编辑丨王多鱼 排版丨水成文 在过去十多年里， 肝脏类器官 研究突飞猛进。从最初基于小鼠或有限人源组织的上皮类器官模型，到如今 不断演进的多细胞共培养体系，科学家们始终在向一个终极目标逼近 —— 在体外真正复刻成年人体肝脏的 结构与功能 。 然而，一个核心难题始终横亘在前： 如何在体外长期、稳定地维持成人肝脏的多细胞复杂性？ 真实的人体肝脏并非单一细胞构成，而是由 肝细胞 、 胆管上皮细胞 、 成纤维细胞 等多种细胞类型共同 组成，并在精细的空间结构中协同工作。遗憾的是，长期以来，大多数肝脏类器官模型仍停留在 " 单一上 皮细胞 " 的层面，难以重建这种复杂而关键的细胞互作网络。 该研究 首次在体外成功重建了 人类肝脏门区的多细胞结构与功能特征 ，构建出一种可长期维持、具备高 度生理相关性的人源肝脏 " 组装体" （ assembloid） 模型。 现有的人体肝脏体外模型 —— 无论是 原代人肝细胞 （ PHH ） ，还是 iPSC 来源的肝细胞类器官 —— 都存在难以回避的局限： 相比之下，小鼠来源的多细胞类器官模型已初露曙光，但 在人类体系中重现具有生理相关性的多细胞肝组 织，依然是一个悬而未决的挑战 。 ...

Core Viewpoint - The article discusses the development of a novel mRNA cancer vaccine utilizing membrane-destabilizing zwitterionic lipids, which addresses two major challenges: limited mRNA expression and unavoidable inflammatory responses [2][4]. Group 1: Research Development - A research team led by Professor Jiang Shaoyi from Cornell University published a study in Nature Biomedical Engineering, highlighting a new mRNA cancer vaccine that exhibits low reactogenicity and high tumor antigen expression [3]. - The study introduces a membrane-destabilizing zwitterionic lipid that enhances mRNA expression by promoting endosomal escape while simultaneously reducing inflammatory responses [6]. Group 2: Lipid Characteristics - The zwitterionic lipid features a pyridinium carboxybetaine (PyCB) head group, a biodegradable multi-tail alkyl chain, and a tertiary amine linker, which allows for effective protonation and biocompatibility under physiological pH conditions [6]. - The PyCB head group forms a zwitterionic PyCB-water complex, which becomes positively charged at pH levels below 6.8, facilitating efficient mRNA release in endosomes [6]. Group 3: Enhanced Vaccine Efficacy - Incorporating this zwitterionic lipid into commercial mRNA vaccine LNP formulations significantly increases mRNA expression levels in antigen-presenting cells within lymph nodes, thereby enhancing cytotoxic T cell activation [7]. - The zwitterionic nature of the lipid results in reduced inflammatory responses and neutrophil infiltration at the injection site, providing an advantage for the nanoparticles containing this lipid [7]. - This lipid is also compatible with existing targeted nanoparticle formulations, which can further optimize mRNA delivery efficiency [7].

撰文丨王聪 编辑丨王多鱼 排版丨水成文 慢性肾病 （ Chronic Kidney Disease ） 影响着全球十分之一的人口，其中被称为 足细胞 （ Podocyte ） 的肾脏特殊滤血细胞的损伤，发挥着关键作用。在肾 病综合征的主要病因—— 膜性肾病 （ membranous nephropathy，MN ） 中，循环 自身抗体 会攻击足细胞足突上的蛋白质，从而损害肾脏的过滤屏障 ， 导致 大量蛋白质从血液泄漏到尿液中 （即 蛋白尿 ） 。 近日，德国 汉堡-埃彭多夫大学医学中心的研究人员在国际顶尖学术期刊 Cell 上发表了题为： Autoantibody-triggered podocyte membrane budding drives autoimmune kidney disease 的研究论文。 我们研究发现， 自身免疫球蛋白触发的细胞外囊泡 （AIT-EV） 的形成是足细胞质膜出芽的重要病理学特征，这一过程由足细胞试图清除与足突跨膜抗原结合的 致病性自身抗体所引发，为 膜性肾 病 （MN） 中异质性的肾小球蛋白质聚集提供了一个统一而保守的机制。此外，该研究还表明，尿液 AIT-EV 分析可 ...

