以下文章来源于赛业生物订阅号 ，作者西米 赛业生物订阅号 . 分享生命科学领域的前沿资讯、解读行业动态、讲解实用的学科知识、实验方法和技巧。 慢性肾脏病 （CKD） 是全球范围内的重大公共卫生挑战，影响着约10%的成年人口，其发病率与死亡率持 续攀升，给患者家庭及医疗卫生系统带来沉重负担。其核心病理特征之一是 肾小管间质纤维化 （TIF） ， TIF以肾小管萎缩、间质成纤维细胞活化、细胞外基质过度沉积与炎症浸润为特征，其严重程度与肾功能下降 速度和预后密切相关 。然而，目前针对TIF的治疗手段有限，开发特异性高、作用明确的新型抗纤维化药 物，已成为打破CKD治疗瓶颈、改善患者预后的迫切需求。 近期， 北京大学聂静教授团队 在 Kidney International 发表的研究论文发现，天然化合物水仙环素 （Narciclasine，Ncls） 能够显著逆转TIF相关基因表达。在多种CKD动物模型中，Ncls不仅减轻了纤维 化和炎症，还改善了肾功能。这一研究成果为CKD的治疗提供了潜在的新策略 [1] 。 新一期 「大咖来了，赛业有约」 系列课程，我们有幸邀请到通讯作者 北京大学聂静教授 ，于12月16日 （ ...

Core Insights - The article discusses the significant impact of rotavirus infections on neonates, particularly highlighting the severe symptoms and systemic infections that can arise, which are not effectively prevented by existing vaccines [2][5] - A recent study reveals that dysregulation of the hepcidin-iron axis plays a critical role in impairing antiviral immunity and causing liver damage in neonates infected with rotavirus, providing new therapeutic targets for related diseases such as biliary atresia [3][11] Summary by Sections Rotavirus and Its Impact - Rotavirus is a major cause of life-threatening gastroenteritis in children under five, leading to severe symptoms in neonates, including blood in stool and unstable vital signs, with current vaccination strategies offering no protection [2][5] - The prevalence of biliary atresia (BA) is noted, affecting 1 in every 5,000 to 18,000 newborns, with its etiology linked to infections, immune dysregulation, and genetic susceptibility [5] Research Findings - The study published in the journal Immunity identifies iron metabolism dysregulation as a key mechanism in rotavirus-related systemic infections in neonates, suggesting new treatment avenues [3][11] - Single-cell RNA sequencing revealed that iron dysregulation is a driving factor for liver damage in rotavirus infections, with elevated hepcidin levels inhibiting iron export and leading to cellular damage [6][9] Clinical Implications - An open-label clinical trial demonstrated that preoperative folic acid supplementation significantly reduced the incidence of cholangitis from 74% to 21% and liver transplantation rates from 41.1% to 11.1% in biliary atresia patients [8] - The study emphasizes the importance of targeting the hepcidin-iron signaling pathway to mitigate liver damage and improve outcomes in neonates with rotavirus infections [9][11]

