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Wild-Type p53-Induced Phosphatase 1 (WIP1/PPM1D) is a serine/threonine phosphatase that plays a significant role in various physiological processes. However, the involvement of WIP1 in kidney remains unclear. Lipopolysaccharide (LPS) was administered to induce acute injury in mice and human kidney 2 (HK2) cells in the study. The WIP1 inhibitor, CCT007093, was administered both in vitro and in vivo to assess its effect on kidney. The single-cell sequencing (scRNA-seq) data revealed that Ppm1d mRNA reached peak on day 2 following unilateral ischemia–reperfusion injury (uni-IRI) in mice, especially in the proximal renal tubules during repair phase. Compared to the control group, WIP1 protein exhibited a significant increase in renal tubules of patients with acute tubular injury (ATI) and mice with LPS-induced acute kidney injury (AKI), as well as in LPS-injured HK2 cells. In vitro experiments showed that CCT007093 increased the protein levels of NLRP3, cleaved-Caspase1, GSDMD-N and IL-1β in HK2 cells and further reduced the viability of LPS-stimulated HK2 cells. In vivo experiments showed that inhibition of WIP1 activity with CCT007093 further increased cleaved-Caspase1, GSDMD-N protein levels in kidney tissue from mice with LPS-induced AKI. In addition, LPS induces phosphorylation of p38 MAPK, a key regulator of pyroptosis, which is further activated by CCT007093. In conclusion, inhibition of WIP1 activity acts as a positive regulator of renal tubular pyroptosis mainly through the mediation of phospho-p38 MAPK.

Abstract Background The objective of this study is to investigate the clinical and pathological differences between patients with IgA nephropathy (IgAN) and IgA vasculitis associated nephritis (IgAVN). Methods A total of 253 patients with IgAN and 71 patients with IgAVN were retrospectively included in the study, and clinical and laboratory data were collected and analysed. Results Compared with IgAVN group, months from onset to kidney biopsy were significantly prolonged in IgAN patients because of the lack of obvious symptoms such as rash, abdominal symptoms, and joint pain (13.5 ± 26.6 vs. 10.2 ± 31.6 months, P = 0.007), and the levels of serum creatinine (92.3 ± 94.7 vs. 68.9 ± 69.2 µmol/L, P = 0.015) was higher and eGFR (99.1 ± 35.2 vs. 123.4 ± 41.8 mL/min/1.73m2, P

In order to investigate the temperature behavior for monolithic microwave integrated circuits (MMICs) under alpine conditions, the performance parameters of a 0.4–3.8 GHz gallium arsenide (GaAs) enhancement pseudomorphic high-electron-mobility transistor (E-pHEMT) low-noise amplifier (LNA) are tested at different temperatures. The typical temperatures of −39.2 °C, −32.9 °C, −25.3 °C, −11.3 °C, −4.9 °C, 0 °C and 23 °C are chosen as the alpine condition. The major performance indexes including the direct current (DC) characteristics, S-parameters, stability, radio frequency (RF) output characteristics, output third-order intersection point (OIP3) and noise figure (NF), which were inspected and analyzed in detail. The results show that the DC characteristics, small-signal gain (S21), RF output characteristics and NF all deteriorate with the rising temperature due to the decrease in two-dimensional electron gas mobility (μ). Contrary to this trend, the special design makes stability and OIP3 increase. For further application of this MMIC LNA under alpine conditions, several measures can be utilized to remedy performance degradation. This paper can provide some significant engineering value for the reliable design of MMICs.