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• EGCG inhibits early and terminal adipocyte differentiation via targeting MCE phase. • EGCG regulates cell cycle in sequential order at the MCE phase of adipogenesis. • EGCG inhibits MCE and terminal adipogenesis via STAT3 (Tyr705) inactivation. • HFD induces a signature change of cell cycle regulators in mouse adipose tissues. • EGCG inhibits adipogenesis and p-STAT3/cell cycle regulator expressions in vivo. Mitotic clonal expansion (MCE) is a prerequisite for preadipocyte differentiation and adipogenesis. Epigallocatechin gallate (EGCG) has been shown to inhibit preadipocyte differentiation. However, the exact molecular mechanisms are still elusive. This study investigated whether EGCG could inhibit adipogenesis and lipid accumulation by regulating the cell cycle in the MCE phase of adipogenesis and its underlying molecular mechanisms. 3T3-L1 preadipocytes were induced to differentiate by a differentiation cocktail (DMI) and were treated with EGCG (25–100 μM) for 9, 18, and 24 h to examine the effect on MCE, or eight days to examine the effect on terminal differentiation. C57BL/6 mice were fed a high-fat diet (HFD) for three months to induce obesity and were given EGCG (50 or 100 mg/kg) daily by gavage. We showed that EGCG significantly inhibited terminal adipogenesis and lipid accumulation in 3T3-L1 cells and decreased expressions of PPARγ, C/EBPα, and FASN. Notably, at the MCE phase, EGCG regulated the cell cycle in sequential order, induced G0/G1 arrest at 18 h, and inhibited the G2/M phase at 24 h upon DMI treatment. Meanwhile, EGCG regulated the expressions of cell cycle regulators (cyclin D1, cyclin E1, CDK4, CDK6, cyclin B1, cyclin B2, p16, and p27), and decreased C/EBPβ, PPARγ, and C/EBPα expressions at MCE. Mechanistic studies using STAT3 agonist Colivelin and antagonist C188–9 revealed that EGCG-induced cell cycle arrest in the MCE phase and terminal adipocyte differentiation was mediated by the inhibition of JAK2/STAT3 signaling cascades and STAT3 (Tyr705) nuclear translocation. Furthermore, EGCG significantly protected mice from HFD-induced obesity, reduced body weight and lipid accumulations in adipose tissues, reduced hyperlipidemia and leptin levels, and improved glucose intolerance and insulin sensitivity. Moreover, RNA sequencing (RNA-seq) analysis showed that the cell cycle changes in epididymal white adipose tissue (eWAT) were significantly enriched upon EGCG treatment. We further verified that EGCG treatment significantly reduced expressions of adipogenic factors, cell cycle regulators, and p-STAT3 in eWAT. EGCG inhibits MCE, resulting in the inhibition of early and terminal adipocyte differentiation and lipid accumulation, which were mediated by inhibiting p-STAT3 nucleus translocation and activation. [Display omitted] [ABSTRACT FROM AUTHOR]

The inhibitory and bactericidal activities of thyme oil against the foodborne multiple antibiotics-resistant Enterococcus faecalis biofilm were evaluated in this study. Gas chromatography-mass spectrometry revealed that more than 70% of the composition of thyme oil is thymol. Crystal violet staining assay showed that 128 and 256 mg/mL thyme oil significantly inhibited the biofilm formation of E. faecalis. The cell adherence of E. faecalis, as shown by its swimming and swarming motilities, was reduced by thyme oil. The exopolysaccharide (EPS) quantification assay showed that thyme oil inhibited the EPS synthesis in E. faecalis biofilms. The 3D-view observations through confocal laser scanning and scanning electron microscopy suggested that cell adherence and biofilm thickness were decreased in thyme oil-treated biofilms. Quantitative real-time analyses showed that the transcription of ebp and epa gene clusters, which were related to cell mobility and EPS production, was inhibited by thyme oil. Thus, thyme oil effectively inhibited the biofilm formation of E. faecalis by affecting cell adherence and EPS synthesis. Furthermore, 2,048 and 4,096 mg/mL thyme oil can effectively inactivate E. faecalis population in the mature E. faecalis biofilms by 5.75 and 7.20 log CFU/mL, respectively, after 30 min of treatment. Thus, thyme oil at different concentrations can be used as an effective antibiofilm or germicidal agent to control E. faecalis biofilms. [ABSTRACT FROM AUTHOR]

An introgression line RBPH660, derived from wild rice Oryza rufipogon , showed stable resistance to brown planthopper (BPH). Segregation analysis indicated BPH resistance of RBPH660 was controlled by multiple genes/QTLs. By using the bulked segregant analysis (BSA)-seq method, two genomic regions harboring QTLs resistance to BPH were identified from 1.20 to 16.70 Mb on chromosome 4 and from 10.20 to 12.60 Mb on chromosome 9 in RBPH660, respectively. A major resistance locus, designated as Bph35 accounting for 51.27% of the phenotypic variation with a LOD score of 42.51, was mapped to the candidate region of chromosome 4 between InDel (insertion-deletion) markers PSM16 and R4M13. For fine mapping of Bph35 , one simple sequence repeat and three newly developed InDel markers were used to screen the recombinants. Finally, the Bph35 locus was delimited in the region from 6.28 to 6.93 Mb and there were 18 predicted protein-encoding genes with a total of 114 non-synonymous single nucleotide polymorphism (SNP) variant sites between the resistant and susceptible parents. Out of these genes, Os04g0193950 , encoding a putative NB-ARC (nucleotide- binding adaptor shared by APAF-1, R proteins and CED-4) and LRR (leucine-rich repeat) domain protein with nine non-synonymous SNP substitutions in its coding sequence regions, might be the candidate gene for Bph35. These findings would facilitate the map-based cloning of the Bph35 gene and development of resistant varieties against BPH in rice. [ABSTRACT FROM AUTHOR]

