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Fructose intolerance in mammals is caused by defects in fructose absorption and metabolism. Fructose-1,6-bisphosphatase 1 (FBP1) is a key enzyme in gluconeogenesis, and its deficiency results in hypoglycemia as well as intolerance to fructose. However, the mechanism about fructose intolerance caused by FBP1 deficiency has not been fully elucidated. Here, we demonstrate that hepatic but not intestinal FBP1 is required for fructose metabolism and tolerance. We generated inducible knockout mouse models specifically lacking FBP1 in adult intestine or liver. Intestine-specific deletion of Fbp1 in adult mice does not compromise fructose tolerance, as evidenced by no significant body weight loss, food intake reduction, or morphological changes of the small intestine during 4 weeks of exposure to a high-fructose diet. By contrast, liver-specific deletion of Fbp1 in adult mice leads to fructose intolerance, as manifested by substantial weight loss, hepatomegaly, and liver injury after exposure to a high-fructose diet. Notably, the fructose metabolite fructose-1-phosphate is accumulated in FBP1-deficient liver after fructose challenge, which indicates a defect of fructolysis, probably due to competitive inhibition by fructose-1,6-bisphosphate and may account for the fructose intolerance. In conclusion, these data have clarified the essential role of hepatic but not intestinal FBP1 in fructose metabolism and tolerance.

Background and aims Lipoprotein lipase (LPL) is responsible for the lipolytic processing of triglyceride-rich lipoproteins, the deficiency of which causes severe hypertriglyceridemia. Liver LPL expression is high in suckling rodents, but relatively low at adulthood. However, the regulatory mechanism and functional significance of liver LPL expression are incompletely understood. We have established the zinc finger protein ZBTB20 as a critical factor for hepatic lipogenesis. Here we evaluated the role of ZBTB20 in regulating liver Lpl gene transcription and plasma triglyceride metabolism. Approach and results Hepatocyte-specific inactivation of ZBTB20 in mice led to a remarkable increase in LPL expression at the mRNA and protein levels in adult liver, in which LPL protein was mainly localized onto sinusoidal epithelial cells and Kupffer cells. As a result, the LPL activity in post-heparin plasma was substantially increased, and postprandial plasma triglyceride clearance was significantly enhanced, while plasma triglyceride levels were decreased. The dysregulated liver LPL expression and low plasma triglyceride levels in ZBTB20-deficient mice were normalized by inactivating hepatic LPL expression. ZBTB20 deficiency protected the mice against high-fat diet-induced hyperlipidemia without causing excessive triglyceride accumulation in the liver. Chromatin immunoprecipitation and gel shift assay studies revealed that ZBTB20 binds to the LPL promoter in the liver. A luciferase reporter assay revealed that ZBTB20 inhibits the transcriptional activity of LPL promoter. The regulation of LPL expression by ZBTB20 is liver-specific under physiological condition. Conclusions Liver ZBTB20 serves as a key regulator of LPL expression and plasma triglyceride metabolism, and could be a therapeutic target for hypertriglyceridemia.

Sphingosine kinase 2 (SphK2) inhibitors are developed for tumor therapy as considering its anti-tumor effect. Many studies also explored SphK2 modulated glucose and lipid homeostasis, which extended its potential function for metabolic diseases therapy. In this study, we discovered a significant reduction of hepatic lipid accumulation as well as recovery of liver function in ob/ob mice with intraperitoneal injection of K145. Also, db/db mice received K145 showed improvement of both NALFD and hyperglycemia. We furtherly analyzed the genes associated with lipid metabolism and found a remarkable decreased expression of lipogenic genes including FAS, ACC1 and SREBP1c whereas elevated mitochondrial fatty acid β-oxidation (FAO) related genes expression including CPT1A, MCAD, LCAD, PPAR-α, UCP2. Consistent to in vivo study, in vitro study also confirmed the role of K145 in decreasing lipid accumulation in human HL7702 cells, while inhibiting FAS, ACC1 and SREBP1c mRNA expression. It indicated a possible mechanism of K145 induced improvement of hepatic lipid accumulation partly via inhibition of lipigenesis. Our study suggested a promising role of K145 in drug development for NAFLD and diabetes therapy.

