Baggerhaney7864

A ruthenium-catalyzed electrochemical dehydrogenative annulation reaction of imidazoles with alkynes has been established, enabling the preparation of various bridgehead N-fused [5,6]-bicyclic heteroarenes through regioselective electrochemical C-H/N-H annulation without chemical metal oxidants. Novel aza-ruthena-bicyclo-[3.2.0]-heptadienes were fully characterized and identified as key intermediates. Mechanistic studies are suggestive of an oxidatively-induced reductive elimination pathway within a ruthenium(II/III) regime. © 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.The transcriptional repressor Hairy Enhancer of Split 1 (HES1) plays an essential role in the development of many organs by promoting the maintenance of stem/progenitor cells, controlling the reversibility of cellular quiescence, and regulating both cell fate decisions. AM1241 concentration Deletion of Hes1 in mice results in severe defects in multiple organs and is lethal in late embryogenesis. Here we have investigated the role of HES1 in hematopoiesis using a hematopoietic lineage-specific Hes1 knockout mouse model. We found that while Hes1 is dispensable for steady-state hematopoiesis, Hes1-deficient hematopoietic stem cells (HSCs) undergo exhaustion under replicative stress. Loss of Hes1 upregulates the expression of genes involved in PPARγ signaling and fatty acid metabolism pathways, and augments fatty acid oxidation (FAO) in Hes1 f/f Vav1Cre HSCs and progenitors. Functionally, PPARγ targeting or FAO inhibition ameliorates the repopulating defects of Hes1 f/f Vav1Cre HSCs through improving quiescence in HSCs. Lastly, transcriptome analysis reveals that disruption of Hes1 in hematopoietic lineage alters expression of genes critical for HSC function, PPARγ signaling, and fatty acid metabolism. Together, our findings identify a novel role of HES1 in regulating stress hematopoiesis and provide mechanistic insight into the function of HES1 in HSC maintenance. ©2020 The Authors. Stem Cells published by Wiley Periodicals, Inc. on behalf of AlphaMed Press 2020.Alcoholic liver disease (ALD) is caused by long-term consumption of alcohol and has become an important social and medical problem. Intestinal fungal flora (mycobiota) play an important role in ALD, so we used the mycobiota as an entry point to explore the mechanism of action of Paeonol against ALD. Here, we found that Paeonol is effective against ALD inflammatory lesions and relieves liver fat lesions. Furthermore, we found that after the treatment of Paeonol, the fungal dysbiosis is improved, and the fungal abundance is reduced, and the translocation of β-glucan to the liver and its mediated Dectin-1/IL-1β signaling pathway is blocked. Our study shows that paeonol ameliorated acute ALD-related inflammatory injury to the liver by alleviating intestinal fungal dysbiosis and inhibiting the mycobiota-mediated Dectin-1/IL-1β signaling pathway. link2 ©2020 Society for Leukocyte Biology.Wilms' tumor, also known as nephroblastoma, is a kind of pediatric renal cancer. Previous studies have indicated that microRNAs (miRNAs) regulate various cancers progression. However, whether miR-200 family regulated Wilms' tumor progression remains to be elucidated. In our study, miR-200b/c/429 expression was down-regulated in Wilms' tumor tissue samples from 25 patients. And data from three independent analyses of RT-qPCR revealed that the expression of miR-200b/c/429 was down-regulated in Wilms' tumor cell lines. Functionally, CCK-8 assay revealed that cell viability was reduced by overexpressing miR-200b/c/429. Transwell assay manifested that cell migration and invasion was hindered by miR-200b/c/429 overexpression. Sphere-forming and Western blot assays demonstrated that miR-200b/c/429 overexpression suppressed sphere formation ability. Mechanically, NF-κB pathway was confirmed to be associated with Wilms' tumor progression, miR-200b/c/429 overexpression inactivated NF-κB pathway as miR-200b/c/429 was identified to target IKK-β, a NF-κB pathway related gene. Moreover, miR-200b/c/429 was sponged by LINC00667 in Wilms' tumor cells. LINC00667 competitively bound with miR-200b/c/429 to regulate IKK-β expression and then activate NF-κB pathway in Wilms' tumor. Subsequently, rescue assays illustrated silence of IKK-β could reverse the effect of miR-200b/c/429 inhibition on the progression of sh-LINC00667-transfected Wilms' tumor cells. In summary, LINC00667 promoted Wilms' tumor progression by sponging miR-200b/c/429 family to regulate IKK-β. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.A high triplet energy host is developed using silane moiety. 9-(4-(triphenylsilyl)dibenzo[b,d]furan-2-yl)-9H-carbazole (SiDBFCz) is designed through extensive density functional theory (DFT) calculations to obtain appropriate hole and electron injection barriers. The chemical hardness and the charge transport characteristics are comprehensively investigated to realize a bipolar host with high triplet energy over 2.9 eV for deep blue phosphorescent organic light-emitting diodes (PHOLEDs). The synthesized SiDBFCz clearly exhibits the bipolar characteristics especially with emitter molecules doped. An external quantum efficiency over 19% without any microcavity optimization is achieved thanks to the good charge balance in the SiDBFCz PHOLED. The device lifetime of the SiDBFCz PHOLED is improved more than 1000%, compared to the unipolar control devices at an initial luminance of 500 cd/m 2 . The dramatic enhancement of the operational stability of the deep blue PHOLED is also thoroughly investigated in terms of electrochemical stability of host molecules in charged or excited states. The results clearly