In this study, we investigated the effects of hinokitiol, a small-molecule natural compound, against neuronal ferroptosis after traumatic brain injury (TBI). A controlled cortical impact (CCI) mouse model and excess glutamate-treated HT-22 cells were used to study the effects of hinokitiol on TBI. Hinokitiol mitigated TBI brain tissue lesions and significantly improved neurological function. Neuron loss and iron deposition were ameliorated after hinokitiol administration. Hinokitiol alleviated excessive glutamate-induced intracellular reactive oxygen species (ROS), lipid peroxidation, and Fe ²⁺ accumulation in HT-22. Mechanistically, hinokitiol upregulated heme oxygenase-1 (HO-1) expression, promoted nuclear factor-erythroid factor 2-related factor 2 (Nrf2) nuclear translocation, and inhibited the activation of microglia and astrocyte after TBI. These results suggest that hinokitiol has neuroprotective effects on rescuing cells from TBI-induced neuronal ferroptosis. In summary, hinokitiol is a potential therapeutic candidate for TBI by activating the Nrf2/Keap1/HO-1 signaling pathway.

Background: Aggrephagy is a lysosome-dependent process that degrades misfolded protein condensates to maintain cancer cell homeostasis. Despite its importance in cellular protein quality control, the role of aggrephagy in glioma remains poorly understood. Objective: To investigate the expression of aggrephagy-related genes (ARGs) in glioma and in different cell types of gliomas and to develop an ARGs-based prognostic signature to predict the prognosis, tumor microenvironment, and immunotherapy response of gliomas. Methods: ARGs were identified by searching the Reactome database. We developed the ARGs-based prognostic signature (ARPS) using data from the Cancer Genome Atlas (TCGA, n = 669) by Lasso-Cox regression. We validated the robustness of the signature in clinical subgroups and CGGA cohorts (n = 970). Gene set enrichment analysis (GSEA) was used to identify the pathways enriched in ARPS subgroups. The correlations between ARGs and macrophages were also investigated at single cell level. Results: A total of 44 ARGs showed heterogeneous expression among different cell types of gliomas. Five ARGs (HSF1, DYNC1H1, DYNLL2, TUBB6, TUBA1C) were identified to develop ARPS, an independent prognostic factor. GSEA showed gene sets of patients with high-ARPS were mostly enriched in cell cycle, DNA replication, and immune-related pathways. High-ARPS subgroup had higher immune cell infiltration states, particularly macrophages, Treg cells, and neutrophils. APRS had positive association with tumor mutation burden (TMB) and immunotherapy response predictors. At the single cell level, we found ARGs correlated with macrophage development and identified ARGs-mediated macrophage subtypes with distinct communication characteristics with tumor cells. VIM+ macrophages were identified as pro-inflammatory and had higher interactions with malignant cells. Conclusion: We identified a novel signature based on ARGs for predicting glioma prognosis, tumor microenvironment, and immunotherapy response. We highlight the ARGs-mediated macrophages in glioma exhibit classical features.

Purpose: The purpose of our study is to assess the clinical performance of the DiveScope, a novel handheld histopathologic microscope in rapidly differentiating glioma from normal brain tissue during neurosurgery. Methods: Thirty-two ex vivo specimens from 18 patients were included in the present study. The excised suspicious tissue was sequentially stained with sodium fluorescein and methylene blue and scanned with DiveScope during surgery. The adjacent tissue was sent to the department of pathology for frozen section examination. They would eventually be sent to the pathology department later for hematoxylin and eosin staining for final confirmation. The positive likelihood ratio, negative likelihood ratio, sensitivity, specificity, and area under the curve of the device were calculated. In addition, the difference in time usage between DiveScope and frozen sections was compared for the initial judgment. Results: The sensitivity and specificity of the DiveScope after analyzing hematoxylin and eosin -staining sections, were 88.29% and 100%, respectively. In contrast, the sensitivity and specificity of the frozen sections histopathology were 100% and 75%, respectively. The area under the curve of the DiveScope and the frozen sections histopathology was not significant (P=0.578). Concerning time usage, DiveScope is significantly much faster than the frozen sections histopathology no matter the size of tissue. Conclusion: Compared with traditional pathological frozen sections, DiveScope was faster and displayed an equal accuracy for judging tumor margins intraoperatively.