Core Viewpoint - Ferroptosis is a newly discovered iron-dependent form of programmed cell death that plays a significant role in the development of various diseases, including cancer, and represents a promising new strategy for cancer treatment by inducing lipid peroxidation [1][6]. Group 1: Research Findings - The study published in Molecular Cell highlights that PRDX6 is a key regulatory factor of GPX4, which helps resist ferroptosis, and targeting PRDX6 can enhance the anti-tumor effects mediated by ferroptosis [2][6]. - The research team identified that PRDX6 influences the localization and function of GPX4, thereby contributing to the resistance against ferroptosis [3][6]. - PRDX6 has phospholipase A2 activity, catalyzing the conversion of peroxidized phospholipids into lysolipids and oxidized fatty acids, which is crucial for its interaction with GPX4 [4][6]. Group 2: Implications for Cancer Treatment - Combining PRDX6 inhibition with ferroptosis inducers can increase lipid peroxidation and effectively suppress tumor growth in mouse models of liver and ovarian cancer, including patient-derived models [4][6]. - High expression of PRDX6 is associated with shorter progression-free survival in various human cancer types, indicating its potential as a therapeutic target [4][6].

Core Viewpoint - Cell Press has launched a new open-access journal, Cell Press Blue, focusing on significant pioneering research in life sciences, physical sciences, medicine, sustainable development, and applied sciences [3] Group 1: Journal Overview - Cell Press Blue welcomes interdisciplinary research that connects biology, medicine, chemistry, physics, materials science, energy, environmental science, and sustainable development [3] - The journal will publish authoritative reviews and opinion articles to showcase emerging opportunities and reflect on the role of science in addressing major contemporary challenges [3] Group 2: Editorial Leadership - The editor-in-chief of Cell Press Blue is Dr. Andy Jobbins, who has a background in molecular and cellular biology and has worked in various prestigious research institutions [5] - A co-editor will be based in China, focusing on the field of physical sciences, with details to be announced soon [6] Group 3: Submission Benefits - Authors submitting to Cell Press Blue will engage with high-impact research that can disrupt scientific paradigms, with all papers selected by a professional editorial team from Cell Press [7] - The journal emphasizes a "service-first" philosophy, providing comprehensive support to authors throughout the submission and publication process [8] Group 4: Impact and Promotion - Cell Press Blue aims to promote disruptive scientific research that transcends disciplinary boundaries and contributes to sustainable development [9] - The journal will utilize a professional promotion team to ensure that every published paper receives broad attention and citation [9] Group 5: Additional Features - Collaborative promotion with other relevant Cell Press journals will enhance the visibility of research findings [10] - The journal maintains high standards aligned with other top-tier Cell Press publications, ensuring rigorous quality control [10] - Efficient review processes and direct communication with editors will streamline the publication timeline for authors [10] Group 6: Visibility and Outreach - Targeted marketing activities will significantly enhance the visibility of research published in Cell Press Blue [11] - The journal actively recommends research with news value to mainstream media, helping authors reach a wider audience [11]

Core Viewpoint - The research identifies CDK3 as a key driver of neuronal death and brain atrophy in Alzheimer's disease, providing a new target for therapeutic intervention and a relevant mouse model for studying the disease [2][5][6]. Group 1: Research Findings - CDK3 levels are elevated in the brains of Alzheimer's patients and correlate with disease severity [5]. - The study developed two mouse models that restore CDK3 activity, leading to significant neuronal death, hippocampal atrophy, and cognitive deficits [5]. - Single-cell RNA sequencing revealed that neurons activated cell cycle and various cell death pathways, indicating that re-entry into the cell cycle leads to cell death [5]. Group 2: Therapeutic Implications - The research team identified BMX330, a small molecule inhibitor that specifically targets CDK3, which significantly reduced neuronal death and hippocampal atrophy in the mouse models [6]. - BMX330 also improved cognitive function, positioning CDK3 as a potential therapeutic target for Alzheimer's disease [6].

