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The hot deformation and dynamic recrystallization (DRX) behaviors of 7055 aluminum alloy were studied at temperatures of 390−470 °C and strain rates of 0.01−1 s−1. A low DRX fraction between 1% and 13% was observed by using EBSD technique. A modified JMAK-type DRX model was proposed for such low DRX fraction problems. The model was used together with commercial FEM software DEFORM-3D to simulate the hot compression of 7055 aluminum alloy. There was a good agreement between experimental and predicted DRX fractions and grain size with an average absolute relative error (AARE) of 13.7% and 6.3%, respectively. In order to further verify the validity of the proposed model, the model was also used to simulate DRX in industrial hot rolling of 7055 aluminum alloys. The results showed that the distribution of DRX fraction was inhomogeneous, and agreed with experimental observations.

The aim of this work was to analyze the recrystallization behavior of cold rolled Aluminum/graphene composites during annealing. The Aluminum/graphene composite was cold rolled firstly, and then annealed at different temperature (250°C, 300°C, 350°C, 400°C) and for various time (1 h, 2 h, 8 h, 32 h). Full recrystallization did not occur until the annealing temperature was above 300 °C. With annealing temperature increasing from 250 to 300°C, the hardness of the composites decreased from 49.6 to 27.6 HV. Grain growth were not observed at high annealing temperature and longer annealing time, which suggested that Graphene has strong pinning effect on the grain boundary of Aluminum.

In this work, Al-Fe-(Cu) alloys for aluminum cables were designed and the related annealing behaviors were discussed in detail to help understand the influence of processing and heat treatment on the electrical conductivity and mechanical properties of the studied alloys. The interaction between different solute elements was tracked by using hardness and electrical conductivity testing. The microstructure was investigated by using Electron Backscattered Diffraction (EBSD) technique, along with Scanning Electron Microscopy with Backscattered Electron Detector (BSE). The results show that the conductivities of Al-Fe-Cu alloy increased with the elongated annealing time, and reaches its maximum at 6 h, when annealed at temperatures from 275 °C to 375 °C. The addition of Fe to Al can strengthen the alloy and decrease its conductivity slightly, while the addition of Cu will influence the alloy conductivity significantly. The morphologies of precipitates will change with different amount of alloying elements as well.

Urban lakes are important natural assets but are exposed to multiple stressors from human activities. Submersed macrophytes, a key plant group that helps to maintain clear-water conditions in lakes, tend to be scarce in urban lakes, particularly when they are eutrophic or hypertrophic, and their loss is linked, in part, to impaired underwater light climate. We tested if enhancing the underwater light conditions using light-emitting diodes (LEDs) could restore submersed macrophytes in urban lakes. Twelve mesocosms (1000 L each) were each planted with tape grass (Vallisneria natans) and monitored over three months (22 August–7 November), using a control and three artificial light intensity treatments (10, 50, and 100 µmol m -2 s -1). Compared with the control, the high light treatment (100 µmol m -2 s -1) had higher leaf number, maximum leaf length, and average leaf length (3.9, 5.8, and 2.8 times, respectively). Shoot number, leaf number, leaf dry mass, root dry mass, and photosynthetic photon flux density in the high-light treatment were significantly greater than the control, but root length and phytoplankton chlorophyll a were not related to plant growth variables and were low in all treatments. Periphyton chlorophyll a increased significantly with the plant growth variables (i.e., shoot number, leaf number, and maximum leaf length) and was high in the light treatments but did not hamper the growth of the macrophytes. These results indicate that LED light supplementation enables the growth of V. natans under eutrophic conditions, at least in the absence of fish as in our experiment, and that the method may have potential as a restoration method in urban lakes. Lake-scale studies are needed, however, to fully evaluate LED light supplementation under natural conditions where other stressors (e.g., fish grazing) may need to be controlled for successful restoration of urban lakes.

