AIM:There is an urgent need for actionable therapeutic targets for glioma. Angiotensin II receptor-associated protein (AGTRAP) is upregulated in glioma, but its functional role and downstream programs remain insufficiently defined. This study aimed to clarify the clinical relevance, biological function, and mechanism of AGTRAP in glioma. METHODS:AGTRAP expression and clinicomolecular associations were analyzed across public glioma cohorts. Loss-of-function studies were performed in glioma cells (A172 and U251), followed by proliferation and apoptosis assays. Recombinant IL-6 was used for rescue experiments. An orthotopic xenograft model was used to evaluate tumor growth in vivo. RESULTS:AGTRAP expression is significantly elevated in gliomas versus normal brain tissues and correlates with tumor grade, age, 1p/19q co-deletion, and IDH mutations. High AGTRAP expression predicted poorer survival. AGTRAP knockdown suppressed proliferation, increased apoptosis, reduced IL-6 mRNA and protein levels, and attenuated JAK2/STAT3 activation. Recombinant IL-6 partially restored JAK2/STAT3 signaling and mitigated the growth-inhibitory phenotype caused by AGTRAP silencing. In vivo, AGTRAP knockdown reduced tumor burden. Transcriptome-based analyses showed that AGTRAP expression was associated with a myeloid/macrophage-enriched microenvironment, and exploratory analyses suggested cross-tumor associations between AGTRAP expression and checkpoint blockade outcomes. CONCLUSION:AGTRAP supports glioma cell survival by engaging an IL-6-linked JAK2/STAT3 program and is associated with a macrophage-rich, inflammatory tumor microenvironment. These findings suggest that AGTRAP may serve as a candidate intervention target for gliomas.

Background: Vestibular schwannoma (VS) is primarily treated with surgery. Safety and the preservation of facial nerve function are the main objectives of the surgery, as patients experiencing facial nerve dysfunction face a multitude of challenges. Therefore, we used preoperative magnetic resonance (MR) images to predict postoperative facial nerve function via artificial intelligence (AI) and compared the performance of the resulting learning models with those of neurosurgeons. Methods: We collected information from 89 VS patients, including data regarding postoperative facial nerve function, patient information, and MR images. The best performing of 9 constructed models was chosen as the final model. Building models to train and test, we analyzed the best-performing model to identify which factors could have the greatest impact on it with SHapley Additive exPlanations (SHAPs). We subsequently evaluated the performance of neurosurgeons at different experience levels and compared their performance with those of the models. Results: The results revealed that the decision tree (DT) model exhibited the best performance. The features selected by the DT model included the color principal component, histogram of oriented gradient (HOG), texture, the discrete cosine transform (DCT) coefficient and flatness, with weights of 0.158, 0.225, 0.275, 0.126, and 0.215, respectively. The results of SHAP analysis revealed that texture made the greatest contribution to the model, followed by HOG. The accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of the DT model were 80.93%, 92.31%, 76.32%, 57.14%, and 96.67%, respectively, all of which were better than those of the neurosurgeons (P<0.05). Besides sensitivity and NPV of experts, the data of the DT model were better than those of neurosurgeons. Conclusions: The DT prediction model could help neurosurgeons to predict postoperative facial nerve function with preoperative MR images as a decision-support tool. In addition, the performance of the model was better than that of the neurosurgeons alone.

BackgroundThe cerebral ischemia/reperfusion injury (CIRI) is an essential pathological process of ischemic stroke (IS). Secondary neuroinflammation exacerbate neuronal damage following CIRI. To identify long non-coding RNAs (lncRNAs) implicated in neuroinflammation subsequent to CIRI would significantly advance the development of potential therapeutic interventions.MethodsThrough comprehensive analysis of whole-genome RNA-seq profiles in focal ischemic mice models, we identified differentially expressed genes utilizing Gene Ontology term enrichment, Kyoto Encyclopedia of Genes and Genomes pathway analysis, and gene set enrichment analysis. We further implemented immune cell infiltration deconvolution, constructed protein–protein interaction networks, and performed co-expression network analysis for lncRNA screening. Subsequently, we established the mice model with lncRNA PVT1 knockdown prior to CIRI induction. Quantitative assessment of cytokine levels was conducted using enzyme-linked immunosorbent assay, while morphological alterations were evaluated through hematoxylin–eosin staining. And T cell infiltration in cerebral tissues was detected with immunofluorescence analysis.ResultsEnrichment analysis demonstrated that differentially expressed mRNAs were implicated in neuroinflammation following cerebral ischemic. Through immune deconvolution analysis, we observed a increased levels in the CD4 + and CD8 + T cells proportion of cerebral ischemic groups compared with control groups. It identified five hub lncRNAs (AI662270, AU020206, Gm20667, PVT1 and Mir142hg) exhibiting significant correlations with the expression of proinflammatory factors. Notably, PVT1 demonstrated the strongest correlation coefficient with pro-inflammatory factor mRNA expression levels. The vivo experimental validation revealed aberrantly elevated PVT1 expression following CIRI. Importantly, PVT1 knockdown substantially ameliorated CIRI through the reduction of activated T cell infiltration and pro-inflammatory cytokine secretion.ConclusionThe identified lncRNA PVT1 correlated with the activated T cell infiltration and pro-inflammatory cytokine secretion, which could be treatment target for neuroinflammation in CIRI.

