Background Severe sepsis, a major health problem worldwide, has become one of the leading causes of death in ICU patients. Further study on the pathogenesis and treatment of acute kidney injury (AKI) is of great significance to reduce high mortality rate of sepsis. In this study, the mechanism by which ubiquitin specific peptidase 10 (USP10) reduces sepsis-induced AKI was investigated. Ligation and perforation of cecum (CLP) was employed to establish C57BL/6 mouse models of sepsis. Hematoxylin-eosin (H&E) staining was performed to detect renal injury. The concentrations of serum creatinine (Cr), urea nitrogen (BUN) and cystatin C (Cys C) were determined using a QuantiChrom™ Urea Assay kit. RT-qPCR and western blot were conducted to assess the USP10 expression level. DHE staining was used to detect reactive oxygen species (ROS) levels. H2O2, MDA and SOD levels were assessed using corresponding colorimetric kits. Western blot was used to examine the expression levels of Bcl-2, Bax, cleaved caspase-3, Sirt6, Nrf2 and HO-1. MTT assay was used to determine cell viability, whereas TUNEL staining and flow cytometry were used to assess cell apoptosis. Results In this study, we found that USP10 was decreased in CLP-induced mouse renal tissues. We identified that USP10 alleviated renal dysfunction induced by CLP. Moreover, USP10 was found to reduce oxidative stress, and abated LPS-induced renal tubular epithelial cell injury and apoptosis. Finally, we discovered that USP10 promoted activation of the NRF2/HO-1 pathway through SIRT6 and attenuated LPS-induced renal tubular epithelial cell injury. Conclusions This study found that USP10 activates the NRF2/ARE signaling through SIRT6. USP10 alleviates sepsis-induced renal dysfunction and reduces renal tubular epithelial cell apoptosis and oxidative stress.
Ultrafast pulsed laser of high intensity and high repetition rate is the combined requisite for advancing strong-field physics experiments and calls for the development of thermal-stable ultrafast laser systems. Noncollinear phasing matching (PM) is an effective solution of optimizing the properties of optical parametric chirped pulse amplification (OPCPA) to achieve broadband amplification or to be temperature-insensitive. But as a cost, distinct noncollinear geometries have to be respectively satisfied. In this paper, a noncollinear quasi-phase-matching (QPM) scheme of both temperature- and wavelength-insensitive is presented. With the assistance of the design freedom of grating wave vector, the independent noncollinear-angle requirements can be simultaneously realized in a tilted QPM crystal, and the temperature-insensitive broadband amplification is achieved. Full-dimensional spatial-temporal simulations for a typical 1064 nm pumped mid-IR OPCPA at 3.4 µm are presented in detail. Compared with a mono-functional temperature-insensitive or broadband QPM scheme, the presented QPM configuration shows a common characteristic that simultaneously optimizes the thermal stability and the gain spectrum. Broadband parametric amplification of a ∼40 fs (FWHM) pulsed laser is achieved with no signs of gain-narrowing. Both of the beam profiles and the amplified spectra stay constant while the temperature is elevated by ∼100°C. Finally, influence of the QPM grating errors on the gain spectrum is discussed.
Thermal-induced phase-mismatch distortion, which will dramatically deteriorate the efficient energy transfer, has become a critical obstacle to power scaling of optical parametric amplifiers. To ease this efficiency deterioration, the noncollinear optical parametric amplification (OPA) configuration widely employed to achieve broadband phase-matching (PM) may also serve as a promising approach to optimize the temperature acceptance. In this paper, starting from the noncollinear wave-vector equations, a required thermo- and angle-relationship analogous to that of noncollinear broadband PM is firstly inferred. Based on the presented mathematical criterion, we have explored the potential spectral boundaries of this ingenious temperature insensitive OPA scheme. Full-dimensional simulations of two types of typical OPA processes were quantitatively discussed. Compared with traditional collinear PM designs, the presented noncollinear PM configurations show significant common characteristics on improving the temperature acceptance and subsequently the overall amplification efficiency. For a typical high power parametric process of the 532 nm pumped near-IR OPA at 800 nm especially, incredible temperature bandwidth exceeding 8000 °C was obtained while a YCOB (xz plane) crystal is adopted. What is more, it can also be applied to ameliorate the gain-spectrum thermo-instability of OPA.
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