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Roscovitine is a cyclin-dependent kinase inhibitor, which has been previously investigated for its anticancer effects. It has also been confirmed that roscovitine can downregulate the expression of myeloid cell leukemia-1 protein to inhibit inflammation. In the present study, roscovitine was used to treat inflammation in lipopolysaccharide (LPS)-induced model mice. At the cellular level, Leydig cells isolated from mouse testis were assessed for inflammatory factors. It was revealed that roscovitine successfully reduced inflammation-associated injury induced by LPS pretreatment. At the molecular level, roscovitine was found to exert this effect through promotion of adenosine monophosphate-activated protein kinase phosphorylation. To the best of our knowledge, the present study was the first to suggest that roscovitine has a protective role in Leydig cells through its anti-inflammatory action. [ABSTRACT FROM AUTHOR]

Background: Liver metastasis is the leading cause of lethal colorectal cancer (CRC). For patients with early stage CRC, metachronous liver metastasis is the primary risk for poor prognosis. Accordingly, identification of prospective biomarkers for metachronous liver metastasis would be invaluable in evaluating patients' clinical outcomes and developing personal treatment therapy. Methods: Here we investigated the role of transducin (b)-like 1 X-linked receptor 1 (TBL1XR1) in predicting liver metastasis for early stage CRC. To accomplish this goal, a multi-center retrospective study was performed which included three stages: exploration stage (43 patients), identification stage (162 patients) and validation stage (38 patients). TBL1XR1 expression was evaluated using immunohistochemical staining and RT-qPCR. The prognostic significance of TBL1XR1 in both stage IV CRC patients and early stage CRC patients were evaluated by Kaplan-Meier survival analysis and multivariate analysis, respectively. Results: For stage IV CRC patients, TBL1XR1 expression was correlated with the number of liver metastases (P = 0.036), and high levels of TBL1XR1 in liver metastases indicated poor overall survival (P = 0.028). Moreover, high expressions of TBL1XR1 can serve as a predictor for liver metastasis in early stage CRC patients (P = 0.003). Conclusions: TBL1XR1 is a promising biomarker for predicting liver metastasis in early stage CRC patients. [ABSTRACT FROM AUTHOR]

In recent years, high-entropy alloys (HEAs) have attracted wide attention for their enormous hydrogen storage potential, fast hydrogen absorption kinetics, and a wide range of composition selectivity, and the fact that alloys with body-centered cubic (BCC) structure are considered to possess large capacity. Herein, three V30Nb10(TixCr1–x)60 HEAs with different Ti contents (Ti25, Ti30, Ti35) forming BCC structures were designed using the method of CALPHAD. The microstructure characteristics and the hydrogen storage performances, especially the kinetics of hydrogen desorption, were systematically investigated. The results show that after absorbing ~3.7 wt.% hydrogen at 300 K with 100 bar hydrogen pressure, the studied alloys exhibit similar hydrogen release behaviors at different temperatures. Taking the V30Nb10Ti25Cr35 alloy as an example, it was able to release 1.96 wt.%, 2.21 wt.%, and 2.48 wt.% of hydrogen at 353, 373, and 423 K, respectively. The higher the temperature, the faster the hydrogen desorption kinetics and the more hydrogen released. The hydrogen desorption kinetics of the alloys were successfully fitted with the Ginstling–Brounshtein model, and the main rate-controlling step was diffusion. In addition, the diffusion activation energy of hydrogen desorption decreases with the substitution of Cr content. The present study is expected to provide valuable information for the better development of high-entropy-based hydrogen storage alloys.

