撰文丨王聪 编辑丨王多鱼 排版丨水成文 2025 年 10 月 9 日， 上海交通大学材料科学与工程学院、氢科学中心 何前军 教授 、 华中科技大学同济医学院附属同济医院 喻波 研究员、金华市中心医院 杨 骐宁 主任医师等，在 Cell 子刊 Cell Biomaterials 上发表了题为： Local sustained H₂ release assisted stem cell transplantation for enhanced osteoarthritic cartilage regeneration 的研究论文。 该研究发现， 氢气 （H₂） 能够 逆转 骨关节炎 （OA） 的软骨细胞表型，进而开发了 Mg₂Si 纳米片 （MSN） ，将其与 脂肪干细胞微球共同封装在水凝胶中， 可实现 超持久水解产氢 （长达 28 天） ， 这种局部持续释放 H₂ 辅助干细胞移植的策略，有效促进了骨关节炎的软骨再生。 骨关节炎 （OA） 微环境会导致移植干细胞迅速失去活力并发生意外分化，这给 干细胞移植 （SCT） 治疗 带来了巨大障碍。 干细胞移植 （SCT） 通过移植干细胞来促进受损组织修复其再生能力的缺 ...

Core Viewpoint - The article discusses the significance of the 2025 Nobel Prize in Physiology or Medicine awarded to Mary Brunkow, Fred Ramsdell, and Shimon Sakaguchi for their groundbreaking work on regulatory T cells (Treg cells) and their role in immune tolerance, which has profound implications for understanding autoimmune diseases and cancer escape mechanisms [3][35]. Group 1 - The Nobel Prize was awarded for the discovery and definition of CD4+ CD25+ FOXP3+ regulatory T cells (Treg cells) and their importance in controlling self-reactive responses, marking a new field of research in peripheral immune tolerance [3][35]. - The research highlights the collaborative effort and curiosity in science, leading to a transformative understanding of immune regulation [3][35]. - The findings have significant implications for the treatment of autoimmune diseases and cancer, emphasizing the potential of Treg cells in clinical applications [35]. Group 2 - Mary Brunkow expressed her surprise at receiving the Nobel Prize, reflecting on the teamwork involved in their research and the changes in her scientific career since then [14][24]. - Fred Ramsdell shared a humorous account of how he learned about his award while camping, illustrating the unexpected nature of the recognition [23][24]. - Shimon Sakaguchi emphasized the importance of persistence in research, stating that the discovery of Treg cells was a result of continuous exploration despite challenges in the field [33][35]. Group 3 - The article highlights the collaboration between biotechnology and academic sectors, showcasing how such partnerships can lead to significant advancements in medical treatments [29][30]. - The historical context of the research is noted, with the original findings based on a mutant mouse model that exhibited severe autoimmune phenotypes, underscoring the importance of foundational research [30][31]. - The recognition of their work is seen as a motivation for further exploration and application of Treg cells in treating various immune diseases and improving organ transplant outcomes [35].

Core Viewpoint - The research reveals that specific mutations in the cGAS protein of naked mole-rats enhance DNA repair mechanisms, potentially leading to extended lifespan and healthspan, suggesting a new strategy for aging intervention in humans [2][3][9]. Summary by Sections Research Findings - The study identifies four specific amino acid mutations in the cGAS protein of naked mole-rats that convert it from a DNA repair inhibitor to a repair enhancer, thereby promoting DNA repair and delaying aging [3][6]. - Compared to humans and mice, naked mole-rat cGAS improves the efficiency of homologous recombination repair, which is crucial for maintaining genomic stability [6][9]. Mechanism of Action - The mutations in cGAS alter its interaction with ubiquitin, extending its retention time on chromatin after DNA damage, which enhances the formation of complexes necessary for DNA repair [6][9]. - The study demonstrates that the naked mole-rat cGAS mitigates stress-induced cellular aging and organ degeneration, contributing to increased lifespan [6][9]. Experimental Validation - Delivery of naked mole-rat cGAS to aged mice using adeno-associated virus (AAV) alleviated signs of frailty, reduced inflammation markers, and decreased cellular aging indicators, thereby extending healthspan [7][9]. Implications for Human Aging - The findings suggest that mimicking the unique mutations of naked mole-rat cGAS through small molecules or gene editing could offer new avenues for delaying aging and enhancing healthspan in humans [3][9].

