Predicting intraoperative major blood loss in microsurgery for brain arteriovenous malformations.

Objective: Intraoperative blood loss poses a great challenge for brain arteriovenous malformation (AVM) microsurgery, although systematic researches are still lacking. This study aimed to identify factors predicting intraoperative major blood loss in brain AVM microsurgery and to investigate its impact on patient outcome. To deal with the fierce bleeding, we introduced a modified hemostatic method, bone-wax (BW) coated bipolar electrocoagulation. Methods: The authors retrospectively analyzed the clinical data of 131 patients (50/81 in intraoperative major/non-major blood loss cohort) with brain AVMs who underwent microsurgery in our center during the period between January 2018 and April 2023. According to previous studies, major blood loss was defined as blood loss of at least 1,000 mL. The accuracy and objectivity of our grouping methodology were validated by comparing the hemoglobin mass loss, hematocrit loss and factors associated with intraoperative bleeding. Potential clinical and radiological predictors for intraoperative major blood loss were evaluated using a multivariate stepwise logistic regression. And outcomes of patients in the two cohorts were also compared. At last, the performance of BW coated bipolar electrocoagulation in brain AVM microsurgery was illustrated by the case presentation, histological staining and transmission electron microscopy of the coagulated nidus vessels. Results: Hemoglobin mass loss, hematocrit loss and factors associated with intraoperative bleeding were significant different between the two cohorts. five independent factors predicting intraoperative major blood loss were identified: (1) clinical manifestations; (2,3) location and size of the nidus; (4) deep venous drainage; and (5) the number of draining veins. And the intraoperative major blood loss can not only adversely affect the surgical progression, but also predict poor perioperative outcomes for patients. Regarding the application of BW coated bipolar electrocoagulation, we found the novel hemostatic method exerted efficient hemostatic effect and reduced the damage to the vascular structure in brain AVM microsurgery. Conclusion: This study proposed a nomogram for neurosurgeons to predict intraoperative major blood loss in brain AVM microsurgery preoperatively. And intraoperative major blood loss is associated with poor patient outcomes. In addition, BW coated bipolar electrocoagulation, can be applied to control ferocious bleeding during brain AVM microsurgery, which still remains further researches.

Potential role of endothelial progenitor cells in the pathogenesis and treatment of cerebral aneurysm.

Cerebral aneurysm (CA) is a significant health concern that results from pathological dilations of blood vessels in the brain and can lead to severe and potentially life-threatening conditions. While the pathogenesis of CA is complex, emerging studies suggest that endothelial progenitor cells (EPCs) play a crucial role. In this paper, we conducted a comprehensive literature review to investigate the potential role of EPCs in the pathogenesis and treatment of CA. Current research indicates that a decreased count and dysfunction of EPCs disrupt the balance between endothelial dysfunction and repair, thus increasing the risk of CA formation. Reversing these EPCs abnormalities may reduce the progression of vascular degeneration after aneurysm induction, indicating EPCs as a promising target for developing new therapeutic strategies to facilitate CA repair. This has motivated researchers to develop novel treatment options, including drug applications, endovascular-combined and tissue engineering therapies. Although preclinical studies have shown promising results, there is still a considerable way to go before clinical translation and eventual benefits for patients. Nonetheless, these findings offer hope for improving the treatment and management of this condition.

TNC upregulation promotes glioma tumourigenesis through TDG-mediated active DNA demethylation.

