Core Viewpoint - Cellular senescence is a phenomenon characterized by growth arrest, impacting various aspects from embryonic development to aging and diseases. Senescent cells accumulate over time, leading to chronic inflammation through the senescence-associated secretory phenotype (SASP), which can promote tumor growth and metastasis despite initially acting as a barrier to tumor development. Combining chemotherapy with senolytic drugs that selectively clear senescent cells may reduce tumor resistance and recurrence [2][6]. Group 1 - Senolytic drugs have been identified with various targets, but issues such as narrow therapeutic range, off-target toxicity, low efficacy, and limited bioavailability remain [2][6]. - The study published in Nature Aging reveals the anti-aging properties of Sticholysin I (StnI), showing its ability to effectively and specifically kill senescent cells and work synergistically with chemotherapy to induce tumor regression in mice [3][8]. Group 2 - StnI, a pore-forming toxin isolated from Caribbean anemones, binds with high affinity to specific lipids on the target cell membrane, leading to the formation of transmembrane pores that disrupt membrane integrity and cause cell death [6][7]. - The mechanism of StnIG involves the influx of sodium and calcium ions and the efflux of potassium ions, triggering a lethal cascade that results in cell death, particularly effective against senescent cells due to their membrane characteristics [7][8].

Core Viewpoint - The research introduces a novel bioprinting strategy called NEAT (Nanoengineered Extrusion-Aligned Tract) that addresses the challenges in spinal cord repair by enabling the construction of aligned structures from nanofibers to centimeter-scale tissues without post-processing, demonstrating significant functional recovery in animal models [3][4][9]. Group 1 - The NEAT strategy utilizes shear stress during the extrusion printing process to induce directional rearrangement and ordered assembly of chemically modified collagen fibers, maintaining the collagen triple helix structure and bioactivity [6][9]. - In vitro functional assessments show that NEAT-printed aligned tissues exhibit significant advantages in cell differentiation and functional maturity, supporting over 8 weeks of culture [7]. - The NEAT approach successfully resolves technical challenges in manufacturing ultra-soft, high-water-content tissues, establishing a methodological foundation for future in vitro functional models and multi-scale biomanufacturing systems [9]. Group 2 - The research team, led by researchers from the Chinese Academy of Sciences, published their findings in the journal Cell Stem Cell, highlighting the potential of NEAT in promoting axonal reconnection and synapse formation in a rat spinal cord injury model [3][4]. - The NEAT technology integrates topological control, cell programming, and functional integration, providing a robust platform for neural tissue engineering and spinal cord regeneration [4]. - The study emphasizes the importance of optimizing key parameters such as nozzle size, printing speed, and extrusion pressure to achieve continuous fiber alignment from hundreds of nanometers to micrometers [6].

Core Viewpoint - The article discusses the relationship between Epstein-Barr virus (EBV) infection and the development of Multiple Sclerosis (MS), highlighting new research that connects environmental and genetic risk factors in MS pathogenesis [3][4][9]. Group 1: Research Findings - A study published in the journal Cell reveals that EBV infection and the HLA-DR15 gene jointly drive the development of MS by presenting myelin peptide antigens and activating autoreactive CD4+ T cells [4][11]. - The research indicates that EBV infection alters the transcriptional and immunopeptidomic profiles of B cells, particularly in individuals carrying the high-risk HLA-DR15 genotype, leading to the presentation of specific myelin basic protein (MBP) peptides [8][9]. - The study provides direct evidence supporting the "molecular mimicry" hypothesis, where similarities between EBV proteins and myelin proteins lead to an autoimmune response against the nervous system [9][18]. Group 2: Implications for Treatment - The findings deepen the understanding of MS etiology and suggest potential new therapeutic approaches targeting specific autoreactive T cells or EBV-infected B cells [11][18]. - The research collectively illustrates how EBV infection can influence both B cell function and induce cross-reactive T cell responses, contributing to MS pathogenesis [18].

