Core Viewpoint - The article discusses the development of a novel peptide, SK56, which selectively blocks the GSDMD-NT pore, thereby delaying pyroptosis and mitigating inflammatory responses, offering new therapeutic options for uncontrolled inflammation-related diseases [3][8][10]. Group 1: Research Findings - The research team utilized artificial intelligence (AI) to generate a specific blocker for the GSDMD-NT pore, which can delay pyroptosis and reduce inflammation, potentially benefiting conditions like sepsis and autoimmune diseases [3][10]. - SK56 effectively targets and blocks the GSDMD-NT pore, preventing cell death induced by inflammatory stimuli and reducing cytokine release from macrophages [8][10]. - The study challenges the traditional belief that pyroptosis is irreversible once triggered, demonstrating that SK56 remains effective even after the pyroptotic response has begun [10][11]. Group 2: Implications and Innovations - The findings highlight the potential of AI-guided peptide design in targeting previously deemed "undruggable" biological structures, paving the way for new biopharmaceutical developments [10]. - The research suggests a paradigm shift in managing inflammation, proposing that humans might coexist with inflammation rather than merely suppressing it [11]. - The AI model and training database used in the study have been made publicly available, promoting further research and development in this area [11].

Core Viewpoint - Tumor immunotherapy, particularly immune checkpoint blockade (ICB) targeting the PD-1/PD-L1 pathway, shows significant promise in treating various advanced cancers, but low immune response rates hinder its efficacy and widespread application [2] Group 1: Research Findings - The study developed a self-luminous nanosystem that enhances the activation of pyroptosis in tumor cells, leading to a strong antitumor immune response when combined with anti-PD-L1 monoclonal antibodies [3][6] - Pyroptosis, a newly discovered form of immunogenic cell death (ICD), releases pro-inflammatory cytokines and damage-associated molecular patterns, triggering a robust antigen-specific immune response [5] - The self-luminous nanoparticles can emit light within the tumor without the need for an external light source, enhancing the generation of reactive oxygen species (ROS) and achieving significant tumor-killing effects [7] Group 2: Mechanism and Components - The nanosystem consists of amphiphilic porphyrin lipids, camptothecin derivatives, and a targeting moiety, which together facilitate the release of oxygen and hydrogen peroxide in the acidic tumor microenvironment [6] - The combination of chemotherapy and self-enhanced photodynamic therapy synergistically activates pyroptosis, driving immune activation that enhances the antitumor response to PD-L1 therapy [7]

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]