DNMT1-mediated regulating on FBXO32 promotes the progression of glioma cells through the regulation of SKP1 activity.

Glioma, a prevalent and serious form of brain cancer, is associated with dysregulation of DNA methylation, where DNA methyltransferase-1 (DNMT1) plays a significant role in glioma progression. However, the involvement of F-box protein 32 (FBXO32) in glioma and its regulation by DNMT1-mediated methylation remain poorly understood. In this study, we investigated FBXO32 expression in glioma cells with high DNMT1 expression using the online dataset and correlated it with patient survival. Then impact of elevated FBXO32 expression on cell proliferation, migration, and invasion was evaluated, along with the examination of EMT-related proteins. Furthermore, a xenograft model established by injecting glioma cells stably transfected with FBXO32 was used to evaluate tumor growth, volume, and weight. The ChIP assay was employed to study the interaction between DNMT1 and the FBXO32 promoter, revealing that DNMT1 negatively correlated with FBXO32 expression in glioma cells and promoted FBXO32 promoter methylation. Moreover, we investigated the interaction between FBXO32 and SKP1 using Co-IP and GST pulldown assays, discovering that FBXO32 acts as an E3 ubiquitin ligase and promotes SKP1 ubiquitination, leading to its degradation. Interestingly, our findings demonstrated that high FBXO32 expression was associated with improved overall survival in glioma patients. Knockdown of DNMT1 in glioma cells increased FBXO32 expression and suppressed malignant phenotypes, suggesting that FBXO32 functions as a tumor suppressor in glioma. In conclusion, this study reveals a novel regulatory mechanism involving DNMT1-mediated FBXO32 expression in glioma cells, where FBXO32 acts as an E3 ubiquitin ligase to degrade SKP1 via ubiquitination. This FBXO32-mediated regulation of SKP1 activity contributes to the progression of glioma cells. These findings provide important insights into the molecular mechanisms underlying glioma progression and may hold promise for the development of targeted therapies for glioma patients.

Prognostic value of m6A regulators and the nomogram construction in glioma patients.

Although N6-methyladenosine (m6A) has been implicated in various biological functions in human cancers, its role in predicting the prognosis of glioma remains unclear. In this study, the transcriptome expression profiles and the clinical data of 961 patients were derived from the Chinese Glioma Genome Atlas (CGGA). We comprehensively evaluated the association between the expression of m6A regulators and the prognosis of glioma and established a 3-gene (YTHDF2, FTO, and ALKBH5) risk signature using least absolute shrinkage and selection operator (LASSO) analysis. Patients with a high-risk signature had significantly adverse prognoses. Gene set enrichment analysis (GSEA) analysis revealed that the G2M checkpoint, MTORC1 signaling, epithelial mesenchymal transition, and PI3K-AKT-mTOR signaling were significantly enriched in the high-risk group. Univariate and multivariate Cox regression analyses confirmed the independent prognostic value of this risk signature. We then constructed a nomogram for individualized prediction of overall survival (OS) by integrating clinicopathological features (age, World Health Organization [WHO] grade), treatment information (radiotherapy, temozolomide therapy), and m6A risk signature. The calibration curves showed excellent agreement between the predicted and actual probabilities for the 1-, 3-, and 5-year OS, with a C-index of 0.780 in the training cohort and 0.717 in the validation cohort. Altogether, our study elucidated the important role of m6A regulators in glioma prognosis, which is valuable for the selection of therapeutic methods and clinical management of patients with glioma.

Blink reflex: A practical test to evaluate the trigeminal nerve injury following percutaneous balloon compression for the treatment of trigeminal neuralgia.

