Core Viewpoint - The article discusses the increasing prevalence of Inflammatory Bowel Disease (IBD) in China, highlighting the role of the IL17REL gene in the disease's susceptibility and its potential as a therapeutic target [2][8]. Group 1: Overview of IBD - IBD includes Ulcerative Colitis (UC) and Crohn's Disease (CD), characterized by chronic, non-specific intestinal inflammation with no known cure, lifelong recurrence, and potential disability [2]. - The incidence of IBD in China has been rising annually, with current treatments focusing on immunomodulators and corticosteroids to alleviate inflammation or surgical removal of affected gastrointestinal sections [2]. Group 2: IL17REL Gene Research - The IL17REL gene locus has been identified as associated with susceptibility to IBD, but its functional protein coding and causal contribution to disease mechanisms remain unclear [3]. - A study published in Nature Immunology reveals that IL-17REL plays a significant protective role in IBD by acting as a decoy receptor for IL-17 family cytokines, inhibiting the activation of the IL-17 signaling pathway and downstream inflammatory gene expression [4][7]. Group 3: Mechanism and Implications - The study confirms that the wild-type IL-17REL protein can bind to IL-17 cytokines and suppress intestinal inflammation, while IBD-related mutations in IL17REL lack this function [7][9]. - TGFβ1 induces IL17REL transcription, and its expression correlates positively with TGFB1 levels in IBD patients [7]. - In mouse models, the introduction of the IL17REL gene alleviates colitis induced by 2,4,6-trinitrobenzenesulfonic acid, whereas the introduction of IBD-related IL17REL mutations does not yield this effect [7]. - Therapeutic administration of IL-17REL protein can reduce colitis symptoms, indicating its potential as a treatment target for IBD [8].

Core Viewpoint - Gastric cancer (GC) is the fifth most common cancer globally and a leading cause of cancer-related deaths, with China accounting for nearly 50% of the world's cases despite having only 20% of the global population [3] Group 1: Research Findings - Helicobacter pylori is a major risk factor for gastric cancer, but only 1%-3% of infected individuals develop the disease, indicating other contributing factors [3] - Recent studies by teams from Hong Kong Chinese University and Shanghai Jiao Tong University have identified Streptococcus anginosus as a promoter of gastric cancer through its metabolic product, methionine [3][5] - The research published in the journal Gut demonstrates that S. anginosus enhances gastric cancer progression, providing new insights for potential personalized treatment targets [3][5] Group 2: Methodology and Results - The research utilized shotgun metagenomic sequencing to explore the interaction between S. anginosus and the host, confirming its pro-inflammatory effects [5] - Experiments showed that the abundance of S. anginosus in gastric cancer patients correlates with a significant enrichment of the methionine biosynthesis pathway [5] - The study identified metE gene as crucial for methionine biosynthesis, with higher abundance observed in cancerous tissues, further validated by constructing a mutant strain of S. anginosus lacking the metE gene [5]

撰文丨王聪 编辑丨王多鱼 排版丨水成文 维持体内平衡 （即在外部变化中保持内部稳定的能力） ，对于生物体的生存至关重要。在神经系统中，这需要一些机制，既能在生理条件下维持神经元功能，又 能对损伤产生适应性反应。然而，与轴突能够再生的 外周神经系统 （PNS） 不同，成年 中枢神经系统 （CNS） 在损伤后无法再生，这既是因为抑制性的环 境，也是由于神经元本身生长能力的不足。这凸显了这两个系统在稳态和修复反应效率上的根本差异。 尽管在寻找再生的分子调控因子方面付出了巨大努力，但有效的再生策略仍然有限。对于 脊髓损伤 （SCI） 来说，目前尚无治愈方法，因此，发现这些再生调控 因子尤为紧迫。 2026 年 1 月 5 日，帝国理工学院 Simone Di Giovanni 团队 （博士生 宋雅玥 为第一作者） 在国际顶尖学术期刊 Cell 上发表了题为： A glycolytic shunt via the pentose phosphate pathway is a metabolic checkpoint for nervous system sensory homeostasis and axonal re ...

