摘要: Germ-free mice exhibit profound immunological immaturity. Despite recent studies emphasizing the role of specific bacterium-derived metabolites in immune cell development and differentiation, the mechanisms linking microbiota absence to systemic immune deficits remain incompletely defined. Here, droplet-based single-cell RNA sequencing of bone marrow and peripheral blood from both germ-free and specific pathogen-free mice was performed, identifying 25 transcriptionally distinct cell types. Neutrophil apoptosis was elevated in germ-free mice, potentially due to the absence of niacin dehydrogenase, a metabolite primarily produced by Pseudomonas. In addition, germ-free mice exhibited increased excretion of 5'-methylthioadenosine, enhanced ERK activation driven by reactive oxygen species, and disruption of bone marrow stromal antigen 2 signaling.Monocytes and CD8⁺ T cells from germ-free mice showed diminished responses to interferon-β and interferon-γ,consistent with heightened viral susceptibility. These findings establish a microbiota-dependent regulatory pathway linking immunodeficiency to microbial absence in germ-free mice, confirmed through complementary validation techniques.

摘要: The genetic regulation of hair density in animals remains poorly understood. The Dazu black goat, characterized by its black coarse hair and white skin, provides a unique model for dissecting coarse hair density(CHD). Using high-resolution micro-camera imaging, this study analyzed905 skin images, 33 skin transcriptomes, 272 wholegenome sequences, and 182 downloaded transcriptomes.Morphological assessment from juvenile to adult stages revealed the thickening of hair shafts accompanied by a progressive decline in density, largely attributable to rapid surface expansion of the trunk skin. Transcriptomic comparison between high-and low-CHD individuals identified 572 differentially expressed genes(DEGs). A genome-wide association study detected 25 significant single nucleotide polymorphisms(P<9.07e-8) and mapped48 annotated genes, with the most prominent association signal located near GJA1 on chr9.15931585-18621011.Literature review and Venn analysis highlighted six genes(GJA1, GPRC5D, CD1D, CD207, TFAM, and CXCL12)with documented roles in skin and hair biology, and three genes(GJA1, GPRC5D, and ATP6V1B1) overlapped with DEGs. Multiple-tissue transcriptomic profiling, western blotting, immunohistochemical staining, and skin single-cell RNA sequencing confirmed that GJA1 and GPRC5D were highly and specifically expressed in skin, particularly within hair follicles. Expression was localized predominantly to follicular stem cells and dermal papilla cells, suggesting a significant role in folliculogenesis and structural maintenance. Cross-validation using four public datasets further demonstrated positive correlations between GJA1and GPRC5D expression and hair follicle density. The innovative micro-camera application allowed the elucidation of spatiotemporal patterns and genes associated with CHD, thereby addressing a significant knowledge gap in animal hair density.

摘要: Adipose-derived mesenchymal stem cells(ADSCs)represent a readily accessible and important source of mesenchymal stem cells(MSCs) capable of multilineage differentiation. The Hippo signaling pathway effector YAP has emerged as a pivotal regulator of stem cell fate, yet the specific molecular mechanism by which it modulates lipogenic differentiation of ADSCs has not been clearly defined. In this study, goat ADSCs(g ADSCs) isolated from Albas goats in Inner Mongolia were used to investigate the role of YAP1 in adipogenic differentiation. Overexpression of YAP1 significantly promoted the differentiation of ADSCs into adipocytes, an effect accompanied by upregulation of LATS2 and activation of the negative feedback loop of the Hippo signaling pathway. Elevated LATS2 expression induced YAP phosphorylation, leading to reduced nuclear levels of YAP and TAZ and their subsequent accumulation in the cytoplasm. YAP1overexpression up-regulated LATS2 expression, which, in turn, enhanced the adipogenic differentiation of ADSCs.This pro-adipogenic effect of YAP1 was dependent on LATS2 kinase activity. These findings indicate that overexpression of YAP1 promotes ADSC adipogenesis by inducing LATS2 expression and activating the Hippo pathway negative feedback loop. Elucidating the molecular role of YAP in ADSC lipogenic differentiation holds great significance for regulating stem cell fate, treating metabolic disorders, and promoting hair follicle growth.

