摘要: Brucellosis, a zoonotic disease caused by Brucella infection, poses a major threat to both global health and livestock productivity. Although reproductive impairment is well established, the molecular mechanisms driving testicular immunopathology remain poorly understood. In this study, single-cell RNA sequencing was used to delineate transcriptional changes in goat testicular tissues under physiological and Brucella-infected conditions,revealing dynamic immunological remodeling of the testicular microenvironment. Infection induced marked shifts in T cell and macrophage phenotypes, with T cells exhibiting pronounced hyperactivation linked to CD45-mediated signaling cascades. Thioredoxin-interacting protein(TXNIP), a gene strongly up-regulated in response to infection, emerged as a potential immunotherapeutic target. Intercellular communication networks were significantly disrupted in infected testes, with CD39-and JAM-dependent signaling pathways implicated in the erosion of immune privilege. Regulon analysis further identified GATA3, IRF5, SEMA4A, and HCLS1 as transcriptional regulators associated with T cells and macrophages in infected testes. These findings provide novel insights into the molecular mechanisms driving testicular immunopathology during Brucella infection and highlight candidate targets for immunomodulatory intervention in disease control and livestock reproductive health.

摘要: Macaques, particularly rhesus(Macaca mulatta) and cynomolgus(M. fascicularis) monkeys, are widely utilized in biomedical and toxicological research. Despite their critical role, effective vaccines against many viral pathogens affecting these primates remain limited, and vaccination is generally avoided in experimental populations to prevent potential confounding outcomes.Consequently, maintaining viral control within macaque colonies depends on stringent surveillance, systematic diagnostic testing, and rigorously enforced quarantine protocols. Accurate and early detection of viral infections is therefore essential for colony management and research integrity. This review synthesizes current knowledge on 10major viruses affecting macaque colonies, outlining their biological characteristics and diagnostic methodologies,and further assesses recent technological advances in viral detection. Drawing upon five years of surveillance data collected by VRL-Asia from breeding facilities across China, this review highlights the prevalence patterns of viral infections among breeding macaques and identifies critical epidemiological trends. These insights provide a valuable reference for researchers, veterinarians, and laboratory personnel seeking to strengthen biosecurity frameworks and ensure the reliability of research involving macaques.

摘要: Effective countermeasures against multidrug-resistant nosocomial pathogens, such as carbapenem-resistant Klebsiella pneumoniae and methicillin-resistant Staphylococcus aureus(MRSA), require the development of innovative antimicrobial strategies. This study presents a structure-function approach to antimicrobial peptide(AMP) design through the strategic integration of a cationic backbone with a hydrophobic core. This dual-domain architecture enables robust hydrophobic and electrostatic interactions, promoting spontaneous self-assembly and efficient membrane engagement. The lead peptide,Tryptolycin(TRPY), formed stable, monodisperse nanoparticles and demonstrated broad-spectrum bactericidal activity, with minimum inhibitory concentrations≤1 μmol/L against multiple strains of MRSA and K.pneumoniae, while exerting minimal cytotoxicity toward mammalian cells. TRPY achieved rapid bacterial elimination, eradicating 99.9% of both planktonic and persister populations within minutes. Mechanistic investigations revealed that TRPY induced membrane permeabilization, promoted reactive oxygen species(ROS)production, and inhibited biofilm formation. In murine infection models, TRPY effectively eradicated established infections, reducing bacterial burden across target organs by 3-to 5-fold without significant cytotoxicity at therapeutic concentrations. Collectively, these findings establish TRPY as a promising therapeutic agent for clinical translation in the treatment of refractory bacterial infections.

摘要: Oral ulcers（OUs） are among the most common lesions of the oral mucosa, typically associated with pain and burning sensations, and remain clinically challenging due to the scarcity of effective treatment options. Cy_RL-QN15, a novel ultra-short cyclic heptapeptide recently shown to promote skin repair, diabetic wound healing, and follicle neogenesis, was evaluated for its therapeutic potential in mucosal repair. Using a rat OU model and a primary oral epithelial cell inflammation model, Cy_RL-QN15 significantly accelerated wound closure through coordinated modulation of immune-epithelial crosstalk, including suppression of inflammatory cytokine release from macrophages and neutrophils, reduction of proinflammatory factor secretion by oral epithelial cells, and enhancement of their proliferation and migration.Mechanistic studies employing alanine scanning mutagenesis and microscale thermophoresis revealed that Cy_RL-QN15 directly interacted with Toll-like receptor 4（TLR4） via a methionine-dependent binding interface（Kd=2.64 μmol/L）, thereby inhibiting downstream My D88/NF-κB signaling. As the first ultra-short cyclic heptapeptide identified to antagonize TLR4, Cy_RL-QN15represents a mechanistically distinct immunomodulatory scaffold that restores mucosal homeostasis and offers a promising therapeutic candidate for TLR4-based OU intervention.

