Genome-wide by environment interaction studies of maternal smoking and educational score in UK biobank.

PURPOSE: This study aimed to investigate the associations between maternal smoking (MS) and education score in adult offspring. METHODS: To better understand this link, we performed a two-stage genome-wide by environment interaction studies (GWEIS) of MS and offspring education score in UK Biobank cohort. Specifically, 276 996 subjects from England were enrolled in the discovery study, while 24 355 subjects from Scotland and 14 526 subjects from Wales were enrolled in the replication study. GWEIS were conducted by PLINK 2.0 with MS used as an environmental risk factor. RESULTS: Significant GWEIS associations ( P  < 0.0001) between MS and offspring education score in both the discovery cohort and two replicate cohorts (Scotland population and Wales population) were identified. GWEIS identified 2 independent significant single nucleotide polymorphism-MS interaction, with one variant located in the chromosomal 16 (rs72768988, Position: 22,768,798, P  = 1.22 × 10 -8 , ß = 6.7662) and the other one located in 2q32.3 region (2 : 196424612_GT_G, Position: 196 424 612, 3.60 × 10 -9 , ß = -0.4721). CONCLUSION: Our results suggested 2q32.3 region and HECW2 gene could negatively moderate the influence of MS on offspring's educational status.

Optimal competition strategy analysis of China Railway Express based on evolutionary game theory.

In the context of the Belt and Road Initiative, China Railway Express achieved rapid development. Determining how to achieve effective marking and determining how to adopt the optimal competitive strategy are the main challenges for CR Express operators. By choosing long-distance transportation as the research object, this research established a competitive model between CR Express and maritime transportation based on game theory. First, we determined the participants of this competition. By dividing common goods into the categories of high-value and high-time-sensitiveness, high-value and low-time-sensitiveness, low-value and high-time-sensitiveness, and low-value and low-time-sensitiveness, the model was used to simulate four situations and to obtain optimal strategies for operators. For CR Express, it was always effective to adopt a service optimizing strategy to improve the service level and earn market share. For maritime transportation, this strategy was effective only for high-value and low-time-sensitiveness goods as well as low value and low-time-sensitiveness goods. Therefore, transportation service suppliers should make competitive strategies based on different good types, and it is effective to use differentiation strategies to earn market share and improve competitiveness only for suitable types of goods.

Optimized design to adverse transportation conditions for railway freight system.

This study proposed a method for transportation agencies to efficiently and accurately formulate or revise rules for the movement of railway transport while ensuring safety under adverse conditions. Determining such a method in general requires trial-and-error experimentation, which consumes large amounts of time and money. We used the uniform experiment (UE) and generalized linear autoregression (GLAR) to establish our method. Based on it, a series of numerical models were proposed to examine the association between the operational indices of safety (derailment coefficient and rate of wheel unloading) and such factors as the type of wagon, cargo weight, partial loading (covering longitudinal and lateral offset), line condition, and operating speed. The models were used to determine the worst transportation conditions. The results of analysis showed the following: 1) the effect of the speed of operation on the safety indices followed a parabolic law, those of cargo weight and part loading followed a linear law, the type of wagon and line condition exhibited no clear regularity, and some of these factors have an interactive influence. 2) A combination of the UE and GLAR helped deal with the complex multivariate process using the fewest multilevel experiments to accurately determine the most adverse conditions for railway freight transportation. The proposed method provided reference schemes for governmental agencies to study and revise freight management regulations.

China's Railway Transportation Safety Regulation System Based on Evolutionary Game Theory and System Dynamics.

China's railways were restructured in 2013. The number of regulatory practitioners has decreased significantly, making real-time regulation more difficult. Regulatory transfers from inside to outside the railway industry increases information risks. A more reasonable regulation mechanism is needed. The article considers introducing a public supervision mechanism into the railway transportation safety regulation system, which includes two regulators and one regulatee. As the government regulator, the State Railway Administration (SRA) regulates the safety of China Railway Corporation (CR) and encourages the public to act as supervisors to expose the CR's unsafe production information. To analyze the risks and effectiveness of the system, a multiplayer evolutionary game and system dynamics-based model for railway transportation safety regulation is established. The decision processes of players under different conditions are simulated. The results show that improving the public supervision ratio is conducive to improve the CR's safe production ratio. However, there is no evolutionarily stable strategy (ESS) in the system. Strategies and evolutionary processes have large fluctuations, which represent high risk. Excessive penalty and reward coefficients can aggravate the amplitude and frequency of fluctuations, causing uncertainty in regulation and making it more difficult to control the actual problems. A dynamic reward and punishment mechanism is proposed to control these fluctuations. The system finally achieves an ESS that results in the lowest regulation investment for the SRA, a safe production ratio for the CR of 95%, and a public supervision ratio of 95.2%. Introducing public supervision and dynamic reward and punishment mechanisms help to stabilize and improve the CR's safe production ratio and to decrease the SRA's regulatory investment.

Resveratrol ameliorates sepsis-induced acute kidney injury in a pediatric rat model via Nrf2 signaling pathway.

Acute kidney injury (AKI) is a hyper-inflammation-induced abrupt loss of kidney function and has become a major public health problem. The cecal ligation and puncture (CLP) model of peritonitis in rat pups mimics the development of sepsis-induced pediatric AKI is pre-renal without morphological changes of the kidneys and high lethality. Resveratrol, a natural polyphenolic compound with low toxicity, has obvious anti-oxidant and anti-inflammatory properties. The present study aimed to determine whether resveratrol alleviates pediatric AKI and investigated the potential mechanism. Thus, a CLP model of 17-18 day-old rat pups was used to mimic the development of sepsis-induced AKI in children. In the group treated with resveratrol, renal injury induced by CLP was alleviated with downregulation of tumor necrosis factor (TNF)-α, interleukin (IL)-1ß and kidney injury molecule (KIM)-1 expression. Nuclear factor-erythroid-2-related factor 2 (Nrf2) signaling is known to effectively inhibit inflammation, the present study found that resveratrol reduced the lipopolysaccharide-induced inflammatory response in kidney cells in vitro and induced the activation of Nrf2 signaling, including accumulation of nuclear Nrf2 and increase of the expression of Nrf2 target genes heme oxygenase (HO)-1 and NAD(P)H dehydrogenase (quinone) 1 (NQO1); this was confirmed by the induction of the expression of HO-1 and NQO1 by treatment of resveratrol in vitro and in vivo. Of note, knockdown of Nrf2 effectively abrogated the downregulation of TNF-α, IL-1ß and KIM-1 expression induced by resveratrol in vitro. These results suggested that resveratrol ameliorates sepsis-induced acute kidney injury in a pediatric model of AKI via the Nrf2 signaling pathway.