编辑丨王多鱼 排版丨水成文 生物钟 控制着 24 小时的节律性过程。然而，经典生物钟基因以外的遗传变异如何影响外周昼夜节律，目前仍知之甚少。 2025 年 8 月 25 日，厦门大学 张永有 教授团队与贝勒医学院 Dongying Guan 团队合作，在 Cell 子刊 Cell Metabolism 上发表了题为： Genetics-nutrition interactions control diurnal enhancer-promoter dynamics and liver lipid metabolism 的研究论文。 该研究表明，遗传-营养相互作用控制着昼夜节律增强子-启动子动态变化及肝脏脂质代谢。 论文链接 ： https://www.cell.com/cell-metabolism/abstract/S1550-4131(25)00356-0 在这项最新研究中，研究团队发现，基因变异导致了人类和小鼠肝脏基因表达的昼夜模式存在差异。 营养挑战会以品系特异性的方式改变小鼠肝脏中基因表达的节律性。值得注意的是，遗传学和营养学相互依存地控制着超过 80% 的节律基因和增强子-启动子相 互作用 （E- ...

Core Viewpoint - The research presents a novel method for constructing embryonic models using chemically induced embryonic founder cells (EFC), which allows for a more efficient and accurate simulation of mouse embryogenesis and organogenesis [2][3][6]. Group 1: Research Methodology - The study utilized small molecules (CHIR-99021, E-616452, Lif, AM580) to induce mouse embryonic stem cells into 8-16 cell stage embryonic founder cells (EFC) [6]. - EFC cells can determine all lineages of blastocysts both in vivo and in vitro, enabling the construction of a complete embryonic model [6][9]. - The model accurately replicates the developmental process starting from organ formation, including the formation of three germ layers and early organ structures [6][9]. Group 2: Research Highlights - The system using EFCs allows for direct, rapid, efficient, and accurate construction of in vitro embryonic development models [8]. - Induced EFCs (iEFC) can generate a scalable and faithful embryonic model (iEFC-EM) that reproduces mouse embryonic development up to the organ formation stage [9]. - The model demonstrates the transformation of epithelial cells to mesenchymal cells during gastrulation, leading to the development of various early organ precursors and structures [6][9].

Core Viewpoint - The research team from the University of Science and Technology of China has developed the world's fastest subcellular resolution 3D imaging technology for small animals, enabling the first detailed 3D mapping of the entire neural network in mice, which provides a new tool for studying peripheral nerve regulation networks and disease mechanisms [1][2]. Group 1 - The innovative imaging technology functions like a "super CT scanner" for small animals, completing full-body imaging of adult mice in just 40 hours, generating approximately 70TB of raw image data, equivalent to thousands of HD movies [2]. - The efficiency of this imaging technology has improved several to dozens of times compared to existing methods, with resolution enhanced from tissue-cell level to uniform subcellular level, allowing clear capture of individual nerve fibers with diameters of a few micrometers [2]. - This breakthrough enables precise analysis of the 3D connectivity of different types of peripheral nerves, including cranial, spinal, and autonomic nerves, providing technical support for mapping central-peripheral nerve structures and understanding disease mechanisms [2]. Group 2 - The technology is expected to address numerous unresolved questions in neurobiology, developmental biology, anatomy, and biomedicine, and can be applied in biomedical research and disease mechanism analysis, laying a solid foundation for the development of precise neural regulation therapies in the future [2].

Core Insights - The article highlights significant research published in the journal Cell, with a focus on studies led by Chinese scholars, covering various biological mechanisms and their implications for health and disease [2]. Group 1: Adeno-Associated Virus Research - A study identified an alternative receptor for adeno-associated viruses (AAV), named AAVR2, which can restore transduction in the absence of AAVR and provide a unique entry pathway for unclassified AAVs [4][6]. - The research suggests that overexpressing a minimal functional AAVR2 can enhance AAV transduction in vivo, allowing low doses of AAV to achieve similar therapeutic effects [6][8]. Group 2: Glucose Restriction and Tumor Metastasis - Research revealed that glucose restriction influences the pre-metastatic immune landscape in the lungs through exosomal TRAIL, suggesting a new mechanism of immune regulation [10][11]. - The study warns that extreme low-carbohydrate diets may inhibit tumor growth but could also promote lung metastasis, highlighting the need for careful evaluation of metabolic intervention strategies [11][13]. Group 3: Neurovascular Coupling - A study demonstrated that endothelial gap junction coupling enables rapid propagation of vasodilation during neurovascular coupling, crucial for meeting the brain's instantaneous energy demands [15][16]. - The findings indicate that the molecular composition of gap junctions varies along the arterial-venous axis, with the strongest connections found in the arterial segments [16][18]. Group 4: pH-Dependent Inflammatory Responses - Research uncovered how acidic environments during inflammation regulate immune responses through pH-dependent transcriptional condensates, identifying BRD4 condensates as pH sensors [20][21]. - The study suggests that pH acts not only as a byproduct of inflammation but also as an active regulator of the inflammatory response, providing new insights into chronic inflammation and autoimmune diseases [23]. Group 5: Thyroid Hormone Transport Mechanism - A study elucidated the structural mechanisms of thyroid hormone transport via MCT8 and OATP1C1, revealing their binding interactions with active thyroid hormones [25][26]. - The research highlights the importance of these transport mechanisms in development and disease, providing insights into the pathogenic mechanisms of related mutations [28].

