Cellular and Molecular Neurobiology最新文献

Magnetic resonance imaging (MRI) is central to noninvasive brain tumor assessment, yet clinical uptake of artificial intelligence depends on both accuracy and transparency. This study presents a lightweight and interpretable hybrid framework that fuses features from two efficient convolutional backbones, MobileNetV2 and EfficientNetV2B0, using late fusion with global average pooling and vector concatenation. Classification is performed with a K‑Nearest Neighbors (KNN) head configured with k = 5, Euclidean distance, and distance‑based weighting. The dataset contains 7,023 MRI images drawn from Figshare, SARTAJ, and BR35H. Data were split with a 20% held‑out test set and a validation set equal to 20% of the remaining training pool, yielding 64%/16%/20% train/val/test. Four diagnostic categories were evaluated: Glioma, Meningioma, Pituitary, and Notumor. The confusion matrix shows a compact diagonal, and class‑wise precision, recall, and F1 are consistently high on the test set. A 5‑fold cross‑validation with normality assessment and paired significance testing supports robustness across folds. On the held‑out test set, class‑wise ROC-AUC was 1.00 for all four classes, and overall accuracy was 99.69%. Results should be interpreted in light of the unified dataset; external validation is warranted. Clinical interpretability is supported by class‑wise Grad‑CAM overlays and SHAP analyses, including waterfall plots that quantify individual feature contributions. These findings indicate that a dual‑backbone late‑fusion design coupled with a simple nonparametric classifier delivers strong, balanced performance while providing anatomically plausible case‑level insight into model decisions.

An association between gastroesophageal reflux disease (GERD) and sleep disorder has been reported. However, the magnitude of this association remains poorly understood. Therefore, we aimed to systematically evaluate this relationship. We conducted a comprehensive search for observational studies in eight databases from their inception to February 28, 2025. The characteristics of each study and pooled risk ratio (RR) with corresponding confidence intervals were calculated. Subgroup analyses were performed to explore sources of heterogeneity. A total of eighteen studies involving 110,417 participants met the inclusion criteria and were included in this meta-analysis. Our findings indicate a statistically significant unidirectional association between GERD and sleep disorder (RR = 2.02, 95% CI 1.71 to 2.37). Subgroup analyses consistently demonstrated an association between sleep disorder and GERD regardless of the diagnostic tools used for either condition (P = 0.32 for GERD diagnosis tools and P = 0.80 for sleep disorder diagnosis tools). Sensitivity analysis indicates that the conclusions are highly stable, and GRADEpro evaluation results have a low level of evidence. This meta-analysis reveals a significant correlation between sleep disorder and GERD. More studies under consistent conditions are needed to validate these findings.

Hemorrhagic transformation (HT) is a common complication of ischemic stroke that significantly increases the rates of disability and mortality, which could be promoted by hyperglycemia as a risk factor for HT after stroke. Neuronal ferroptosis was implicated as a key contributor to neuronal death during the development of HT which currently has few effective therapies in clinic. The compound fasudil dichloroacetate (FDCA), synthesized with ROCK inhibitor fasudil (F) and PDK inhibitor dichloroacetate (DCA) was previously reported to exhibit neuroprotective effects in ischemic stroke, but whether FDCA could ameliorate HT post-stroke remains unknown. In this study, FDCA was synthesized by combining the Rho kinase inhibitor F with the PDK inhibitor DCA. Rats with acute hyperglycemia and ischemic stroke were divided into the control group, 10 mg/kg FDCA treatment group, 7.875 mg/kg F + 3.6 mg/kg DCA combination treatment group, and other relevant control groups. Our findings demonstrate that FDCA treatment significantly reduced the area of cerebral HT, HT scores, and hemoglobin content in rat brains, improved neurological function, and decreased mortality. Mechanistically, FDCA inhibited neuronal ferroptosis in peri-hematomal region by downregulating the ACSL4 protein expression and the phosphorylation levels of MYPT1 and PDH, while upregulating the GPX4 protein expression. Additionally, FDCA attenuated RSL3-induced neuronal ferroptosis in SH-SY5Y cells in vitro. These results suggest that FDCA holds promise as a potential therapeutic agent for the clinical treatment of HT following ischemic stroke.

Nicotine dependence is characterized by high relapse rates compared to other addictive substances, yet the molecular mechanisms underlying relapse vulnerability during early abstinence remain poorly understood. Here we provide the first integrated transcriptomic and epigenomic profile of nicotine extinction in the medial prefrontal cortex (mPFC). Using RNA-seq and ATAC-seq at 1 and 6 days after nicotine or cocaine self-administration, we uncovered a dynamic and drug-specific molecular response. Nicotine was associated with minimal changes at day 1 but robust transcriptional and chromatin remodelling at day 6, possibly consistent with incubation of craving. Notably, we identified sustained upregulation of the dual specificity phosphatase Dusp4 (first report in nicotine), implicating compensatory regulation of MAPK signalling in abstinence-related plasticity. Chromatin accessibility changes were enriched in intergenic regions containing FOS and JUND motifs, possibly indicative of enhancer-mediated transcriptional control rather than promoter remodelling. Together, these findings highlight nicotine-specific, time-dependent molecular adaptations in the mPFC and identify MAPK phosphatase signalling and enhancer activity as potential targets for relapse prevention during early abstinence.

