Core Viewpoint - The article discusses the potential of a newly identified gut bacterium, YB328, in enhancing the efficacy of immune checkpoint blockade (ICB) therapies, particularly in cancer treatment, by promoting dendritic cell maturation and CD8+ T cell activation [1][4][7]. Group 1: Research Findings - A study published in Nature identified a gut bacterium that accelerates dendritic cell maturation and migration, increasing the response of CD8+ T cells to various tumor antigens, thereby enhancing anti-tumor immunity [2]. - The research analyzed fecal samples from 50 cancer patients undergoing PD-1 blockade therapy, revealing that the YB328 strain was significantly enriched in patients who responded to the treatment [4]. - In mouse models, fecal transplants from non-responding patients supplemented with YB328 showed significantly improved anti-tumor effects of PD-1 blockade therapy, indicating YB328's potential role in enhancing cancer immunotherapy [4]. Group 2: Mechanism of Action - YB328 promotes the differentiation of CD103+ CD11b- conventional dendritic cells (cDC), which are crucial for cross-presenting antigens to CD8+ T cells [5]. - The bacterium stimulates various Toll-like receptors (TLRs), leading to the phosphorylation of S6K and STAT3, and induces the expression of IRF8, facilitating cDC differentiation [5]. - The activated cDC migrate to tumor-draining lymph nodes and the tumor microenvironment, where they activate CD8+ T cells and induce PD-1+ CD8+ T cells targeting multiple tumor antigens [5][7]. Group 3: Future Directions - The research team is collaborating with a biotechnology company to conduct human clinical trials within the next three years to test whether YB328 can improve cancer patients' responses to checkpoint inhibitors [8].

Core Viewpoint - The study highlights the pathogenic role of meningeal B cells in driving neuroinflammation relapses in central nervous system autoimmune diseases, particularly multiple sclerosis (MS) [2][6]. Group 1: Research Findings - Meningeal autoreactive B cells interact with antigen-specific T cells, accelerating neuroinflammation [3][6]. - In an experimental autoimmune encephalomyelitis (EAE) mouse model, meningeal autoreactive B cells amplify local pro-inflammatory mechanisms through their interaction with T cells, promoting neutrophil recruitment and endothelial cell activation prior to clinical disease onset [4][6]. - The mechanism requires B cells to express major histocompatibility complex class II (MHC II) molecules and T cells to produce granulocyte-macrophage colony-stimulating factor (GM-CSF) [5]. Group 2: Implications for Treatment - The findings confirm that local autoreactive B cells in the brain are key initiators of neuroinflammation in relapsing MS and represent promising therapeutic targets [6][7]. - Selective depletion of brain-resident B cells can alleviate relapses in experimental autoimmune encephalomyelitis [7].

Core Viewpoint - Copper is an essential element for life, playing a critical role as a cofactor in various enzymatic processes. The discovery of cuproptosis, a new form of programmed cell death linked to copper ion homeostasis, presents significant implications for cancer therapy [1][2]. Group 1: Copper and Cuproptosis - Copper is a vital trace element in human life, necessary for various biological functions, but can become toxic at elevated levels, leading to cell death [1]. - Cuproptosis, identified in 2022, is characterized by the disruption of copper ion homeostasis and abnormal regulation of protein acylation, resulting in unique cell death pathways [1]. Group 2: Research and Development - A research team from Tianjin University published a study on July 11, 2025, focusing on a covalent organic framework designed to induce intracellular copper accumulation for cuproptosis cancer therapy [3]. - The study developed a nano-system, P1+P2@COF@F127-D, which utilizes endogenous copper to achieve copper-based cancer treatment through a cascade reaction [6]. Group 3: Mechanism of Action - The nano-system initiates a cascade reaction by introducing a copper output inhibitor, DC_AC50, which specifically increases intracellular levels of cuprous ions (Cu+) in cancer cells, leading to irreversible cuproptosis [6][10]. - The system employs small molecule inhibitors of glutaminase-1 (GLS1) encapsulated in a glutathione-responsive covalent organic framework, facilitating the release of DC_AC50 and the GLS1 inhibitors upon cellular uptake [7]. Group 4: Highlights of the Study - The research successfully developed a copper death therapy nano-system that does not require exogenous copper, instead utilizing endogenous copper to trigger a copper-glutathione-mediated intracellular cascade reaction, amplifying the anti-tumor effect [10][11]. - The design features a self-reinforcing feedback loop characterized by increased Cu+, enhanced GLS1 inhibitor production, and reduced glutathione (GSH) levels, further promoting the accumulation of Cu+ and enhancing the therapeutic effect [7][11].