This paper puts forward a kind of compound district heating method for* recycling waste heat of wasting water for building heat supply. The way is to the sewage treatment plant and the district heating plant in combination with heating operation, through the sewage source heat pump system for recycling the sewage heat energy for urban heating system returns water preheating. Research results show that compared with the other two heating methods, under the same heat loading, the sewage source heat pump combined type district heating method has the advantages of high energy consumption, low operation cost, distance from heating and good suitability. [ABSTRACT FROM AUTHOR]

• GLP attenuates CCl 4 -induced liver injury, inflammation, and fibrosis in mice. • GLP inhibits HSCs activation and collagen formation in vivo and in vitro. • GLP elicits dual effects on apoptosis in vivo (inhibit) and in vitro (promote). • GLP inhibits ECM-receptor interaction pathway including integrin expressions. • GLP alleviates liver fibrosis via suppressing the TGF-β/Smad signaling pathway. Ganoderma lucidum polysaccharide (GLP) has many biological properties, however, the anti-fibrosis effect of GLP is unknown at present. This study aimed to examine the anti-fibrogenic effect of GLP and its underlying molecular mechanisms in vivo and in vitro. Both CCl 4 -induced mouse and TGF-β1-induced HSC-T6 cellular models of fibrosis were established to examine the anti-fibrogenic effect of a water-soluble GLP (25 kDa) extracted from the sporoderm-removed spores of G. lucidum.. Serum markers of liver injury, histology and fibrosis of liver tissues, and collagen formation were examined using an automatic biochemical analyzer, H&E staining, Sirius red staining, immunohistochemistry, immunofluorescence, ELISA, Western blotting, and qRT-PCR. RNA-sequencing, enrichment pathway analysis, Western blotting, qRT-PCR, and flow cytometry were employed to identify the potential molecular targets and signaling pathways that are responsible for the anti-fibrotic effect of GLP. We showed that GLP (150 and 300 mg/kg) significantly inhibited hepatic fibrogenesis and inflammation in CCl 4 -treated mice as mediated by the TLR4/NF-κB/MyD88 signaling pathway. We further demonstrated that GLP significantly inhibited hepatic stellate cell (HSCs) activation in mice and in TGF-β1-induced HSC-T6 cells as manifested by reduced collagen I and a-SMA expressions. RNA-sequencing uncovered inflammation, apoptosis, cell cycle, ECM-receptor interaction, TLR4/NF-κB, and TGF-β/Smad signalings as major pathways suppressed by GLP administration. Further studies demonstrated that GLP elicits anti-fibrotic actions that are associated with a novel dual effect on apoptosis in vivo (inhibit) or in vitro (promote), suppression of cell cycle in vivo , induction of S phase arrest in vitro , and attenuation of ECM-receptor interaction-associated molecule expressions including integrins ITGA6 and ITGA8. Furthermore, GLP significantly inhibited the TGF-β/Smad signaling in mice, and reduced TGF-β1 or its agonist SRI-011381-induced Smad2 and Smad3 phosphorylations, but increased Samd7 expression in HSC-T6 cells. This study provides the first evidence that GLP could be a promising dietary strategy for treating liver fibrosis, which protects against liver fibrosis and HSC activation through targeting inflammation, apoptosis, cell cycle, and ECM-receptor interactions that are mediated by TGF-β/Smad signaling. [Display omitted] [ABSTRACT FROM AUTHOR]

This study evaluated the antibacterial effect of the combination of e-polylysine (e-PL) and nisin against Enterococcus faecalis strains. The combination of e-PL and nisin showed synergistic antibacterial activity against three Enterococcus strains. Scanning electron microscopy and a membrane permeability assay revealed that the combined treatment with e-PL and nisin synergistically damaged the cell morphology of E. faecalis strain R612Z1 cells. Both e-PL and nisin can dissipate the transmembrane electric potential of E. faecalis R612Z1 cells, but these peptides did not affect the transmembrane pH gradient. The combination of e-PL and nisin can produce a high reactive oxygen species level in E. faecalis R612Z1 cells. The results indicated that the uptake of e-PL into cells was promoted through nisin and that the combination of e-PL and nisin could produce a high reactive oxygen species level in E. faecalis R612Z1 cells, leading to cell growth inhibition. [ABSTRACT FROM AUTHOR]

The effect of NaCl stress (0 to 8%, wt/vol) on the growth and tyramine production in two Enterococcus faecalis strains was examined during culture time. The growth of E. faecalis was inhibited by the increase in NaCl concentration, but tyramine production was unaffected. Tyramine accumulated rapidly during the logarithmic phase of the strains, and the final tyramine levels were approximately 800 gg/ml. Relative gene expression of four genes in the tyrosine decarboxylase locus, namely, tyrRS, tyrDC, tyrP, and nhaC, was evaluated at different incubation times. The results showed that NaCl stress could upregulate the expression of tyrDC and tyrP to improve the tyramine production of a single E. faecalis strain under certain conditions, and TyrS could act as a negative regulator on the genetic regulation of the tyramine cluster. [ABSTRACT FROM AUTHOR]