The autonomic networks of the central nervous system tightly coordinate metabolic and cardiovascular functions. The frequent coexistence of metabolic and cardiovascular disorders suggests cross talk between neural circuits governing energy balance and cardiovascular regulation. In this study, we used trans-neuronal tracing to define the higher-order neurons involved in the coordination of cardiometabolic regulation in mice. We identified several nuclei that contain neurons associated with a cardiovascular organ (kidney) and metabolic tissues (brown adipose tissue [BAT] or liver), with substantial overlap across regions. Co-projecting neurons (kidney-BAT or kidney-liver) were observed in areas including the cortical, hypothalamic, midbrain, and brainstem regions. Analysis of soma size revealed regional and organ-specific differences, with some nuclei exhibiting multiple morphological phenotypes. Notably, soma size distributions differed significantly between kidney- and BAT-projecting neurons in the motor cortex and locus coeruleus, but not in the paraventricular nucleus or lateral hypothalamus. These findings indicate that while cardiometabolic control involves overlapping neuronal populations, morphological specialization may distinguish neurons regulating cardiovascular versus metabolic functions. Together, this work provides anatomical evidence supporting the integrative organization of autonomic networks that coordinate cardiovascular and metabolic regulation.

Sleep deprivation, resulting from factors such as lifestyle, disease, or environmental influences, directly contributes to cognitive decline. Research has found that the impact of sleep deprivation on microglia may be a key factor in cognitive impairment. The specific mechanisms through which microglia contribute to this process are not yet fully understood. It may act through multiple pathways, including the accumulation of excitatory neurotransmitters, Aβ plaque deposition, neuroinflammation, disrupted autophagy, abnormal cell death, and impaired synaptic plasticity. This review synthesizes evidence from the past two decades on the interplay between microglia, sleep deprivation, and cognitive impairment. It provides a comprehensive overview of associated factors and their operational pathways, analyzes the network of pathological interactions, and identifies possible treatment directions. It also emphasizes the dual functions of microglia in worsening and alleviating cognitive impairment while investigating possible therapeutic strategies targeting microglial function. This review aims to clarify microglial pathways in sleep-loss-related cognitive deficits, thereby advancing the field and providing a foundation for new therapeutic strategies.

Aberrant aggregation of specific proteins-such as amyloid beta, α-synuclein, tau, TDP-43, and PrPSc-is a hallmark anomaly in the brain micro-environment, leading to a cascade of pathological events including neuroinflammation, neuronal death, cognitive impairment, and memory loss. The dysregulation in cellular protein homeostasis promotes pathological protein aggregation and hastening disease progression. Degrons are short amino acid motifs within proteins that are recognized by E3 ubiquitin ligases, which target them for degradation via the ubiquitin-proteasome system or autophagy. Recent studies emphasize that alterations in degron sequences, changes after translation or structural modifications can hinder protein homeostasis, leading to their accumulation and contributing neural toxicity. This review integrates the mechanistic role of degron with their pathological relevance and therapeutic significance in neurodegenerative diseases includes Alzheimer's disease, Parkinson's disease, Sclerosis, frontotemporal dementia, and prion diseases and further investigates the translational potential of degron-targeting techniques, including emerging biotechnological startups developing degron-based therapeutic platforms.

Hypoxic preconditioning (HPC) activates intracellular anti-hypoxia molecular defense mechanisms through short-term non-lethal repeated hypoxic stimulation, leading to the subsequent acquisition of high tolerance to lethal hypoxic damage in cells. Cyclophilin D (CypD) regulates the function of mitochondria by controlling the opening of the mitochondrial permeability transition pore. However, the mechanism of action of CypD in hypoxia and HPC is poorly understood. Here, we examined the role of CypD under HPC using both wild-type (WT) and Ppif gene knockout (KO) mice. The results showed that HPC could induce increased hypoxia tolerance in WT and KO mice. Compared to the WT group, KO mice showed a more significant improvement in hypoxia tolerance. Moreover, there are differences in the activation time of HIF-1α and the number of apoptotic cells in the brain tissues of WT and KO mice. Further investigation indicated that proteins related to cell apoptosis, as well as the expression levels of MAPKs, including JNK and ERK, were changed in the brains of mice. The above results demonstrate that the key regulatory role of mitochondrial function-related protein CypD in HPC processes affects cell survival. This study will provide valuable support for the selection of CypD as a key new target for the future treatment of hypoxia and hypoxia-related diseases.