Background: Intracranial space-occupying lesions (IOLs) often require precise surgical resection. Intraoperative neurophysiological monitoring (IONM), including somatosensory evoked potentials (SEPs) and motor evoked potentials (MEPs), is widely used to preserve neurological function. However, interpretation of IONM data still relies heavily on the experience of the surgeon. The aim of this study was to develop machine-learning (ML) models based on IONM data to support the assessment of lesion location relative to functional brain areas and surgical outcomes. Methods: We initially screened 377 patients undergoing microsurgical resection of IOLs. The clinical data on these patients included demographic characteristics, quantitative IONM parameters (SEP and MEP amplitude and latency), lesion localization, and postoperative adverse events. Four ML models were developed: support vector machine (SVM), decision tree, random forest, and naïve Bayes. Model performance was evaluated using several metrics, including accuracy, sensitivity, specificity, precision, F1-score, and the area under the curve (AUC). Results: Significant differences in SEP and MEP parameters were observed between patient groups with lesions located in functional and non-functional brain areas (all p < 0.05). SEP and MEP parameters were both associated with lesion localization and postoperative adverse events, with differential correlation patterns observed between the two modalities. The ML models demonstrated moderate discriminative performance in predicting lesion involvement in functional areas, with the highest accuracy of 79.2% in the training set and 65.00% in the test set. The models showed good performance in predicting serious adverse events, with the best accuracy of >78% in both datasets. Conclusions: ML models based on IONM data may help to assess lesion location relative to functional brain areas, as well as the prediction of postoperative outcomes. These findings suggest that ML-assisted analysis of IONM data may provide an exploratory framework for understanding lesion localization and postoperative outcomes, rather than a clinically deployable decision-support tool.

Background: Glioblastoma (GBM) is the most aggressive primary brain tumor with extremely poor prognosis. Conventional diagnostic and prognostic approaches remain inadequate, highlighting the need for integrative strategies to improve patient outcomes. Methods: We analyzed ligand-receptor (L-R) interactions in TCGA-GBM transcriptomes using BulkSignaL-R, and validated their spatial expression patterns with single-cell RNA sequencing (scRNA-seq) and spatial transcriptomics datasets. Prognostic histopathological features were extracted from hematoxylin and eosin (H&E)-stained sections through omics-guided feature identification, followed by classification using machine learning algorithms. Results: We identified four pivotal L-R pairs (LTB-CD40, VEGFA-ITGB1, FN1-COL13A1, and TGM2-ITGB1) to construct a risk model, which served as an independent prognostic factor for overall survival. The multivariate Cox regression analyses revealed that the risk score was significantly associated with Overall Survival (OS) (HR = 1.67, 95% CI: 1.25-2.25, p < 0.001). High-risk patients exhibited distinct molecular signatures, including CALN1 mutations, specific CNV patterns, and enriched Notch/interferon-γ signalings. scRNA-seq and spatial transcriptomics revealed that these L-R pairs were predominantly expressed in gMES-like glioma cells, OPC-like cells, and pericytes. Finally, our deep learning model successfully stratified risk groups based on histological features, identifying specific tumor regions (Clusters 0, 2, 4, and 5) as critical determinants of prognosis (AUC = 0.750 by Logistic Regression). Conclusions: We developed a novel multi-modal framework integrating L-R interactomics and deep learning-based pathomics. This approach not only elucidates the molecular and spatial landscape of glioma intercellular communication but also provides a methodological framework for risk stratification.

