Polydatin ameliorates renal fibrosis in a streptozotocin–induced rat model of diabetic nephropathy by inhibiting TLR4/NF-κB signaling

Purpose: To determine the effects of polydatin (PD) on a streptozotocin (STZ)-induced rat model of diabetic nephropathy (DN) and NRK-52E cells treated with high glucose (HG). Methods: Sprague Dawley rats received 65 mM STZ to model DN in vivo. NRK-52E cells were treated with HG, to model DN in vitro. Both models were treated with PD. Fasting blood glucose, kidney/body weight, urinary protein, serum creatinine, and blood urea nitrogen levels, interstitial injury score, as well as protein expression levels of connective tissue growth factor (CTGF), fibronectin, and collagen I were determined in DN rats after PD treatment. Enzyme-linked immunosorbent assay was used to measure inflammatory factors. Protein expression was determined by Western blot analysis while apoptosis was assessed by flow cytometry. Results: STZ successfully induced DN in rats. PD treatment significantly reduced kidney/body weight; decreased fasting blood glucose, urinary protein, serum creatinine, and blood urea nitrogen levels; lowered interstitial injury scores; and downregulated protein expression levels of CTGF, fibronectin, and collagen I. It also inhibited inflammatory reaction and suppressed Toll-like receptor (TLR4)/nuclear factor (NF)-κB signaling. Furthermore, PD suppressed apoptosis, reduced inflammatory factor levels, and suppressed TLR4/NF-κB signaling induced by HG in NRK-52E cells. Conclusion: PD exerts a protective role in DN by decreasing interstitial injury, reducing renal fibrosis, inhibiting inflammatory responses, and suppressing cell apoptosis, at least, partly via inactivation of TLR4/ NF-κB pathway

An Optimization to Schedule Train Operations with Phase-Regular Framework for Intercity Rail Lines

The most important operating problem for intercity rail lines, which are characterized with the train operations at rapid speed and high frequency, is to design a service-oriented schedule with the minimum cost. This paper proposes a phase-regular scheduling method which divides a day equally into several time blocks and applies a regular train-departing interval and the same train length for each period under the period-dependent demand conditions. A nonlinear mixed zero-one programming model, which could accurately calculate the passenger waiting time and the in-train crowded cost, is developed in this study. A hybrid genetic algorithm associated with the layered crossover and mutation operation is carefully designed to solve the proposed model. Finally, the effectiveness of the proposed model and algorithm is illustrated through the application to Hefei-Wuhan intercity rail line in China

A Bilevel Programming Model to Optimize Train Operation Based on Satisfaction for an Intercity Rail Line

The passenger travel demands for intercity rail lines fluctuate obviously during different time periods, which makes the rail departments unable to establish an even train operation scheme. This paper considers an optimization problem for train operations which respond to passenger travel demands of different periods in intercity rail lines. A satisfactory function of passenger travelling is proposed by means of analyzing the passengers’ travel choice behavior and correlative influencing factors. On this basis, the paper formulates a bilevel programming model which maximizes interests of railway enterprises and travelling satisfaction of each passenger. The trains operation in different periods can be optimized through upper layer planning of the model, while considering the passenger flow distribution problem based on the Wardrop user equilibrium principle in the lower layer planning. Then, a genetic algorithm is designed according to model features for solving the upper laying. The Frank-Wolfe algorithm is used for solving the lower layer planning. Finally, a numerical example is provided to demonstrate the application of the method proposed in this paper

Study on the Train Operation Optimization of Passenger Dedicated Lines Based on Satisfaction

The passenger transport demands at a given junction station fluctuate obviously in different time periods, which makes the rail departments unable to establish an even train operation schedule. This paper considers an optimization problem for train operations at the junction station in passenger dedicated lines. A satisfaction function of passengers is constructed by means of analyzing the satisfaction characteristics and correlative influencing factors. Through discussing the passengers’ travel choice behavior, we formulate an optimization model based on maximum passenger satisfaction for the junction and then design a heuristic algorithm. Finally, a numerical example is provided to demonstrate the application of the method proposed in this paper

Modeling and Algorithms of the Crew Rostering Problem with Given Cycle on High-Speed Railway Lines

This paper studies the modeling and algorithms of crew roster problem with given cycle on highspeed railway lines. Two feasible compilation strategies for work out the crew rostering plan are discussed, and then an integrated compilation method is proposed in this paper to obtain a plan with relatively higher regularity in execution and lower crew members arranged. The process of plan making is divided into two subproblems which are decomposition of crew legs and adjustment of nonmaximum crew roster scheme. The decomposition subproblem is transformed to finding a Hamilton chain with the best objective function in network which was solved by an improved ant colony algorithm, whereas the adjustment of nonmaximum crew rostering scheme is finally presented as a set covering problem and solved by a two-stage algorithm. The effectiveness of the proposed models and algorithms are testified by a numerical example

BmILF and I-motif Structure Are Involved in Transcriptional Regulation of \u3cem\u3eBmPOUM2\u3c/em\u3e in \u3cem\u3eBombyx mori\u3c/em\u3e

Guanine-rich and cytosine-rich DNA can form four-stranded DNA secondary structures called G-quadruplex (G4) and i-motif, respectively. These structures widely exist in genomes and play important roles in transcription, replication, translation and protection of telomeres. In this study, G4 and i-motif structures were identified in the promoter of the transcription factor gene BmPOUM2, which regulates the expression of the wing disc cuticle protein gene (BmWCP4) during metamorphosis. Disruption of the i-motif structure by base mutation, anti-sense oligonucleotides (ASOs) or inhibitory ligands resulted in significant decrease in the activity of the BmPOUM2 promoter. A novel i-motif binding protein (BmILF) was identified by pull-down experiment. BmILF specifically bound to the i-motif and activated the transcription of BmPOUM2. The promoter activity of BmPOUM2 was enhanced when BmILF was over-expressed and decreased when BmILF was knocked-down by RNA interference. This study for the first time demonstrated that BmILF and the i-motif structure participated in the regulation of gene transcription in insect metamorphosis and provides new insights into the molecular mechanism of the secondary structures in epigenetic regulation of gene transcription