gasdermin （GSDM） 家族包括人类的 GSDMA 至 GSDME 等成员，它们通过在细胞膜上打孔，引发细胞 焦亡 （ Pyroptosis ） 。在炎症性疾病中， GSDMD 介导的细胞焦亡通过其 N 端片段 （ GSDMD-NT ） 在细胞膜上形成 孔道，触发细胞裂解与细胞因子风暴，且可经细胞胞外囊泡传播至邻近细胞，加剧炎症扩 散。 GSDMD-NT 孔道形成过程中的主要结构变化，使得难以获得稳定的 GSDMD-NT 孔道蛋白，从而阻碍了传统高通量筛选方法识别用于孔道阻断的先导分子，且 其孔道直径达到了 21 纳米，这限制了小分子抑制剂的作用。此外，完全阻断 GSDMD 会 干扰其免疫稳态功能，因此，开发可逆、精准封堵成熟孔道的配体，是 当前的关键挑战。 2025 年 9 月 15 日， 大坪医院创伤与化学中毒全国重点实验室 （现就职于中国科学院成都生物研究所） 王淦 研究员，昆明市延安医院云南省心血管重点实验 室 孟平 副研究员和大坪医院创伤与化学中毒全国重点实验室 曾灵 研究员团队合作 （ 孙剑会 、 杨俊 为论文共同第一作者） ，在 Nature 子刊 Nature Immunology ...

Core Viewpoint - Sleep deprivation activates the body's inflammatory response, leading to cognitive impairment and increased risk of various diseases [2][3][6]. Group 1: Impact of Sleep Deprivation - A study involving 2,641 participants found that sleeping less than 6 hours triggers systemic inflammation and increases the risk of cognitive impairment [3]. - Sleep deprivation causes a series of inflammatory responses in the brain, releasing pro-inflammatory factors that adversely affect neurons and cognitive functions [3]. - Chronic sleep deprivation leads to oxidative stress and cellular damage, further exacerbating cognitive decline [3][6]. Group 2: Health Risks Associated with Sleep Deprivation - Insufficient sleep and chronic inflammation are linked to various diseases, including metabolic disorders, cancer, and mental health issues [6]. - Research indicates that sleeping less than 6 hours per night for a week can negatively impact metabolism, inflammation, immunity, and stress response [6]. - Prolonged sleep deprivation keeps the body in a state of stress, lowering immune function and increasing disease risk [6]. Group 3: Recommendations for Mitigating Damage - Adults typically need 7-8 hours of sleep per night, while older adults may require 5-7 hours [11]. - To combat sleep deprivation, lifestyle adjustments and medical interventions are recommended, such as increasing sunlight exposure and regular exercise [13]. - A balanced diet rich in anti-inflammatory foods, such as whole grains, deep-sea fish, cruciferous vegetables, and berries, can help reduce inflammation [14][15].

Core Viewpoint - The article emphasizes the potential health benefits of mango consumption, particularly its role in improving insulin sensitivity and metabolic health in overweight or obese individuals with chronic low-grade inflammation [3][10]. Summary by Sections Blood Sugar Regulation - Blood sugar is a crucial health indicator, with normal fasting levels between 3.9-6.1 mmol/L and postprandial levels not exceeding 7.8 mmol/L. Dietary choices significantly impact blood sugar control, where a balanced diet stabilizes blood sugar, while poor eating habits can lead to spikes [3]. Mango's Nutritional Benefits - Mango is highlighted for its high dietary fiber content and various vitamins and minerals. Previous studies have shown that moderate mango intake may positively affect blood sugar regulation and inflammation [3][10]. Clinical Study Overview - A recent randomized, placebo-controlled trial involved 48 participants with specific metabolic characteristics, including a BMI of ≥25 kg/m² and fasting blood glucose levels between 100-126 mg/dL. Participants were divided into two groups: one consuming fresh mango (approximately 230 grams daily) and the other receiving a mango-flavored placebo drink [6][7]. Study Findings - After four weeks, the study assessed blood sugar control using the oral glucose tolerance test (OGTT) and measured various metabolic parameters. Results indicated that regular mango consumption significantly improved insulin sensitivity, evidenced by decreased fasting insulin levels and improved HOMA-IR index [7][9]. Inflammation Markers - No significant statistical differences were found in inflammation markers between the mango and control groups, suggesting that mango's effect on insulin sensitivity may not directly involve inflammation pathways. The study primarily focused on IL-6, TNF-α, and hs-CRP, leaving out other relevant inflammatory markers [8]. Nrf-2 Gene Expression - An interesting finding was the approximately twofold increase in Nrf-2 gene expression in the mango group, although not statistically significant. Nrf-2 is crucial for activating antioxidant genes, which may enhance cellular antioxidant defenses and alleviate oxidative stress, potentially explaining the improvement in insulin sensitivity [9][10]. Conclusion and Future Research - The study concludes that mango, rich in active polyphenols and antioxidants, may serve as a dietary intervention for improving insulin resistance. Further research is recommended to explore the mechanisms and broader health benefits of mango consumption [10][11].

Core Viewpoint - The article highlights the significant contributions of four award-winning scientists from the Beijing Institute of Life Sciences (BILS) to the field of life sciences, emphasizing the institute's unique environment that fosters innovation and original research [1][3][6]. Group 1: Achievements of Award-Winning Scientists - In the past decade, 14 scientists have received the Future Science Prize in the life sciences category, with notable contributions from Shao Feng, Li Wenhui, Zhou Jianmin, and Chai Jijie, all of whom conducted their groundbreaking research at BILS [3][4][5]. - Shao Feng was awarded the Future Science Prize in 2018 for his discovery of receptors and execution proteins involved in the inflammatory response to bacterial endotoxin LPS [3]. - Li Wenhui received the Future Science Prize in 2022 for identifying receptors for hepatitis B and D viruses, aiding in the development of more effective treatments [4]. - In 2023, Chai Jijie and Zhou Jianmin were recognized for their pioneering work on the structure and function of anti-disease bodies in combating plant pests [5]. Group 2: Unique Environment at BILS - BILS, established in 2003, operates without administrative levels or fixed positions, allowing scientists to independently determine their research directions and alleviating funding concerns [6][7]. - The institute's supportive environment encourages scientists to take risks and explore new research areas, as exemplified by Shao Feng's transition from studying bacterial infections to discovering the molecular mechanisms of cell death [12][14]. - Li Wenhui emphasized the importance of a "fact-based" approach at BILS, where open discussions and constructive criticism during weekly meetings foster a culture of rigorous scientific inquiry [23][25]. Group 3: Collaborative Research and Innovation - The collaboration between Chai Jijie and Zhou Jianmin began serendipitously during their time at BILS, leading to significant advancements in understanding plant immunity [31][33]. - Their joint research efforts culminated in the discovery of anti-disease bodies, marking a milestone in the field of plant innate immunity, which was recognized with the Future Science Prize [33][34]. - The institute's culture of collaboration and mutual support among scientists has been pivotal in driving innovative research and achieving notable scientific breakthroughs [36][39].