The Quadratic Shortest Path Problem and its Genetic Algorithm

The quadratic shortest path (QSP) problem is to find a path from a node to another node in a given network such that the total cost includes two kinds of costs, say direct cost and interactive cost, is minimum. The direct cost is the cost associated with each arc and the interactive cost occurs when two arcs appear simultaneously in the shortest path. In this paper, the concept of the quadratic shortest path is initialized firstly. Then a spanning tree-based genetic algorithm is designed for solving the quadratic shortest path problem. Finally, a numerical example is given

Protective Effect of Phillyrin on Lethal LPS-Induced Neutrophil Inflammation in Zebrafish

Background/Aims: Forsythia suspensa Vahl. (Oleaceae) fruits are widely used in traditional Chinese medicine to treat pneumonia, typhoid, dysentery, ulcers and oedema. Antibacterial and anti-inflammatory activities have been reported for phillyrin (PHN), the main ingredient in Forsythia suspensa Vahl fruits, in vitro. However, the underlying mechanisms in vivo remain poorly defined. In this study, we discovered that PHN exerted potent anti-inflammatory effects in lethal LPS-induced neutrophil inflammation by suppressing the MyD88-dependent signalling pathway in zebrafish. Methods: LPS-yolk microinjection was used to induce a lethal LPS-infected zebrafish model. The effect of PHN on the survival of zebrafish challenged with lethal LPS was evaluated using survival analysis. The effect of PHN on neutrophil inflammation grading in vivo was assessed by tracking neutrophils with a transgenic line. The effects of PHN on neutrophil production and migration were analysed by SB+ cell counts during consecutive hours after modelling. Additionally, key cytokines and members of the MyD88 signalling pathway that are involved in inflammatory response were detected using quantitative RT-PCR. To assess gene expression changes during consecutive hours after modelling, the IL-1β, IL-6, TNF-α, MyD88, TRIF, ERK1/2, JNK, IκBa and NF-κB expression levels were measured. Results: PHN could protect zebrafish against a lethal LPS challenge in a dose-dependent manner, as indicated by decreased neutrophil infltration, reduced tissue necrosis and increased survival rates. Up-regulated IL-1β, IL-6 and TNF-α expression also showed the same tendencies of depression by PHN. Critically, PHN significantly inhibited the LPS-induced activation of MyD88, IκBa, and NF-κB but did not affect the expression of ERK1/2 MAPKs or JNK MAPKs in LPS-stimulated zebrafish. Additionally, PHN regulated the MyD88/IκBα/NF-κB signalling pathway by controlling IκBα, IL-1β, IL-6, and TNF-α expression. Conclusion: This study provides a rationale for the clinical application of PHN as an anti-inflammatory agent

Liquiritin exhibits anti-acute lung injury activities through suppressing the JNK/Nur77/c-Jun pathway

Abstract Background Licorice (Glycyrrhiza uralensis Fisch.), a well-known traditional medicine, is traditionally used for the treatment of respiratory disorders, such as cough, sore throat, asthma and bronchitis. We aim to investigate the effects of liquiritin (LQ), the main bioactive compound in licorice against acute lung injury (ALI) and explore the potential mechanism. Methods Lipopolysaccharide (LPS) was used to induce inflammation in RAW264.7 cells and zebrafish. Intratracheal instillation of 3 mg/kg of LPS was used for induction an ALI mice model. The concentrations of IL-6 and TNF-α were tested using the enzyme linked immunosorbent assay. Western blot analysis was used to detect the expression of JNK/Nur77/c-Jun related proteins. Protein levels in bronchoalveolar lavage fluid (BALF) was measured by BCA protein assay. The effect of JNK on Nur77 transcriptional activity was determined by luciferase reporter assay, while electrophoretic mobility shift assay was used to examine the c-Jun DNA binding activity. Results LQ has significant anti-inflammatory effects in zebrafish and RAW264.7 cells. LQ inhibited the expression levels of p-JNK (Thr183/Tyr185), p-Nur77 (Ser351) and p-c-Jun (Ser63), while elevated the Nur77 expression level. Inhibition of JNK by a specific inhibitor or small interfering RNA enhanced the regulatory effect of LQ on Nur77/c-Jun, while JNK agonist abrogated LQ-mediated effects. Moreover, Nur77-luciferase reporter activity was suppressed after JNK overexpression. The effects of LQ on the expression level of c-Jun and the binding activity of c-Jun with DNA were attenuated after Nur77 siRNA treatment. LQ significantly ameliorated LPS-induced ALI with the reduction of lung water content and BALF protein content, the downregulation of TNF-α and IL-6 levels in lung BALF and the suppression of JNK/Nur77/c-Jun signaling, which can be reversed by a specific JNK agonist. Conclusion Our results indicated that LQ exerts significant protective effects against LPS-induced inflammation both in vivo and in vitro via suppressing the activation of JNK, and consequently inhibiting the Nur77/c-Jun signaling pathway. Our study suggests that LQ may be a potential therapeutic candidate for ALI and inflammatory disorders

