Wei Wei

Background: Intracranial dural arteriovenous fistulas (DAVFs) with pial arterial supply (PAS) constitute a distinct subgroup characterized by more complex angioarchitecture and potential implications for treatment planning. This study evaluated the incidence, angiographic characteristics, and clinical predictors of PAS in a cohort of patients with DAVFs. Methods: This retrospective study included 227 consecutive patients with intracranial DAVF treated at our institution. Clinical and imaging data were reviewed and analyzed to characterize DAVF angioarchitecture and determine the presence of PAS. Results: A total of 227 patients with DAVFs were included, and PAS was identified in 44 patients (19.4%). DAVFs with PAS were more frequently located at the cerebral convexity and tentorium than DAVFs without PAS. In addition, DAVFs with PAS were associated with higher angiographic grades and greater venous dilation. Clinical presentation rates were comparable between the two groups. Fistulas with PAS were more often managed with endovascular treatment. Microsurgery and hybrid surgery may represent effective treatment options in selected patients with complex DAVFs such as DAVFs located in the anterior cranial fossa (ACF) or foramen magnum (FM). Rates of surgical disconnection or hybrid surgery were similar between the two groups. Compared with DAVFs without PAS, DAVFs with PAS had significantly lower complete obliteration rates. Major complication rates, including postoperative ICH and cerebral infarction, were similar between the groups. Conclusion: DAVFs with PAS are associated with higher angiographic grades and increased venous dilation. DAVFs with PAS pose unique therapeutic challenges, as reflected by lower complete obliteration rates. Nevertheless, with careful technique and appropriate surgical strategies, major complication rates can be comparable to those of DAVFs without PAS.

Moyamoya disease (MMD) features progressive intracranial artery stenosis and collateralization. Growing evidence implicates a dysregulated gut–brain

The pivotal role of small non-coding RNAs (ncRNAs) in gene expression highlights their potential as therapeutic targets and biomarkers in neuropsychiatric disorders. However, their transcriptional dynamics during fear extinction (EXT) remain poorly understood, limiting insights into disorders such as post-traumatic stress disorder (PTSD). We profiled the small ncRNAs transcriptome in the medial prefrontal cortex (mPFC) following EXT training using small RNA array and explored the potential biological functions of differentially expressed (DE) miRNAs. Publicly available miRNA expression data from peripheral blood mononuclear cells (PBMCs) of PTSD patients was integrated to identify conserved miRNAs biomarkers. Validation of the expression of candidate miRNA in mouse mPFC, plasma and PTSD patients’ PBMCs were performed by RT-qPCR. Inhibitor of candidate miRNA was infused into the infralimbic prefrontal cortex (ILPFC) of mice to assess its effect on fear extinction memory. To assess the impact of Dnmt3a, a common candidate hsa- and mmu-miRNA target, on DNA methylation, publicly available whole-genome bisulfite sequencing (WGBS) data from Dnmt3a knockout or mutant mice across four brain regions were analyzed. Based on the small RNA data, we also analyzed DE tsRNAs, including their subtype distributions, tRNA origins, and potential functions. We identified 63 DE miRNAs following EXT training, with predicted targets enriched in dendritic and synaptic function. In PTSD patient PBMCs, 250 DE miRNAs were identified, including three conserved extinction-induced miRNAs that were downregulated in PBMCs, which were further confirmed in our mouse model and PTSD human blood samples. We next demonstrated that miR-29b-3p facilitates the formation of fear extinction memory. Bioinformatic analysis suggests that miR-29b-3p targets the 3’ untranslated region of Dnmt3a mRNA, which encodes a DNA methyltransferase involved in de novo non-CG methylation in brain. For other small ncRNAs, we identified 75 DE tsRNAs, with 5′tiRNA and 3′tiRNA being the most abundant in the up-regulated and down-regulated groups, respectively. Gln-CTG, Lys-CTT and Lys-TTT was identified as the predominant tRNA contributing to the biogenesis of DE tsRNAs. Our findings emphasize the critical role of small ncRNA regulation in fear extinction learning and highlight miR-29b-3p as a promising functional biomarker for PTSD.

RNA modifications serve as dynamic regulators of neural plasticity through their ability to fine-tune transcript stability and splicing. Pseudouridine (Ψ), an evolutionarily conserved RNA modification catalyzed by pseudouridine synthases, plays established roles in neurodevelopment, yet its functional significance in activity-dependent behavioral adaptation remains poorly defined. Here, we investigate Ψ-mediated epitranscriptomic regulation within the infralimbic prefrontal cortex (ILPFC), a brain region requiring precise synaptic remodeling for the clinically relevant form of fear extinction memory. Combining transcriptome-wide pseudouridylation profiling with behavioral analysis in mice, we identified selective Ψ enrichment at exons of synaptic regulatory genes within ILPFC during fear extinction learning. Fear extinction in the ILPFC drives concomitant exonic Ψ deposition and upregulation of synaptogenic transcripts, processes that involve pseudouridine synthase PUS7. Crucially, PUS7 knockdown in the ILPFC selectively impaired fear extinction memory formation without altering baseline fear expression, establishing a causal link between Ψ-dependent RNA processing and activity-dependent synaptic structural remodeling in this microcircuit. Our findings demonstrate that PUS7-mediated Ψ modification spatiotemporally regulates activity-dependent RNA dynamics in the ILPFC, providing the evidence that epitranscriptomic mechanisms precisely coordinate synaptic gene expression within behaviorally defined brain sub-region. This work bridges molecular RNA biology with systems neuroscience, revealing a novel mechanism for activity-dependent regulation of fear extinction in ILPFC.

