Zoological Research最新文献

Lipid droplets (LDs) serve as dynamic organelles central to host immune response and bacterial infection resistance by recruiting multiple proteins and peptides with established antiviral and antibacterial properties. Although macrophage polarization is integral to both innate immunity and lipid homeostasis, the regulatory influence of LDs on this process remains unclear. In this study, augmentation of LDs via oleic acid (OA) treatment attenuated M1 polarization in RAW264.7 macrophages. Given that LD budding is mediated by fat storage-inducing transmembrane protein 2 (FIT2) encoded by FITM2, transcriptomic analysis following FITM2 knockdown revealed suppressed expression of fatty acid-binding protein 5 (FABP5), a lipid-binding protein that further modulated LD abundance. Both FIT2 and FABP5 were found to regulate LD content and collectively contributed to inhibition of M1 macrophage polarization. This shift impaired macrophage capacity to mount effective antibacterial responses. These findings identify a coordinated role for LDs and FABP5 in modulating M1 macrophage polarization, establishing a mechanistic link between lipid metabolism and innate host defense against bacterial infection.

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.

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.

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.

Liver-expressed antimicrobial peptide 2 (LEAP2) is a key regulator of innate immune defense in teleosts, yet the molecular basis of its chemotactic function remains largely unidentified. Boleophthalmus pectinirostris MOSPD2 ( BpMOSPD2) was previously identified as a candidate receptor for BpLEAP2 in monocytes/macrophages (MO/MΦ). In the present study, BpLEAP2 stimulation was found to trigger a retromer-dependent intracellular trafficking program essential for BpMOSPD2-mediated chemotaxis. Exposure to BpLEAP2 significantly enhanced BpMO/MΦ migration and promoted the accumulation of BpMOSPD2 at the plasma membrane. Subcellular fractionation and immunofluorescence analyses revealed that BpMOSPD2 translocated from the endoplasmic reticulum (ER) to early endosomes upon BpLEAP2 stimulation, followed by redistribution to the cell surface. Blockade of ER export or knockdown of core retromer subunits ( BpVPS35, BpVPS26, or BpVPS29) abolished membrane localization and attenuated BpLEAP2-induced migration. Co-immunoprecipitation combined with mass spectrometry confirmed direct binding between BpMOSPD2 and BpVPS35, while domain-mapping indicated that this interaction was not exclusively dependent on MSP or CRAL-TRIO domains. Depletion of individual retromer components led to retention of BpMOSPD2 in early endosomes, establishing the necessity of the retromer complex for receptor recycling. Functionally, disruption of this complex eliminated the pro-migratory activity of BpLEAP2 on BpMO/MΦ. These findings identify the retromer complex as a critical regulator of BpMOSPD2 trafficking and uncover a previously unrecognized mechanism through which BpLEAP2 promotes MO/MΦ migration in teleosts.

Estrus represents a critical phase in the porcine reproductive cycle and relies on functional ovarian development and coordinated steroidogenesis. Granulosa cells (GCs) mediate these processes by secreting estradiol (E ₂) and progesterone (P ₄), which are essential for follicular maturation and ovulatory competence. While circular RNAs (circRNAs) have been implicated in steroid hormone synthesis, their involvement in the regulation of gilt estrous remains unclear. In this study, circRNA sequencing was performed on ovarian tissues of estrus (ES) and non-estrus (NES) gilts, resulting in the identification of a novel circRNA, termed circular SHOC2 leucine rich repeat scaffold protein (circSHOC2), which exhibited marked up-regulation in ES ovaries. Functional assays demonstrated that circSHOC2 overexpression enhanced E ₂ and P ₄ synthesis and increased the protein levels of key steroidogenic enzymes. Mechanistic investigation revealed that circSHOC2 sponges miR-130b-5p. Silencing miR-130b-5p significantly enhanced E ₂ and P ₄ production, along with the up-regulation of steroidogenic proteins. Additionally, miR-130b-5p targeted ASH1-like histone lysine methyltransferase (ASH1L), while its overexpression significantly inhibited ASH1L. Cotransfection experiments revealed that ASH1L mitigated the inhibitory effects of miR-130b-5p on E ₂ and P ₄ synthesis in GCs. These findings establish a regulatory axis in which circSHOC2 modulates steroidogenic capacity in porcine GCs via the miR-130b-5p/ASH1L pathway, offering mechanistic insight into the molecular basis of gilt estrus and providing potential targets to enhance reproductive efficiency.