Multiple phenolic compounds in the extract of Erigeron breviscapus synergistically contribute to the neurovascular protective effects. We conducted a phase I and pharmacokinetic study with the phenolic compound-enriched product extracted from Erigeron breviscapus, Erigerontis hydroxybenzenes injection (EHI), in healthy Chinese volunteers. A randomized, open-label, single-center, double-arm, dose-escalation study of EHI was conducted. The tolerability of intravenously EHI administrated in single- or multiple-dose (once daily for 7 days) was studied in 40 healthy Chinese volunteers and the pharmacokinetics of EHI was studied in additional 10 volunteers. The tolerated dose of intravenous infusion of EHI in healthy Chinese volunteers was 6 vials (equivalent to 90 mg bioactive phenolic compounds). The main limitations to dose escalation of EHI were transit changes in electrocardiogram and mild, transit increase in alanine aminotransferase. After intravenous administration of EHI, the average systemic clearance of multiple phenolic compounds of scutellarin, 1,3-dicaffeoylquinic acid, 3,5-dicaffeoylquinic acid, and 3,4-dicaffeoylquinic acid were 131, 29, 262, 112 L/h for male volunteers and 202, 28, 252, 117 L/h for female volunteers. The intervention of intravenous infusion of EHI in healthy Chinese volunteers was generally tolerated. The findings from this study provide data on the tolerability and pharmacokinetics of the extract from Erigeron breviscapus and support further trials. [ABSTRACT FROM AUTHOR]

Gastrointestinal probiotics are important members of intestinal microflora in both healthy animals and human beings, and these bacteria may reduce the risk of infection caused by certain opportunistic pathogens through exclusive inhibition, competition, and displacement. The lp_1643 protein on the cell surface of Lactobacillus plantarum WCFSI was assumed to possess a mucus-binding capability. This study aimed to determine if purified His-N2 protein exclusively inhibits pathogen adhesion to porcine mucus. The interaction of the His-N2 protein with porcine mucus was determined by indirect enzyme-linked immunosorbent assay (ELISA), and the adhesion was assessed by a traditional plating method to count the bacteria adhered to the porcine mucus. Indirect ELISA showed that His-N2 protein adhered to porcine mucus, and its interacting molecules existed. The His-N2 protein effectively inhibited the adhesion of Escherichia coli DH5α, Listeria monocytogenes CMCC54004, Salmonella Typhimurium ATCC 14028, and Shigella flexneri CMCC(B)51572 to porcine mucus. Results showed that inhibition of pathogen adhesion to porcine mucus depended on dose and strain. The adhesion of L. monocytogenes CMCC54004, Salmonella Typhimurium ATCC 14028, and S. flexneri CMCC(B)51572 was reduced by 95.7, 97.0, and 95.7%, respectively, by pre-adding 100 µl of 3.92 mg/ml of His-N2 protein, whereas that of E. coli DH5α was only 50.4%. The inhibition of adhesion of some pathogens by His-N2 was different at pH 6.6 and 7.5. The inhibition of E. coli DH5α, L. monocytogenes CMCC54004, and Salmonella Typhimurium ATCC 14028 at pH 6.6 was significantly higher than that at pH 7.5, whereas no statistically significant difference was observed in S. flexneri CMCC(B)51572. These results suggest that various types of inhibition mechanisms of His-N2 were involved in different pathogens. [ABSTRACT FROM AUTHOR]

This paper first analyzes the causality of the maintenance and support (M&S) cost's generation; then draws the stock and flow diagram, establishes the correlation equation of stock, flow, instrumental variables, constants and determines their initial value; on the basis of the model reasonable, analyzes the model's calculation results, observes the change of the model results by adjusting model's parameters to determine the optimal strategy, provides decision support for decision-makers. Emphatically analyzes the influence of parts’ failure rate and preventive maintenance rate on maintenance costs during the equipment's life circle. The analysis results have verified this paper's simulation method's practicality. [ABSTRACT FROM AUTHOR]

The hardness of grain boundaries with or without twinning boundaries have impact on mechanical behaviors of stainless steels. In this paper, Nanoindentation experiments were conducted by using a Triboindenter instrumented nanoindenter (Hysitron, USA), calibrated on pure aluminum and silica on the deformed stainless steel 904L and 316L, respectively. It can be seen that the hardness distributions are all random in those grains, no matter with or without twinning. Grain boundaries with twinning boundaries is higher than that without twinning boundaries for 904L SS, it should be the effect of twin boundaries existence. No obvious difference can be observed between the hardness distribution of 316L SS. The texture evolution of rolled 904L stainless steel which is austenitic phase were symmetrically at room temperature to different reductions, i.e., 0%, 20%, 40%, 60%and 80% were also researched, the result suggest a strong influence of the micromechanical incompatibility of the austenite phases on the texture evolution. [ABSTRACT FROM AUTHOR]

Tyramine production by Enterococcus faecalis R612Z1 in water-boiled salted ducks was evaluated during storage at different temperatures. The results showed that E. faecalis R612Z1 could produce tyramine in meat samples when the storage temperature was no less than 4°C. The E. faecalis R612Z1 counts of the meat samples reached 108 CFU/g on day 7 at 4°C and on day 4 at 10°C. However, the tyramine content of the meat samples stored at 10°C increased to 23.73 µg/g (on day 10), which was greater than the level in the samples stored at 4°C (7.56 µg/g). Reverse transcription quantitative PCR detection of the expression level of the tyrDC gene in E. faecalis R612Z1 in the meat samples revealed no significant changes at different storage temperatures. Thus, the changes in tyramine production of E. faecalis R612Z1 may be due to the different enzymatic activities at different storage temperatures. [ABSTRACT FROM AUTHOR]

Tyrosine decarboxylase (TDC) is responsible for tyramine production and can catalyze phenylalanine to produce β-phenylethylamine. Enterococcus strains are a group of bacteria predominantly producing tyramine and β-phenylethylamine in water-boiled salted duck. In this study, the heterologous expression and characterization of two TDCs from Enterococcusfaecalis R612Z1 (612TDC) and Enterococcus faecium R615Z1 (615TDC) were studied. The recombinant putative proteins of 612TDC and 615TDC were heterologously expressed in Escherichia coli. 612TDC is a 620-amino-acid protein with a molecular mass of 70.0 kDa, whereas 615TDC is a 625-amino-acid protein with a molecular mass of 70.3 kDa. Both 612TDC and 615TDC showed an optimum temperature of 25°C for the tyrosine and phenylalanine substrates. However, 612TDC revealed maximal activity at pH 5.5, whereas 615TDC revealed maximal activity at pH 6.0. Kinetic studies showed that 612TDC and 615TDC exhibited higher specificity for tyrosine than for phenylalanine. The catalysis abilities of both 612TDC and 615TDC for phenylalanine were restrained significantly with the increase in NaCl concentration, but this was not the case for tyrosine. This study revealed that the enzyme properties of the purified recombinant 612TDC and 615TDC were similar, although their amino acid sequences had 84% identity. [ABSTRACT FROM AUTHOR]

