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Neurological diseases are expected to become the leading cause of death in the next decade. Although little is known about it, the interaction between oxidative stress and inflammation is harmful to the nervous system. To find an advanced tool for neural genetics, mouse haploid neural stem cells (haNSCs) from the somite of chimeric mouse embryos at E8.5 is established. The haNSCs present a haploid neural progenitor identity for long‐term culture, promising to robustly differentiate into neural subtypes and being able to form cerebral organoids efficiently. Thereafter, haNSC mutants via a high‐throughput approach and screened targets of oxidative stress is generated using the specific mutant library. Deletion of Nfkbia (the top hit among the insertion mutants) reduces damage from reactive oxygen species (ROS) in NSCs exposed to H2O2. Transcriptome analysis revealed that Atp2b4 is upregulated significantly in Nfkbia‐null NSCs and is probably responsible for the observed resistance. Additionally, overexpression of Atp2b4 itself can increase the survival of NSCs in the presence of H2O2, suggesting that Atp2b4 is closely involved in this resistance. Herein, a powerful haploid system is presented to study functional genetics in neural lineages, shedding light on the screening of critical genes and drugs for neurological diseases. [ABSTRACT FROM AUTHOR]

Endometrioid endometrial carcinoma (EEC) stands as a prevalent gynecologic malignancy in developed regions. However, predicting relapse cases remains challenging, necessitating the identification of a novel biomarker for EEC relapse. The assessment of tumor mutational burden (TMB) is pivotal for immunotherapy in EEC patients. However, both whole-exome sequencing (WES) and targeted sequencing encountered application-related difficulties. In light of this, standardized and simplified techniques for TMB measurement are imperative. In this study, we employed WES on 25 EEC patients (12 relapsed cases and 13 non-relapsed cases) who accepted hysterectomy surgery (CHCAMS cohort). We additionally obtained a total of 391 tumor samples with clinicopathological features from TCGA website to broaden the study cohort. In the CHCAMS cohort, the TTN mutant group showed shorter progression-free survival (p < 0.001) and overall survival (p < 0.001) than TTN wild-type group. Additionally, we discovered that the number of TTN mutations per sample was significantly linked with TMB-WES in CHCAMS cohort and TCGA cohort (p < 0.05). And the number of TTN mutations per sample in POLE mutant group was greater than in the POLE wild-type group (p < 0.0001). In conclusion, TTN mutation may serve as a biomarker for EEC prognosis. TTN mutation is also associated with WES-TMB, and could be a simplified TMB measurement technique. [ABSTRACT FROM AUTHOR]

Human rhomboid family-1 ( RHBDF1 ) gene is recognized as an oncogene involved in breast cancer development. Previous studies have indicated that RHBDF1 contributes significantly to endoplasmic reticulum (ER) protein homeostasis by stabilizing the binding immunoglobulin protein (BiP) and promoting the unfolded protein response (UPR). Here, we report a relationship between RHBDF1 and the ER stress sensors PERK, IRE1, and ATF6. We show that RHBDF1 deficiency in breast cancer cells results in decreased levels of PERK, pPERK, and peIF2α. These protein levels can be restored in RHBDF1-deficient breast cancer cells by artificial overexpression of RHBDF1 but not IRE1 or ATF6. Additionally, we show that the transcription factor FoxO3 is essential for the RHBDF1-mediated production of PERK. Subsequent analysis reveals that RHBDF1 activates JNK, which causes FoxO3 to translocate into the cell nucleus. These findings demonstrate that RHBDF1 supports the UPR by upregulating the PERK/peIF2α pathway via the JNK/FoxO3 axis and that the functions of RHBDF1 are essential for preserving the homeostasis of ER proteins.

Background and Objectives: There remains significant debate regarding the performance of deep brain stimulation (DBS) procedures for Parkinson disease (PD) under local or general anesthesia. The aim of this meta-analysis was to compare the clinical outcomes between "asleep" DBS (general anesthesia) and "awake" DBS (local anesthesia) for PD., Methods: We conducted a comprehensive literature review of all published studies on DBS for PD following PRISMA guideline on PubMed and Cochrane library from January 2004 to April 2023. Inclusion criteria included cohort ≥15 patients, clinical outcomes data which included Unified Parkinson's Disease Rating Scale (UPDRS) score and levodopa equivalent daily dosage (LEDD), and ≥3 months of follow-up. Analysis was conducted using Stata software., Results: There were 18 articles that met inclusion criteria. On meta-analysis, there were no significant differences between awake or asleep DBS with regard to percent change in UPDRS III "off" med/"on" DBS condition ( P = .6) and LEDD score ( P = .99). On subgroup analysis, we found that the choice of target had no significant effect on improvement of UPDRS III ( P = 1.0) or LEDD ( P = .99) change for the asleep vs awake operative approach. There were also no statistically significant differences between microelectrode recording (MER) use and no MER use in postoperative UPDRS III ( P = 1.0) or LEDD improvement ( P = .90) between awake and asleep surgery., Conclusion: There was no significant difference in the primary motor outcomes and LEDD improvement between asleep vs awake DBS. The variables of target selection and MER use had no statistically significant impact on outcome. We find that asleep techniques are both safe and effective compared with the awake technique., (Copyright © Congress of Neurological Surgeons 2024. All rights reserved.)