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Maleic acid (MA) induces renal tubular cell dysfunction directed to acute kidney injury (AKI). AKI is an increasing global health burden due to its association with mortality and morbidity. However, targeted therapy for AKI is lacking. Previously, we determined mitochondrial-associated proteins are MA-induced AKI affinity proteins. We hypothesized that mitochondrial dysfunction in tubular epithelial cells plays a critical role in AKI. In vivo and in vitro systems have been used to test this hypothesis. For the in vivo model, C57BL/6 mice were intraperitoneally injected with 400 mg/kg body weight MA. For the in vitro model, HK-2 human proximal tubular epithelial cells were treated with 2 mM or 5 mM MA for 24 h. AKI can be induced by administration of MA. In the mice injected with MA, the levels of blood urea nitrogen (BUN) and creatinine in the sera were significantly increased (p < 0.005). From the pathological analysis, MA-induced AKI aggravated renal tubular injuries, increased kidney injury molecule-1 (KIM-1) expression and caused renal tubular cell apoptosis. At the cellular level, mitochondrial dysfunction was found with increasing mitochondrial reactive oxygen species (ROS) (p < 0.001), uncoupled mitochondrial respiration with decreasing electron transfer system activity (p < 0.001), and decreasing ATP production (p < 0.05). Under transmission electron microscope (TEM) examination, the cristae formation of mitochondria was defective in MA-induced AKI. To unveil the potential target in mitochondria, gene expression analysis revealed a significantly lower level of ATPase6 (p < 0.001). Renal mitochondrial protein levels of ATP subunits 5A1 and 5C1 (p < 0.05) were significantly decreased, as confirmed by protein analysis. Our study demonstrated that dysfunction of mitochondria resulting from altered expression of ATP synthase in renal tubular cells is associated with MA-induced AKI. This finding provides a potential novel targ

Determination of hematite contributions to sedimentary magnetizations is an important but difficult task in quantitative environmental studies. The poorly crystalline and fine-grained nature of hematite nanoparticles makes quantification of their concentrations in natural environments challenging using mineralogical and spectroscopic methods, while the weak magnetization of hematite and often significant superparamagnetic nanoparticle concentrations make quantification difficult using magnetic remanence measurements. We demonstrate here that much-used magnetic parameters, such as the S-ratio and "hard" isothermal remanent magnetization (HIRM), tend to significantly underestimate relative and absolute hematite contents, respectively. Unmixing of isothermal remanent magnetization (IRM) acquisition curves is among the more suitable approaches for defining magnetic mineral contributions, although it has under-appreciated uncertainties that limit hematite quantification. Diffuse reflectance spectroscopy and other methods can enable relative hematite and goethite content quantification under some conditions. Combined use of magnetic, mineralogical, and spectroscopic approaches provides valuable cross-checks on estimated hematite contents; such an integrated approach is recommended here. Further work is also needed to rise to the challenge of developing improved methods for hematite quantification.