The TEAD (transcriptional enhancer activator domain) proteins share an evolutionarily conserved DNA-binding TEA domain, which binds to the MCAT cis-acting regulatory element. Previous studies have shown that TEAD proteins are involved in regulating the expression of smooth muscle α-actin. However, it remains undetermined whether TEAD proteins play a broader role in regulating expression of other genes in vascular smooth muscle cells. In this study, we show that the expression of TEAD1 is significantly induced during smooth muscle cell phenotypic modulation and negatively correlates with smooth muscle-specific gene expression. We further demonstrate that TEAD1 plays a novel role in suppressing expression of smooth muscle-specific genes, including smooth muscle α-actin, by abolishing the promyogenic function of myocardin, a key mediator of smooth muscle differentiation. Mechanistically, we found that TEAD1 competes with myocardin for binding to serum response factor (SRF), resulting in disruption of myocardin and SRF interactions and thereby attenuating expression of smooth muscle-specific genes. This study provides the first evidence demonstrating that TEAD1 is a novel general repressor of smooth muscle-specific gene expression through interfering with myocardin binding to SRF. [ABSTRACT FROM AUTHOR]

When platelets are strongly stimulated, a procoagulant platelet subpopulation is formed that is characterized by phosphati-dylserine (PS) exposure and epitope modulation of integrin αIIbβ3 or a loss of binding of activation-dependent antibodies. Mitochondrial permeability transition pore (mPTP) formation, which is essential for the formation of procoagulant platelets, is impaired in the absence of cyclophilin D (CypD). Here we investigate the mechanisms responsible for these procoagulant platelet-associated changes in integrin αIIbβ3 and the physiologic role of procoagulant platelet formation in the regulation of platelet aggregation. Among strongly stimulated adherent platelets, integrin αIIbβ3 epitope changes, mPTP formation, PS exposure, and platelet rounding were closely associated. Furthermore, platelet mPTP formation resulted in a decreased ability to recruit additional platelets. In the absence of CypD, integrin αIIbβ3 function was accentuated in both static and flow conditions, and, in vivo, a prothrombotic phenotype occurred in mice with a platelet- specific deficiency of CypD. CypD-dependent proteolytic events, including cleavage of the integrin β3 cytoplasmic domain, coincided closelywith integrin αIIbβ3 inactivation.Calpain inhibition blocked integrin3 cleavage and inactivation but not mPTP formation or PS exposure, indicating that integrin inactivation and PS exposure are mediated by distinct pathways subsequent to mPTP formation. mPTP-dependent alkalinization occurred in procoagulant platelets, suggesting a possible alternative mechanism for enhancement of calpain activity in procoagulant platelets. Together, these results indicate that, in strongly stimulated platelets, mPTP formation initiates the calpain-dependent cleavage of integrin β3 and associated regulatory proteins, resulting in integrin αIIbβ3 inactivation, and demonstrate a novel CypD-dependent negative feedback mechanism that limits platelet aggregation and thrombotic occlusion. [ABSTRACT FROM AUTHOR]

Abstract: The reaction between methyl-hydrazine and Tc(VII) in nitric acid in present of U(VI) was studied in this paper, the influence of acidity, methyl-hydrazine concentration, and temperature on the reaction was investigated meanwhile. Results showed that U(VI) can accelerate this reaction distinctly. When U(VI) concentration is 80g/l, Tc(VII) can be deoxidized in 1.5hours, on the contrary, the reaction will last 6hours if there is no U(VI) in the system. The behavior of technetium in the U/Pu splitting stage was investigated using a multistage mixer-setter. In this experiment about 90% Tc(VII) was deoxidized within 3 stages when contacting with the reducing regent and uranium. Finally nearly 99.9% of technetium went to plutonium stream. [Copyright &y& Elsevier]

The potential to produce biogenic amines was investigated with 15 Lactococcus lactis and 15 Enterococcusfaecalis strains isolated from water-boiled salted duck. The production of biogenic amines from the isolated strains grown in de Man Rogosa Sharpe broth containing precursor amino acids was determined by thin-layer chromatography and high-performance liquid chromatography. None of the L. lactis strains produced any biogenic amines, whereas 12 strains of E. faecalis produced tyramine and β-phenylethylamine. PCR assays were used to detect the presence of tyrosine decarboxylase genes in all of the isolated strains. Only the 12 biogenic amine-producing Enterococcus strains had a 924-bp fragment characteristic for the tyrosine decarboxylase gene. The comparison of the amplified partial tyrDC gene sequences of the 12 positive Enterococcus strains revealed 99% similarity within the same species. The tyramine production of the sterilized water-boiled salted duck inoculated with E. faecalis R612Z1 increased significantly during storage. This study reveals that the isolated E. faecalis strains can produce tyramine and β-phenylethylamine in the medium; however, they can only produce tyramine in water-boiled salted duck. [ABSTRACT FROM AUTHOR]

