Adenosine accumulation causes metabolic disorders in testes and associates with lower testosterone level in obese mice

Overweight and obese men face numerous health problems, including type 2 diabetes, subfertility, and even infertility. However, few studies have focused on the effects of nutritional status and obesity‐related regulatory signals on fertility deficiency. Our previous observations have shown that the elevation of plasma 5'‐adenosine monophosphate (5'‐AMP) and the accumulation of adenosine in liver and muscle of obese diabetic db/db mice are related to insulin resistance. Here, we found that adenosine accumulation in testis is a common marker of both genetic obesity and high‐fat‐diet induced obese mice. An messenger RNA sequencing analysis indicated that 78 upregulated genes and 155 downregulated genes in the testis of 5'‐AMP‐treated mice overlapped with the same genes in the testis of ob/ob mice, and these genes belonged to the clusters of steroid metabolic process and regulation of hormone levels, respectively. Serum testosterone was reduced in ob/ob and 5'‐AMP‐treated mice. Metabolomic analysis based on ¹H nuclear magnetic resonance showed that the testicular metabolic profiles of ob/ob mice were similar to those of 5'‐AMP treated mice. Exogenous 5'‐AMP inhibited the phosphorylation of AKT and mammalian target of rapamycin signal transduction and reduced the proliferating cell nuclear antigen expressions in testes. Our results suggest that the accumulation of adenosine causes metabolic disorders in testes and associates lower testosterone level in obese mice.     

Potent and novel 11β-HSD1 inhibitors identified from shape and docking based virtual screening

Several potent and novel 11β-hydroxysteroid dehydrogenase 1 (11β-HSD1) inhibitors were discovered from in silico screening the commercially available Maybridge database. Among them, seven hit compounds showed good affinity, with IC(50) values lower than 100 nM and the best one 3.7 nM. To select the lead for further optimization, computational ADME/T prediction, the CYP3A4 inhibition and 11β-HSD1 over 11β-HSD2 selectivity test were also performed. Taking all of the above factors into consideration, two promising compounds were selected as lead structures for further development. The employed hierarchical virtual screening protocol not only demonstrates its efficiency, but also provides novel and selective compounds for developing 11β-HSD1 inhibitors to protect against metabolic syndrome.     

Network Intrusion Detection Based on a General Regression Neural Network Optimized by an Improved Artificial Immune Algorithm

To effectively and accurately detect and classify network intrusion data, this paper introduces a general regression neural network (GRNN) based on the artificial immune algorithm with elitist strategies (AIAE). The elitist archive and elitist crossover were combined with the artificial immune algorithm (AIA) to produce the AIAE-GRNN algorithm, with the aim of improving its adaptivity and accuracy. In this paper, the mean square errors (MSEs) were considered the affinity function. The AIAE was used to optimize the smooth factors of the GRNN; then, the optimal smooth factor was solved and substituted into the trained GRNN. Thus, the intrusive data were classified. The paper selected a GRNN that was separately optimized using a genetic algorithm (GA), particle swarm optimization (PSO), and fuzzy C-mean clustering (FCM) to enable a comparison of these approaches. As shown in the results, the AIAE-GRNN achieves a higher classification accuracy than PSO-GRNN, but the running time of AIAE-GRNN is long, which was proved first. FCM and GA-GRNN were eliminated because of their deficiencies in terms of accuracy and convergence. To improve the running speed, the paper adopted principal component analysis (PCA) to reduce the dimensions of the intrusive data. With the reduction in dimensionality, the PCA-AIAE-GRNN decreases in accuracy less and has better convergence than the PCA-PSO-GRNN, and the running speed of the PCA-AIAE-GRNN was relatively improved. The experimental results show that the AIAE-GRNN has a higher robustness and accuracy than the other algorithms considered and can thus be used to classify the intrusive data.     

Co-Circulation of the Rare CPV-2c with Unique Gln370Arg Substitution,New CPV-2b with Unique Thr440Ala Substitution,and New CPV-2a with High Prevalence and Variation in Heilongjiang Province,Northeast China

To trace evolution of canine parvovirus-2 (CPV-2), a total of 201 stool samples were collected from dogs with diarrhea in Heilongjiang province of northeast China from May 2014 to April 2015. The presence of CPV-2 in the samples was determined by PCR amplification of the VP2 gene (568 bp) of CPV-2. The results revealed that 95 samples (47.26%) were positive for CPV-2, and they showed 98.8%–100% nucleotide identity and 97.6%–100% amino acid identity. Of 95 CPV-2-positive samples, types new2a (Ser297Ala), new2b (Ser297Ala), and 2c accounted for 64.21%, 21.05%, and 14.74%, respectively. The positive rate of CPV-2 and the distribution of the new2a, new2b and 2c types exhibited differences among regions, seasons, and ages. Immunized dogs accounted for 48.42% of 95 CPV-2-positive samples. Coinfections with canine coronavirus, canine kobuvirus, and canine bocavirus were identified. Phylogenetic analysis revealed that the identified new2a, new2b, and CPV-2c strains in our study exhibited a close relationship with most of the CPV-2 strains from China; type new2a strains exhibited high variability, forming three subgroups; type new2b and CPV-2c strains formed one group with reference strains from China. Of 95 CPV-2 strains, Tyr324Ile and Thr440Ala substitutions accounted for 100% and 64.21%, respectively; all type new2b strains exhibited the Thr440Ala substitution, while the unique Gln370Arg substitution was found in all type 2c strains. Recombination analysis using entire VP2 gene indicated possible recombination events between the identified CPV-2 strains and reference strains from China. Our data revealed the co-circulation of new CPV-2a, new CPV-2b, and rare CPV-2c, as well as potential recombination events among Chinese CPV-2 strains.     