摘要: Tauopathies represent a class of neurodegenerative diseases(NDs), including Alzheimer's disease(AD),progressive supranuclear palsy(PSP), Pick's disease(PiD), and corticobasal degeneration(CBD), defined by intracellular accumulation of misfolded and hyperphosphorylated tau protein. The pathogenic cascade involves hyperphosphorylation, conformational changes,and aggregation into neurofibrillary tangles(NFTs), which are spatially and functionally linked to neuronal dysfunction, synaptic loss, and progressive cognitive and motor decline. To elucidate tau-mediated mechanisms,diverse transgenic rodent models expressing wild-type or mutant forms of human TAU have been generated.Although these models have advanced understanding of tau aggregation and propagation, tau-targeting therapies have failed to produce clinical benefits, raising concerns about the precise mechanism underlying tauopathies and the fidelity of animal models in evaluating therapeutic targets. This review systematically examines the neuropathological and behavioral phenotypes across established rodent and non-human primate(NHP)tauopathy models, highlighting mechanistic insights into tau-driven pathology. The advantages, limitations, and translational barriers of each model are critically evaluated to inform the development of more predictive preclinical platforms for therapeutic discovery.

摘要: Zona pellucida glycoprotein-1(ZP1) is essential for maintaining oocyte structural integrity and facilitating fertilization. Mutations in ZP1 are strongly associated with primary infertility disorders such as fertilization failure and empty follicle syndrome; however, the absence of accurate experimental models has hindered mechanistic understanding and obscured the etiological basis of ZP1-related infertility. In this study, CRISPR/Cas9-mediated genome editing was employed to generate two ZP1-edited cynomolgus macaques(Macaca fascicularis), designated#ZP1-1(male) and #ZP1-2(female). Following sexual maturation, oocytes retrieved from #ZP1-2 through superovulation exhibited a marked increase in zona pellucida-deficient oocytes and a significant reduction in maturation rates compared to controls. Integrated analyses, including immunofluorescence staining,transmission electron microscopy, transcriptomic profiling of oocytes, and histopathological examination of ovarian tissue, revealed disrupted folliculogenesis and oocyte anomalies consistent with phenotypes observed in human empty follicle syndrome. These findings establish the ZP1-knockout cynomolgus macaque as the first non-human primate model of ZP1-related infertility, providing a valuable platform for elucidating disease mechanisms and informing the development of targeted interventions for infertility arising from ZP gene mutations.

摘要: Male infertility constitutes a major global public health concern, with the underlying etiology remaining unidentified in nearly half of the diagnosed cases. Protein kinase CK1α(CK1α) functions as a pivotal regulator of cell cycle progression, pre-mRNA processing, and spliceosome-associated pathways through interactions with specific splicing factors. Comprehensive analyses revealed CK1α expression in both germ cells and somatic cells of mouse testes, implicating its involvement in spermatogenic regulation. However, the physiological roles and mechanistic basis of CK1α function in Sertoli cells remain unclear. In this study, CK1α was highly expressed in Sertoli cells, and conditional knockout of CK1α in murine Sertoli cells induced profound testicular atrophy and complete infertility. This phenotype was characterized by rapid depletion of Sertoli cells and spermatogenic dysfunction. Subsequent analyses demonstrated that CK1α regulated the fate determination of fetal and neonatal Sertoli cells in mice. At the molecular level, CK1α promoted Sertoli cell survival through interaction with the splicing factor ZRSR1 to modulate apoptosis. Collectively,these findings establish CK1α as a key regulator of alternative splicing and male reproduction, providing critical insights into the molecular mechanisms underlying testicular development and reproductive function.

