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 multi-target mechanisms of quercetin in treating endometriosis(EMT)through integrative network pharmacology analysis.Methods Active targets of quercetin were collected from the TCMSP database,while EMT-related differentially expressed genes(DEGs)were identified through the Gene Expression Omnibus(GEO)dataset.A comparative analysis was conducted to pinpoint potential therapeutic targets of quercetin for EMT treatment.Functional enrichment analyses were employed to investigate the biological functions associated with these targets,and a protein-protein interaction(PPI)network was conducted to identify core targets.Molecular docking and dynamics simulations were performed to validate the binding characteristics between quercetin and the core targets.The top 2 target protein pairs,HSP90AB1 and AR,exhibiting the lowest binding energy,were selected for subsequent cellular experimental validation.Human EMT-immortalized ectopic endometrial epithelial cell line 12Z(n=6,independent replicates)was subjected,and CCK-8 assay was used to determine ehe effects of quercetin on cell viability and proliferation,and the half-maximal inhibitory concentration(IC50)was calculated at 48 h after treatment.Then the 12Z cells were treated with quercetin at a concentration gradient of 0,30,60 and 90 μmol/L,the migration and invasion abilities were assessed with cell scratch and cell invasion assays.Western blotting was conducted to detect the changes in the expression of HSP90AB1 and AR proteins after different doses of treatment.Results There were 49 potential EMT-related therapeutic targets and 10 core targets identified.Functional enrichment analyses revealed that these targets were significant enriched in inflammation-related signaling pathways,including AGE-RAGE,ErbB and TNF;immune-related pathways,such as Th17 cell differentiation,T/B cell receptor signaling;angiogenesis-related pathways like VEGF;and hormonal regulatory pathways involving estrogen and GnRH.Molecular docking demonstrated that quercetin exhibited favorable binding activity(binding energy<-5 kcal/mol)with all core target proteins,with particularly strong binding energies(<-7 kcal/mol)observed for AR,EGFR,FOS,ERBB2,and HSP90AB1.Molecular dynamics simulations revealed that quercetin forms sustained hydrogen bond interactions with AR and HSP90AB1,facilitating the formation of stable complexes.CCK-8 assay,cell scratch assay,and transwell invasion assay indicated that quercetin inhibited the proliferative activity,and migrative and invasive abilities of 12Z cells in a concentration-dependent manner,with more pronounced inhibitory effects observed at 60 and 90 μmol/L quercetin(P<0.001);Western blotting revealed that treatment of 12Z cells with varying quercetin concentrations for 48 h up-regulated the expression of HSP90AB1 and AR,with the most significant increase observed at 90 μmol/L quercetin(HSP90AB1,P<0.05;AR,P<0.001).The restored expression levels of HSP90AB1 and AR showed positive correlations with the proliferative activity,migrative and invasive abilities of ectopic endometrial cells.Conclusion Quercetin effectively addresses endometriosis through multiple molecular targets and signaling pathways,and stabilization of the HSP90AB1/AR complex and subsequent protein upregulation represents a key therapeutic mechanism.

Objective To explore the needs of community pharmacy services in elderly hypertensive patients in the community, especially empty-nest elderly patients. Methods Elderly hypertensive patients living in Ouyang street were randomly selected and divided into empty-nest and non-empty-nest groups by cluster random sampling method. The basic information of the respondents, the frequency of hypertension monitoring, the taking of hypertensive drugs, and the taking of other drugs were compared and analyzed. Results In term of “blood pressure monitoring frequency”, the daily pressure measurement of the empty-nest group and the non-empty-nest group accounted for 33.6% and 19.3%, respectively. There was significant difference between the two groups (P<0.05).In term of “the varieties of hypertension drugs” and taking 3 kinds of hypertension drugs at the same times, the empty-nest group accounted for 28.8% and the non-empty-nest group accounted for 16.7%, and the difference between the two groups was significant (P<0.05)；In term of “the varieties of drugs” and taking 1-2 kinds of Chinese patent drugs at the same time, the empty-nest group accounted for 39.6% and the non-empty-nest group accounted for 26.0% , and the difference between the two groups was significant (P<0.05)。Conclusion Community elderly patients with hypertension, especially empty-nest elderly patients have an urgent need for community pharmacy services，Community pharmacy services personnel should provide personalized and targeted medication education and guidance to elderly patients, especially empty-nest elderly patients, to promote the rational drug use in elderly patients.

Objective: To investigate risk factors and epidemiological characteristics of bacillary dysentery outbreaks in three schools, and to provide scientific basis for the prevention and control of the epidemic in the future. Methods: Case definition was established. All suspected, possible and confirmed cases of all students and faculty members from 3 schools (A, B, C) were selected for epidemiological investigation. Control group was used for case-control analysis, and relevant samples were collected for laboratory testing. Results: A total of 132 cases were found in 3 schools, all of which were from students, with the incidence rate of 17.74%. The morbidity in kindergarten A was 20.00%, in center primary school B it was 21.74%, and in junior middle school C it was 11.61%. Cohort studies and casecontrol studies suggested that schools are exposed places and that washing hands with raw water in schools was possible risk factor [OR(95%CI) =4.50(1.01-20.11)]. Nine stool samples were tested in laboratory, among which 8 were positive for Shigella(88.99%), and Shigella was detected in the end nodes of school s pipeline network, the water samples from canteen bucket, and the floor drains of sewer pipe. Conclusion The bacillary dysentery outbreaks in 3 schools was caused by Shigella, which may be due to fecal contamination of domestic water in 3 schools before the start of the school year. It is suggested to strengthen the management of centralized water supply and construction in rural areas, intensify the supervision at all levels, and sanitation and disinfection before school opens at all levels.