Background and purpose Disturbed flow induces endothelial dysfunction and contributes to uneven distribution of atherosclerotic plaque. Emerging evidence suggests that harmine, a natural constituent of extracts of Peganum harmala, has potent beneficial activities. Here, we investigated if harmine has an atheroprotective role under disturbed flow and the underlying mechanism. Experimental approach Mice of ApoE-/- , LDLR-/- , and endothelial cell (EC)-specific overexpression of yes-associated protein (YAP) in ApoE-/- background were fed with a Western diet and given harmine for 4 weeks. Atherosclerotic lesion size, cellular composition, and expression of inflammatory genes in the aortic roots were assessed. HUVECs were treated with oscillatory shear stress (OSS) and harmine and also used for proteomic analysis. Key results Harmine retarded atherogenesis in both ApoE-/- and LDLR-/- mice by inhibiting the endothelial inflammatory response. Mechanistically, harmine blocked OSS-induced YAP nuclear translocation and EC activation by reducing phosphorylation of YAP at Y357. Overexpression of endothelial YAP blunted the beneficial effects of harmine in mice. Proteomic study revealed that protein tyrosine phosphatase non-receptor type 14 (PTPN14) could bind to YAP. Moreover, harmine increased PTPN14 expression by stabilizing its protein level and inhibiting its degradation in proteasomes. PTPN14 knockdown blocked the effects of harmine on YAPY357 and EC activation. Finally, overexpression of PTPN14 mimicked the effects of harmine and ameliorated atherosclerosis, and knockdown of PTPN14 blunted the atheroprotective effects of harmine and accelerated atherosclerosis, in a partial ligation mouse model. Conclusion and implications Harmine alleviated OSS-induced EC activation via a PTPN14/YAPY357 pathway and had a potent atheroprotective role.

In this article, we have systematically investigated the impact of different structural parameters on the breakdown voltage for GaN-based trench MIS barrier-controlled Schottky (TMBS) rectifier. Compared with the planar Schottky rectifier, the TMBS rectifier has field plates on the mesa sidewalls so that the drift region can be depleted in a 2-D manner, which helps to decrease the electric field at the metal/mesa interface. However, the adoption of mesas can make the electric potential lines at the mesa corner dense and has large curvatures. Therefore, the premature breakdown can occur when the electric field therein reaches the critical condition. We find that the electric field profiles can be affected by insulation layer thickness, mesa width, trench depth, and different types of insulation layers. Then, we increase the breakdown voltage by homogenizing the electric field distribution in the mesa region, e.g., the electric field at mesa corners can be decreased by adopting properly thick sidewall insulator and small trench depth. Meanwhile, TMBS rectifier using sidewall insulating material with a large dielectric constant more favors a large breakdown voltage.

The development of bimetallic-based ternary materials (BTMs) has attracted much attention due to their multi-component flexibility and synergistic effect. Herein, BTM (Ce2Sn2O7) nanoparticles are encapsulated into graphene (Ce2Sn2O7/RGO), which served as a novel anode material for lithium-ion batteries and capacitors (LIBs/LICs). Benefiting from the synergistic effects from two metal elements and the conductive networks of graphene, the optimized Ce2Sn2O7/RGO delivers a reversible capacity of 814.6 mA h g−1 at 0.05 A g−1, good cycling performance with a reversible capacity of 369.5 mA h g−1 after 1500 cycles at 1 A g−1 and a superior rate capability of 432.4 mA h g−1 at 2 A g−1 in Li+ half cells. Meanwhile, the detailed phase transition and kinetics analysis as well as the theoretical calculation are performed to investigate the reaction mechanisms behind the good electrochemical performance. Furthermore, the Ce2Sn2O7/RGO also shows good lithium-ion full cell and capacitor performances coupled with commercial LiCoO2 and activated carbon, respectively, which further demonstrates the application prospect of Ce2Sn2O7/RGO.

