Acoustic divergence is a fundamental component of signal-based communication in animals, including humans, and has major implications for individual recognition, mate choice, and speciation. Bats have recently become an important model system for investigating acoustic communication due to their structurally complex vocal repertoires. This study explored communication calls of greater horseshoe bats ( Rhinolophus nippon) to determine whether geographically structured dialects occur and to identify factors associated with dialect formation. Communication calls from nine populations distributed across three regions were analyzed, and 12 syllable types shared among populations were identified. The associations of dialect differentiation with acoustic, climatic, morphological, and genetic distances, together with the influence of geographic barriers, were investigated. Results demonstrated significant acoustic variation among populations and regions for each syllable type, and this divergence was driven by diverse factors. As bats typically emit syllables in combination, all shared syllable types were subsequently analyzed as an integrated dataset. At this broader level, acoustic distance showed significant correlations with both geographic and genetic distance. Causal modeling further revealed that geographic distance and geographic barriers exerted direct effects on dialect differentiation. The sampled populations were classified into three dialect regions: Northeast, Central-East, and Southwest. The Qinling Mountains formed the boundary between the Central-East and Southwest regions. These findings provide clear evidence for the existence of dialect structure in communication calls of greater horseshoe bats and identify geographic isolation as a major force in the formation and preservation of vocal divergence. This study advances current understanding of animal acoustic evolution and offers insight into mechanisms linking vocal diversification with the generation of biological diversity.

Understanding how birds perceive and recognize visual objects remains a fundamental question in neuroscience. The entopallium, a key node in the avian tectofugal pathway, has long been implicated in complex visual processing, yet its internal functional architecture remains incompletely understood. In this study, neuronal activity in the pigeon entopallium was systematically mapped using controlled visual stimuli that independently varied in color, shape, and motion. Recordings revealed marked hue selectivity that remained invariant across luminance levels, pronounced orientation tuning in response to shape stimuli, and robust direction selectivity for moving stimuli. Spatial mapping further revealed distinct functional segregation, with color-selective neurons localized anteroventrally, shape-selective neurons dorsally, and motion-selective neurons posteriorly. At the same time, partial overlap among these response classes was observed, with a subset of neurons exhibiting joint tuning across stimulus dimensions, suggesting an organizational scheme characterized by regional specialization and partial cross-feature integration. Notably, entopallium neurons exhibited a moderate level of visual feature integration and shared important functional properties with early to intermediate stages of mammalian visual processing. Together, these findings establish the entopallium as a major site for multidimensional visual analysis in birds and provide evidence for convergent principles underlying the evolution of complex visual systems across vertebrates.

Impaired nuclear translocation of glucocorticoid receptor (GR) has been implicated in hippocampal vulnerability in Alzheimer's disease (AD), yet the molecular basis of this defect remains poorly understood. This study identified Huntingtin-associated protein 1 (Hap1) as a critical regulator of GR nuclear translocation in the hippocampus. Specifically, Hap1 expression progressively declined in the hippocampus of APP/PS1 mice with advancing age and pathological burden. Hippocampal Hap1 knockdown induced pronounced cognitive deficits and synaptic deterioration, as indicated by reduced dendritic arborization, decreased spine density, impaired long-term potentiation, and exacerbated amyloid-β deposition. Mechanistic analyses showed that Hap1 deficiency increased GR ubiquitination and proteasomal degradation and, more importantly, disrupted ligand-dependent GR translocation to the nucleus, thereby attenuating GR-dependent brain-derived neurotrophic factor transcription. In parallel, Hap1 knockdown elevated corticosterone concentration and induced depression-like behavior, consistent with hypothalamic-pituitary-adrenal axis dysregulation. Collectively, these findings establish defective GR nuclear trafficking driven by loss of Hap1 function as a key pathomechanism linking intracellular transport failure to synaptic dysfunction in AD and highlight Hap1 as a potential therapeutic target.

