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Study of the positive effects of LMET-SFP in high-fat diet and streptozotocin-induced diabetic rats, and the underlying mechanisms of LMET-SFP as compared to metformin alone in managing diabetes.

MPP could improve diabetes by remodeling intestinal flora and regulating gene expression related to glycolipid metabolism.

Rheumatoid arthritis (RA) is an autoimmune disease characterized by synovial joint hyperplasia, joint inflammation, cartilage erosion and bone destruction. Macrophages play an essential role in the pathogenesis of RA, and folate receptor β (FR-β) is highly expressed on the surface of activated synovial macrophages in RA patients. Triptolide (TP) has anti-inflammatory properties, and it can protect the cartilage matrix, but its clinical application has been limited due to poor solubility, low bioavailability and systemic toxicity. Therefore, we constructed folate-modified triptolide liposomes (FA-TP-Lips) to target macrophages, thereby treating RA in a safe and effective way. The experiments indicated that FA-TP-Lips had properties of small particle size, uniform particle size distribution, high drug encapsulation and long circulation. Furthermore, FA-TP-Lips showed reduced cytotoxicity, increased cellular uptake and significant anti-inflammatory effects

During the tension process, single crystal and polycrystal bear plastic strain through stacking faults and grain boundaries, respectively. In addition metallic glass bears plastic strain through tacking faults and grain boundaries.

This paper proposes a bilevel game-theoretic model for multiple strategic retailers participating in both wholesale and local electricity markets while considering customers’ switching behaviors. At the upper level, each retailer maximizes its own profit by making optimal pricing decisions in the retail market and bidding decisions in the day-ahead wholesale (DAW) and local power exchange (LPE) markets. The interaction among multiple strategic retailers is formulated using the Bertrand competition model. For the lower level, there are three optimization problems. First, the welfare maximization problem is formulated for customers to model their switching behaviors among different retailers. Second, a market-clearing problem is formulated for the independent system operator (ISO) in the DAW market. Third, a novel LPE market is developed for retailers to facilitate their power balancing. In addition, the bilevel multi-leader multi-follower Stackelberg game forms an equilibrium problem with equilibrium constraints (EPEC) problem, which is solved by the diagonalization algorithm. Numerical results demonstrate the feasibility and effectiveness of the EPEC model and the importance of modeling customers’ switching behaviors. We corroborate that incentivizing customers’ switching behaviors and increasing the number of retailers facilitates retail competition, which results in reducing strategic retailers’ retail prices and profits. Moreover, the relationship between customers’ switching behaviors and welfare is reflected by a balance between the electricity purchasing cost (i.e., electricity price) and the electricity consumption level.

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A key objective for herbicide research is to develop new compounds with improved bioactivity. Protoporphyrinogen IX oxidase (PPO) is an essential target for herbicide discovery. Here, we report using an in silico structure-guided optimization approach of our previous lead compound 1 and designed and synthesized a new series of compounds 2-6. Systematic bioassays led to the discovery of a highly potent compound 6g, 1-methyl-3-(2,2,7-trifluoro-3-oxo-4-(prop-2-yn-1-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazin-6-yl)thieno[2,3-d]pyrimidine-2,4(1H,3H)-dione, which exhibited an excellent and wide spectrum of weed control at the rates of 30-75 g ai/ha by the postemergence application and is relatively safe on maize at 75 g ai/ha. Additionally, the Ki value of 6g to Nicotiana tabacum PPO (NtPPO) was found to be 2.5 nM, showing 3-, 12-, and 18-fold higher potency relative to compound 1 (Ki = 7.4 nM), trifludimoxazin (Ki = 31 nM), and flumioxazin (Ki = 46 nM), respectively. Furthermore, molecular simulations further suggested that the thieno[2,3-d]pyrimidine-2,4-dione moiety of 6g could form a more favorable π-π stacking interaction with the Phe392 of NtPPO than the heterocyclic moiety of compound 1. This study provides an effective strategy to obtain enzyme inhibitors with improved performance through molecular simulation and structure-guided optimization.