摘要: Teleost peripheral blood contains a remarkably high proportion of B cells, accounting for 15%–50% of circulating lymphocytes. However, their immune responses to bacterial infection are yet to be elucidated. In the present study, 10× Genomics single-cell RNA sequencing（scRNA-seq） was employed to characterize the transcriptomic landscape of peripheral blood IgM⁺ B cells in grass carp（Ctenopharyngodon idella） following challenge with Aeromonas hydrophila, a major aquatic pathogen. Six transcriptionally distinct IgM⁺ B cell subpopulations were identified, including（im）mature B cells, innate B cells, proliferating B cells, IgD^high B cells,and two infection-induced subsets denoted as infection Ⅰand Ⅱ B cells. Bacterial infection altered the cellular heterogeneity of IgM⁺ B cells, triggered metabolic reprogramming in（im）mature and innate B cell subpopulations, and enhanced the immunological activation of circulating B cells. Notably, infection Ⅰ B cells demonstrated robust induction of interferon φ1（IFNφ1）, a type I IFN, following A. hydrophila exposure. This induction was further validated through in vitro bacterial stimulation,indicating that teleost B cells actively contribute to innate antibacterial responses through IFN signaling. Additionally,the IgD^high B cell subpopulation remained consistently present in peripheral blood across both infected and uninfected states, pointing to a constitutive and likely mature phenotype. These findings significantly advance our understanding of the heterogeneity of peripheral blood IgM⁺ B cells and provide new insights into IgM⁺ B cell-mediated immune responses in teleost fish.

摘要: Red light therapy is a clinically validated, noninvasive approach for improving skin structure and stimulating collagen renewal. However, the molecular mechanisms by which light therapy reverses collagen-related skin degeneration remain unclear. Using a natural aging mouse model, this study investigated the effects of red light therapy on skin structure and regeneration. Unlike other wavelengths, red light rapidly increased dermal thickness and stimulated epidermal renewal by enhancing collagen synthesis in dermal fibroblasts and activating collagen/integrin-induced proliferation and differentiation of epidermal keratinocytes, resulting in significant improvements in skin morphology. Mechanistically, red light increased endogenous TGFβ expression in fibroblasts, which up-regulated type Ⅰ collagen mRNA and protein expression via activation of SMAD2/3/4 nuclear translocation. Simultaneously, red light elevated intracellular c AMP, triggering AKT activation that inhibited matrix metalloproteinase expression via the NRF2/HO-1-dependent pathway, thereby reducing collagen degradation. The accumulation of type I collagen in dermal fibroblasts stimulated integrin signaling, promoting epidermal keratinocyte proliferation and differentiation.Red light-induced AKT activation also enhanced fibroblast proliferation, further amplifying collagen production and collagen-mediated epidermal renewal. These findings elucidate the mechanisms by which red light stimulates endogenous TGFβ and AKT signaling to regulate type I collagen production, driving coordinated dermis-epidermis remodeling. This pathway represents a potential therapeutic target for the prevention and treatment of agerelated dermal degeneration.

摘要: Life-history traits represent evolutionary adaptations that mediate responses to external environments. Analyzing variation in these traits provides valuable insights into macroecological processes and supports the development of effective conservation and restoration strategies.However, large-scale biogeographic patterns in life-history trait diversity among terrestrial vertebrates remain insufficiently characterized, and the processes shaping these patterns are not well understood. This study integrated life-history and spatial distribution data for 2?334terrestrial vertebrate species in China, including 398amphibians, 211 reptiles, 541 mammals, and 1?184 birds,to evaluate spatial patterns of trait diversity and identify underlying drivers. Assemblages in South and Southwest China exhibited high species richness, substantial assemblage-level evolutionary distinctiveness, expanded trait volumes, and elevated trait densities compared to null expectations, indicating roles as both evolutionary museums and cradles. In contrast, assemblages on the Tibetan Plateau showed expanded trait volumes but low trait densities, reflecting niche expansion among limited taxa. These findings emphasize the importance of niche packing before assemblages reach environmental carrying limits. Assemblages with high evolutionary distinctiveness tended to display high trait volumes and low trait densities,suggesting a consistent relationship between phylogenetic structure and functional diversification. Among the four groups, amphibians showed the highest sensitivity to environmental variation, highlighting the need for focused conservation efforts. Overall, this study revealed pronounced spatial heterogeneity in trait diversity across China, shaped by species richness, evolutionary distinctiveness, and environmental variation, providing valuable insights for refining conservation priorities for terrestrial vertebrate taxa.