// Xiao-Dong Wu 1, * , Ting Guo 4, * , Li Liu 5, * , Chao Wang 5 , Kun Zhang 1, 6 , Han-Qiang Liu 4 , Feng Wang 4 , Wen-Dong Bai 7 and Meng-Yao Zhang 1, 2, 3 1 Department of Cell Biology, National Translational Science Center for Molecular Medicine, Fourth Military Medical University, Xi’an 710032, China 2 Beijing Institute of Biotechnology, Beijing 100071, China 3 Department of Clinical Immunology, Xijing Hospital, Fourth Military Medical University, Xi’an 710032, China 4 Department of Nutrition and Food Hygiene, Fourth Military Medical University, Xi’an 710032, China 5 Department of Stomatology, PLA General Hospital, Beijing 100700, China 6 College of Life Science and Bioengineering, School of Science, Beijing Jiaotong University, Beijing 100044, China 7 Clinical Laboratory Medicine Center, Xinjiang Command General Hospital of PLA, Urumqi 830000, China * These authors have contributed equally to this work Correspondence to: Meng-Yao Zhang, email: dudybaby@126.com Wen-Dong Bai, email: bwddcgzl@163.com Feng Wang, email: wfeng@fmmu.edu.cn Keywords: angiogenesis, ginsenoside Rg1, miR-23a, runt-related transcription factor 2, vascular endothelial growth factor Received: May 01, 2017 Accepted: June 19, 2017 Published: July 22, 2017 ABSTRACT Rg1 is a predominant protopanaxatriol-type of ginsenoside found in Panax ginseng, and it has been shown to have anti-cancer effects in multiple types of cancer cells. However, Rg1 also induces the expression of proangiogenic factors, such as vascular endothelial growth factor (VEGF-A), in endothelial cells. Unfortunately, angiogenesis positively correlates with cancer development. In this study, we identified RUNX2 as a regulator of ginsenoside Rg1-induced angiogenesis for the first time. We found that RUNX2 was directly targeted and regulated by miR-23a. Additionally, miR-23a was shown to inhibit angiogenesis in both human umbilical vein endothelial cells (HUVECs) and in zebrafish. Furthermore, a decrease in RUNX2 expression resulted in translational repression of VEGF-A in HUVECs. Taken together, this study identified a MiR-23a/RUNX2/VEGF-A pathway in angiogenesis and shed light on the molecular mechanism of Rg1-induced angiogenesis. Thus, RUNX2 might be a potential therapeutic target in Rg1-mediated angiogenesis in cancer.

Heliciopsis lobata is a medicinal plant, which is exclusively used to treat tumor in Li folk region. Two new arbutin derivatives, 6'-((E)2-methoxy-5-hydroxycinnamoyl) arbutin (1) and 2'-((E)2, 5-dihydroxycinnamoyl) arbutin (2) along with five known compounds (3-7), were isolated from the leaves of Heliciopsis lobata. Their structures were elucidated on the basis of extensive spectroscopic interpretations. They were evaluated for their potential anticancer activity. Compounds 6 and 7 exhibited cytotoxicity against MGC-803 cells with IC50 values being 44.1 and 11.3 μg·mL-1, respectively. Additionally, compounds 1, 2 and 5-7 exhibited a moderate inhibition of MGC-803 cells invasion; compound 2 at 20 μg·mL-1 inhibited the invasion of MGC-803 cells by 43.0%, compared with the controls.

Atherosclerotic lesions create obvious vascular stenosis due to the presence of plaque, and a large number of inflammatory macrophages are enriched in the thrombus. In this study, we develop a composite hydrogel drug delivery system that is capable of both mechanically-sensitive drug release and of targeting inflammatory macrophages at the thrombus. The hydrogel is a high molecular weight hyaluronic acid (HA) modified with glycidyl methacrylate as a hydrogel precursor; a cross-linkable block copolymer (CBC) is used as the drug coating material and a microscopic cross-linking agent. The difference in drug release rate of the composite hydrogel (HACBC) in simulated blood vessels with 0 % and 75 % occlusion was as high as 49.3 %. Under long-term cycling conditions in stenotic vessels, dynamic shear rheometry revealed that the HACBC still maintained the hydrogel properties. However, the micelles were deformed and recombined to produce smaller sized micelles. An in vitro cell culture demonstrated precise targeting of the HACBC to inflammatory macrophages, and our rabbit experiments with simvastatin-coated HACBC confirmed the effective release of simvastatin in the plaque of the drug carrier. Moreover, we demonstrated the precise targeting of HACBC in vivo in apoE-/- mice by using HACBC coated with cy7. The mechanical stress-sensitive and CD44 receptor-targeted dual-response drug delivery system prepared by micellar composite hydrogel is the first application in the field of atherosclerosis, which provides a new method for diagnosing and treating atherosclerosis.

Apoptosis of cartilage endplate (CEP) chondrocytes is associated with the pathogenesis of intervertebral disk degeneration (IDD). Recent studies have shown that miR-34a is crucially involved in chondrocyte apoptosis during osteoarthritic cartilage. Here, we investigated the involvement of miR-34a in CEP chondrocyte apoptosis in IDD. In human degenerated CEP chondrocytes, miRNA (miR)-34a was markedly elevated in association with increased apoptosis. Bioinformatics target prediction identified Bcl-2 as a putative target of miR-34a. Furthermore, miR-34a inhibited Bcl-2 expression by directly targeting their 3'-untranslated regions, and this inhibition was abolished by mutation of the miR-34a binding sites. In vitro, knockdown of miR-34a in human endplate chondrocytes resulted in overexpression of Bcl-2, whereas upregulation of miR-34a led to repression of Bcl-2. Fas-mediated apoptosis was decreased when antagonizing miR-34a with locked nucleotide analog-miR-34a in human endplate chondrocytes. Taken together, our results demonstrate that upregulated miR-34a potentiates Fas-mediated endplate chondrocyte apoptosis, which is associated with IDD.

