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 conduct a hierarchical classification analysis of the nonreportable results of noninvasive prenatal testing in an attempt to reduce failure rates and provide pregnant women with accurate information to alleviate their anxiety.Methods::In this study, 30,039 singleton pregnancies who underwent noninvasive prenatal testing in a single center from May 2019 to April 2022 were collected, and 811 samples with initial noninvasive prenatal testing failure were retrospectively analyzed. Grouping was based on the reasons for initial test failure; tracking the noninvasive prenatal testing results and prenatal diagnosis results (if any) of the "z-scores in the gray area" group and analyzing the possible influencing factors of the "low fetal fraction" group in the pre-experimental and experimental period by using one-way analysis of variance, Mann-Whitney U test, and χ 2 test; and tracking the pregnancy outcomes of the test failures samples to analyze the risk of perinatal complications and adverse pregnancy outcomes of the different types of test failures. Results::None of the samples' initial inconclusive results because of z-scores in the gray area were found to have chromosomal aneuploidy. However, pregnancy complications ( P = 0.018) and a high likelihood of adverse pregnancy outcomes ( P = 0.048) may still occur. Maternal gestational age ( P < 0.001), body mass index ( P < 0.001), library concentration ( P < 0.001), and fetal gender ( P < 0.001) were considered to be the associated factors for the initial low fetal fraction results. This may be associated with pregnancy complications ( P < 0.001) and a high likelihood of adverse pregnancy outcomes ( P = 0.034). The body mass index ( P = 0.015) and time between draws ( P = 0.001) were associated with the second test’s success. The incidence of low fetal fraction samples was more frequent with blood collection tubes of the G type than with the K type ( P < 0.001). Conclusion::Initial inconclusive results because of z-scores in the gray area did not imply an increased risk of aneuploidy, but vigilance is needed for an increased risk of pregnancy complications and adverse pregnancy outcomes. Because of the low fetal fraction, the initial absence of results may be related to the assay method, as well as the effect of blood collection tubes and the need to be alert to the risk of pregnancy complications and adverse pregnancy outcomes.

Objective::To conduct a hierarchical classification analysis of the nonreportable results of noninvasive prenatal testing in an attempt to reduce failure rates and provide pregnant women with accurate information to alleviate their anxiety.Methods::In this study, 30,039 singleton pregnancies who underwent noninvasive prenatal testing in a single center from May 2019 to April 2022 were collected, and 811 samples with initial noninvasive prenatal testing failure were retrospectively analyzed. Grouping was based on the reasons for initial test failure; tracking the noninvasive prenatal testing results and prenatal diagnosis results (if any) of the "z-scores in the gray area" group and analyzing the possible influencing factors of the "low fetal fraction" group in the pre-experimental and experimental period by using one-way analysis of variance, Mann-Whitney U test, and χ 2 test; and tracking the pregnancy outcomes of the test failures samples to analyze the risk of perinatal complications and adverse pregnancy outcomes of the different types of test failures. Results::None of the samples' initial inconclusive results because of z-scores in the gray area were found to have chromosomal aneuploidy. However, pregnancy complications ( P = 0.018) and a high likelihood of adverse pregnancy outcomes ( P = 0.048) may still occur. Maternal gestational age ( P < 0.001), body mass index ( P < 0.001), library concentration ( P < 0.001), and fetal gender ( P < 0.001) were considered to be the associated factors for the initial low fetal fraction results. This may be associated with pregnancy complications ( P < 0.001) and a high likelihood of adverse pregnancy outcomes ( P = 0.034). The body mass index ( P = 0.015) and time between draws ( P = 0.001) were associated with the second test’s success. The incidence of low fetal fraction samples was more frequent with blood collection tubes of the G type than with the K type ( P < 0.001). Conclusion::Initial inconclusive results because of z-scores in the gray area did not imply an increased risk of aneuploidy, but vigilance is needed for an increased risk of pregnancy complications and adverse pregnancy outcomes. Because of the low fetal fraction, the initial absence of results may be related to the assay method, as well as the effect of blood collection tubes and the need to be alert to the risk of pregnancy complications and adverse pregnancy outcomes.

Parkinson's disease (PD) is the most common neurodegenerative movement disease. It is featured by abnormal alpha-synuclein (α-syn) aggregation in dopaminergic neurons in the substantia nigra. Macroautophagy (autophagy) is an evolutionarily conserved cellular process for degradation of cellular contents, including protein aggregates, to maintain cellular homeostasis. Corynoxine B (Cory B), a natural alkaloid isolated from Uncaria rhynchophylla (Miq.) Jacks., has been reported to promote the clearance of α-syn in cell models by inducing autophagy. However, the molecular mechanism by which Cory B induces autophagy is not known, and the α-syn-lowering activity of Cory B has not been verified in animal models. Here, we report that Cory B enhanced the activity of Beclin 1/VPS34 complex and increased autophagy by promoting the interaction between Beclin 1 and HMGB1/2. Depletion of HMGB1/2 impaired Cory B-induced autophagy. We showed for the first time that, similar to HMGB1, HMGB2 is also required for autophagy and depletion of HMGB2 decreased autophagy levels and phosphatidylinositol 3-kinase III activity both under basal and stimulated conditions. By applying cellular thermal shift assay, surface plasmon resonance, and molecular docking, we confirmed that Cory B directly binds to HMGB1/2 near the C106 site. Furthermore, in vivo studies with a wild-type α-syn transgenic drosophila model of PD and an A53T α-syn transgenic mouse model of PD, Cory B enhanced autophagy, promoted α-syn clearance and improved behavioral abnormalities. Taken together, the results of this study reveal that Cory B enhances phosphatidylinositol 3-kinase III activity/autophagy by binding to HMGB1/2 and that this enhancement is neuroprotective against PD.

