CagA^+ H.pylori Induces Akt1 Phosphorylation and Inhibits Transcription of p21^(WAF1/CIP1) and p27^(KIP1) via PI3K/Akt1 Pathway

Objective Cytotoxin-associated protein （CagA） of H. pylori has been confirmed to be closely associated with gastric inflammation and tumorigenesis, but the mechanism behind it is little understood. In this study, we try to determine roles of CagA＋ strain in activating PI3K/Akt1 signaling pathway, and affecting expression of p21WAF1/CIP1 and p27KIP1, and also in releasing IL-8 in host cells. Methods Akt1 phosphorylation and IL-8 levels of CagA＋ and CagAˉ strain infected AGS cells were detected by ELISAs. Two quantitative RT-PCRs were established to measure p21WAF1/CIP1 and p27KIP1 mRNA levels in the CagA＋ and CagAˉ strain infected cells. LY294002, an inhibitor of PI3K/Akt pathway, was used to define effect of the pathway in IL-8 release. Results CagA＋ strain could induce an obvious elevation of Akt1 phosphorylation in the infected AGS cells while CagAˉ strain failed to do so. The CagA＋ H. pylori strain infected AGS cells showed significant drops both in p21WAF1/CIP1 and p27KIP1 mRNA levels, whereas the CagAˉ H. pylori strain caused a remarkable increase in p21WAF1/CIP1 mRNA without affecting p27KIP1 gene transcription in the AGS cells. Both the CagA＋ and CagAˉ H. pylori strains enabled AGS cells to produce close elevated levels of IL-8, and the LY294002 block resulted in unexpected elevations of IL-8 levels. Conclusion CagA can activate PI3K/Akt1 pathway that plays an inhibitory role in IL-8 release in H. pylori infected AGS cells. Activation of PI3K/Akt1 pathway and subsequent negative regulation of p21^WAF1/CIP1 and p27^KIP1 expression might be involved in CagA-associated carcinogenesis.

Effects of different chemotherapy regimens before radical operation for lung cancer on cancer cell growth and anti-tumor immune response

Objective:To investigate the effects of different chemotherapy regimens before radical operation for lung cancer on cancer cell growth and antitumor immune response.Methods: A total of 180 patients with primary lung cancer who underwent surgery in this hospital between February 2013 and August 2017 were divided into the cisplatin group (n=93) who received cisplatin & paclitaxel chemotherapy and the lobaplatin group (n=87) who received lobaplatin & paclitaxel chemotherapy according to different preoperative neoadjuvant chemotherapy regimens. The differences among the expression of proliferation genes and apoptosis genes in tumor tissues as well as the contents of Th1/Th2 cytokines in serum were compared between the two groups.Results: Proliferation genes DDX17, GPx1, MACC1, RACK1 and SIRT1 mRNA expression levels in tumor tissue of lobaplatin group were lower than those of cisplatin group whereas LRRC3B mRNA expression level was higher than that of cisplatin group;apoptosis gene Fas, FasL and Caspase-3 mRNA expression levels were higher than those of cisplatin group whereas Survivin and Bcl-2 mRNA expression levels were lower than those of cisplatin group;serum Th1 cytokines IFN-γ and IL-12 contents were higher than those of cisplatin group whereas Th2 cytokines IL-5 and IL-10 contents were lower than those of cisplatin group.Conclusion: Lobaplatin chemotherapy before radical operation for lung cancer is more effective than cisplatin chemotherapy to inhibit the proliferation activity and enhance the apoptosis activity of lung cancer cells and optimize the anti-tumor immune response.

A comparative study of differential evolution and genetic algorithms for optimizing the design of water distribution systems

The differential evolution(DE) algorithm has been received increasing attention in terms of optimizing the design for the water distribution systems(WDSs).This paper aims to carry out a comprehensive performance comparison between the new emerged DE algorithm and the most popular algorithm-the genetic algorithm(GA).A total of six benchmark WDS case studies were used with the number of decision variables ranging from 8 to 454.A preliminary sensitivity analysis was performed to select the most effective parameter values for both algorithms to enable the fair comparison.It is observed from the results that the DE algorithm consistently outperforms the GA in terms of both efficiency and the solution quality for each case study.Additionally,the DE algorithm was also compared with the previously published optimization algorithms based on the results for those six case studies,indicating that the DE exhibits comparable performance with other algorithms.It can be concluded that the DE is a newly promising optimization algorithm in the design of WDSs.

