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A compression module system placed under a microscope was utilized to conduct uniaxial compression testing of sandstone samples. The test system can acquire the image of crack propagation on the specimen surface in real time. The focus of this study was to analyze how the motion of sandstone composition particles affect the failure mechanism of the samples under minimal loading rates. The results indicate that the load displacement curves align with the macroscopic failure laws under different loading rates. Furthermore, the lower the loading rate, the greater the deformation and crushing degree of sandstone during failure. The failure mode becomes more complex and gradually transitions from tension failure to shear-tension failure. The crack evolution of sandstone was caused by the uncoordinated movement of its components, and the weak structure induces cracks under the action of external load. Microcracks are initially generated at the interface between mineral particles and the sandstone matrix and propagate along the boundary between mineral and matrix. The interaction between component particles in sandstone leads to the connection break between particles which forms microcracks, and results in local deformation of the sample. The aggregation of multiple cracks leads to the instability and failure of sandstone. [ABSTRACT FROM AUTHOR]

Fibrosis is the progressive accumulation of excess extracellular matrix and can cause organ failure. Fibrosis can affect nearly every organ including kidney and there is no specific treatment currently. Although Epidermal Growth Factor Receptor (EGFR) signaling pathway has been implicated in development of kidney fibrosis, underlying mechanisms by which EGFR itself mediates kidney fibrosis have not been elucidated. We find that EGFR expression increases in interstitial myofibroblasts in human and mouse fibrotic kidneys. Selective EGFR deletion in the fibroblast/pericyte population inhibits interstitial fibrosis in response to unilateral ureteral obstruction, ischemia or nephrotoxins. In vivo and in vitro studies and single-nucleus RNA sequencing analysis demonstrate that EGFR activation does not induce myofibroblast transformation but is necessary for the initial pericyte/fibroblast migration and proliferation prior to subsequent myofibroblast transformation by TGF-ß or other profibrotic factors. These findings may also provide insight into development of fibrosis in other organs and in other conditions. Fibrosis is the progressive accumulation of excess extracellular matrix produced by myofibroblasts leading to organ failure. Here the authors show that expression of the Epidermal Growth Factor Receptor (EGFR) increases in interstitial myofibroblasts in human and mouse fibrotic kidneys, and selective EGFR deletion in the fibroblast/pericyte population inhibits interstitial fibrosis in response to unilateral ureteral obstruction, ischemia or nephrotoxins. [ABSTRACT FROM AUTHOR]

Obesity and obesity-related health complications are increasing in prevalence. Adipose tissue from obese subjects has low-grade, chronic inflammation, leading to insulin resistance. Adipose tissue macrophages (ATMs) are a source of proinflammatory cytokines that further aggravate adipocyte dysfunction. In response to a high fat diet (HFD), ATM numbers initially increase by proliferation of resident macrophages, but subsequent increases also result from infiltration in response to chemotactic signals from inflamed adipose tissue. To elucidate the underlying mechanisms regulating the increases in ATMs and their proinflammatory phenotype, we investigated the role of activation of ATM epidermal growth factor receptor (EGFR). A high fat diet increased expression of EGFR and its ligand amphiregulin in ATMs. Selective deletion of EGFR in ATMs inhibited both resident ATM proliferation and monocyte infiltration into adipose tissue and decreased obesity and development of insulin resistance. Therefore, ATM EGFR activation plays an important role in adipose tissue dysfunction. In obesity, adipose tissue is chronically inflamed, leading to insulin resistance, and adipose tissue macrophages (ATMs) are a major source of cytokines that aggravate adipocyte dysfunction. Here, the authors show that selective deletion of the epidermal growth factor receptor in ATMs decreased obesity and development of insulin resistance. [ABSTRACT FROM AUTHOR]

Purpose: Vitamin K deficiency, expressed by a high level of desphospho-uncarboxylated matrix GLA protein (dp-ucMGP), is highly prevalent in dialysis patients. However, the predictive ability of the vitamin K status remains unclear in continuous ambulatory peritoneal dialysis (CAPD) patients.Methods: 158 prevalent CAPD patients with a median level of dp-ucMGP of 1093 (752, 1485) pmol/L were enrolled. Patient outcomes including all-cause mortality and cardiovascular events (CVEs) were recorded during follow-up. Survival curves were performed using Kaplan-Meier method, and the influences of dp-ucMGP on outcomes were analyzed by Cox regression models.Results: A total of 59 deaths and 82 new episodes of CVEs occurred during median follow-up of 31.4 ± 13.1 months (range: 3.8-48.0 months). Kaplan-Meier analysis revealed patients with higher dp-ucMGP levels (≥ 1093 pmol/L) had an increased risk for both mortality (P = 0.005) and CVEs (P < 0.001). Multivariable Cox regression confirmed that higher dp-ucMGP levels increase the mortality risk [hazard ratio (HR), 1.763; 95% CI 1.045-3.291] and CVEs (HR, 1.846; 95% CI 1.074-3.172). For every 100 pmol/L increase in serum dp-ucMGP, the adjusted HRs for mortality and CVEs were 1.054 (95% CI 1.008-1.106) and 1.034 (95% CI 1.012-1.089), respectively.Conclusions: Vitamin K deficiency, as expressed by high dp-ucMGP levels, showed independently associations with mortality and CVEs in CAPD patients. [ABSTRACT FROM AUTHOR]