Gliomas represent the most predominant primary malignant tumor in central nervous system. Thymine DNA glycosylase (TDG) is a central component in active DNA demethylation. However, the specific mechanisms of TDG-mediated active DNA demethylation in gliomas remain unclear. This research indicates TDG expression is overexpressed in gliomas and correlated with poor prognosis. TDG knockdown suppressed the malignant phenotype of gliomas both in vitro and vivo. Notably, RNA-seq analysis revealed a strong association between TDG and tenascin-C (TNC). ChIP-qPCR and MeDIP-qPCR assays were undertaken to confirm that TDG participates in TNC active DNA demethylation process, revealing decreased DNA methylation levels and elevated TNC expression as a result. Silencing TNC expression also suppressed the tumor malignant phenotype in both in vitro and in vivo experiments. Additionally, simultaneous silencing of TNC reduced or even reversed the glioma promotion caused by TDG overexpression. Based on our findings, we conclude that TDG exerts an indispensable role in TNC active DNA demethylation in gliomas. The DNA demethylation process leads to alternations in TNC methylation levels and promotes its expression, thereby contributing to the development of gliomas. These results suggest a novel epigenetic therapeutic strategy targeting active DNA demethylation in gliomas.

Insights into the regulatory role of epigenetics in moyamoya disease: Current advances and future prospectives.

Moyamoya disease (MMD) is a progressive steno-occlusive cerebrovascular disorder that predominantly affecting East Asian populations. The intricate interplay of distinct and overlapping mechanisms, including genetic associations such as the RNF213-p.R4810K variant, contributes to the steno-occlusive lesions and moyamoya vessels. However, genetic mutations alone do not fully elucidate the occurrence of MMD, suggesting a potential role for epigenetic factors. Accruing evidence has unveiled the regulatory role of epigenetic markers, including DNA methylation, histone modifications, and non-coding RNAs (ncRNAs), in regulating pivotal cellular and molecular processes implicated in the pathogenesis of MMD by modulating endothelial cells and smooth muscle cells. The profile of these epigenetic markers in cerebral vasculatures and circulation has been determined to identify potential diagnostic biomarkers and therapeutic targets. Furthermore, in vitro studies have demonstrated the multifaceted effects of modulating specific epigenetic markers on MMD pathogenesis. These findings hold great potential for the discovery of novel therapeutic targets, translational studies, and clinical applications. In this review, we comprehensively summarize the current understanding of epigenetic mechanisms, including DNA methylation, histone modifications, and ncRNAs, in the context of MMD. Furthermore, we discuss the potential challenges and opportunities that lie ahead in this rapidly evolving field.

Vacuum Sealing Drainage against Surgical Site Infection after Intracranial Neurosurgery.

Background: Surgical site infections (SSIs) remain a conundrum for neurosurgeons. This study examines the efficacy and outcome of vacuum sealing drainage (VSD) in the treatment of pyogenic SSIs following intracranial neurosurgery. Methods: Twenty patients with SSIs, who received surgical intervention, were treated retrospectively with VSD during the past five years. Primary surgical procedure types, SSI types, VSD replacements, pathogenic germs, antibiotic therapy, and infection control were reviewed and discussed. Results: Of the 20 infections, 13 (65%) were extradural and 7 (35%) were extradural SSIs combined with intracranial infections (including 5 meningitis, 1 subdural abscess, and 1 brain abscess). All the patients consented to medical device implantation (including 5 titanium webs, 6 bone flap fixation devices, and 12 duraplasties), most of which were removed during debridement. The median duration from primary surgical procedure to an SSI diagnosis was 19 days (range: 7 to 365 d). All the patients also agreed to debridement and VSD treatment; VSD was replaced 0 to 5 times (median, one time) every 4 to 7 days and kept for 4 to 35 days (median, 14 d). Seven (35%) patients had defined bacterial infections, with Staphylococcus aureus being the dominant infection. The deployed standard VSD and antibiotic treatment ensured full recovery from SSIs, including from intracranial infections: 14 (70%) patients had recovered fully by follow-up, and no infection-associated death was registered; 6 (30%) patients died of severe primary affections. Conclusion: VSD-assisted therapy is safe and effective against SSIs after intracranial neurosurgery.

Study the local metabolic changes of aneurysms through microcatheter sampling.