Enhancing the selectivity of catalytic processes has potential for substantially increasing the sustainability of chemical production. Herein, we establish relationships between reaction selectivity and molecular structure for a homologous series of key intermediates for oxidative coupling of alcohols on gold using a combination of experiment and theory. We establish a scale of binding for molecules with different alkyl structures and chain lengths and thereby demonstrate the critical nature of noncovalent van der Waals interactions in determining the selectivity by modulating the stability of key reaction intermediates bound to the surface. The binding hierarchy is the same for Au(111) and Au(110), which demonstrates a relative lack of sensitivity to the surface structure. The hierarchy of binding established in this work provides guiding principles for predicting how molecular structure affects the competition for binding sites more broadly. Besides the nature of the primary surface-molecule bonding, three additional factors that affect the stabilities of the reactive intermediates are clearly established: (1) the number of C atoms in the alkyl chain, (2) the presence of C-C bond unsaturation, and (3) the degree of branching of the alkyl group of the adsorbed molecules. We suggest that this is a fundamental principle that is generally applicable to a broad range of reactions on metal catalysts. [ABSTRACT FROM AUTHOR]

Matrix metalloproteinase-2 (MMP-2) is a member of the MMP family, which is associated with numerous types of cancer. Although it has been widely reported, the prognostic value of MMP-2 expression in prostate cancer (PCa) remains controversial. Thus, the present meta-analysis was conducted to investigate the association and prognostic value of MMP-2 expression in PCa. PubMed, Cochrane Library and the China National Knowledge Infrastructure databases were searched for all the published case-control studies on the association between MMP-2 expression and PCa until July 2015. The odd ratios (ORs) and 95% confidence intervals (CIs) were used to estimate the association of MMP-2 expression and PCa. ORs and 95% CIs were applied to clarify this association. Several subgroup analyses were also conducted according to different indexes in the case group. In total, 8 studies including 675 patients were included in the final meta-analysis. The results of the meta-analysis showed that MMP-2 expression in the PCa group was significantly higher than that in the benign prostatic hyperplasia (BPH) group (95% CI, 0.06-0.15; Z=10.48; P<0.00001). Furthermore, MMP-2 expression was significantly associated with Gleason Score (95% CI, 0.18-0.68; Z=3.09; P=0.002) and clinical stages (95% CI, 0.12-0.82; Z=2.36; P=0.02), and not significantly associated with Gleason score serum prostate specific antigen (95% CI, 0.30-1.66; Z=0.80; P=0.43). In conclusion, MMP-2 is overexpressed in PCa tissues compared with BPH. The expression of MMP-2 was significantly associated with the grade of PCa malignancy. [ABSTRACT FROM AUTHOR]

The resistance of the Al0.5Cr0.9FeNi2.5V0.2 high-entropy alloy (HEA) to hydrogen embrittlement (HE) was investigated by a slow strain rate test (SSRT), and the fracture surface was examined through a scanning electron microscope. Compared with other high-strength steels, Al0.5Cr0.9FeNi2.5V0.2 showed insignificant strength loss after hydrogen charging. The fracture surface of the hydrogen-charged specimens mainly consisted of dimples, and no intergranular morphology was observed. The coupling effect of the dispersed nano-structured precipitates and high-density dislocations in Al0.5Cr0.9FeNi2.5V0.2 improves the resistance to hydrogen-induced strength loss.

Preparing bulk WNiFe alloys with high strengths and low W content (

High entropy alloys usually emphasize equiatomic compositions, which restrict the compositions available to induce strengthening via precipitation. Here the authors use spinodal decomposition in a five-element alloy to obtain high content nanophases and the highest tensile strength reported to date.

