撰文丨王聪 编辑丨王多鱼 排版丨水成文 慢性肾病 （ Chronic Kidney Disease ） 影响着全球十分之一的人口，其中被称为 足细胞 （ Podocyte ） 的肾脏特殊滤血细胞的损伤，发挥着关键作用。在肾 病综合征的主要病因—— 膜性肾病 （ membranous nephropathy，MN ） 中，循环 自身抗体 会攻击足细胞足突上的蛋白质，从而损害肾脏的过滤屏障 ， 导致 大量蛋白质从血液泄漏到尿液中 （即 蛋白尿 ） 。 近日，德国 汉堡-埃彭多夫大学医学中心的研究人员在国际顶尖学术期刊 Cell 上发表了题为： Autoantibody-triggered podocyte membrane budding drives autoimmune kidney disease 的研究论文。 我们研究发现， 自身免疫球蛋白触发的细胞外囊泡 （AIT-EV） 的形成是足细胞质膜出芽的重要病理学特征，这一过程由足细胞试图清除与足突跨膜抗原结合的 致病性自身抗体所引发，为 膜性肾 病 （MN） 中异质性的肾小球蛋白质聚集提供了一个统一而保守的机制。此外，该研究还表明，尿液 AIT-EV 分析可 ...

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]

撰文丨王聪 2025 年 11 月 25 日， 遵义医科大学第二附属医院 马虎 教授、 周建国 副主任医师作为共同通讯作者，在 Therapeutic Advances in Medical Oncology 期刊发 表了题为： CircRNA signature predicts immunotherapy response in advanced non-small cell lung cancer 的研究论文。 该研究系统性分析了两项 非小细胞肺癌 （NSCLC） 临床研究中的 circRNA 表达谱，识别出差异表达的 circRNA，进而 确定了一个由 11 个 circRNA 组成的 circRNA 特征谱—— circRNA-Sig ， 可用于预测晚期 非小细胞肺癌 （NSCLC） 对免疫治疗的响应，有望为肺癌的临床治疗提供指导。 编辑丨王多鱼 排版丨水成文 扫描 文末二维码 ，获取 生物世界 专属投稿折扣 肺癌 是全世界范围内最常见的恶性肿瘤，也是癌症相关死亡的首要原因，其中 非小细胞肺癌 （NSCLC） 占肺癌病例总数的 85%以上。尽管临床管理方面有所 进步，但非小细胞肺癌患者的 5 年总生 ...

新华社赫尔辛基12月4日电（记者朱昊晨 徐谦）斯德哥尔摩消息：瑞典卡罗琳医学院参与的一项国际研 究发现，大脑中两种受体可调控与阿尔茨海默病密切相关的贝塔淀粉样蛋白的分解过程。 ...

Core Viewpoint - Obesity is identified as a chronic metabolic disease characterized by excessive fat accumulation and is a major global public health concern, with nearly 50% of the adult population estimated to be overweight, leading to various non-communicable diseases [2] Group 1: Chronic Inflammation and Obesity - Chronic inflammation in adipose tissue is a key link between obesity and several chronic diseases, including type 2 diabetes, non-alcoholic fatty liver disease, and cardiovascular diseases [7] - The interaction between adipocytes and resident immune cells in adipose tissue plays a crucial regulatory role in this pathological process, although the underlying mechanisms remain largely unclear [7] Group 2: Research Findings - A recent study published in Signal Transduction and Targeted Therapy reveals that hypertrophic adipocytes mediate inflammation through a β2-microglobulin (B2M)-dependent mechanism, activating resident CD8+ T cells and macrophages in adipose tissue [4][5] - The study emphasizes the potential of targeting B2M in adipocytes as a therapeutic strategy for obesity-related chronic inflammation and metabolic disorders [5] Group 3: Mechanisms of Action - The research indicates that during obesity, the expression of B2M in hypertrophic adipocytes is upregulated, which not only activates CD8+ T cells but also promotes iron overload and ferroptosis in adipocytes, leading to M1 polarization of macrophages [7] - Specific knockout of B2M in adipocytes effectively inhibits the activation and accumulation of CD8+ T cells, as well as iron-induced cell death and M1 polarization, preventing obesity and related inflammation and metabolic disorders induced by a high-fat diet [7] Group 4: Correlation with Human Data - Bioinformatics analysis of human adipose tissue transcriptome data shows a strong correlation between B2M levels and obesity, with significantly elevated B2M expression found in adipocytes isolated from obese patients [9] - Overall, the findings highlight the critical role of adipocytes in obesity-related chronic inflammation and metabolic disorders through a B2M-dependent mechanism [9]