Core Viewpoint - A research team from Zhejiang University has developed a novel cancer immunotherapy platform by repurposing mast cells, traditionally involved in allergic reactions, to deliver anti-cancer drugs directly to tumor sites, enhancing the immune response against cancer [2][5]. Group 1: Research Background and Methodology - The study published in the journal Cell describes a targeted therapy platform using engineered mast cells that act as "couriers" to deliver anti-tumor drugs by utilizing tumor-associated antigens as "allergens" [2][5]. - The engineered mast cells, sensitized with IgE antibodies specific to tumor markers, can migrate to tumor sites and trigger a rapid immune response, transforming "cold tumors" into "hot tumors" that are more susceptible to immune attack [5][11]. Group 2: Drug Delivery Mechanism - The engineered IgE-MC platform can carry various therapeutic agents, including oncolytic viruses, chemotherapy drugs, immune checkpoint inhibitors, and mRNA vaccines, with a focus on delivering oncolytic viruses [7][9]. - The oncolytic viruses can selectively infect and lyse tumor cells, and the IgE-MC protects these viruses from being cleared by the immune system during intravenous administration [9][10]. Group 3: Efficacy and Safety - In mouse models, treatment with OV@IgE-MC showed significant efficacy, with 60% of mice surviving beyond 25 days in the B16F10-OVA melanoma model, compared to a control group that all died within 15 days [11][12]. - Safety assessments indicated that injected IgE-MC are cleared within two weeks without disrupting mast cell homeostasis or inducing systemic allergic reactions, and they reduced liver toxicity compared to free oncolytic viruses [16][15]. Group 4: Future Prospects - The technology allows for personalized cancer treatment by matching specific IgE antibodies to patient tumor markers, simplifying the preparation process compared to traditional CAR-T cell therapies [18][19]. - The research team plans to establish a screening process for patient-specific IgE and explore combinations with existing immunotherapies, aiming to bring this innovative "tumor allergy" therapy from the lab to clinical application [19][18].

编辑丨王多鱼 排版丨水成文 2025 年 12 月 9 日， 在第 67 届 美国血液学会 （ASH） 年会上， 启函生物 进行了一场口头报告及多场 海报展示，公布了其 同种异体 CAR-T 项目 积极的临床结果，以及支持其 in vivo CAR-T 项目 开发的基 础性临床前数据。 启函生物 的口头报告重点介绍了三项评估 QT-019B 治疗多种 自身免疫疾病 的 IIT 临床数据，共纳入 20 例受试者。治疗耐受性良好，未发生超过 1 级的细胞因子释放综合征 （CRS） 事件，且未报告免疫效应 细胞相关神经毒性综合征 （ICANS） 或严重感染。 QT-019B 是由启函生物开发的一种"现货型"同种异体 CAR-T 细胞产品，其以健康供者外周血的白细胞单 采产物为起始原材料，经基因编辑，稳定表达两种不同的嵌合抗原受体 （CAR） ，分别靶向 CD19 和 BCMA，从而使 QT-019B 具备同时识别并清除表达 CD19 和 BCMA 细胞的能力。此外，为降低移植物 抗宿主病 （GvHD） 风险，该细胞产品通过基因敲除方式消除了 T 细胞受体 （TCR） 的表达；同时，为 减少同种异体免疫排斥，通过多重 ...

Core Viewpoint - The article highlights the achievements of prominent scientists awarded the Tengchong Science Prize, emphasizing their contributions to various fields of science and technology, particularly in quantum physics, biomedicine, and genetic research [3][7][10][12][15][17]. Group 1: Tengchong Science Prize - The Tengchong Science Prize was awarded for the first time in 2023, with recipients including Professors Lu Yuming and Zhang Feng [8]. - In 2024, the awardees were Professors Xue Qikun and Xie Xiaoliang [8]. - The prize is notable for being the first science and technology award initiated in mainland China with a single prize amount of 10 million RMB, focusing on significant breakthroughs in various scientific fields [17]. Group 2: Notable Awardees - Academician Pan Jianwei received the Tengchong Science Prize for his pioneering work in quantum optics and quantum information, making global secure quantum communication a feasible reality [3]. - Academician Xue Qikun's team discovered the quantum anomalous Hall effect, marking a significant experimental observation in physics [10]. - Academician Xie Xiaoliang is recognized for his foundational work in single-molecule biophysical chemistry and advancements in genome amplification technology, benefiting thousands of families with genetic disorders [12]. - Professor Lu Yuming is acknowledged as a pioneer in non-invasive prenatal testing, revolutionizing prenatal diagnostics and benefiting millions of pregnant women globally [15]. - Professor Zhang Feng is a leading figure in CRISPR-Cas gene editing technology, significantly impacting life sciences and molecular diagnostics [17]. Group 3: Tengchong Young Scientist Award - The Tengchong Young Scientist Award was established this year, covering ten subfields including mathematics, physics, materials science, and ecology [7]. - Notable recipients include Professor Wang Jianwei from Peking University and Professor Qian Xiaoshi from Shanghai Jiao Tong University, among others [7].

