Core Viewpoint - The article discusses recent research on sepsis, highlighting the importance of anatomical infection sites in determining prognosis and the potential for precision immunotherapy based on specific immune features identified in adult and pediatric patients [4][6]. Group 1: Research Findings - A study published in Nature Immunology reveals anatomical-specific immune features in sepsis, providing candidate targets for precision immunotherapy [4]. - The research utilized multi-omics analysis on samples from 281 adult and pediatric sepsis patients, identifying a CD4+ T cell subset that is enriched in abdominal, pulmonary, and skin sepsis, which exhibits exhaustion characteristics [5]. - The study found that the expression of pro-inflammatory CD8+ T cells, NK cells, and NKT cells is amplified in adult abdominal and pulmonary sepsis, while pediatric pulmonary sepsis is characterized by proliferative CD14+ monocytes [6]. Group 2: Biomarker Discovery - Another study published in Science Translational Medicine identifies Bone Morphogenetic Protein 9 (BMP9) as a potential prognostic biomarker for sepsis, with higher levels at admission correlating with better survival rates [7]. - BMP9 treatment improved outcomes in sepsis mouse models by enhancing macrophage recruitment, phagocytosis, and bacterial clearance [7].

编辑丨王多鱼 排版丨水成文 小胶质细胞是中枢神经系统（CNS）内的常驻免疫细胞，在先天免疫防御、神经发育、组织稳态维持和神 经疾病调控中发挥关键作用。基因突变会破坏这些功能，使小胶质细胞由健康状态转变为致病状态，从而 诱发或加速多类神经退行性病变。如何从根源上恢复其正常功能，成为神经免疫学与神经退行性疾病领域 的核心科学问题之一。 2020 年，复旦大学 彭勃 团队在 Cell Reports 期刊发表论文 【1】 ， 首次在小鼠模型中实现了高效小胶质 细胞替换 ，并提出以基因正常的小胶质细胞替换突变细胞，从而治疗由病理性小胶质细胞引起或加速的中 枢神经系统疾病。 这一概念进一步发展为小胶质细胞替换治疗策略—— MISTER （microglia intervention strategy for therapy and enhancement by replacement） 。 2025 年 12 月 4 日， 彭勃 / 饶艳霞 团队在 Cell Stem Cell 期刊发表了题为： A New Paradigm for CNS Disease: The Evolution of Microglia Rep ...

Core Insights - The research highlights the diverse and protective biocrust microbiome associated with the Great Wall of China, emphasizing its significance for the preservation of this historical monument [3][7]. Group 1: Research Findings - The study investigated six sampling points along a 600 km section of the Great Wall, revealing a patchy landscape of biocrust and bare wall, which may harbor unique microbial communities [4][6]. - Compared to bare wall areas, the abundance, diversity, and co-occurrence network complexity of bacteria and fungi in biocrust-covered regions increased significantly by 12%-62% [6]. - Metagenomic analysis indicated that biocrust enhanced the overall functional gene abundance and stress resistance metabolic pathways by 4%-15%, while significantly reducing pathways related to biological corrosion [6]. Group 2: Environmental Factors - Drought severity was identified as a key environmental factor shaping the microbial community associated with the Great Wall [6]. Group 3: Implications for Preservation - The findings provide a scientific basis for the protection of the Great Wall, contributing to efforts to preserve this unique human heritage for future generations [7][8].

