Core Viewpoint - The research presents a new model of human gastric organoids, termed "gastroids," which successfully replicates the asymmetric tissue patterning along the anterior-posterior axis during early stomach development, addressing the WNT "signal gradient paradox" in gastric development [4][5][6]. Group 1 - The study was conducted by a collaborative team from Tsinghua University, Kunming University of Science and Technology, and other institutions, and published in the journal Nature [3]. - The gastroids developed from human pluripotent stem cells (hPSCs) exhibit a dual gastric fundus-antrum pattern and closely resemble in vivo gastric development at molecular, cellular, structural, and anatomical levels [5][6]. - The research identifies NR2F2 as a key factor mediating the formation of the gastric fundus-antrum pattern during the development of gastric organoids [5]. Group 2 - The study provides a unified new theory to resolve the existing paradox regarding the WNT signaling gradient in gastric organ development, which has challenged traditional developmental biology paradigms [5][6]. - The gastroids serve as a more realistic experimental platform for advancing research on gastric organogenesis and the development of gastric organoids [4][6].

Core Viewpoint - Organoid technology has emerged as a revolutionary tool in disease mechanism research, drug development, and precision medicine, but traditional manual operations face challenges in standardization, throughput, and reproducibility, which hinder research breakthroughs and clinical translation. The integration of automation technology is injecting new momentum into organoid research, facilitating efficient transitions from research outcomes to industrial applications [2]. Group 1: Event Details - An online seminar titled "Automation Innovation in High-Throughput Organoid Disease Modeling" will be held on September 17, 2025, from 15:00 to 16:20 [4]. - The seminar will focus on the application of automated liquid handling technology in organoid construction, drug screening, and disease modeling, bringing together experts and technology pioneers to discuss how automation solutions can enhance experimental efficiency, data reliability, and research scalability [2][4]. Group 2: Speaker Profiles - Professor Zhou, an assistant professor at the University of Hong Kong's Department of Microbiology, specializes in establishing organoid models and viral research based on organoid technology. Her team has successfully developed the world's first human respiratory organoid culture system and bat intestinal organoids, significantly advancing biomedical research and drug development [6]. - Lin Delin, a senior application support engineer at Opentrons, graduated with a master's degree in biochemistry and molecular biology. He focuses on the application of automated liquid handling technology in the biotechnology field and has accumulated extensive practical experience and published multiple research papers [8].

Core Insights - On September 10, 2025, the journal Nature published 23 papers, with 9 authored by Chinese scholars, highlighting the significant contribution of Chinese researchers to international scientific discourse [3]. Group 1: Research Contributions - Tsinghua University’s Professor Zhang Qiang published a paper on the health impacts of PM2.5 pollution from the 2023 Canadian wildfires, emphasizing the long-range effects of environmental disasters on public health [3]. - A collaborative study from Tsinghua University and other institutions focused on human gastroids to model early stomach development, showcasing advancements in biomedical engineering [5]. - Research from Southern University of Science and Technology explored the stabilizing effects of amino acids on proteins and colloidal dispersions, contributing to the understanding of biochemical interactions [6]. - A study from Zhejiang University investigated the loss-of-function mutations in the PLD4 gene and its link to systemic lupus erythematosus, providing insights into genetic factors in autoimmune diseases [8]. - A paper from the Chinese Academy of Sciences discussed amplifying cellular responses using proximity labeling, which could have implications for immunology and therapeutic strategies [10]. - MIT's research on ABCA7 variants highlighted their impact on phosphatidylcholine and mitochondria in neurons, relevant for neurodegenerative disease studies [12]. - Tsinghua University’s Yanhong Gu contributed to research on observing differential spin currents, which may advance the field of quantum physics [14]. - A study from Westlake University and Fudan University examined the heterogeneous nature of LiF in solid-electrolyte interphases, relevant for battery technology [16]. - Stanford University’s research on the structure and mechanism of the mitochondrial calcium transporter NCLX adds to the understanding of cellular calcium homeostasis [17].