Local flow patterns determine the uneven distribution of atherosclerotic lesions. This research aims to elucidate the mechanism of regulation of nuclear translocation of Yes-associated protein (YAP) under oscillatory shear stress (OSS) in the atheroprone phenotype of endothelial cells (ECs). We report here that OSS led to tyrosine phosphorylation and strong, continuous nuclear translocation of YAP in ECs that is dependent on integrin α5β1 activation. YAP overexpression in ECs blunted the anti-atheroprone effect of an integrin α5β1–blocking peptide (ATN161) in Apoe(–/–) mice. Activation of integrin α5β1 induced tyrosine, but not serine, phosphorylation of YAP in ECs. Blockage of integrin α5β1 with ATN161 abolished the phosphorylation of YAP at Y(357) induced by OSS. Mechanistic studies showed that c-Abl inhibitor attenuated the integrin α5β1–induced YAP tyrosine phosphorylation. Furthermore, the phosphorylation of c-Abl and YAP(Y357) was significantly increased in ECs in atherosclerotic vessels of mice and in human plaques versus normal vessels. Finally, bosutinib, a tyrosine kinase inhibitor, markedly reduced the level of YAP(Y357) and the development of atherosclerosis in Apoe(–/–) mice. The c-Abl/YAP(Y357) pathway serves as a mechanism for the activation of integrin α5β1 and the atherogenic phenotype of ECs in response to OSS, and provides a potential therapeutic strategy for atherogenesis.

Diabetic nephropathy (DN) is the major cause of chronic kidney disease and end-stage renal disease. Previous studies have demonstrated that long-chain omega-3 polyunsaturated fatty acids (PUFAs) might have therapeutic potential in reducing proteinuria in DN. However, the local level of eicosanoids derived from PUFAs in the plasma of DN patients remains unclear. This work aims to study the eicosanoid profile difference in plasma of DN patients and type 2 diabetes (T2D) without DN. A total of 27 T2D patients with similar diabetic duration were recruited and divided into T2D+DN group and T2D+NDN (non-DN) group based on urinary albumin excretion (UAE) detection. Using LC-MS/MS-based metabolomics, DN patients showed increased level of lipoxygenase (LOX) metabolites (5-HETE and LTB4) and decreased levels of eicosanoids derived according to the cytochrome P450s (CYP450) metabolic pathway (5,6-DHET; 14,15-DHET and 9,10-diHOME). Receiver operating characteristics and logistic regression analysis revealed increased level LOX metabolites and decreased level of CYP450 metabolites were significantly correlated with the incidence of DN in T2D patients. LOX and CYP450 metabolites correlated with DN incidence in T2D patients, which might be treatment targets for DN in T2D patients.

Salvianolic acid B (Sal B) the most abundant bioactive member in Salvia miltiorrhiza and has been reported lots of benefits on the treatment of cardio-cerebral vascular diseases and metabolic diseases. Lipid droplets are dynamic organelles, excessive lipid droplets accumulation in liver caused fatty liver disease. In this study, we are interested in the effect of Sal B on hepatic lipid accumulation and its possible mechanism. We found Sal B treatment significantly decreased lipid accumulation and TG level in primary hepatocytes, this is the first demonstration for the effect of Sal B on lipid droplets. Meanwhile, a stimulation of Sal B on autophagy of hepatocytes was discovered, further we used autophagy inhibitor 3-MA and reveled that after administration of 3-MA Sal B showed little effect on improving hepatic lipid accumulation, this means the effects of Sal B on lipid drop depend on autophagy. This study demonstrates Sal B ameliorate hepatic lipid accumulation through activation of autophagy. These findings contribute to its benefit on liver disease related to hepatic lipid accumulation and hepatic autophagy.

