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Lung cancer ranks topmost among the most frequently diagnosed cancers. Despite increasing research, there are still unresolved mysteries in the molecular mechanism of lung cancer. Long noncoding RNA small nucleolar RNA host gene 11 (SNHG11) was found to be upregulated in lung cancer and facilitated lung cancer cell proliferation, migration, invasion, and epithelial-mesenchymal transition progression while suppressed cell apoptosis. Moreover, the high expression of SNHG11 was correlated with poor prognosis of lung cancer patients, TNM stage, and tumor size. Further assays demonstrated that SNHG11 functioned in lung cancer cells via Wnt/β-catenin signaling pathway. Subsequently, Wnt/β-catenin pathway was found to be activated through SNHG11/miR-4436a/CTNNB1 ceRNA axis. As inhibiting miR-4436 could only partly rescue the suppression of cell function induced by silencing SNHG11, it was suspected that β-catenin might enter cell nucleus through other pathways. Mechanism investigation proved that SNHG11 would directly bind with β-catenin to activate classic Wnt pathway. Subsequently, in vivo tumorigenesis was also demonstrated to be enhanced by SNHG11. Hence, SNHG11 was found to promote lung cancer progression by activating Wnt/β-catenin pathway in two different patterns, implying that SNHG11 might contribute to lung cancer treatment by acting as a therapeutic target. © 2020 Wiley Periodicals, Inc.Prolonged survival of a typical postmitotic neuron hinges on a balance between multiple processes, among these are a sustenance of ATP production and protection against reactive oxygen species. In neuropathological conditions, mitochondrial defects often lead to both a drop in ATP levels, as well as increase reactive oxygen species production from inefficient electron transport processes and NADPH-oxidases activities. The former often resulted in the phenomenon of compensatory aerobic glycolysis. The latter stretches the capacity of the cell's redox buffering capacity, and may lead to damages of key enzymes involved in energy metabolism. Several recent reports have indicated that enhancing glucose availability and uptake, as well as increasing glycolytic flux via pharmacological or genetic manipulation of glycolytic enzymes, could be protective in animal models of several major neurodegenerative diseases, including Parkinson's disease, Huntington's disease, and Amyotrophic lateral sclerosis. Activation of canonical Wnt signaling, which improves disease symptoms in mouse models of Alzheimer's disease also appears to work via an elevation of glycolytic enzymes and enhance glucose metabolism. Here, I discuss these findings and the possible underlying mechanisms of how an increase in glucose uptake and glycolysis could be neuroprotective. Increased glycolytic production of ATP would help alleviate energy deficiency, and ATP's hydrotropic effect may enhance solubility and clearance of toxic aggregates prevalent in many neurodegenerative diseases. Furthermore, channeling of glucose into the Pentose Phosphate Pathway would increase the redox buffering capacity of the cell. © 2020 Wiley Periodicals, Inc.Cardiac fibrosis is a common pathway leading to heart failure and involves continued activation of cardiac fibroblasts (CFs) into myofibroblasts during myocardium damage, causing excessive deposition of the extracellular matrix (ECM) and thus increases matrix stiffness. Increasing evidence has shown that stiffened matrix plays an important role in promoting CF activation and cardiac fibrosis, and several signaling factors mediating CF mechanotransduction have been identified. However, the key molecules that perceive matrix stiffness to regulate CF activation remain to be further explored. Here, we detected significantly increased expression and nuclear localization of Yes-associated protein (YAP) in native fibrotic cardiac tissues. By using mechanically regulated in vitro cell culture models, we found that a stiff matrix-induced high expression and nuclear localization of YAP in CFs, accompanied by enhanced cell activation. We also demonstrated that YAP knockdown decreased fibrogenic response of CFs and that YAP overexpression promoted CF activation, indicating that YAP plays an important role in mediating matrix stiffness-induced CF activation. Further mechanistic studies revealed that the YAP pathway is an important signaling branch downstream of angiotensin II type 1 receptor in CF mechanotransduction. The findings help elucidate the mechanism of fibrotic mechanotransduction and may contribute to the development of new approaches for treating fibrotic diseases. © 2020 Wiley Periodicals, Inc.We investigate the dynamics of water in contact with the solid calcium fluoride, where at low pH localized charge can develop upon fluorite dissolution. We use two-dimensional surface specific vibrational spectroscopy to quantify the heterogeneity of the interfacial water (D 2 O) molecules and to provide information about the sub-picosecond vibrational energy relaxation dynamics at the buried solid/liquid interface. We find that strongly hydrogen-bonded OD groups, with a vibrational frequency below 2500 cm-1 , display very rapid spectral diffusion and vibrational relaxation; for weakly H-bonded OD groups, above 2500 cm-1 , the dynamics slows down substantially. Atomistic simulations, based on the electronic structure theory, reveal the molecular origin of energy transport through the local hydrogen-bond network. We conclude that strongly oriented hydrogen-bonded water molecules in the adsorbed layer, whose orientation is pinned by the localized charge defects, can exchange vibrational energy very rapidly due to the strong collective dipole, compensating for a partially missing solvation shell. © 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.OBJECTIVES Pediatric appendicitis remains a challenging diagnosis in the emergency department (ED). Available risk prediction algorithms may contribute to excessive ED imaging studies. Incorporation of physician gestalt assessment could help refine predictive tools and improve diagnostic imaging decisions. METHODS This study was a subanalysis of a parent study that prospectively enrolled patients ages 5 to 20.9 years with a chief complaint of abdominal pain presenting to 11 community EDs within an integrated delivery system between October 1, 2016, and September 30, 2018. Prior to diagnostic imaging, attending emergency physicians enrolled patients with ≤5 days of right-sided or diffuse abdominal pain using a Web-based application embedded in the electronic health record. Predicted risk (gestalt) of acute appendicitis was prospectively entered using a sliding scale from 1% to 100%. selleck chemicals As a planned secondary analysis, we assessed the performance of gestalt via c-statistics of receiver operating characteristic (ROC) curves; tested associations between gestalt performance and patient, physician, and facility characteristics; and examined clinical characteristics affecting gestalt estimates.
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