Core Viewpoint - The article discusses the rapid development of medical AI, particularly focusing on the limitations of single models and the introduction of the "Model Confrontation and Collaboration" (MCC) framework to enhance medical reasoning and decision-making in AI systems [3][4]. Group 1: MCC Framework - The MCC framework aims to transition medical AI from "single-point intelligence" to "collaborative reasoning" by creating a dynamic, debate-based model that enhances reliability, interpretability, and collaboration [4]. - It establishes a "shared context workspace" where different language models can generate answers and key arguments in parallel, ensuring that all models have visibility into the complete dialogue history during debates [8]. Group 2: Core Process of MCC - The MCC process consists of three main steps: 1. **Independent Reasoning**: Multiple models generate answers and key arguments simultaneously, with a gate system activating debates only when discrepancies arise [9]. 2. **Debate as Action**: Models engage in multi-round messaging, performing actions like questioning, providing evidence, rebutting, and reflecting on their reasoning chains to enhance accuracy [10]. 3. **Consensus Optimization**: After each round, a consensus is determined, and if no agreement is reached within three rounds, a majority vote is used as the fallback output strategy [10]. Group 3: Performance Metrics - The MCC framework has demonstrated strong performance on various medical benchmarks, achieving an average accuracy of 92.6% on MedQA and maintaining over 90% accuracy across multiple subjects in MMLU [13]. - It also shows robust performance in more challenging assessments, such as achieving approximately 40% accuracy on MedXpertQA and effectively managing uncertainty in MetaMedQA [14]. Group 4: Long-form Question Answering - In long-form question-answering tasks, the MCC framework outperformed other models in key dimensions, with improvements of 8-12 percentage points in critical areas such as reasoning correctness and bias control [16]. - The framework achieved a comprehensive score of 92.1 on HealthBench, indicating its robustness and safety in complex clinical scenarios [16]. Group 5: Interactive Diagnostic Conversations - The MCC framework was tested in simulated diagnostic conversations, capturing over 80% of key patient information points and demonstrating higher relevance in questioning compared to single models [19]. - In diagnostic conclusions, the MCC framework achieved an 80% accuracy rate in preferred diagnoses, showcasing its ability to enhance diagnostic reasoning through collaborative questioning [19]. Group 6: Implications and Future Directions - The study indicates that multi-model confrontation and collaboration can enhance medical reasoning capabilities without additional task training or external knowledge bases, improving the quality and stability of outputs in complex scenarios [22]. - The MCC framework is not intended to replace physicians but to provide multi-faceted arguments and traceable debate logs to assist clinical personnel in reducing diagnostic errors and enhancing decision transparency [22].

编辑丨王多鱼 排版丨水成文 基因与细胞治疗正处于疾病创新性治疗手段的最前沿，已成为肿瘤、代谢性疾病、遗传病等多类重大疾病 的重要突破口，有望显著提升临床疗效并改善患者生活质量。然而，传统细胞与基因治疗在实际临床应用 中仍面临诸多挑战，例如给药方式复杂、体内调控精度不足以及患者长期治疗依从性较低等问题。 这些瓶 颈在一定程度上制约了相关技术从实验室走向临床转化。 在此背景下， 如何实现对 " 活体药物 " 的个性化、精准化和可控化调节 ，成为医学界、产业界和学术界 共同关注的前沿难题 。 阿洛酮糖 是一种天然存在的稀有单糖，已被美国食品药品监督管理局 （ FDA ） 认定为"普遍认为安全 （ GRAS ） "的食品成分。其甜度约为蔗糖的 70% ，热量极低，血糖生成指数接近于零，并被认为具有辅助 调节血糖和脂质代谢的潜在益处，因此广泛应用于无糖食品和饮料中。 2025 年，我国国家卫生健康委员 会亦正式批准阿洛酮糖作为新食品原料，为其在健康与生物医学领域的应用奠定了政策基础。 PURE 系统 以来源于土壤农杆菌 （ Agrobacterium tumefaciens ） 的转录因子 PsiR 为核心调控元件。 ...

Core Viewpoint - Colorectal cancer (CRC) is the third most common cancer globally and the second leading cause of cancer-related deaths, with limited efficacy of immunotherapy in most cases [2] Group 1: Research Findings - A study published by Professor Zhou Weijie’s team reveals that APC deficiency inhibits CD8+ T cell infiltration and allows CRC to evade the immune response through PTPN13's dephosphorylation of STAT1, independent of the β-catenin pathway [3][6] - The use of an 11-amino-acid peptide from the C-terminus of APC (APC11) targets PTPN13, blocking the PTPN13-STAT1 interaction, promoting STAT1 phosphorylation, and enhancing the effectiveness of PD-1 blockade therapy [6][8] - The research uncovers a previously unknown APC/PTPN13/STAT1-dependent tumor immune suppression mechanism [7] Group 2: Implications for Treatment - The significant anti-tumor effects observed from the combination of anti-PD-1 antibodies and APC11 peptides provide important targets and theoretical foundations for the development of anti-tumor drugs for CRC patients [8]