Intestinal inflammation is a common challenge in intensive aquaculture, yet its pathogenesis remains unclear. While interleukin 22 (IL-22) is recognized as a critical regulator of cellular homeostasis during inflammation in higher vertebrates, its roles in fish are not well understood. This study established hypoxia-induced models in intestinal tissues and primary intestinal epithelial cells of yellow catfish to investigate the involvement of IL-22 in maintaining intestinal homeostasis. Results revealed that Pelteobagrus fulvidraco IL-22 ( Pf_ IL-22) was abundantly expressed in mucosal tissues, with the highest levels in the gill and intestine. Hypoxia induced pronounced intestinal injury, characterized by loosening of the lamina propria and extensive vacuolization, while activating hypoxia-inducible factor (HIF) signaling and markedly up-regulating IL-22 expression. IL-22 levels peaked at 24 h post-hypoxia, suggesting a role in early immune responses. Recombinant Pf_IL-22 also induced transcription of pro-inflammatory mediators, including IL-1β and tumor necrosis factor α (TNF-α), in primary intestinal epithelial cells, indicating a dual regulatory function in balancing protection and inflammation. Mechanistic analyses revealed that HIF-1α directly interacted with a hypoxia response element within the IL-22 promoter to drive transcription, as confirmed by dual-luciferase assays, electrophoretic mobility-shift assays, and HIF-1α knockdown. Silencing Pf_IL-22 significantly suppressed Th17 cell differentiation pathways, demonstrating its role in shaping downstream immune responses. These findings establish the HIF-1α/IL-22 axis as a key regulatory pathway modulating immune responses and alleviating intestinal inflammation, providing a basis for developing IL-22-targeted immunotherapies and selective breeding strategies in aquaculture.

Major depressive disorder (MDD) is a debilitating psychiatric condition associated with substantial personal, societal, and economic costs. Despite considerable advances in research, most conventional antidepressant therapies fail to achieve adequate response in a significant proportion of patients, underscoring the need for novel, mechanism-based interventions. Lycium barbarum glycopeptide (LbGp), a bioactive compound with emerging neuroprotective properties, has been proposed as a candidate for antidepressant development; however, its therapeutic efficacy and underlying mechanisms remain largely uncharacterized. In this study, ventral forebrain organoids were generated from patients with MDD to investigate disease-related neurophysiological abnormalities. These organoids exhibited disrupted neuronal morphology, diminished calcium signaling, and impaired electrophysiological activity. Administration of LbGp effectively restored structural and functional deficits in MDD-derived organoids. Transcriptomic profiling revealed that LbGp ameliorated endoplasmic reticulum (ER) stress responses. To investigate the causative role of ER stress, control organoids were treated with the ER stress agonist CCT020312, which elicited neural activity impairments resembling those observed in MDD organoids. Notably, LbGp reversed the phenotypic consequences of CCT020312 exposure in control organoids. In conclusion, ventral forebrain organoids derived from individuals with MDD demonstrated that LbGp ameliorates disease-associated phenotypes by modulating ER stress.

Recent advances have deepened our understanding of the evolutionary and developmental origins of feather branching architectures. However, the internal tissue differentiation within these branches has received limited attention. This study examined eight fossilized feathers preserved in early Late Cretaceous Burmese amber, characterized by barb rami composed entirely of cortical tissue with no internal medulla. Based on barb rami morphology, the feathers were categorized into three distinct morphotypes. Comparative analysis with feather development in extant chickens suggested minimal tissue differentiation in these early feathers. Functional simulations further revealed that modern barb rami configurations provide greater aerodynamic stability than medulla-free early feathers under most conditions, highlighting flexural stiffness as a key factor in the evolution of feather branches. The presence of medulla-free barb rami suggests that although the three-level hierarchical branching pattern characteristic of modern feathers had emerged by the Jurassic, tissue differentiation within feather branches remained developmentally unstable during the Late Cretaceous. This instability likely contributed to the structural variability of early feathers, enabling morphologies that no longer persist in modern birds.

Astrocytes are associated with varying brain size between rodents and primates. As a close evolutionary relative of primates, the tree shrew ( Tupaia belangeri) provides a valuable comparative model for investigating glial architecture. However, the anatomical distribution and morphological characteristics of astrocytes in the tree shrew brain remain poorly characterized. In this study, glial fibrillary acidic protein (GFAP) immunofluorescence was employed to systematically examine the spatial distribution and morphology of astrocytes in the whole brain of tree shrews. Notably, GFAP-immunoreactive (ir) astrocytes were detected throughout the telencephalon, diencephalon, mesencephalon, metencephalon, and myelencephalon. Distinct laminar distribution was evident in regions such as the main olfactory bulb and hippocampus. Semi-quantitative comparisons revealed significant regional differences in astrocyte density between tree shrews and mice, encompassing the main olfactory bulb, accessory olfactory bulb, olfactory tubercle, cortex, hippocampus, cortical amygdaloid nucleus, hypothalamus, thalamus, superior colliculus, interpeduncular nucleus, median raphe nucleus, and parabrachial nucleus. Compared to mice, tree shrews exhibited higher astrocyte density with increased morphological complexity in the posterior hypothalamic nucleus, dorsomedial hypothalamic nucleus, ventromedial hypothalamic nucleus, and periaqueductal gray, but lower density with greater morphological complexity in the hippocampus and substantia nigra. In the paraventricular hypothalamic nucleus and lateral hypothalamic area, GFAP-ir astrocytes displayed comparable densities between tree shrews and mice but exhibited region-specific differences in morphological complexity. This study provides the first brain-wide mapping of GFAP-ir astrocytes in tree shrews, revealing marked interspecies differences in their distribution and morphology, and establishing a neuroanatomical framework for understanding astrocyte involvement in diverse physiological and behavioral functions.