The relationship between music training and cognitive flexibility: an ERP study.

Background: Music training involves several cognitive functions in the brain, particularly executive function. Numerous studies have proven a link between the two. Cognitive flexibility is an important component of executive function, however, there has been little study investigating the association between music training and cognitive flexibility. Method: Music training (N = 22) and the control groups (N = 26) were included in the present study. A tone-related oddball task was used to investigate the tone-related inhibition and the switch task was to investigate cognitive flexibility. During the switch task, EEG data were collected. Results: The behavioral results of the oddball task showed that the individuals in the music training group had a shorter reaction time and higher accuracy in both the between-tone and within-tone categories compared to the controls. The behavioral results of the switch task showed similar results, with the music training group exhibiting better reaction time and accuracy performance than the controls. ERP results showed that the music training group had smaller P3 amplitudes and greater N2 and N450 amplitudes than the control group. Discussion: The findings further supported the link between music training and enhanced cognitive function.

Recursive structures modulate the electrophysiological correlates of visual perspective taking.

An increasing number of studies have focused on the neural basis of complex mental inferences, which requires an understanding of the recursive nature of thought; however, the precise electrophysiological response to a recursive structure remains unclear. The present event-related potential (ERP) study investigated the recursive structure effect on the neural correlates of visual perspective taking by modifying a third-person visual perspective-taking task. Participants were required to determine how many dots in the presented scenes could be seen from the cued perspective, including the perspectives in the self, other, and recursive (one avatar's belief of another avatar) conditions. The ERP results showed that the N100 and P200 components specific to the recursive-perspective condition showed greater attentional allocation; the N200 component increased in the recursive condition and was related to the conflict process; and larger late slow waves were found in the other- and recursive-perspective conditions compared with those in the self-perspective condition, which reflected the decoupling mechanism. The results suggested that high-order perspective taking requires more attentional resources and conflict processing for further decoupling from the self-perspective.

A computer-aided diagnosis system using white-light endoscopy for the prediction of conventional adenoma with high grade dysplasia.

OBJECTIVES: We developed a computer-aided diagnosis system called ECRCCAD using standard white-light endoscopy (WLE) for predicting conventional adenomas with high-grade dysplasia (HGD) to optimise the patients' management decisions during colonoscopy. METHODS: Pretraining model was used to fine-tune the model parameters by transfer learning. 2,397 images of HGD and 2,487 low-grade dysplasia (LGD) images were randomly assigned (8:1:1) to the training, optimising, and internal validation dataset. The prospective validation dataset is the frames accessed from colonoscope videoes. One independent rural hospital provided an external validation dataset. Histopathological diagnosis was used as the standard criterion. The capability of the ECRCCAD to distinguish HGD was assessed and compared with two expert endoscopists. RESULTS: The accuracy, sensitivity and specificity for diagnosis of HGD in the internal validation set were 90.5%, 93.2%, 87.9%, respectively. While 88.2%, 85.4%, 89.8%, respectively, for the external validation set. For the prospective validation set, ECRCCAD achieved an AUC of 93.5% in diagnosing HGD. The performance of ECRCCAD in diagnosing HGD was better than that of the expert endoscopist in the external validation set (88.2% vs. 71.5%, P < 0.0001). CONCLUSION: ECRCCAD had good diagnostic capability for HGD and enabled a more convenient and accurate diagnosis using WLE.

Sempervirine Mediates Autophagy and Apoptosis via the Akt/mTOR Signaling Pathways in Glioma Cells.

The potential antitumor effects of sempervirine (SPV), an alkaloid compound derived from the traditional Chinese medicine Gelsemium elegans Benth., on different malignant tumors were described in detail. The impact of SPV on glioma cells and the basic atomic components remain uncertain. This study aimed to investigate the activity of SPV in vitro and in vivo. The effect of SPV on the growth of human glioma cells was determined to explore three aspects, namely, cell cycle, cell apoptosis, and autophagy. In this study, glioma cells, U251 and U87 cells, and one animal model were used. Cells were treated with SPV (0, 1, 4, and 8 µM) for 48 h. The cell viability, cell cycle, apoptosis rate and autophagic flux were examined. Cell cycle, apoptotic, autophagy, and Akt/mTOR signal pathway-related proteins, such as CDK1, Cyclin B1, Beclin-1, p62, LC3, AKT, and mTOR were investigated by Western blot approach. As a result, cells induced by SPV led to G2/M phase arrest and apoptosis. SPV also promoted the effect of autophagic flux and accumulation of LC3B. SPV reduced the expression of p62 protein and induced the autophagic death of glioma cells. Furthermore, SPV downregulated the expressions of AKT and mTOR phosphorylated proteins in the mTOR signaling pathway, thereby affecting the onset of apoptosis and autophagy in U251 cells. In conclusion, SPV induced cellular G2/M phase arrest and blockade of the Akt/mTOR signaling pathway, thereby triggering apoptosis and cellular autophagy. The in vivo and in vitro studies confirmed that SPV inhibits the growth of glioma cancer.