Turcot syndrome (TS) is an extremely rare genetic disorder characterized by the concurrent occurrence of primary brain tumors and colorectal cancer. The prognosis for patients with TS is typically poor. A 57-year-old man with TS who developed recurrent glioblastoma and had a family history of colon cancer is reported. In 2022, the patient underwent robot-assisted stereotactic surgery for the resection of a central nervous system (CNS) tumor. Molecular genetic analysis identified microsatellite instability in the DNA mismatch repair (MMR) gene, confirming the diagnosis of TS. Additional mutations in the ATM and TP53 genes were also detected, which are rarely associated with TS. Despite treatment with the Stupp regimen, the patient experienced acute neurological deterioration, ultimately resulting in death 15 months after the onset of symptoms. Molecular diagnostics play a crucial role in guiding appropriate care and management for patients with TS. Early diagnosis, genetic testing, and preventive measures are essential for the effective management of this condition.

BACKGROUND:Secondary brain injury (SBI) following spontaneous intracerebral hemorrhage (ICH) is a critical determinant of neurological outcome. It is closely associated with neuronal death, and inflammatory responses. However, current research on SBI after ICH remains limited, and effective therapeutic targets are still lacking. METHODS:In this study, a collagenase-induced intracerebral hemorrhage (ICH) model was employed, and experiments were conducted 24 h after hemorrhage induction. For in vitro experiments, differentiated PC12 cells were stimulated with hemin and the CKLF1 agonist peptide C27 to evaluate the potential of CKLF1 to induce neuronal ferroptosis. Mechanistically, the CKLF1 antagonist peptide C19, the CCR5 inhibitor Maraviroc (MVC), and a p38 MAPK inhibitor were applied, in combination with immunoprecipitation (Co-IP) assays and overexpression of p53 site mutation, to elucidate the molecular mechanisms underlying CKLF1-induced ferroptosis in PC12 cells. In vivo, the effects of CKLF1 knockdown on secondary brain injury after ICH were assessed using quantitative real-time PCR (qPCR), Western blotting (WB), immunohistochemistry (IHC), and immunofluorescence (IF) analyses. RESULTS:Mechanistic studies revealed that CKLF1 binds to its receptor CCR5 to activate p38 MAPK, which promotes ferroptosis by regulating p53 phosphorylation and nuclear translocation, while the mutation of p53 partially reversed the effect. This signaling cascade leads to the downregulation of ferroptosis-suppressing proteins (SLC7A11 and GPX4) and the upregulation of pro-ferroptotic proteins (COX2 and ACSL4), thereby exacerbating lipid peroxidation and oxidative stress. Conversely, AAV-mediated knockdown of CKLF1 significantly suppressed this ferroptotic signaling pathway in vivo/vitro, reduced iron deposition and neuronal ferroptosis in perihematomal tissue, improved blood-brain barrier (BBB) integrity, inhibited microglial activation, and enhanced both neurological function scores and 7-day survival rates in ICH rats. CONCLUSION:The present study identifies CKLF1 as a previously unrecognized regulator of neuronal ferroptosis following ICH through the CCR5/p38/p53 signaling pathway. These findings provide new mechanistic insights into ICH pathogenesis and highlight CKLF1 as a promising therapeutic target for precision treatment of hemorrhagic stroke.

Background Despite advances in reperfusion therapy, effective neuroprotective interventions for ischemic stroke that can be reliably translated into clinical benefit are lacking. A persistent obstacle is the frequent disconnect between mechanistic validity and effective drug exposure within the injured brain, a limitation that is particularly evident for natural products with pleiotropic but weakly defined modes of action. Nootkatone (NKT), a naturally occurring sesquiterpenoid, has antioxidant and neuroprotective activity, yet its direct molecular target and translational limitations in ischemic stroke remain unresolved. This study aimed to define a target-anchored mechanism for NKT and to determine whether improving brain exposure is required to translate this mechanism into effective neuroprotection.Results Through an integrative disease-informed target discovery strategy combining network-based prediction, structure-informed docking, and cross-species biochemical validation, monoamine oxidase B was identified as the primary molecular target engaged by NKT. Pharmacological inhibition or genetic suppression of monoamine oxidase B (MAOB) activated an Nrf2-dependent antioxidant program, reinforced glutathione homeostasis, suppressed lipid peroxidation and ferroptotic injury, preserved mitochondrial integrity, and conferred robust neuroprotection in neuronal oxygen-glucose deprivation models and in mice subjected to transient cerebral ischemia. NKT was encapsulated within a hyaluronic acid modified polyethylene glycol nanocarrier engineered to increase circulation stability and lesion-associated accumulation and to improve brain exposure. This nanodelivery strategy markedly strengthened the neuroprotective efficacy and functional recovery in vivo while preserving the same intracellular signaling mechanisms observed with the free compound, indicating improved pharmacological activity rather than altered bioactivity.Conclusions These findings establish MAOB as a druggable mitochondrial redox regulator underlying NKT-mediated neuroprotection. In parallel, the results demonstrated that insufficient brain exposure represents a critical barrier to converting this mechanism into a consistent therapeutic benefit after stroke. By resolving both target definitions and exposure limitations within a single experimental framework, this study explains a major source of inconsistency in natural product-based neuroprotection and provides a practical strategy for achieving reproducible neuroprotective efficacy in ischemic stroke.