Core Viewpoint - The study reveals a signaling axis involving visceral adipose tissue-derived extracellular vesicles (VAT-EV) that promotes pancreatic cancer development and resistance to immune checkpoint blockade therapy in obese patients, suggesting potential new therapeutic strategies for obesity-related cancers [4][7]. Group 1: Research Findings - The research identifies that VAT-EV from obese patients facilitates communication with pancreatic ductal adenocarcinoma (PDAC) tissues [4]. - PDAC cells can internalize VAT-EV, leading to the stabilization of ribonuclease Rnaset2b and the production of free pseudouridine [4][5]. - Pseudouridine activates mast cells by increasing reactive oxygen species (ROS) and reducing H3K27me3 modifications, creating an immunosuppressive tumor microenvironment that promotes cancer progression [4][5]. Group 2: Implications for Therapy - Targeting the VAT-EV-CTSA-pseudouridine-mast cell signaling pathway could enhance the efficacy of immune checkpoint blockade therapy for PDAC [5][7]. - The study provides hope for developing new treatment strategies for obesity-related cancers by elucidating the molecular mechanisms linking obesity and cancer [7].

Core Viewpoint - The recent research from the University of California, Berkeley, challenges the traditional belief that high-calorie foods are solely responsible for obesity, suggesting that the pleasure derived from eating can play a positive role in weight management [4][7]. Group 1: Research Findings - The study titled "Changes in neurotensin signalling drive hedonic devaluation in obesity" reveals that the enjoyment of food can help maintain energy balance, redefining the relationship between food pleasure and obesity [4][7]. - High-fat diets were shown to impair the brain's reward system, leading to reduced appetite for high-calorie foods in obese mice, despite weight gain [9][11]. - The research identified neurotensin (NTS) as a key player in this process, with high-fat diets significantly suppressing NTS expression, which is crucial for enhancing dopamine neuron activity during food enjoyment [11][12]. Group 2: Implications for Weight Management - Restoring NTS levels through dietary intervention or gene therapy resulted in obese mice regaining normal food responses, reducing overall food intake, and improving anxiety symptoms [12]. - The findings suggest a shift from traditional weight loss strategies focused on appetite suppression to approaches that enhance the brain's reward mechanisms related to food enjoyment, potentially leading to the development of "happy dieting" therapies [12]. - This research opens new avenues for addressing obesity and related metabolic disorders, emphasizing the intersection of neuroscience and nutrition [12].