撰文丨王聪 编辑丨王多鱼 排版丨水成文 葡萄糖代谢 是支撑肿瘤快速增殖的核心能量来源。近年来，靶向葡萄糖代谢 （例如低碳水饮食） 已成为抑制肿瘤生长的一种很有前景的策略。 2025 年 7 月 15 日，中山大学生命科学学院 邝栋明 教授、 魏瑗 副教授团队 （ 吴财源 博士、 黄春祥 博士、中山大学肿瘤防治中心 劳向明 主任医师为共同第 一作者） 在国际顶尖学术期刊 Cell 上发表了题为： Glucose Restriction Shapes Pre-Metastatic Innate Immune Landscapes in Lung through Exosomal TRAIL 的研究论文。 该研究系统揭示了 葡萄糖限制 通过 外泌体-免疫 调控轴影响 肺转移前微环境 的新机制，并提出了代谢与免疫联合干预的潜在治疗策略。这项研究也提示我们， 极端低碳水饮食 （过度控糖） 会抑制肿瘤的生长，但也可能促进肿瘤的肺转移 ，因此，需要 谨慎评估代谢干预策略的系统性影响。 在这项最新研究中，研究团队揭示了一个出人意料的悖论： 尽管通过低碳水饮食或原位代谢受损导致的葡萄糖剥夺会抑制原发性肿瘤的生长，但同时会通过肺 ...

Core Viewpoint - The article discusses the advancements in the field of medium-sized rings (MSR) with a focus on non-traditional chiral types, including axial chirality, inherent chirality, and planar chirality, highlighting their synthesis strategies and stability factors [1][5]. Group 1: Overview of Medium-Sized Rings - Medium-sized rings (MSR) consist of 7-11 atoms and exhibit a unique "rigid-flexible" characteristic, making them significant in drug chemistry and functional materials [1]. - The review published by researchers from Zhengzhou University in Nature Reviews Chemistry emphasizes the importance of exploring non-traditional chiral MSRs, which have not been extensively studied compared to traditional central chirality [3][5]. Group 2: Types of Non-Traditional Chirality - Axial Chirality: This type arises from restricted rotation around a non-covalent bond axis, often constructed through dynamic kinetic resolution or asymmetric catalysis [4]. - Inherent Chirality: This chirality originates from the asymmetry of the ring framework itself, typically synthesized via cyclization reactions or template-directed methods [4]. - Planar Chirality: This involves the asymmetric arrangement of substituents within a molecular plane, requiring steric hindrance or ligand control for selective synthesis [4]. Group 3: Progress and Evaluation - The past decade has seen rapid advancements in the synthesis and application of non-traditional chiral MSRs, with significant breakthroughs reported [5]. - The review critically evaluates the key synthesis strategies for these chiral types and discusses the factors influencing the conformational stability of chiral medium-sized rings through structural and energy analysis [5].

Core Viewpoint - The excessive intake of added sugars has become a significant public health issue, particularly among children and adolescents, leading to potential long-term effects on obesity, metabolic disorders, and cognitive functions [2][4]. Group 1: Research Findings - A study published by a team from Beijing Normal University indicates that excessive sucrose consumption during early life alters cortical dynamics and adaptive behavior in adulthood [2][5]. - The research utilized wide-field calcium imaging to monitor the activity of the dorsal cortex in adult mice that had consumed high-sugar beverages since weaning, comparing them to a control group [4]. - Findings revealed that mice consuming high-sugar beverages exhibited changes in cortical dynamics and behavioral flexibility, despite no abnormalities in weight gain or glucose tolerance [4][7]. Group 2: Specific Observations - Mice exposed to sucrose during early life showed reduced cortical responses to sucrose in adulthood [7]. - These mice displayed delayed and prolonged learning-related cortical activity during early learning stages [7]. - There was a noted decrease in functional connectivity between the anterior and posterior cortices in mice that consumed sucrose early in life, along with heightened sensitivity to cue-reward association changes [7].

