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In recent years, fatigue cracking in orthotropic steel bridge deck pavements has become a significant concern, so the investigation of the mechanical response of the pavement layer has become a central focus in pavement structure design. This experiment subjected a full-scale specimen to a constant amplitude dynamic load of 60 kN to 300 kN over 2 million cycles. Throughout the testing, a circulating water bath elevated the temperature of the pavement layer from 15 °C to 50 °C. Key locations were monitored for strain and deflection data, facilitating an investigation into the mechanical response of the epoxy asphalt pavement system under the effects of temperature and load. The results indicate that the maximum transverse strain at the bottom of the steel deck occurs at the U-rib weld aligned with the load center, reaching 190% of the initial loading strain. Meanwhile, the maximum transverse strain on the pavement surface is observed at the U-rib weld adjacent to the loaded area, measuring 167% of the initial strain. The maximum longitudinal strain is lower than the maximum transverse strain. In the load zone, the longitudinal strain between the U-ribs exceeds that at the U-rib weld. Both transverse strain and relative deflection increase as the load intensifies. The relationship between transverse strain and applied load is characterized by an exponential function, while deflection exhibits a cubic relationship with the applied load. Elevated temperatures also contribute to increased transverse strains at both the bottom of the steel deck and the pavement surface, following an exponential trend. Relative deflection is primarily influenced by the applied load and remains relatively unaffected by temperature variations. When accounting for the coupling of load and temperature, the maximum transverse strains at both the bottom of the steel deck and the pavement surface can be modeled as an exponential function of the independent variables: load and temperature. [ABSTRACT FROM AUTHOR]

Diabetic nephropathy (DN) is a worldwide health problem with increasing incidence. Diosgenin (DIO) is a natural active ingredient extracted from Chinese yams (Rhizoma dioscoreae) with potential antioxidant, anti-inflammatory, and antidiabetic effects. However, the protective effect of DIO on DN is still unclear. The present study explored the mitigating effects and underlying mechanisms of DIO on DN in vivo and in vitro. In the current study, the DN rats were induced by a high-fat diet and streptozotocin and then treated with DIO and metformin (Mef, a positive control) for 8 weeks. The high-glucose (HG)-induced HK-2 cells were treated with DIO for 24 h. The results showed that DIO decreased blood glucose, biomarkers of renal damage, and renal pathological changes with an effect comparable to that of Mef, indicating that DIO is potential active substance to relieve DN. Thus, the protective mechanism of DIO on DN was further explored. Mechanistically, DIO improved autophagy and mitophagy via the regulation of the AMPK-mTOR and PINK1-MFN2-Parkin pathways, respectively. Knockdown of CaMKK2 abolished AMPK-mTOR and PINK1-MFN2-Parkin pathways-mediated autophagy and mitophagy. Mitophagy and mitochondrial dynamics are closely linked physiological processes. DIO also improved mitochondrial dynamics through inhibiting fission-associated proteins (DRP1 and p-DRP1) and increasing fusion proteins (MFN1/2 and OPA1). The effects were abolished by CaMKK2 and PINK1 knockdown. In conclusion, DIO ameliorated DN by enhancing autophagy and mitophagy and by improving mitochondrial dynamics in a CaMKK2-dependent manner. PINK1 and MFN2 are proteins that concurrently regulated mitophagy and mitochondrial dynamics. [ABSTRACT FROM AUTHOR]

Diosgenin (DIO) is a dietary steroid sapogenin possessing multiple biological functions, such as the amelioration of diabetes. However, the remission effect of DIO on diabetic nephropathy (DN) underlying oxidative stress and cell apoptosis remains unclear. Here, the effect of DIO on ROS generation and its induced cell apoptosis was studied in vitro and in vivo. Renal proximal tubular epithelial (HK-2) cells were treated with DIO (1, 2, 4 µM) under high glucose (HG, 30 mM) conditions. DN rats were induced by a high-fat diet combined with streptozotocin, followed by administration of DIO for 8 weeks. Our data suggested that DIO relieved the decline of HK-2 cell viability and renal pathological damage in DN rats. DIO also relieved ROS (O2− and H2O2) production. Mechanistically, DIO inhibited the expression of NOX4 and restored mitochondrial respiratory chain (MRC) complex I-V expressions. Further, DIO inhibited mitochondrial apoptosis by ameliorating mitochondrial membrane potential (MtMP) and down-regulating the expressions of CytC, Apaf-1, caspase 3, and caspase 9, while up-regulating Bcl2 expression. Moreover, the ER stress and its associated cell apoptosis were inhibited through decreasing PERK, p-PERK, ATF4, IRE1, p-CHOP, and caspase 12 expressions. Collectively, DIO inhibited ROS production by modulating NOX4 and MRC complexes, which then suppressed apoptosis regulated by mitochondria and ER stress, thereby attenuating DN. [ABSTRACT FROM AUTHOR]

Patulin (PAT) is a natural mycotoxin that commonly contaminates fruits and fruit-based products. Previous work indicated that PAT-induced apoptosis in which reactive oxygen species (ROS) are involved in human embryonic kidney (HEK293) cells. To uncover novel aspects of the possible mechanism of PAT nephrotoxicity, the transcriptome and proteome profiles were investigated using the digital gene expression (DGE) and isobaric tags for relative and absolute quantitation (iTRAQ) proteomic approaches. A total of 127 genes and 85 proteins were found to express differentially in response to 5 μM PAT for 10 h in HEK293 cells. The most dramatic changes of expression were noticed with genes or proteins related to apoptosis, oxidative phosphorylation ribosome and cell cycle. Especially, the activation of caspase 3, UQCR11, active transport form and endocytosis appeared to be crucial in PAT kidney cytotoxicity. PAT also seemed to be associated with cancer and neuropathic disease as pathways associated with carcinogenesis, Alzheimer's disease and Parkinson's disease were induced. Overall, this study served to uncover overall insights associated with signaling pathway that modulated the PAT toxicity mechanism. [ABSTRACT FROM AUTHOR]