Core Viewpoint - The article discusses the relationship between aging and the immune system, emphasizing how immune responses change with age and the potential for manipulating immune function to extend healthy lifespan [2][24]. Group 1: Aging and Immune Response - Aging leads to significant changes in immune cell function, including a bias towards myeloid output from bone marrow, accumulation of senescent T cells, and increased levels of systemic inflammatory cytokines [6][24]. - The immune system is increasingly recognized as a key regulator of systemic aging, potentially driving the aging process rather than merely responding to it [24]. Group 2: Mitochondrial Function and Immune Aging - Mitochondrial dysfunction is central to immune aging, as age-related decline in mitochondrial function weakens immune responses and promotes chronic inflammation [7][8]. - Mitochondria also play a role in systemic signaling, influencing immune responses across different tissues, which is often overlooked in current models of immune aging [7][8]. Group 3: Spaceflight as a Model for Aging - Research using spaceflight environments reveals that many immune changes observed in aging, such as increased inflammatory mediators and impaired adaptive immune responses, can also occur in microgravity [9][12]. - This suggests that spaceflight can serve as a valuable model for studying the mechanisms of immune aging [9][12]. Group 4: Vaccine Response in the Elderly - Elderly individuals typically exhibit lower antibody titers and fewer memory B cells post-vaccination, leading to impaired protective immune responses [14]. - Recent findings indicate that the germinal center response in older adults can be enhanced, paving the way for improved vaccine strategies tailored to aging populations [14]. Group 5: T Cell Changes with Age - Aging is associated with various changes in T cells, including reduced diversity in T cell receptor repertoires and a shift towards inflammatory phenotypes [15][16]. - Understanding whether these changes are adaptive or degenerative is crucial for developing therapeutic strategies targeting age-related immune dysfunction [15][16]. Group 6: Personalized Immunotherapy - The potential of immune modulation in treating diseases is significant, with a focus on how aging affects the efficacy of immunotherapies like CAR-T cell therapy [19]. - Tailoring immunotherapy strategies based on age-related changes in immune cell function could enhance treatment outcomes across different age groups [19]. Group 7: Future Directions in Aging Research - The field must transition from defining aging processes to developing interventions, including identifying biomarkers and strategies to selectively target pathological aging cells [21]. - Integrating artificial intelligence with systems immunology could provide new insights into the regulatory nodes of immune aging, potentially allowing for interventions that recalibrate immune responses to slow aging [24][21].

撰文丨王聪 编辑丨王多鱼 排版丨水成文 肺癌 是一种极为常见的恶性肿瘤，是全球癌症相关死亡的主要原因。其中， 非小细胞肺癌 （NSCLC） 约 占所有肺癌病例的 85%， 其预后通常不佳。 免疫治疗领域的最新进展，尤其是 PD-1/PD-L1 单克隆抗体的应用，为 NSCLC 患者带来了新希望。临床 上，关键免疫检查点 PD-L1 表达情况常被评估以选择合适的免疫治疗药物，阻断 PD-1/PD-L1 通路能够 使耗竭的 CD8 + T 细胞重新活跃并恢复其肿瘤杀伤功能。 然而，PD-L1 并非理想的预测性生物标志物，因为一些 PD-L1 低表达的患者仍能从免疫治疗中获益。尽 管免疫治疗在晚期 NSCLC 患者中取得了令人鼓舞的 5 年生存率，但仍有部分患者出现复发或远端转移。 因此，寻找更有效的免疫治疗预测性生物标志物，对于 NSCLC 患者而言 至关重要。 近日，山东第一医科大学附属肿瘤医院 （山东省肿瘤防治研究院、山东省肿瘤医院） 陈大卫 团队在 Therapeutic Advances in Medical Oncology 期刊发表了 题为： Neutrophil extracellular trap ...

撰文丨王聪 编辑丨王多鱼 排版丨水成文 卵巢癌 （ Ovarian cancer ） 是全球最致命的妇科恶性肿瘤。这种癌症相对罕见，但在患有 子宫内膜异位 症 （ Endometriosis ） 的女性中更为常见，尤其是 透明细胞卵巢癌 。 子宫内膜异位症相关卵巢癌 （EAOC） 在子宫内膜异位症患者中的发生率高达 4.5%，其主要由卵巢病变 （子宫内膜异位囊肿） 恶变所致。在过去的几十年里，子宫内膜异位症的发病率有所上升，与此同时，在 子宫内膜异位症患者中卵巢肿瘤的检出率也有所增加。 与其它卵巢癌相比，EAOC 存在一些尚未解决的问 题，包括化疗耐药性、预后较差以及发病年龄更小。 然而，子宫内膜异位症与卵巢癌之间的因果关系仍有待确定。因此，阐明这种恶性肿瘤的发病机制对于防 止诊断延误以及降低其长期发病率至关重要。 2025 年 11 月 20 日，暨南大学医学院 李平 、香港中文大学（深圳）第二附属医院 王明华 、暨南大学附 属第一医院 周宏 等人 ， 在 Cell 子刊 Cell Reports Medicine 上发表了题为： Therapeutic targeting of interleukin-1 ...