CtBP2 has been demonstrated to possess tumor-promoting capacities by virtue of up-regulating epithelial-mesenchymal transition (EMT) and down-regulating apoptosis in cancer cells. As a result, cellular CtBP2 levels are considered a key factor determining the outcome of oncogenic transformation. How pro-tumorigenic and anti-tumorigenic factors compete for fine-tuning CtBP2 levels is incompletely understood. Here we report that the cyclin H/cyclin-dependent kinase 7 (CCNH/CDK7) complex interacted with CtBP2 in vivo and in vitro. Depletion of either CCNH or CDK7 decreased CtBP2 protein levels by accelerating proteasome-dependent CtBP2 clearance. Further analysis revealed that CCNH/CDK7 competed with the tumor repressor HIPK2 for CtBP2 binding and consequently inhibited phosphorylation and dimerization of CtBP2. Phosphorylation-defective CtBP2 interacted more strongly with CCNH/CDK7 and was more resistant to degradation. Finally, overexpression of CtBP2 increased whereas depletion of CtBP2 dampened the invasive and migratory potential of breast cancer cells. CtBP2 promoted the invasion and migration of breast cancer cells in a CCNH-dependent manner. Taken together, our data have delineated a novel pathway that regulates CtBP2 stability, suggesting that targeting the CCNH/CDK7-CtBP2 axis may yield a viable anti-tumor strategy. [ABSTRACT FROM AUTHOR]

Abstract: In life sign detection, radar echo signal is very weak and hard to extract. For solve this problem, weak life signal de-noising based on wavelet transform is studied. Through the studies of wavelet threshold de-noising method, the use of it in weak life signal de-noising in strong noise background, and the verification of simulation by Matlab, the results shows that wavelet threshold de-noising method can remove the noise signal from weak life signal effectively and be an effective de-noising and extraction method for weak life signal. [Copyright &y& Elsevier]

Abstract: From the basic concept of Internet of Things and digital mine, the article described the theory and framework of using the Internet of Things technology constructing digital mines, aiming at explaining that as a new technology the Internet of Things will gradually be applied to mine production practice. Digital mine construction based on the Internet of Things technology has a very broad application prospect in coal mine data acquisition, remote monitoring, personnel management and safety production information and other fields. Not only can create a safe and comfortable working environment for ground and underground work personnel, and can greatly improve coal anti-disaster ability and production efficiency. [Copyright &y& Elsevier]

Abstract: Laboratory continuous flow-through riverbank filtration (RBF) models were developed to study the organic substances and ammonia nitrogen removal efficiency in the riverbank filtration process. The results indicated that the priority pollutants, organic substances and ammonia nitrogen, could be removed to a great extent. The results also indicate that the quality of the Huai River water is acceptable to operate the abstraction system with the riverbank filtration. [Copyright &y& Elsevier]

Abstract: Base on the previous study of organic substances and ammonia nitrogen removal efficiency through laboratory continuous flow-through riverbank filtration (RBF) models, field study were carried out to evaluate the results drawn from small model experiments. Five wells were selected to in this riverbank filtration process field study. The results indicated that the priority pollutants, organic substances and ammonia nitrogen, could be removed to a great extent. The results also indicate that the quality of the Huai River water is acceptable to operate the abstraction system with the riverbank filtration. [Copyright &y& Elsevier]

Abstract: The closed-closed-loop supply chain is a complex system with many uncertain factors, but it is certain that the gains of the participants in the system after the formation of a coalition are greater than the gains without cooperation. In the process of applying the cooperative game model to get an income allocation scheme which maintains a stable coalition, the researchers of this paper found that classical solutions to cooperative games - Shapley values suffer unreasonable high uncertainty. Therefore, this paper modifies the Shapley value method, and then uses the modified method to solve the allocation problem of the closed-loop supply chain under the third-party reclaim mode. The results show that the modified Shapley value has lower uncertainty. © 2011 Published by Elsevier Ltd. Selection and peer-review under responsibility of RIUDS [Copyright &y& Elsevier]

Abstract: The lack of accurate and efficient methods for target identification has been the bottleneck in drug discovery. In recent years, inverse docking has been applied as an efficient method in target identification, and several specific inverse docking strategies have been employed in academic and industrial researches. However, the effectiveness of these docking strategies in multiple targets identification is unclear. In this study, five inverse docking schemes were evaluated to find out the most effective approach in multiple targets identification. A target database containing a highly qualified dataset that is composed of 1714 entries from 1594 known drug targets covering 18 biochemical functions was collected as a testing pool for inverse docking. The inverse docking engines including GOLD, FlexX, Tarfisdock and two in-house target search schemes TarSearch-X and TarSearch-M were evaluated by eight multiple target systems in the dataset. The results show that TarSearch-X is the most effective method in multiple targets identification and validation among these five schemes, and the effectiveness of GOLD in multiple targets identification is also acceptable. Moreover, these two inverse docking strategies will also be helpful in predicting the undesirable effects of drugs, such as toxicity. [ABSTRACT FROM AUTHOR]

Transgenic mice that overexpress angiotensinogen, the sole precursor of angiotensins, in their renal proximal tubular cells develop hypertension, albuminuria, and tubular apoptosis. These pathological changes are due to enhanced generation of reactive oxygen species in the proximal tubule cells. Here, we determined whether overexpression of catalase to decrease oxidant injury in the proximal tubular cells could reverse these abnormalities. Double-transgenic mice specifically overexpressing angiotensinogen and catalase in their renal proximal tubular cells were created by cross-breeding the single transgenics. Non-transgenic littermates served as controls. Overexpression of catalase prevented hypertension, albuminuria, tubulointerstitial fibrosis, and tubular apoptosis in the angiotensinogen transgenic mice. Furthermore, the double transgenics had lower reactive oxygen species generation and reduced pro-fibrotic and apoptotic gene expression in the renal proximal tubular cells. Renal angiotensin converting enzyme-2 expression and urinary angiotensin 1–7 levels were downregulated in the single but normal in the double-transgenic mice. Thus, we suggest that the intrarenal renin-angiotensin system and reactive oxygen species generation have an important role in the development of hypertension and renal injury. [ABSTRACT FROM AUTHOR]