From the perspective of risk management, all kinds of risks potentially encountered by each actor involved in the clinical trials in China, including the sponsors, investigators,subjects ethics committee and medical institutions, were analyzed, and some suggestions and expectations on how to minimize the risks were accordingly proposed.Appropriate and effective strategies of risk control and management should be performed to optimize the resource of each actor involved and reduce risks, and eventually to guanrantee the safety of subjects and obtain high quality of study data.

Objective To observe the influence of Simvastatin on the ATP-sensitive K+Channels and L-type Ca2+ Channels in mouse pancreatic beta cell line MIN6.Methods MIN6 cells were divided into 0.05 ％ dimethyl sulfoxide (DMSO) group,normal control group and low-,middle-,high-concentration of Simvastatin treatment groups,that were cultured for 48 h with high-glucose DMEM containing 15％ fetal bovine serum plus 0.05％ dimethyl sulfoxide,0,2,5 and 10 μmol/Lsimvastatin,respectively.Whole-cell patch-clamp technology was used to record the currents of ATP-sensitive K+ channels and L-type Ca2+ channels in MIN6 cells.Results The mean potassium current density in normal external solution perfusion group was (92.81 ±4.10) pA/pF.Compared with normal external solution perfusion control group,2,5 and 10 μmol/L Simvastatin treatments markedly enhanced the current density of ATP-sensitive K+ Channels,reaching to (117.94 ± 3.67)pA/pF,(153.91±12.38) pA/pF,(307.01±6.40) pA/pF (all P＜0.01),respectively.The current density in L-type Ca2+ Channels was (-21.03 ± 0.55) pA/pF in glucose external solution group.Compared with glucose external solution group,the current density in 2,5 and 10 μmol/L Simvastatin treatment groups were decreased to (16.31±0.51) pA/pF,(-10.75±0.71) pA/pF,(-3.30±0.46) pA/pF (all P＜0.01),respectively.Conclusions Simvastatin inhibits insulin secretion and glycometabolism in mouse pancreatic beta cell line MIN6 via enhancing the current density of ATP-sensitive K+ Channels and inhibiting the current density of L-type Ca2+ Channels.

Objective To evaluate the importance of plasma MicroRNAs in early diagnosis of acute myocardial infarction (AMI).Methods 24 patients with AMI as the test group and 20healthy volunteers as the control group were enrolled in this study.Plasma levels of microRNA-1,microRNA-133a,microRNA-208a and microRNA-499 were detected by quantitative real time polymerase chain reaction (qRT-PCR) at 3 h,6 h,12 h,24 h,48 h,72 h after the onset of AMI.Results Plasma microRNA-1 level was greatly increased and reached the peak at 3 h after AMI,then was decreased gradually to normal level at 72 h after AMI.Plasma microRNA-133a level was significantly elevated at 6 h after AMI,reached peak at 12 h after AMI,then was decreased to normal level at 48 h after AMI.Plasma microRNA-1 and microRNA-133a levels were correlated with cTnI expression.The peak time of microRNA-1 was earlier than that of cTnI,while the peak time of microRNA-133a was the same as that of cTnI.Conclusions Increased circulating microRNA-1 and microRNA-133a may serve as potential and novel biomarkers for early diagnosis of AMI.

Objective To explore the predictive value of ventricle late potential (LP) for arrhythmic events in the patients with Brugada syndrome. Methods Totally 43 patients with Brugada syndrome were divided into symptom group (n=24) and asymptom group (n=19).Signalaveraged electrocardiography(SAECG) was performed to analyze characteristics of LP in all subjects.The occurrence of arrhythmic events was observed in all patients during the dynamic follow-up for (33.8±9.0) months.Results There were 22 cases (91.7％) and 7 cases (36.8％) with LP positive in patients with symptom and asymptom,respectively.The incidences of arrhythmic events were 72.4％ in Brugada syndrome patients with positive LP and 14.3％ in patients with negative LP,respectively.The relative risk (RR,95％ CI) for LP prediction of the arrhythmic events was [5.1,(1.4～ 18.6)] (P =0.002). ConclusionsLP may be one of effective factors predicting arrhythmic events in the patients with Brugada syndrome.