Based on the thermodynamic calculation, the conditions of calcium treatment to sulfur gear steel are analyzed and the samples of rolled steel are studied. Results show that Calcium treatment to melting steel after RH refining can make the sulfide inclusions and calcium aluminates bind together and form the spindle shaped low melting compound inclusions. In the meanwhile, controlling of w (O) in steel below 0.0012% before calcium treatment is more beneficial to modify the Al2O3 and sulfide by the added calcium and to form the oxide-sulfide compound inclusions only if w (AlS) in steel is adjusted to 0.015%~0.025% before continuous casting. The Ca wire should also be fed at higher temperature.

The inclusions in ultra-low oxygen spring steel during process were studied. Sufficient aluminium was used during tapping. The refining slag has high basicity and strong reducibility. The total oxygen is only 10×10-6 in billet and the oxide inclusions in the steel have finished the transformation during refining and some complex oxide inclusions are easy to remove at steelmaking temperature. Residual oxide inclusions in the steel are CaO-MgO-Al2O3 complex inclusions with a relatively lower melting point, which have a little deform-ability during hot-working and can improve the fatigue properties of high speed wheel steel effectively.

Inhibition of angiogenesis can attenuate tumor growth. Hence, mathematical modeling of tumor-induced angiogenesis can be a tool for predicting outcome of angiogenesis inhibitors. We have generated a two-dimensional cornea model of angiogenesis and have tested the effectiveness of the inhibitor through testing representative examples. The effects of thrombospondin and the way it interacts in the cornea with the endothelial cells and tumor angiogenic factors were examined. We were then able to define the inhibitor's role specific to our benchmark model. Finally, a thorough sensitivity analysis was performed to verify baseline values and determine the precise effects of the different parameters. Our findings can be used to design strategies involving manufacturing inhibitors to regulate the angiogenesis process.

At present the concept of instantaneous equilibrium is often adopted for simulating the wellbore pressure and temperature distribution in heavy oil wells. In this paper, the mathematical model was built and the diffusion of gas in the oil phase was researched. It proves that the non-equilibrium phenomenon is not obvious in convenient oil wells and it could be overlooked, while in heavy oil wells the non-equilibrium phenomenon is too prominent to be overlooked. Basing on the mass conservation principle, the momentum conservation principle and the energy conservation principle, the calculated model for wellbore pressure and temperature in heavy oil wells considering of the non-equilibrium effect was established. One example shows that the model can accurately reflect the flowing laws in heavy oil wells, which has a relative value for engineering.

Objectives Intervertebral disc (IVD) related diseases and age-related IVD degeneration are responsible for significant morbidity. Inflammatory mediators and pro-inflammatory cytokines, including interleukin (IL)-17, show elevated expression in degenerated disc tissue. IL-17 is reported to transduce signals across the cell membrane predominantly via the Janus kinase/signal transducer and activator of transcription (JAK/STAT) signal transduction pathway, leading to transcriptional activation of target genes. Methods In this study, we investigated whether the JAK/STAT pathway plays a role in IL-17-mediated signaling in the nucleus pulposus (NP) cells of IVDs. Vascular endothelial growth factor (VEGF) and IL-17 were found to be highly expressed in human degenerated NP tissue. In isolated rat NP cells, IL-17-induced VEGF expression in a time- and dose-dependent manner. Rat NP cells were co-transfected with VEGF promoter plasmid along with constitutively active STAT1, STAT3 or JAK2 plasmid. VEGF promoter activity was found to be increased by STAT1, STAT3 and JAK2 in IL-17-treated cells. Transfection of cultured rat NP cells with STAT1 or STAT3 lentiviral short hairpin RNAs or treatment with the JAK2 inhibitor AG490 significantly reduced IL-17-stimulated VEGF expression. Conclusions IL-17 upregulated VEGF expression in rat NP cells mediated by the JAK/STAT pathway, and elevated levels of IL-17 and VEGF are present in human degenerated NP tissue. These findings provide new insight into the pathology of IVD degeneration.

Some of the heavy oil reservoirs show high primary recovery and high flow rate under solution gas drive. The foamy oil theory has been proposed for the anomalous behavior. There have been numerous studies of diffusion-induced growth or collapse of bubbles in a fluid. However, there are some limits about them such as the determination of initial bubbles radius. Pointed to the problem that how to determine the initial bubble radius, this article proposes a new method base on the hydrodynamic equation, and then regards the bubble as a production well with source and sink theory based on the similarity between the bubbles concentration distribution and the pressure distribution of production well. According to the model established, the bubble growth by pressure and time is predicted, that is, how the amount and size of bubbles change during solution-gas drive is presented, which provided the guidance to determine the parameters of foamy oil due to bubbles change, such as foamy oil viscosity, compres...