Tubulin post-translational modifications confer diverse functions to microtubules, with polyglutamylation representing a dynamic modification governed by coordinated glutamylation and deglutamylation. AGBL5 functions as a deglutamylase that removes glutamate residues at branch points within polyglutamate chains. While pathogenic variants in human AGBL5 are associated with retinitis pigmentosa, the underlying mechanism remains poorly defined. In the present study, an Agbl5 knockout mouse model was established and exhibited pronounced tubulin hyperglutamylation in photoreceptors, followed by progressive retinal degeneration. Transcriptomic profiling identified widespread disruption of ciliary function in Agbl5 knockout mice. Ultrastructural analysis by transmission electron microscopy revealed an impaired inner scaffold within the connecting cilium. Consistent with this defect, key phototransduction proteins were mislocalized or down-regulated in both mutant rod and cone photoreceptors, accompanied by severe disorganization of outer segment disk membranes. Immunofluorescence further demonstrated impaired recruitment of IFT88, kinesin-II, and dynein-2 to the CC, suggesting defective intraflagellar transport. Collectively, these findings indicate that AGBL5-dependent tubulin glutamylation homeostasis is essential for photoreceptor survival through preservation of CC architecture and normal protein trafficking mediated by intraflagellar transport.

Accurate taxonomic identification based on mammalian craniodental features remains critical for evolutionary, ecological, and paleontological research, yet conventional approaches are time-intensive and demand expert input. To overcome these limitations, a deep learning framework, HISNET-FF, was developed with a dual-stream architecture that integrates global cranial morphology with local diagnostic signals from teeth and auditory bullae. The model operates within a hierarchical classification pipeline, processing from genus-level discrimination to species-level resolution. Evaluation on an extensive image dataset encompassing 51 species across 18 genera of Talpidae achieved exceptional accuracy at both the genus (99.6%±0.4%) and species (96.5%±1.3%) levels. This species-level performance substantially exceeded that of single- stream models employing either flat (91.2%±2.3%) or hierarchical (93.9%±2.1%) strategies. To support end-to-end automation, a YOLO-based annotation module was implemented to localize key morphological traits with 97.8% recall, 97.9% precision, and 81.5% mean average precision (mAP@[.50:.95]). Incorporating this module incurred only a marginal reduction of 1.9% in identification accuracy. Thus, HISNET-FF offers a robust and accurate framework that accelerates morphology-based species identification and enables automated taxonomic classification, with strong potential for broader implementation across diverse biological research domains.

Pain encompasses both sensory discrimination and affective evaluation, yet the precise behavioral and neurobiological mechanisms of this well-conserved phenomenon are still incompletely understood. Although the lateral hypothalamus area (LHA) has been implicated in nociceptive modulation, its underlying circuitry and causal mechanisms remain elusive. In this study, formalin-induced pain-like behaviors in mice were associated with attenuated activity in LHA GAD2-positive neurons, a pattern also observed during acute restraint stress in adult male transgenetic mice. Chemogenetic activation of LHA GAD2 neurons significantly alleviated formalin-evoked nociceptive responses and reduced aversive behavioral phenotypes. Additionally, functional analyses revealed a GABAergic projection from the LHA to the lateral habenula that selectively mitigated affective disturbances in a neuropathic pain model. In parallel, projections from LHA GAD2 neurons to specific neuronal subsets within the ventrolateral periaqueductal gray modulated nociceptive responses under neuropathic pain conditions. These findings delineate a dual-pathway mechanism by which LHA GAD2 neurons independently regulate sensory and affective dimensions of pain-like behavior, offering a basis for targeted pain relief. Collectively, the results reveal previously uncharacterized aspects of pain processing by discrete LHA GABAergic subpopulations and potentially inform the development of subregion- or cell type-specific therapies for pain management.

The genus Paramesotriton Chang, 1935, comprising 15 species classified into two groups, exhibits the broadest geographical distribution among modern Asian newts, extending across southern China from west to east and representing a prominent example of adaptive radiation. Despite this success, intrageneric phylogenetic relationships among species remain unresolved, with particularly poor resolution within the Paramesotriton caudopunctatus species group (PCSG). In this study, restriction-site-associated DNA sequencing from five representative PCSG species was combined with previously published mitochondrial genomes to generate a genome-scale phylogenomic framework. The resulting analyses yielded robust support for interspecific relationships within PCSG. Gene tree discordance was primarily attributable to incomplete lineage sorting, with additional contributions from pre-speciation gene flow, as indicated by ASTRAL, HyDe, Dsuite, and PhyloNet. Evidence also supported hybridization between P. longliensis and an unidentified Paramesotriton lineage, consistent with a hybrid origin for P. zhijinensis. Comparative genomic and biogeographic inference further indicated that erosional isolation associated with exposure of carbonate sedimentary rocks facilitated allopatric divergence among PCSG lineages. Moreover, divergence timing aligned PCSG origin and diversification with Miocene paleoclimatic variability and progressive erosion of carbonate substrates, directly implicating karst landscape evolution in lineage formation within Asian warty newts. An erosion-driven speciation framework is therefore supported, in which recurrent episodes of geomorphological restructuring of karst mountain systems repeatedly imposed geographic isolation, driving successive allopatric diversification during both tectonically active and tectonically stable periods.

