Core Viewpoint - Immunogenic cell death (ICD) is a promising method for eliciting anti-tumor immune responses, but challenges remain in the spatial and temporal activation of tumor-specific immune responses [1][2]. Group 1: Research Development - A modular metalloprotein in situ vaccine (PPTV) has been developed for cancer immunotherapy, specifically targeting breast cancer [1]. - The research team utilized ferritin as a vaccine framework, integrating optimal mitochondrial-disrupting peptides and loading manganese ions (Mn²⁺) into its core [2]. - A prodrug strategy activated by proteases was developed to address major issues associated with ferritin, such as liver retention and drug leakage [2]. Group 2: Mechanism and Efficacy - In mouse models, PPTV effectively co-delivered mitochondrial-disrupting peptides and Mn²⁺ to tumors, triggering strong anti-tumor immune responses through ICD and the cGAS-STING pathway [2]. - The combination of PPTV with anti-PD-L1 monoclonal antibodies resulted in the eradication of established tumors, highlighting the potential of PPTV as an innovative in situ vaccine platform [2]. Group 3: Clinical Implications - The modular metalloprotein vaccine demonstrates simple preparation and safety features, indicating promising prospects for clinical translation [2].

Core Viewpoint - The research identifies the origin cells of multiple myeloma (MM) and develops a CAR-T cell therapy targeting FCRL5, demonstrating good safety and efficacy in treating relapsed or refractory multiple myeloma (RRMM) patients [3][9]. Group 1: Research Findings - The study utilized single-cell sequencing and genetic tracing analysis to investigate each developmental stage from hematopoietic stem cells to lymphoid lineage, identifying abnormal differentiation stages in multiple myeloma patients [5]. - The research team discovered that the long arm amplification of chromosome 1 (1q Amp) originates from a specific B cell subset, while the short arm deletion of chromosome 17 (17p Del) occurs at the plasma cell stage [6]. - 1q Amp is present in the CD24- FCRL5+ B cell subset, enhancing B cell proliferation and promoting plasma cell differentiation, which initiates the transformation of B cells into malignant plasma cells [6]. Group 2: Implications for Treatment - The findings establish genetic events associated with the initiation and malignant transformation of multiple myeloma in the B cell lineage, laying the groundwork for potential treatment strategies targeting multiple myeloma initiating cells (MIC) and their driver oncogenes in RRMM patients [11].

撰文丨王聪 编辑丨王多鱼 排版丨水成文 卵巢癌 （ Ovarian cancer ） 是全球最致命的妇科恶性肿瘤。这种癌症相对罕见，但在患有 子宫内膜异位 症 （ Endometriosis ） 的女性中更为常见，尤其是 透明细胞卵巢癌 。 子宫内膜异位症相关卵巢癌 （EAOC） 在子宫内膜异位症患者中的发生率高达 4.5%，其主要由卵巢病变 （子宫内膜异位囊肿） 恶变所致。在过去的几十年里，子宫内膜异位症的发病率有所上升，与此同时，在 子宫内膜异位症患者中卵巢肿瘤的检出率也有所增加。 与其它卵巢癌相比，EAOC 存在一些尚未解决的问 题，包括化疗耐药性、预后较差以及发病年龄更小。 然而，子宫内膜异位症与卵巢癌之间的因果关系仍有待确定。因此，阐明这种恶性肿瘤的发病机制对于防 止诊断延误以及降低其长期发病率至关重要。 2025 年 11 月 20 日，暨南大学医学院 李平 、香港中文大学（深圳）第二附属医院 王明华 、暨南大学附 属第一医院 周宏 等人 ， 在 Cell 子刊 Cell Reports Medicine 上发表了题为： Therapeutic targeting of interleukin-1 ...