Some of the heavy oil reservoirs in Canada, Venezuela, and China under solution gas drive illustrate important features: low gas–oil ratio, high production rates, and very high ultimate oil recovery. It is generally believed that the foamy oil flow is one of the important mechanisms contributing to these unusual performances. A series of two-dimensional etched glass micromodel experiments was carried out to gain an insight into the processes involved in foamy oil flow. In these experiments, the bubble nucleation, migration, coalescence, breakup, and ultimate generation of a continuous gas phase can be observed continuously. On the basis of the experimental analysis, there are two bubble-point pressures in the foamy oil: One is the true bubble-point pressure, and the other is the pseudo-bubble-point pressure. The greater the difference between these two bubble-point pressures, the more stable the foamy oil flow is and the greater the contribution to oil recovery from the foamy oil drive mechanism ...

The aim of the study was to investigate the effects of baicalin on blood glucose, insulin and cytokine levels. Rat diabetes was induced by intraperitoneal (i.p.) injection of nicotinamide and streptozotocin. Diabetic rats were dosed with i.p. baicalin or oral metformin daily for 8 days. Blood glucose, insulin and hepatic glycogen were determined using conventional methods. The activity of hepatic hexokinase was determined using a coupled assay with glucose-6-phosphate dehydrogenase. Serum levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and adiponectin were measured by enzyme-linked immunosorbent assay. Administration of baicalin at 50 or 100 mg/kg significantly decreased plasma glucose levels in a dose dependent manner. The serum insulin level was not increased by baicalin treatment. Administration of baicalin at a high dose (100 mg/kg) resulted in a significant increase of liver glycogen content and a reduction of serum TNF-α. The activity of hepatic hexokinase was significantly increased after dosing baicalin at 25, 50 or 10 mg/kg. Administration of baicalin (50 or 10 mg/kg) or metformin (10 mg/kg) significantly alleviated the morphological injury to the pancreas caused by STZ. The possible mechanisms contributing to the hypoglycemic effect include increasing the hepatic glycogen content and glycolysis, and reducing the serum levels of TNF-α. Copyright © 2010 John Wiley & Sons, Ltd.

The major challenge of prion disease diagnosis at the presymptomatic stage is how to sensitively or selectively discriminate and detect the minute quantity of disease-associated prion protein isoform (PrP(Res)) in complex biological systems such as serum and brain homogenate. In this contribution, we developed a dual-aptamer strategy by taking the advantages of aptamers, the excellent separation ability of magnetic microparticles (MMPs), and the high fluorescence emission features of quantum dots (QDs). Two aptamers (Apt1 and Apt2), which can recognize their two corresponding distinct epitopes of prion proteins (PrP), were coupled to the surfaces of MMPs and QDs, respectively, to make MMPs-Apt1 and QDs-Apt2 ready at first, which then could be coassociated together through the specific recognitions of the two aptamers with their two corresponding distinct epitopes of PrP, forming a sandwich structure of MMPs-Apt1-PrP-Apt2-QDs and displaying the strong fluorescence of QDs. Owing to the different binding affinities of the two aptamers with PrP(Res) and cellular prion protein (PrP(C)), both of which have distinct denaturing detergent resistance, our dual-aptamer strategy could be applied to discriminate PrP(Res) and PrP(C) successfully in serum. Further identifications showed that the present dual-aptamer assay could be successfully applied to the detection of PrP in 0.01% brain homogenate, about 1000-fold lower than that of commonly applied antibody-mediated assays, which can detect PrP just in 10% brain homogenate, indicating that the present designed dual-aptamer assay is highly sensitive and adequate for clinical diagnosis without isolation of target protein prior to assay.

The aim of present study was to investigate the effect of baicalin on hypoxia/reoxygenation (H/R) injury in cardiomyocytes and the mechanisms involved, particularly in relation to cytokines. The cardiomyocytes for the H/R groups were placed into a hypoxic chamber for 12 h and then underwent reoxygenation for 1 h. The cells in the TNF-alpha groups were administered 100 ng/mL rrTNF-alpha and incubated for 13 h under normal conditions. The cells in the baicalin pretreatment groups were administered 10 microM baicalin 30 min prior to exposure to H/R or TNF-alpha. It was observed that pretreatment with baicalin (10 microM) significantly reduced the cell damage and death induced by H/R or TNF-alpha. In the culture medium of the H/R cells, the SOD activity increased, while TNF-alpha was decreased by baicalin. The levels of IL-6 in culture medium for H/R or TNF-alpha treated cells were suppressed by baicalin pretreatment. In contrast, the levels of IL-10 in culture medium for H/R or TNF-alpha treated cells were significantly elevated by baicalin. Moreover, baicalin inhibited the nuclear translocation of NF-kappaB induced by H/R or TNF-alpha. In conclusion, baicalin may protect cardiomyocytes from H/R injury through an anti-inflammatory mechanism.