Core Viewpoint - The research identifies loss-of-function mutations in the PLD4 gene as a cause of systemic lupus erythematosus (SLE), providing a theoretical basis for precise diagnosis and treatment of the disease [3][10]. Group 1: Research Findings - The study published in Nature confirms that mutations in the PLD4 gene can lead to SLE and elucidates the pathogenic mechanism involved [3]. - The research team reported five SLE patients with renal lesions exhibiting PLD4 biallelic mutations [8]. - PLD4 is highly expressed in dendritic cells, monocytes, and B cells, and functions as a 5' nucleic acid exonuclease that limits the overactivation of TLR7 and TLR9 [7]. Group 2: Mechanism of Action - TLR7 and TLR9 play critical roles in sensing RNA and DNA, initiating downstream inflammatory signaling pathways that contribute to SLE development [6]. - The absence of PLD4 leads to excessive activation of TLR7 and TLR9, resulting in heightened inflammatory responses and the production of autoantibodies [10]. Group 3: Potential Therapeutic Implications - PLD4-deficient mice exhibited autoimmune phenotypes and responded to the JAK inhibitor baricitinib, suggesting that targeting type I interferon may be a potential therapy for SLE patients with PLD4 deficiency [10].

Core Insights - The article discusses a significant research study on the heterogeneous nature of lithium fluoride (LiF) in solid-electrolyte interphases (SEI), which challenges the long-held belief that components in the electrode interface layer are in pure phases [3][6] - The findings provide new explanations for rapid ion transport mechanisms in high-performance secondary batteries and offer important theoretical guidance for the design of high-performance electrolyte and electrode interface materials [3][6] Group 1 - The research team utilized 19F solid-state NMR technology to discover that LiF SEI exhibits rich spectral characteristics due to the formation of a limited LiF-LiH solid solution, consisting of hydrogen-rich (LiH1−yFy) and fluorine-rich (LiF1−xHx) phases [6] - The study confirmed that in high Coulomb efficiency electrolytes, the hydrogen-rich phase dominates, which can be explained by the superior ionic conductivity of the LiF-LiH solid solution compared to LiF alone [6] - As a proof of concept, the research demonstrated that a LiH1−yFy coating in lithium metal batteries shows significant advantages over a LiF coating, providing a new understanding of the component heterogeneity in SEI [6] Group 2 - The research was conducted by a collaborative team from Westlake University and Fudan University, with key contributors including Liu Xiangsi, Li Shuyang, Yuan Chen, and Zheng Bizhu as co-first authors, and Xiang Yuxuan, Song Yun, and Zhu Yizhou as corresponding authors [7]

Core Value - Eli Lilly's Lilly TuneLab is a machine learning platform that leverages over $1 billion worth of drug development models accumulated over years, making it one of the most valuable datasets in the industry [4] - The platform utilizes Federated Learning technology, allowing biotech companies to use Lilly's AI models for drug discovery without sharing their proprietary data [4] Collaboration Model - Biotech companies using the platform are required to contribute their training data, which is aimed at improving the platform and benefiting the entire ecosystem and patients [5] - The initiative is designed to empower smaller biotech firms with the advanced AI capabilities typically available to larger companies [5] Addressing Pain Points - The platform addresses a fundamental barrier faced by small biotech companies, which is the lack of large-scale, high-quality data necessary for training effective models [7] - Lilly TuneLab compresses decades of learning into an immediately usable intelligence resource, thus alleviating the data scarcity issue [7] Future Plans - Eli Lilly plans to enhance TuneLab with additional features, such as in vivo small molecule prediction models, to continuously expand its capabilities [8] - The launch of the AI drug development platform represents a proactive attempt by a pharmaceutical giant to reshape the industry ecosystem and accelerate innovation for data-deficient biotech companies [8]

Core Insights - The article discusses the impact of intrauterine hyperglycemia (IUHG) on the development of primordial germ cells (PGC) and fertility, particularly emphasizing its detrimental effects on female offspring [2][5][8] - A recent study published in Cell Discovery reveals that IUHG disrupts sex-specific epigenetic reprogramming during PGC development, leading to reproductive health issues and intergenerational effects [2][8] Group 1: Research Findings - IUHG significantly disrupts the development of PGCs, with a more pronounced effect on female offspring, resulting in reduced fertility [5][8] - The study utilized transgenic mice exposed to high glucose environments to systematically investigate the effects of IUHG on PGC development, revealing that IUHG affects chromatin accessibility and DNA methylation reprogramming in a sex-specific manner [5][6] Group 2: Mechanisms of Impact - In female embryos, IUHG leads to abnormal retention of chromatin accessibility at pluripotency gene promoters, inhibiting normal gene silencing and blocking the initiation of meiosis, ultimately hindering oocyte maturation [6][8] - In contrast, male embryos experience less severe effects on chromatin accessibility and gene transcription, but global DNA methylation reprogramming is impaired, particularly in key imprinted gene regions, indicating potential developmental impacts on future generations [6][8] Group 3: Implications and Future Directions - The findings underscore the importance of blood sugar management during pregnancy and suggest new avenues for improving reproductive health in offspring through metabolic intervention or epigenetic regulation [8]