撰文丨王聪 编辑丨王多鱼 排版丨水成文 逆转座子 （ Retrotransposon ） 通过 RNA 中间体复制并将其编码序列插入新的基因组位置，对基因组完 整性构成风险。在人类中，唯一自主活跃的逆转座子是 LINE-1 （ long interspersed nuclear element–1 ） ，它通过靶标启动的逆转录 （TPRT） 入侵基因组。这一过程由 LINE-1 编码的 ORF2p 催化， ORF2p 具有内切酶 （EN） 和逆转录酶 （RT） 活性。 然而， ORF2p 如何精确调控 LINE-1 的基因组靶 向及 TPRT 的执行机制，目前仍不清楚。 2025 年 10 月 9 日，中国科学院生物物理研究所 许瑞明 、 金文 星 团队在国际顶尖学术期刊 Science 上 发表了题为： Mechanism of DNA targeting by human LINE-1 的研究论文。 在这项最新研究中，研究团队在真核细胞中表达了人类 ORF2p，并纯化了 ORF2p 与内源性核酸形成的复 合物。通过冷冻电镜 （cryo-EM） 、脱氧核糖核酸酶和核糖核酸酶消化以及 DNA 和 RNA 测序 ...

撰文丨王聪 编辑丨王多鱼 排版丨水成文 世界卫生组织 （WHO） 曾发一份多重耐药菌名单，统称为 ESKAPE ， 代表了六种最棘手、最常见的多重耐药细菌， 名单之首是 耐碳青霉烯类鲍曼不动杆菌 （CRAB） 。碳青霉烯类抗生素是所有其他治疗手段都失败时的"最后一道防线"，但其极易受到抗生素耐药性的出现和传播的影响。鉴于这一紧迫问题，人们越 来越关注 抗菌肽 （AMP） 作为传统抗生素的有前景替代品。 与传统抗生素相比， 抗菌肽 （AMP） 因其广谱活性、快速杀菌机制以及诱导耐药性的可能性较小，成为很有前景的抗生素替代品。发现针对临床多重耐药菌的 新型抗菌肽，对于应对持续的抗生素耐药危机至关重要。 2025 年 10 月 3 日，山东大学齐鲁医学院 张磊 教授、 赵国平 教授团队在 Nature 子刊 Nature Microbiology 上发表了 题为： A generative artificial intelligence approach for the discovery of antimicrobial peptides against multidrug-resistant bacteria ...

Core Viewpoint - The effectiveness of REDD+ projects, aimed at reducing emissions from deforestation and degradation, has been questioned recently, leading to a decline in the value of carbon offsets [2][6]. Group 1: REDD+ Project Analysis - A study published in the journal Science analyzed 52 REDD+ projects across 12 countries in South America, Africa, and Southeast Asia, finding that only 19% of these projects met their self-reported emission reduction targets [3][6]. - The study indicates that while the climate benefits of REDD+ projects are higher than previous assessments, the overall effectiveness remains low, with significant regional variations in project success [6][7]. - The research highlights a concerning issue of "over-crediting," where the number of carbon credits issued exceeds the actual emissions reductions achieved [6][7]. Group 2: Recommendations for Improvement - To enhance the credibility and impact of forest carbon offsets, the study suggests improving baseline setting methods and strengthening verification frameworks [7]. - The findings emphasize that while many REDD+ projects are not as effective as claimed, some have achieved tangible results, particularly in Brazil and Africa [7].

Core Insights - On October 8, 2025, 15 papers were published in the prestigious journal Nature, with 4 authored by Chinese scholars [2][4][6][8] Group 1: Research Contributions - Professor Zhao Huimin from the University of Illinois Urbana-Champaign published a paper titled "Enzyme specificity prediction using cross attention graph neural networks," introducing an innovative AI model called EZSpecificity that predicts enzyme substrate specificity with high accuracy, aiding in enzyme engineering and synthetic biology [2] - Professor Zhou Peng from Fudan University published a paper titled "A full-featured 2D flash chip enabled by system integration I," focusing on advancements in 2D flash memory technology through system integration [4] - MIT's Liu Qi co-authored a paper titled "Quantum-amplified global-phase spectroscopy on an optical clock transition," contributing to the field of quantum spectroscopy [6] - Professors Lou Zhenkun and Huang Jinzhu from Mayo Clinic published a paper titled "KCTD10 is a sensor for co-directional transcription–replication conflicts," revealing a ubiquitin ligase complex that detects transcription-replication conflicts and regulates replication body progression to prevent DNA damage [8]