摘要: The Chinese tree shrew(Tupaia belangeri chinensis) has gained prominence as a model organism due to its phylogenetic proximity to primates, offering distinct advantages over traditional rodent models in biomedical research. However, the neuroanatomy of this species remains insufficiently defined, limiting its utility in neurophysiological and neuropathological studies. In this study, immunofluorescence microscopy was employed to comprehensively map the distribution of three calciumbinding proteins, parvalbumin, calbindin D-28k, and calretinin, across the tree shrew cerebrum. Serial brain sections in sagittal, coronal, and horizontal planes from 12 individuals generated a dataset of 3?638 cellular-resolution images. This dataset, accessible via Science Data Bank(https://doi.org/10.57760/sciencedb.23471), provides detailed region-and laminar-selective distributions of calcium-binding proteins valuable for the cyto-and chemoarchitectural characterization of the tree shrew cerebrum. This resource will not only advance our understanding of brain organization and facilitate basic and translational neuroscience research in tree shrews but also enhance comparative and evolutionary analyses across species.

摘要: The ancient Neo-Tethyan region underwent profound tectonic transformations, including the orogenesis of the Xizang Plateau and the westward retreat and ultimate closure of the Neo-Tethyan Ocean. These events significantly influenced the diversification and biogeography of aquatic animals. However, the impact of these large-scale sea-land shifts on the long-range evolutionary history of terrestrial fauna remains unclear.This study investigated how geological changes in the Neo-Tethyan region shaped the evolutionary trajectories and dispersal patterns of Pholcus sensu lato cellar spiders across the Old World. Molecular dating, ancestral area reconstructions, and diversity analyses were conducted using sequences from seven genes across 234 samples representing 209 species. Results indicated that these spiders originated in the eastern Neo-Tethyan region during the Early Eocene, with their subsequent diversification driven by a series of concomitant geological events. The Eurasian(ER) Group dispersed into Europe following the westward retreat of the Neo-Tethyan Ocean in the Early Miocene, while the African(AF) Group migrated into Africa via the Arabian Plate land bridge following the closure of the Neo-Tethyan Ocean in the Oligocene. The East Asian(EA) Group, which expanded along the southeastern margin of the Himalayas,experienced explosive diversification in response to sustained orogenesis at the Eocene-Oligocene boundary.These findings illustrate how large-scale geological processes and sea-land changes shaped the evolutionary history of terrestrial fauna in the Neo-Tethyan region.

摘要: Birch mice(family Sicistidae) are small dipodoid rodents distributed in regions surrounding the Qinghai-Xizang Plateau and extending across the Palearctic. In China,members of the genus Sicista are rarely recorded, and their systematics remain poorly resolved. As part of the Second Xizang Plateau Expedition by the Kunming Institute of Zoology, Chinese Academy of Sciences,systematic surveys conducted in southern Xizang and the western Tianshan Mountains yielded two previously unrecognized species. Two specimens from southern Xizang were found to occupy a deeply divergent phylogenetic position within Sicistidae. Morphological assessments and molecular phylogenetic analyses of both extant and fossil Sicistidae, along with total-evidence dating and ancestral distribution reconstruction, identified these specimens as representatives of an ancient extant lineage that diverged from Sicista approximately 20.38 million years ago. This lineage is designated as a new genus, defined by the new species Breviforamen shannanensis gen. et sp. nov. Furthermore, 11 specimens from the Tianshan Mountains are described as a second new species, Sicista brevicauda sp. nov., based on diagnostic morphological and genetic features.Ancestral distribution reconstructions, combined with fossil records, indicate an early Miocene origin for Sicistidae across a broad region spanning the “Gobi” Desert to parts of North America. Climatic deterioration and increasing desertification during the mid-Miocene likely drove southward dispersal of Breviforamen gen. nov. into southern Xizang prior to the complete formation of the Yarlung Zangbo River. Overall, these findings broaden current understanding of Sicistidae diversity, elucidate the origin and dispersal patterns of the family, and highlight the presence of an ancient relict lineage in China.