Angiotensin II stimulates the formation of reactive oxygen species by increased NADPH oxidase activity, which contributes to proapoptotic and profibrotic mechanisms critical in renal injury. Here we determine if apocynin, an inhibitor of NADPH oxidase, interferes with the action of the intrarenal renin–angiotensin system to minimize the progression of renal disease. Transgenic mice that overexpress rat angiotensinogen in their proximal tubule cells were given either apocynin, perindopril, or hydralazine while untreated or apocynin-treated non-transgenic littermates served as controls. Untreated transgenic mice had significant elevations of their systolic blood pressure, albuminuria, reactive oxygen species production, NADPH oxidase activity, tubular apoptosis, active caspase-3, Bax, transforming growth factor-β1, plasminogen activator inhibitor-1, extracellular matrix proteins, collagen type IV, and phosphorylated p47phox expression compared to untreated non-transgenic mice. Apocynin and perindopril blunted these changes; however, apocynin had no effect on the systolic blood pressure whereas hydralazine prevented hypertension and tubulointerstitial fibrosis but not proximal tubule cell apoptosis. Our study shows that the intrarenal renin–angiotensin system stimulates proximal tubule cell apoptosis and tubulointerstitial fibrosis, in part, by enhanced NADPH oxidase activity and reactive oxygen species generation independent of systemic hypertension.Kidney International (2009) 75, 156–166; doi:10.1038/ki.2008.509; published online 15 October 2008 [ABSTRACT FROM AUTHOR]

Accumulating evidence suggests that multiple complex mechanisms may be involved, simultaneously or complementarily, in the emergence and development of multidrug resistance (MDR) in various cancers. Cell adhesion-mediated MDR is one such mechanism. In the present study, we initially observed increased cell adhesion to extracellular matrix proteins by the MDR human breast tumor cell line MCF-7/MX compared to its parental cells. We then used a strategy that combined antibody-based screening technique and mass spectrometry-based proteomics to identify membrane proteins that contribute to the enhanced adhesion of MCF-7/MX cells. Using MCF-7/ MX cells as immunogen, we isolated a mouse monoclonal antibody, 9C6, that preferentially reacts with MCF-7/MX cells over the parental MCF-7 cells. The molecular target of 9C6 was identified as cytokeratin 8 (CK8), which was found to be overexpressed on the cell surface of MCF-7/MX cells. We further observed that down-regulation of cell surface levels of CK8 through siRNA transfection significantly inhibited MCF-7/MX cell adhesion to fibronectin and vitronectin. In addition, anti-CK8 siRNA partially reversed the MDR phenotype of MCF-7/MX cells. Taken together, our results suggest that alterations in the expression level and cellular localization of CK8 may play a significant role in enhancing the cellular adhesion of MDR MCF-7/MX cells. [ABSTRACT FROM AUTHOR]

The Insulin Receptor Substrate (IRS) proteins are key players in insulin signal transduction and are the best studied targets of the insulin receptor. Ser/Thr phosphorylation of IRS proteins negatively modulates insulin signaling; therefore, the identification of IRS kinases and their target Ser phosphorylation sites is of physiological importance. Here we show that in Fao rat hepatoma cells, the IκB kinase β (IKKβ) is an IRS-1 kinase activated by selected inducers of insulin resistance, including sphingomyelinase, ceramide, and free fatty acids. Moreover, IKKβ shares a repertoire of seven potential target sites on IRS-i with protein kinase C ζ (PKCζ), an IRS-1 kinase activated both by insulin and by inducers of insulin resistance. We further show that mutation of these seven sites (Ser-265, Ser-302, Ser-325, Ser-336, Ser-358, Ser-407, and Ser-408) confers protection from the action of IKKβ and PKCζ when they are overexpressed in Fao cells or primary hepatocytes. This enables the mutated IRS proteins to better propagate insulin signaling. These findings suggest that insulin-stimulated IRS kinases such as PKCζ overlap with IRS kinases triggered by inducers of insulin resistance, such as IKKβ, to phosphorylate IRS-1 on common Ser sites. [ABSTRACT FROM AUTHOR]

Obesity is a major risk factor for Syndrome X and type II diabetes (T2D). However, most antidiabetic drugs that are hypoglycemic also promote weight gain, thus alleviating one symptom of T2D while aggravating a major risk factor that leads to T2D. Adipogenesis, the differentiation and proliferation of adipocytes, is a major mechanism leading to weight gain and obesity. It is highly desirable to develop pharmaceuticals and treatments for T2D that reduce blood glucose levels without inducing adipogenesis in patients. Previously, we reported that an extract from Lagerstroemia speciosa L. (banaba) possessed activities that both stimulated glucose transport and inhibited adipocyte differentiation in 3T3-L1 cells. Using glucose uptake assays and Western/Northern blot analyses as major tools and 3T3-L1 cells as a model, we showed that the banaba extract (BE) with tannin removed was devoid of the 2 activities, and tannic acid (TA), a major component of tannins, had the same 2 activities as BE. Inhibitors known to abolish insulin-induced glucose transport also blocked TA-induced glucose transport. We further detected that TA induced phosphorylation of the insulin receptor (IR) and Akt, as well as translocation of glucose transporter 4 (GLUT 4), the protein factors involved in the signaling pathway of insulin-mediated glucose transport. We also demonstrated that TA inhibited the expression of key genes for adipogenesis. Differences between samples with or without TA in all of the quantitative assays were significant (P < 0.05). These results suggest that TA may be useful for the prevention and treatment of T2D and its associated obesity. TA may have the potential to become the lead compound in the development of new types of antidiabetic pharmaceuticals that are able to reduce blood glucose levels without increasing adiposity. [ABSTRACT FROM AUTHOR]

