As a calcineurin inhibitor, tacrolimus is commonly used as a first-line immunosuppressant in organ transplant recipients. Post-transplantation diabetes mellitus (PTDM) is a common complication following kidney transplantation and is associated with immunosuppressant drugs, such as tacrolimus. PTDM caused by tacrolimus may be related to its influence on insulin secretion and insulin resistance. However, the specific mechanism has not been fully elucidated. The aim of the present study was to investigate whether the PI3K/Akt/mTOR signaling pathway served an important role in the pathogenesis of PTDM induced by tacrolimus. In the present study, the Cell Counting Kit-8 assay was used to measure the effect of tacrolimus on the viability of Min6 mouse insulinoma cells. The effects of tacrolimus on the insulin secretion and the activity of caspase-3 of Min6 cells stimulated by glucose exposure were measured by ELISA. Superoxide dismutase (SOD) and malondialdehyde (MDA) levels were measured using WST-8 and thiobarbituric acid assays, respectively. The effects of tacrolimus on the mRNA expression levels of PI3K, Akt and mTOR were detected by reverse transcription-quantitative PCR (RT-qPCR), whereas the protein expression levels of PI3K, Akt, mTOR, phosphorylated (p)-AKT and p-mTOR in Min6 cells were assessed using western blotting. The present data indicated that, compared with the control group, 5, 25 and 50 ng/ml tacrolimus treatment could inhibit the insulin secretion of Min6 cells stimulated by glucose solution, and 50 ng/ml tacrolimus could notably decrease the stimulation index (P<0.05). Moreover, 50 ng/ml tacrolimus markedly increased the activity of caspase-3 by 175.1% (P<0.05), it also decreased the SOD activity (P<0.01) and increased MDA levels (P<0.05). The RT-qPCR results demonstrated that the mRNA expression levels of PI3K, Akt and mTOR were downregulated by 25 and 50 ng/ml tacrolimus (P<0.01). Furthermore, the western blotting results suggested that tacrolimus had no significant effects on the expression levels of total PI3K, Akt and mTOR proteins (P>0.05), but 25 and 50 ng/ml tacrolimus could significantly inhibit the expression levels of p-Akt and p-mTOR (P<0.01). In conclusion, tacrolimus decreased the activity and insulin secretion of pancreatic β cells and induced the apoptosis of islet β cells by inhibiting the mRNA expression levels of PI3K, Akt and mTOR and reducing the phosphorylation of Akt and mTOR proteins in the PI3K/Akt/mTOR signaling pathway, which may ultimately lead to the occurrence of diabetes mellitus, and may be considered as one of the specific mechanisms of PTDM caused by tacrolimus.

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Droughts, considered one of the most dangerous and costly water cycle expressions, always occurs over a certain region, lasting several weeks or months, and involving multiple variables. In this work, a multivariate approach was used for the statistical characterization of hydrological droughts in Shaying River Basin with data from 1959–2008. The standard runoff index (SRI) and the run theory were employed to defined hydrological drought character variables (duration, severity, and intensity peak). Then, a multivariate joint probability analysis with four symmetric and corresponding asymmetric Archimedean Copulas was presented; and the multivariate frequency analysis with the joint return periods (Tand and Tor) were estimated. The results showed that the hydrological droughts have a severity of 4.79 and 5.09, and the drought intensity peak is of 1.35 and 1.50 in Zhoukou station and Luohe station, respectively; the rank correlation coefficients τ are more than 0.5, which means multivariate copulas can effectively describe the joint frequency distributions among multivariate variables. Drought risk shows a spatial variation: the downstream observed at Zhoukou station is characterized by a higher multivariate drought risk. In general, multivariate copulas provide a reliable method when constructing a comprehensive drought index and evaluating multivariate drought characteristics. Thus, this paper can provide useful indications for the multi-dimensional droughts’ risks assessment in Shaying River Basin.

This study aimed at investigating the applicability of a SWAT (Soil and Water Assessment Tool) model in understanding the effects of drought on summer maize. A real-time irrigation module was developed for the downstream irrigation area of the Yellow River to estimate the real-time irrigation of crops. By further simulating the dynamic evolution process of soil moisture content, a dynamic drought evaluation model of summer maize was established, and the relative soil moisture was set as the evaluation index to assess and analyze the dynamic variation of drought evolution during the growth of summer maize. The results showed that the improved SWAT model has strong applicability. During the growth of summer maize, the variation trend of drought is consistent with that of natural precipitation. Moreover, drought mainly occurs during the sowing-seedling and seedling-jointing stages, and the average frequency is 84.8 and 78.3%, respectively. Moderate drought is most likely to occur during the growth of summer maize and occurs mainly during the sowing-seedling and seedling-jointing stages, and the occurrence frequency is 55.3 and 32.6%, respectively. Extra-severe drought has the greatest impact, mainly in the jointing-tasseling, tasseling-milking and milking-maturity stages, and the occurrence frequency is 17.4, 15.2 and 10.9%, respectively.