Aristolochic acid nephropathy (AAN) is a progressive form of kidney disease marked by acute tubular injury and interstitial fibrosis, ultimately leading to end-stage renal disease (ESRD). Despite regulatory restrictions, aristolochic acid (AA) remains a global health threat due to its presence in traditional herbal medicines. While mitochondria-mediated apoptosis is a hallmark of AA-induced tubular epithelial cell (TEC) injury, the upstream molecular mechanisms remain unclear. Here, we identify Z-DNA-binding protein 1 (ZBP1) as a key mediator of AA-induced kidney injury. Using Zbp1 knockout (Zbp1-/-) and Zα domain-mutant (ZαMut) mice, we show that loss of ZBP1 or its Z-form nucleic acid sensing capability protects against AA-induced renal dysfunction, apoptosis, and inflammation. Mechanistically, aristolochic acid I (AAI) induces mitochondrial oxidative stress and release of mitochondrial DNA (mtDNA), which adopts a Z-conformation and is recognized by ZBP1. The ZBP1 binding subsequently promotes RHIM-dependent interaction with RIPK1, culminating in caspase-8 activation and apoptotic cell death. Notably, ZBP1-mediated cell death was abolished by RIPK1 kinase inhibition or mutation, but unaffected by Ripk3 or Mlkl deletion, revealing a mechanism distinct from RIPK3/MLKL-dependent necroptosis. These findings uncover a previously unrecognized ZBP1-RIPK1-caspase-8 signaling axis driving non-canonical apoptosis in AAN and suggest that targeting this pathway may provide a novel therapeutic approach for nephrotoxin-induced kidney injury.

Microbiota assembly during early ontogeny in teleost fish plays a central role in shaping immune maturation and establishing host-microbe homeostasis, yet the regulatory mechanisms driving microbial succession across key developmental windows remain poorly understood. In this study, Larimichthys crocea was used to delineate microbiota assembly dynamics and the impact of stochastic and deterministic processes. Results indicated that community assembly peaked at day 18 post-hatching (DPH18), coinciding with the highest neutral model fit (R 2=0.71) and migration rate (m=0.88). Alpha (α)-diversity exhibited a hump-shaped pattern, with Comamonas dominance inversely correlating with Vibrio at DPH18. Microbial source tracking indicated that host-associated taxa played a more prominent role than dietary or environmental sources. Transcriptomic profiling revealed pronounced immune modulation during early development. Pro-inflammatory signaling, including IL-17 pathway activation, was elevated prior to DPH18, while anti-inflammatory regulators, such as transforming growth factor beta 2 ( tgfb2), declined over time, consistent with a transient reduction in immune restraint. Immune constraints in dexamethasone-treated zebrafish produced intestinal barrier impairment and microbial dysbiosis, demonstrating functional consequences of compromised early immune regulation. Collectively, these patterns defined DPH3-DPH18 as a critical colonization window in L. crocea, during which reduced immune constraint facilitates niche establishment by early colonizers. This temporally restricted window optimizes microbial resilience and long-term resistance to dysbiosis, providing a mechanistic basis for early-life microbiota-directed strategies in teleost development.

Heterozygous variants in ARR3, encoding cone arrestin, have emerged as a frequent cause of early-onset high myopia with a unique X-linked female-limited inheritance pattern. However, the mechanistic basis for this unusual anti-X-linked pattern is still unclear. Developmental expression profiling in mice demonstrated robust Arr3 expression in the retina from postnatal day 14 onward, with localization confined predominantly to outer segments of cones marked by red/green opsins, including a subset co-labeled with both red/green and blue opsins. Retinal flatmounts from Arr3 mutation knock-in mice and Arr3 knockout rats revealed a mosaic pattern of Arr3 expression in heterozygous individuals. Retinal single-cell RNA sequencing revealed significant shifts in cone subtype proportions in Arr3 +/- rats, with a marked reduction in M/S cones and a corresponding increase in S cones. Among differentially expressed genes, Pde6h was the only transcript altered in M/S cones across both Arr3 +/+ vs. Arr3 +/- and Arr3 -/0 vs. Arr3 +/- comparisons but not in Arr3 +/+ vs. Arr3 -/0 . These findings suggest that heterozygous Arr3 deficiency induces cone mosaicism that may mimic retinal defocus-like signals during phototransduction, potentially driving the development of high myopia under this distinctive inheritance model.