Hydrogen generation from methanol reforming under unprecedented mild conditions

A homogeneous catalyst [Cp＊Rh（NH3）（H2O）2]-（3＋） has been found for the clean conversion of methanol and water to hydrogen and carbon dioxide. The simple and easily available reaction steps can circumvent the formation of CO, therefore, making it possible to avoid inactivating catalysts and contaminating the hydrogen fuel. Different from conventional reforming method for hydrogen production, no additional alkaline or organic substances are required in this method. Valuable hydrogen can be obtained under ambient pressure at 70 C, corresponding TOF is 83.2 h 1. This is an unprecedented success in reforming methanol to hydrogen. Effects of reaction conditions, such as reaction temperature, initial methanol concentration and the initial p H value of buffer solution on the hydrogen evolution are all systematically investigated. In a certain range, higher reaction temperature will accelerate reaction rate. The slightly acidic condition is conducive to rapid hydrogen production. These findings are of great significance to the present establishment of the carbon-neutral methanol economy.

Identification of a novel mutation in the SRD5A2 gene of one patient with 46,XY disorder of sex development

Dear Editor, 46,XY disorder of sex development （DSD） is characterized by a female phenotype in an individual with a normal 46,XY karyotype.1 The clinical phenotTpe of 46,XY DSD is characterized by bilateral undescended testes and a normal female appearance, including breasts, female external genitalia, and other secondary sex characteristics, but the absence of a uterus or ovaries.2 Development of the male external genitalia in the fetal period depends on the biosynthesis of testosterone （T）, the conversion ofT into dihydrotestosterone （DHT） by steroid 5α-reductase type 2 （SRD5A2）, and the response of functionally active androgen receptors in genital tissues） The disruption of any of these stages will block the differentiation of internal and external genitalia and cause 46,XY DSD.

Integrated rainfall-runoff process with shallow water model by mass varied smoothed particle hydrodynamics:Infiltration effect implementation

Rainfall-runoff modeling is essential for addressing a wide range of issues in urban drainage system design and operation in both scientific research and engineering practice.Recently,it has become increasingly attractive to use the smoothed particle hydrodynamics(SPH)method to model rainfall-runoff because of its inherent features such as mesh-free and automatic adaptiveness for wet-dry interfaces.However,one of its inadequacies is the lack of an infiltration effect within rainfall-runoff modeling.Hence,we propose a new methodology that innovatively integrates the infiltration effect into the shallow water equation(SWE)system with the SPH method(SPH-SWE)to represent a more complete rainfall-runoff process.In the proposed method,the mass-varied SPH-SWE(MVSPH-SWE)method is enhanced by integrating the infiltration model.A naked area treatment(NAT)method is subsequently proposed to improve the modeling efficiency and accuracy.The obtained numerical results are validated using experimental data from the literature.The results demonstrate that the proposed method is accurate and reliable.The achievements and findings of this study are expected to improve and extend the use of existing hydrological process models.

Epidemic Spreading with Time Delay on Complex Networks

In this paper, we propose a susceptible-infected-susceptible （SIS） model on complex networks, small-world （WS） networks and scale-free （SF） networks, to study the epidemic spreading behavior with time delay which is added into the infected phase. Considering the uniform delay, the basic reproduction number R0 on WS networks and ~ on SF networks are obtained respectively. On WS networks, if R0 〈 1, there is a disease-free equilibrium and it is locally asymptotically stable; if R0 〉 1, there is an epidemic equilibrium and it is locally asymptotically stable. On SF networks, if R0 〈_4 1, there is a disease-free equilibrium; if -R0 〉 1, there is an epidemic equilibrium. Finally, we carry out simulations to verify the conclusions and analyze the effect of the time delay T, the effective rate A, average connectivity 〈k） and the minimum connectivity m on the epidemic spreading.