No abstract

The curative effect for patients with advanced gastric cancer is still unsatisfactory. Proton pump inhibitors could be a promising treatment strategy that could sensitize gastric cancer cells to antitumor drugs further; however, the underlying molecular mechanism remains to be further elucidated. In this research, it was found that omeprazole pretreatment could enhance the inhibitory effect of 5-Fu, DDP and TAX on gastric cancer cells. Interestingly, omeprazole pretreatment enhanced the total m6A level of cells due to the decreased FTO. TCGA analysis showed that FTO expression is up-regulated in GC tissues and is negatively correlated with disease-free survival of GC patients. It was also found that FTO inhibition induced by omeprazole enhanced the activation of mTORC1 signal pathway that inhibited the prosurvival autophagy so as to improve the antitumor efficiency of chemotherapeutic drugs on GC cells. Meanwhile, transcript level of DDIT3, which is an apoptosis-related tumor suppressor gene downstream of mTORC1, was regulated by omeprazole-induced FTO silence through an m6A-dependent mechanism. The present study, for the first time, found that m6A modification and its eraser FTO may play a role in the improvement of chemosensitivity mediated by proton pump inhibitor omeprazole.

One of the important functions of a communication network is the routing. The communication and performance of a network whose efficiency can be directly affected by edge-forwarding index of the routing and the edge-forwarding index can be used to deterministically measure its efficiency. This paper investigates edge-forwarding index of routing in the lexicographic product network, which is used to measure the congestion of an edge. Congestion of any edge is limited by the capacity of the edge; the original study of edge-forwarding index was motivated by the problem of maximizing network capacity, which is achieved by minimizing the forwarding index of a network. Thus, it is an important parameter to measure the quality of a routing. By applying the combination design and interconnection network, we characterize a closed upper bound on edge-forwarding index of the lexicographic product network. Such a boundary depends only on the parameters of the factor network, such as the edge-forwarding index of the factor network.

PurposeThe promotion of new energy vehicles (EVs) is an effective way to achieve low carbon emission reduction. This paper aims to investigate the optimal pricing of automotive supply chain members in the context of dual policy implementation while considering consumers' low-carbon preferences.Design/methodology/approachThis article takes manufacturers, retailers and consumers in a main three-level supply chain as the research object. Stackelberg game theory is used as the theoretical guidance. A game model in which the manufacturer is the leader and the retailer is the follower is established. The author also considered the impact of carbon tax policies, subsidy policies and consumer preferences on the results. Furthermore, the author investigates the optimal decision-making problem under the profit maximization model.FindingsThrough model solving, it is found that the pricing of EVs is positively correlated with the unit price of carbon and the amount of subsidies. The following conclusions can be obtained by numerical analysis of each parameter. Changes in carbon prices have a greater impact on conventional gasoline vehicles. Based on the numerical analysis of parameter β, it is also found that when the government subsidizes consumers, supply chain members will increase their prices to obtain partial subsidies. Compared with retailers, low-carbon preferences have a greater impact on manufacturers.Research limitations/implicationsThe new energy automobile industry involves many policies, including tax cuts, tax exemptions and subsidies. The policy environment faced by the members of a supply chain is complex and diverse. Therefore, the analysis in this article is based only on partial policies.Originality/valueThe authors innovatively combine the three factors of subsidy policy, carbon tax policy and consumer low-carbon preference, with research on the pricing of EVs. The influence of policy factors and consumer preferences on the pricing of EVs is studied.

Structural stability problem is the key problem in design of steel structural. The structural stability behavior of suspended dome is investigated by employing a computation model of the Kiewitt suspend-dome with a span of 92m. ANSYS were used in the investigation. The load-displacement path of the structure is studied by using the Newton-Raphson and arc-length method. The parameters that affect the structural elastic-plastic ultimate load-carrying capacity such as rise to span ratio, height of struts, and prestress of the cables below were analyzed. Some conclusions are drawn that improving the prestress can’t improve the ultimate load-carrying capacity and higher rise to span ratio, heights of struts can improve the ultimate load-carrying capacity.