Core Viewpoint - The article announces the recruitment of PhD and postdoctoral researchers by Professor Shen Haosheng's team at Nankai University's School of Life Sciences, focusing on synthetic biology and microbiome research for therapeutic applications in cancer and metabolic diseases [2][4]. Group 1: Research Direction - The research focuses on the interaction mechanisms between symbiotic bacteria and hosts, exploring the application of live probiotics in treating tumors, metabolic diseases, and brain disorders [3]. - Specific research areas include: 1) Modifying tumor-associated symbiotic microorganisms for targeted drug delivery to enhance local drug concentration and reduce systemic toxicity [3]. 2) Utilizing Lactobacillus plantarum for drug delivery to the brain via the olfactory mucosa, aiming to develop a nasal-to-brain drug delivery system [3]. 3) Investigating natural products from insect microbiomes and plant genomes [3]. Group 2: Recruitment Information - The team is looking to recruit 2 PhD students with backgrounds in synthetic biology, microbiology, or cell biology [4]. - For postdoctoral positions, 1-2 candidates with relevant backgrounds are sought, offering a salary range of 21,000-30,000 yuan per month [5]. - Applicants should generally be under 35 years old and have obtained their PhD within the last 3 years, with a requirement to have published or be about to publish SCI papers as the first author [5]. Group 3: Contact Information - Interested applicants are encouraged to send their application materials, including a CV and representative papers, via email to the provided address [6].

撰文丨王聪 编辑丨王多鱼 排版丨水成文 大脑健康 与 骨骼稳态 密切相关。骨骼衰老的特征是骨形成不足和骨髓脂肪过多，但大脑是否导致了这种 骨脂失衡 （ bone-fat imbalance ） ，目前仍不得而 知。 在这项最新研究中，研究团队发现，衰老的大脑神经元 （主要是海马体和大脑皮层中的神经元） 会产生过量的 WDFY1 蛋白，并通过 细胞外囊泡 （EV） 将其转 运到 骨骼 中，进而导致 骨脂失衡 （ bone-fat imbalance ） 和 骨质疏松 （ osteoporosis ） 。 研究团队进一步证实，大脑中 Wdfy1 基因表达增加会导致骨骼过早衰老。相反，在整个大脑、海马体或神经元中抑制 Wdfy1 基因表达 ，在神经元中敲除 Wdfy1 基因，以及选择性抑制神经元的细胞外囊泡释放，均可改善骨骼健康。 从机制上来说，WDFY1 与 R etromer 复合体结合，促进组织蛋白酶 D （ cathepsin D ） 和过氧化还原酶-2 （ peroxiredoxin 2 ） 从 内体向高尔基体的 再循 环，从而抑制成骨作用并促进脂肪生成。 总的来说，该研究揭示了衰老大脑神经元的细胞外囊泡 ...

Core Insights - Spatial transcriptomics is transforming the understanding of cellular interactions and functions by providing measurable data on "where cells are, what they are doing, and who they are interacting with" [1] - The future competition in spatial omics will focus on constructing interpretable spatial coordinate systems and establishing evidence chains linking location, interaction, signal, and phenotype [1] Course Features - Comprehensive teaching covering the entire workflow of spatial transcriptomics, including data structure, quality control, annotation, and visualization, with supportive R/Python code templates [6] - One-on-one guidance tailored to individual datasets (Xenium/VisiumHD/MERFISH), ensuring practical application of learned skills [6] - Integration of AI tools and detailed breakdown of Nature articles to enhance understanding of biological significance behind the code [7] - In-depth learning of source code and project structure to enable customization and application of published methods to personal research [7] - Live teaching sessions with recorded materials and ongoing Q&A support to ensure effective learning [7] Course Schedule - The first session will run from January 10 to February 2026, consisting of thirteen classes held on weekends, focusing on both detailed instruction and Q&A sessions [8] Course Core Modules - The first class will focus on understanding the narrative framework of Nature articles and how to apply these insights to personal research [9] - Subsequent classes will cover data processing, spatial statistics, cell segmentation, and the reproduction of figures from published studies, emphasizing practical skills and reproducibility [10][12][14][16][18][20][22][24][26][28][30][32][34][35][37] Course Outcomes - Participants will achieve the ability to reproduce high-quality figures from top journals, understanding the input data, key steps, and validation processes involved [46] - Mastery of core methodologies in spatial transcriptomics, enabling the construction of interpretable spatial coordinate systems and the visualization of cellular interactions and signaling pathways [46]