Glioblastoma (GBM; WHO grade IV) is well known for its highly aggressive and recurrent nature and accounts for approximately 50% of all gliomas. Dysregulation of epithelial-mesenchymal transition (EMT) can lead to malignant progression of GBM. Therefore, it is an urgent need to delineate the mechanisms by which molecular drivers affect EMT in GBM. We found for the first time that transmembrane BAX inhibitor motif-containing 1 (TMBIM1) was overexpressed in GBM tissues compared with nontumor brain tissues and that its expression level was correlated with the degree of malignancy of glioma. Patients with high TMBIM1 expression had shorter overall survival times than those with low TMBIM1 expression. Importantly, TMBIM1 induced EMT and autophagy, and inhibition of autophagy reversed TMBIM1-induced EMT in both in vitro and in vivo assays. TMBIM1 induced EMT by downregulating E-cadherin expression, which mediated by in-habitation of autophagic degradation of E-cadherin. Inhibition of TMBIM1 expression dramatically decreased the levels of p-AMPKα Thr172 and p-ULK1 Ser317 in U87 and U251 cells and increased the level of p-mTOR Ser2448. In addition, inhibition of AMPK (adenosine monophosphate-activated protein kinase)/mTOR (mammalian target of rapamycin)/ULK1 (unc-51-like autophagy-activating kinase 1) axis partially attenuated TMBIM1-induced autophagy. Our study provides a novel mechanism for the regulation of EMT in the process of GBM invasion and migration, indicating that suppression of TMBIM1 activity to attenuate autophagy may be a potential strategy for the treatment of GBM.

OBJECTIVE:Recurrent high-grade gliomas have a poor prognosis and limited therapeutic options. This study aimed to evaluate the safety and efficacy of SYHA1813, a dual inhibitor of VEGFR and CSF1R, in patients with recurrent high-grade gliomas. METHODS:Eligible patients (aged ≥ 18) with histologically or cytologically confirmed recurrent high-grade gliomas were included. Patients were administered different doses of SYHA1813 daily to assess its safety and initial efficacy. RESULTS:Sixty-four individuals with high-grade gliomas were enrolled. Treatment-related adverse events (TRAEs) were reported in 92.2% of the patients, with 40.6% experiencing grade 3 or higher TRAEs. No grade 5 TRAE was reported. The overall objective response rate (ORR) and disease control rate (DCR) were 18.8% (95% confidence interval [CI], 10.1-30.5) and 51.6% (95% CI, 38.7-64.3), respectively. With a median follow-up duration of 9.5 months, the median progression-free survival (PFS) was 2.8 months (95% CI, 2.3-4.2) with PFS-6 of 22.5% (95% CI, 11.8-35.4) and the median OS was 15.1 months (95% CI, 10.2-NE) with OS-12 of 63.3% (95% CI, 49.3-74.4). Among the 38 patients with glioblastoma, the ORR was 18.4% (95% CI, 7.7-34.3), with a DCR of 52.6% (95% CI, 35.8-69.0). The median PFS and OS were 4.1 months (95% CI, 2.3-5.3) and 13.0 months (95% CI, 9.1-NE), respectively. SYHA1813 was detected in cerebrospinal fluid samples and the drug concentration to plasma free drug concentration ratio was 0.30-1.27. INTERPRETATION:SYHA1813 exhibits encouraging anti-tumor activity with a manageable safety profile for the treatment of recurrent high-grade gliomas, especially glioblastoma. TRIAL REGISTRATION:chictr.org.cn (ChiCTR2100045380).