Tuning homogenization of high-strength aluminum alloys through thermodynamic alloying approach

The alloy design and homogenization processes are intimately associated with the microstructure, phase composition and performance for Al-Zn-Mg-Cu alloys. The microstructures and phase composition of a series of Al-Zn-Mg-Cu alloys before and after the homogenization treatments were investigated along with thermodynamic calculation to understand the underlying relationship. The eutectic microstructures (α-Al + M (Mg(ZnAlCu)2)) are dominating with Cu-enriched [AlCuMgZn] particles, both depending on the Zn:Mg ratio and (Cu + Mg) content, in addition to minor constituent θ (Al2Cu) and Al7Cu2Fe phases in the as-cast alloys. The optimal homogenization process was suggested based on the analysis of the residual phases (i.e., the S (Al2CuMg) phase) since all (for low/mediate-(Cu + Mg) alloys) or partially (for high-(Cu + Mg) alloys (∼>4.24 wt%)) S (Al2CuMg) particles were dissolved during the homogenization. This residual S phase may be transformed from the primary M and/or Cu-enriched [AlCuMgZn] phases. The homogenization kinetics calculation results agreed well with above experimental results. A critical (Cu + Mg) level and a linear correlation between Cu and Mg concentrations were revealed based on the thermodynamically modelling, which can be conductive to determine the optimal homogenization process. Furthermore, the solubility limit and stoichiometric balance principles based on controlling the homogenized microstructures can guide the composition design for advanced high-strength aluminum alloys.Team Jilt Sietsm

ISL suppressed sprout formation on the chick aortic ring.

<p>The chick aortic ring was embedded in Matrigel and fed with M199 serum free medium containing various concentrations of ISL in the presence of VEGF. (A) ISL exhibited dose-dependently inhibition effects (a: 0; b: 5 µM, c: 10 µM; d: 20 µM) on the sprout formation after 3 days; (B) ISL at 20 µM significantly inhibited sprout formation in a time-dependent manner from 24 h to 72 h; (C) Sprout inhibition effects of ISL was reversed after ISL removed from the culture system. Aortic rings were firstly incubated with ISL (20 uM ) for 48 h. The culture medium was then replaced with fresh medium without ISL and further incubation with VEGF stimulation for 72 h, the sprout was re-organized and growing, indicating ISL brought little toxicity effects on the normal tissues. (All values represented as means ± SD, n = 3, * <i>P</i><0.05 <i>versus</i> untreated control).</p

ISL inhibited endothelial cells proliferation.

<p>(A) After incubation with various concentrations of ISL for 48 h with and without VEGF stimulation, the number of endothelial cells were counted. The results showed that the HUVEC proliferation was inhibited by ISL in a dose-dependent manner; (B) Breast cancer cells MDA-MB-231, MCF-7 and endothelial cells were treated with various concentrations of ISL and cells were counted after 48 h. ISL exhibited a specific proliferation inhibition effect on endothelial cells in comparison with that of breast cancer cells. Data are represented as a percentage of the vehicle-treated control; (C) Endothelial cells were treated with various concentrations of ISL plus with VEGF stimulation for 48 h and labeling with BrdU. DNA synthesis was measured by enzyme-linked immunosorbent assay. ISL significantly suppressed DNA synthesis of endothelial cells in a dose-dependent manner; (D) Cell cycle analysis revealed that after ISL (20 µM) treatment for 48 h, the cell cycle of HUVECs was significantly arrested at G2/M checkpoint; (E) Endothelial cells culture supernatants after ISL treatment were collected and analyzed for LDH activity assay. The results showed that ISL administration did not lead to LDH release from cells, indicating that ISL has little cytotoxicty effect on endothelial cells; (F) After ISL (20 µM) administration for 48 h, there has little morphological changes of endothelial cells, further implying that ISL brought limited toxicity effects on HUVECs at low doses. (All values represented as mean ± SD, n = 6, *<i>P</i><0.05, ** <i>P</i><0.01 <i>versus</i> untreated control).</p