Intracranial aneurysm is the primary cause of nontraumatic subarachnoid hemorrhage. To assess aneurysm metabolism, we present a method of intra-operatively collecting blood samples from the aneurysm neck, as well as the proximal and distal responsible vessels, using microcatheters. Through these paired comparisons, we can eliminate the interpatient variation usually observed in plasma samples taken from the peripheral vein. We utilized 39 plasma samples from 13 intracranial patients to characterize the metabolite profiles using untargeted liquid chromatography-mass spectrometry. Our findings revealed that L-tyrosine is upregulated at relatively high levels at the aneurysm neck than the proximal and distal aneurysm, whereas phenylpyruvic acid, L-cystine, and L-ornithine are downregulated. Based on this, there was also a significant decrease in arginine within small aneurysm of the internal carotid artery. The 6-month follow-up indicated that patients who experienced good recovery had lower levels of biliverdin, bilirubin, and metabolites of coenzyme Q within the aneurysm. In conclusion, our investigation provides a comprehensive overview of plasma metabolites in patients with intracranial aneurysms, shedding light on potential pathogenetic mechanisms in unruptured intracranial aneurysms. Moreover, the study proposes innovative ideas for establishing postoperative follow-up timelines for flow diverter devices.

C9orf72 controls hepatic lipid metabolism by regulating SREBP1 transport.

Sterol regulatory element binding transcription factors (SREBPs) play a crucial role in lipid homeostasis. They are processed and transported to the nucleus via COPII, where they induce the expression of lipogenic genes. COPII maintains the homeostasis of organelles and plays an essential role in the protein secretion pathways in eukaryotes. The formation of COPII begins at endoplasmic reticulum exit sites (ERES), and is regulated by SEC16A, which provides a platform for the assembly of COPII. However, there have been few studies on the changes in SEC16A protein levels. The repetitive expansion of the hexanucleotide sequence GGGGCC within the chromosome 9 open reading frame 72 (C9orf72) gene is a prevalent factor in the development of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Here, we found that the absence of C9orf72 leads to a decrease in SEC16A protein levels, resulting in reduced localization of the guanine nucleotide exchange factor SEC12 at the ERES. Consequently, the small GTP binding protein SAR1 is unable to bind the endoplasmic reticulum normally, impairing the assembly of COPII. Ultimately, the disruption of SREBPs transport decreases de novo lipogenesis. These results suggest that C9orf72 acts as a novel role in regulating lipid homeostasis and may serve as a potential therapeutic target for obesity.

Bridge-layered decompression technique for vertebral artery-involved hemifacial spasm: technical note.

BACKGROUND: Hemifacial spasm (HFS) is most effectively treated with microvascular decompression (MVD). However, there are certain challenges in performing MVD for HFS when the vertebral artery (VA) is involved in compressing the facial nerve (VA-involved). This study aimed to introduce a "bridge-layered" decompression technique for treating patients with VA-involved HFS and to evaluate its efficacy and safety to treat patients with HFS. METHODS: A single-center retrospective analysis was conducted on the clinical data of 62 patients with VA-involved HFS. The tortuous trunk of VA was lifted by a multi-point "bridge" decompression technique to avoid excessive traction of the cerebellum and reduce the risk of damage to the facial-acoustic nerve complex. To fully decompress all the responsible vessels, the branch vessels of VA were then isolated using the "layered" decompression technique. RESULTS: Among the 62 patients, 59 patients were cured immediately after the surgery, two patients were delayed cured after two months, and one had occasional facial muscle twitching after the surgery. Patients were followed up for an average of 19.5 months. The long-term follow-up results showed that all patients had no recurrence of HFS during the follow-up period, and no patients developed hearing loss, facial paralysis, or other permanent neurological damage complications. Only two patients developed tinnitus after the surgery. CONCLUSION: The "bridge-layered" decompression technique could effectively treat VA-involved HFS with satisfactory safety and a low risk of hearing loss. The technique could be used as a reference for decompression surgery for VA-involved HFS.

Liquid chromatography coupled to mass spectrometry metabolomic analysis of cerebrospinal fluid revealed the metabolic characteristics of moyamoya disease.

