Loss-of-function variants in CSDE1 have been strongly linked to neuropsychiatric disorders, yet the precise role of CSDE1 in neurogenesis remains elusive. In this study, we demonstrate that knockout of Csde1 during cortical development in mice results in impaired neural progenitor proliferation, leading to abnormal cortical lamination and embryonic lethality. Transcriptomic analysis revealed that Csde1 upregulates the transcription of genes involved in the cell cycle network. Applying a dual thymidine-labelling approach, we further revealed prolonged cell cycle durations of neuronal progenitors in Csde1-knockout mice, with a notable extension of the G1 phase. Intersection with CLIP-seq data demonstrated that Csde1 binds to the 3' untranslated region (UTR) of mRNA transcripts encoding cell cycle genes. Particularly, we uncovered that Csde1 directly binds to the 3' UTR of mRNA transcripts encoding Cdk6, a pivotal gene in regulating the transition from the G1 to S phases of the cell cycle, thereby maintaining its stability. Collectively, this study elucidates Csde1 as a novel regulator of Cdk6, sheds new light on its critical roles in orchestrating brain development, and underscores how mutations in Csde1 may contribute to the pathogenesis of neuropsychiatric disorders.
Animals ; Neurogenesis/genetics* ; Cell Cycle/genetics* ; Mice, Knockout ; Mice ; Neural Stem Cells/metabolism* ; DNA-Binding Proteins/metabolism* ; Cyclin-Dependent Kinase 6/genetics* ; Cell Proliferation ; 3' Untranslated Regions ; Cerebral Cortex/embryology* ; RNA-Binding Proteins ; Mice, Inbred C57BL

Objective:To investigate the predictive value of gadobenate dimeglumine (GD-BOPTA) multi-phase enhanced MRI for the expression of cytokeratin19 (CK19) in hepatocellular carcinoma (HCC).Methods:A total of 153 patients of HCC confirmed by pathology from June 2016 to February 2020 in First Affiliated Hospital of Fujian Medical University were enrolled retrospectively. According to the post-operative pathology, the patients were divided into CK19-negative group ( n=122) and CK19-positive group ( n=31). All the patients underwent MRI scan and Gd-BOPTA multi-phase enhanced scan before operation. MRI features on Gd-BOPTA MRI were compared between two groups. The qualitative indicators included tumor morphology, mosaic signs, intratumoral hemorrhage, intratumoral fat, non-rim arterial phase hyper-enhancement (APHE), non-peripheral washout, targetoid manifestation, enhanced capsule, corona enhancement, DWI signal, vascular invasion and hepatobiliary phase (HBP) enhancement. The quantitative indicator of tumor-to-liver signal ratio (SR) on HBP was recorded. The χ 2 test or Fisher exact probability method was used to compare the qualitative parameters between two groups, and student′s t test or Mann -Whitney U test was used for quantitative data. Predictive parameters were identified by univariate and multivariate logistic regression analysis to predict the value of the expression of CK19. The ROC curve was used to analyze the diagnostic efficacy of MRI parameters. Results:There were statistically significant differences between CK19-positive and CK19-negative groups ( P<0.05) in alpha fetoprotein, tumor morphology, non-rim APHE, non-peripheral washout, targetoid manifestation, corona enhancement, HBP enhancement and SR. Multivariate logistic regression analysis showed tumor morphology, corona enhancement, HBP enhancement and SR were independent predictors of CK19 expression in HCC. The area under the ROC curve of the combined four indicators for predicting CK19 expression in HCC was 0.823, and the sensitivity and specificity were 80.7% and 75.4%, respectively. Conclusions:Gd-BOPTA multi-phase enhanced MRI has an important value in the prediction of the expression of CK19 in HCC. The combination of signs of HBP can improve the prediction efficiency of CK19.

Objective To investigate the effect of lower thoracic epidural block on intestinal epithelial cell apoptosis during hemorrhagic shock and resuscitation in rats.Methods Sixty-four male SD rats placed with lower thoracic epidural catheter were randomly divided into four groups (n=1 6 each):group Sham (sham operation),group HSR (hemorrhagic shock and resuscitation),group NS (hemorrhagic shock and resuscitation+epidural saline 100 μl/kg),and group TEA (hemorrhagic shock and resuscitation+epidural 0.075% ropivacaine 100 μl/kg).The hemorrhagic shock was made described by Chaudry.Rats were resuscitated by transfusing shed blood and normal saline 60 min after hemorrhagic shock.Malondialdehyde (MDA)content,superoxide dismutase (SOD)activity, and protein expression of Bax and Bcl-2 in intestinal epithelium were detected,and epithelial apoptosis index was calculated at 2 h after resuscitation.Results Compared with group Sham,intestinal epithe-lial MDA,Bax expression and epithelial apoptosis were significantly increased,while SOD activity were markedly decreased in groups HSR,NS and TEA (P<0.05).Compared with groups HSR and NS,intestinal epithelial MDA,Bax expression and epithelial apoptosis were significantly decreased, while SOD activity and Bcl-2 expression were markedly increased in group TEA (P <0.05 ). Conclusion Lower thoracic epidural block can enhance the antioxidant and anti-apoptotic ability,and inhibit the oxidative stress and cell apoptosis of intestinal epithelium.Therefore,it can promote the survival rate after hemorrhagic shock and resuscitation through protecting intestinal barrier.