Core Viewpoint - Glioblastoma (GBM) is the most common and aggressive malignant brain tumor in adults, with a median survival of only 12-18 months post-diagnosis, and current treatments have limited efficacy in extending life expectancy [3] Group 1: Research Findings - A recent study published in Nature Cell Biology indicates that inhibiting lactate transport derived from tumor-associated macrophages (TAM) can restore cGAS-STING signaling and enhance antitumor immunity in glioblastoma [4] - The research team discovered that lactate is transported from TAM to glioblastoma stem cells (GSC) via MCT4-MCT1, promoting GSC proliferation and inducing lactylation modification of the non-homologous end joining protein KU70 at lysine 317 (K317), which inhibits cGAS-STING signaling and remodels the immunosuppressive tumor microenvironment [7] - Overall, the study reveals that lactate and lactylation modifications produced by TAM are key regulatory factors in maintaining the immunosuppressive tumor microenvironment in GSC, opening new avenues for combination therapies in glioblastoma [9]

撰文丨王聪 编辑丨王多鱼 排版丨水成文 动脉粥样硬化 （ Atherosclerosis， AS） 是一种由脂质代谢异常和免疫介导的炎症驱动的慢性炎症疾病，会导致动脉壁受损以及坏死斑块的积聚。其发病机制复 杂，受斑块微环境中具有不同功能的多种免疫细胞的调节，这些细胞共同作用，既促进动脉粥样硬化的发展，也促进其消退。具体而言，巨噬细胞/单核细胞在促 进斑块形成方面发挥着关键作用，其途径包括诱导泡沫细胞的生成以及激活炎症细胞因子的分泌。 此外，T 淋巴细胞和 B 淋巴细胞还能进一步调控免疫环境，其亚群既表现出促进动脉粥样硬化的作用，也表现出抑制动脉粥样硬化的作用。此外，树突状细胞 （DC） 会放大炎症和免疫激活。因此，了解并调控免疫细胞群，对于 动脉粥样硬化的治疗 至关重要。 2026 年 1 月 6 日，四川大学华西医院 何中山 团队在 Cell 子刊 Cell Reports Medicine 上发表了题为： Restoring immune homeostasis in atherosclerotic plaques via inorganic violet phosphorus nano-immunoth ...

撰文丨王聪 编辑丨王多鱼 排版丨水成文 跨生物膜的分子转运对于生命活动至关重要，它使细胞能够获取营养、排出废物、维持细胞稳态并与环境进行信息交互。尽管 跨膜功能蛋白的从头设计 已取得一 定进展，但如何构建能够稳健、选择性转运特定小分子的人工跨膜转运体系，仍是一项重大挑战。 近日，西湖大学 卢培龙 、 马丹 、 陈子博 等在 " 浪淘沙预印本平台 "发布了题为： De novo design of dual-topology membrane transporters 的研究论文。 该研究从头设计了 双拓扑结构的 膜转运蛋白 （ dual-topology membrane transporter ） ， 这些设计蛋白能在 活细胞 和 人工囊泡 中介导小分子染料的选择 性摄取，其功能类似于天然单向转运蛋白。冷冻电镜结构分析显示，其实际构象与设计模型高度吻合，功能实验验证了双拓扑结构及其作用机制。 这项研究证实了以原子级精度从头设计功能性动态膜转运蛋白是可行的，为了解转运蛋白的进化起源提供了新视角，并为靶向药物递送、代谢通路工程等应用开 辟了新途径。 生物膜 是细胞的屏障，控制着物质进出。 膜转运蛋白 就像是细胞 ...

Core Viewpoint - The cGAS-STING pathway plays a crucial role in detecting tumor-derived DNA, influencing both spontaneous and treatment-induced responses, and establishing a delicate balance between pathological inflammation and protective immune responses [2][3]. Group 1: Overview of cGAS-STING Pathway - The review published in Nature Reviews Cancer discusses the dual roles of the cGAS-STING pathway in cancer, highlighting both its pro-cancer and anti-cancer effects [5]. - It provides a comprehensive analysis of the diverse sources of cGAS-STING activating ligands and their prevalence in various human cancers, including DNA abnormalities caused by chromosomal instability, replication stress, telomere shortening, and treatment-induced DNA damage [7][8]. Group 2: Dual Role in Tumor Progression - The review emphasizes the different outcomes mediated by cGAS-STING activation at various stages of tumor initiation, progression, and metastasis, noting its critical anti-tumor role during tumor initiation and potential pro-tumor effects during tumor progression [8][12]. Group 3: Clinical Implications and Challenges - The review systematically reviews clinical trial results of STING agonists, such as ADU-S100 and MK-1454, and analyzes the limited efficacy due to factors like short drug half-life and differences in tumor microenvironments between humans and mice [14]. - It details the multi-layered negative regulatory networks that limit the anti-tumor effects of the cGAS-STING pathway, including DNA uptake barriers and differential responses of innate and adaptive immune cells [14]. Group 4: Future Directions - The review proposes several optimization strategies for enhancing the efficacy of cGAS-STING-targeted therapies, such as selective induction of mitochondrial DNA release and the development of drug delivery systems that enable spatiotemporal control of activation [15]. - It also suggests that transient inhibition of cGAS-STING signaling may normalize immune responses and enhance the effectiveness of immunotherapy, referencing recent successful cases in early clinical trials [16][17].