Atypical GATA protein TRPS1 plays indispensable roles in mouse two-cell embryo.

Zygotic genome activation (ZGA) is one of the most critical events at the beginning of mammalian preimplantation embryo development (PED). The mechanisms underlying mouse ZGA remain unclear although it has been widely studied. In the present study, we identified that tricho-rhino-phalangeal syndrome 1 (TRPS1), an atypical GATA family member, is an important factor for ZGA in mouse PED. We found that the Trps1 mRNA level peaked at the one-cell stage while TRPS1 protein did so at the two/four-cell stage. Knockdown of Trps1 by the microinjection of Trps1 siRNA reduced the developmental rate of mouse preimplantation embryos by approximately 30%, and increased the expression of ZGA marker genes MuERV-L and Zscan4d via suppressing the expression of major histone markers H3K4me3 and H3K27me3. Furthermore, Trps1 knockdown decreased the expression of Sox2 but increased Oct4 expression. We conclude that TRPS1 may be indispensable for zygotic genome activation during mouse PED.

Protective Effect of Icariin on the Development of Preimplantation Mouse Embryos against Hydrogen Peroxide-Induced Oxidative Injury.

During in vitro cultivation of preimplantation embryos, the balance between ROS production and clearance is disturbed and may lead to incompetent embryos, which might be a main reason of IVF-ET failure. Icariin (ICA) is reported to be active in clearing ROS. The present study aimed to investigate whether ICA could reverse H2O2 pretreatment-induced mouse preimplantation embryo development arrest and, furthermore, to study the underlying mechanisms by detecting ROS levels, mitochondrial membrane potential (ΔΨm), and zygotic gene expression. The results showed that, after pretreating mouse 1-cell embryos with 40 µM or 60 µM H2O2 for 30 min, the developmental rate of each stage embryos decreased obviously. And by adding 40 µM ICA, the developmental arrest of 60 µM H2O2 pretreated preimplantation embryos was significantly reversed. Immunostaining results showed that, comparing with the control group, ROS levels of H2O2 pretreated 1-cell embryos were elevated and ΔΨm levels decreased. By adding ICA, the ROS levels of H2O2 pretreated 1-cell embryos were decreased and ΔΨm levels were elevated. Furthermore, RT-qPCR results showed that the addition of ICA reversed the H2O2-induced downregulation of eIF-1A mRNA expression levels. These results indicate that ICA, when used in appropriate concentration, could decrease ROS levels, increase ΔΨm levels, and modulate the expression of zygotic gene activation (ZGA) marker gene eIF-1A, and thus promote the development of H2O2-pretreated mouse preimplantation embryos.

Simultaneous quantification of L-tetrahydropalmatine and its urine metabolites by ultra high performance liquid chromatography with tandem mass spectrometry.

l-tetrahydropalmatine (l-THP) is a tetrahydroprotoberberine isoquinoline alkaloid that has been used as an analgesic agent in China for more than 40 years. Recent studies indicated its potential application in the treatment of drug addiction. In this study, a sensitive and rapid method using ultra high performance liquid chromatography with MS/MS was developed and validated for simultaneous quantitation of l-THP and its desmethyl metabolites. Enzymatic hydrolysis was integrated into sample preparation to enable the quantitative determination of both free and conjugated metabolites. Chromatographic separation was achieved on an Agilent Poroshell 120 EC-C18 column. Detection was performed by MS in the positive ion ESI mode. The calibration curves of the analytes were linear (r(2) > 0.9936) over the concentration range of 1-1000 ng/mL with the lower limit of quantification at 1 ng/mL. The precision for both intra- and interday determinations was <8.97%, and the accuracy ranged from -8.74 to 8.65%. The recovery for all the analytes was >70% without significant matrix effect. The method has been successfully applied to the urinary excretion study of l-THP in rats. The conjugates were found to be the major urine metabolites of the drug.

[Inhibitory effect of imperatorin and isoimperatorin on activity of cytochrome P450 enzyme in human and rat liver microsomes].