Objective: Metabolomics has found extensive applications in the field of neurological diseases, significantly contributing to their diagnosis and treatment. However, there has been limited research applying metabolomics to moyamoya disease (MMD). This study aims to investigate and identify differential metabolites associated with MMD. Methods: We employed a liquid chromatography coupled with mass spectrometry (LC-MS) approach, complemented by univariate and multivariate analyses, to discern metabolic biomarkers in cerebrospinal fluid samples. We then compared these biomarkers between MMD patients and healthy controls (Ctl). Results: Sixteen patients diagnosed with MMD via cerebral angiography and eight healthy controls were enrolled in this study. Comparative analyses, including univariate and multivariate analyses, correlation studies, heatmaps, Volcano Plots, and KEGG pathway enrichment, were performed between MMD patients and controls. As a result, we identified 129 significant differential metabolites in the cerebrospinal fluid between MMD patients and controls. These metabolic biomarkers are associated with various pathways, with notable involvement in purine and pyrimidine metabolism. Conclusion: Utilizing an LC-MS-based metabolomics approach holds promise for enhancing the clinical diagnosis of MMD. The identified biomarkers offer potential avenues for the development of novel diagnostic methods for MMD and offer fresh insights into the pathogenesis of the disease.

A nomogram based on radiomics and clinical information to predict prognosis in percutaneous balloon compression for the treatment of trigeminal neuralgia.

OBJECTIVE: To develop a clinical-radiomics nomogram based on clinical information and radiomics features to predict the prognosis of percutaneous balloon compression (PBC) for the treatment of trigeminal neuralgia (TN). METHODS: The retrospective study involved clinical data from 149 TN patients undergoing PBC at Zhongnan Hospital, Wuhan University from January 2018 to January 2022. The free open-source software 3D Slicer was used to extract all radiomic features from the intraoperative X-ray balloon region. The relationship between clinical information and TN prognosis was analyzed by univariate logistic analysis and multivariate logistic analysis. Using R software, the optimal radiomics features were selected using the least absolute shrinkage and selection operator (Lasso) algorithm. A prediction model was constructed based on the clinical information and radiomic features, and a nomogram was visualized. The performance of the clinical radiomics nomogram in predicting the prognosis of PBC in TN treatment was evaluated using the area under the receiver operating characteristic curve (AUC) and decision curve analysis (DCA). RESULTS: A total of 149 patients were eventually included. The clinical factors influencing the prognosis of TN in univariate analysis were compression severity score and TN type. The lasso algorithm Max-Relevance and Min-Redundancy(mRMR) was used to select two predictors from 13 morphology-related radiomics features, including elongation and surface-volume ratio. A total of 4 predictors were used to construct a prediction model and nomogram. The AUC was 0.886(95% confidence interval (CI), 0.75 to 0.96), indicating that the model's good predictive ability. DCA demonstrated the nomogram's high clinical applicability. CONCLUSION: Clinical-radiomics nomogram constructed by combining clinical information and morphology-related radiomics features have good potential in predicting the prognosis of TN for PBC treatment. However, this needs to be further studied and validated in several independent external patient populations.

The Rejuvenation and Functional Restoration of Aged Adipose Stem Cells by DUXAP10 Knockdown via the Regulation of the miR-214-3p/RASSF5 Axis.