Core Insights - The article discusses the rapid advancement of AI agents, particularly in cancer research and oncology, highlighting their capabilities beyond traditional AI systems [3][4][6] - AI agents can autonomously optimize drug design, propose treatment strategies, and handle complex multi-step problems that previous AI systems could not address [3][4][27] Group 1: AI Agents Overview - AI agents differ from traditional AI systems by possessing "action capabilities," allowing them to perceive their environment, plan multi-step tasks, and execute complex workflows with minimal human intervention [8][14] - The integration of large language models (LLMs) with external tools enables AI agents to actively gather information, analyze data, and take actions rather than merely responding to commands [14] Group 2: Applications in Cancer Research - AI agents can autonomously generate research hypotheses, design experimental protocols, execute data analysis, and write academic papers, marking a significant shift towards fully automated research processes [17][15] - Multi-agent collaborative systems are emerging, where different AI agents simulate human research teams by taking on specific expert roles, enhancing problem-solving comprehensiveness and decision-making transparency [18] Group 3: Clinical Oncology Applications - In clinical settings, AI agents can integrate various medical data sources, support treatment decisions, and automate clinical trial matching, significantly improving efficiency and patient outcomes [22][20] - AI agents are capable of simulating human expert reasoning in image analysis, allowing for more complex clinical problem-solving [23] Group 4: Future Outlook and Challenges - The article outlines a three-phase process of "agentification" in cancer research and oncology, predicting a transition from current AI interfaces to fully integrated systems with autonomous capabilities [28][29] - Challenges include the need for new evaluation metrics for AI agents' performance, integration hurdles from research prototypes to clinical tools, and ethical considerations regarding the autonomy of AI systems [27][29]

Core Viewpoint - The article discusses the complex interactions between cancer cells and the tumor microenvironment (TME), emphasizing the potential of targeted cancer immunotherapies to disrupt immunosuppressive interactions, although many therapies show limited durability due to a lack of understanding of these interactions [2][3]. Group 1: Research Findings - A study published by a team from the University of Chicago reveals that tumor-initiating stem cells (tSC) regulate the plasticity of neutrophils through metabolic reprogramming, creating a protective niche that allows them to survive cancer immunotherapy, leading to cancer recurrence [4]. - The research indicates that targeting the SOX2-FADS1-PGE2 signaling axis could serve as a novel combination therapy strategy to prevent immunotherapy resistance and tumor recurrence [4]. Group 2: Mechanisms of Immune Evasion - The study highlights the heterogeneity of tumor-associated neutrophils (TAN) and how different states of TAN arise and evolve, impacting the effectiveness of cancer immunotherapy [8]. - It was found that anti-PDL1 + CD40 agonist immunotherapy can induce TAN to regain anti-tumor activity in squamous cell carcinoma (SCC), while TAN at the tumor-stroma interface maintain their immunosuppressive state [8]. Group 3: Key Pathways and Implications - The SOX2 high-expressing tSCs enhance PGE2 signaling in TAN, which may disrupt interferon responses and inhibit the anti-tumor functions of TAN [9]. - Specific knockout of PGE2 receptors in neutrophils or using COX-2 inhibitors to block PGE2 synthesis can effectively restore the anti-tumor functions of neutrophils, enhancing the efficacy of immunotherapy and significantly reducing tumor recurrence rates [9]. Group 4: Overall Conclusions - The research explores how effective immunotherapies influence the plasticity of TAN, revealing how tSCs evade TAN-mediated anti-tumor immunity, allowing them to survive cancer immunotherapy and promote recurrence [12].

Core Viewpoint - The research indicates that targeting GPR81 represents a potential new strategy for treating hyperglycemia independent of insulin [5] Group 1: Research Findings - The study identifies L-lactate as an insulin-independent glucose uptake regulator that can alleviate hyperglycemia [4] - The absence of LDHA in muscle reduces lactate production, impairing glucose homeostasis in mice, while administering lactate or genetically enhancing lactate production improves glucose control [4] - Knockout of the lactate receptor GPR81 in skeletal muscle worsens glucose tolerance, whereas its ectopic expression or pharmacological activation enhances carbohydrate metabolism [4] Group 2: Mechanism of Action - Mechanistically, GPR81 recruits FARP1 to activate RAC1, promoting GLUT4 translocation independent of insulin signaling [4] - Notably, the expression of LDHA, GPR81, and FARP1 is upregulated after exercise, and the GPR81 variant is highly correlated with human fasting insulin levels, emphasizing the synergistic role of the GPR81-FARP1-GLUT4 signaling axis in glucose regulation alongside insulin [4]