Histone deacetylase 4 (HDAC4) is a class II HDAC implicated in controlling gene expression important for diverse cellular functions, but little is known about how its expression and stability are regulated. We report here that this deacetylase is unusually unstable, with a half-life of less than 8 h. Consistent with the instability of HDAC4 protein, its mRNA was also highly unstable (with a half-life of less than 4 h). The degradation of HDAC4 could be accelerated by exposure of cells to ultraviolet irradiation. HDAC4 degradation was not dependent on proteasome or CRM1-mediated export activity but instead was caspase-dependent and was detectable in diverse human cancer lines. Of two potential caspase consensus motifs in HDAC4, both lying within a region containing proline-, glutamic acid-, serine-, and threonine-rich (PEST) sequences, we identified, by site-directed mutagenesis, Asp-289 as the prime cleavage site. Notably, this residue is not conserved among other class IIa members, HDAC5, -7, and -9. Finally, the induced expression of caspase-cleavable HDAC4 led to markedly increased apoptosis. These results therefore unexpectedly link the regulation of HDAC4 protein stability to caspases, enzymes that are important for controlling cell death and differentiation. [ABSTRACT FROM AUTHOR]

The Ski protein has been proposed to serve as a corepressor for Smad4 to maintain a transforming growth factor-β (TGF-β)-responsive promoter at a repressed, basal level. However, there have been no reports so far that it indeed acts on a natural promoter. We have previously cloned the human Smad7 promoter and shown that it contains the 8-base pair palindromic Smad-binding element (SBE) necessary for TGF-β induction. In this report, we have characterized the negative regulation of Smad7 promoter basal activity by Ski. We show that Ski inhibits the Smad7 promoter basal activity in a SBE-de- pendent manner. Mutation of the SBE abrogates the inhibitory effect of Ski on the Smad7 promoter. Moreover, mutation of the SBE increases the Smad7 promoter basal activity. Using the chromatin immunoprecipitation assay, we further show that Ski together with Smad4 binds to the endogenous Smad7 promoter. Finally, we show that RNAi knockdown of Ski increases Smad7 reporter gene activity in transient transfection assays as well as elevating the endogenous level of Smad7 mRNA. Taken together, our results provide the first evidence that Ski is indeed a corepressor for Smad4, which can inhibit a natural TGF-β responsive gene at the basal state. [ABSTRACT FROM AUTHOR]

Focuses on a study which examined the effects of extracts isolated from Lagerstroemia speciosa L., or banaba, on glucose transport and adipocyte differentiation in 3T3-L1 cells. Materials and methods; Results and discussion.

N-Methyl-D-aspartate type glutamate receptors (NMDARs) are key mediators of synaptic activity-regulated gene transcription in neurons, both during development and in the adult brain. Developmental differences in the glutamate receptor ionotropic NMDA 2 (GluN2) subunit composition of NMDARs determines whether they activate the transcription factor cAMP-responsive element-binding protein 1 (CREB). However, whether the developmentally regulated GluN3A subunit also modulates NMDAR-induced transcription is unknown. Here, using an array of techniques, including quantitative real-time PCR, immunostaining, reporter gene assays, RNA-Seq, and two-photon glutamate uncaging with calciumimaging, we show that knocking down GluN3A in rat hippocampal neurons promotes the inducible transcription of a subset of NMDAR-sensitive genes. We found that this enhancement is mediated by the accumulation of phosphorylated p38 mitogen-activated protein kinase in the nucleus, which drives the activation of the transcription factor myocyte enhancer factor 2C (MEF2C) and promotes the transcription of a subset of synaptic activity-induced genes, including brain-derived neurotrophic factor (Bdnf) and activity-regulated cytoskeleton-associated protein (Arc). Our evidence that GluN3A regulates MEF2C-dependent transcription reveals a novel mechanism by whichNMDAR subunit composition confers specificity to the program of synaptic activityregulated gene transcription in developing neurons. [ABSTRACT FROM AUTHOR]

During mammary development, the transdifferentiation of mammary preadipocytes is one of the important sources for lactating mammary epithelial cells (MECs). However, there is limited knowledge about the mechanisms of dynamic regulation of transcriptome and genome-wide DNA methylation in the preadipocyte transdifferentiation process. Here, to gain more insight into these mechanisms, preadipocytes were isolated from adipose tissues from around the goat mammary gland (GM-preadipocytes). The GM-preadipocytes were cultured on Matrigel in conditioned media made from goat MECs to induce GM-preadipocyte-to-MEC transdifferentiation. The transdifferentiated GM-preadipocytes showed high abundance of keratin 18, which is a marker protein of MECs, and formed mammary acinar-like structures after 8 days of induction. Then, we performed transcriptome and DNA methylome profiling of the GM-preadipocytes and transdifferentiated GM-preadipocytes, respectively, and the differentially expressed genes and differentially methylated genes that play underlying roles in the process of transdifferentiation were obtained. Sub-sequently, we identified the candidate transcription factors in regulating the GM-preadipocyte-to-MEC transdifferentiation by transcription factor-binding motif enrichment analysis of differentially expressed genes and differentially methylated genes. Meanwhile, the secretory proteome of GM-preadipocytes cultured in conditioned media was also detected. By integrating the transcriptome, DNA methylome, and proteome, three candidate genes, four proteins, and several epigenetic regulatory axes were further identified, which are involved in regulation of the cell cycle, cell polarity establishment, cell adhesion, cell reprogramming, and adipocyte plasticity. These findings provide novel insights into the molecular mechanism of preadipocyte transdifferentiation and mammary development. [ABSTRACT FROM AUTHOR]

