enhancing regulatory T cell (Treg) function and promoting bacterial survival within macrophages, thus providing new targets for tuberculosis treatment [3][6][10]. Group 1: Research Findings - The study published in Nature Microbiology identifies a novel mechanism by which Mycobacterium tuberculosis uses linoleic acid to upregulate CTLA-4 expression in Treg cells, thereby suppressing the host's anti-tuberculosis immune response [3][6]. - The research demonstrates that the bacterium is not merely evading the immune system but is actively creating a favorable intracellular environment for its survival by secreting specific metabolites [6][10]. - Increased levels of cytoplasmic calcium ions in Treg cells, triggered by linoleic acid, lead to enhanced CTLA-4 expression, which further inhibits immune responses, allowing the bacteria to persist within macrophages [7][8]. Group 2: Implications for Treatment - The findings suggest that targeting the mechanisms involving Rv1272c, linoleic acid, ATP2a3, and CTLA-4 could lead to the development of new therapeutic strategies against tuberculosis [10]. - This research opens up new avenues for designing drugs that can disrupt the immune suppression caused by Mycobacterium tuberculosis, potentially improving treatment outcomes for tuberculosis patients [10].