The objective of this study was to purify cells in the Leydig cell lineage following regeneration after ethane dimethanesulfonate (EDS) treatment and compare their steroidogenic capacity. Regenerated progenitor (RPLCs), immature (RILCs), and adult Leydig cells (RALCs) were isolated from testes 21, 28 and 56 days after EDS treatment respectively. Production rates for androgens including androsterone and 5a-androstane-17β, 3α-diol (DIOL), testosterone and androstenedione were measured in RPLCs, RILCs and RALCs in media after 3-h in vitro culture with 100 ng/ml LH. Steady-state mRNA levels of steroidogenic enzymes and their activities were measured in freshly isolated cells. Compared to adult Leydig cells (ALCs) isolated from normal 90-day-old rat testes, which primarily produce testosterone (69.73%), RPLCs and RILCs primarily produced androsterone (70.21%) and DIOL (69.79%) respectively. Leydig cells isolated from testes 56 days post-EDS showed equivalent capacity of steroidogenesis to ALCs and primarily produced testosterone (72.90%). RPLCs had cholesterol side-chain cleavage enzyme, 3β-hydroxysteroid dehydrogenase 1 and 17α-hydroxylase but had almost no detectable 17β-hydroxysteroid dehydrogenase 3 and 11β-hydroxysteroid dehydrogenase 1 activities, while RILCs had increased 17β-hydroxysteroid dehydrogenase 3 and 11β-hydroxysteroid dehydrogenase 1 activities. Because RPLCs and RILCs had higher 5α-reductase 1 and 3α-hydroxysteroid dehydrogenase activities they produced mainly 5α-reduced androgens. Real-time PCR confirmed the similar trends for the expressions of these steroidogenic enzymes. In conclusion, the purified RPLCs, RILCs and RALCs are similar to those of their counterparts during rat pubertal development. [ABSTRACT FROM AUTHOR]

Polyacrylonitrile (PAN) nanofibers were prepared by electrospinning and they were modified with hydroxylamine to synthesize amidoxime polyacrylonitrile (AOPAN) chelating nanofibers, which were applied to adsorb copper and iron ions. The conversion of the nitrile group in PAN was calculated by the gravimetric method. The structure and surface morphology of the AOPAN nanofiber were characterized by a Fourier transform infrared spectrometer (FT-IR) and a scanning electron microscope (SEM), respectively. The adsorption abilities of Cu2+ and Fe3+ ions onto the AOPAN nanofiber mats were evaluated. FT-IR spectra showed nitrile groups in the PAN were partly converted into amidoxime groups. SEM examination demonstrated that there were no serious cracks or sign of degradation on the surface of the PAN nanofibers after chemical modification. The adsorption capacities of both copper and iron ions onto the AOPAN nanofiber mats were higher than those into the raw PAN nanofiber mats. The adsorption data of Cu2+ and Fe3+ ions fitted particularly well with the Langmuir isotherm. The maximal adsorption capacities of Cu2+ and Fe3+ ions were 215.18 and 221.37 mg/g, respectively. [ABSTRACT FROM AUTHOR]

Background: Reactive oxygen species play important roles in renal calcium crystallization. In this study, we examined the effects of catechin, which have been shown to have antioxidant properties on the renal calcium crystallization. Methods: In the vitro experiment, the changes of the mitochondrial membrane potential, expression of superoxide dismutase (SOD), 4-hydroxynonenal (4-HNE), cytochrome c, and cleaved caspase 3 were measured to show the effects of catechin treatment on the NRK-52E cells induced by calcium oxalate monohydrate (COM). In the vivo study, Sprague–Dawley rats were administered 1% ethylene glycol (EG) to generate a rat kidney stone model and then treated with catechin (2.5 and 10 mg/kg/day) for 14 days. The urine and serum variables were dected on 7 and 14 days after EG administration. The expression of cytochrome c, cleaved caspase 3, SOD, osteopontin (OPN), malondialdehyde (MDA), 8-hydroxy-2′-deoxyguanosine (8-OHdG) in kidney were measured. Furthermore, the mitochondrial microstructure in the kidney was also examined by transmission electron microscopy. Results: Catechin treatment could prevent the changes in mitochondrial membrane potential and expression of SOD, 4-HNE, cytochrome c, and cleaved caspase 3 in NRK-52E cells induced by the COM. For the in vivo experiments, the EG administration induced renal calcium crystallization was also prevented by the catechin. The expression of SOD, OPN, MDA, OPN and 8-OHdG, were increased after EG administration and this increase was diminished by catechin. Moreover, catechin also prevented EG induced mitochondrial collapse in rat. Conclusions: Catechin has preventive effects on renal calcium crystallization both in vivo and in vitro, and provide a potential therapeutic treatment for this disease. [ABSTRACT FROM AUTHOR]