indicate that the device lifetime is strongly correlated with the bond dissociation energy and the activation energy for the bond dissociation reaction in triplet excited state. © 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.Manipulating the collective molecular movements to implement macroscopic mechanical response of bulk material is attractive and challenging. Here, we synthesize an organic-inorganic hybrid single crystal that exhibits a giant macroscopic shape transformation with a remarkable thermal hysteretic feature. The colossal anisotropic shape change, which manifests as an abrupt elongation of ca. 9% along crystallographic c-axis and a concomitant contraction of ca. link3 9% in a perpendicular direction, is induced by a significant reorientation of imidazoliums accompanied with a substantial configurational variation in CuBr 4 2- complex anions. The synergistic motions of both the molecular cations and anions engender a remarkable large thermal hysteresis (> 30 K) in the shape transformation of single crystal, implying this material may play a role in alternating memory media. Furthermore, due to the stable crystal lattice, a single crystal that demonstrates naked-eye detectable large shape transformation was used as a thermal actuator to spontaneously control an electric circuit by temperature variation. © 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.AIM AND OBJECTIVE To critically review contemporary transition theories to determine how they apply to the newly qualified graduate registered nurse programmes. BACKGROUND Graduate nurse transition to employment is the time of significant change which has resulted in high attrition rates. Graduates are often challenged by their expectation of nursing practice and the reality of the role. The transition from hospital-based training to university-based training has resulted in the need for primary employment to commence with graduate/orientation/internship programmes to help support new graduates transition into clinical practice. One transition model, Duchscher's stages of transition theory, utilised three former theories to develop a final model. DESIGN A narrative critical literature review. METHOD The theories selected for the review were Kramer's reality shock theory, Benner's novice to expert theory, Bridges transition theory and Duchscher's stages of transition theory. CONCLUSION Duchscher's stages of transition theory reflects the experiences of registered nursing transition into the workforce directly from university. The application of the theory is effective to guide understanding of the current challenges that new graduate nurse's experience today. There is a need for new graduates to complete their university degree as advanced beginners in order to decrease the experience of transition shock and keep pace with rapidly changing demands of the clinical environment. This may be achieved by increasing ward-based simulation in university education. A theoretical framework can provide a deep understanding of the various stages and processes of transition and enable development of successful programmes. RELEVANCE TO CLINICAL PRACTICE Both universities and hospitals need to adapt their current practice to align with the needs of new graduates due to large student numbers and ongoing systematic advancements to decrease the attrition rate. © 2020 John Wiley & Sons Ltd.AIM AND OBJECTIVES To explore the experiences and views of nurses who provide nonpharmacological therapies for chronic pain management in palliative care. BACKGROUND Nursing expertise in palliative care is essential in providing pain relief to patients with chronic diseases. Examinations of the use of nonpharmacological therapies for chronic pain management in palliative care have revealed what nonpharmacological therapies have been used, but there is insufficient knowledge regarding nurses' attitudes, views and experiences regarding pain therapies in this context. DESIGN A qualitative descriptive design was chosen. METHODS Data were collected through individual interviews in a purposive sample with 15 nurses to ensure maximum variation. The data were analysed using qualitative content analysis. This study aligns with the consolidated criteria for reporting qualitative research (COREQ) checklist. RESULTS The analysis yielded four categories, as follows "building and sustaining favourable therapeutic relationsrses should be encouraged and given the opportunity to attend specialised training in palliative care and pain management. © 2020 The Authors. Journal of Clinical Nursing published by John Wiley & Sons Ltd.The analysis of multivariate time-to-event (TTE) data can become complicated due to the presence of clustering, leading to dependence between multiple event times. For a long time, (conditional) frailty models and (marginal) copula models have been used to analyze clustered TTE data. In this article, we propose a general frailty model employing a copula function between the frailty terms to construct flexible (bivariate) frailty distributions with the application to current status data. The model has the advantage to impose a less restrictive correlation structure among latent frailty variables as compared to traditional frailty models. Specifically, our model uses a copula function to join the marginal distributions of the frailty vector. In this article, we considered different copula functions, and we relied on marginal gamma distributions due to their mathematical convenience. Based on a simulation study, our novel model outperformed the commonly used additive correlated gamma frailty model, especially in the case of a negative association between the frailties.