摘要: The immunomodulatory function of estrogen within the ovary remains a subject of ongoing debate, and the neonatal ovarian immune microenvironment, particularly its modulation by estrogen, has not been comprehensively characterized. In this study, the effects of 17β-estradiol（E₂）, a key regulator of immune function, were investigated using single-cell transcriptomic profiling of C57BL/6J neonatal mouse ovaries after E₂ treatment. Results revealed dynamic alterations in the proportion of immune cell types after E₂ treatment, accompanied by changes in cytokine and chemokine expression. Detailed analyses of gene expression, cell states, and developmental trajectories across distinct cell types indicated that E₂treatment influenced cell differentiation and development.Notably, E₂ treatment reduced the abundance of macrophages and promoted a phenotypic transition from M1 to M2 macrophages. These findings demonstrate that the neonatal mouse ovarian immune microenvironment is sensitive to estrogenic modulation, which governs both the distribution and functional specialization of resident immune cells, offering novel mechanistic insights into the immunomodulatory roles of estrogen across various immune cell types.

摘要: Chorionic gonadotropin α（Cgα） functions as the shared subunit for thyroid-stimulating hormone subunit β（Tshβ）,luteinizing hormone subunit β（Lhβ）, and follicle-stimulating hormone subunit β（Fshβ）. While these β-subunits have been extensively studied using effective gene knockout models in zebrafish, the biological role of Cgα remains elusive. In this study, cgα-deficient zebrafish generated via transcription activator-like effector nucleases（TALENs）exhibited viability but displayed pronounced developmental abnormalities, including growth retardation,hyperpigmentation, reduced thyroxine（T4） levels, and defective anterior swim bladder inflation during juvenile stages. In adults, cgα deficiency led to disrupted gonadal development, impaired secondary sex characteristics（SSCs）, and severely impacted reproductive behavior in both female and male fish. Notably, both testicular and ovarian differentiation were observed in cgα-deficient fish and lhβ^-/-;fshβ^-/-mutants. Gonadal sex differentiation in cgα-deficient zebrafish exhibited a pronounced shift toward testicular fate upon additional disruption of fshβ(cgα^-/-;fshβ^-/-), marked by elevated anti-Müllerian hormone（amh） expression, or following loss of follicle-stimulating hormone receptor（fshr）(cgα^-/-;fshr^-/-). In vitro assays in Chinese hamster ovary（CHO） cells revealed increased cAMP response element（CRE） promoter activity following transfection with constructs encoding Fshr, Fshβ/Fshr, or Cgα/Fshβ/Fshr. Collectively, the phenotypes observed in cgα-deficient fish recapitulate those of thyrotropin-and gonadotropin-disrupted models, highlighting the essential role of Cgα in thyroid and gonadal function. Importantly,these findings uncover the role of Fsh signaling in maintaining proper ovarian differentiation in zebrafish,including Cgα-independent Fshβ activity and the constitutive functionality of Fshr.

摘要: Over the last three decades, microglia have been recognized as essential components of central nervous system(CNS)development, homeostasis, immune surveillance, and neurodegenerative pathogenesis(Lin & Wang, 2024; Prinz et al., 2019). Historically, microglia were regarded as exclusive to the CNS, based on the absence of cells bearing microglial morphology, transcriptional identity, and ontogeny in tissues outside the CNS in standard mouse and rat models.

摘要: Comprehensive phylogeographic insights require the integration of evidence across diverse taxa, ecosystems,and geographical regions. However, our understanding of the arid biota of the vast Asian drylands remains limited.Accordingly, this study combined phylogeographic analyses with ecological niche modeling to investigate patterns of diversification and demography of the Central Asian racerunner(Eremias vermiculata), a widespread lizard inhabiting arid eastern-Central Asia(AECA). Mitochondrial DNA(mtDNA) sequences were obtained from 876 individuals across 113 localities, while three nuclear genes—CGNL1, MAP1A, and β-fibint7—were sequenced from 204, 170, and 138 individuals,respectively. Analyses identified four distinct mtDNA lineages corresponding to specific geographic subregions within the AECA, reflecting the topographic and ecological heterogeneity of the region. The detection of mito-nuclear discordance indicated the presence of complex evolutionary dynamics. Divergence dating placed the initial lineage splits at approximately 1.18 million years ago,coinciding with major tectonic activity and climatic aridification that likely promoted allopatric divergence. In particular, lineage diversification within the Tarim Basin suggests that recent environmental shifts may have contributed to genetic divergence. Demographic reconstructions revealed signatures of population expansion or range shifts across all lineages during the Last Glacial Maximum, signifying the combined influence of the unique topography and climate dynamics of the AECA on diversification and demographic change. These results highlight the need for fine-scale genomic investigations to clarify the mechanisms underlying mitonuclear discordance and local adaptation. Such efforts are essential for advancing understanding of how genetic diversity in dryland taxa responds to environmental change, providing insights into the evolutionary adaptability of species in dynamic landscapes.