OBJECTIVE: To evaluate the blink reflex (BR) in estimating the potential injury of trigeminal nerve following percutaneous balloon compression (PBC) surgery, and to determine the association between BR alterations and early surgical outcomes. METHODS: In this single-center, prospective before-and-after study, a total of 74 patients who had primary trigeminal neuralgia and scheduled for PBC between October 2020 and June 2021 were prospectively included. BR testing and facial sensory assessment were performed pre- and post-PBC. The latency and the area under the curve (AUC) of pre- and postoperative R1 (R1pre /R1post ) and R2 (R2pre /R2post ) were measured. RESULTS: The BR components were noticeably delayed or diminished following PBC. R1post was elicited in only 26 patients, and absent in 48 patients. The residual R1post had markedly reduced AUC (median difference [Hodges-Lehmann]: -59.5, 95% confidence interval [CI]: -217.5 to -6.9, p = 0.023). Compared with R2pre , the latency of R2post was considerably delayed (mean difference: 4.3, 95% CI: 2.9 to 5.7, p < 0.001) and the AUC was greatly suppressed (median difference [Hodges-Lehmann]: -388.4, 95% CI: -548.4 to -259.5, p < 0.001). After PBC, 58 patients had immediate total pain relief, and 16 had partial relief. The absence of R1post was found in 46 of 58 (79.3%) patients with complete remission, whereas in only 2 of 16 (12.5%) patients with partial relief. Association analysis showed that the absence of R1post was strongly associated with total pain relief (46/58 [79.3%] vs. 2/16 [12.5%], odds ratio [OR]: 26.8, 95% CI: 5.4 to 134.5, Cramér's V: 0.6, p < 0.001). The latency of R2post in patients with total relief was significantly delayed (mean difference: 2.5, 95% CI: 0.3 to 4.6, p = 0.028). Patients experienced graded facial numbness after PBC, of whom 31 reported mild numbness (Grades I-II) and 43 reported more severe numbness (Grades III-IV). The absence of R1post was significantly associated with facial numbness severity, 33/43 (76.7%) in Grades III-IV vs. 15/31 (48.4%) in Grades I-II (OR: 0.284, 95% CI: 0.105 to 0.771, Cramér's V: 0.3, p = 0.012). In patients with more severe numbness, the latency of R2post was significantly delayed (mean difference: 2.7, 95% CI: 0.1 to 5.3, p = 0.043), and the reduction of AUC was much greater (median difference [Hodges-Lehmann]: 17.2, 95% CI: 0.5 to 35.4, p = 0.041). CONCLUSION: Both R1 and R2 were significantly diminished after PBC and these alterations were associated with early surgical outcomes, suggesting that the BR is useful in evaluating trigeminal injury following PBC and could provide objective information about early prognosis.

Facial root entry/exit zone contact in microvascular decompression for hemifacial spasm: a historical control study.

BACKGROUND: Microvascular decompression (MVD) surgery is recognized as an effective treatment for hemifacial spasm (HFS). In MVD surgery, biocompatible materials are usually implanted in situ at the neurovascular conflict site in contact with the offending vessel and the facial root entry/exit zone (REZ). Another procedure of implanting the materials between the responsible vessel and the supraolivary fossa without REZ contact has also been applied. However, it is unclear whether there are any differences between these 2 procedures (REZ-contact procedure vs. REZ-non-contact procedure). Therefore, the aim of the present study was to investigate the effect of the placement of implants (contacting or not contacting the facial REZ) on surgical operations and outcomes. METHODS: A historical control study was performed. Clinical data of HFS patients who underwent MVD between December 2016 and November 2018 were reviewed and categorized into 1 group with the REZ-contact procedure or another group with the REZ-non-contact procedure according to the decompression strategy they received. Clinical demographics, postoperative outcomes, and complications were collected and compared between the two groups. RESULTS: Not all patients are suitable for REZ-non-contact decompression. A total of 205 patients were enrolled: 112 in the REZ-contact group and 93 in the REZ-non-contact group. In the early postoperative period, the complete cure rate in the REZ-non-contact group was significantly higher than that in the REZ-contact group. The reappearance and partial relief rates in the REZ-contact group were significantly higher than those in the REZ-non-contact group. The incidence of short-term neurological complications, especially hearing loss and transient facial palsy, was lower in the REZ-non-contact group (P=0.043). But for long-term follow-up of >1 year, there was no significant difference between the two groups in either curative effects or neurological complications. The operating time for REZ-non-contact decompression was relatively longer than for REZ-contact decompression (P=0.000). An unexpected subdural hemorrhage occurred in the REZ-non-contact group. CONCLUSIONS: REZ-non-contact decompression procedure showed superiority only in short-term postoperative outcomes. Given its limitations and potential risks, the REZ-non-contact procedure can be used as an alternative individualized strategy in MVD, and there is no need to pursue REZ-non-contact during the decompression.

Micromachined Planar Supercapacitor with Interdigital Buckypaper Electrodes.

