Potential Blood Pressure Goals in IgA Nephropathy: Prevalence, Awareness, and Treatment Rates in Chronic Kidney Disease Among Patients with Hypertension in China (PATRIOTIC) Study

Background/Aims: IgA nephropathy is the most prevalent form of primary glomerulonephritis worldwide. Among patients with kidney disease, hypertension is one of the most important risk factors of disease progression. Considering the limited evidence regarding the appropriate blood pressure (BP) goal for patients with IgA nephropathy, our aim was to critically appraise the potential BP goal in IgA nephropathy. Methods: We performed a retrospective analysis of the BP data from 1055 patients with IgA nephropathy, extracted from the database of a nationwide, multi-center, cross-sectional study, including 61 tertiary hospitals in China. Hypertension was defined by a BP ≥140/90 mmHg. Three BP cutoff levels were evaluated as control values: < 140/90 mmHg, < 130/80 mmHg and < 125/75 mmHg. The primary outcome of our study was the prevalence of BP control among patients with a 24-h proteinuria < 1 g/d or ≥ 1 g/d. Multivariate logistic regression analysis was used to identify demographic and clinical factors associated with a decrease in renal function for the different target levels of BP. Results: The overall prevalence of hypertension was 63.3%. BP was controlled under 140/90 mmHg in 49.1% of patients, with 34.3% of patients with proteinuria < 1 g/d reaching the target BP < 130/80 mmHg and only 12.9% of patients with proteinuria > 1 g/d achieving a BP < 125/75 mmHg. Among patients with proteinuria < 1 g/d, the adjusted odds ratios (OR) and 95% confidence interval (95% CI) of a decrease in renal function, for the 3 target BP levels, were as follows (P > 0.05): < 140/90 mmHg, 0.9 (0.5 - 1.6); < 130/80 mmHg, 1.0 (0.5 - 1.8); and < 125/75 mmHg, 1.0 (0.5 - 2.0). With proteinuria ≥1 g/d, the adjusted ORs (95%CI) of attaining the BP targets of < 140/90 mmHg, < 130/80 mmHg and < 125/75 mmHg were 0.4 (0.2 - 0.6), 0.2 (0.1 - 0.4) and 0.3 (0.1 - 0.5), respectively (P < 0.05). Conclusion: Hypertension was common in IgA nephropathy and hypertensive control was suboptimal. Our result supports a benefit of intensive control of BP < 130/80 mmHg for patients with proteinuria ≥1 g/d. However, in patients with proteinuria < 1 g/d, a renoprotective effect of this BP goal was not identified

Structural Requirements of N-Substituted Spiropiperidine Analogues as Agonists of Nociceptin/Orphanin FQ Receptor

The nociceptin/orphanin FQ (NOP) receptor is involved in a wide range of biological functions, including pain, anxiety, depression and drug abuse. Especially, its agonists have great potential to be developed into anxiolytics. In this work, both the ligand- and receptor-based three-dimensional quantitative structure–activity relationship (3D-QSAR) studies were carried out using comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) techniques on 103 N-substituted spiropiperidine analogues as NOP agonists. The resultant optimal ligand-based CoMSIA model exhibited Q2 of 0.501, R2ncv of 0.912 and its predictive ability was validated by using an independent test set of 26 compounds which gave R2pred value of 0.818. In addition, docking analysis and molecular dynamics simulation (MD) were also applied to elucidate the probable binding modes of these agonists. Interpretation of the 3D contour maps, in the context of the topology of the active site of NOP, provided insight into the NOP-agonist interactions. The information obtained from this work can be used to accurately predict the binding affinity of related agonists and also facilitate the future rational design of novel agonists with improved activity

Study on corrosion resistance of HAZ and TMAZ in friction stir welding joint of 7075 aluminum alloy by thermal simulation

It is difficult to characterize the variation of corrosion resistance of the narrow areas in friction stir welding (FSW) joints due to the large temperature gradient. In this paper, the welding thermal simulation was performed to simulate the heat affected zone (HAZ) and thermo-mechanical affected zone (TMAZ) of the FSW 7075-T6 aluminum alloy, and the corrosion resistance and microstructure of the simulated samples were studied. Results show that the corrosion potential changes greatly under different thermal simulation temperatures. The pitting corrosion of the HAZ simulated samples presents two pitting potentials, but for the TMAZ simulated samples, two pitting potentials will gradually evolve to one pitting potential with the increase of the maximum temperature. The electrochemical impedance spectroscopy results show that the corrosion mechanism of the HAZ and TMAZ is completely inconsistent, which is related to the differences in precipitate and grain characteristics

Effect of retrogression re-aging treatment on corrosion behavior of 7055 Al-Zn-Mg alloy

The effect of retrogression re-aging treatment (RRA) on the corrosion behavior of 7055 Al-Zn-Mg alloy was studied in this paper. Results provided that corrosion resistance could be greatly improved by RRA. After the RRA treatment, the isolated precipitates occurred on grain boundaries (GBs) and the low angle grain boundaries (LAGBs) presented a larger fraction compared to that of single-stage peaking aging treatment. The samples after RRA treatment also show better corrosion resistance than that of single-stage peak aging treatment. In addition, of the electrochemical impedance spectroscopy (EIS) analysis showed that the impedance spectrum was consisted of semi-infinite layer diffusion impedance and stagnant Weber impedance. The semi-infinite layer diffusion impedance corresponded to a limited retention layer on the electrode surface while the Weber impedance represented a stagnant layer of corrosion products generated by the anode branches. The aluminum alloy after RRA treatment achieved higher R _f and low C _f , C _p values and its corrosion current density was ten times smaller compared to the single-stage peak aging samples with the 10% hardness losing