Extensive research has demonstrated the critical role of selenium (Se) and selenoproteins in brain function and cognition. However, the impact of Se on brain cortical structure remains enigmatic. Therefore, this study used Mendelian randomization (MR) analysis to investigate the causal effect between Se levels and brain cortical structure.Methods: This study utilizes 11 genetic variants associated with Se level variations, extracted from a large‐scale genome‐wide association study (GWAS) encompassed circulating Se levels (n = 5477) and toenail Se levels (n = 4162) in the European population. Outcome data were sourced from the summary statistics of the ENIGMA Consortium, comprising GWAS data from 51,666 individuals. The variables include cortical surface area (SA), thickness (TH) at the global level, and 34 functional cortical regions evaluated by magnetic resonance imaging. The inverse‐variance‐weighted method was used as the primary estimate. Additionally, sensitivity analyses were conducted to detect potential violations of assumptions underlying MR.Results: At the global level, Se levels were not correlated with SA but showed a significant negative correlation with TH (β = −0.00485 mm, SE = 0.00192, p = .0115). Heterogeneity was observed across different brain regions, with positive correlations found between Se levels and the TH of the parahippocampal gyrus, superior frontal gyrus, and frontal pole, whereas negative correlations were found with the TH of the inferior parietal lobe and middle temporal lobe. Regarding SA, Se levels exhibit positive correlations with the pars triangularis, caudal anterior cingulate, inferior parietal lobe, and banks of the superior temporal sulcus. Conversely, negative correlations were observed with the medial orbitofrontal cortex, posterior cingulate gyrus, insula, and the middle, superior, and transverse gyrus of the temporal lobe. No pleiotropy was detected.Results: This MR study indicated that Se levels causally influence the brain cortical structure.

To investigate the identification and management techniques and strategies for cortical dangerous veins during neurosurgical craniotomies. We retrospectively analyzed 37 patients who underwent craniotomies involving the intraoperative protection of cortical dangerous veins between July 2022 and June 2024. Preoperatively, high-resolution MRI data were used for three-dimensional visualization to delineate the resection margins and plan the management of related cortical dangerous veins, including bridging veins, superficial Sylvian veins, anastomotic veins, and veins in the eloquent cortex. Intraoperatively, attention was paid to preserving the cortical dangerous veins. Postoperatively, venous flow disturbances were assessed on the basis of symptoms, imaging findings, physical examinations, and other clinical findings. Preoperative three-dimensional visualization of the cerebral structures and veins corresponded to the intraoperative observations in all 37 patients. Forty-seven cortical dangerous veins were dissected and protected intraoperatively, including 14 bridging veins, five superficial Sylvian veins, eight anastomotic veins, and 20 veins involving the central lobe. Six patients experienced intraoperative venous injury, which was managed by suturing or pressure hemostasis. No patient exhibited definite postoperative symptoms or radiological changes attributable to venous infarction. This study highlights the importance of integrating cortical dangerous vein protection into surgical planning and lesion resection. Employing three-dimensional visualization to advance identification of cortical dangerous veins and preserve vein integrity during resection may mitigate postoperative venous infarction-related deficits without adversely affecting treatment efficacy.

Background: Glioblastoma (GBM) is the most malignant brain tumor, with a cellular hierarchy dominated by glioma stem cells (GSCs). Understanding global communications among GSCs and other cells helps us identify potential new therapeutic targets. In this study, multi-transcriptomic analysis was utilized to explore the communication pattern of GSCs in GBM. Methods: CellChat was used to quantitatively infer and analyze intercellular communication networks from GBM single-cell RNA-sequencing (scRNA-seq) data. Gene set enrichment analysis (GSEA) was conducted to identify specific biological pathways (epithelial–mesenchymal transition, EMT) involved in the communication pattern of GSCs. Spatial transcriptomic database was used to support the relationship between EMT and GSC proliferation. Single-sample GSEA (ssGSEA) was employed to assess which GSC state exhibited the strongest association with the EMT signature. Results: The cell communication pattern of GSCs is mostly related to EMT. Multiple EMT-related genes are highly expressed in GBM, particularly in GSCs, which are associated with poor prognosis. In addition, EMT-related genes are most enriched in mesenchymal-like (MES-like) GSCs. Tumor patients with MES-like GSC-enriched signatures demonstrate the most unfavorable prognosis compared to those harboring proneural-like (PN-like) or classical-like (CL-like) GSCs. Conclusions: This study suggests that GSCs facilitate GBM progression through intercellular communication in the pattern of EMT. EMT-associated genes may drive the differentiation of GSCs toward a MES-like phenotype, thereby leading to poorer clinical outcomes. Consequently, targeting EMT-related pathways could represent a novel therapeutic strategy for GBM treatment.