摘要: Extreme heat and chronic water scarcity present formidable challenges to large desert-dwelling mammals.In addition to camels, antelopes within the Hippotraginae and Alcelaphinae subfamilies also exhibit remarkable physiological and genetic specializations for desert survival. Among them, the critically endangered addax(Addax nasomaculatus) represents the most desertadapted antelope species. However, the evolutionary and molecular mechanisms underlying desert adaptations remain largely unexplored. Herein, a high-quality genome assembly of the addax was generated to investigate the molecular evolution of desert adaptation in camels and desert antelopes. Comparative genomic analyses identified 136 genes harboring convergent amino acid substitutions implicated in crucial biological processes,including water reabsorption, fat metabolism, and stress response. Notably, a convergent R146S amino acid mutation in the prostaglandin EP2 receptor gene PTGER2 significantly reduced receptor activity, potentially facilitating large-mammal adaptation to arid environments. Lineagespecific innovations were also identified in desert antelopes, including previously uncharacterized conserved non-coding elements. Functional assays revealed that several of these elements exerted significant regulatory effects in vitro, suggesting potential roles in adaptive gene expression. Additionally, signals of introgression and variation in genetic load were observed, indicating their possible influence on desert adaptation. These findings provide insights into the sequential evolutionary processes that drive physiological resilience in arid environments and highlight the importance of convergent evolution in shaping adaptive traits in large terrestrial mammals.

摘要: Ischemic heart disease(IHD) remains a leading contributor to cardiovascular disease(CVD) worldwide. Despite advances in diagnostic and therapeutic approaches,translational research demands robust large animal models to bridge the gap between experimental interventions and clinical application. Among these,porcine models have gained prominence due to their anatomical, physiological, immunological, and genomic similarities to humans. This review provides a comprehensive overview of current methodologies for establishing porcine IHD models, critically assesses emerging rehabilitative strategies, and outlines innovative therapeutic technologies, with the goal of guiding model selection and fostering the development of novel treatment strategies.

摘要: Pigs have emerged as valuable large-animal models for cardiac xenotransplantation; however, the temporal dynamics of myocardial development in this species remains insufficiently defined. This study analyzed gene expression patterns across four key developmental stages(neonatal, juvenile, sexual maturity, and adulthood) to delineate the molecular mechanisms driving porcine myocardial development. Increases in heart weight were accompanied by proportional expansion of myocardial fiber area and chamber size, reflecting coordinated structural development. Transcriptomic profiling of myocardial tissue by RNA sequencing(RNA-seq) identified 2 189 differentially expressed genes(DEGs) across stage comparisons. Short time-series expression miner(STEM)analysis classified these DEGs into four major expression clusters enriched in pathways associated with myocardial development, immune responses, cell proliferation, and metabolic processes. Among 359 DEGs conserved across all developmental stages, six candidate genes were strongly associated with myocardial development. Reverse transcription-quantitative real-time polymerase chain reaction(RT-qPCR) confirmed a significant correlation between the expression of these candidate genes and myocardial development in porcine tissue. These findings establish a transcriptomic framework for porcine myocardial maturation and provide a molecular basis for advancing cardiac xenotransplantation.

摘要: The DNA replication stress(RS) response is crucial for maintaining cellular homeostasis and promoting physiological longevity. However, the mechanisms by which long-lived species, such as bats, regulate RS to maintain genomic stability remain unclear. Also, recent studies have uncovered noncanonical roles of ribosomeassociated factors in maintaining genomic stability. In this study, somatic skin fibroblasts from the long-lived bigfooted bat(Myotis pilosus) were examined, with results showing that bat cells exhibited enhanced RS tolerance compared to mouse cells. Comparative transcriptome analysis under RS conditions revealed pronounced species-specific transcriptional differences, including robust up-regulation of ribosome biogenesis genes in bat cells and a markedly reduced activation of the P53 signaling pathway. These features emphasize a distinct homeostatic strategy in bat cells. Nuclear fragile X mental retardation-interacting protein 1(Nufip1), a ribosomeassociated factor highly expressed in bat fibroblasts, was identified as a potential integrator of ribosomal and P53 signaling via its association with ribosomal protein S27-like(Rps27l). These findings provide direct cellular and molecular evidence for a noncanonical RS response in bats, highlighting a deeper understanding of the biological characteristics and genomic maintenance mechanisms of long-lived species.