Core Viewpoint - mRNA vaccines have shown strong clinical efficacy in preventing COVID-19, which has spurred the development of mRNA cancer vaccines as a promising strategy to elicit robust and specific anti-tumor immune responses [2][3]. Group 1: Research Development - The research team from Fudan University developed a novel single-component lipid-mRNA delivery system called OncoLRC, which efficiently targets mRNA delivery to splenic antigen-presenting cells, activating a strong anti-tumor immune response [3][11]. - Traditional lipid nanoparticles (LNPs) used in mRNA vaccines have a significant limitation of accumulating in the liver after systemic administration, prompting researchers to focus on developing splenic-targeting mRNA-LNP delivery systems [4][11]. Group 2: Mechanism and Efficacy - OncoLRC demonstrates nearly exclusive splenic targeting for mRNA delivery, outperforming traditional four-component LNP formulations, with in vivo experiments showing that mRNA is predominantly expressed in splenic antigen-presenting cells after intravenous injection [6][11]. - The OncoLRC formulation requires a lipid-to-mRNA weight ratio of 1.5:1, compared to the typical 10:1 ratio in standard LNPs, which enhances the maturation and activation of dendritic cells, leading to a strong antigen-specific immune response [8][9]. Group 3: Clinical Implications - Mechanistic studies indicate that the splenic delivery of OncoLRC is mediated primarily through macropinocytosis, enhancing the secretion of endogenous cytokines like IL-12, which further stimulates T cell activation and cytotoxic activity [9]. - In a B16F10-OVA cold tumor model, OncoLRC demonstrated significant preventive anti-tumor efficacy and exhibited a notable synergistic effect when combined with immune checkpoint blockade therapy, effectively inhibiting tumor growth [9][11].

Core Viewpoint - The recent research by Professor Michel Sadelain and his team introduces a novel approach to enhance CAR-T cell therapy for solid tumors by integrating the pTα-1A domain into CAR structures, significantly improving the proliferation, cytokine production, and longevity of CAR-T cells, while reducing exhaustion [2][3][6]. Group 1: Research Background and Significance - CAR-T cell therapy has shown remarkable success in treating blood cancers but has struggled with solid tumors, which account for over 90% of cancer cases, primarily due to the suppressive tumor microenvironment and T cell exhaustion [8][10]. - The study provides a new perspective for developing next-generation CAR-T therapies, offering hope for overcoming the challenges associated with solid tumors [3][6]. Group 2: Mechanism and Innovation - The research draws inspiration from the natural development of T cells in the thymus, particularly the "pre-TCR" activation that triggers a significant proliferation response [10][11]. - By incorporating the pTα-1A domain into the CAR structure, specifically between the CD28 and CD3ζ signaling domains, the new CAR design (19-28z-1A) demonstrated enhanced expansion and cytokine secretion capabilities [12][14]. Group 3: Experimental Results - In vitro tests showed that 19-28z-1A CAR-T cells exhibited superior proliferation and cytokine production compared to traditional CAR-T cells, with these advantages becoming more pronounced with increased stimulation [14]. - In mouse models of leukemia, the 19-28z-1A CAR-T cells effectively eliminated tumors and significantly improved survival rates, indicating better persistence and reduced exhaustion markers [14][18]. Group 4: Broader Applications and Future Directions - The research team successfully targeted CD70, a marker for renal cell carcinoma and glioblastoma, with the 70-28z-1A CAR-T cells, which showed promising tumor control in various models, outperforming traditional CAR-T cells [20]. - The combination of the 1A domain with another advanced CAR design (1XX CAR) resulted in a synergistic effect, enhancing anti-tumor efficacy and providing a promising avenue for clinical development [23]. Group 5: Implications for CAR-T Therapy - This study opens a new dimension for optimizing CAR-T cell therapy by focusing on mRNA translation regulation, which is a departure from traditional methods that concentrate on transcription factors or epigenetics [25]. - The enhanced efficacy of the 1A CAR-T cells has been validated in multiple preclinical models, particularly for solid tumors, indicating significant potential for clinical application [26]. - Preliminary safety assessments suggest that the activation of 1A CAR-T cells remains antigen-dependent, with no observed safety concerns such as autonomous proliferation, indicating a favorable translational outlook [27].