Due to their fast response ability and high ramping rates, pumped-storage hydropower (PSH) plants are playing an increasingly critical role in mitigating power generation fluctuations induced by the growing proliferation of renewable energy resources. However, because they are energy-limited resources, actual reserve deployment from PSHs would cause the deviation of state-of-charge (SOC) from the scheduled value, which, once accumulated over time, could induce potential violations of SOC limits and cause non-dispatchability of PSHs. In recognizing this potential issue, it can become important to securing the reserve schedule of PSHs and other energy limited resources preventively in the day-ahead market clearing. To ensure reserve dispatchability of PSHs despite SOC deviations, this paper proposes the reserve secure constraints, which are cast as a distributionally robust chance-constrained formulation by judiciously introducing random parameters to describe deployment ratios of scheduled regulation reserve from PSHs. These constraints are converted into tractable second-order cone constraints, and further approximated as linear constraints to be compatible with the current ISO day-ahead market clearing model. A modified IEEE 118-bus system with multiple PSHs is adopted to verify the proposed approach.

Objective To discover the mechanism of the sirtuin 1 (SIRT1)-mediated nuclear factor-κB (NF-κB) pathway in the protection against necrotizing enterocolitis (NEC) in neonatal mice. Materials and Methods Neonatal mice were treated with EX527 (an inhibitor of SIRT1) and/or pyrrolidine dithiocarbamate (PDTC, an inhibitor of NF-κB). The survival rate of the mice was recorded. Hematoxylin and eosin (HE) staining was performed to observe the pathological changes in the intestines. Furthermore, western blotting, enzyme-linked immunosorbent assay, and real-time quantitative polymerase chain reaction were conducted to measure the protein and gene expression, while corresponding kits were used to detect the levels of oxidative stress indicators. Results PDTC increased the survival rate of NEC mice. When compared with the NEC+ EX527 + PDTC group, the histological NEC score was higher in the NEC + EX527 group but lower in the NEC + PDTC group. SIRT1 expression in the intestines of NEC mice was downregulated, with an increase in p65 nuclear translocation. Additionally, malondialdehyde increased and glutathione peroxidase decreased in the intestines of NEC mice, with the upregulation of interleukin (IL)-6, IL-1β, and tumor necrosis factor-α, as well as the downregulation of ZO-1, occludin, and claudin-4 in the intestines. However, the above changes could be improved by PDTC, which could be further reversed by EX527. Conclusion SIRT1 can mitigate inflammation and the oxidative stress response and improve intestinal permeability by mediating the NF-κB pathway, playing an important role in the alleviation of NEC.

A molecular dynamics simulation has been conducted in Ni73Co27 and Ni74Co26 alloys during rapid solidification at the cooling rate of 1 × 1012 K/s. It indicates that two phase transitions occur with twice drops, and the number of FCC increases suddenly in Ni73Co27 alloy. And finally, FCC atoms are dominant with the amount of 92.94% at 300 K, which neatly arranges themselves into the crystalline structure. A lot of topologically close-packed clusters are formed in Ni74Co26 alloy, indicating the formation of metallic glass. The differences between the formations in crystalline hexagon and amorphous pentagon are demonstrated by three-dimensional visualization.

In this study, molecular dynamics (MD) was used to simulate the rapid solidification process of Ni47Co53 and Ni48Co52 alloys at a cooling rate of 1012 K/s. The effects of HCP on the formation of twin boundaries and dislocations in two Ni–Co alloys are studied. It is found that the difference of HCP clusters is the main effect that producing discrepancies on microstructure of two alloys. The number of HCP clusters accounted for 9.23% in Ni47Co53 alloy. They are regularly arranged to form the number of single-layer twin boundaries, and each twin boundary ends in a dislocation. The FCC and HCP structures coexist in the same atomic layers, which is easy to create dislocations. The relatively standard FCC crystal and only 0.32% HCP clusters are formed in Ni48Co52 alloy at 300 K. That small amount of HCP clusters are dispersed on the surface, and cause the formation of dislocation in the border with FCC clusters.

