Core Insights - The article discusses the significant relationship between maternal gut microbiome during early pregnancy and the risk of preterm birth, highlighting the need for further understanding of this connection [2][3][4]. Group 1: Research Findings - A study involving a cohort of 5,313 pregnant women identified a direct association between early pregnancy gut microbiome characteristics and preterm birth risk [3][6]. - The gut bacterium Clostridium innocuum was identified as a novel biomarker for predicting preterm birth, with its presence correlating positively with preterm birth risk [3][7]. - The research established a preterm microbiome risk score (MRS) that effectively differentiates between women with shorter gestation periods and higher preterm birth risk [6][7]. Group 2: Mechanisms and Implications - Clostridium innocuum was found to degrade 17β-estradiol, a hormone linked to pregnancy outcomes, suggesting a mechanism by which it influences preterm birth risk [6][8]. - The study indicates that maternal polygenic risk for preterm birth is amplified by the presence of Clostridium innocuum, emphasizing the interaction between genetic susceptibility and microbiome composition [6][7].

Core Viewpoint - Aging is a major risk factor for various neurodegenerative diseases, including Alzheimer's disease, and is associated with the accumulation of senescent cells that propagate the aging process through paracrine signaling [2] Group 1: Research Findings - The research published in Nature Aging demonstrates that border-associated macrophages (BAM) regulate cognitive aging by inducing paracrine senescence in microglia through migrasome-mediated mechanisms [4][8] - In the early stages of brain aging, BAM acquire senescence-related characteristics, potentially due to prolonged exposure to beta-amyloid (Aβ) [7] - Senescent-like BAM exhibit increased production of migrasomes, which transmit aging-related signals to neighboring cells, particularly microglia, inhibiting their apoptosis and promoting senescence induction [8] Group 2: Intervention Strategies - The research team developed intervention strategies targeting migrasome production by delivering siRNA to block Tspan4, which can improve cognitive deficits in aged mice [8] - These findings suggest that migrasomes are powerful carriers of aging regulatory signals and represent a promising target for Senomorphic therapies, which aim to inhibit the senescence-associated secretory phenotype without affecting cell death [8]

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 - The study highlights the significant role of the oral virome in human health, particularly its connection to obesity and type 2 diabetes, and introduces the Human Oral Virome Database (HOVD) as a valuable resource for understanding these relationships [3][5][7]. Group 1: Research Findings - The research team constructed the Human Oral Virome Database (HOVD), which includes 24,440 viral operational taxonomic units (vOTUs) and 83 eukaryotic viruses, providing a comprehensive resource for studying oral viromes [3][5][7]. - The study found that the oral virome diversity is reduced in obese patients with type 2 diabetes, indicating a weak correlation with clinical features and enhanced oral-gut virus transmission [6][7]. - The research identified phages that infect Porphyromonas gingivalis, a key pathogen in periodontal disease, and screened for six potential endolysins that can inhibit its growth, suggesting a new therapeutic avenue for managing periodontal disease associated with type 2 diabetes [6][7]. Group 2: Implications for Disease Understanding - The findings suggest that oral viruses may influence the progression of diseases such as oral cancer, periodontal disease, and rheumatoid arthritis, indicating potential prognostic and diagnostic applications based on microbiome composition [5][6]. - The study enhances understanding of host-virus interactions within the oral microbiome and provides new insights for the diagnosis and treatment of human diseases [9].

Core Viewpoint - The integration of artificial intelligence (AI) with biomaterials and biofabrication is revolutionizing the simulation of tumor extracellular matrix (ECM), enhancing physiological relevance and establishing patient-specific drug testing platforms [30]. Group 1: AI in Tumor ECM Modeling - AI methods are incorporated into three key stages of tumor ECM modeling: material formulation, optimization of biofabrication processes, and post-manufacturing analysis [4]. - AI enables the rational development of bioinks with tunable mechanical, chemical, and biological properties, improving printing accuracy and consistency [4]. - AI-enhanced in vitro tumor modeling aids in the rational design and real-time optimization of engineered tumor models, providing powerful tools for drug discovery and cancer mechanism research [4]. Group 2: Limitations of Current Methods - Existing in vitro models struggle to replicate the biochemical complexity and dynamic physical properties of the ECM, limiting their effectiveness [2][7]. - Advances in biomaterials and biofabrication technologies have allowed for the simulation of certain ECM features, but challenges remain in capturing the inherent complexity and dynamic behavior of ECM [7]. Group 3: AI's Role in Biofabrication - AI improves precision and adaptability in the three stages of ECM modeling: pre-process, in-process, and post-process [7]. - In the pre-process stage, AI facilitates the design of biomaterials through predictive modeling and exploration of initial design options [7]. - During the in-process stage, AI enables real-time monitoring and optimization of biofabrication methods, ensuring accurate replication of tumor ECM structures and properties [7]. - In the post-process stage, AI assists in high-throughput analysis of ECM datasets, linking biophysical properties to tumor behavior [7]. Group 4: Future Directions - Establishing standardized datasets, improving model interpretability, and incorporating clinical validation are crucial for bridging the gap between AI-driven ECM modeling and real-world translational impact [4]. - The framework developed for tumor ECM modeling can be extended to other diseases involving ECM dysfunction, such as fibrosis, neurodegenerative diseases, and inflammatory bowel disease [4].

Core Viewpoint - The study reveals that genetic-nutrition interactions control diurnal enhancer-promoter dynamics and liver lipid metabolism, highlighting the importance of genetic and environmental factors in metabolic processes [3][5]. Group 1 - Genetic variations lead to differences in the circadian patterns of gene expression in the liver of humans and mice [4]. - Nutritional challenges alter the rhythmic expression of liver genes in a strain-specific manner [4]. - Over 80% of rhythmic genes and enhancer-promoter interactions are interdependent on genetic and nutritional factors [5]. Group 2 - An atypical clock regulatory factor, estrogen-related receptor gamma (ESRRγ), emerges as a key transcription factor in the study [4]. - Knockout of the Esrrγ gene in mice eliminates strain-specific metabolic responses to diet [4]. - Single nucleotide polymorphisms (SNPs) associated with rhythmic gene expression are enriched in enhancer-promoter interactions and correlate with lipid metabolism characteristics in humans [6]. Group 3 - The findings emphasize the previously underappreciated temporal dimension of genetic-environment interactions in regulating lipid metabolism traits [8]. - The research has significant implications for understanding individual differences in susceptibility to obesity-related diseases and personalized timing therapies [8].

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].