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Corin is a type II transmembrane serine protease mainly expressed in the heart. Recently, corin was detected in the kidney and was reported to be associated with multiple kidney diseases. To date, its effect on acute kidney injury (AKI) has not been clarified. Here, we found that corin was constitutively expressed in renal tubules, especially in proximal and distal tubular epithelial cells. The expression of corin was dramatically reduced in ischemia/reperfusion injury (IRI)-induced AKI mouse model and oxygen-glucose deprivation (OGD)-induced human proximal tubular epithelial (HK-2) cells injury model, suggesting a potential role of corin in AKI. Corin deficient mice exhibited aggravated renal injury in AKI, as indicated by higher elevation of serum creatinine (SCr) and blood urea nitrogen (BUN), more severe tubular damage, and increased cell death versus wild type mice, demonstrating a protective effect of corin on AKI. In vitro overexpression of corin didn't directly alleviate hypoxia-induced HK-2 cells death, revealing that the protective effect of corin against AKI is not due to direct protection of tubular epithelial cells but may be through indirect protection. Microarray analysis showed enhanced inflammatory chemokines signaling and leukocyte chemotaxis in corin-/- mice after AKI, identifying an important role of corin in halting leukocyte chemotaxis and inflammatory response. Consistently, corin-/- mice after AKI displayed increased tubulointerstitial neutrophils and macrophages infiltration, as well as higher inflammatory mediators in kidneys. Taken together, our study indicates that tubular corin exerts a protective effect against AKI through negative regulation of chemotaxis signaling and inflammation in the kidney.

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Phloretin is a dihydrochalcone flavonoid from natural plants, which has protective activities against oxidative stress and inflammation. To date, its effect on diabetic nephropathy (DN) has not been investigated. In this study, we examined the potential role of phloretin in diabetes-induced renal damage and associated mechanisms in a type 2 diabetes mellitus (T2DM) model induced by streptozotocin (STZ) and high-fat diet (HFD) in Apolipoprotein E knockout (ApoE-/-) mice. We found that daily treatment with a low dose (20 mg kg-1) of phloretin, as a dietary supplement, significantly alleviated polyuria, proteinuria, and glomerular histopathological changes in the T2DM mice, indicating a protective effect of phloretin on diabetic renal dysfunction. In the phloretin-treated T2DM mice, major metabolic parameters, including blood glucose levels, were not altered significantly, suggesting that the observed beneficial effects of phloretin may be due to a mechanism independent of blood glucose control. Further experiments revealed that phloretin had a protective effect on glomerular podocytes as indicated by ameliorated glomerular basement membrane (GBM) thickening and podocyte foot process effacement. Moreover, phloretin treatment restored levels of nephrin and podocin, two podocyte slit diaphragm proteins that were decreased in T2DM mice. Our results indicate that low-dose phloretin treatment has a protective effect on podocytes in DN via a non-hypoglycemic mechanism in preserving nephrin and podocin expression levels. These data suggest that phloretin may be exploited as a novel therapeutic agent for DN.

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In order to analyze the competitive relationship of different deformation mechanisms in wrought AZ31 magnesium alloy, the dynamic compressive experiments were conducted by a Split Hopkinson Pressure Bar (SHPB) apparatus and a resistance-heated furnace in the range of temperature between 20 and 350 °C at the strain rate of 1000 s-1. With the help of Electron Backscattered Diffraction (EBSD) observation, theoretical calculated Schmid Factor (SF), Critical Resolved Shear Stress (CRSS), and critical equivalent stress (σ0.2), the dynamic compressive deformation behavior and corresponding mechanism of wrought AZ31 magnesium alloy along the normal direction (ND) were revealed in the current study. The results demonstrate that the c-axis of grains are gradually reoriented parallel to the normal direction of wrought AZ31-ND sheet with the temperature increasing, except the dynamic recrystallization (DRX) mechanism was activated or grains grew up. The non-basal slip and 101¯2 tension twinning are respectively the predominant deformation mechanisms at lower temperatures (≤250 °C) and higher temperatures (≥250 °C). The predominant type of DRX mechanism of wrought AZ31-ND sheet is rotational dynamic recrystallization (RDRX), which is regarded as an obstacle for the kernel misorientation concentration region enhancement.