Endothelial progenitor cell (EPC) dysfunction contributes to diabetes-induced delay in endothelium repair after vessel injury, prominently associated with diabetic cardiovascular complications such as neointima formation. ATP-binding cassette transporter G1 (ABCG1) promotes cholesterol efflux to HDL, which may favorably affect EPC function. However, whether ABCG1 improves EPC function, especially in diabetes, remains unknown. Here we investigated the role of ABCG1 in EPCs by using Tie2-mediated ABCG1 transgenic (Tie2- ABCG1Tg) mice. Mice were injected with streptozotocin to induce diabetes mellitus. As compared with wild-type (WT) mice, in Tie2- ABCG1Tg mice, diabetes-impaired EPC migration and tube formation were reversed. In vitro gain-of-function and loss-of-function studies further revealed that ABCG1-overexpressing EPCs showed increased migration and tube formation and differentiation via the Lck/Yes-related novel protein tyrosine kinase /Akt/endothelial NO synthase pathway by enhancing cellular cholesterol efflux. Finally, type 1 and type 2 diabetic mouse models with arterial injury were intravenously injected with labeled EPCs from WT or Tie2- ABCG1Tg mice. Re-endothelialization in diabetic mice was improved to a greater extent by injection of ABCG1-overexpressing than WT EPCs. Our study demonstrated that ABCG1 in EPCs improved repair after vascular injury in diabetes by increasing EPC function such as migration, tube formation and differentiation, and subsequent re-endothelialization. ABCG1 might be a promising therapeutic target for diabetes-associated vascular diseases.-Shi, Y., Lv, X., Liu, Y., Li, B., Liu, M., Yan, M., Liu, Y., Li, Q., Zhang, X., He, S., Zhu, M., He, J., Zhu, Y., Zhu, Y., Ai, D. Elevating ATP-binding cassette transporter G1 improves re-endothelialization function of endothelial progenitor cells via Lyn/Akt/eNOS in diabetic mice.

Background & Aims Nonalcoholic steatohepatitis (NASH) is an increasingly prevalent nonalcoholic fatty liver disease, characterized by inflammatory cell infiltration and hepatocellular damage. Mammalian target of rapamycin complex 1 (mTORC1) has been investigated extensively in the context of cancer, including hepatocellular carcinoma. However, the role of mTORC1 in NASH remains largely unknown. Methods mTORC1 activity in macrophages in human mild and severe NASH liver was compared. Mice with macrophage-specific deletion of the regulatory-associated protein of mTOR (Raptor) subunit and littermate controls were fed a high-fructose, palmitate, and cholesterol diet for 24 weeks or a methionine- and choline-deficient diet for 4 weeks to develop NASH. Results We report that in human beings bearing NASH, macrophage mTORC1 activity was lower in livers experiencing severe vs mild NASH liver. Moreover, macrophage mTORC1 disruption exacerbated the inflammatory response in 2 diet-induced NASH mouse models. Mechanistically, in response to apoptotic hepatocytes (AHs), macrophage polarization toward a M2 anti-inflammatory phenotype was inhibited in Raptor-deficient macrophages. During the digestion of AHs, macrophage mTORC1 was activated and coupled with dynamin-related protein 1 to facilitate the latter’s phosphorylation, leading to mitochondrial fission-mediated calcium release. Ionomycin or A23187, calcium ionophores, prevented Raptor deficiency–mediated failure of lysosome acidification and subsequent lipolysis. Blocking dynamin-related protein 1–dependent mitochondria fission impaired lysosome function, resulting in reduced production of anti-inflammatory factors such as interleukins 10 and 13. Conclusions Persistent mTORC1 deficiency in macrophages contributes to the progression of NASH by causing lysosome dysfunction and subsequently attenuating anti-inflammatory M2-like response in macrophages during clearance of AHs., Graphical abstract