Hypertension is a common complication in hemodialysis patients during erythropoietin (EPO) treatment. The underlying mechanisms of EPO-induced hypertension still remain to be determined. Increased transient receptor potential canonical (TRPC) channels have been associated with hypertension. Now, TRPC gene expression was investigated using quantitative real-time RT-PCR and immunoblotting in cultured human endothelial cells and in monocytes from hemodialysis patients. EPO dose-dependently increased TRPC5 mRNA in endothelial cells. EPO increased TRPC5 mRNA stability, that is, EPO prolonged the half-life period for TRPC5 mRNA from 16 hours (control) to 24 hours (P<0.05). The poly(A) tail length was measured by rapid amplification of cDNA ends-poly(A) test. Increased TRPC5 mRNA stability was attributed to longer 3' poly(A) tail lengths after EPO administration. EPO also significantly increased TRPC5 channel protein abundance by 70% (P<0.05). Whole-cell patch clamp showed that angiotensin II-induced, TRPC5-mediated currents were dramatically increased in endothelial cells treated with EPO. Fluorescent dye techniques confirmed that increased calcium influx after EPO treatment was abolished after TRPC5 knockdown (P<0.05). EPO also significantly increased intracellular reactive oxygen species production. Knockdown of TRPC5 alleviated EPO-induced reactive oxygen species generation in endothelial cells (P<0.05). In vivo, EPO-treated hemodialysis patients showed significantly increased amounts of TRPC5 mRNA in monocytes compared with EPO-free hemodialysis patients (6.0±2.4 [n=12] versus 1.0±0.5 [n=9]; P<0.01). Patients undergoing EPO treatment also showed significantly elevated systolic blood pressure (160±7 versus 139±6 mm Hg; P<0.05). Our findings suggest that upregulated functional TRPC5 gene may be one cause of EPO-induced hypertension in patients with chronic kidney disease. [ABSTRACT FROM AUTHOR]

This paper presents a novel class of self-organizing sensing agents that adaptively learn an anisotropic, spatio-temporal Gaussian process using noisy measurements and move in order to improve the quality of the estimated covariance function. This approach is based on a class of anisotropic covariance functions of Gaussian processes introduced to model a broad range of spatio-temporal physical phenomena. The covariance function is assumed to be unknown a priori. Hence, it is estimated by the maximum a posteriori probability (MAP) estimator. The prediction of the field of interest is then obtained based on the MAP estimate of the covariance function. An optimal sampling strategy is proposed to minimize the information-theoretic cost function of the Fisher Information Matrix. Simulation results demonstrate the effectiveness and the adaptability of the proposed scheme. [ABSTRACT FROM AUTHOR]

The prognostic value of serum cystatin-C (Cys-C) in renal cell carcinoma (RCC) remains unknown. The purpose of this study is to explore the prognostic value of Cys-C for RCC patients.The levels of preoperative Cys-C, creatinine (CRE) and estimated glomerular filtration rate (e-GFR) were retrospectively collected in 325 RCC patients undergoing surgery. The cutoff values of Cys-C, CRE and e-GFR were determined by the standardized Cutoff Finder algorithm. The receiver operating characteristic (ROC) curve and pairwise comparison were performed to compare the three variables. Univariate and multivariate Cox regression analyses were performed to investigate the prognostic value of serum Cys-C in RCC.Based on the analysis of Cutoff Finder algorithm, ROC curve and pairwise comparison, the preoperative Cys-C was superior to CRE and e-GFR as a predictive factor in RCC. Multivariate Cox regression analyses showed that high preoperative Cys-C (>1.09 mg/L) was significantly associated with shorter overall survival (OS) in all RCC patients (hazard ratio [HR], 1.59; P = 0.012), patients at pT1-2 (P

The effect of laser shock peening (LSP) on mechanical properties of Ti-based bulk metallic glass (BMG) was investigated under nanoindentation. Two regions were generated within the specimen after the LSP: (I) the extremely thick softened region (∼300 µm) in which amounts of shear bands and excess free volume were generated; (II) the middle region where the free volume increased but nearly no shear bands were induced. The hardness decreased with the increase of the indenter depth (h), exhibiting indentation size effect (ISE). The ISE increased with the increase of the measured distance away from the laser shocked tip, indicating that the ISE was inhibited by the shear bands and excess free volume was generated by the LSP.

