Astragaloside IV alleviates 1-deoxysphinganine-induced mitochondrial dysfunction during the progression of chronic kidney disease through p62-Nrf2 antioxidant pathway

Introduction: Chronic kidney disease (CKD) can lead to significant elevation of 1-deoxysphingolipids (1-deoxySL). The increase of 1-deoxySL in turn can result in mitochondrial damage and oxidative stress, which can cause further progression of CKD.Methods: This study assessed the therapeutic effect of Astragaloside IV (AST) against 1-deoxySL-induced cytotoxicity in vitro and in rats with CKD. HK-2 cells were exposed to 1-deoxysphinganine (doxSA) or doxSA + AST. doxSA-induced mitochondrial dysfunction and oxidative stress were evaluated by immunostaining, real-time PCR, oxidative stress sensor, and transmission electron microscopy. The potential effects of AST on kidney damage were evaluated in a rat 5/6 nephrectomy (5/6 Nx) model of CKD.Results: The findings of in vitro experiments showed that doxSA induced mitochondrial damage, oxidative stress, and apoptosis. AST markedly reduced the level of mitochondrial reactive oxygen species, lowered apoptosis, and improved mitochondrial function. In addition, exposure to AST significantly induced the phosphorylation of p62 and the nuclear translocation of Nrf2 as well as its downstream anti-oxidant genes. p62 knock-down fully abolished Nrf2 nuclear translocation in cells after AST treatment. However, p62 knock-down did not affect TBHQ-induced Nrf2 nuclear translocation, indicating that AST can ameliorate doxSA-induced oxidative stress through modulation of p62 phosphorylation and Nrf2 nuclear translocation.Conclusion: The findings indicate that AST can activate Nrf2 antioxidant pathway in a p62 dependent manner. The anti-oxidative stress effect and the further mitochondrial protective effect of AST represent a promising therapeutic strategy for the progression of CKD

Pile Installation Assessment of Offshore Wind Jacket Foundation in Completely Weathered Rock: A Case Study of the South China Sea

The assessment of pile drivability is the premise of successful pile installation, and completely weathered (CW) rock may bring the risk of pile refusal. This paper presents a case of pile driving refusal that occurred in a CW gneiss layer. The physical and mechanical properties of the CW gneiss are analyzed based on the results of a laboratory test, a cone penetration test (CPT), and a standard penetration test (SPT). By comparing the properties of CW gneiss with those from intact gneiss, the CW gneiss layer in this study was found to be soil-like. Additionally, it is a sand-like layer according to CPT-based soil classification systems. The soil resistance to driving (SRD) in pile driving was calculated with different methods for sand and compared with the SRD inferred from the pile-driving records. The results show that the modified Fugro’s method assuming a fully plugged condition may provide good pile drivability assessment in this study. It was found that it is necessary to determine the properties of the CW rock layer reasonably before conducting pile driving analysis, and a framework is proposed for analyzing the pile drivability in a CW rock layer based on this case study

Dynamic Mechanical Behavior of Fiber-Reinforced Seawater Coral Mortars

Coral aggregate has been widely used for island construction because of its local availability. However, the addition of coral aggregate exaggerates the brittle nature of cement-based materials under dynamic loading. In this study, polyvinyl alcohol (PVA) fiber was used to improve dynamic mechanical behavior of seawater coral mortars (SCMs). The effects of coral aggregate and PVA fiber on the workability, static mechanical strengths, and dynamic mechanical behavior of fiber-reinforced SCMs were investigated. Results showed that the workability of the SCM decreased with increasing coral aggregate replacement rate and PVA fiber content. Mechanical strengths of the SCM increased with increasing PVA fiber content, but decreased with increasing coral aggregate replacement rate. Dynamic mechanical behavior at varying coral aggregate replacement rates was analyzed by combining dynamic mechanical analysis and micro-scale elastic modulus experiment. With increasing coral aggregate replacement rate, the storage modulus, loss factor, and elastic modulus of the interfacial transition zone in the SCM decreased. Nevertheless, with the incorporation of PVA fibers (1 vol.%), the storage modulus and loss factor were improved dramatically by 151.9 and 73.3%, respectively, compared with the reference group. Therefore, fiber-reinforced coral mortars have a great potential for use in island construction, owing to the excellent anti-vibrational performance