Dawsongravgaard8966

Ciclesonide is an FDA-approved glucocorticoid used to treat asthma and allergic rhinitis. However, whether it has anticancer and anti-cancer stem cell (CSC) effects is unknown. This study focused on investigating the effect of ciclesonide on breast cancer and CSCs and determining its underlying mechanism. Here, we showed that ciclesonide inhibits breast cancer and CSC formation. Similar glucocorticoids-dexamethasone and prednisone-did not inhibit CSC formation. Ciclesonide-induced glucocorticoid receptor (GR) degradation was dependent on ubiquitination. We showed via GR small interfering RNA (siRNA) that GR plays an important role in CSC formation. We showed via western blot and immunofluorescence assays that ciclesonide reduces the nuclear level of GR. The GR antagonist RU-486 also inhibited CSC formation. Ciclesonide reduced the protein level of the Hippo transducer Yes-associated protein (YAP). GR siRNA induced a decrease in YAP protein expression and inhibited mammosphere formation. The YAP inhibitor verteporfin inhibited CSC formation and transcription of the connective tissue growth factor and cysteine-rich protein 61 genes. The GR/YAP1 pathway regulated breast CSC formation. We showed that the GR/YAP signaling pathway regulates breast CSC formation and revealed a new approach for targeting GR and YAP to inhibit CSC formation.As an important part of the wetland ecosystem, alpine wetland is not only one of the most important ecological water conservation areas in the Qinghai-Tibet Plateau region, but is also an effective regulator of the local climate. In this study, using three machine learning algorithms to extract wetland, we employ the landscape ecological index to quantitatively analyze the evolution of landscape patterns and grey correlation to analyze the driving factors of Zoige wetland landscape pattern change from 1995 to 2020. The following results were obtained. (1) The random forest algorithm (RF) performs best when dealing with high-dimensional data, and the accuracy of the decision tree algorithm (DT) is better. The performance of the RF and DT is better than that of the support vector machine algorithm. (2) The alpine wetland in the study area was degraded from 1995 to 2015, whereas wetland area began to increase after 2015. (3) The results of landscape analysis show the decrease in wetland area from 1995 to 2005 was mainly due to the fragmentation of larger patches into many small patches and loss of the original small patches, while the 2005 to 2015 decrease was caused by the loss of many middle patches and the decrease in large patches from the edge to the middle. The 2015 to 2020 increase is due to an increase in the number of smaller patches and recovery of original wetland area. (4) The grey correlation degree further shows that precipitation and evaporation are the main factors leading to the change in the landscape pattern of Zoige alpine wetland. The results are of great significance to the long-term monitoring of the Zoige wetland ecosystem.Estrogen receptor α expressing breast cancers (BC) are classically treated with endocrine therapy. Prolonged endocrine therapy often results in a metastatic disease (MBC), for which a standardized effective therapy is still lacking. Selleck MitoSOX Red Thus, new drugs are required for primary and metastatic BC treatment. Here, we report that the Food and Drug Administration (FDA)-approved drugs, ouabain and digoxin, induce ERα degradation and prevent proliferation in cells modeling primary and metastatic BC. Ouabain and digoxin activate the cellular proteasome, instigating ERα degradation, which causes the inhibition of 17β-estradiol signaling, induces the cell cycle blockade in the G2 phase, and triggers apoptosis. Remarkably, these effects are independent of the inhibition of the Na/K pump. The antiproliferative effects of ouabain and digoxin occur also in diverse cancer models (i.e., tumor spheroids and xenografts). Additionally, gene profiling analysis reveals that these drugs downregulate the expression of genes related to endocrine therapy resistance. Therefore, ouabain and digoxin behave as 'anti-estrogen'-like drugs, and are appealing candidates for the treatment of primary and metastatic BCs.The measurement of the rotational speed of rotating machinery is typically performed based on mechanical adherence; for example, in encoders. Nevertheless, it can be of interest in various types of applications to develop contactless vision-based methodologies to measure the speed of rotating machinery. In particular, contactless rotor speed measurement methods have several potential applications for wind turbine technology, in the context of non-intrusive condition monitoring approaches. The present study is devoted exactly to this problem a ground level video-tachometer measurement technique and an image analysis algorithm for wind turbine rotor speed estimation are proposed. The methodology is based on the comparison between a reference frame and each frame of the video through the covariance matrix a covariance time series is thus obtained, from which the rotational speed is estimated by passing to the frequency domain through the spectrogram. This procedure guarantees the robustness of the rotational speed estimation, despite the intrinsic non-stationarity of the system and the possible signal disturbances. The method is tested and discussed based on two experimental environments with different characteristics the former is a small wind turbine model (with a 0.45 m rotor diameter) in the wind tunnel facility of the University of Perugia, whose critical aspect is the high rotational speed (up to the order of 1500 RPM). The latter test case is a wind turbine with a 44 m rotor diameter which is part of an industrial wind farm in this case, the critical point regards the fact that measurements are acquired in uncontrolled conditions. It is shown that the method is robust enough to overcome the critical aspects of both test cases and to provide reliable rotational speed estimates.Frailty in middle-aged and older adults is associated with diabetes-related complications. The impact of and interaction between diabetes and frailty on psychosocial wellbeing and mortality in Ireland for adults aged ≥50 years were assessed using data from the Survey of Health, Ageing and Retirement in Europe. Measures included diabetes status (self-reported), frailty phenotype (≥3/5 criteria), low self-rated health ("fair" or "poor"), depression screening (EURO-D index score ≥4), and low quality of life (QoL) (CASP-12 index score less then 35). Among the 970 participants, those with diabetes (n = 87) were more likely to be frail (23% vs. 8%; p less then 0.001), have low self-rated health (46% vs. 19%; p less then 0.001), depression (25% vs. 17%; p = 0.070), and low QoL (25% vs. 18%, p = 0.085). Adjusting for diabetes, age and sex, frailty independently predicted low self-rated health (OR 9.79 (5.85-16.36)), depression (9.82 (5.93-16.25)), and low QoL (8.52 (5.19-13.97)). Adjusting for frailty, age and sex, diabetes independently predicted low self-rated health (2.