Two hydroxyl-terminated Schiff base probe molecules have been prepared and their configurations have been assigned on the basis of 2D-NOESY experiments. Surface-enhanced Raman scattering (SERS) spectra of the probe molecules have been recorded on the silver surface. In addition, theoretical studies by density functional theory (DFT) method at B3PW91/Lanl2dz level have been applied to predict the vibrational modes and the probable adsorption behavior of Schiff bases on Ag surface. Interestingly, both the theoretical and experimental results suggest that these hydroxyl-terminated Schiff bases are anchored, in a tilted way (with a certain angle between the two non-coplanar benzene rings and the silver surface), on the silver surface via the oxygen atoms instead of the nitrogen ones. Furthermore, the SERS enhancement factor (EF) has been calculated, indicating that the selected probes can be applied in trace analysis.

A simple rapid detection of antibody to hepatitis delta virus (anti-HDV) in human serum was developed by using double antigen sandwich ELISA. HDV gene fragment encoding HDAg was isolated from a Chinese patient infected with HDV by RT-PCR, and a high-efficient expression HD-PQE31 strain was constructed with the fragment. We obtained high titer and good quality hepatitis delta virus protein purified by Ni-NTA metal-affinity chromatography, which was identified by Western blot and ELISA, then we set up the double antigen sandwich ELISA for detection of anti-HDV in human serum, and the performance of the sandwich ELISA was evaluated in terms of specificity and sensitivity. Results were: 1) The purified HDAg protein’s purity was 90%, and its ELISA titer was 1/100 000. 2) 42 anti-HDV positive sera were detected and showed that the sensitivity of sandwich ELISA was higher than that of competitive ELISA (t=2.44, p

Bacterial beta-ketoacyl-ACP reductase (FabG) and the beta-ketoacyl reductase domain in mammalian fatty acid synthase (FAS) have the same function and both are rendered as the novel targets for drugs. Herein we developed a convenient method, using an available compound ethyl acetoacetate (EAA) as the substitutive substrate, to measure their activities by monitoring decrease of NADPH absorbance at 340 nm. In addition to the result, ethyl 3-hydroxybutyrate (EHB) was detected by HPLC analysis in the reaction system, indicating that EAA worked effectively as the substrate of FabG and FAS since its beta-keto group was reduced. Then, the detailed kinetic characteristics, such as optimal ionic strength, pH value and temperature, and kinetic parameters, for FabG and FAS with this substitutive substrate were determined. The Km and kcat values of FabG obtained for EAA were 127 mM and 0.30 s(-1), while those of this enzyme for NADPH were 10.0 microM and 0.59 s(-1), respectively. The corresponding Km and kcat values of FAS were 126 mM and 4.63 s(-1) for EAA; 8.7 microM and 4.09 s(-1) for NADPH. Additionally, the inhibitory kinetics of FabG and FAS, by a known inhibitor EGCG, was also studied.

Particulate organic matter (POM), dissolved organic matter (DOM), bacteria and cladoceran were sampled seasonally at Zhihugang Estuary and Lake Center in Taihu Lake. The δ 13 C of the four organic matter fractions showed consistent temporal variation, with heaviest values in summer and lower at other times of the year. The cladoceran δ 13 C showed a significant correlation with that of POM, reflecting a heavy dietary dependence on POM during the study period. The bacteria became enriched in 13 C compared with that of DOM throughout the sampling dates, although no significant relationship was found between the two fractions. δ 13 C values of POM, cladoceran and bacteria were all negative significantly correlated with oxidation and reduction potential (ORP), and specific conductivity (SpCond). As for δ 15 N, the seasonal pattern of food web components was variable. The POM δ 15 N signature exhibited the most enriched isotope ratios during the summer months when dissolved inorganic nitrogen (DIN) nutrients were at their lowest concentrations. The consumption of DIN in summer can explain in part the progressive accumulation of heavy nitrogen isotopes during this period. Spatially, δ 13 C and δ 15 N of the food web components were all slightly depleted at Estuary than that at Lake Center during the study period, possibly due to large allochthonous inputs at Zhihugang Estuary. Relatively wide ranges of stable isotopic values from both sites suggest that seasonality should be considered when attempting to establish food web structures in a eutrophic lake.