Core Viewpoint - The study reveals a novel regulatory axis involving GPX4 and ZP3 receptors that impairs antitumor immunity during ferroptosis, suggesting new therapeutic targets for cancer immunotherapy, especially for patients unresponsive to existing treatments [2][3][16]. Group 1: Mechanism of Action - The research identifies that during ferroptosis, cancer cells release GPX4 protein, which binds to ZP3 receptors on dendritic cells, activating a signaling cascade that inhibits glycolysis and impairs dendritic cell maturation and activation, leading to T cell activation defects [3][6][14]. - Disruption of the GPX4-ZP3 interaction can restore dendritic cell metabolic activity and enhance antitumor immunity, indicating a potential therapeutic strategy [3][16]. Group 2: Clinical Implications - Clinical data show that higher serum levels of GPX4 correlate with poorer treatment outcomes, and elevated ZP3 expression is associated with unfavorable prognosis across various solid tumors [16][18]. - In preclinical models, blocking the GPX4-ZP3 interaction significantly enhances the efficacy of chemotherapy, immunotherapy, and radiotherapy, providing a new approach to overcoming tumor resistance [16][19]. Group 3: Future Directions - The findings open avenues for personalized cancer immunotherapy by targeting the GPX4-ZP3 pathway, potentially benefiting patients who do not respond to current immunotherapies [18][19]. - Ongoing research aims to translate these discoveries into clinical applications, with the possibility of using GPX4 and ZP3 levels as biomarkers for tailored treatment strategies [19][20].

撰文丨王聪 编辑丨王多鱼 排版丨水成文 嵌合抗原受体 （CAR） T 细胞疗法，在血液类肿瘤中展现了强大的治疗效果，然而，其在占据癌症大多数 的 实体瘤 中的临床应用仍受到显著安全性问题的限制， 尤其是 非肿瘤靶向毒性 （ on-target, off-tumor toxicity） 和 细胞因子释放综合征 （CRS） 。 2026 年 1 月 2 日，深圳湾实验室分子生理学研究所 蔡羽轩 团队联合厦门大学 吴川六 教授、 深圳湾实验 室转化创新中心 康曦 研究员， 在 J ournal of the American Chemical Society 期刊发表了题为： Disulfide-directed multicyclic peptides for chimeric antigen receptors targeting solid tumors 的研究 论文。 该研究将嵌合抗原受体 （CAR） 的抗原识别域从传统抗体片段 （scFv） 换成 定向二硫键多环肽 （DDMP） ，让 CAR-T 细对抗原高表达肿瘤细胞保持强杀伤，而对抗原低表达细胞则显著减少结合与杀 伤，从而减轻 非肿瘤靶向毒性 （ on ...

Core Insights - Shenzhen Medical Academy of Research and Translation (SMART) aims to pave new paths in future medical science by fostering original innovation and developing a top-tier talent team to address urgent challenges in healthcare [3] - SMART employs a comprehensive approach to break down barriers between clinical medicine, basic research, and industrial transformation, positioning Shenzhen as a hub for biomedical science [3] Group 1: Organizational Overview - SMART is dedicated to transforming scientific technology into public health, emphasizing the importance of innovation in biomedical research [3] - The organization is rooted in Shenzhen and aspires to make the city a gathering place for talent and a powerful force in global biomedical science [3] Group 2: Job Overview - The i-BRAIN Nanofabrication Facility at SMART is a world-class international facility supporting cutting-edge brain-computer interface (BCI) and neurotechnology research [6] - The facility is seeking proactive senior engineers to lead in one of four technical areas, focusing on process development, tool operation, and user training [6] Group 3: Responsibilities and Qualifications - Key responsibilities include process development and optimization, equipment operation and maintenance, and collaboration for facility support [9][10] - Candidates should have a bachelor's degree or higher in relevant fields, with a minimum of 5 years of hands-on experience in cleanroom environments and expertise in areas such as EBL, DUV Stepper, Photolithography, or PVD/Metrology [13][11] Group 4: Benefits of Joining - Joining SMART offers the opportunity to contribute directly to transformative BCI and medical device development, work with advanced lithography and deposition systems, and be part of a global team shaping the future of neurotechnology [18]

Core Findings - High altitude exposure leads to gut microbiome imbalance, resulting in decreased sperm quality [5] - Increased levels of C. symbiosum produce succinic acid, which damages sperm quality [5] - Succinic acid activates the GPR91/TRPV4/Ca2+ signaling pathway in testicular macrophages, promoting the polarization of these cells [5][4] - The polarization of macrophages induced by succinic acid increases apoptosis of spermatogenic cells [5] Mechanism Insights - The study reveals that high altitude induces changes in the gut microbiome, specifically an increase in C. symbiosum, which negatively impacts sperm quality [4] - Succinic acid acts on G protein-coupled receptor GPR91, leading to the activation of TRPV4/Ca2+ signaling in testicular macrophages, resulting in inflammatory polarization [4][5] - The impact of C. symbiosum or succinic acid on sperm quality is dependent on TRPV4 signaling [4] Implications for Treatment - The research suggests potential therapeutic pathways based on gut microbiome modulation to address altitude-induced sperm damage [7]