Core Insights - The article discusses the launch of the LangTaoSha Preprint Server, a collaborative open science platform aimed at enhancing academic communication in the life sciences field [3][4]. - The platform is established by Shenzhen Medical Academy, Shenzhen Bay Laboratory, Tsinghua University, Westlake University, and other leading institutions, focusing on rapid dissemination of research findings prior to formal peer review [3]. - The introduction of blockchain technology ensures the integrity and traceability of scientific records by generating unique, immutable timestamps and encrypted certificates for each published paper [3]. Group 1: Platform Overview - The LangTaoSha Preprint Server officially launched in November 2025, providing a reliable and efficient environment for researchers [3]. - The platform has already published 11 research papers, including two from the team led by Academician Yan Ning [4]. - The platform aims to integrate AI-driven tools to streamline manuscript screening processes and improve manuscript quality [3]. Group 2: Research Highlights - The paper titled "Open-state structure of veratridine-activated human Nav1.7 reveals the molecular choreography of fast inactivation" focuses on capturing the open-state structure of the sodium channel Nav1.7 using veratridine [5][8]. - The research team identified two complexes of Nav1.7 with veratridine, revealing insights into the dual-mode regulatory mechanism of veratridine on sodium channels [9][11]. - Another paper, "High-throughput cryo-EM characterization and automated model building of glycofibrils via CryoSeek," introduces a new strategy combining cryo-electron microscopy with AI for discovering novel biological entities [12][13]. Group 3: Methodologies and Innovations - The CryoSeek methodology allows for high-throughput processing of cryo-EM data and automated modeling of glycan structures, establishing a workflow for reconstructing three-dimensional electron microscopy maps [14]. - The research team proposed a unified naming scheme for the fibers discovered through CryoSeek, which will aid in understanding glycan folding principles [14]. - A CryoSeek database has been created for data archiving and sharing, accommodating the large volume of structures obtained through this strategy [14].

这一关乎 " 同一性 " 与 " 异质性 " 的辩证矛盾，是困扰生物学界数十年的 " 生命同源异质 " 之问。其核心便隐藏在每 个细胞不尽相同的转录活动中，一种被称为 " 基因表达噪声 " 的微观波动，是探索生命复杂性的关键入口。 长期以来，相关研究多聚焦于基因表达的平均水平，而将这种噪声波动视为技术误差。然而，它恰恰蕴藏着细胞命运决 策、机体衰老与疾病发生的关键线索。为什么在高度一致的条件下，细胞仍表现出如此丰富的转录异质性？这些波动又 如何在生理与病理过程中发挥作用？解析 基因表达噪声 的遗传基础，不仅有望填补 " 遗失的遗传力 " ，更将为复杂疾 病的机制研究开辟全新视角，具有重要的科学价值与临床意义。 202 5 年 11 月 23 日，中国医学科学院基础医学研究所 龙尔平 / 倪晓琳 团队与美国国家癌症研究所 张同武 团队合 作，在 Cell Reports 期刊 在线发表了题为： Genetic determinants of gene expression noise and its role in complex trait variation 的研究论文 。 该研究建立了基于百万级单细胞数据 ...

Core Viewpoint - The article discusses the emergence of Severe Fever with Thrombocytopenia Syndrome (SFTS) caused by the Dabie bandavirus (SFTSV), highlighting its public health challenges and the development of a novel nanobody cocktail for potential treatment [2][8]. Group 1: Disease Overview - SFTS is caused by SFTSV, transmitted by ticks, and has been prevalent in regions such as Anhui, Jiangsu, Zhejiang, and Shandong in China, as well as in Japan and South Korea [2]. - Symptoms include fever and thrombocytopenia, with severe cases leading to multi-organ failure and a mortality rate ranging from 6% to 30% [2]. Group 2: Research Development - A research team led by Professor Wu Xilin from Nanjing University published a study on a cocktail of nanobodies designed to protect against SFTSV in preclinical models [3]. - The study utilized a "sequential heterologous immunization" strategy to isolate and identify nanobodies targeting SFTSV from llamas, leading to the design of a nanobody cocktail (Nb261 + Nb318) [6]. Group 3: Treatment Efficacy - The nanobody cocktail demonstrated complete neutralization of various SFTSV subtypes in vitro and showed excellent therapeutic effects in mouse and aged ferret models, achieving a 100% survival rate, complete viral clearance, and significant improvement in thrombocytopenia and tissue damage [7]. - This research represents the first systematic validation of mixed nanobodies for treating SFTSV in large animal models, providing unprecedented evidence for developing safe and effective SFTSV treatments [8]. Group 4: Future Directions - The research integrates multiple fields, including structural biology, immunology, virology, and translational medicine, showcasing a novel strategy for broad-spectrum antiviral development [9]. - The research team has initiated preclinical studies on pharmacokinetics, toxicology, and process scaling for the Nb261 + Nb318 cocktail, aiming to provide new preventive and therapeutic options for SFTS [9].