This paper deals with the microstructure and property of zinc based composites ZA27Six under the treatment of the sodium salt and the rare earth. The test material was prepared with pure zinc ingot (Zn≥99.99wt %) and the Al-Si matrix alloy. Basic composition of the test sample was Al (25~30 wt %), Si (2.5~6.0 wt %) and Zn for the rest. Impact toughness test, tensile test and wear test were conducted. The test results show that under the treatment of sodium the massive primary silicon crystal can transform to nodular silicon on which eutectic silicon crystal can form and grow in rod-like. It is also found that the combined effect of rare earth and sodium salt can obviously refine the silicon phase and the zinc based composites enhanced by nodular silicon has better hardness and wear- resistance.

Casting magnesium alloys are heterogeneous materials containing numerous voids. Assuming the voids are spherical, in the present investigation, the evolution equations of the growth and nucleation of the voids have been presented. Combining the evolution equation of the void growth with that of the void nucleation, the evolution rule of the voids was obtained. Based on the void evolution rule a nonclassical elastoplastic constitutive model involving void evolution was developed. The corresponding numerical algorithm and finite element procedure were developed and applied to the analyses of the elastoplastic response and the porosity of casting magnesium alloy. The calculated results show the satisfactory agreement with experiments.

It was found that chlorogenic acid inhibited in vitro animal fatty acid synthase (FAS I) and the ss-ketoacyl-ACP reductase (FabG) from Escherichia coli in a concentration-dependent manner with respective IC50 of 94.8 and 88.1 microM. The results of Lineweaver-Burk plots indicated that chlorogenic acid inhibited competitively the binding of NADPH to FAS I, while left those of acetyl-CoA and malonyl-CoA unaffected. Further kinetic studies showed that chlorogenic acid blocked the activity of FAS I mainly by inhibiting the ss-ketoacyl reductase domain, which catalyzed the same reaction as that done by FabG in the fatty acid synthesis. The ss-ketoacyl reduction reactions accomplished by both FAS I and FabG required nucleotide cofactor, NADPH. Furthermore, the Lineweaver-Burk and Yonetani-Theorell analyses implicated that chlorogenic acid filled competitively in the binding-pocket of NADPH in the ss-ketoacyl reductase domain of FAS I. The similar results were also obtained from the inhibition of FabG by chlorogenic acid. As observed in these results, the inhibitions of FAS I and FabG by chlorogenic acid were highly related to the interference of the inhibitor with NADPH, which was possibly due to the similarity between chlorogenic acid and some portion of NADPH, maybe the section consisting of the two ribose groups.

The incidence of colorectal cancer (CRC) is increasing in many Asian countries and microRNAs have already been proven to be associated with tumorigenesis. Currently, microRNA-376a (miR-376a) expression and association with clinical factors in CRC remains unclear. In this study, real-time quantitative reverse transcriptase- polymerase chain reaction (qRT-PCR) was carried out on 53 matched pairs of CRC and adjacent normal mucosa to investigate the expression levels of miR-376a. According to the high or low expression of miR-376a, patients were divided into two groups. The relationship between miR-376a expression and clinicopathological factors of 53 patients was evaluated. Survival analysis of 53 CRC patients was performed with clinical follow- up information and survival curves were assessed by the Kaplan-Meier method. Immunohistochemistry (IHC) staining was performed on sections of paraffin-embedded tissue to investigate the vascular endothelial growth factor (VEGF) expression. MiR-376a showed low expression in cancer tissues compared to the adjacent normal tissues and altered high miR-376a expression tended to be positively correlated with advanced lymph node metastasis and shorter patient survival. VEGF IHC positivity was significantly more common in patients with high expression levels of miR-376a.Those results demonstrated that miR-376a may be a meaningful prognostic biomarker and potential therapeutic target in colorectal cancer.

Proteomics was used to identify a protein encoded by ORF 3a in a SARS-associated coronavirus (SARS-CoV). Immuno-blotting revealed that interchain disulfide bonds might be formed between this protein and the spike protein. ELISA indicated that sera from SARS patients have significant positive reactions with synthesized peptides derived from the 3a protein. These results are concordant with that of a spike protein-derived peptide. A tendency exists for co-mutation between the 3a protein and the spike protein of SARS-CoV isolates, suggesting that the function of the 3a protein correlates with the spike protein. Taken together, the 3a protein might be tightly correlated to the spike protein in the SARS-CoV functions. The 3a protein may serve as a new clinical marker or drug target for SARS treatment.

Fatty acid synthase (EC 2. 3. 1. 85, abbr. FAS) is reported as a potential new therapeutic target for the treatment of obesity. Thirty one Chinese medicinal herbs used in weight reducing prescriptions of Traditional Chinese Medicine (TCM) were investigated for FAS inhibition. It was found that 17 of these herbs exhibited FAS inhibitor activity, and 9 were highly potent FAS inhibitors. The inhibitory potencies of the active components of tuber fleeceflower root, parasitic loranthus, green tea leaf and ginkgo leaf were similar to or greater than cerulenin and C75. The first three of these four herbs significantly reduced body weight of rats upon their oral incubation. Moreover, tuber fleeceflower root and parasitic loranthus significantly reduced food intake in rats. These results indicate that many of weight reducing herbs used in TCM do so by inhibiting FAS. They also hold promise for the development of new nontoxic and low cost weight reducing substances from these herbs.