Diabetic retinopathy (DR) is the most frequent microvascular complications of diabetes and the leading cause of blindness in adults worldwide. Non-proliferative DR (NPDR) is the first stage of DR but currently has few recommended intervention. Eicosanoids play important roles in maintaining vessel homeostasis. However, the functions of eicosanoids in NPDR are still unknown. In this study, we investigated the eicosanoids profile difference in plasma between type 2 diabetes with NPDR or not. A total of 50 patients with type 2 diabetes were recruited and divided into non-DR (NDR) group and NPDR group based on fundus photographs. The eicosanoids profiles in plasma were determined by LC-MS/MS. Adhesion and transwell assay were used to detect the adhesion and migration effects of metabolites on primary bovine retinal pericyte cells (BRPC), respectively. Streptomycin (STZ)-induced diabetic mouse model was used to test the protective effects of selected metabolites according to retinal immunofluorescence staining and fluorescence confocal microscopy. Prostaglandin 2α (PGF2α) was decreased significantly in NPDR group compared to NDR group and negatively correlated with NPDR. In vitro, PGF2α was found to accelerate adhesion and migration by activating prostaglandin F receptor (FP receptor) and subsequent increasing RhoA activity in primary bovine retinal pericyte. Administration of PGF2α analogue diminished the damage on retinal capillary in an STZ-induced diabetic mouse model. Our results suggested that PGF2α may be a protective factor in the progression of NPDR in T2D patients. The protective mechanism of PGF2α was to increase pericyte mobility through FP receptor/RhoA pathway.

Two new all-metal molecules Be6Li8 and Be6Li14 have been designed theoretically. They possess Oh symmetric geometries and centrosymmetric electric structures. The number of their valence electrons satisfying Hirsch's rule and the highly negative nucleus independent chemical shifts at their centers reveal that they are spherical aromatic, which leads to their good chemical stabilities. When an external electric field is applied to Be6Li8 and Be6Li14, the centrosymmetry of their electric structures is broken, which brings high first hyperpolarizability (β0) contrasts. We find that β0 of Be6Li14 is larger than that of Be6Li8 under an electric field. The reason for this is that the electron density is altered more easily in Be6Li14 than in Be6Li8, which is clearly shown in the evolutions of their HOMOs with increasing electric field strength. The calculated electron spectra show that Be6Li8 and Be6Li14 have infrared transparent wavebands from 2.5 to 8.0 μm. Thus, our calculated results demonstrate that they can act as electric-field-induced infrared nonlinear optical switches.

Background and purpose Atherosclerosis results from a maladaptive inflammatory response initiated by the intramural retention of LDL in susceptible areas of the arterial vasculature. The ω-3 polyunsaturated fatty acids (ω-3) have protective effects in atherosclerosis; however, their molecular mechanism is still largely unknown. The present study used a metabolomic approach to reveal the atheroprotective metabolites of ω-3 and investigate the underlying mechanisms. Experimental approach We evaluated the development of atherosclerosis in LDL receptor-deficient mice (LDLR-/- ) fed a Western-type diet (WTD) plus ω-3 and also LDLR-/- and fat-1 transgenic (LDLR-/- -fat-1tg ) mice fed a WTD. The profiles of ω-3 in the plasma were screened by LC-MS/MS using unbiased systematic metabolomics analysis. We also studied the effect of metabolites of eicosapentaenoic acid (EPA) on endothelial activation in vitro. Key results The ω-3 diet and fat-1 transgene decreased monocyte infiltration, inhibited the expression of pro-inflammatory genes and significantly attenuated atherosclerotic plaque formation and enhanced plaque stability in LDLR-/- mice. The content of 18-hydroxy-eicosapentaenoic acid (18-HEPE) and 17,18-epoxy-eicosatetraenoic acid (17,18-EEQ), from the cytochrome P450 pathway of EPA, was significantly higher in plasma from both ω-3-treated LDLR-/- and LDLR-/- -fat-1tg mice as compared with WTD-fed LDLR-/- mice. In vitro in endothelial cells, 18-HEPE or 17,18-EEQ decreased inflammatory gene expression induced by TNFα via NF-κB signalling and thereby inhibited monocyte adhesion to endothelial cells. Conclusions and implications EPA protected against the development of atherosclerosis in atheroprone mice via the metabolites 18-HEPE and/or 17,18-EEQ, which reduced endothelial activation. These compounds may have therapeutic implications in atherosclerosis. Linked articles This article is part of a themed section on Spotlight on Small Molecules in Cardiovascular Diseases. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v175.8/issuetoc.

