摘要: 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(Lb Gp), 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 Lb Gp effectively restored structural and functional deficits in MDD-derived organoids. Transcriptomic profiling revealed that Lb Gp 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, Lb Gp reversed the phenotypic consequences of CCT020312 exposure in control organoids. In conclusion, ventral forebrain organoids derived from individuals with MDD demonstrated that Lb Gp ameliorates disease-associated phenotypes by modulating ER stress.

摘要: Ovarian aging is characterized by a progressive decline in oocyte quality and quantity with age. Icariin(ICA), a flavonoid compound derived from Epimedium species, has demonstrated potential as an agent for ovarian restoration.In this study, a subcutaneous implantation system using gelatin methacryloyl(Gel MA) hydrogel embedded with ICA was developed to restore ovarian function in aged female mice. Mice were assigned to receive subcutaneous implantation of Gel MA alone(Gel MA group), Gel MA containing ICA(Gel MA/ICA group), or a sham operation.Ovarian morphology, serum hormone levels, follicle counts across developmental stages, and reproductive outcomes were evaluated. In vitro fertilization(IVF) and embryo culture assays were performed to assess oocyte developmental potential, while a 10 day natural mating trial was conducted to determine fertility restoration. RNA sequencing(RNA-seq) and RT-q PCR were performed to elucidate the underlying molecular mechanisms. Results showed that Gel MA/ICA treatment significantly increased ovarian index(0.19±0.01 vs. 0.13±0.01, P<0.0001) and follicle numbers at all developmental stages, including primordial(383.33±151.65 vs. 107.14±32.26, P<0.0001),primary(203.33±83.22 vs. 91.43±27.04, P=0.003), and secondary follicles(154.17±52.00 vs. 59.28±20.50,P=0.029) compared to the sham controls. Hormonal analyses revealed a significant reduction in serum folliclestimulating hormone(FSH, 11.97±3.53 vs. 53.10±17.89 ng/m L, P=0.0008), accompanied by elevated antiMüllerian hormone(AMH, 22.97±2.26 vs. 5.54±1.56 ng/m L, P<0.0001) and estradiol(E2, 315.30±37.62 vs.168.5±14.78 pg/m L, P<0.0001). Oocyte yield and developmental potential improved significantly, as reflected by the increased number of superovulated MII oocytes(17.83±5.15 vs. 4.83±4.79, P=0.0002), and higher proportions of two-cell(85.90%±6.16% vs. 50.00%±10.00%, P=0.0009), four-cell(81.67%±9.76% vs.50.00%±10.00%, P=0.0061), and blastocyst stage embryos(64.25%±10.55% vs. 23.33%±15.28%,P=0.0067). Live birth numbers were significantly increased following Gel MA/ICA treatment(6.90±3.21 vs. 1.72±2.05,P=0.0001). Transcriptomic analysis revealed up-regulation of genes associated with cytoskeletal organization(Vil1,Tubb3), lipid storage(Soat2, Plin4), oocyte maturation(Oosp2), and cytokine secretion(Cxcl12). Collectively,these findings suggest that Gel MA/ICA hydrogels effectively reverse key hallmarks of ovarian aging and restore reproductive function in aged mice, offering a promising platform for fertility preservation and a novel therapeutic for future investigations into ovarian aging.

摘要: General anesthesia(GA) is a pharmacologically induced,reversible state characterized by unconsciousness,amnesia, analgesia, and immobility in response to noxious stimuli. Accumulating evidence from animal models has elucidated diverse mechanisms of the action underlying GA, including disruption of large-scale brain network connectivity, regulation of multiple neural pathways, and modulation of specific receptors and ion channels. Despite advances in dissecting the neurobiological basis of anesthetic action, the precise cellular and circuit-level processes remain incompletely understood, limiting the development of safer and more effective strategies.Recent studies in Drosophila melanogaster, a genetically tractable model organism offering robust genetic analysis,advanced imaging capabilities, and compact neural architecture, have yielded critical insights into the conserved neurobiological mechanisms of GA, offering translational value for mammalian systems. This review outlines: 1) experimental paradigms used to evaluate anesthetic sensitivity and behavioral responses in Drosophila; 2) molecular targets and their mechanistic roles in mediating GA; and 3) neural circuit architectures and activity patterns shared by GA and sleep. Crossspecies comparisons are integrated to highlight conserved mechanisms that may guide the development of more refined anesthetic strategies.