Biodegradation of 2,4,6-trinitrophenol (picric acid) in a biological aerated filter (BAF)

This study demonstrated the microbial purification of a model wastewater containing 2,4,6-trinitrophenol (TNP), which was carried out in a continuously working biological aerated filter (BAF). The main emphasis was on the operating performance of the reactor as a function of the pollution load. TNP was degraded at a maximum volumetric removal rate of 2.53 g TNP/L d, with low residual COD and TNP concentration. Overloading of TNP inhibited the nitrite-oxidizing activity, resulting in poor TNP degradation performance in the BAF system. The inhibition depended on some factors, such as influent concentrations and flow rates of the influent. It is assumed that nitrite-oxidizing occurred spontaneously during TNP degradation in the BAF system, could have significant influence on TNP wastewater treatment. One year after the reactor start-up, the dominance of Rhodococcus, which was initially inoculated in the reactor, was confirmed by analysis of 16S rDNA sequence of the PCR products separated by DGGE.     

Gangliosides activate the phosphatase activity of the erythrocyte plasma membrane Ca2+-ATPase

The previous studies showed that gangliosides modulated the ATPase activity of the PMCA from porcine brain synaptosomes [Yongfang Zhao, Xiaoxuan Fan, Fuyu Yang, Xujia Zhang, Arch. Biochem. Biophys. 427 (2004) 204-212]. The effects of gangliosides on the hydrolysis of p-nitrophenyl phosphate (pNPP) catalyzed by the erythrocyte plasma membrane Ca(2+)-ATPase, which was characterized as E(2) conformer of the enzyme, were studied. The results showed that pNPPase activity was stimulated up to seven-fold, depending upon the different gangliosides used with GD1b>GM1>GM2>GM3 approximately Asialo-GM1. Under the same conditions, the ATPase activity was also activated, suggesting that gangliosides should modify both E(1) and E(2) conformer of the enzyme. The Ca(2+), which drove the enzyme to E(1) conformation, inhibited the pNPPase activity, but with the similar half-maximal inhibitory concentrations (IC(50)) in the presence and the absence of gangliosides. Moreover, the pNPPase activity was also inhibited by the raise in ATP concentrations. Gangliosides caused a large increase in V(max), but had no effect on the apparent affinity (K(m)) of the enzyme for pNPP. The kinetic analysis indicated that gangliosides could modulate the erythrocyte PMCA through stabilizing E(2) conformer.     

A novel soluble beta-glucan salecan protects against acute alcohol-induced hepatotoxicity in mice

This investigation was designed to determine the effect of a novel soluble beta-glucan salecan on acute alcohol-induced hepatic injury in mice. Mice were given salecan (15 or 30 mg/kg) or PBS for 4 d. Ethanol (6 g/kg) was administered orally 1 h after the last injection. The animals were sacrificed at 10 h after alcohol administration. Pretreatment with salecan significantly ameliorated the hepatic damage induced by ethanol, as evidenced by markedly reduced serum aminotransferase activities and hepatocyte steatosis. Salecan administration remarkably alleviated the formation of thiobarbituric acid-reactive substances and counteracted glutathione depletion. The mRNA level of peroxisome proliferator activated receptor alpha, a major gene responsible for fatty acid oxidation, was significantly increased after salecan pretreatment. The expression of diacylglycerol acyltransferase 1, an important gene responsible for triacylglycerol synthesis, was markedly decreased after salecan was administrated. These findings suggest that salecan might represent a novel protective strategy against alcoholic liver injury.     

金针菇光受体隐花色素Ffcry基因的鉴定及其表达模式

光照对金针菇生长发育及形态建成有重要作用。光受体隐花色素(cryptochrome)是响应光信号的主要受体之一。本研究首先鉴定了黄色金针菇FL19隐花色素基因Ffcry的基因和蛋白结构,并对其启动子中的顺式作用元件进行预测,其中包含有3个光响应元件。进一步对Ffcry基因在不同光照条件下的表达模式进行了系统研究,结果显示Ffcry基因在蓝光下表达量显著高于黑暗以及其他波长的光照条件;蓝光强度则在光通量为10 μmol/(m²·s)时Ffcry表达量最高,且Ffcry在蓝光照射20 min后逐渐上调表达,在180 min后表达量趋于稳定。最后,检测金针菇子实体不同发育时期发现,Ffcry基因在幼菇期菌盖中表达量最高,其次是伸长期菌盖和成熟期菌盖。该研究为后续研究隐花色素的分子功能以及深入揭示金针菇的光形态建成奠定了基础。     

Effect of adding surfactant for transforming lignocellulose into fermentable sugars during biocatalysing

Fuel ethanol is one of the most important alternative fuels used as a substitute for fossil fuel. Lignocellulose is the most abundant biomass resource for the production of fuel ethanol. However, the hydrolysis of lignocellulose requires high enzyme loading. In order to strengthen the process of enzyme hydrolysis of lignocellulose, surfactant-polyethylene glycol (PEG) was applied to the catalysis of lignocellulose into fermentable sugars. The effect of PEG on both the enzymatic hydrolysis and adsorption of cellulose were investigated. The addition of surfactant obviously facilitated enzymatic hydrolysis. In particular, upon addition of PEG4000, the enzyme catalytic efficiency increased by 51.06%. Meanwhile, the adsorption quantity of cellulase decreased by 11.25%. In addition, the mechanism of the effect of PEG on enzymatic hydrolysis and cellulase adsorption is discussed.