Background: The precise role of RNA modification in post-traumatic stress disorder (PTSD) remains incompletely understood. This study aims to elucidate the effects of five common RNA modifications in PTSD, specifically m⁶A, m⁵C, m¹A, m⁷G, and ψ. Methods: We extracted data from the GEO repository to conduct a series of bioinformatics analyses. These included differential analysis to identify key regulators of five common RNA modifications, model construction using random forest (RF), least absolute shrinkage and selection operator (LASSO), and nomogram techniques, as well as consensus clustering of RNA modification subtypes. Furthermore, GO enrichment analysis was performed on DEGs associated with various RNA modification patterns. Immune cell infiltration was assessed using PCA and ssGSEA. RT-qPCR was performed to validate RNA modification-related genes (RMGs). Results: Twenty-one differentially expressed RMGs were identified. LASSO and RF intersection yielded eight signature genes (YTHDC1, IGFBP1, IGF2BP1, ALKBH5, NSUN4, TET2, TET3, WDR4) that robustly diagnosed PTSD (AUC = 0.804). Furthermore, these feature genes were validated using RT-qPCR, which was basically consistent with the results of bioinformatics analysis. Consensus clustering analysis may reveal two distinguishable subtypes: clusterA marked by high immunoinflammation, and clusterB characterized by high-neuroendocrine dysregulation. Conclusions: RMGs may play a crucial role in the pathogenesis of PTSD. Analyzing RNA modification patterns could offer potential diagnostic markers and help to guide immunotherapeutic approaches or neurotransmitter system interventions for PTSD in the future.

The prefrontal cortex subregions—particularly the prelimbic (PLPFC) and infralimbic (ILPFC) cortices in rodents and dorsal anterior cingulate (dACC) and ventromedial prefrontal cortex (vmPFC) in humans—exhibit functionally specialized yet interconnected roles in PTSD pathogenesis. While PLPFC/dACC are implicated in fear memory, ILPFC/vmPFC are associated with fear extinction. However, the inherent difference and cross-species molecular signatures underlying these functional parallels remain unresolved. To bridge the gap, we integrate single-nucleus RNA-seq, ATAC-seq, and spatial transcriptomics across mouse PLPFC/ILPFC and human dACC/vmPFC to construct a cross-species, multi-omic atlas. We then delineate conserved/divergent gene regulatory networks (GRNs), with emphasis on excitatory neuron evolution. By incorporating PTSD GWAS data and gene expression changes from vmPFC of PTSD patients, we identify cell-type-specific PTSD risks, SNP-anchored GRNs linked to PTSD heritability, and stress-induced chromatin-primed genes. This work provides a multiregion atlas and advances translational understanding of PTSD-related gene regulation divergence from mouse transition to human and complement the present multi-omic research of PTSD.

Purpose: Post-traumatic stress disorder (PTSD) is a debilitating psychiatric disorder triggered by exposure to traumatic events. Emerging evidence suggests that mitochondrial dysfunction may contribute to PTSD pathogenesis by disrupting cellular energy metabolism, increasing oxidative stress, and impairing neuroplasticity. This study investigates mitochondrial dysfunction-associated biomarkers, potentially opening new avenues for targeted therapeutic approaches. Methods: Gene expression matrices from datasets GSE199841 and GSE81761 were derived from peripheral blood samples, used to identify differentially expressed genes (DEGs) between PTSD patients and healthy controls. Functional annotation and enrichment analysis were carried out using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. Next, least absolute shrinkage and selection operator (LASSO), support vector machine recursive feature elimination (SVM-RFE), and random forest were employed to screen and prioritize potential biomarkers, followed by validation through receiver operating characteristic (ROC) analysis and independent cohort from human verification. We also examined the expression of mitoDEGs in peripheral blood from PTSD-related mouse models by RT-qPCR. Given the close interplay between mitochondrial metabolism and immune function, we investigated the relationship between key MitoDEGs and immune infiltration proportions. Results: DEGs in PTSD were enriched in mitochondrial pathways, including mitochondrial ribosome function and nitric oxide synthase regulation. Machine learning identified UCP2, CISD1, NADK2 and IDE as key MitoDEGs. Then we assessed the diagnostic performance of four key genes through ROC curve analysis. We evaluated four key genes using ROC analysis, showing good diagnostic performance in the discovery cohort (AUC=0.871). Results were replicated in validation cohorts (GSE81761 AUC=0.745; GSE97356 AUC=0.638). These genes correlated with immune cell proportions (regulatory T cells, naïve B cells, CD4+/CD8+ T cells) and showed conserved dysregulation in murine blood, aligning with human data. Conclusion: Mitochondrial-related genes UCP2, CISD1, NADK2 and IDE may serve as cross-species diagnostic biomarkers for PTSD, with potential links to neuroimmune mechanisms.