Core Insights - The article discusses the critical role of thyroid hormone transport to the brain for normal neural development, mediated by the transport proteins MCT8 and OATP1C1 [2][3]. Group 1: Research Findings - A recent study published in the journal Cell by researchers from Baylor College of Medicine and the National Institutes of Health provides structural insights into the transport mechanisms of thyroid hormones via MCT8 and OATP1C1 [4][5]. - The study utilized cryo-electron microscopy to analyze the structures of MCT8 and OATP1C1 in complex with active thyroid hormones T3 and its precursor T4, achieving resolutions of 2.9 Å and 2.3 Å respectively [7]. - Key findings include the high transport specificity of MCT8 for thyroid hormones, the selective transport mechanism of OATP1C1 for thyroxine, and the discovery of a conserved extracellular regulatory site in OATP1C1 that can be allosterically inhibited by E1G [9][11].

Core Viewpoint - The article discusses a groundbreaking study that developed a high-speed 3D imaging technology for mapping the peripheral nervous system (PNS) in mice, significantly enhancing the understanding of its complex structure and functions [4][10]. Group 1: Technological Advancements - The research team from the University of Science and Technology of China introduced a novel imaging technique called blockface-VISoR, achieving subcellular resolution in whole-mouse imaging within 40 hours, which is several times faster than existing methods [4][10]. - This technology allows for the visualization of nerve pathways and connections in the PNS, which has been challenging due to the complexity and size of the mammalian body [3][10]. Group 2: Research Findings - The study successfully created a detailed peripheral nerve map, revealing intricate structures such as spinal motor and sensory nerves, visceral sympathetic nerves, and their interactions with various non-neural tissues and organs [13][21]. - The research utilized multiple labeling techniques, including fluorescent, immuno, and viral markers, to visualize different types of nerves, providing unprecedented insights into the PNS [12][19]. Group 3: Implications and Future Directions - The findings from this research are expected to facilitate a better understanding of the regulatory networks of the peripheral nervous system and the mechanisms of related diseases [4][10]. - The research team plans to share the image datasets online and is working on a platform for researchers to explore these data, which may offer new insights even to professional anatomists [22].

Core Viewpoint - The emergence of large language models (LLMs) like ChatGPT has significantly transformed academic writing, particularly in the biomedical field, raising concerns about research integrity and the accuracy of generated content [2][5]. Group 1: Impact of LLMs on Academic Writing - A study published in July 2025 revealed that approximately 200,000 out of 1.5 million biomedical papers indexed by PubMed in 2024 showed signs of LLM-generated text, accounting for about 1/7 of the abstracts [3][4]. - The use of LLM-assisted writing in biomedical publications is accelerating, with an earlier assessment indicating that about 1/9 of abstracts in the first half of 2024 exhibited similar signs [4]. - The study found that at least 13.5% of abstracts in 2024 were processed using LLMs, with some sub-corpora reaching as high as 40%, indicating a profound impact on scientific writing [5][10]. Group 2: Methodology and Findings - Researchers analyzed over 15 million abstracts from PubMed between 2010 and 2024, identifying 454 words that appeared significantly more frequently in 2024 compared to previous years, many of which were stylistic rather than content-related [7][9]. - The study highlighted that the vocabulary changes were more pronounced following the rise of LLMs than during significant events like the COVID-19 pandemic, with a notable increase in the use of adjectives and verbs [9][10]. - The proportion of LLM-assisted writing varies across disciplines, countries, and journals, with over 20% of abstracts in certain regions and fields utilizing LLMs [10]. Group 3: Challenges and Adaptations - Previous attempts to assess the impact of LLMs on academic writing faced challenges due to the lack of disclosure from users, making it difficult to evaluate the true extent of LLM usage [6]. - As authors become aware of specific vocabulary associated with AI-generated text, such as "delves," its usage may decline, complicating the assessment of AI's influence on academic writing [12]. - While using AI for text refinement or translation is deemed reasonable, generating large volumes of text without oversight raises concerns regarding research integrity [13].