摘要: Mammalian scent glands mediate species-specific chemical communication, yet the mechanistic basis for convergent musk production remain incompletely understood. Forest musk deer and muskrat have independently evolved specialized musk-secreting glands,representing a striking case of convergent evolution.Through an integrated multi-omics approach, this study identified cyclopentadecanone as a shared key metabolic precursor in musk from both forest musk deer and muskrat, although downstream metabolite profiles diverged between the two lineages. Single-cell RNA sequencing revealed that these specialized apocrine glands possessed unique secretory architecture and exhibited transcriptional profiles associated with periodic musk production, distinct from those in conventional apocrine glands. Convergent features were evident at the cellular level, where acinar, ductal, and basal epithelial subtypes showed parallel molecular signatures across both taxa. Notably, acinar cells in both species expressed common genes involved in fatty acid and glycerolipid metabolism(e.g., ACSBG1, HSD17B12, HACD2, and HADHA), suggesting a conserved molecular framework for musk precursor biosynthesis. Metagenomic analysis of musk samples further revealed parallel microbial community structures dominated by Corynebacterium and enriched in lipid metabolic pathways. These findings suggest multi-level convergence in musk biosynthesis,from molecular pathways to microbial communities,providing novel insights into mammalian chemical signaling and artificial musk production.

摘要: Coat color polymorphism in domestic animals provides a robust framework for elucidating mechanisms of species adaptation, domestication, and genomic diversity. Leiqiong cattle, a representative indicine breed from southern China, are predominantly yellow-coated, although a subset exhibits a solid black phenotype. To determine the genetic basis of this variation, a genome-wide association study(GWAS) was performed in 212 Leiqiong bulls. A pronounced association signal was detected on chromosome 6 within the fifth intron of the CORIN gene,providing the first evidence of the potential influence of CORIN on bovine coat color variation. Integration of these results with publicly available genomic datasets and haplotype analyses indicated that the yellow coat phenotype is derived from Indian indicine ancestry,whereas the black coat phenotype emerged through introgression from wild bovine lineages and artificial hybridization with Wagyu cattle. Comparative analysis of Indian indicine cattle with divergent coat colors revealed distinct LEF1 haplotypes within a shared CORIN background, suggesting an ancient and complex domestication history underlying coat color variation.These findings provide direct evidence that introgression has shaped phenotypic variation in East Asian cattle and offer novel insights into the genetic architecture of pigmentation, with implications for future breeding strategies.

摘要: Ectothermic organisms may expand their thermal tolerance by producing multiple protein isoforms with differing thermal sensitivities. While such isoforms commonly originate from allelic variation at a single locus(allozymes)or from gene duplication that gives rise to paralogs with distinct thermal responses, this study investigated mRNA editing as an alternative, post-transcriptional mechanism for generating mRNA variants. Cytosolic malate dehydrogenase(cMDH) was examined in foot tissue of two congeners of the marine mussel genus Mytilus, which occupy different thermal environments. Multiple editing events were detected within the mRNA coding region in both species. Editing sites were species-specific, with no shared positions identified. In M. coruscus, editing occurred at 117, 123, 135, 190, 195, 204, 279, and 444,while in M. galloprovincialis, editing was detected at 216 and 597. Each species exhibited multiple edited mRNA variants, and these isoforms were associated with differential protein expression. These findings suggest that mRNA editing may contribute an additional layer of molecular variation. The generation of diverse mRNA isoforms from a single DNA coding sequence may enhance enzymatic flexibility across temperature ranges,supporting eurythermal physiological performance and mitigating thermal stress. Moreover, the presence of multiple edited transcripts within individual organisms raises important caveats about the limitations of approaches that deduce amino acid sequences or estimate adaptive variation solely from genomic data.