RESUMEN

Corin is a serine protease mainly expressed in the heart, where it regulates blood pressure and cardiac function through activating pro-atrial natriuretic peptide (pro-ANP) to ANP. Its expression has also been detected in non-cardiac tissues. However, there is no report so far about the distribution and function of corin in aorta and in related diseases such as atherosclerosis. This study was the first to explore corin expression in aorta both under normal conditions and in atherosclerosis models. In vivo, we found corin had a basal level of expression in aortas, mainly in intimal endothelial cells and was significantly elevated in mouse atherosclerosis model. Moreover, we observed pro-ANP, the specific substrate of corin, was also expressed in mice aortas and increased in mouse atherosclerosis model. In vitro, we further demonstrated corin expression in cultured vascular endothelial cells and its induced expression after ox-LDL stimulation. Our results suggested that corin may play important roles in aorta physiology and in the pathophysiological process of atherosclerosis in an autocrine manner and has potential clinical value for the treatment of atherosclerosis.

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Although studies have seen dramatic advances in the understanding of the pathogenesis of stroke such as oxidative stress, inflammation, excitotoxicity, calcium overload and apoptosis, the delivery of stroke therapies is still a great challenge. In this study, we designed and synthesized a series of novel twin compounds containing tetramethylpyrazine and carnitine substructures and explored their therapeutic potential and mechanism in stroke-related neuronal injury. We first screened the neuroprotective effects of candidate compounds and found that among the tested compounds, LR134 and LR143 exhibited significant neuroprotection as evidenced by reducing cerebral infarct and edema, improving neurological function as well as blood-brain barrier integrity in rats after cerebral ischemia/reperfusion injury. We further demonstrated that the neuroprotective effects of compounds LR134 and LR143 were associated with the reduced inflammatory responses and NADPH oxidase- (NOX2-) mediated oxidative stress and the protection of mitochondria accompanied by the improvement of energy supply. In summary, this study provides direct evidence showing that the novel twin compounds containing tetramethylpyrazine and carnitine substructures have neuroprotective effects with multiple therapeutic targets, suggesting that modulation of these chemical structures may be an innovative therapeutic strategy for treating patients with stroke.

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The periodic number dependence of the femtosecond laser-induced crystallization threshold of [Si(5nm)/Sb80Te20(5nm)]x nanocomposite multilayer films has been investigated by coherent phonon spectroscopy. Coherent optical phonon spectra show that femtosecond laser-irradiated crystallization threshold of the multilayer films relies obviously on the periodic number of the multilayer films and decreases with the increasing periodic number. The mechanism of the periodic number dependence is also studied. Possible mechanisms of reflectivity and thermal conductivity losses as well as the effect of the glass substrate are ruled out, while the remaining superlattice structure effect is ascribed to be responsible for the periodic number dependence. The sheet resistance of multilayer films versus a lattice temperature is measured and shows a similar periodic number dependence with one of the laser irradiation crystallization power threshold. In addition, the periodic number dependence of the crystallization temperature can be fitted well with an experiential formula obtained by considering coupling exchange interactions between adjacent layers in a superlattice. Those results provide us with the evidence to support our viewpoint. Our results show that the periodic number of multilayer films may become another controllable parameter in the design and parameter optimization of multilayer phase change films.

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Multiple parameters of nanocomposite Si/Sb80Te20 multilayer films are possibly optimized simultaneously to satisfy the development of ideal phase-change memory devices by adjusting chemical composition and physical structure of multilayer films. The crystallization and structure of the films are studied by coherent phonon spectroscopy. Laser irradiation power dependence of coherent optical phonon spectroscopy reveals laser-induced crystallization of the amorphous multilayer film, while coherent acoustic phonon spectroscopy reveals the presence of folded acoustic phonons which suggests a good periodic structure of the multilayer films. Laser irradiation-induced crystallization shows applicable potentials of the multilayer films in optical phase change storage.