Core Viewpoint - The study highlights the potential of AI-assisted molecular subtyping to enhance treatment efficacy in HR+/HER2- breast cancer, particularly for the newly identified subtypes SNF2 and SNF4 [4][22]. Group 1: Research Background - HR+/HER2- breast cancer accounts for approximately two-thirds of all breast cancer cases, with limited treatment options available after resistance to CDK4/6 inhibitors [3][4]. - The study published in Cancer Cell on December 4, 2025, by researchers from Fudan University, introduces a new approach to classify HR+/HER2- breast cancer into four subtypes using AI [3][4]. Group 2: AI Subtyping Methodology - The research team utilized multi-omics data and a similarity network fusion (SNF) algorithm to classify HR+/HER2- breast cancer into four new subtypes: SNF1, SNF2, SNF3, and SNF4 [8][11]. - An AI model was developed to predict these subtypes accurately from routine H&E stained pathology slides, making clinical application feasible without expensive multi-omics testing [11][21]. Group 3: LINUX Trial Design - The LINUX trial is a multi-center, randomized controlled Phase II study involving 105 HR+/HER2- advanced breast cancer patients who are resistant to CDK4/6 inhibitors [13][14]. - Patients were categorized based on their SNF subtype and randomly assigned to either a precision treatment group or a standard treatment group [13][14]. Group 4: Treatment Protocols - Treatment regimens were tailored to each subtype: - SNF1: Everolimus + endocrine therapy - SNF2: Camrelizumab + Famitinib + chemotherapy - SNF3: Olaparib + chemotherapy - SNF4: Apatinib + chemotherapy [14]. Group 5: Trial Results - The trial demonstrated significant efficacy, with objective response rates (ORR) for the precision treatment group compared to the control group as follows: - SNF1: 10% vs 0% - SNF2: 65% vs 30% - SNF3: 40% vs 30% - SNF4: 70% vs 20% [17]. - Notably, the probability of effective treatment for SNF2 and SNF4 was 86.7% and 97.6%, respectively, indicating successful patient selection for specific therapies [19]. Group 6: Safety and Clinical Implications - The safety profile of the precision treatment group was comparable to the standard treatment group, with a 37% incidence of grade 3-4 treatment-related adverse events [19]. - The LINUX trial results provide strong evidence for new treatment strategies in HR+/HER2- advanced breast cancer, particularly identifying SNF2 as an "immune hot tumor" type [22][24]. Group 7: Future Outlook - The success of the LINUX trial validates the feasibility of using low-cost pathology and AI for clinical precision subtyping and treatment guidance [21]. - This research paves the way for personalized treatment approaches in breast cancer, aiming for a "one patient, one plan" strategy in precision medicine [24].

Core Viewpoint - The commercialization of perovskite photovoltaic technology faces three key obstacles: the use of toxic solvents during manufacturing, the issue of uneven quality in large-area perovskite films, and limited operational reliability [3][6]. Group 1: Research Development - A research team from Nanjing University, in collaboration with the National Defense Science and Technology Innovation Research Institute and other researchers, published a paper in the journal Science, detailing the development of a three-component green solvent system for the preparation of commercially viable perovskite photovoltaic modules [3][5]. - The new solvent system, based on γ-valerolactone, 2-methyltetrahydrofuran, and dimethyl sulfoxide, replaces toxic solvents like N,N-dimethylformamide and optimizes the evaporation rate of the film's edge regions through the addition of surfactants [5]. Group 2: Performance Metrics - The research team successfully produced a stable perovskite photovoltaic module with an area of 7200 square centimeters, achieving a certified power conversion efficiency of 17.2% by the U.S. National Renewable Energy Laboratory [5]. - The module passed all IEC 61215 reliability standard tests, receiving certification from TÜV Rheinland [5]. Group 3: Environmental Impact - This research opens an environmentally friendly pathway for the commercial production of perovskite photovoltaic technology [6].

