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 ...

撰文丨王聪 编辑丨王多鱼 排版丨水成文 肿瘤免疫疗法一直是一种很有前景的治疗方法，因其在摧毁肿瘤方面效果显著，尤其是在抑制肿瘤转移方面。在不同类型的免疫疗法中，基于 PD-1/PD-L1 通路 的免疫检查点阻断 （ICB） 疗法在多种晚期癌症中取得了巨大成功，通过缓解免疫抑制微环境发挥作用。然而，免疫应答率低阻碍了 ICB 在肿瘤治疗中的疗效和 广泛应用。 幸运的是， 邵峰 / 刘志博 等人发现，细胞 焦亡 （P yroptosis ） 能够引发强烈且有效的免疫反应，不到 15% 肿瘤细胞发生焦亡就足以消除整个肿瘤 【1】 ，这 为增强抗肿瘤免疫提供了一种很有前景的策略。 近日，北京大学第三医院 梁晓龙 团队在 Cell 子刊 Cell Biomaterials 上发表了题 为： Camptothecin amplified self-luminous nanosystem for highly efficient activation of pyroptosis to stimulate antitumor immunity 的研究论文 。 该研究开发了 喜树碱 增强型 自发光纳米系统 ，高效激活肿瘤细胞 ...

Core Viewpoint - The study highlights that high-dose ascorbic acid can selectively induce pyroptosis in LKB1-deficient non-small cell lung cancer (NSCLC) cells and enhance their sensitivity to immune checkpoint inhibitors (ICIs) [4][6]. Group 1: LKB1 Deficiency and Immune Resistance - LKB1 mutations lead to primary resistance to ICIs in NSCLC, characterized by a "cold tumor" subtype with insufficient Tpex cell infiltration [2][6]. - Tpex cells, which are crucial for responding to PD-1/PD-L1 blockade therapies, show high expression levels of the transcription factor TCF1 [2]. Group 2: Mechanism of Action - High-dose ascorbic acid exacerbates oxidative stress in LKB1-deficient NSCLC cells by upregulating the transporter GLUT1, leading to increased accumulation of ascorbic acid [6][8]. - The oxidative stress triggers pyroptosis in LKB1-deficient NSCLC cells through the H₂O₂/ROS-caspase-3-GSDME signaling axis [6][8]. Group 3: Clinical Implications - In preclinical models, high-dose ascorbic acid reverses ICI resistance and reshapes the immune microenvironment characterized by TCF1+ CD8+ T cell infiltration [7][8]. - Pyroptosis-driven immunogenic cell death promotes the maturation of cross-presenting dendritic cells, which is essential for Tpex cell expansion [7][8]. - The study provides a theoretical basis for clinical trials combining ICIs with high-dose ascorbic acid [7][8].

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].

Core Insights - The Future Science Prize, initiated by Yang Zhenning, celebrates its 10th anniversary in July 2025, recognized as one of the most significant scientific awards in China [2] - Over the past decade, 14 winners in the life sciences have emerged, with notable contributions from researchers at the Beijing Institute of Life Sciences (BILS) [2][3] Group 1: Achievements of Award Winners - Shao Feng received the Future Science Prize in 2018 for discovering receptors and execution proteins involved in the inflammatory response to bacterial endotoxin LPS [2] - Li Wenhui was awarded in 2022 for identifying receptors for hepatitis B and D viruses, aiding in the development of more effective treatments [3][14] - In 2023, Chai Jijie and Zhou Jianmin were recognized for their groundbreaking work on disease-resistant proteins and their structural elucidation [3] Group 2: Environment and Structure of BILS - BILS, established in 2003, operates without administrative levels or fixed positions, allowing scientists to autonomously determine research directions and secure funding [3][4] - The institute has attracted numerous talented young scholars, including Shao Feng, Chai Jijie, Zhou Jianmin, and Li Wenhui, who joined between 2004 and 2007 [3][4] Group 3: Research Philosophy and Collaboration - The culture at BILS emphasizes a "trial and error" approach, encouraging scientists to explore and innovate without the pressure of guaranteed success [10][15] - Regular meetings, such as the PI Club, foster open discussions and critical feedback among researchers, enhancing collaborative efforts and idea generation [17] Group 4: Personal Experiences of Researchers - Shao Feng chose to return to China from Harvard, believing in the potential for significant contributions to modern life sciences [5][6] - Li Wenhui, motivated by personal experiences with hepatitis patients, shifted his focus to hepatitis research upon joining BILS [11][13] - Both researchers attribute their successes to the supportive and flexible environment at BILS, which allows for independent exploration and innovation [8][10][15] Group 5: Impact of BILS on Scientific Community - BILS has played a crucial role in advancing China's scientific landscape through innovative research, talent cultivation, and fostering a collaborative environment [23] - The institute's ability to provide substantial research funding without competitive pressures has attracted top talent and facilitated groundbreaking discoveries [22][25]