In men, newly developed criterion ((RI + RV5 + SII + SV2 + SV6) × QRS duration) was equally sensitive as 12-lead sum with a sensitivity of 44% (95% CI 37-51%) and outperformed the other criteria. In an independent cohort, the Groningen-LVH criteria were strongest associated with change in systolic blood pressure. Our proposed CMR sex-specific Groningen-LVH criteria improve the sensitivity to detect LVH, especially in women. Further validation and its association with clinical outcomes is warranted.In the wake of climate change, extreme events such as heatwaves are considered to be key players in the terrestrial biosphere. In the past decades, the frequency and severity of heatwaves have risen substantially, and they are projected to continue to intensify in the future. One key question is therefore how do changes in extreme heatwaves affect the carbon cycle? Although soil respiration (Rs) is the second largest contributor to the carbon cycle, the impacts of heatwaves on Rs have not been fully understood. Using a unique set of continuous high frequency in-situ measurements from our field site, we characterize the relationship between Rs and heatwaves. We further compare the Rs response to heatwaves across ten additional sites spanning the contiguous United States (CONUS). Applying a probabilistic framework, we conclude that during heatwaves Rs rates increase significantly, on average, by ~ 26% relative to that of non-heatwave conditions over the CONUS. Since previous in-situ observations have not measured the Rs response to heatwaves (e.g., rate, amount) at the high frequency that we present here, the terrestrial feedback to the carbon cycle may be underestimated without capturing these high frequency extreme heatwave events.Cancer metastasis is a major cause of the high mortality rate in lung cancer patients. The cytoskeletal rearrangement and degradation of extracellular matrix are required to facilitate cell migration and invasion and the suppression of these behaviors is an intriguing approach to minimize cancer metastasis. Even though Erianthridin (ETD), a phenolic compound isolated from the Thai orchid Dendrobium formosum exhibits various biological activities, the molecular mechanism of ETD for anti-cancer activity is unclear. In this study, we found that noncytotoxic concentrations of ETD (≤ 50 μM) were able to significantly inhibit cell migration and invasion via disruption of actin stress fibers and lamellipodia formation. The expression of matrix metalloproteinase-2 (MMP-2) and MMP-9 was markedly downregulated in a dose-dependent manner after ETD treatment. Mechanistic studies revealed that protein kinase B (Akt) and its downstream effectors mammalian target of rapamycin (mTOR) and p70 S6 kinase (p70S6K) were strongly attenuated. An in silico study further demonstrated that ETD binds to the protein kinase domain of Akt with both hydrogen bonding and van der Waals interactions. In addition, an in vivo tail vein injection metastasis study demonstrated a significant effect of ETD on the suppression of lung cancer cell metastasis. This study provides preclinical information regarding ETD, which exhibits promising antimetastatic activity against non-small-cell lung cancer through Akt/mTOR/p70S6K-induced actin reorganization and MMPs expression.The purpose of this study is to evaluate the levels and clinical diagnosis value of CA15-3, CEA, and SF in canine mammary gland tumors (CMGTs). In this study, the levels of tissues/serum CA15-3, CEA, and SF in 178 CMGT patients or healthy dogs were determined by ELISA and qRT-PCR assay. CA15-3, CEA, and SF levels of the malignant tumor group were significantly higher than that of the benign tumor group and the healthy control group. In the malignant tumor group, CA15-3 held a sensitivity of 51.8%, a specificity of 93.9%, and an accuracy of 76.8%. The sensitivity, specificity, and accuracy of CEA were 44.6%, 84.1%, and 68.1% respectively. SF held a sensitivity of 62.5%, a specificity of 85.4%, and an accuracy of 76.1%. SF showed the highest sensitivity and CA15-3 showed the highest specificity. The sensitivity, specificity, and accuracy of the combined detection of the three biomarkers in malignant tumor groups were 80.4%, 78.0%, and 80.0%, respectively, therefore combined detection increased sensitivity and accuracy but decreased specificity. In conclusion, the combined detection of serum/tissue markers CA15-3, CEA, and SF may improve the detection sensitivity of CMGTs, providing reference value for clinical application.8-Oxoguanine (8-oxoG), a major oxidative base lesion, is highly accumulated in Alzheimer's disease (AD) brains during the pathogenic process. MTH1 hydrolyzes 8-oxo-dGTP to 8-oxo-dGMP, thereby avoiding 8-oxo-dG incorporation into DNA. 8-OxoG DNA glycosylase-1 (OGG1) excises 8-oxoG paired with cytosine in DNA, thereby minimizing 8-oxoG accumulation in DNA. Levels of MTH1 and OGG1 are significantly reduced in the brains of sporadic AD cases. To understand how 8-oxoG accumulation in the genome is involved in AD pathogenesis, we established an AD mouse model with knockout of Mth1 and Ogg1 genes in a 3xTg-AD background. MTH1 and OGG1 deficiency increased 8-oxoG accumulation in nuclear and, to a lesser extent, mitochondrial genomes, causing microglial activation and neuronal loss with impaired cognitive function at 4-5 months of age. https://www.selleckchem.com/products/dir-cy7-dic18.html Furthermore, minocycline, which inhibits microglial activation and reduces neuroinflammation, markedly decreased the nuclear accumulation of 8-oxoG in microglia, and inhibited microgliosis and neuronal loss. Gene expression profiling revealed that MTH1 and OGG1 efficiently suppress progression of AD by inducing various protective genes against AD pathogenesis initiated by Aß/Tau accumulation in 3xTg-AD brain. Our findings indicate that efficient suppression of 8-oxoG accumulation in brain genomes is a new approach for prevention and treatment of AD.The appreciation that cell interactions in tissues is dependent on their three dimensional (3D) distribution has stimulated the development of 3D cell culture models. We constructed an artificial 3D tumour by culturing human breast cancer JIMT-1 cells and human dermal fibroblasts (HDFs) in a 3D network of electrospun polycaprolactone fibres. Here, we investigate ECM components produced by the cells in the artificial 3D tumour, which is an important step in validating the model. Immunostaining and confocal fluorescence microscopy show that the ECM proteins fibronectin, collagen I, and laminin are deposited throughout the entire 3D structure. Secreted soluble factors including matrix metalloproteinases (MMPs) and interleukine-6 (IL-6) were analysed in collected medium and were found to be mainly derived from the HDFs. Treatment with transforming growth factor-β1 (TGF-β1), a major cytokine found in a tumour, significantly alters the MMP activity and IL-6 concentration. In addition, TGF-β1 treatment, changes the morphology of the HDFs to become more elongated and with increased linearized actin filaments compared to non-treated HDFs.