Hyperhomocysteinemia (HHcy) is associated with liver diseases such as fatty liver and hepatic fibrosis; however, the underlying mechanism is still largely unknown. The current study aimed to explore the signaling pathway involved in HHcy-induced hepatic steatosis (HS). C57BL/6 mice were fed a high-methionine diet (HMD) for 4 and 8 weeks to establish the HHcy mouse model. Compared to a chow diet, the HMD induced hepatic steatosis and elevated hepatic expression of CD36, a fatty acid transport protein. The increased CD36 expression was associated with activation of the aryl hydrocarbon receptor (AHR). In primary cultured hepatocytes, high levels of homocysteine (Hcy) treatment up-regulated CD36 and increased subsequent lipid uptake; both were significantly attenuated by small interfering RNA (siRNA) knockdown of CD36 and AHR. Chromatin immunoprecipitation assay revealed that Hcy promoted binding of AHR to the CD36 promoter, and transient transfection assay demonstrated markedly increased activity of the AHR response element by Hcy, which was ligand dependent. Mass spectrometry revealed significantly increased hepatic content of lipoxin A4 (LXA4), a metabolite of arachidonic acid, in HMD-fed mice. Furthermore, overexpression of 15-oxoprostaglandin 13-reductase 1, a LXA4 inactivation enzyme, inhibited Hcy-induced AHR activation, lipid uptake, and lipid accumulation. Moreover, LXA4-induced up-regulation of CD36 and lipid uptake was inhibited by AHR siRNA in vitro in hepatocytes. Finally, treatment with an AHR antagonist reversed HHcy-induced lipid accumulation by inhibiting the AHR-CD36 pathway in mice. Conclusion: HHcy activates the AHR-CD36 pathway by increasing hepatic LXA4 content, which results in hepatic steatosis. (Hepatology 2016;64:92-105)

Moisture content is an important indicator of the insulation and arc extinguishing performance of SF6 insulated electrical equipment. The research shows that moisture measurements are strongly influenced by altitude pressures and the different order of pressure correction and temperature correction calculation, different calculation results will result. Therefore, in this paper, we studies the pressure and temperature environment based on moisture test of SF6 gas insulated equipment in power industry. Firstly, the PVT characteristics of pure SF6 gas and water vapor were analyzed and put forward the necessity of pressure correction, then combined the Pitzer-Veli equation of SF6 gas and Water Pitzer-Veli equation to fit PVT equation of state of SF6-H20 that suitable for electric power industry and deduced the Correction Formula of Moisture Measurement in SF6 Gas. Finally, through experiments, completion of the calibration formula optimization and verification SF6 electrical equipment on, proof of the applicability and effectiveness of the correction formula.