Core Viewpoint - The article emphasizes the significant health benefits of natural daylight exposure in office environments, particularly for managing type 2 diabetes, as supported by recent research findings [2][3]. Group 1: Research Findings - A study published in Cell Metabolism indicates that exposure to natural light during office hours improves glucose control and whole-body substrate metabolism in type 2 diabetes patients [2][3]. - The research involved 13 type 2 diabetes patients working in two different office environments: one with natural light and the other with artificial light, maintaining consistent dietary and activity conditions [6][8]. - Results showed that patients in natural light environments had 50.9% of their time with blood glucose levels in the normal range (4.4-7.2 mmol/L), compared to 43.3% in artificial light environments, equating to nearly 2 additional hours of normal blood glucose time daily [10]. Group 2: Metabolic Changes - Natural light exposure led to a significant increase in fat oxidation rates, indicating a shift in the body's energy source from carbohydrates to fats [12]. - The study also found that participants had higher evening melatonin levels in natural light, which is crucial for regulating the sleep-wake cycle and maintaining metabolic health [15]. Group 3: Molecular Insights - Multi-omics analysis revealed that beneficial metabolites like choline, glutamate, and threonine increased in natural light conditions, while harmful lipids such as cholesterol esters and ceramides decreased, aligning with improved glucose control [17]. Group 4: Practical Implications - The findings suggest that simple environmental adjustments, such as working near windows to increase natural light exposure, could provide significant clinical benefits for type 2 diabetes and obesity patients [19][21].

鉴于 IMID 的复发性，严格遵循用药方案对于促进疾病改善和保持生活质量至关重要。然而，长期治疗期间 （可能持续一生） 需要侵入性、毫克级的抗体注射， 给患者带来了巨大的生理、心理和经济负担，从而对治疗依从性构成了挑战。 2025 年 12 月 19 日， 西安电子科技大学 王忠良 教授 、 乔晁强 副教授及 空军军医大学第一附属医院（西京医院） 邵帅 副教授等， 在 Cell 子刊 Cell Reports Medicine 上发表了题为： Engineered probiotics platform for oral delivery of antibody as a high-compliance alternative for immune-mediated 撰文丨王聪 编辑丨王多鱼 排版丨水成文 免疫介导的炎症疾病 （ Immune-mediated inflammatory disease， IMIDs ） 具有诸如"公共"免疫通路等共同的发病特征，通常无法治愈，需要终身管理。靶 向关键介质 （例如肿瘤坏死因子-α、IL-17、IL-23 或其受体） 的抗体疗法，因其特异性、中和能力以及较长的半衰 ...

编辑丨王多鱼 排版丨水成文 能源 是人类社会赖以生存及社会发展的重要物质基础，然而在使用过程中约有超过 50% 的能量以 废热 的形式浪费掉，若能将 这些热能回收并转成电能，将产生深远影响。 热电技术 可将热能和电能进行直接转换，既可基于塞贝克效应实现温差发电，又可基于珀尔帖效 应实现热电制冷，在深空探测电源、集成电路热管理等关键领域具有重要应用价值。 | 2025 年 | | 12 月 | 18 日，北京航空航天大学 | 赵立东 / | | 常诚 | 团队联合太原科技大学 | 白培康 | | --- | --- | --- | --- | --- | --- | --- | --- | --- | | / | 宿力中 | 团队 | | （ | 高天 | 、 | 文熠 | 、 | | 白树林 | | 、 | 宿力中 | 为论文共同通讯作者 | | | ） | ，在国际顶尖学术期刊 | | Science | | 上发表了题为： | | Extending the temperature range of the Cmcm | | phase of SnSe for high thermoelectric pe ...

编辑丨王多鱼 排版丨水成文 牛 在东亚的农牧社会中长期以来一直扮演着核心角色。其他地区的基因组研究揭示了一段复杂的进化史，其中涉及了多次扩散事件和广泛的基因混合。 普通牛 （ Taurine cattle ） 最初约在距今 10000 年前从近东的原牛驯化而来，随后扩散到欧洲和非洲。在这些地方，它们与当地野生原牛的基因渗入留下了持久的遗 传印记。在南亚，驯化的 瘤牛 （ Indicine cattle ） 首次出现于约距今 8000 年前。它们后来的扩散在西亚、中亚、东亚以及非洲带来了广泛的普通牛-瘤牛杂交 混合。 尽管动物考古学和考古遗传学研究已证实它们在约 5000 年前就已存在，但由于古基因组数据有限，早期 东亚家牛 的起源与扩散过程仍不明确。此外，现已灭绝 的原牛以及如瘤牛、牦牛和大额牛等驯养牛种的存在，表明东亚地区牛的进化历史复杂，但相关探索仍不充分。 2025 年 12 月 18 日， 吉林大学 蔡大伟 教授团队联合、韩国首尔大学 Choongwon Jeong 教授团队，在国际顶尖学术期刊 Science 上 发表了 题 为： Ancient genomes illuminate the ori ...