Abstract: Superoxide dismutase (SOD) is an enzyme that removes free radicals from cells in many organisms. In order to further characterize these repair effects and their mechanism when subjected to radiation, Bacillus subtilis cells were exposed to gamma radiation and the cell survival rate, intracellular SOD activity, and DNA double-strand breakage were investigated. Vegetative cells of B. subtilis were irradiated by 60Co gamma radiation at varying doses and subsequently exposed to varying levels of exogenous SOD. Standard plate-count, xanthine oxidase, and pulsed-field gel electrophoresis (PFGE) methods were employed to investigate the repair effects. The results showed that the exogenous SOD could significantly improve cell survival rate and intracellular SOD activity after gamma radiation. The cell survival rate was elevated 30–87 times above levels observed in control samples. Adding exogenous SOD into gamma irradiated cells may dramatically increase intracellular SOD activity (p < 0.01), while percentage of DNA release (PR) values may decrease significantly when cells are treated with SOD. The repair effects were observed to vary with the gamma radiation dose and SOD concentration. These findings suggest that exogenous SOD may have the ability to repair vegetative B. subtilis cell damage after irradiated by gamma radiation. DNA strand scission may also be prevented by addition of SOD. This research contributes to better understanding of protection from the effects of free radicals and their mechanisms, an ongoing process in many organisms that involves the cellular response to gamma radiation, which occurs naturally in soil and water, as well as in unusual cases of high-dosage exposure. [Copyright &y& Elsevier]

ATP-binding cassette transporter A1 (ABCA1), which promotes cholesterol efflux from cells and inhibits inflammatory responses, is highly expressed in the kidney. Research has shown that exendin-4, a glucagon-like peptide-1 receptor (GLP-1R) agonist, promotes ABCA1 expression in multiple tissues and organs; however, the mechanisms underlying exendin-4 induction of ABCA1 expression in glomerular endothelial cells are not fully understood. In this study we investigated the effect of exendin-4 on ABCA1 in glomerular endothelial cells of diabetic kidney disease (DKD) and the possible mechanism. We observed a marked increase in glomerular lipid deposits in tissues of patients with DKD and diabetic apolipoprotein E knock-out (apoE-/-) mice by Oil Red O staining and biochemical analysis of cholesterol. We found significantly decreased ABCA1 expression in glomerular endothelial cells of diabetic apoE-/- mice and increased renal lipid, cholesterol, and inflammatory cytokine levels. Exendin-4 decreased renal cholesterol accumulation and inflammation and increased cholesterol efflux by up-regulating ABCA1. In human glomerular endothelial cells, GLP-1R-mediated signaling pathways (e.g. Ca2+/ calmodulin-dependent protein kinase, cAMP/PKA, PI3K/AKT, and ERK1/2) were involved in cholesterol efflux and inflammatory responses by regulating ABCA1 expression. We propose that exendin-4 increases ABCA1 expression in glomerular endothelial cells, which plays an important role in alleviating renal lipid accumulation, inflammation, and proteinuria in mice with type 2 diabetes. [ABSTRACT FROM AUTHOR]

Interleukin-17 (IL-17)-secreting T helper 17 cells were recently identified as a CD4+ T helper subset and implicated in various inflammatory and autoimmune diseases. The issues of whether and by what mechanism hyperlipidemic stress induces IL-17A to activate aortic endothelial cells (ECs) and enhance monocyte adhesion remained largely unknown. Using biochemical, immunological, microarray, experimental data mining analysis, and pathological approaches focused on primary human and mouse aortic ECs (HAECs and MAECs) and our newly generated apolipoprotein E (ApoE)-/-/IL-17A-/- mice, we report the following new findings. 1) The hyperlipidemia stimulus oxidized low density lipoprotein up-regulated IL-17 receptor(s) in HAECs and MAECs. 2) IL-17A activated HAECs and increased human monocyte adhesion in vitro. 3) A deficiency of IL-17A reduced leukocyte adhesion to endothelium in vivo. 3) IL-17A activated HAECs and MAECs via up-regulation of proinflammatory cytokines IL-6, granulocyte-macrophage colony-stimulating factor (GM-CSF), chemokine CXC motif ligand 1 (CXCL1), and CXCL2. 4) IL-17A activated ECs specifically via the p38 mitogen-activated protein kinases (MAPK) pathway; the inhibition of p38MAPKin ECs attenuated IL-17Amediated activation by ameliorating the expression of the aforementioned proinflammatory cytokines, chemokines, and EC adhesion molecules including intercellular adhesion molecule 1. Taken together, our results demonstrate for the first time that IL-17A activates aortic ECs specifically via p38 MAPK pathway. [ABSTRACT FROM AUTHOR]

The polysaccharide carrageenan is used as a natural precursor to prepare micro-mesoporous carbon spheres. The carbon spheres were synthesized by hydrothermal carbonization of carrageenan, and subsequent chemical activation by KOH at different temperatures. The obtained micro-mesoporous carbon spheres have high surface area (up to 2502 m² g-1) and large pore volume (up to 1.43 cm³ g-1). Moreover, the micro- and mesoporosity can be finely tuned be modifying the activation temperatures in the range of 700-900 °C. The carbon spheres activated at 900 °C present high specific capacitance of 230 F g-1 at a current density of 1 A g-1 and good ion transport kinetics. The good capacitive performance can be ascribed to the high specific surface area, well-controlled micro- and mesoporosity and narrow pore size distribution. [ABSTRACT FROM AUTHOR]

This paper studies the behavior and capacity of stainless steel lipped C-section stub columns under axial compression. A total of 10 tests were conducted on stub columns to investigate the failure mechanism and mode, the load–displacement curves, the section strain variation and the capacity. A comparison of the test results with code predictions indicates that the design strengths are lower than the experimental strengths and that the deviation between the test and predicted results decreases as the section plate slenderness coefficient increases. A finite element model is built to conduct parametric studies on the influential factors of member strength. Finally, based on the finite element analysis of 98 stub column specimens, a direct strength equation for stainless steel lipped C-section stub columns is proposed. [ABSTRACT FROM AUTHOR]