With the development of endoscopic technology, neuroendoscopy utilizes its advantages such as good illumination, close range observation, and flexible degrees of freedom. Neuroendoscopic surgery can achieve advantages such as minimally invasive, high clearance rate, low incidence of complications, good brain tissue protection, and fewer surgery-related injuries. However, minimally invasive endoscopic surgery also has inherent limitations, since its narrow surgical channels are prone to collapse and require special instrument support. By summarizing the literature on the use of endoport technology in previous neuroendoscopic surgeries, and providing a detailed introduction and summary of our team’s newly developed simple variable endoport clinical experience, we analyzed the advantages, disadvantages, and precautions of flexible and variable transparent endport technology. After years of development and refinement, fixed endoport technology has been widely used in neuroendoscopic surgery, but it has certain shortcomings. Our team has developed a variable endoport system using simple and easily accessible materials. Although it has shortcomings in support, it provides good compensation for the flexibility of endport length and diameter, which is of great help for multi-instrument operation and bipolar electrocoagulation hemostasis, making surgical hemostasis more reliable. Meanwhile, the flexible and variable transparent endport system can be completely placed within the bone window, with significantly higher mobility than the hard endport system that cannot be completely placed below the bone window. The flexible and variable transparent endport system material is easy to obtain, manufacture, operate, and has extremely low cost, making it suitable for promotion and use in the vast majority of neurosurgery units, including primary hospitals.

The World Health Organization tumor classification emphasizes the key role of molecular biomarkers in glioma diagnosis, particularly the importance of isocitrate dehydrogenase (IDH) mutation status and 1p/19q co-deletion status. There's little research that combines glioma segmentation with the prediction of their genetic or histological characteristics using multimodal magnetic resonance imaging (MRI) scans. We proposed a one-stage multi-task network that uses MRI scans to predict IDH mutation status, 1p/19q co-deletion status, and glioma grading while simultaneously segmenting tumors. The network features an encoder-decoder architecture with three main components: an encoder that extracts multi-scale features, a decoder that gradually aggregates these features for segmentation, and a masked multi-scale fusion module that merges the features with the segmentation output to perform classification. A multi-task learning loss is then used to balance all tasks. The proposed method was evaluated using a public dataset and a local hospital's dataset. The results demonstrate that the proposed method achieves superior performance while consuming fewer computational resources compared to existing networks. In the testset of the public dataset, it achieves Area Under Curves (AUC) of 0.9851 (IDH), 0.7695 (1p/19q), and 0.8949 (grade) with a mean dice score of 0.8485 and a mean Hausdorff distance of 19.60 mm; in the local hospital's dataset, the AUCs were 0.9313, 0.8254, and 0.8638, with a mean dice score of 0.7490 and a mean Hausdorff distance of 24.50 mm. The proposed method can be potentially used in clinical practice to alleviate patient suffering, serving as a diagnostic tool for glioma patients.

Although both Taurine Upregulated Gene 1(TUG1) and Human Antigen R (HuR) play significant regulatory roles in Cerebral Ischemic Reperfusion Injury (CIRI), their potential pro-angiogenesis mechanisms in CIRI remain unclear. METHODS:Herein, the biological roles of TUG1 and HuR in angiogenesis are first confirmed. Following that, HuR-binding VEGFA mRNAs are identified via the Fluorescence In Situ Hybridization (FISH), RNA Immunoprecipitation (RIP), and Cross-Linking Immunoprecipitation (CLIP) assays. Actinomycin D and polysomal assays are also employed to confirm VEGFA mRNA stability. The co-localization of TUG1 with HuR is confirmed using FISH, while the RIP and RNA pull-down assays are employed to elucidate their interplay. The direct binding between TUG1 and HuR is confirmed through the CLIP assay. Co-Immunoprecipitation (Co-IP) and rescue experiments are performed to further elucidate TUG1-HuR interactions. RESULTS:While TUG1 repressed angiogenesis and aggravated CIRI, HuR exerted contrary effects. Specifically, HuR bound directly to VEGFA mRNA, a phenomenon that enhanced VEGFA mRNA stability. Conversely, TUG1 binds to HuR directly, inhibiting its nuclear translocation and promoting its ubiquitination, ultimately reducing VEGFA mRNA stability. CONCLUSIONS:It is found that TUG1 can inhibit angiogenesis in CIRI through the HuR/VEGFA mRNA axis.