Eicosanoids are hundreds of metabolites derived from poly-unsaturated fatty acids (PUFAs), which regulate biological processes from multiple angles via a complex metabolic network. Targeted eicosanoid metabolomics is used to study the eicosanoid profile in biological samples but only for eicosanoids with available standards. To expand the coverage of eicosanoids detected, we identified the eicosanoids without available standards by estimation of the retention time and comparison of the MS/MS spectra with the reference ones which was collected in a database from literature. Scheduled multiple reaction monitoring- information dependent acquisition- enhanced product ion (sMRM-IDA-EPI) scan mode was applied in this method, which was called Spectrum Evaluation-assisted Eicosanoid Metabolomics (SEEM). By using this method, 243 eicosanoids (167 without standards) could be relatively quantified with precision over 90 percent. We applied the method to analyze the global profile of eicosanoids secreted by human umbilical vascular endothelial cells at the basal level and with n-3 PUFA treatment. 26 putative eicosanoids showed altered levels, despite no available standards. In general, n-3 PUFA treatment increased most of their own metabolites and decreased the epoxy-, hydroxyl- and keto- linoleic acid metabolites. The application of the SEEM method proved its potency of identification and quantification of eicosanoids without standards.

Circulating monocytes play pivotal roles in chronic inflammatory diseases. Epoxyeicosatrienoic acids (EETs), metabolites of arachidonic acid, are known to have anti-inflammatory effects and are hydrolyzed by soluble epoxide hydrolase (sEH).We aimed to investigate the effect of sEH inhibition in atherogenesis.Mice with low-density lipoprotein receptor deficiency (Ldlr(-/-)) with or without sEH inhibitor, and Ldlr/sEH double-knockout (DK) mice were fed a Western-type diet (WTD) for 6weeks to induce arteriosclerosis. Both sEH inhibition and gene depletion decreased the WTD-induced hyperlipidemia, plaque area and macrophage infiltration in mice arterial wall. Ly6C(hi) infiltration of monocytes remained similar in blood, spleen and bone marrow of DK mice, but was decreased in aortic lesions. To further assess the role of sEH or EETs in monocyte/macrophage infiltration in atherogenesis, we transplanted DK bone marrow into Ldlr(-/-) recipients, and then fed mice the WTD. Aortic lesions and Ly6C(hi) monocyte infiltration were reduced in mice with transplanted bone marrow of DK mice without diminishing the cholesterol level. Furthermore, sEH inhibition or gene depletion increased the ratio of EETs/DHETs and diminished the expression of P-selectin glycoprotein ligand 1 (PSGL-1) in mice peripheral-blood mononuclear cells. Monocyte adhesion to P-selectin and to tumor necrosis factor α-activated endothelial cells was also diminished by sEH inhibition.sEH inhibition and gene depletion attenuated atherosclerosis in mice by decreasing the infiltration of monocytes into the artery wall. EET and PSGL-1 may play pivotal roles in monocyte/macrophage infiltration and atherogenesis.

Arachidonic acid (AA) metabolism plays an important role in vascular homeostasis. We reported that DNA hypomethylation of EPHX2 induced a pro-inflammatory response in vascular endothelial cells (ECs). However, the change in the whole AA metabolism by DNA methylation is still unknown. Using a metabolomic approach, we investigated the effect of DNA methylation on the balance of AA metabolism and the underlying mechanism. ECs were treated with a DNA methyltransferase inhibitor 5-aza-2'-deoxycytidine (5-AZA), and AA metabolic profiles were analyzed. Levels of prostaglandin D2 (PGD2) and thromboxane B2 (TXB2), metabolites in the cyclooxygenase (COX) pathway, were significantly increased by 5-AZA treatment in ECs resulting from the induction of PGD2 synthase (PTGDS) and thromboxane A synthase 1 (TBXAS1) expression by DNA hypomethylation. This phenomenon was also observed in liver and kidney cell lines, indicating a universal mechanism. Pathophysiologically, homocysteine, known to cause DNA demethylation, induced a similar pattern of the change of AA metabolism. Furthermore, 5-AZA activated ECs, as evidenced by the upregulation of adhesion molecules. Indomethacin, a COX inhibitor, reversed the effects of 5-AZA on the levels of PGD2 and TXB2, EC activation and monocyte adhesion. In vivo, the plasma levels of PGD2 and TXB2 and the expression of In vivo PTGDS and TBXAS1 as well as adhesion molecules were increased in the aorta of the mice injected with 5-AZA. In conclusion, using a metabolomic approach, our study uncovered that DNA demethylation increased AA metabolites PGD2 and TXB2 by upregulating the expression of the corresponding enzymes, which might contribute to the DNA hypomethylation-induced endothelial activation.