Core Insights - The article highlights the significant growth in the number of research papers published by Chinese scientists in Cell Press journals over the past decade, indicating advancements in originality, systematic approaches, and openness in Chinese research [2] - In 2024, the total number of research papers published by Chinese institutions in Cell Press journals reached 2,446, marking a 17.6% increase from the previous year and nearly quadrupling the publication volume from 2020 [2] Summary by Categories Research Output - The number of research papers published by Chinese institutions in Cell Press journals has shown a remarkable increase, with 2,446 papers published in 2024, reflecting a 17.6% year-over-year growth [2] - This figure represents nearly four times the publication volume from 2020, showcasing the rapid development of Chinese scientific research [2] Award Recognition - Cell Press has announced the "Cell Press 2024 China Annual Papers," recognizing 50 outstanding papers across five fields: life sciences, material sciences, medicine, interdisciplinary studies, and sustainable development [2] - Each field includes 10 selected papers, emphasizing the diversity and quality of research being conducted in China [2] Notable Papers in Life Sciences - The article lists several notable papers in the life sciences category, including: - "3D reconstruction of a gastrulating human embryo" published in Cell [4] - "Amino acid is a major carbon source for hepatic lipogenesis" published in Cell Metabolism, with lead author Fu Suneng [7] - "Distinct roles of TREM2 in central nervous system cancers and peripheral cancers" published in Cancer Cell [9] - "Efficient expansion and CRISPR-Cas9-mediated gene correction of patient-derived hepatocytes for treatment of inherited liver diseases," led by Hui Lijian [12] - "Growth hormone promotes myelin repair after chronic hypoxia via triggering pericyte-dependent angiogenesis," led by Mei Feng [15] - "PDGFRα + ITGA11 + fibroblasts foster early-stage cancer lymphovascular invasion and lymphatic metastasis," led by Lin Tianxin [18] - "Reciprocal conversion between annual and polycarpic perennial flowering behavior in the Brassicaceae," led by Wang Jiawei [21] - "Streptococcus anginosus promotes gastric inflammation, atrophy, and tumorigenesis in mice" [24] - "Targeting APT2 improves MAVS palmitoylation and antiviral innate immunity," led by Guo Jianping [27] - "Using artificial intelligence to document the hidden RNA virosphere," led by Shi Mang [29]

Core Insights - Metabolic dysfunction-associated fatty liver disease (MASLD), previously known as non-alcoholic fatty liver disease (NAFLD), is increasingly recognized as a global health crisis, with potential progression to severe liver conditions [3] - Currently, only one drug, Remetiro, is approved specifically for the treatment of metabolic dysfunction-associated steatohepatitis (MASH), highlighting the urgent need for alternative strategies, with prebiotics emerging as a promising candidate [3] Research Findings - A study published in Cell Metabolism revealed that individual variability in gut microbiome mediates the efficacy of resistant starch (RS) on MASLD, indicating that different baseline gut microbiomes can drive variations in intervention responses [4] - The research team conducted a randomized, placebo-controlled clinical trial showing that RS, a natural prebiotic, has therapeutic effects on MASLD, although 30% of participants exhibited limited benefits, a finding corroborated in a multicenter clinical trial [6] - Multi-omics analysis and fecal microbiota transplantation (FMT) indicated that baseline gut microbiome is a major determinant of treatment response, with Prevotella inhibiting the degradation of RS, leading to low response rates [7] - Bifidobacterium pseudocatenulatum was isolated from the cohort, which can restore RS degradation and improve the response to RS inhibited by Prevotella [7] - A predictive model integrating baseline microbiome and clinical characteristics was developed, achieving an AUC of 0.74 - 0.87 for personalized intervention [8] Key Findings - Approximately one-third of MASLD participants showed poor response to RS intervention [11] - Prevotella mediates low response to RS by inhibiting RS-degrading bacteria [11] - Bifidobacterium pseudocatenulatum enhances the efficacy of RS [11] - A machine learning model based on baseline gut microbiome characteristics can predict responses to RS treatment [11] - The study suggests that gut microbiome determines the heterogeneity of RS treatment for MASLD, offering a potential for microbiome-guided precision therapy [12]

