Core Viewpoint - The study highlights the impact of maternal oral microbiome dysbiosis on the gut microbiome of offspring, leading to long-term health implications, particularly an increased susceptibility to enteritis in adulthood [3][5][8]. Group 1: Research Findings - Maternal oral pathobionts can be transmitted to the infant gut, altering gut immunity and predisposing offspring to enteritis [3][10]. - The research demonstrated that periodontal disease in mother mice, induced by dental floss ligation, led to the expansion of oral pathogenic bacteria, which were then transmitted to their offspring [6][10]. - Despite the eventual clearance of these pathogenic symbionts from the offspring's microbiome, the imprint of susceptibility to enteritis persists into adulthood [7][10]. Group 2: Implications - Dysbiosis of the maternal oral microbiome not only affects the early gut microbiome of infants but may also have lasting effects on the long-term health of the offspring [8][10].

Core Viewpoint - The study published in Nature highlights the significant increase in hospitalization due to extreme temperatures in China by 2100, emphasizing the urgent need for climate change mitigation strategies to reduce temperature-related health risks and associated costs [2][8]. Summary by Sections Research Overview - The research analyzed hospitalization data related to six climate-sensitive diseases across 301 cities in China, covering over 90% of urban areas, and utilized a nonlinear distributed lag model to assess historical associations between temperature and hospitalizations [5][6]. Predictions and Findings - Predictions indicate that, without adaptation measures, the number of additional hospitalizations due to extreme high temperatures could reach 5.1 million by 2100 under high carbon emission scenarios. The associated hospitalization costs are projected to increase by $5.19 billion [7]. - The study found that the additional hospitalization risk from extreme high temperatures is expected to rise across all carbon emission scenarios, while the impact of extreme low temperatures is minimal [6][7]. Regional and Socioeconomic Insights - Historical data suggests that the northwest and southwest regions of China are particularly vulnerable to temperature-related health risks, especially concerning pregnancy-related diseases. The northern regions are more susceptible to extreme heat, while southern regions are more vulnerable to extreme cold [6][7]. - The research also highlights socioeconomic disparities, indicating that densely populated and economically developed areas, such as the Beijing-Tianjin-Hebei region, face relatively lower additional hospitalization risks during extreme heat events [7][8].

Core Viewpoint - The research led by Tsinghua University focuses on a novel strategy for enhancing plant immunity against pathogens, addressing the growing threats to global food security and environmental sustainability posed by plant diseases [1][4]. Group 1: Research Innovation - The study introduces a simple and efficient method for designing artificial plant disease resistance genes by utilizing protein engineering [1]. - A fusion protein is expressed in plants, combining a pathogen protease recognition cleavage site (PCS) with an active plant NLR immune receptor (aNLR) [4]. - The aNLR remains inactive until cleaved by the pathogen's protease, which triggers a strong immune response in the plant [4]. Group 2: Experimental Validation - The engineered NLR receptor has been shown to confer broad-spectrum and complete resistance to various potyviruses in model plants like Nicotiana benthamiana and economically important crops such as soybeans [6]. - This approach demonstrates the potential for a single engineered receptor to provide extensive protection against multiple viral threats [6]. Group 3: Broader Implications - The strategy is promising for developing universal plant disease resistance, as various pathogens across different kingdoms encode proteases [7]. - This could lead to enhanced resistance against a wide range of pathogens, including viruses, bacteria, fungi, and nematodes [7].

Core Viewpoint - The article discusses the advancements in mRNA therapies, particularly focusing on the development of non-inflammatory lipid nanoparticles (NIF-LNP) to enhance the delivery and efficacy of mRNA treatments for chronic lung injuries [1][2][9]. Group 1: mRNA Therapy and Challenges - mRNA therapies have revolutionized the treatment of various diseases, but the use of lipid nanoparticles (LNP) is limited due to systemic inflammatory responses and side effects [1][5]. - Therapeutic mRNA requires significantly higher protein levels (up to 1000 times) compared to preventive mRNA vaccines, which may lead to increased reactogenicity and reduced transfection efficiency [1]. Group 2: Research Development - A study published in Nature Communications introduced a novel non-inflammatory lipid nanoparticle (NIF-LNP) that activates V-ATPase to enhance RNA nanotherapeutics for chronic lung injury [2][3]. - The NIF-LNP formulation, incorporating ursolic acid, demonstrated a 40-fold increase in protein expression in the lungs compared to traditional LNPs without significant reactogenicity [5]. Group 3: Mechanism and Clinical Application - The study revealed that ursolic acid activates the V-ATPase complex, promoting endosomal acidification and enhancing mRNA cytoplasmic release while maintaining endosomal stability [6]. - A lyophilized formulation of NIF-LNP was developed, showing good aerosolization and stability for over 90 days, with effective mRNA transfection in preclinical models [7].

Core Viewpoint - The article discusses the potential of antler blastema progenitor cells (ABPC) and their extracellular vesicles (EV ABPC) in promoting healthy aging and reversing age-related conditions in mice and macaques, highlighting their unique regenerative capabilities and implications for anti-aging therapies [4][10][12]. Group 1: Research Findings - A recent study published in Nature Aging demonstrates that EV ABPC can reverse bone loss and mitigate aging-related phenotypes in animal models [3][4]. - The study identifies unique factors within EV ABPC that alleviate aging symptoms, such as improving bone mineral density and enhancing cognitive function in aged mice and macaques [11][12]. - EV ABPC treatment resulted in a reversal of epigenetic age by over three months in mice and over two years in macaques, indicating significant anti-aging effects [11]. Group 2: Characteristics of ABPC - ABPC, a type of mesenchymal stem cell found in deer antlers, exhibits remarkable regenerative potential, capable of driving rapid bone growth at a rate of 2.75 cm per day, leading to antlers weighing up to 15 kg and measuring 120 cm in three months [10]. - Unlike traditional mesenchymal stem cells, which show signs of aging after 10-15 culture cycles, ABPC maintains its proliferation and regenerative abilities even after 50 culture cycles [10]. - ABPC is noted as the only postnatal mammalian stem cell capable of complete organ regeneration, underscoring its potential as a source for anti-aging therapies [10].

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].