Effects of the Addition of Co or Ni Atoms on Structure and Magnetism of FeB Amorphous Alloy: Ab Initio Molecular Dynamics Simulation

The effects of the substitution of Fe by Co or Ni on both the structure and the magnetic properties of FeB amorphous alloy were investigated using first-principle molecular dynamics. The pair distribution function, Voronoi polyhedra, and density of states of Fe80−xTMxB20 (x = 0, 10, 20, 30, and 40 at.%, TM(Transition Metal): Co, Ni) amorphous alloys were calculated. The results show that with the increase in Co content, the saturation magnetization of Fe80−xCoxB20 (x = 0, 10, 20, 30, and 40 at.%) amorphous alloys initially increases and then decreases upon reaching the maximum at x = 10 at.%, while for Fe80−xNixB20 (x = 0, 10, 20, 30, and 40 at.%), the saturation magnetization decreases monotonously with the increase in Ni content. Accordingly, for the two kinds of amorphous alloys, the obtained simulation results on the variation trends of the saturation magnetization with the change in alloy composition are in good agreement with the experimental observation. Furthermore, the relative maximum magnetic moment was recorded for Fe70Co10B20 amorphous alloy, due to the induced increased magnetic moments of the Fe atoms surrounding the Co atom in the case of low Co dopant, as well as the increase in the exchange splitting energy caused by the enhancement of local atomic symmetry

Precipitates evolution during artificial aging and their influence on mechanical properties of a cast Al–Cu–Li alloy

Al–Cu–Li cast alloy components also show a promising application in the aerospace industry due to their relatively good combination of density and performance. According to the conventional processing procedures for cast products, a novel cast Al–Cu–Li alloy was directly solution treated and aged after homogenization, then the aging precipitation behavior and its effect on the mechanical properties of the alloy were investigated in this article. It was found that the naturally aged precipitates are rapidly dissolved during artificial aging at 175 °C, and the cubic phase, θ′ phase, T1 phase, Ω phase, and S phase will precipitate successively. In the early stage of artificial aging, the cubic phase and θ′ phase are formed prior to the T1 phase. With the aging time increasing, numerous T1 phases also precipitate with relatively large diameters, so the hardness of the alloy keeps rising until to the peak value. The naturally aged specimens show good plasticity and relatively low strength. After artificial aging, the tensile strength of the cast alloy can be increased to 423 MPa, but the corresponding elongation has a significant reduction. Moreover, the predominant precipitates—T1 phase and cubic phase show excellent thermal stability during 175 °C aging, they still exist with a large population even aged for 40 days

In-situ electrochemical analytical effect of aging treatment on stress corrosion behavior of Al–Zn–Mg–Cu aluminum alloy

The stress corrosion cracking (SCC) behavior of Al–Zn–Mg–Cu alloys in different aging treatment states was dynamically studied by slow strain rate tensile (SSRT) combining in-situ electrochemical impedance spectroscopy (EIS). By analyzing the influence of microstructure and precipitation phase on stress corrosion resistance under different aging conditions, it was found that the stress corrosion process can be divided into three stages, the corresponding charge transfer resistance (Rct) shows three evolutionary patterns, with the maximum value occurred when the alloys were under the maximum stress. The regression re-aging (RRA) treatment obtained coarse and discrete grain boundary precipitates (GBPs) with higher Cu content, which improved the SCC resistance of alloys significantly

Knockdown of Cxcl10 Inhibits Mesangial Cell Proliferation in Murine Habu Nephritis Via ERK Signaling

Background/Aims: IFN-γ-inducible protein 10 (IP-10, CXCL10) has been widely demonstrated to be involved in chemotaxis, cell growth regulation and angiogenesis inhibition. It has been reported that CXCL10 expression is significantly increased in patients with MesPGN (Mesangial proliferative glomerulonephritis). However, the underlying mechanism of CXCL10 in MesPGN reminds unclear. Methods: Wildtype (Cxcl10+/+) mice and Cxcl10-deficient (Cxcl10-/-) mice were used to generate a murine model of MesPGN. The histological changes in glomeruli were examined by PAS staining (Periodic Acid-Schiff staining), and cell proliferation was detected by PCNA immunohistochemistry staining. The expression of cell cycle regulatory proteins was analyzed by Western blotting and the effects of CXCL10 on primary mouse renal mesangial cells (MRMC) proliferation were detected using the EDU assay. Furthermore, the specific mechanisms by which CXCL10 affected mesangial cells were investigated in vitro using a specific inhibitor. Results: Typical pathological phenotypes were observed in both mouse types, while the Cxcl10-/- mice had lighter accumulation of extracellular matrix, less cell proliferation and diminished up-regulation of cell cycle regulatory proteins compared to Cxcl10+/+ mice at day 7. Furthermore, we observed that CXCL10 inhibition resulted in less activation of ERK phosphorylation, and ERK pathway inhibition by a specific inhibitor, U0126, prevented CXCL10 induced MRMC proliferation and the activation of phosphorylated ERK. Conclusions: CXCL10 may aggravate mesangial proliferation in MesPGN by activating the ERK signaling pathway. These results provide a novel insight into the mechanism and potential therapy target of MesPGN