Core Viewpoint - The article emphasizes the significance of cell biology research in various biomedical fields, including tissue barrier functions, receptor signaling networks, enzyme inhibition studies, amyloid protein research, and the future of medical revolutions [3]. Group 1: Global Hot Topics - Topic 1: Nanomedicine in Metabolic Disorders focuses on innovative nanotechnology-based approaches for diagnosing and treating metabolic diseases, highlighting advancements in targeted drug delivery systems, nano-diagnostic platforms, and integrated therapeutic systems [4]. - Topic 2: Stem Cells and 3D Cellular Models discusses the transformative impact of stem cells and tissue engineering, particularly in conjunction with 3D models and nanotechnology, on biomedical research objectives [7]. Group 2: Submission Deadlines and Journals - Submission deadline for Topic 1 is March 31, 2026, and it is associated with the journal "Artificial Cells, Nanomedicine, and Biotechnology" [5]. - Submission deadline for Topic 2 is May 31, 2026, also linked to the journal "Artificial Cells, Nanomedicine, and Biotechnology" [7]. Group 3: High-Impact Journals - The journal "Amyloid" has an impact factor of 7.4 and focuses on amyloid proteins and related diseases, covering various aspects such as etiology, epidemiology, and clinical research [11]. - The "Journal of Enzyme Inhibition and Medicinal Chemistry" has an impact factor of 5.4, concentrating on enzyme inhibitors and their role in drug development [15]. - The journal "Artificial Cells, Nanomedicine, and Biotechnology" has an impact factor of 4.5, emphasizing interdisciplinary research in artificial cells and nanomedicine [20].

撰文丨王聪 编辑丨王多鱼 排版丨水成文 免疫球蛋白 E （ Immunoglobulin E， IgE） 是循环系统中含量最少的抗体类型。然而，它在哮喘、食物 过敏以及其他影响全球约三分之一人口的过敏性疾病中发挥着重要作用。在过敏个体接触过敏原时，过敏 原会被其组织肥大细胞和血液嗜碱性粒细胞表面的高亲和力受体 FcεRI 上结合的特异性 IgE 识别。这会促 使这些细胞脱颗粒，并释放预先形成的和新合成的介质，包括组胺。这种反应是大多数过敏症状的核心， 并可能导致一种 严重且可能致命的全身性过敏反应—— 过敏性休克 。 奥马珠单抗 （Omalizumab） 是一种重组人源化抗 IgE 单克隆抗体，已获美国 FDA 批准用于治疗中重度 过敏性哮喘和慢性自发性荨麻疹，还获批用于治疗 食物过敏 ，这也是首个获批的用于治疗食物过敏的生物 疗法。 抗 IgE 单克隆抗体成本高昂，且需要 频繁输注 （两周注射一次） 才能维持临床疗效，导 致其使用仅限于 少数症状最严重的患者。因此，尽管 IgE 在过敏和过敏性休克中已被证实为有效的治疗靶点，但仍需开发 其他策略来阻断该分子以实现长期治疗效果。鉴于奥马珠单抗重复给药长达 8 ...

Core Viewpoint - The research highlights the critical role of GPX4 in preventing ferroptosis, a form of cell death linked to neurodegenerative diseases, emphasizing the importance of its membrane localization alongside its enzymatic activity [2][10]. Group 1: Ferroptosis and GPX4 - Ferroptosis is a newly identified iron-dependent form of cell death characterized by the accumulation of lipid peroxides, distinct from other forms of programmed cell death [1]. - GPX4 is recognized as a key regulator of ferroptosis, primarily known for its enzymatic activity in detoxifying lipid peroxides [5]. - The study identifies a specific mutation in the GPX4 gene (GPX4 R152H) that disrupts its membrane localization, impairing its protective function against ferroptosis despite retaining enzymatic activity [5][8]. Group 2: Implications for Neurodegenerative Diseases - The research provides molecular evidence linking ferroptosis to neurodegenerative diseases, particularly through the study of a rare condition known as Sedaghatian type spondyloepiphyseal dysplasia (SSMD) [2][4]. - In mouse models, the absence of GPX4 or expression of the GPX4 R152H mutation leads to neuronal death and neuroinflammation, mirroring the pathological processes observed in SSMD [7]. - The findings suggest that ferroptosis may also play a significant role in more common neurodegenerative diseases, such as Alzheimer's disease, as similar protein expression patterns were observed in both conditions [7][10]. Group 3: Research Findings and Future Directions - The study establishes that the membrane localization of GPX4 is as crucial as its enzymatic activity for neuroprotection against ferroptosis [10]. - It underscores the potential of targeting ferroptosis as a therapeutic strategy for neurodegenerative diseases, providing a strong theoretical basis for future drug development [10]. - The research chain from genetic mutation to animal models and human cell models reinforces the conclusion that ferroptosis is a key driver of neurodegenerative changes [10].