Adipose stem cell (ASC)-based therapies provide an encouraging option for tissue repair and regeneration. However, the function of these cells declines with aging, which limits their clinical transformation. Recent studies have outlined the involvement of long non-coding RNAs in stem cell aging. Here, we reanalyzed our published RNA sequencing (RNA-seq) data profiling differences between ASCs from young and old donors and identified a lncRNA named double homeobox A pseudogene 10 (DUXAP10) as significantly accumulated in aged ASCs. Knocking down DUXAP10 promoted stem cell proliferation and migration and halted cell senescence and the secretion of proinflammatory cytokines. In addition, DUXAP10 was located in the cytoplasm and functioned as a decoy for miR-214-3p. miR-214-3p was downregulated in aged ASCs, and its overexpression rejuvenated aged ASCs and reversed the harm caused by DUXAP10. Furthermore, Ras Association Domain Family Member 5 (RASSF5) was the target of miR-214-3p and was upregulated in aged ASCs. Overexpressing DUXAP10 and inhibiting miR-214-3p both enhanced RASSF5 content in ASCs, while DUXAP10 knockdown promoted the therapeutic ability of aged ASCs for skin wound healing. Overall, this study offers new insights into the mechanism of age-related ASC dysfunction and names DUXAP10 and miR-214-3p as potential targets for energizing aged stem cells.

Mechanistic insight into glioma through spatially multidimensional proteomics.

Characterizing the tumor microenvironment at the molecular level is essential for understanding the mechanisms of tumorigenesis and evolution. However, the specificity of the blood proteome in localized region of the tumor and its linkages with other systems is difficult to investigate. Here, we propose a spatially multidimensional comparative proteomics strategy using glioma as an example. The blood proteome signature of tumor microenvironment was specifically identified by in situ collection of arterial and venous blood from the glioma region of the brain for comparison with peripheral blood. Also, by integrating with different dimensions of tissue and peripheral blood proteomics, the information on the genesis, migration, and exchange of glioma-associated proteins was revealed, which provided a powerful method for tumor mechanism research and biomarker discovery. The study recruited multidimensional clinical cohorts, allowing the proteomic results to corroborate each other, reliably revealing biological processes specific to gliomas, and identifying highly accurate biomarkers.

Clinical and Economic Insights into Parkinson's Disease Hospitalization: A Comprehensive Study of 19,719 Inpatient Cases in Hubei Province, China.

OBJECTIVE: Parkinson's disease (PD) is a profoundly incapacitating neurodegenerative disorder, which presents a substantial challenge to the economic sustainability of the global healthcare system. The present study seeks to clarify the factors that contribute to the costs associated with PD hospitalization and analyze the economic burden it imposes. METHODS: We examined data of 19,719 patients with a primary diagnosis of PD who were admitted to hospitals in Hubei Province, China, during the study period. Healthcare data were obtained from the database of electronic medical records. The study presents a comprehensive analysis of the demographic characteristics and investigates the factors that affect their healthcare expenditure. RESULTS: The cohort consisted of 10,442 (53.0%) males and 9,277 (47.0%) females. The age-group of 66-70 years experienced the highest incidence of hospitalization among PD patients, with a mortality rate of 0.76‰. The average length of stay for patients was 9.9 ± 8.6 days and the average cost per patient was USD 1,759.9 ± 4,787.7. Surgical interventions were conducted on a mere 2.0% of the total inpatient population. The primary cost component for these interventions was material expenses, accounting for 70.1% of the total. Non-surgical patients primarily incurred expenses related to diagnosis and medication. Notably, surgical patients faced a substantial out-of-pocket rate, reaching up to 90.6%. Surgery was identified as the most influential factor that negatively affected both length of stay and hospitalization costs. Inpatients exhibited significant associations with prolonged length of stay and increased medical expenditure as age increased. Male patients had significantly longer hospital stays and higher medical costs than did females. Additionally, patient's occupation and type of medical insurance exerted significant effects on both length of stay and medical expense. CONCLUSION: Age significantly affects PD hospitalization costs. Given the prevailing demographic shift toward an aging population, the government's medical insurance burden related to PD will continue to escalate. Meanwhile, high treatment expenses and out-of-pocket rates impose substantial financial burdens on patients, limiting surgical intervention access to a small fraction of patients. Addressing these issues is of utmost importance in order to ensure comprehensive disease management for the majority of individuals affected by PD.

Intraoperative evaluation of local cerebral hemodynamic change by laser speckle contrast imaging for predicting postoperative cerebral hyperperfusion during STA-MCA bypass in adult patients with moyamoya disease.