摘要: Bromodomain(BRD)-containing proteins are central mediators of gene regulation, serving as key components of chromatin remodeling complexes and histone recognition scaffolds. By specifically recognizing acetylated lysine residues on histones(Kac) via their conserved BRD, these proteins influence chromatin structure and gene expression. Although their overarching role is well-established, the precise molecular functions and mechanisms of individual BRD proteins remain incompletely characterized. The ciliate Tetrahymena thermophila, a unicellular eukaryote with a transcriptionally active macronucleus enriched in histone acetylation, is an excellent model for exploring the significance of BRDcontaining proteins. In this comprehensive review, all BRDcontaining proteins encoded in the T. thermophila genome are systematically examined, including their expression profiles, histone acetylation targets, interacting proteins,and potential roles. This review lays the groundwork for future investigations into the complex roles of BRD proteins in chromatin remodeling and transcription regulation, offering insights into basic eukaryotic biology and the molecular mechanisms underlying BRD-linked diseases.

摘要: Flight feathers represent a hallmark innovation of avian evolution. Recent comparative genomic analyses identified a 284 bp avian-specific highly conserved element(ASHCE) located within the eighth intron of the SIM b HLH transcription factor 1(Sim1) gene, postulated to act as a cis-regulatory element governing flight feather morphogenesis. To investigate its functional significance,genome-edited(GE) primordial germ cell(PGC) lines carrying targeted ASHCE deletions were generated using CRISPR/Cas9-mediated editing, with germline chimeric males subsequently mated with wild-type(WT) hens to obtain GE progeny. The resulting GE chickens harbored 257–260 bp deletions, excising approximately half of the Sim1-ASHCE sequence. Reverse transcription-quantitative real-time polymerase chain reaction(RT-qPCR) analysis showed an average 0.32-fold reduction in Sim1 expression in the forelimbs of GE embryos at day 8(E8) compared to WT counterparts. Despite this, GE chickens developed structurally normal flight and tail feathers. In situ hybridization localized Sim1 expression to the posterior mesenchyme surrounding flight feather buds in E8 WT embryos, but not within the buds themselves. These results suggest that partial deletion of Sim1-ASHCE,despite diminishing Sim1 expression, does not disrupt flight feather formation. The excised region appears to possess enhancer activity toward Sim1 but is dispensable for flight feather development. Complete ablation of the ASHCE will be necessary to fully resolve the regulatory role of Sim1 in avian feather morphogenesis.

摘要: Chronic pancreatitis（CP） is a progressive and irreversible fibroinflammatory disease that markedly increases susceptibility to pancreatic cancer and remains without effective targeted therapies. Among the genetic contributors to CP, the carboxypeptidase A1 p.Ser282Pro(CPA1^S282P) variant has been proposed to promote disease through misfolding-induced endoplasmic reticulum stress（ERS）, although the broader pathogenic landscape remains incompletely defined. This study generated a rabbit model mimicking the human CPA1^S282P mutation using the Sp RY-ABE-8.17 system. Homozygous CPA1^S282P rabbits exhibited characteristic human CP phenotypes following alcohol induction, including visceral pain, elevated serum lipase and amylase, inflammatory cell infiltration, and extensive pancreatic fibrosis.Biochemical analyses confirmed that the p.S282P mutation induced CPA1 misfolding and elevated the expression of ERS markers GRP78 and CHOP in both transfected HEK293T cells and homozygous mutant rabbits. Notably,the CPA1^S282P mutation markedly disrupted intrapancreatic lipid homeostasis, contributing to the development of CP in mutant rabbits. This study successfully established the first rabbit model of CP that accurately recapitulates CP caused by a defined human point mutation. Additionally, this study provides insights into a previously unrecognized link between CPA1 and intra-pancreatic lipid metabolism, offering a foundation for identifying novel therapeutic targets for human CP.