撰文丨王聪 编辑丨王多鱼 排版丨水成文 一名 8 岁小男孩在短短几个月内病情迅速恶化。2023 年 8 月，他还在跑步、踢足球，而到 9 月，他的双踝就出现了不自主的肌肉收缩，10 月，他已无法跑步 和进行体育运动，而到了 11 月底，他开始频繁摔倒，医生建议他靠轮椅行动。 基因检测确认了这个小男孩的病因：他遗传了来自父母的 HPDL 基因纯合突变，HPDL 蛋白有助于生成一种名为 辅酶 Q10 （CoQ10） 的抗氧化剂，这种抗氧化 剂对于线粒体发挥正常功能至关重要。实际上，他的两个哥哥姐姐因为该疾病在婴儿时期就已离世，而他的严重程度略低，在 8 岁时才突然病情恶化。 该疾病没有可用的治疗药物或方法，幸运的是， 纽约大学的 Michael Pacold 教授 团队此前发现了 一种 辅酶 Q10 前体 分子—— 4-HB ，有望治疗辅酶 Q10 合成缺陷相关线粒体脑病，但这尚未在人体上验证过。在美国 FDA 的特别许可下，研究团队对这名小男孩进行了 实验性治疗。 经过不到一个月的治疗，这个小男孩就可以走上 1 公里的路，现如今，他已经可以徒步 6 公里，还能跑步，甚至还能骑自行车了 ，他的力气正在恢复，精力和 ...

Core Viewpoint - The article discusses the challenges and advancements in assessing Variants of Uncertain Significance (VUS) in the ATM gene, which is crucial for DNA damage response and cancer susceptibility [2][5][6]. Group 1: ATM Gene and Its Importance - The ATM gene plays a key role in DNA damage response and is associated with Ataxia Telangiectasia when mutated [2][5]. - Mutations in the ATM gene can lead to increased risks of various cancers, including breast, colorectal, pancreatic, and prostate cancers [5]. - Comprehensive functional assessment of all possible single nucleotide variants (SNVs) in the ATM gene is essential for predicting cancer risk and patient prognosis [5][10]. Group 2: Recent Research Findings - Researchers from Yonsei University published a study in Cell that functionally assessed all 27,513 possible ATM SNVs using prime editing and deep learning [3][10]. - The study identified critical amino acid residues in the kinase domain that cannot tolerate missense mutations [10]. - A deep learning model named DeepATM was developed to predict the functional effects of the remaining 4,421 SNVs with unprecedented accuracy [9][10]. Group 3: Implications for Precision Medicine - The comprehensive evaluation of ATM gene mutations aids in precision medicine and provides a framework for addressing VUS in other genes [12]. - The research findings contribute to cancer risk assessment and prognosis, enhancing the understanding of ATM's role in cancer [9][10].

编辑丨王多鱼 排版丨水成文 有 结核分枝杆菌 （ Mycobacterium tuberculosis ） 感染史的患者，往往会出现不可逆且进行性的 肺损 伤 ，但其潜在机制尚不完全清楚。 2025 年 7 月 14 日，中国科学院动物研究所 刘光慧 研究员联合天津大学海河医院 陈怀永 教授、首都医 科大学宣武医院 王思 教授及中国科学院动物研究所 曲静 研究员团队，在 Nature Microbiology 期刊 发表了 题为： A single-cell transcriptomic atlas reveals senescence and inflammation in the post-tuberculosis human lung 的研究论文。 该研究构建了首个 结核杆菌 感染后肺组织的高精度细胞分子网络，并运用多维度分析策略系统阐明： 细胞 衰老与炎症是结核感染后肺损伤的关键病理特征，而内皮细胞衰老及血管炎症则是这一过程中的核心事件 。并进一步首次阐明了 FOXO3 表达下调协同凝血酶-炎症信号通路驱动结核杆菌感染导致的慢性肺损伤的 分子机制，为该疾病提供了潜在干预靶点。 在这项最新研究中，研究团 ...

Core Viewpoint - The article discusses the discovery of an alternative receptor for adeno-associated viruses (AAV), named AAVR2, which enhances the efficacy of AAV-mediated gene therapy and provides insights into reducing dose-related toxicity associated with AAV vectors [3][8]. Group 1: AAV and Its Applications - AAV is currently the most commonly used vector for in vivo gene therapy, approved for treating various diseases such as retinitis pigmentosa, spinal muscular atrophy, Duchenne muscular dystrophy, and hemophilia [1]. - The clinical success of human gene therapies relies on the safe and effective transduction of AAV into various tissues [2]. Group 2: Research Findings - AAVR2 (CPD) was identified as an alternative receptor that can restore the transduction of E branch AAVs, including AAV8, in the absence of AAVR, and provides a unique entry pathway for unclassified AAV11 and AAV12 [3][6]. - The research team characterized the direct binding between AAV8 capsid and AAVR2 using cryo-electron microscopy, identifying the amino acid residues involved in the interaction [6][9]. - A minimal functional AAVR2 (miniAAVR2) was overexpressed to enhance in vivo AAV transduction, allowing low doses of AAV to achieve similar therapeutic effects [6][9]. Group 3: Implications for AAV Biology - This research provides new insights into AAV biology and offers clinically applicable solutions to mitigate dose-related toxicity associated with AAV vectors [8].