Cerebral hyperperfusion (CHP) occurred frequently after direct superficial temporal artery-middle cerebral artery (STA-MCA) bypass surgery for moyamoya disease (MMD). We analyzed cortical microvascular density (CMD) and the change of cerebral blood flow (LΔCBF) using intraoperative laser speckle contrast imaging (LSCI) on 130 hemispheres of 95 consecutive adult patients with MMD. The demographic characteristics, cortical hemodynamic sources, bypass methods, intraoperative blood flow data, and relative CBF changes on single-photon emission computed tomography (SPECT) examination (SΔrCBF) were compared between the groups with and without CHP. The median values for CMD, LΔCBF, and SΔrCBF were significantly higher in the CHP group than in the non-CHP group (CMD 0.240 vs 0.206, P = 0.004; LΔCBF 2.285 vs 1.870, P < 0.001; SΔCBF 1.535 vs 1.260, P < 0.001). Multivariate analysis revealed that hemodynamic sources of recipient parasylvian cortical arteries from MCA (M-PSCAs), end-to-side (E-S) bypass method, CMD ≥ 0.217, and LΔCBF ≥ 1.985 were the risk factors for CHP. Intraoperative LSCI was useful for evaluating hemodynamics and predicting CHP in patients with MMD.

Identification and validation of chromatin regulator-related signatures as a novel prognostic model for low-grade gliomas using translational bioinformatics.

AIMS: The purpose of this study is to explore the potential biological role and prognostic significance of chromatin regulators (CRs) in low-grade gliomas (LGGs). MAIN METHODS: CRs were obtained from the FACER database. Transcription profiles of LGG patients were collected from the TCGA and CGGA databases. Differentially expressed CRs (DECRs) between LGGs and normal controls were identified using DESeq2. The consensus clustering algorithm was employed to distinguish subtypes of LGGs based on prognosis-related DECRs. The differences in clinical and molecular characteristics between different subtypes were explored. R packages, GSVA, ssGSEA, and ESTIMATE were utilized to elucidate the tumor microenvironment and activated pathways in different subtypes. Subsequently, a CRs-related signature was developed using LASSO Cox regression. Its performance was evaluated by Kaplan-Meier curve and ROC curve analyses. In vitro experiments were performed to explore the function of JADE3 in LGGs, which predominantly expressed in glioma cells. KEY FINDINGS: We identified 43 DECRs and two CRs-related subtypes of LGGs. The subtype characterized by shorter survival displayed significant enrichment for pathways associated with DNA damage response and repair, along with heightened immune cell infiltration. Furthermore, the CRs-based signature exhibited excellent prognostic performance in both the TCGA and CGGA databases. Knockdown of JADE3 significantly increased the invasion, migration, and proliferation abilities of Hs683. SIGNIFICANCE: Our study reveals the aberrant expression and prognostic value of CRs in LGGs. It emphasizes the potential regulatory role of CRs in the microenvironment and DNA damage repair in LGGs. JADE3 could be a possible therapeutic target for LGGs.

Clinical Features and Risk Factors of Postoperative Stroke in Adult Moyamoya Disease.

