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      • KCI등재

        A new model of flavonoids affinity towards P-glycoprotein: genetic algorithm-support vector machine with features selected by a modified particle swarm optimization algorithm

        Ying Cui,Qinggang Chen,Yaxiao Li,Ling Tang 대한약학회 2017 Archives of Pharmacal Research Vol.40 No.2

        Flavonoids exhibit a high affinity for the purifiedcytosolic NBD (C-terminal nucleotide-binding domain) ofP-glycoprotein (P-gp). To explore the affinity of flavonoidsfor P-gp, quantitative structure–activity relationship(QSAR) models were developed using support vectormachines (SVMs). A novel method coupling a modifiedparticle swarm optimization algorithm with randommutation strategy and a genetic algorithm coupled withSVM was proposed to simultaneously optimize the kernelparameters of SVM and determine the subset of optimizedfeatures for the first time. Using DRAGON descriptors torepresent compounds for QSAR, three subsets (training,prediction and external validation set) derived from thedataset were employed to investigate QSAR. Withexcluding of the outlier, the correlation coefficient (R2) ofthe whole training set (training and prediction) was 0.924,and the R2 of the external validation set was 0.941. Theroot-mean-square error (RMSE) of the whole training setwas 0.0588; the RMSE of the cross-validation of theexternal validation set was 0.0443. The mean Q2 value ofleave-many-out cross-validation was 0.824. With moreinformations from results of randomization analysis andapplicability domain, the proposed model is of good predictiveability, stability.

      • KCI등재

        Effects of Intravesical Electrical Stimulation on Urinary Adenosine Triphosphate and Nitric Oxide in Rats With Detrusor Underactivity Induced By Bilateral Pelvic Nerve Crush Injury: The Possible Underlying Mechanism

        Han Deng,Limin Liao,Xing Li,Qinggang Liu,Xuesheng Wang,Zhonghan Zhou 대한배뇨장애요실금학회 2022 International Neurourology Journal Vol.26 No.4

        Purpose: To explore the effect of intravesical electrical stimulation (IVES) on urinary adenosine triphosphate (ATP) and nitric oxide (NO) in rats with detrusor underactivity (DU) induced by bilateral pelvic nerve crush (bPNC), and to determine the underlying peripheral mechanism. Methods: Twenty-four female Sprague-Dawley rats were equally divided into 3 groups: sham; bPNC; and IVES. Rats in the IVES group began to receive IVES treatment 10 days after bPNC (20 minutes per day for 14 consecutive days). After the 14th IVES, rat urine was collected and cystometry was performed. The serum creatinine, blood urea nitrogen, and urinary ATP and NO levels were measured, and a routine urinalysis was performed. Results: The maximum cystometric capacity (MCC), maximum changes in bladder pressure during filling (∆FP), and postvoid residual urine (PVR) in the IVES group were significantly lower than the bPNC group, and the maximum changes in bladder pressure during voiding (∆VP) was significantly higher than the bPNC group. Compared with the sham group, the MCC, ∆FP and PVR were significantly increased, and the maximum voiding pressure (MVP) and ∆VP were significantly decreased in the bPNC group. After bPNC, urinary ATP was significantly decreased, and urinary NO was significantly increased. In IVES-treated rats, urinary ATP was significantly higher than the bPNC group, and NO was significantly lower than the bPNC group. In addition, the ATP-to-NO ratio of the rats in the bPNC group was significantly lower than the sham and IVES groups. Correlation analysis showed that the ATP and NO were not correlated with the MCC, ∆FP, MVP, ∆VP, and PVR. Conclusions: Promoting the release of urothelial ATP and inhibiting the release of urothelial NO may be one of the peripheral mechanisms underlying IVES in the treatment of DU. Specifically, IVES may shift the balance between excitation and inhibition toward excitation

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        Removal of Feedback Inhibition of Corynebacterium glutamicum Phosphoenolpyruvate Carboxylase by Addition of a Short Terminal Peptide

        Deyu Xu,Jing Zhao,Guoqiang Cao,Jinyu Wang,Qinggang Li,Ping Zheng,Shuxin Zhao,Jibin Sun 한국생물공학회 2018 Biotechnology and Bioprocess Engineering Vol.23 No.1

        Phosphoenolpyruvate carboxylase (PEPC) catalyzes the carboxylation of phosphoenolpyruvate (PEP) in the presence of bicarbonate to form oxaloacetate (OAA), and it plays an important role in high-efficient production of OAA-derived metabolites such as lysine, glutamate and succinate. However, PEPCs often suffered from serious feedback inhibition by various metabolic effectors like aspartate. Here, the feedback inhibition of PEPC from Corynebacterium glutamicum was removed by adding a short terminal peptide like His-tag. The effect of His-tag location on the structure and important properties such as activity, thermostability and feedback inhibition of PEPC has been investigated. The purified untagged PEPC, Nterminal His-tagged PEPC (PEPC-N-His) and C-terminal His-tagged PEPC (PEPC-C-His) were characterized. PEPCN- His (439.71/sec/mM) showed a 1.26 and 186-fold higher catalytic efficiency than untagged PEPC (348.59/sec/mM) and PEPC-C-His (2.36/sec/mM), respectively. Both PEPCN- His and untagged PEPC were significantly inhibited by aspartate at the concentrations above 4 mM (residual activities < 10%), while PEPC-C-His was almost desensitized to aspartate within 10 mM (around 90% of residual activity). Structural analysis showed that the extension of C-terminus may cause steric hindrance for aspartate binding with enzymes, leading to the deregulation of feedback inhibition of PEPC-C-His. This study provides a deeper understanding of the effect of terminal fragments on the structure and function of PEPCs, and helps to engineer the feedback inhibition of PEPCs and structurally similar enzymes.

      • KCI등재

        Identification of differentially expressed genes in longissimus dorsi muscle between Wei and Yorkshire pigs using RNA sequencing

        Jingen Xu,Chonglong Wang,Erhui Jin,Youfang Gu,Shenghe Li,Qinggang Li 한국유전학회 2018 Genes & Genomics Vol.40 No.4

        Intramuscular fat (IMF) content is an important trait closely related to meat quality, which is highly variable among pig breeds from diverse genetic backgrounds. High-throughput sequencing has become a powerful technique for analyzing the whole transcription profiles of organisms. In order to elucidate the molecular mechanism underlying porcine meat quality, we adopted RNA sequencing to detect transcriptome in the longissimus dorsi muscle of Wei pigs (a Chinese indigenous breed) and Yorkshire pigs (a Western lean-type breed) with different IMF content. For the Wei and Yorkshire pig libraries, over 57 and 64 million clean reads were generated by transcriptome sequencing, respectively. A total of 717 differentially expressed genes (DEGs) were identified in our study (false discovery rate < 0.05 and fold change > 2), with 323 up-regulated and 394 down-regulated genes in Wei pigs compared with Yorkshire pigs. Gene Ontology analysis showed that DEGs significantly related to skeletal muscle cell differentiation, phospholipid catabolic process, and extracellular matrix structural constituent. Pathway analysis revealed that DEGs were involved in fatty acid metabolism, steroid biosynthesis, glycerophospholipid metabolism, and protein digestion and absorption. Quantitative real time PCR confirmed the differential expression of 11 selected DEGs in both pig breeds. The results provide useful information to investigate the transcriptional profiling in skeletal muscle of different pig breeds with divergent phenotypes, and several DEGs can be taken as functional candidate genes related to lipid metabolism (ACSL1, FABP3, UCP3 and PDK4) and skeletal muscle development (ASB2, MSTN, ANKRD1 and ANKRD2).

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