Core Viewpoint - The article discusses the increasing prevalence of Inflammatory Bowel Disease (IBD) in China, highlighting the role of the IL17REL gene in the disease's susceptibility and its potential as a therapeutic target [2][8]. Group 1: Overview of IBD - IBD includes Ulcerative Colitis (UC) and Crohn's Disease (CD), characterized by chronic, non-specific intestinal inflammation with no known cure, lifelong recurrence, and potential disability [2]. - The incidence of IBD in China has been rising annually, with current treatments focusing on immunomodulators and corticosteroids to alleviate inflammation or surgical removal of affected gastrointestinal sections [2]. Group 2: IL17REL Gene Research - The IL17REL gene locus has been identified as associated with susceptibility to IBD, but its functional protein coding and causal contribution to disease mechanisms remain unclear [3]. - A study published in Nature Immunology reveals that IL-17REL plays a significant protective role in IBD by acting as a decoy receptor for IL-17 family cytokines, inhibiting the activation of the IL-17 signaling pathway and downstream inflammatory gene expression [4][7]. Group 3: Mechanism and Implications - The study confirms that the wild-type IL-17REL protein can bind to IL-17 cytokines and suppress intestinal inflammation, while IBD-related mutations in IL17REL lack this function [7][9]. - TGFβ1 induces IL17REL transcription, and its expression correlates positively with TGFB1 levels in IBD patients [7]. - In mouse models, the introduction of the IL17REL gene alleviates colitis induced by 2,4,6-trinitrobenzenesulfonic acid, whereas the introduction of IBD-related IL17REL mutations does not yield this effect [7]. - Therapeutic administration of IL-17REL protein can reduce colitis symptoms, indicating its potential as a treatment target for IBD [8].

Core Viewpoint - Gastric cancer (GC) is the fifth most common cancer globally and a leading cause of cancer-related deaths, with China accounting for nearly 50% of the world's cases despite having only 20% of the global population [3] Group 1: Research Findings - Helicobacter pylori is a major risk factor for gastric cancer, but only 1%-3% of infected individuals develop the disease, indicating other contributing factors [3] - Recent studies by teams from Hong Kong Chinese University and Shanghai Jiao Tong University have identified Streptococcus anginosus as a promoter of gastric cancer through its metabolic product, methionine [3][5] - The research published in the journal Gut demonstrates that S. anginosus enhances gastric cancer progression, providing new insights for potential personalized treatment targets [3][5] Group 2: Methodology and Results - The research utilized shotgun metagenomic sequencing to explore the interaction between S. anginosus and the host, confirming its pro-inflammatory effects [5] - Experiments showed that the abundance of S. anginosus in gastric cancer patients correlates with a significant enrichment of the methionine biosynthesis pathway [5] - The study identified metE gene as crucial for methionine biosynthesis, with higher abundance observed in cancerous tissues, further validated by constructing a mutant strain of S. anginosus lacking the metE gene [5]

撰文丨王聪 编辑丨王多鱼 排版丨水成文 维持体内平衡 （即在外部变化中保持内部稳定的能力） ，对于生物体的生存至关重要。在神经系统中，这需要一些机制，既能在生理条件下维持神经元功能，又 能对损伤产生适应性反应。然而，与轴突能够再生的 外周神经系统 （PNS） 不同，成年 中枢神经系统 （CNS） 在损伤后无法再生，这既是因为抑制性的环 境，也是由于神经元本身生长能力的不足。这凸显了这两个系统在稳态和修复反应效率上的根本差异。 尽管在寻找再生的分子调控因子方面付出了巨大努力，但有效的再生策略仍然有限。对于 脊髓损伤 （SCI） 来说，目前尚无治愈方法，因此，发现这些再生调控 因子尤为紧迫。 2026 年 1 月 5 日，帝国理工学院 Simone Di Giovanni 团队 （博士生 宋雅玥 为第一作者） 在国际顶尖学术期刊 Cell 上发表了题为： A glycolytic shunt via the pentose phosphate pathway is a metabolic checkpoint for nervous system sensory homeostasis and axonal re ...