Studies of the new oxidative Mannich cyclization reaction of α-silyl-amines and -amides demonstrate advantageous features of the process when applied to stereocontrolled hydropyridine syntheses.

In the presence of sodium hydride, benzoyl-substituted heterocyclic ketene aminals 1 reacted with benzyl chloride 2 to give exclusively the N-benzylated products 3 in moderate yields.

The carbide strain-induced precipitation kinetics of a 2000 MPa grade Nb-V high-strength spring steel during isothermal deformation is quantitatively investigated using the stress relaxation method. The stress relaxation technique was employed to determine the precipitation start (P s ) and finish (P f ) times. The evolution of carbides during the isothermal holding is observed by Transmission Electron Microscope (TEM). The results show that the precipitation-time-temperature (PTT) diagrams of the carbides in the experimental steel exhibit a C-curve, with a nose temperature of 900 °C. The precipitation kinetics of carbides in the experimental steel is slower than that of plain carbon steels, which is attributed to the reduced activity of Nb. The result indicates that the precipitate is a Nb, V, Ti and C-containing complex carbide at deformation temperatures ranging from 850 °C to 1050 °C. Large parts of the precipitates are (Nb,V)C, and there is also a tiny amount of TiC. The carbides are dispersed below 900 °C and distributed in clusters near dislocations and grain boundaries above 950 °C.

Studies focusing on the development and application of a new oxidative methodology for promoting Mannich cyclizations have been conducted. The general features of these processes were explored with selected α-silylamino and α-silylamido allyl- and vinylsilanes. Representative conditions for affecting conversion of the α-silylamine and -amide functionalities into intermediate N-alkyl and N-acyliminium cations involve either 9,10-dicyanoanthracene SET-sensitized photooxidation or ceric ammonium or tetra-n-butylammonium nitrate oxidations. The applicability of these procedures for promoting Mannich cyclizations was first demonstrated by the preparation of methylidenepiperidines and -hydroazepines. Further studies have led to observations which show that Mannich cyclizations of stereochemically labeled α-silylamino vinylsilanes proceed to furnish tetrahydropyridines. Also, unlike their amine analogues, α-silylamido (E)-vinylsilanes undergo cyclization to produce tetrahydropyridines with retention of absolute ...

Sinomenine (SIN) is an alkaloid isolated from the Chinese medicinal plant Sinomenium acutum. It is widely used as an immunosuppressive drug for treating autoimmune diseases. Due to its poor efficiency, the large-dose treatment presents some side effects and limits its further applications. In this study, we used chemical modification to improve the therapeutic effect of SIN in vitro and in vivo. A new derivative of sinomenine, named 1032, demonstrates significantly improved immunosuppressive activity over that of its parent natural compound (SIN). In an experimental autoimmune encephalomyelitis (EAE) model, 1032 significantly reduced encephalitogenic T cell responses and induced amelioration of EAE, which outcome was related to its selective inhibitory effect on the production of IL-17. By contrast, SIN treatment only led to a moderate alleviation of EAE severity and the expression level of IL-17 was not significantly reduced. Furthermore, 1032 exhibited suppression of Th17, but not Treg, cell differentiation, a result probably related to its inhibitory effect on IkappaB-alpha degradation as well as on IL-6 and TNF-alpha secretion in BMDCs. We speculate that 1032 as a novel anti-inflammatory agent may target DC to block IL-6 production, which in turn would terminate Th17 cell development. Thus, SIN derivative 1032 presents considerable potential in new drug development for treating autoimmune and inflammatory disease.

Objective:Aprotinin is frequentlyusedto reduce bloodlossduring cardiacsurgery; however, it also causes renalinjury. Sinceaprotinin reduces nitric oxide (NO) and prostaglandin I2 (PGI2), and both cause vasodilation and inhibit activation of neutrophils and platelets, their reduction may be responsible for the injury. This study was to determine whether the combination of aprotinin with NO and prostaglandin E1 (PGE1, an analogue of PGI2) can attenuate renal injury associated with aprotinin during cardiopulmonary bypass (CPB). Methods: Thirty mongrel dogs were equally divided into five groups, with each group receiving CPB and aprotinin, NO, PGE1, a combination of the three or no treatment (control). Serum creatinine and creatinine clearance were determined. To elucidate the mechanism, neutrophil, platelet and thrombin activations were also assessed. Results: After CPB, serum creatinine increased and creatinine clearance decreased in all dogs. These changes were similar among the NO, PGE1, aprotinin and control groups, but were significantly smaller in the combination group. Similarly, myeloperoxidase activities in tissues, CD11b expression, plasma elastase, prothrombin fragment (PTF) 1 + 2 and platelet activation factor were lower, whereas neutrophil and platelet counts were higher in the combination group than in the other groups (P < 0.05). Conclusions: Aprotinin combined with NO and PGE1 produced synergistic protective effects and improved renal function, due partly to inhibition of platelet and neutrophil activation and suppression of thrombin formation. # 2010 European Association for Cardio-Thoracic Surgery. Published by Elsevier B.V. All rights reserved.