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，在血液类癌症中取得了显著效果，但对于占据癌症大多数的 实体瘤 ，由于受到实体瘤的免疫抑制性微环境的限制，其治疗 效果仍差强人意。 2 025 年 11 月 21 日，CAR-T 细胞疗法先驱、宾夕法尼亚大学 Carl June 教授在 Immunity 期刊发 表了题为： IL-9 signaling redirects CAR T cell fate toward CD8 + memory and CD4 + cycling states, enhancing antitumor efficacy 的研究论文。 该研究表明，在 CAR-T 细胞中共表达 IL-9 受体 ，能够在抗原压力下重编程 CAR-T 细胞命运，从而显著增强其对抗 实体瘤 的疗效。 在这项最新研究中，研究团队证明，通过共表达白介素-9 （IL-9） 受体赋予 CAR-T 细胞异位 IL-9 信号转导，能够在抗原压力下重塑 CAR-T 细胞命运，从而 增强其对实体瘤的抗肿瘤疗效。 在临床前实体瘤模型中，IL-9 信号 CAR-T 细胞表现出更强的扩增、持久性和 ...

Core Viewpoint - The article discusses the development of the world's first three-dimensional (3D) hydrogel semiconductor transistor, which combines the softness and biocompatibility of biological tissues with the precise electronic control of traditional transistors, paving the way for advanced bioelectronic systems [2][3][25]. Group 1: Research Breakthrough - A collaboration between researchers from the University of Hong Kong and the University of Cambridge led to the publication of a paper in Science, detailing the creation of a 3D hydrogel semiconductor transistor [2]. - The new transistor features a modulation thickness of millimeters and possesses biological tissue-level softness and biocompatibility, breaking the barrier between 2D electronic devices and 3D biological systems [3][25]. Group 2: Material Innovation - The research team focused on hydrogels, which are soft and high-water-content materials, traditionally lacking semiconductor properties. Recent advancements in redox-active hydrogels have enabled semiconductor characteristics, but thickness limitations remained a challenge [13]. - The team innovatively designed a dual-network hydrogel system that allows for 3D assembly, ensuring continuous electronic transport while optimizing ionic transport pathways [13][15]. Group 3: Performance Metrics - The 3D hydrogel transistors demonstrated exceptional performance, achieving a switching ratio of approximately 10,000 at a thickness of 1 millimeter, significantly outperforming traditional organic electrochemical transistors (OECT) [20]. - The hydrogel semiconductor's volumetric capacitance maintains a linear relationship with thickness up to millimeters, unlike traditional films that fail to do so beyond approximately 10 micrometers [20]. Group 4: System Applications - The research team successfully created self-supporting fibers from the 3D hydrogel semiconductors, constructing brain-like 3D neuromorphic circuits for data computation and analysis [23]. - In handwritten digit recognition tasks, the system achieved a recognition accuracy of 91.93%, comparable to traditional artificial neural networks, and maintained high predictive accuracy even under 30% strain [23][24]. Group 5: Future Implications - This research signifies a breakthrough in simultaneously controlling the electronic, ionic, and mechanical properties of soft materials at the millimeter scale, potentially leading to a new generation of bio-integrated electronic devices [25]. - The hydrogel semiconductors' biocompatibility and stretchability could establish robust 3D interfaces between electronic devices and biological systems, blurring the lines between technology and life [25].