In recent years, with the rapid development of network and extensive adoption of J2EE platform, multi-layer Web structure based on B/S grows up gradually. Aiming at the intelligent and standardized management of power plant, this paper gives a detailed introduction of the structure and function of the identification system for power plants, as well as designing a database with great flexibility and extensibility and a system based on J2EE design. This system has improved the encoding specification, correctness and efficiency greatly. That is to say, the system, having been put into practice in a power plant in Guangxi, saves time and labor to a great extent.

The Pressurizer is important equipment in PWR nuclear power station. There is only one Pressurizer, which adjust and keep pressure stable, overall the One Loop System. It is very important for safe operation of nuclear power station to keep integrity of Pressurizer. To carry out the work of aging and life management of Pressurizer more effectively and ensure the Pressurizer run safe and stably, this paper does research on Aging and Life Management Methods of Pressurizer. On the basis of PDCA Cycle, this paper realize the management of leading principles to aging management, operation control, checking, monitoring, evaluation and program of lifetime maintenance.

The process of transformer fault diagnosis and the theory of DFTA are first presented in this paper and then we apply DFTA to the field of transformer faults diagnosis. By establishing the fault tree of transformer, a practical, easily-extended, interactive and self-learning enabled fault diagnosis system based on DFTA for transformer is designed and implemented. With the implementation and application of the DFTA diagnosis system, it's easy to get a reasonable result from the computer with the help of experts. The practical results demonstrated that the system can highly improve the accuracy of transformer fault diagnosis and effectively improve the reliability and safety transformer which brings much economic benefits in return.

With the development of power industry, power plants have been expanding. So in the planning and design, construction and operation stages, there is a wealth of information produced. However, the information management in all power plants are all complex and not standardized, which make the management's work very inconvenient, and that include all system, equipments and etc. In order to achieve the standardization and intelligent management, hydropower industry is placing more importance on the ERP implementation, while the core foundation data of the ERP system are from the device code. On the basis of a comprehensive study of domestic and foreign industrial applications, building the encoding software in the identification system of hydropower plant has been studied and corresponding design and instances of system are given. This paper studies achieves the management of the power plant information code and laid a stable foundation for the implementation of the ERP project.

Simulation of hydraulic turbine governing system plays an important role in teaching, testing and experimental study. This paper presents the overall structure of the ARM-based real-time simulation system on the basis of a comprehensive analysis of the characteristics of hydroelectric process. For the different object to build different fineness of model, this paper uses multi-scale modeling approach and rational scheduling mechanism to realize optimal operation of simulation, as well as designing the real-time enhanced program on a LINUX system. By comparison with the off-line system simulation of SIMULINK, the results show that the system is fully capable to meet the requirement of hydraulic turbine governing system on real-time, reflecting the advantages of real-time continuous simulation.

The necessity, significance and benefits of the research was analyzed, and the frame work and implementation scheme of the remote condition monitoring and diagnostic support system (RCMDSS) presented based on B/C/S. The distributed monitoring, diagnosis and information integration was realized by establishing the condition monitoring subsystem based on the field bus technology, and the difference among the soft-hardware platform, database and network protocol was shielded. The intelligent expression and interaction of knowledge were materialized through virtual reality technology. The multi-agent system (MAS) was incorporated, making the system more intelligent and independent in the remote condition monitoring and diagnostic decision. The system shows its integration, opening, safe and extension, etc.