Imperatorin (IM) and isoimperatorin (ISOIM) are major active components of common herbal medicines from Umbelliferae plants, and widely used in clinic. This article studies the inhibitory effect of IM and ISOIM on the activity of cytochrome P450 (CYP) enzyme, and assesses their potential drug-drug interaction. IM and ISOIM were incubated separately with human or rat liver microsomes for 30 min, with phenacetin, bupropion, tolbutamide, S-mephenytoin, dextromethorphan and midazolam as probe substrates. Metabolites of the CYP probe substrates were determined by LC-MS/MS, and IC50 values were calculated to assess the inhibitory effect of the two drugs on human CYP1A2, 2B6, 2C9, 2C19, 2D6 and 3A4 enzymes, as well as on rat CYP1A2, 2B6, 2D2 and 3A1/2, and grade their inhibitory intensity. In human liver microsomes, IM and ISOIM showed different inhibitory effects on all of the six CYP isoenzymes. They were strong inhibitors for 1A2 and 2B6. The IC50 values were 0.05 and 0.20 micromol x L(-1) for 1A2, and 0.18 and 1.07 micromol x L(-1) for 2B6, respectively. They also showed moderate inhibitory effect on 2C19, and weak effect on 2C9, 2D6 and 3A4. In rat liver microsomes, IM and ISOIM were identified as moderate inhibitors for 1A2, with IC50 values of 1.95 and 2.98 micromol x L(-1). They were moderate and weak inhibitors for 2B6, with IC50 values of 6.22 and 21.71 micromol x L(-1), respectively. They also had weaker inhibitory effect on 2D2 and 3A1/2. The results indicated that IM and ISOIM had extensive inhibitory effects on human CYP enzymes. They are strong inhibitors of CYP1 A2 and 2B6 enzymes. However, it is worth noting the interaction arising from the inhibitory effect of CYP enzymes in clinic.

Identification and characterization of psoralen and isopsoralen as potent CYP1A2 reversible and time-dependent inhibitors in human and rat preclinical studies.

Naturally occurring furanocoumarin compounds psoralen (PRN) and isopsoralen (IPRN) are bioactive constituents found in herbaceous plants. They are widely used as active ingredients in several Chinese herbal medicines. In this study, the CYP1A2 inhibitory potential of PRN and IPRN was investigated in rats in vitro and in vivo as well as in human liver microsomes. Both compounds exhibited reversible and time-dependent inhibition toward rat microsomal cyp1a2. The IC(50), k(inact), and K(I) values were 10.4 ± 1.4 µM, 0.060 ± 0.002 min(-1), and 1.13 ± 0.12 µM for PRN, and 7.1 ± 0.6 µM, 0.10 ± 0.01 min(-1), and 1.95 ± 0.31 µM for IPRN, respectively. In human liver microsomal incubations, potent reversible CYP1A2 inhibition was observed for both compounds, with IC(50) values of 0.26 ± 0.01 µM and 0.22 ± 0.03 µM for PRN and IPRN, respectively. However, time-dependent inhibition was only observed for IPRN, with kinact and KI values of 0.050 ± 0.002 min(-1) and 0.40 ± 0.06 µM, respectively. Coadministration with PRN or IPRN significantly inhibited cyp1a2 activity in rats, with the area under the curve (AUC) of phenacetin increasing more than 5-fold. Simcyp simulation predicted that PRN would cause 1.71- and 2.12-fold increases in the phenacetin AUC in healthy volunteers and smokers, respectively. IPRN, on the other hand, would result in 3.24- and 5.01-fold increases in phenacetin AUCs in healthy volunteers and smokers, respectively. These findings represent the first detailed report comparing the potential drug-drug interactions of PRN and IPRN, and provide useful information for balancing safe and efficacious doses of PRN and IPRN.

Pre-column derivatization combined with UHPLC-MS/MS for rapid and sensitive quantification of bakuchiol in rat plasma.

Psoralea corylifolia L. (Fabaceae) is a traditional Chinese medicine with many beneficial effects in medical therapies. Bakuchiol was the main active ingredient of Psoralea corylifolia L. In this study, a novel method of pre-column derivatization with dansyl chloride followed by analysis of ultra high-performance liquid chromatographic-tandem mass spectrometry (UHPLC-MS/MS) was established and validated for quantification of bakuchiol in rat plasma. The linearity of this approach was confirmed to be within the concentration range of 0.5-1000 ng/mL and the lower limit of quantification was at 0.5 ng/mL. The total analysis time was 1.5 min for each pretreated sample. Also, the precision, accuracy, stability, recovery and matrix effect of this method were proved to meet the requirements for bioanalysis. The intravenous and oral pharmacokinetic profiles of bakuchiol were obtained by utilizing this approach. The oral bioavailability of bakuchiol in rats (3.2%) was identified.