PURPOSE:This study investigates NR4A1's paradoxical roles in glioblastoma (GBM) progression, focusing on its mechanistic link to ferroptosis regulation. We aimed to resolve conflicting reports of NR4A1 as both an oncogene and a tumor suppressor by defining its transcriptional control over xCT/GPX4-mediated iron homeostasis and its clinical relevance in glioma survival. METHODS:TCGA cohort analysis (n = 163) correlated NR4A1 expression with survival endpoints (OS/PFI/DSS, log-rank p < 0.05). Functional validation employed U87/U251 GBM models for viability (CCK-8), proliferation (EdU/colony formation), and migration assays (Transwell/wound healing). RNA sequencing (DESeq2, FDR < 0.05) and ChIP-qPCR identified NR4A1-xCT transcriptional regulation. Ferroptosis was quantified via lipid peroxidation (MDA/GSH/Fe2+ ELISA, C11 BODIPY), while Western blotting mapped the NR4A1/xCT/GPX4/P53 axis. Orthotopic xenografts (n = 6/group) evaluated therapeutic efficacy using biweekly tumor volumetry. All data were analyzed in triplicate (GraphPad Prism 8.0; t-test/ANOVA, *p < 0.05). CONCLUSION:NR4A1 drives GBM progression by transcriptionally activating xCT/GPX4 to suppress ferroptosis. Dual targeting of NR4A1 and ferroptosis pathways synergistically inhibits tumor growth (64% reduction vs. controls, p = 0.008), providing a mechanistic rationale for overcoming therapy resistance in GBM.

Glioblastoma (GBM) exhibits a high ROS character, giving rise to an immunosuppressive microenvironment and tumor vascular abnormality. This study investigated the potential effect of N-acetylcysteine (NAC), an antioxidant, on primary and recurrent mouse brain tumors. We measured reactive oxygen species (ROS)/ glutathione (GSH) levels in human GBM. Additionally, we conducted NAC trials on primary mouse brain tumor models (GL261-Luc, CT2A-Luc) and a recurrent mouse GBM model (GL261-iCasp9-Luc). After brain tumor inoculation, mice received a daily 100 mg/kg NAC treatment, and the tumor volume was monitored via IVIS imaging. The efficacy of NAC was evaluated through survival time, tumor volume, ROS/GSH levels, M1/M2 macrophages, immune cells infiltration, and tumor vascularization. Human GBM suffered from significant oxidative stress. With NAC treatment, mouse brain tumors exhibited a lower ROS level, more M1-like tumor-associated macrophages/microglia (TAMs), more CD8 + T cell infiltration, and a normalized vascular character. NAC inhibited tumor growth and suppressed recurrence in mouse brain tumor models. NAC is a promising adjunctive drug to remodel the brain tumors microenvironment.

Glioblastoma multiforme (GBM) is the deadliest brain tumour with an extremely poor prognosis. Tryptophan catabolism could enhance an array of protumour-genic signals and promoted tumour progression in GBM. However, the mechanisms of oncogenic signalling under tryptophan catabolism and potential therapy targeting this pathway have not been completely understood. Interleukin 4-induced 1 (IL4I1) is newly defined as a tryptophan metabolic enzyme and the potential function in GBM cells still remains unclear. In our study, we found IL4I1 was upregulated in GBM patients and predicted poor prognosis. Upregulation of IL4I1 inhibited GBM ferroptosis in vitro and in vivo. Further, we found that indole-3-pyruvic acid (I3P) from tryptophan mediated by IL4I1 could scavenge free radical and had an impressive role in inhibiting ferroptosis. To clarify the potential mechanism of I3P in GBM ferroptosis, we performed transcriptomic analyses of GBM cells treated with I3P and found that Nrf2 related genes was upregulated. Further, we found that the ubiquitination of Nrf2 could be attenuate by I3P binding with Nrf2 directly. Knockdown of Nrf2 attenuated the induction of anti-ferroptosis by IL4I1, pointing to Nrf2 as a key mediator of this process. In vivo, overexpression of IL4I1 with ML385 in GBM xenografts promoted ferroptosis. Collectively, this study emphasises the crucial roles of IL4I1 in anti-ferroptosis through Nrf2 signalling pathway but not AHR pathway by catabolism tryptophan, suggesting IL4I1 and tryptophan reprogramming as potential therapeutic targets for GBM.

