Core Insights - Immune therapy has fundamentally changed the clinical approach to tumor treatment, particularly with PD-1/PD-L1 immune checkpoint inhibitors, which have received continuous FDA approvals for both monotherapy and combination therapy. However, the clinical benefits in advanced tumor patients remain limited due to low somatic mutation rates, few infiltrating lymphocytes, and low PD-L1 expression levels, indicating these tumors are "cold tumors" [2] - Various immune cytokines such as IL-2, IL-7, IL-12, and IL-15 have been identified to regulate T cell proliferation, survival, and function, with the potential to convert "cold tumors" into "hot tumors" and enhance anti-tumor responses when used in conjunction with immune checkpoint inhibitors. Nonetheless, their clinical application faces challenges including technical difficulties, safety concerns, and insufficient efficacy observed in advanced tumors [2] Group 1 - The recent study published in Cell Reports Medicine demonstrates the local delivery of IL-15 and anti-PD-L1 nanobody via in vitro transcribed circILNb, which activates robust anti-tumor immunity in "cold tumors" that are unresponsive to conventional immunotherapy [3][4] - The research team engineered a circCV-B3 vector to achieve scarless circular RNA (circRNA) engineering, allowing circILNb to co-encode IL-15 and anti-PD-L1 nanobody. This circILNb is purified through a biotin-avidin purification system and encapsulated in lipid nanoparticles (LNP) for intratumoral injection, leading to in situ protein expression and activation of existing CD8+ T cells and NK cells for local tumor control [6][8] Group 2 - The study highlights the potential of the circCV-B3 vector and BAPS as circRNA engineering methods, confirming that circILNb can serve as a non-protein therapeutic strategy for tumor immunotherapy [8]

撰文丨王聪 编辑丨王多鱼 排版丨水成文 生理学中的一个基本问题是了解组织如何适应并改变其细胞构成以响应饮食信号。哺乳动物的小肠由快速更新的 LGR5 + 肠道干细胞 （ISC） 维持，这些细胞会对诸如禁食方案和致肥胖饮食等宏量营养素的变化作出反应，然而，在稳态和损伤期间，特定氨 基酸如何控制肠道干细胞的功能，目前仍不清楚。 放疗和化疗等癌症治疗，以及炎症性肠病，都会导致肠道损伤。然而，长期以来，肠道损伤修复的复杂动态一直 困扰着研究人员，能够刺激 肠道内壁的肠道干细胞再生的干预措施，寥寥无几。 2025 年 10 月 1 日，麻省理工学院 Ömer H. Yilmaz 团队 （博士后 迟方涛 为第一作者） ，在国际顶尖学术期刊 Nature 上发表了题为： Dietary cysteine enhances intestinal stemness via CD8+ T cell-derived IL-22 的研究论文。 饮食来源的半胱氨酸 能够增强肠道损伤后肠道干细胞介导的肠 道再生。 该研究证实，饮食中的 半胱氨酸 ，通过 刺激 CD8+ T 细胞分泌 IL-22 ，增强肠道损伤后肠道干细胞介导的损伤修复和 ...

撰文丨王聪 编辑丨王多鱼 排版丨水成文 胰腺癌 （Pancreatic Cancer） ，是一种恶性程度很高，诊断和治疗都很困难的消化道恶性肿瘤，其中 胰腺导管腺癌 （PDAC） 占全部胰腺癌的 95% 以上。 胰腺癌早期的确诊率不高，发现时往往已是晚期，由于生存率低、预后差，胰腺癌也被称为" 癌中之王 "。 2025 年 10 月 9 日， 浙江大学医学院附属第一医院 梁廷波 教授团队在 Cell 子刊 Cancer Cell 上发表了题为： Neoadjuvant nab-paclitaxel plus gemcitabine followed by modified FOLFIRINOX for resectable pancreatic cancer: A randomized phase 3 trial 的研究论文。 这项随机 3 期临床试验， 在 324 例可切除的 胰腺癌 患者中，评估了 序贯新辅助治疗方案 与 直接手术方案 的疗效对比，结果显示，这种 新辅助白蛋白结合型 紫杉醇联合吉西他滨序贯改良 FOLFIRINOX 方案 ， 可显著 改善无事件生存期 ，且 安全性可控 ，为可切除的胰腺癌患 ...

Core Viewpoint - The research led by José C.R. Silva and Chen Chuanxin at Guangzhou National Laboratory presents a significant advancement in human post-implantation embryo modeling through the activation of the STAT3 signaling pathway, achieving high-fidelity models that address previous limitations in efficiency and accuracy [3][4][10]. Summary by Sections Research Background - The study addresses the inefficiencies and limited fidelity of current systems in simulating the post-implantation stage of human embryo development [3][6]. Key Findings - **STAT3 Mediated Pluripotent Stem Cell Reprogramming**: A specialized medium (SAM) enhances STAT3 activity, allowing pluripotent stem cells (PSCs) to be reprogrammed into various early cell lineages within 60 hours, including hypoblast, trophectoderm, naive epiblast, and extraembryonic mesoderm [7]. - **Efficient 3D Self-Organizing Model Construction**: Cells treated with SAM for 60-120 hours can be cultured in 3D, resulting in a significant increase in efficiency to 52.41% ± 8.92% for developing post-implantation embryo-like structures, surpassing current mainstream methods [8]. - **High Simulation of Natural Embryo Development**: The structures formed on day 6 closely resemble Carnegie stages 5-7 (CS5-CS7) human embryos, exhibiting features such as bilaminar disc structure, amniotic cavity formation, mesenchymal cell distribution, chorionic cavity, and trophoblast cell differentiation [8]. - **Successful Formation of Primitive Streak**: The CS6/7 stage embryo-like structures demonstrate key developmental events, including the correct formation and localization of the primitive streak, epithelial-mesenchymal transition (EMT), and differentiation of mesoderm and definitive endoderm [8]. - **Molecular Level Validation**: Single-cell transcriptome analysis shows that the model aligns closely with real CS6/7 human embryo data at the molecular level, confirming its biological relevance and research application value [8]. Implications - The STAT3 activation-induced model represents a breakthrough in overcoming existing efficiency bottlenecks (over 50% generation rate) and provides a more accurate in vitro platform for studying early human embryonic development mechanisms, congenital disease modeling, and drug toxicity testing [10]. This advancement marks a transition from "morphological simulation" to "functional simulation" in embryo modeling, opening new pathways for research in developmental biology and regenerative medicine [10].

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 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 ...

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 ...

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].