Noisy condition is an important extrinsic degradation affecting speaker verification system performance. A feature-recovery approach is proposed to eliminate noise-dependent variability in feature space. A frame of the noisy feature vector is recovered using the information of itself and the neighbour feature vectors. Experiments are conducted on noisy test sets for text-dependent speaker verification tasks and the results indicate that the system can achieve significant performance improvement by using recovered feature vectors. [ABSTRACT FROM AUTHOR]

To realize the efficient transient simulation of a grid-connected power generation system based on multiple inverters, this paper proposes a hybrid simulation method integrating the models of electromagnetic transient and dynamic phasors. Based on a demonstration of the concepts and properties of dynamic phasors, the models of single-phase and three-phase inverters described by dynamic phasors are established first. Considering the numerical compatibility problem between dynamic phasors and instantaneous values, an interface scheme between dynamic phasors and instantaneous values is designed, and the efficiency and precision differences of various transformation methods are compared in detail. Finally, by utilizing MATLAB/Simulink, a hybrid simulation platform of a multi-inverter grid-connected system is built, and the efficiency and accuracy of the hybrid simulation are validated via comparison with the full electromagnetic transient simulation. [ABSTRACT FROM AUTHOR]

In order to meet the flexibility and efficiency requirement in convolutional neural network (CNN), an architecture of re-configurable CNN based on software definition was proposed. In the architecture, the process of CNN could be normalized and the operation mode could be accelerated. The calculation pipeline was implemented by using dual bus architecture based on AHB and AXI protocols. By software definition, the proposed architecture, which could realize the real-time processing of data among different CNN structure, was implemented on FPGA. The result shows that at least 2 CNN models can be software defined on the FPGA circuit. The output measures an operation processing capacity of 10 times that of CPU, and an operation energy consumption ratio of 2 times that of GPU.

Porcine reproductive and respiratory syndrome virus (PRRSV) is a devastating pathogen in the swine industry worldwide. miRNAs are reported to be involved in virus-host interaction. Here, we used high-throughput sequencing and miRNA inhibitors to screen possible miRNAs that can inhibit PRRSV infection on its target cell, porcine alveolar macrophages. We observed that miR-218 was downregulated upon virus infection, and knockdown of miR-218 significantly enhanced PRRSV replication. Overexpression of miR-218 resulted in a decrease in PRRSV replication, and this overexpression did not alter viral genomic RNA levels, but rather increased antiviral interferon signaling. Further analysis revealed that miR-218 regulated PRRSV replication by directly targeting porcine suppressor of cytokine signaling 3 (SOCS3), a JAK2 kinase inhibitor. Knockdown of the endogenous SOCS3 expression led to augmentation of type I interferon genes and resulted in decreased PRRSV replication, and vice versa. During PRRSV infection in vivo and in vitro, cellular miR-218 expression was downregulated and SOCS3 expression was upregulated, further supporting the inverse correlation between miR-218 and SOCS3 expression. The data on SOCS3 depletion in combination with miR-218 inhibition suggested that the antiviral activity of miR-218 required the SOCS3-mediated signaling pathway. Similarly, miR-218 negatively regulated PRRSV replication in Marc-145 cells, as well as the replication of porcine epidemic diarrhea virus and transmissible gastroenteritis virus in Vero and ST cells respectively. Taken together, these results demonstrate that PRRSV-induced miR-218 downregulation serves to inhibit the type I interferon response and may provide a novel therapeutic target for treatment of PRRSV and other viral infections. [ABSTRACT FROM AUTHOR]