Core Viewpoint - The FDA has announced an immediate review of clinical trials involving the transfer of live human cells from American citizens to laboratories in China and other "hostile countries" for genetic engineering, indicating a shift towards stricter biotechnology restrictions against China [4][5]. Group 1 - The FDA's review is prompted by concerns that international transfers and genetic engineering operations may occur without patient knowledge or consent, potentially leading to the misuse of sensitive genetic data by foreign governments, including those of hostile nations [5]. - The Biden administration's data security rules set in December 2024 included export controls but allowed a "comprehensive exemption" for clinical trial biological samples, creating regulatory loopholes that permitted participation from Chinese-funded enterprises [5]. - FDA Commissioner Marty Makary emphasized the importance of the integrity of the biomedical research system and stated that actions are being taken to protect patients, rebuild public trust, and defend America's biomedical leadership [5].

Core Viewpoint - The article discusses the development of a new method for rapidly generating functional vascular organoids from induced pluripotent stem cells (iPSCs) through the orthogonal activation of transcription factors ETV2 and NKX3.1, which significantly improves the efficiency and potential applications of vascular organoids in research and clinical settings [4][12][14]. Group 1: Vascular Organoids Overview - Vascular organoids (VO) are important models in cardiovascular research, capable of simulating dynamic interactions between endothelial cells and vascular wall cells, and replicating organ-specific vascular microenvironments [2][6]. - Current differentiation protocols for vascular organoids face challenges such as high heterogeneity, long time requirements, dependency on matrix gels and growth factors, high costs, and low in vivo vascularization capabilities [2][4]. Group 2: Research Development - A collaborative research team from Peking University and Harvard Medical School published a study in Cell Stem Cell detailing a new method for generating vascular organoids [3]. - The new method allows for the generation of uniform vascular organoids within 5 days from iPSCs, establishing a controllable vascular lineage differentiation model [4][10]. Group 3: Methodology and Findings - The method employs orthogonal activation of transcription factors ETV2 and NKX3.1 to induce iPSCs into endothelial cells (iEC) and mural cells (iMC), respectively, without the need for extracellular matrix [10][12]. - The vascular organoids formed have a diameter of approximately 250 μm and can mature further when embedded in extracellular matrix, leading to larger and more structured vessels [10][11]. - Single-cell RNA sequencing revealed that the duration of transcription factor activation influences the identity and heterogeneity of vascular cells, allowing for the potential to create specific types of vascular networks on demand [10][12]. Group 4: Applications and Implications - The vascular organoids demonstrated the ability to form perfused vessels when implanted in immunodeficient mice, promoting vascular reconstruction in ischemia and transplantation models [11][12]. - This research establishes a new platform for rapid and versatile vascular organoid generation, enhancing the potential for applications in vascular modeling, disease research, and regenerative cell therapies [14].

Core Insights - This week, four research papers authored by Chinese scholars were published in the prestigious journal Cell, covering topics such as mitochondrial influence on pluripotency, a multimodal genetic screening platform, anti-aging mesenchymal progenitor cell therapy, and a key switch in complement protein attack [1][2][3][4]. Group 1: Mitochondrial Influence on Pluripotency - A study led by Professor Wu Jun from the University of Texas Southwestern Medical Center developed a new technique for enforced mitophagy, revealing the impact of mitochondria on cell pluripotency and demonstrating that reduced mitochondrial numbers delay pre-implantation mouse embryo development [3]. Group 2: Perturb-Multi Genetic Screening Platform - Professor Zhuang Xiaowei from Harvard University introduced Perturb-Multi, a novel platform that combines imaging and sequencing technologies to enable parallel perturbation of hundreds of genes in intact mammalian tissues, facilitating the discovery of genetic bases for complex cellular and tissue physiology [7]. Group 3: Anti-Aging Mesenchymal Progenitor Cell Therapy - Researchers Liu Guanghui, Wang Si, and Qu Jing from the Chinese Academy of Sciences and Capital Medical University developed engineered human anti-aging mesenchymal progenitor cells (SRC) that exhibit resistance to aging, stress, and malignant transformation, significantly delaying multi-organ aging in primate models [11]. Group 4: Key Switch in Complement Protein Attack - A study by Zhicheng Wang from the University of Pennsylvania focused on the complement system, identifying a critical parameter—the surface density of potential complement attachment sites—that triggers a significant increase in complement activation, providing insights for the design of long-lasting drug carriers and biocompatible implants [15][17].