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Y2O3 dispersion-strengthened Molybdenum (Mo) composites were prepared by the mechanical alloying of Mo and Y powders then consolidation by spark plasma sintering. The effects of Chromium (Cr) addition (0 wt. %, 5 wt. %, 10 wt. % and 15 wt. %, respectively) on the mechanical performance and high-temperature oxidation resistance of Mo-Y2O3 were investigated. The introduction of Cr had a significant influence on the mechanical property and oxidation resistance of the Mo-Y2O3 composite. The highest bending strength reached 932 MPa when the addition of Cr content was 5 wt. % (Mo–5Cr–1Y sample). This improvement is likely attributable to the dual mechanism of grain refinement and solid solution strengthening. Moreover, the Mo–5Cr–1Y sample showed the thinnest oxide layer thickness after high-temperature oxidation tests, and exhibited the best oxidation resistance performance compared with the other samples. First principle calculation reveals that Cr could improve the Mo–MoO3 interface bonding to prevent rapid spalling of the oxide layer. Meanwhile, Cr also facilitates the formation of the dense Cr2(MoO4)3 layer on the surface, which can inhibit further oxidation. [ABSTRACT FROM AUTHOR]

Background and Purpose: Muscle protein catabolism in patients with diabetic nephropathy (DN) results in striking loss of muscle proteins, which increases morbidity and mortality risks. Evidence shows that short‐chain fatty acids (SCFAs) play an important role in health maintenance and disease development. Recently, the connection between butyrate (a SCFA) and DN has been revealed, although the relationship between butyrate and muscle atrophy remains unclear. Experimental Approach We studied changes in serum butyrate levels in DN patients using metabolomic analyses. In db/db mice, protective effects of butyrate on DN‐induced muscle atrophy. were explored. Inhibition of muscle atrophy by butyrate and the underlying mechanism(s) were studied in C2C12 cells exposed to high glucose/lipopolysaccharide (HG/LPS). Key Results: Butyrate levels in DN patients were significantly decreased. In db/db mice, supplementing normal diet with butyrate improved intestinal barrier function. Concurrently, butyrate alleviated muscle atrophy, promoted PI3K/Akt/mTOR signalling, and suppressed oxidative stress and autophagy in skeletal muscle of db/db mice, and in HG/LPS‐exposed C2C12 cells. Further, FFA2 receptors, key components of SCFA signalling, were decreased in skeletal muscle of db/db mice and in HG/LPS‐exposed C2C12 cells. Overexpression of FFA2 receptors activated PI3K/Akt/mTOR signalling and inhibited oxidative stress and autophagy in HG/LPS‐exposed C2C12 cells. Silencing of FFA2 blocked PI3K/Akt/mTOR signalling that was improved by butyrate, as well as the suppression of oxidative stress and reduction of autophagy. Conclusion and Implication: Butyrate exerts protective effects on muscle atrophy induced by DN by enhancing intestinal barrier function and activating the FFA2 receptor‐mediated PI3K/Akt/mTOR pathway. [ABSTRACT FROM AUTHOR]

Aims: To test the hypothesis that in non-diabetic patients with early-stage chronic kidney disease (CKD), the renal excretion of urate and glucose transportation are coupled and interconnected. Methods: A cross-sectional study of 255 non-diabetic participants with stage 1–2 CKD recruited from our department was conducted. Spearman's correlation and multiple linear regression analyses were used to study the correlation between urinary glucose and renal uric acid excretion. ANOVA was used to compare urinary uric acid excretion among three tertiles of urinary glucose (UG; UG1: UG<0.24 mmol/24 h/1.73 m2, UG2: 0.24 mmol/24 h/1.73 m2≤ UG≤0.55 mmol/24 h/1.73 m2, and UG3: UG>0.55 mmol/24 h/1.73 m2), the fractional excretion of glucose (FEG; FEG1: FEG<0.04%, FEG2: 0.04%≤FEG≤0.09%, and FEG3: FEG>0.09%) and the excretion of glucose per volume of glomerular filtration (EgGF; EgGF1: EgGF<1.95 μmol/L, EgGF2: 1.95 μmol/L≤ EgGF≤3.99 μmol/L, and EgGF3: EgGF>3.99 μmol/L). Results: According to the multiple linear regression analysis, FEG and EgGF were positively correlated with the excretion of uric acid per volume of glomerular filtration (EurGF) after adjusting for confounding factors. The EurGF levels in the highest tertiles of UG, FEG and EgGF were higher than those in the lowest tertiles of UG, FEG and EgGF. Conclusion: Urinary glucose excretion is closely related to renal excretion of uric acid in non-diabetic patients with stage 1–2 CKD. [ABSTRACT FROM AUTHOR]

Increasing evidence indicates that hyperuricaemia (HUA) is not only a result of decreased renal urate excretion but also a contributor to kidney disease. Na + -K + -ATPase (NKA), which establishes the sodium gradient for urate transport in proximal tubular epithelial cells (PTECs), its impairment leads to HUA-induced nephropathy. However, the specific mechanism underlying NKA impairment-mediated renal tubular injury and increased urate reabsorption in HUA is not well understood. In this study, we investigated whether autophagy plays a key role in the NKA impairment signalling and increased urate reabsorption in HUA-induced renal tubular injury. Protein spectrum analysis of exosomes from the urine of HUA patients revealed the activation of lysosomal processes, and exosomal expression of lysosomal-associated membrane protein-2 was associated with increased serum levels and decreased renal urate excretion in patients. We demonstrated that high uric acid (UA) induced lysosome dysfunction, autophagy and inflammation in a time- and dose-dependent manner and that high UA and/or NKA α1 siRNA significantly increased mitochondrial abnormalities, such as reductions in mitochondrial respiratory complexes and cellular ATP levels, accompanied by increased apoptosis in cultured PTECs. The autophagy inhibitor hydroxychloroquine (HCQ) ameliorated NKA impairment-mediated mitochondrial dysfunction, Nod-like receptor pyrin domain-containing protein 3 (NLRP3)-interleukin-1β (IL-1β) production, and abnormal urate reabsorption in PTECs stimulated with high UA and in rats with oxonic acid (OA)-induced HUA. Our findings suggest that autophagy plays a pivotal role in NKA impairment-mediated signalling and abnormal urate reabsorption in HUA-induced renal tubular injury and that inhibition of autophagy by HCQ could be a promising treatment for HUA., Competing Interests: Declaration of competing interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022. Published by Elsevier B.V.)