Core Insights - The article discusses the development of nucleic acid aptamer-based therapeutics by a research team led by Academician Tan Weihong from the Chinese Academy of Sciences, focusing on potential treatments for Alzheimer's disease and triple-negative breast cancer [2][9]. Group 1: Alzheimer's Disease Treatment - The research team developed Apt-M, a nucleic acid aptamer-armed monocyte therapy, which targets and clears extracellular Tau protein, alleviating neuroinflammation in mouse models of Alzheimer's disease [4][6]. - Treatment with Apt-M resulted in reduced activation of glial cells, alleviated neuroinflammation, and preserved neuronal and mitochondrial integrity, leading to improved memory and spatial learning abilities in the Alzheimer's mouse model without causing toxicity or behavioral side effects [6][8]. Group 2: Triple-Negative Breast Cancer Treatment - The team introduced CD4 aptamer-engineered cell platforms (Apt CD4-LNT) that selectively recruit and activate CD4+ T cells, enhancing anti-tumor immunity in triple-negative breast cancer [10][12]. - This approach aims to overcome challenges related to poor tumor infiltration and immunosuppressive tumor microenvironments, thereby promoting targeted infiltration and activation of CD4+ T cells, which in turn enhances the activity of NK cells, B cells, and dendritic cells [12][14]. Group 3: Cancer Therapy with Aptamer-Drug Conjugates - The research also presented Sgc8c-M, an aptamer-drug conjugate (ApDC) combining a potent anti-mitotic agent MMAE with the PTK7 nucleic acid aptamer, showing promise in treating cancers that overexpress PTK7 [16][17]. - Comprehensive evaluations from rodents to non-human primates indicated that Sgc8c-M effectively induced sustained tumor regression in xenograft models, outperforming unlinked MMAE, the chemotherapy drug paclitaxel, and a PTK7-targeted antibody-drug conjugate [17][19].

撰文丨王聪 编辑丨王多鱼 排版丨水成文 肾细胞癌 （RCC） 是泌尿系统常见的恶性肿瘤，其确切病因仍有待探究。 肾透明细胞癌 （ccRCC） 是肾细胞癌最常见的病理类型，约占 70%。 越来越多的证据表明，作为人体关键组成部分的 肠道微生物群 在肿瘤发生以及对治疗的响应方面具有重要影响。尽管已有研究显示某些肠道微生物及其相关活性 产物与 ccRCC 的治疗有关，但肠道微生物组与 ccRCC 形成之间的关系仍不确定。因此，阐明肠道微生物组对 ccRCC 肿瘤进展的潜在影响至关重要。 2025 年 10 月 8 日，上海交通大学医学院附属 仁济医院 翟炜 研究员、上海交通大学医学院 刘尽尧 研究员团队合作，在 Cell 子刊 Cell Reports Medicine 上发 表了题为： Intestinal Lachnospiraceae bacterium -derived propionate inhibits the progression of clear cell renal cell carcinoma 的研究论文。 该研究表明，肠道细菌 Lachnospiraceae bacterium （ L. ...

Core Viewpoint - The article discusses a groundbreaking AI model named EZSpecificity, developed by a research team led by Professor Zhao Huimin from the University of Illinois at Urbana-Champaign, which predicts enzyme substrate specificity with high accuracy, aiding in enzyme engineering and synthetic biology applications [2][3]. Group 1: Enzyme Specificity and Challenges - Enzymes are large protein molecules that catalyze reactions, and their specificity refers to the degree of fit between an enzyme and its substrate, often likened to a "lock and key" mechanism [6]. - Identifying the optimal enzyme-substrate combinations is challenging due to the dynamic nature of enzyme conformations during interactions and the existence of enzyme polymorphism, which complicates predictions [6][8]. Group 2: Development of EZSpecificity Model - The EZSpecificity model combines cross-attention mechanisms with SE(3)-equivariant graph neural networks to accurately predict enzyme substrate specificity, thus providing a new methodological foundation for AI applications in enzyme engineering and green manufacturing [3][8]. - The research team collaborated to create a comprehensive database that includes enzyme sequences, structural information, and conformational data around various substrates, enhancing the model's predictive capabilities [8]. Group 3: Performance and Validation - In tests across four practical scenarios, EZSpecificity outperformed the leading model ESP, achieving a success rate of 91.7% in accurately identifying unique reaction substrates, compared to ESP's 58.3% [11]. - The model is designed to be user-friendly, allowing researchers to input substrate and protein sequences to predict compatibility, marking a shift from "intelligent annotation" to "intelligent recognition" in enzyme research [11]. Group 4: Future Directions - Future plans include expanding the model to analyze enzyme selectivity regarding specific substrate sites, which will help eliminate off-target effects, and continuing to refine EZSpecificity with additional experimental data [11].