Inhibitory effects on bacterial growth showed that 40% ethanol extract of galangal (rhizome of Alpinia officinarum Hance) can inhibit Staphylococcus aureus, alpha-Hemolytic streptococcus, beta-Hemolytic streptococcus and Streptococcus pneumoniae. beta-ketoacyl-ACP reductase (FabG, EC.1.1.1.100) is a key enzyme in type II fatty acid synthase system in bacteria and catalyzes beta-ketoacyl-ACP reduction. The galangal extracts inhibited FabG with an IC(50) value of only 4.47 +/- 0.10 microg/mL and is more potent than other previously published inhibitors. Kinetics studies showed that the inhibition consisted of both reversible and irreversible inhibition. The extracts of galangal inhibit FabG in a competitive pattern against NADPH. So far, no inhibitor has been reported to exhibit irreversible inhibition of FabG, whereas the galangal ethanol extract can inhibit FabG irreversibly. The irreversible inhibition presented two phases. It is probable that the galangal extract inhibit FabG, thereby displaying antibacterial ability.

The inhibitory effects of a black tea extract on fatty acid synthase were measured through inhibition kinetics. The Keemun black tea extract showed more potent inhibitory activity on fatty acid synthase than green tea extract. Additionally, the inhibitory ability of the black tea extract depended on the extracting solvent and the conditions used. Only 10-23% of the inhibitory activity from the black tea was extracted by the general method of boiling with water. The results suggested that the main fatty acid synthase inhibitors in black tea might be theaflavins. Which were more potent than epigallocatechin gallate or C75. The reaction site on the fatty acid synthase and the inhibition kinetics for the extract were different from those of epigallocatechin gallate or C75. In addition, Keemun black tea extract significantly reduced food intake, body weight and blood triglyceride of diet-induced obesity SD rats via oral administration.

Metal films have been used extensively in very-large-scale integration (VLSI) devices. They are used to build interconnects, field-effect transistor gates, diffusion barriers, and conduction pads for input or output leads. Metals such as aluminum, tungsten, titanium and platinum are deposited on an insulating layer [1,2]. The metal film thicknesses range from 100 A to 1 µm. Due to the ever-growing need for high speed, high density, and low power dissipation in integrated circuit (IC) technology, accurate control of the metallization process becomes essential to ensure the quality and yield of the final product. One of the important parameters in the metallization process control is the film thickness.

The spike (S) protein of severe acute respiratory syndrome coronavirus (SARS-CoV) is an important viral structural protein. Based on bioinformatics analysis, 10 antigenic peptides derived from the S protein sequence were selected and synthesized. The antigenicity and immunoreactivity of all the peptides were tested in vivo and in vitro. Four peptides (P6, P8, P9 and P10) which contain B cell epitopes of the S protein were identified, and P8 peptide was confirmed in vivo to have a potential in serological diagnosis. By using a syncytia formation model, we tested the neutralization ability of all 10 peptides and their corresponding antibodies. It is interesting to find that P8 and P9 peptides inhibited syncytia formation, suggesting that the P8 and P9 spanning regions may provide a good target for anti-SARS-CoV drug design. Our data suggest that we have identified peptides derived from the S protein of SARS-CoV, which are useful for SARS treatment and diagnosis.

The zirconia-doped mullite fibers were prepared via a sol-gel method from aluminum isopropoxide-aluminum nitrate-tetraethyl orthosilicate system. The effects of zirconia doping on the sol spinnability, mullitization, structure and thermal stability of mullite fibers were investigated by means of Fourier transform infrared (FT-IR) spectroscopy, scanning electron microscopy (SEM) and X-ray diffraction (XRD). The results showed that Zr—O—C bond was presented with the involvement of zirconium acetate, which accelerated the gelation process of the precursor sol. The mullitization process of the doped fibers was promoted by the formation of less middle-phase residues such as spinel. Among the samples investigated, the 1% ZrO2-doped fibers exhibited the highest thermal stability with a grain growth rate of 11% (from 1 000 °C to 1 300 °C), which is only a half of that for pure mullite fibers.