撰文丨王聪 编辑丨王多鱼 排版丨水成文 3D 生物打印 是一种三维生物制造技术，用于精确地排列细胞和含细胞生物材料 （生物墨水） ，以构建具有所需功能的立体生物组织。通常，生物墨水依靠水凝 胶基质在生物打印之前、期间或之后稳定并交联构建体。尽管此类方法推进了仿生学的发展，但其难以实现体内细胞的高密度，且大量水凝胶成分可能会阻碍细 胞间相互作用，导致表型丧失并降低组织功能。 近年来，无支架的 3D 生物打印技术被提出以解决细胞密度问题，但这类方法通常依赖于挤出式生物打印，难以无法达到复杂组织所需的分辨率和复杂度。 2025 年 12 月 8 日， 哈佛医学院 张宇 教授团队在国际大奖学术期刊 Cell 上发表了题为： Biomaterial-minimalistic photoactivated bioprinting of cell- dense tissues 的研究论文。 王冕 （现为同济大学研究员） 、 李婉露 （现为 上海交通大学 助理教授） 、 郝晋 （现为上海交通大学助理研究员） 、 蔡玲 为 论文共同第一作者 。 该研究开发了一种去材料化、无支架的 高细胞密度生物墨水 （ Cell-dense ...

Core Viewpoint - The article discusses the development of a multimodal AI model named eSPARK, which aims to enhance personalized treatment decisions for esophageal cancer, particularly esophageal squamous cell carcinoma (ESCC) [4][9]. Group 1: Background and Importance - Esophageal cancer (EC) is a common malignant tumor and the seventh leading cause of cancer-related deaths, with ESCC accounting for approximately 80% of cases [2]. - The prognosis for ESCC is poor, primarily due to late-stage diagnosis, and traditional surgical interventions have limited effectiveness for advanced cases [2][3]. Group 2: New Treatment Approaches - Neoadjuvant immunochemotherapy (nICT) has emerged as a promising treatment for esophageal cancer, but it only achieves optimal results in 20%-40% of patients, highlighting the need for reliable biomarkers to predict treatment response [3][6]. - The urgency to identify biomarkers is driven by the potential for improving patient outcomes and reducing unnecessary toxic side effects associated with over-treatment [3]. Group 3: Research Development - The study published in Cell Reports Medicine introduces the eSPARK model, which integrates multimodal deep learning to enhance predictive performance for nICT efficacy in ESCC [4][6]. - The model utilizes data from 344 patients, incorporating pre-treatment CT images and pathology slides, along with post-operative pathological complete response (pCR) outcomes [7]. Group 4: Key Findings - eSPARK demonstrates superior generalization capabilities compared to unimodal models and achieves robust predictive accuracy across multicenter datasets [7]. - The model identifies several biomarkers related to nICT treatment response, including the neutrophil-to-lymphocyte ratio (NLR), where a lower NLR may indicate better treatment response [7][9]. - The research emphasizes the potential of eSPARK in personalized treatment decision-making for locally advanced esophageal cancer and its broader implications for precision oncology through multidisciplinary data integration [9].