摘要: Static magnetic field(SMF) exposure exerts notable regulatory effects on metabolic disorders, yet its influence on metabolic dysfunction-associated fatty liver disease(MAFLD) and gut microbiota during disease progression remains unclear. In this study, MAFLD was induced in mice via a high-fat diet(HFD), followed by exposure to a0.2 T SMF for 12 h per day over a 10 week period. SMF treatment significantly attenuated body weight gain,alleviated hepatic lipid accumulation, and improved liver function. Sequencing analysis of intestinal contents revealed a significant increase in microbial diversity and enrichment of beneficial bacterial taxa under SMF exposure. Integrated multi-omics analysis and Spearman correlation further demonstrated that SMF significantly reduced the expression of genes involved in fatty acid synthesis and modulated pathways related to polyunsaturated fatty acid and glutamate metabolism, in close association with shifts in beneficial gut microbiota.Furthermore, transcriptomic profiling of liver tissue indicated that SMF inhibited fatty acid synthesis and elongation by regulating the expression of peroxisome proliferator-activated receptor γ(PPARγ), thereby contributing to reduced hepatic burden. These findings highlight SMF as a promising non-invasive strategy for MAFLD intervention and provide insights into the microbiota-mediated metabolic axis underlying its therapeutic effects.

摘要: 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 regionspecific 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.

摘要: In adult mammals, optic nerve injury leads to irreversible vision loss due to its extremely limited regenerative capacity. In contrast, adult zebrafish possess a robust capacity for spontaneous visual system regeneration,although the spatiotemporal coordination of recovery across the retina, optic nerve, and brain remains poorly understood. In the present study, the regenerative dynamics following optic nerve transection were systematically characterized in adult zebrafish over a 5week period using hematoxylin-eosin staining,immunohistochemistry, transmission electron microscopy,single-cell RNA sequencing, and optokinetic response(OKR) behavioral assessments. At 1 week post-injury(1 wpi), retinal ganglion cell depletion was evident but showed significant recovery by 2 wpi. Concurrently, the injured optic nerve displayed a marked increase in diameter and cell number at 2 wpi, including widespread expression of proliferating cell nuclear antigen, consistent with heightened proliferative activity. Single-cell transcriptomic profiling at 2 wpi revealed five principal cell populations: fibroblasts, mural cells, immune cells, mature oligodendrocytes, and myelin-forming oligodendrocytes.By 4–5 wpi, remyelination within the optic nerve and reestablishment of synaptic architecture in the optic tectum were strongly correlated with functional restoration of OKR behavior. These findings provide a comprehensive spatiotemporal framework of visual pathway regeneration in zebrafish, establishing a valuable model for elucidating conserved mechanisms of neural repair with translational potential for human vision restoration.

摘要: Ring finger protein 122(RNF122), an E3 ubiquitin ligase,orchestrates antiviral immune responses in mammals by targeting retinoic acid-inducible gene 1 and melanoma differentiation-associated gene 5 for ubiquitination.However, its functional relevance in teleosts has yet to be clearly defined, particularly regarding the identification of substrate-specific regulatory sites. This study characterized RNF122 from mandarin fish(Siniperca chuatsi), termed sc RNF122, and investigated its regulatory impact on stimulator of interferon genes(STING)-mediated antiviral signaling. Results showed that sc RNF122expression was up-regulated in response to mandarin fish ranavirus(MRV) infection, and its overexpression suppressed sc STING-mediated interferon(IFN) production and enhanced MRV replication. Co-immunoprecipitation confirmed a direct interaction between sc RNF122 and sc STING. Functional assays demonstrated that sc RNF122facilitated sc STING degradation through the ubiquitinproteasome pathway, a process impeded by MG132treatment. Ubiquitination analyses of various sc STING mutants revealed that sc RNF122 catalyzed sc STING ubiquitination at K95, K117, and K155 residues. Moreover,sc RNF122 significantly impaired sc STING-dependent antiviral responses by engaging negative regulatory elements within the signaling cascade. Overall, sc RNF122was identified as a negative modulator of STING-mediated IFN signaling in mandarin fish, diminishing STINGdependent antiviral activity and promoting its degradation via the ubiquitin-proteasome pathway at lysine residues K95, K117, and K155. These findings provide mechanistic insight into the post-translational control of STING in teleosts and establish a foundation for future investigations into antiviral immune regulation.

摘要: 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 medullafree 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.

摘要: Ants rank among the most ecologically dominant and evolutionarily remarkable insects on the planet, capturing the imagination of both curious children and thoughtful scholars alike. Aristotle, impressed by their division of labor and cooperative behavior, described them as “political animals”. In Aesop's Fables, they are celebrated for their foresight and diligence in preparing for hardship. Traditional Chinese narratives similarly portray ants as modest creatures that,through collective effort, achieve extraordinary power and influence.

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.