Dong-Mei Cai,1,&ast; Fan-Biao Mei,1,&ast; Chao-Jun Zhang,1 San-Chun An,1 Rui-Bo Lv,1 Guan-Hua Ren,1 Chan-Chan Xiao,1 Long Long,1,2 Tian-Ren Huang,1,2 Wei Deng1,2 1Department of Experimental Research, Guangxi Medical University Cancer Hospital, Nanning, Guangxi, 530021, People’s Republic of China; 2Guangxi Cancer Molecular Medicine Engineering Research Center, Nanning, Guangxi, 530021, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wei Deng; Tianren Huang, Department of Experimental Research, Guangxi Medical University Cancer Hospital, No. 71, Hedi Road, Nanning, Guangxi, 530021, People’s Republic of China, Email dengwei@gxmu.edu.cn; tianrenhuang@sina.comBackground: Microcystin-LR (MC-LR) and hepatitis B virus (HBV) are associated with hepatocellular carcinoma (HCC). However, the concentrations of MC-LR in drinking water and the synergistic effect of MC-LR and HBV on hepatocellular carcinogenesis through their disturbance of redox balance have not been fully elucidated.Methods: We measured the MC-LR concentrations in 168 drinking water samples of areas with a high incidence of HCC. The relationships between MC-LR and both redox status and liver diseases in 177 local residents were analyzed. The hepatoma cell line HepG2 transfected with C-terminal truncated hepatitis B virus X gene (Ct-HBX) were treated with MC-LR. Reactive oxygen species (ROS), superoxide dismutase (SOD), glutathione (GSH) and malondialdehyde (MDA) were measured. Cell proliferation, migration, invasion, and apoptosis were assessed with cell activity assays, scratch and transwell assays, and flow cytometry, respectively. The mRNA and protein expression-related redox status genes were analyzed with qPCR and Western blotting.Results: The average concentration of MC-LR in well water, river water and reservoir water were 57.55 ng/L, 76.74 ng/L and 132.86 ng/L respectively, and the differences were statistically significant (P < 0.05). The MC-LR levels in drinking water were correlated with liver health status, including hepatitis, clonorchiasis, glutamic pyruvic transaminase abnormalities and hepatitis B surface antigen carriage (all P values < 0.05). The serum MDA increased in subjects who drank reservoir water and were infected with HBV (P < 0.05). In the cell experiment, ROS increased when Ct-HBX-transfected HepG2 cells were treated with MC-LR, followed by a decrease in SOD and GSH and an increase in MDA. MC-LR combined with Ct-HBX promoted the proliferation, migration and invasion of HepG2 cells, upregulated the mRNA and protein expression of MAOA gene, and downregulated UCP2 and GPX1 genes.Conclusion: MC-LR and HBV may synergistically affect redox status and play an important role in hepatocarcinoma genesis.Keywords: hepatocellular carcinoma, microcystins-LR, hepatitis B virus X gene, redox balance

To prevent the scale formation in the equipments and pipelines after pre-treated coal gasification gray water (CGGW) entering the reuse system and reduce the influence of various pollutants in the effluent on subsequent biochemical treatment, this study presented a coupled use of pulse electrocoagulation (PEC) and chemical precipitation (CP) coupling method for the pretreatment of coal gasification gray water (CGGW). In addition, the operation parameters of PEC and the reaction conditions of PEC-CP were optimized based on iron plate as electrode and total hardness, turbidity and sludge yield as assessment indicators. Due to the formation of multi-hydroxyl iron by several minutes of pulse current, and the addition of pH regulator and coagulant aid, the efficient removal of various ions, hardness and turbidity was significantly reduced via various mechanism such as redox, precipitation, adsorption and coagulation reaction. The result indicated that under the optimal operation conditions, the total hardness, turbidity, and Fe

Smart grid is built by combination of electric and information technologies and achieves the two-way interaction between power utilization and power generation. Unfortunately, new security threats appears together with cyber-physical communication systems. In order to properly monitor power network, an effective cyber attack detection and state estimation method are required to know attack and system states. This article considers the problem of robust grid state estimation and suggests a technique for distributed state estimation in power networks. First, the distribution power system incorporating multiple synchronous generators is modeled as a state-space framework, where attack occurs in measurements. Basically, the false data injection attacks can interfere with state estimation process by tampering with sensor measurements. Using mean squared error principle, the distributed dynamic state estimation algorithm is designed where local and neighboring gains are obtained using optimal filter and graph theory. For local gain computation, the attack parameter is obtained using the Bayesian learning process. The convergence condition of the proposed approach is derived. Extensive simulation results show that the proposed approach is able to estimate the system state within a short period of time. Hopefully, the proposed methodology can be used to tolerate the cyber attacks for improving the confidence of the grid state estimation process.

