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Kinases, a class of enzymes controlling various substrates phosphorylation, are pivotal in both physiological and pathological processes. Although their conserved ATP binding pockets pose challenges for achieving selectivity, this feature offers opportunities for drug repositioning of kinase inhibitors (KIs). This study presents a cost‐effective in silico prediction of KIs drug repositioning via analyzing cross‐docking results. We established the KIs database (278 unique KIs, 1834 bioactivity data points) and kinases database (357 kinase structures categorized by the DFG motif) for carrying out cross‐docking. Comparative analysis of the docking scores and reported experimental bioactivity revealed that the Atypical, TK, and TKL superfamilies are suitable for drug repositioning. Among these kinase superfamilies, Olverematinib, Lapatinib, and Abemaciclib displayed enzymatic activity in our focused AKT‐PI3K‐mTOR pathway with IC50 values of 3.3, 3.2 and 5.8 μM. Further cell assays showed IC50 values of 0.2, 1.2 and 0.6 μM in tumor cells. The consistent result between prediction and validation demonstrated that repositioning KIs via in silico method is feasible. [ABSTRACT FROM AUTHOR]

Studies of perceptual learning have revealed a great deal of plasticity in adult humans. In this study, we systematically investigated the effects and mechanisms of several forms (trial-by-trial, block, and session rewards) and levels (no, low, high, subliminal) of monetary reward on the rate, magnitude, and generalizability of perceptual learning. We found that high monetary reward can greatly promote the rate and boost the magnitude of learning and enhance performance in untrained spatial frequencies and eye without changing interocular, interlocation, and interdirection transfer indices. High reward per se made unique contributions to the enhanced learning through improved internal noise reduction. Furthermore, the effects of high reward on perceptual learning occurred in a range of perceptual tasks. The results may have major implications for the understanding of the nature of the learning rule in perceptual learning and for the use of reward to enhance perceptual learning in practical applications.

Species of the family Microdochiaceae (Xylariales, Sordariomycetes) have been reported from worldwide, and collected from different plant hosts. The proposed new genus and two new species, viz., Macroidriella gen. nov., M. bambusae sp. nov. and Microdochium australe sp. nov., are based on multi-locus phylogenies from a combined dataset of ITS rDNA, LSU, RPB2 and TUB2 with morphological characteristics. Microdochium sinense has been collected from diseased leaves of Phragmites australis and this is the first report of the fungus on this host plant. Simultaneously, we annotated 10,372 to 11,863 genes, identified 4,909 single-copy orthologous genes, and conducted phylogenomic analysis based on genomic data. A gene family analysis was performed and it will expand the understanding of the evolutionary history and biodiversity of the Microdochiaceae. The detailed descriptions and illustrations of species are provided. [ABSTRACT FROM AUTHOR]

The aim of the experiment was to investigate the regulatory effect of Chinese herbal extract (ZY) on lipopolysaccharide-induced mastitis in mice. A total of 72 Kunming female rats with SPF grade 3~5 d postpartum were selected, 12 were randomly selected as the blank control group (BC group), and the other 60 were randomly divided into five groups, namely the model group (M group), the positive control group (Dex group), the high dose (ZY-H group), the medium dose (ZY-M group) and the low dose (ZY-L group) of Chinese herbal extract, with 12 mice in each group. Mice in other groups except BC group were subjected to mastitis modeling after environmental adaptation. 2 h after the modeling was completed, mice in the ZY-H group, ZY-M group and ZY-L group were given 16, 8 and 4 mg/g Chinese herbal extract, respectively. Mice in the Dex group were injected with 5 mg/kg dexamethasone sodium phosphate injection peritoneally, and mice in the BC group and the M group were gavaged fed with normal saline of the same volume. After molding, it was treated continuously for 7 d. The results showed that the mammary gland acinar and acinar duct structures were destroyed and accompanied by inflammatory infiltration in the mammary gland tissue of mice in M group. Compared with the BC group, histopathological scores in the M group were extremely increased (P<0.01), the content of cytokines TNF-α, IL-1β, IL-6, IL-8 and MPO were extremely increased (P<0.01), and the content of PPAR-γ were extremely decreased (P<0.01). Compared with M group, the histopathological conditions of mammary gland in Dex group and ZY groups were recovered to a certain extent, the histopathological scores were extremely decreased (P<0.01), the content of TNF-α, IL-1β, IL-6, IL-8 and MPO were extremely decreased (P<0.01), and the content of PPAR-γ were extremely increased (P<0.01). The study indicates that each dose of Chinese herbal extract has a positive regulatory effect on LPS-induced mastitis in mice. [ABSTRACT FROM AUTHOR]

In coal mining industry, equipment safety and reliability during operation are essential in the production process. In recent years, along with the continuous improvement of intelligent coal mining equipment, reliable production requirements have simultaneously increased. Therefore, this article aims to study the maintenance decision making method that considers the safety inspection of a fully mechanized mining equipment group. The goal is to establish a maintenance decision making model that considers the safety overhaul of fully mechanized mining equipment group in order to minimize the total maintenance, production costs and safety risks. Firstly, the regular safety inspection procedure and the maintenance process were introduced. Then, a model guideline method that considers a fully mechanized mining equipment group's safety inspection was established. Finally, through the comparison of algorithms and maintenance strategies, it is proved that the maintenance decision optimization method proposed in this paper is of great significance for improving equipment reliability, improving comprehensive operation rate, reducing maintenance costs, and ensuring coal mine safety production.

The study was to investigate in vitro and in vivo antibacterial effect andantibacterial mechanism of selenide Glycyrrhiza polysaccharide (SeGUP) and Glycyrrhiza polysaccharide (GUP) combined with antibiotics against Proteus mirabilis (PM). In vitro and in vivo bacteriostatic effect of SeGUP and GUP were analyzed by drug susceptibility test, minimum inhibitory concentration (MIC), growth curve, in vitro synergy, and effect of SeGUP and GUP on mortality of PM-infected mice. Bacteriostasis mechanism was analyzed by studying changes of PM cell wall, cell membrane, biofilm and antioxidant enzyme activities. The results showed that compared with GUP, SeGUP at same concentration had a larger inhibitory circle and a smaller MIC, which inhibited the growth of PM more strongly. SeGUP combined with CI showed a synergistic effect, while GUP combined with CI showed a additive effect. SeGUP extremely reduced mortality of PMinfected mice (P<0.01). Compared with control group, SeGUP, GUP, CI could extremely increase the activity of alkaline phosphatase (AKP), β -galactosidase (β -gal) and protein content in culture medium (P<0.01), extremely reduced intracellular DNA concentration, inhibited biofilm formation, reduced activity of catalase (CAT) and superoxide dismutase (SOD) (P<0.01). The study indicates that in vitro and in vivo antibacterial effect of SeGUP and its antibacterial mechanism are better than that of GUP. [ABSTRACT FROM AUTHOR]