Core Insights - Lung cancer is the most common malignant tumor globally and the leading cause of cancer-related deaths, with non-small cell lung cancer (NSCLC) accounting for over 85% of cases. Despite advancements in clinical management, the 5-year overall survival rate for NSCLC patients has only increased from 15% to 25% [2] - Immune checkpoint inhibitors (ICIs), such as PD-1 and PD-L1 inhibitors, have transformed the treatment landscape for NSCLC. However, the objective response rate (ORR) for unselected NSCLC patients receiving ICI treatment is only 10%-30%, with some patients experiencing accelerated disease progression or early death [2] - A new study identified a circRNA signature (circRNA-Sig) consisting of 11 circRNAs that can predict the response to immunotherapy in advanced NSCLC, potentially guiding clinical treatment [3][8] Summary by Sections CircRNA and Cancer - CircRNA is associated with dysregulated RNA expression in cancer and has potential as a biomarker for predicting responses to ICIs [3] Research Findings - The research team analyzed circRNA expression profiles from 891 advanced NSCLC patients in the OAK and POPLAR clinical trials, identifying significantly differentially expressed circRNAs [4] - A predictive model was constructed using machine learning, which was validated and revealed key circRNAs that may influence the efficacy of NSCLC immunotherapy [4] CircRNA-Sig Model - The circRNA-Sig model demonstrated an area under the curve (AUC) of 0.71 in the OAK trial and 0.67 in the POPLAR trial for predicting the efficacy of atezolizumab [5] - Survival analysis indicated that patients with low circRNA-Sig scores benefited significantly more from ICI treatment compared to chemotherapy (HR=1.347), while high-score patients showed no significant difference [5] - Enrichment analysis suggested that low-score patients exhibited an activated tumor immune microenvironment, indicating a mechanistic link between circRNA and ICI treatment sensitivity [5] Clinical Application - The circRNA-Sig model, validated across two large clinical trial cohorts, offers a new stratification tool for NSCLC patients undergoing atezolizumab treatment, enhancing personalized treatment strategies [8]

Core Viewpoint - The article discusses a novel cancer treatment strategy called "Decaging-to-Ligation" (D2L), which enables precise recruitment of proteins or immune cells to tumor sites, significantly inhibiting tumor growth while minimizing systemic toxicity [3][12]. Group 1: Research Findings - The study successfully synthesized proteolysis-targeting chimeras (PROTAC) in tumor-localized concentrations sufficient for effective target protein degradation, leading to a 14.8-fold increase in T cell activation levels [2][10]. - The D2L strategy effectively overcomes On-target Off-tumor (OTOT) toxicity, a major barrier for therapies like PROTAC and T cell-mediated immunotherapy [5][12]. - The research team demonstrated the feasibility of the D2L strategy by achieving selective imaging of FAP-positive cells and successfully degrading the target protein BRD4 in tumors with minimal toxicity to the small intestine [10][12]. Group 2: Technological Innovations - The D2L strategy represents an innovative approach in the intersection of chemical biology and drug discovery, facilitating tumor-selective reactions that can induce proximity effects between proteins and cells [7][12]. - The study highlights the potential of bioorthogonal chemistry in achieving selective drug release at tumor sites, bridging the gap between bioorthogonal connection technology and tumor-selective regulation [6][12]. Group 3: Implications for Cancer Treatment - The D2L strategy is positioned as a promising platform for precise cancer treatment, aiming to activate therapeutic assemblies in vivo and address critical limitations of proximity-mediated cancer therapies [12].

撰文丨王聪 编辑丨王多鱼 Nature 特写部编辑 Brendan Maher 表示： 今年的榜单颂扬了对新前沿的探索，医疗领域突破性进 展的希望，对科研诚信的坚定守护，以及那些可以拯救生命的全球政策的制定者。我们激动地看到这么多人在不遗余力地理解自然世界，并在许多情况下帮助 排版丨水成文 | 日前， | | Nature | | 公布了 | 2025 | 年度 | 十大人物榜单 | （Nature's 10） | | --- | --- | --- | --- | --- | --- | --- | --- | --- | | ，入选者包括 | | | DeepSeek 创始人 | | | 梁文锋 | 、 | 中国科学院深海科学与工 | | 程研究所 | 杜梦然 | | 研究员 | | ，以及 | Susan Monarez | 、 | Achal Agrawal | | 、 | Tony Tyson | | 、 | | Precious Matsoso | 、 | Sarah Tabrizi | 、 | | Luciano Moreira | | 、 | Yifat Merbl | | 和 | KJ Mu ...