In this work, a flexible micro-supercapacitor with interdigital planar buckypaper electrodes is presented. A simple fabrication process involving vacuum filtration method and SU-8 molding techniques is proposed to fabricate in-plane interdigital buckypaper electrodes on a membrane filter substrate. The proposed process exhibits excellent flexibility for future integration of the micro-supercapacitors (micro-SC) with other electronic components. The device's maximum specific capacitance measured using cyclic voltammetry was 107.27 mF/cm² at a scan rate of 20 mV/s. The electrochemical stability was investigated by measuring the performance of charge-discharge at different discharge rates. Devices with different buckypaper electrode thicknesses were also fabricated and measured. The specific capacitance of the proposed device increased linearly with the buckypaper electrode thickness. The measured leakage current was approximately 9.95 µA after 3600 s. The device exhibited high cycle stability, with 96.59% specific capacitance retention after 1000 cycles. A Nyquist plot of the micro-SC was also obtained by measuring the impedances with frequencies from 1 Hz to 50 kHz; it indicated that the equivalent series resistance value was approximately 18 Ω.

Novel Splice-Site Mutation of KRT1 Underlies Diffuse Palmoplantar Keratoderma in a Large Chinese Pedigree.

AIMS: To identify potential causative gene mutations in a large Han Chinese pedigree with diffuse nonepidermolytic palmoplantar keratoderma (NEPPK). METHODS: We enrolled 11 patients and 8 healthy individuals from a pedigree with NEPPK and 100 randomly selected healthy controls. Biopsy samples were obtained from the proband. Genomic DNA was extracted from a peripheral blood sample from each participant. Mutation detection via polymerase chain reaction and Sanger sequencing of relevant potential causative genes, including KRT1, KRT6C, KRT10, KRT16, AQP5, and SERPINB7, was performed. Comparisons were made between sequencing outcomes and currently available reference genome databases, including HGMD Pro, Pubmed, 1000 Genomics, and dbSNP. RESULTS: Histological findings, clinical features, and medical history were in accordance with the diagnosis of diffuse NEPPK. We identified a novel splice-site mutation c.1255-1G > C in intron 6 of KRT1 in all individuals with NEPPK in the pedigree. CONCLUSIONS: Diffuse NEPPK is a relatively rare subtype of palmoplantar keratoderma. The results of this study expand the spectrum of KRT1 mutations in diffuse NEPPK and provide insights into the understanding of its underlying pathological mechanisms and phenotype-genotype correlations.

Eight Novel Mutations of the ADAR1 Gene in Chinese Patients with Dyschromatosis Symmetrica Hereditaria.

AIMS: To identify potential novel gene mutations in Chinese patients with dyschromatosis symmetrica hereditaria (DSH). METHODS: We enrolled 8 Chinese patients with familial DSH, 5 Chinese patients with sporadic DSH, and 100 randomly selected healthy individuals in this study. The genome of each participant was extracted from peripheral blood samples. Sanger sequencing of the ADAR1 gene was performed after polymerase chain reaction amplifications. Comparisons between the DNA sequences of the affected individuals and the NCBI database were performed. RESULTS: We detected eight novel heterozygous mutations and five previously reported mutations in the ADAR1 gene in our patients. The novel mutations include c.1934 + 3A>G, c.2749A>G, c.2311insA, c.3233G>A, c.3019 + 1G>T, c.2894C>A, c.1202_1205del, and c.2280C>A. These detected novel mutations are predicted to induce two frame-shift mutations, one nonsense mutation, three missense mutations, and two splice-site mutations. CONCLUSIONS: The findings of this study expand our knowledge of the range of ADAR1 gene mutations in DSH and will contribute to identifying correlations between the various DSH phenotypes and genotypes. Furthermore, they may provide insight into the underlying pathogenic mechanism.

Low-Actuation Voltage MEMS Digital-to-Analog Converter with Parylene Spring Structures.

We propose an electrostatically-actuated microelectromechanical digital-to-analog converter (M-DAC) device with low actuation voltage. The spring structures of the silicon-based M-DAC device were monolithically fabricated using parylene-C. Because the Young's modulus of parylene-C is considerably lower than that of silicon, the electrostatic microactuators in the proposed device require much lower actuation voltages. The actuation voltage of the proposed M-DAC device is approximately 6 V, which is less than one half of the actuation voltages of a previously reported M-DAC equipped with electrostatic microactuators. The measured total displacement of the proposed three-bit M-DAC is nearly 504 nm, and the motion step is approximately 72 nm. Furthermore, we demonstrated that the M-DAC can be employed as a mirror platform with discrete displacement output for a noncontact surface profiling system.