To explore techniques, advantages and disadvantages of 3D Slicer reconstruction and 3D printing localization technology combined with transcranial neuroendoscopy in ventriculoperitoneal shunt surgery. Retrospective analysis of clinical data of patients with hydrocephalus treated by ventriculoperitoneal shunt surgery using 3D Slicer reconstruction and 3D printing positioning technology combined with transcranial neuroendoscopy in our hospital from October 2021 to March 2023. A total of 33 patients with complete data were collected, including 19 males and 14 females, aged 10-81 years. Pre operative use of 3D Slicer reconstruction and 3D printing localization, and intraoperative use of neuroendoscopy assisted catheterization to complete ventriculoperitoneal shunt surgery. The drainage tube position was confirmed by brain CT and 3D Slicer reconstruction after operation, of which 30 cases were located in the frontal horn or center of the ipsilateral lateral ventricle, and 3 cases were located in the frontal horn or center of the contralateral lateral ventricle. All patients were successfully catheterized and well positioned. According to the unique ventricular system characteristics of each hydrocephalus patient, the 3D Slicer reconstruction technology was used to determine the individualized puncture point and direction, measure the puncture depth, accurately locate the puncture through the 3D printing guide plate, and accurately send the tip of the ventricular catheter into the frontal or central part of the lateral ventricle with the assistance of neuroendoscopic visualization, which improved the success rate of the operation and reduced the risk of tube blockage. At the same time, our team has newly developed a puncture point ("Cai's point"), which has a puncture path in a non-vascular area and can reduce the risk of puncture bleeding. However, further prospective clinical research is needed to determine its routine location.

Ferroptosis is closely related to disease progression and treatment response in human brain gliomas; however, the regulatory mechanisms involved remain to be elucidated. Identifying new ferroptosis regulatory factors holds promise for addressing the aberrant regulation of ferroptosis in glioblastoma (GBM) and overcoming its treatment resistance. In this research, bioinformatics revealed that SLC10A3 is upregulated in GBM and correlates with poor patient prognosis. Functional analysis showed that SLC10A3 regulates GBM growth and progression through ferroptosis and that silencing SLC10A3 enhances sensitivity to the ferroptosis inducer Erastin. Mechanistically, SLC10A3 modulates STAT3 transcription and phosphorylation, impacting GBM ferroptosis via the STAT3-GPX4 pathway, and the STAT3 phosphorylation inhibitor Stattic effectively reverses this process. In vivo experiments also demonstrated that silencing SLC10A3 effectively induces ferroptosis in GBM and inhibits GBM progression. Our findings may help elucidate the mechanisms behind GBM resistance and offer new potential therapeutic targets.

Research has demonstrated that circular RNAs (circRNAs) play important roles in acute ischemic stroke (AIS). However, the functions of circRNA-mediated competitive endogenous RNA (ceRNA) in AIS-related immunological inflammation are not well understood. In our study, we aimed to construct a circRNA-mediated immune-related ceRNA network and identify diagnostic circRNAs for AIS. R software was used to analyze the microarray data obtained from the GEO database. The bioinformatics database was then used to develop the circRNA-mediated ceRNA network. A topological property study of the ceRNA network was performed to identify new circRNAs. Subsequently, we validated the potential circRNAs in both mice middle cerebral artery occlusion (MCAO) model and clinical samples obtained from our center with quantitative real-time polymerase chain reaction (qRT-PCR). An AIS immune-related ceRNA (AISIRC) network was constructed, comprising immune-related genes (IRGs), circRNAs, and miRNAs. A subnetwork was then extracted from the AISIRC network and we identified seven circRNAs associated with immune response. The qRT-PCR assays were conducted to validate the circRNAs candidate using blood samples from MCAO mice. The results demonstrated that circulating circOXCT1 and circSLC8A1 were significantly up-regulated in AIS patients. Receiver-operating characteristic (ROC) curve analyses and logistic regression demonstrated the perfect predictive and discriminative features of these two circRNAs biomarkers in AIS. Longitudinal analysis of circRNA expression after AIS indicated the promising potential of circSLC8A1 for monitoring AIS progression and dynamics. We successfully constructed circRNA-mediated immune-related ceRNA network and identified two circulating circRNAs (circOXCT1 and circSLC8A1), which showed high diagnostic sensitivity for AIS.