Mei Liu,1,2 Rui-Bo Wang,1 Jian-Hong Xing,2 Ying-Xue Tang3 1Chinese Medicine College, Shandong University of Traditional Chinese Medicine, Jinan, 250355, Shandong, People’s Republic of China; 2Department of Obstetrics, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, 250011, Shandong, People’s Republic of China; 3Postgraduate Department, Shandong University of Traditional Chinese Medicine, Jinan, 250355, ShandongCorrespondence: Ying-Xue TangPostgraduate Department, Shandong University of Traditional Chinese Medicine, Changqing Campus of Shandong University of Traditional Chinese Medicine, Jinan, 250355, Shandong, People’s Republic of ChinaTel +8653189628067Email doctortyx@163.comBackground: Preeclampsia (PE), a serious pregnancy disorder, is responsible for maternal and fetal mortality worldwide. At present, numerous candidate biomarkers have been studied to predict PE.Objective: To explore the role of Corin in PE risk prediction and then evaluate the predictive ability of soluble vascular endothelial growth factor receptor-1 (sFlt-1), placenta growth factor (PLGF), and sFlt-1/PLGF after the addition of Corin.Methods: A total of 135 pregnant women from Affiliated Hospital of Shandong University of Traditional Chinese Medicine participated in this study in their first trimester. A nested case–control study was conducted and all subjects were divided into PE groups (n=46) and controls (n=89). The levels of PLGF, sFlt-1, sFlt-1/PLGF ratio, and Corin of the two groups at 12– 16 weeks of gestation were measured and analyzed. Receiver operating characteristic (ROC) curve, net reclassification index (NRI) and integrated discrimination index (IDI) were calculated to evaluate the predictive ability of various biomarkers.Results: The concentrations of sFlt-1, sFlt-1/PLGF, and Corin in PE group were significantly higher than that in controls, while the concentration of PLGF in the PE group was lower. The area under curve (AUC) of sFlt-1, PLGF and sFlt-1/PLGF for predicting PE was 0.786, 0.719 and 0.866, respectively. Combined with Corin, the prediction ability of the above biomarkers could be improved to 0.876, 0.847, and 0.897, respectively. Corin in combination with sFlt-1/PLGF resulted in improvements with 12.6% being reclassified and a resulting NRI of 0.142 (0.020∼ 0.263) and IDI of 0.087 (0.037∼ 0.137).Conclusion: The addition of Corin to sFlt-1, PLGF and sFlt-1/PLGF can improve the ability of each marker to predict PE risk. Corin in combination with sFlt-1/PLGF can be used as ideal markers to identify the pregnant women who subsequently develop PE, which will help in risk stratification and better therapeutic management.Keywords: preeclampsia, Corin, soluble vascular endothelial growth factor receptor-1, placental growth factor, prediction

Objective To discover the mechanism of Sirtuin1 (SIRT1)-mediated NF-κB pathway in the protection of necrotizing enterocolitis (NEC) in neonatal mice. Methods Neonatal mice were treated with EX527 (an inhibitor of SIRT1) and/or pyrrolidine dithiocarbamate (PDTC, an inhibitor of NF-κB). The survival rate of mice was recorded. Hematoxylin & eosin (HE) staining was performed to observe the pathological changes of intestines. Furthermore, western blotting, Enzyme-linked immuno sorbent assay (ELISA), and real-time quantitative polymerase chain reaction (qRT-PCR) were conducted to measure the protein and gene expression, while corresponding kits to detect the levels of oxidative stress indicators. Results PDTC increased the survival rate of NEC mice. When compared with the NEC + EX527 + PDTC group, the histological score of NEC was higher in the NEC + EX527 group but was lower in the NEC + PDTC group. SIRT1 expression in the intestines of NEC mice was down-regulated, with an increase in p65 nuclear translocation. Also, MDA increased and GPx decreased in the intestines of NEC mice, with the up-regulations of IL-6, IL-1β and TNF-α, as well as the down-regulations of ZO-1, occludin and claudin-4 in the intestines. However, changes above could be improved by PDTC, which would be further reversed by EX527. Conclusion SIRT1 could mitigate inflammation and oxidative stress response and improve the intestinal permeability by mediating NF-κB pathway, playing an important role in the alleviation of NEC.