BACKGROUND AND PURPOSE: The clinical features of and risk factors for postoperative stroke after surgical revascularization in adult moyamoya disease (MMD) have not been fully elucidated. To this end, the baseline clinical features were hereby described, and the risk factors for postoperative stroke were determined. METHODS: Data of 4078 MMD inpatients were collected retrospectively across all secondary- and higher-level hospitals of Hubei Province from January 2019 to December 2020. In accordance with inclusion and exclusion criteria, 559 adult MMD inpatients were finally enrolled. The associated characteristics and potential risk factors were analyzed, and the Kaplan-Meier risk of stroke was also calculated. RESULTS: The patients consisted of 286 females and 273 males, with a mean age of 49.1 ± 10.0 years, all of whom had at least 1 year of follow-up (median 25.1 months). There were 356 cases of preoperative ischemic symptoms and 203 cases of preoperative hemorrhage symptoms. Indirect, direct, and combined revascularization were conducted on 97, 105 and 357 patients, respectively. Among these patients, 17 had postoperative hemorrhagic stroke (PHS), and 43 had postoperative ischemic stroke (PIS). A comparison between PHS/PIS group and control group (patients without postoperative stroke events) showed that preoperative hemorrhage was significantly associated with PHS (p = 0.003), while hypertension (p = 0.003), diabetes mellitus (p = 0.003) and modified Rankin scale (mRS) (p = 0.034) at admission were associated with a higher rate of PIS. Furthermore, preoperative hemorrhagic stroke was identified as a risk factor for PHS (odds ratio [OR], 4.229 [95% CI, 1.244-14.376]; p = 0.021), while hypertension (odds ratio [OR], 0.424 [95% CI, 0.210-0.855]; p = 0.017), diabetes mellitus (odds ratio [OR], 0.368 [95% CI, 0.163-0.827]; p = 0.016) and admission mRS (odds ratio [OR], 2.301 [95% CI, 1.157-4.575]; p = 0.017) were found to be risk factors for PIS. CONCLUSIONS: The age distribution of adult MMD patients with revascularization was predominantly concentrated within the range from 46 to 55 years. Preoperative hemorrhage events were considered the risk factor for PHS. Hypertension, diabetes and admission mRS were correlated with PIS, and were also the risk factors for PIS. These results indicated the possible contribution of enhancing systematic disease management to the prevention of postoperative cerebrovascular accidents.

Insights into the regulatory role of RNA methylation modifications in glioma.

Epitranscriptomic abnormalities, which are highly prevalent in primary central nervous system malignancies, have been identified as crucial contributors to the development and progression of gliomas. RNA epitranscriptomic modifications, particularly the reversible modification methylation, have been observed throughout the RNA cycle. Epitranscriptomic modifications, which regulate RNA transcription and translation, have profound biological implications. These modifications are associated with the development of several cancer types. Notably, three main protein types-writers, erasers, and readers, in conjunction with other related proteins, mediate these epitranscriptomic changes. This review primarily focuses on the role of recently identified RNA methylation modifications in gliomas, such as N6-methyladenosine (m6A), 5-methylcytosine (m5C), N7-methylguanosine (m7G), and N1-methyladenosine (m1A). We delved into their corresponding writers, erasers, readers, and related binding proteins to propose new approaches and prognostic indicators for patients with glioma.

Genome-Wide 5-Formylcytosine Redistribution in KCl-Stimulated Mouse Primary Cortical Neurons is Associated with Neuronal Activity.

An abundant accumulation of DNA demethylation intermediates has been identified in mammalian neurons. While the roles of 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) in neuronal function have been extensively studied, little is known about 5-formylcytosine (5fC) in neurons. Therefore, this study was to investigate the genome-wide distribution and potential functions of 5fC in neurons. In an in vitro culture model of mouse primary cortical neurons, we observed a dynamic increase in the total 5fC level in the neuronal genome after potassium chloride (KCl) stimulation. Subsequently, we employed chemical-labeling-enabled C-to-T conversion sequencing (CLEVER-seq) to examine the 5fC distribution at a single-base resolution. Bioinformatic analysis revealed that 5fC was enriched in promoter regions, and gene ontology (GO) analysis indicated that the differential formylation positions (DFP) were correlated with neuronal activities. Additionally, integration with previously published nascent RNA-seq data revealed a positive correlation between gene formylation and mRNA expression levels. As well, 6 neuro-activity-related genes with a positive correlation were validated. Furthermore, we observed higher chromatin accessibility and RNA pol II binding signals near the 5fC sites through multiomics analysis. Motif analysis identified potential reader proteins for 5fC. In conclusion, our work provides a valuable resource for studying the dynamic changes and functional roles of 5fC in activated mammalian neurons.