Core Viewpoint - The research identifies CD160⁺ CD8⁺ T cells as a key factor in enhancing the efficacy of anti-PD-1 immunotherapy in colorectal cancer by regulating T cell exhaustion and overcoming resistance [2][5][7]. Group 1: Research Findings - The study found that CD160⁺ CD8⁺ T cells are specifically enriched in the ileum and possess unique characteristics, including resistance to terminal exhaustion and strong clonal expansion [5]. - CD160⁺ CD8⁺ T cells significantly inhibited tumor growth in colorectal cancer models with high microsatellite instability and inflammation [5]. - CD160 gene knockout accelerated tumor growth, while the transfer of CD160⁺ CD8⁺ T cells alleviated this effect, indicating their potential therapeutic role [5]. Group 2: Mechanism of Action - The research revealed that CD160 interacts with PI3K (p85α) and promotes the expression of FcεR1γ and 4-1BB through the AKT-NF-κB pathway, enhancing the cytotoxicity of CD8⁺ T cells [5][7]. Group 3: Therapeutic Implications - The study proposes an innovative immunotherapy strategy involving the infusion of CD160⁺ CD8⁺ T cells to overcome anti-PD-1 resistance, presenting advantages over existing therapies like TIL and CAR-T [7]. - A prospective, open-label interventional clinical trial has been initiated to explore the safety and preliminary efficacy of CD160⁺ CD8⁺ T cells combined with anti-PD-1 monoclonal antibodies in treating colorectal cancer [7]. Group 4: Commentary - A commentary published in Nature Cell Biology highlights the potential of CD160⁺ CD8⁺ T cells in regulating anti-tumor immune responses and improving treatment outcomes when combined with immune checkpoint blockade [8].

肠道寄生蠕虫适应脊椎动物的过程涉及进化出一系列策略，以减轻对宿主组织的损害，从而支持自己的繁殖以及后代向环境中的传播。肠道寄生蠕虫会启动由 IL- 25 介导的簇状细胞-2 型固有淋巴细胞 （ILC2） 回路，从而增强宿主的屏障保护，尽管活的肠道寄生蠕虫能够靶向并限制这一通路。 2025 年 9 月 5 日，加州大学旧金山分校的研究人员在国际顶尖学术期刊 Cell 上发表了题为： IL-25-induced memory type 2 innate lymphoid cells enforce mucosal immunity 的研究论文。 该研究揭示了 IL-25 诱导的一种 效应记忆 2 型固有淋巴细胞 （ effector-memory ILC2 ） ，其可 在多种警报素缺失的情况下仍能保持激活状态，强化黏膜免 疫，同时避免对慢性炎症产生不良的敏感性，从而揭示了一条利用先天免疫细胞协调分布式黏膜防御的通路。 撰文丨王聪 编辑丨王多鱼 排版丨水成文 组织 在生命周期中的适应性可视为 压力累积 驱动的系统性调整，这些压力通过诱导转录重编程、表观遗传修饰及细胞组分重构，促使组织以更高效的损伤应答 和感染防御机 ...

撰文丨王聪 编辑丨王多鱼 排版丨水成文 乳腺癌 复发可能源于潜伏在骨髓及其他部位的 播散性肿瘤细胞 （DTC） 。临床上，DTC 与乳腺癌复发和死亡独立相关。在小鼠模型中的临床前研究表明， 细 胞自噬 和 mTOR 信号转导是肿瘤休眠和逃逸的关键机制。 近日，宾夕法尼亚大学的研究人员在 Nature Medicine 期刊发表了题为： Targeting dormant tumor cells to prevent recurrent breast cancer: a randomized phase 2 trial 的研究论文。 这项随机 2 期临床试验结果显示，使用细胞自噬抑制剂 羟氯喹 ， 或 mTOR 抑制剂 依维莫司 ， 或二者联合使用， 可靶向休眠的 残留肿瘤细胞 （RTC） ，从 而清除 播散性肿瘤细胞 （DTC） ，预防乳腺癌复发。 在这项研究中，研究团队测试了用 氯喹 或 羟氯喹 （HCQ） 短暂抑制或长期抑制细胞自噬以及使用 雷帕霉素 （RAPA） 或 依维莫司 （EVE） 抑制 mTOR 信 号转导对 残留肿瘤细胞 （RTC） 负荷和 无复发生存期 （RFS） 的影响。 在携带休眠的 残 ...