Porcine epidemic diarrhea virus (PEDV), the causative agent of porcine epidemic diarrhea, has caused huge economic losses in pig-producing countries. Although PEDV was long believed to replicate in the intestinal epithelium by using aminopeptidase N as a receptor, the mechanisms of PEDV infection are not fully characterized. In this study, we found that PEDV infection of epithelial cells results in disruption of the tight junctional distribution of occludin to its intracellular location. Overexpression of occludin in target cells makes them more susceptible to PEDV infection, whereas ablation of occludin expression by use of small interfering RNA (siRNA) in target cells significantly reduces their susceptibility to virus infection. However, the results observed with occludin siRNA indicate that occludin is not required for virus attachment. We conclude that occludin plays an essential role in PEDV infection at the postbinding stages. Furthermore, we observed that macropinocytosis inhibitors blocked occludin internalization and virus entry, indicating that virus entry and occludin internalization are closely coupled. However, the macropinocytosis inhibitors could not impede virus replication once the virus had entered host cells. This suggests that occludin internalization by macropinocytosis or a macropinocytosis-like process is involved in the virus entry events. Immunofluorescence confocal microscopy showed that PEDV was trapped at cellular junctional regions upon macropinocytosis inhibitor treatment, indicating that occludin may serve as a scaffold in the vicinity of virus entry. Collectively, these data show that occludin plays an essential role in PEDV infection during late entry events. Our observation may provide novel insights into PEDV infection and related pathogenesis. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the clinical curative effect and safety of transurethral (bipolar) plasmakinetic resection of the prostate (PKRP) combined with thulium laser in the treatment of large prostates (> 80mL). Materials and Methods: From January 2014 to December 2015, 61 patients with benign prostate hyperplasia (BPH) were treated with PKRP combined with thulium laser (n = 25) or PKRP only (n = 36). We retrospectively analyzed the perioperative status of patients status during 3-month follow-up. Results: There was no significant difference between the two groups before treatment (P > .05). PKRP combined with thulium laser was significantly superior to PKRP in terms of surgical duration, intraoperative blood loss, postoperative bladder washing time, postoperative complications and time of hospital stay (P < .05). There were no significant improvements at international prostatic symptom score (IPSS), quality of life (QOL), maximum flow rate (Qmax), and post-void residual (PVR) urine between two groups after 3 months (P > .05). Conclusion: PKRP combined with thulium laser is superior than PKRP only for better surgical duration, less bleeding, higher efficiency and much quicker recovery. It may be a better choice for the treatment of BPH with large prostate (> 80mL). [ABSTRACT FROM AUTHOR]

Porcine epidemic diarrhea virus (PEDV) is a worldwide-distributed alphacoronavirus, but the pathogenesis of PEDV infection is not fully characterized. During virus infection, type I interferon (IFN) is a key mediator of innate antiviral responses. Most coronaviruses develop some strategy for at least partially circumventing the IFN response by limiting the production of IFN and by delaying the activation of the IFN response. However, the molecular mechanisms by which PEDV antagonizes the antiviral effects of interferon have not been fully characterized. Especially, how PEDV impacts IFN signaling components has yet to be elucidated. In this study, we observed that PEDV was relatively resistant to treatment with type I IFN. Western blot analysis showed that STAT1 expression was markedly reduced in PEDV-infected cells and that this reduction was not due to inhibition of STAT1 transcription. STAT1 downregulation was blocked by a proteasome inhibitor but not by an autophagy inhibitor, strongly implicating the ubiquitin-proteasome targeting degradation system. Since PEDV infection-induced STAT1 degradation was evident in cells pretreated with the general tyrosine kinase inhibitor, we conclude that STAT1 degradation is independent of the IFN signaling pathway. Furthermore, we report that PEDV-induced STAT1 degradation inhibits IFN-signal transduction pathways. Pharmacological inhibition of STAT1 degradation rescued the ability of the host to suppress virus replication. Collectively, these data show that PEDV is capable of subverting the type I interferon response by inducing STAT1 degradation. [ABSTRACT FROM AUTHOR]