Core Views - Beijing University Shenzhen Graduate School (PKUSZ) aims to integrate its research and teaching with the resources of the Greater Bay Area, focusing on academic innovation and societal service [2] - The establishment of the School of AI for Science (PKUSAI4S) in 2025 represents a strategic initiative to merge artificial intelligence with fundamental sciences, fostering interdisciplinary research and innovation [3][4] - The School of Intelligent Engineering (PKUSECE) emphasizes the integration of education, academic research, and industry, leveraging the advantages of the Greater Bay Area [7] Recruitment Areas - PKUSZ is recruiting in three core areas: - Integrated Circuit Science and Engineering, focusing on analog circuit design, micro-nano electronic devices, or electronic design automation for tenured or tenure-track assistant professors [8] - Computer Science and Technology, with emphasis on video and audio processing, XR/3D media processing, computer vision, computer graphics, haptic information processing, artificial intelligence, and robotics for tenure-track assistant professors [8] - Communication and Information Systems, concentrating on wireless communication, intelligent communication, the Internet of Things, and RF devices for tenured or tenure-track assistant professors [8] Academic Vision - The vision of PKUSZ is to accelerate scientific discovery and define the future of industries, promoting a collaborative and innovative academic environment [4] - The educational philosophy emphasizes fundamental principles, wisdom-driven approaches, and cross-disciplinary integration to shape the future [5]

Core Viewpoint - The study reveals a mechanism by which the STING-CD38 signaling axis in macrophages promotes the survival of regulatory T cells (Tregs) and accelerates the progression of non-small cell lung cancer (NSCLC) driven by KRAS mutations, providing insights into the limited efficacy of STING agonists in clinical settings [2][3][6]. Group 1 - The STING-CD38 signaling axis in macrophages depletes NAD+ in the tumor microenvironment, thereby promoting Treg survival and creating an immunosuppressive state that facilitates tumor progression [3][4]. - In a KRAS G12D-driven NSCLC mouse model, STING activation in macrophages was found to enhance Treg survival and accelerate NSCLC progression [4][6]. - Mechanistic studies indicate that STING-mediated NF-κB activation upregulates CD38 in Siglec-F low macrophages, leading to the hydrolysis of extracellular NAD+ in the tumor microenvironment [5][6]. Group 2 - Genetic knockout of STING or CD38, or treatment with CD38 inhibitors, restores NAD+ levels, induces Treg apoptosis via the ART2-P2RX7 signaling axis, and enhances anti-tumor CD8+ T cell responses [6][9]. - Importantly, CD38 inhibitors can increase the sensitivity of NSCLC mice to low-dose anti-CTLA4 therapy, suggesting a potential therapeutic strategy for overcoming resistance in immune checkpoint blockade (ICB) [6][9].

编辑丨王多鱼 排版丨水成文 组蛋白乙酰转移酶 （Histone acetyltransferase， HAT ） 通过修饰染色质来调控基因表达。该类酶并非独立发挥作用，而是与其他蛋白质形成复合物，从而改 变其底物特异性、基因组定位及细胞功能。 在这项最新研究中，为探究组蛋白乙酰转移酶 （HAT） 的复合物依赖性功能研究团队开发了一种化学方法，可在不干扰其他复合物的情况下特异性解离染色质上 的 ATAC 复合物。 ATAC 特有亚基 YEATS2 包含的 YEATS 结构域，是一种新型组蛋白乙酰化"阅读器" （Reader） ，研究团队针对 YEATS2 设计化学抑制剂 （而非靶向共有的 组蛋白乙酰转移酶） ，其中最高效的抑制剂—— LS-170 ，能够特异性降低 ATAC 复合物的染色质占据率，减少其介导的组蛋白乙酰化水平，并下调 ATAC 调 控基因的表达，在 肺癌 小鼠模型中显著抑制肿瘤生长。 ATAC 组蛋白乙酰转移酶复合物是一种重要的表观遗传调控因子，其异常激活与多种癌症的发生发展密切相关。然而， ATAC 与 SAGA 复合物共享催化亚基 GCN5/PCAF，这导致 传统的催化活性抑制剂或基因敲除手 ...

Group 1 - The core finding of the research indicates that obesity impairs gut repair through elevated levels of adipocyte fatty acid-binding protein (AFABP), which leads to iron overload in intestinal stem cells (ISCs) [2][6] - The study identifies the adipose tissue-gut signaling axis as a new therapeutic target for obesity-related intestinal diseases [3][7] - Increased AFABP secretion in obesity disrupts iron homeostasis in ISCs, hindering their differentiation, which is crucial for gut repair after injury [6] Group 2 - Overexpression of AFABP in adipocytes of lean mice obstructs ISC differentiation and gut repair, while reducing AFABP levels or using AFABP inhibitors, iron chelators, or peroxisome proliferator-activated receptor (PPAR) agonists can alleviate colitis in obese mice [6]