Noonanbentzen7036

© 2020 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.Inspired by the diverse protein-based structures and materials in organisms, proteins have been expected as promising biological components for constructing nanomaterials toward various applications. In numerous studies protein-based nanomaterials have been constructed with the merits of abundant bioactivity and good biocompatibility. However, self-assembly of proteins as a dominant approach in constructing anticancer nanodrugs has not been reviewed. Here, we provide a comprehensive account of the role of protein self-assembly in fabrication, regulation, and application of anticancer nanodrugs. The supramolecular strategies, building blocks, and molecular interactions of protein self-assembly as well as the properties, functions, and applications of the resulting nanodrugs are discussed. The applications in chemotherapy, radiotherapy, photodynamic therapy, photothermal therapy, gene therapy, and combination therapy are included. Especially, manipulation of molecular interactions for realizing cancer-specific response and cancer theranostics are emphasized. By expounding the impact of molecular interactions on therapeutic activity, rational design of highly efficient protein-based nanodrugs for precision anticancer therapy can be envisioned. Also, the challenges and perspectives in constructing nanodrugs based on protein self-assembly are presented to advance clinical translation of protein-based nanodrugs and next-generation nanomedicine. © 2020 Wiley-VCH Verlag GmbH & Co. AM 095 KGaA, Weinheim.The Hippo signaling pathway is involved in the pathophysiology of various cardiovascular diseases. Yes-associated protein (YAP) and transcriptional enhancer activator domain (TEAD) transcriptional factors, the main transcriptional complex of the Hippo pathway, were recently identified as modulators of phenotypic switching of vascular smooth muscle cells (VSMCs). However, the intrinsic regulator of YAP/TEAD-mediated gene expressions involved in vascular pathophysiology remains to be elucidated. Here, we identified Homeobox A4 (HOXA4) as a potent repressor of YAP/TEAD transcriptional activity using lentiviral shRNA screen. Mechanistically, HOXA4 interacts with TEADs and attenuates YAP/TEAD-mediated transcription by competing with YAP for TEAD binding. We also clarified that the expression of HOXA4 is relatively abundant in the vasculature, especially in VSMCs. In vitro experiments in human VSMCs showed HOXA4 maintains the differentiation state of VSMCs via inhibition of YAP/TEAD-induced phenotypic switching. We generated Hoxa4-deficient mice and confirmed the downregulation of smooth muscle-specific contractile genes and the exacerbation of vascular remodeling after carotid artery ligation in vivo. Our results demonstrate that HOXA4 is a repressor of VSMC phenotypic switching by inhibiting YAP/TEAD-mediated transcription. © 2020 The Authors. Published under the terms of the CC BY 4.0 license.BACKGROUND The aim of this study was to determine the function of long non-coding RNA small nucleolar RNA host gene 6 (SNHG6) in non-small cell lung cancer (NSCLC) and its underlying mechanisms. METHODS The association of SNHG6 or miR-101-3p with clinicopathological characteristics and prognosis in patents with NSCLC was assessed by TCGA dataset. Cell proliferation and invasion were evaluated by MTT and Transwell assays and SNHG6-specific binding with miR-101-3p was verified by bioinformatic analysis, luciferase gene report and RNA immunoprecipitation assays. qRT-PCR and Western blot was used to assess the effects of SNHG6 on the expression of miR-101-3p and chromodomain Y like (CDYL) in NSCLC cells. A xenograft tumor model in vivo was established to observe the effects of SNHG6 knockdown on tumor growth. RESULTS We found that increased expression of SNHG6 was associated with pathological stage and lymph node infiltration, and acted as an independent prognostic factor of tumor recurrence in patients with NSCLC. Silencing SNHG6 expression repressed cell growth and invasion in vitro and in vivo, but overexpression of SNHG6 reversed these effects. Furthermore, SNHG6 was identified to act as a sponge of miR-101-3p, which could reduce cell proliferation and attenuate SNHG6-induced CDYL expression. Low expression of miR-101-3p or high expression of CDYL was related to poor survival in patients with NSCLC. CONCLUSIONS Our findings demonstrated that lncRNA SNHG6 contributed to the proliferation and invasion of NSCLC by downregulating miR-101-3p. © 2020 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.Published case studies on the DSM-5 (section III) Alternative Model for Personality Disorders (AMPD) generally utilized unstandardized assessment procedures or mono-method approaches. We present a case from clinical practice to illustrate a standardized, clinically feasible procedure for assessing personality pathology according to the full AMPD model, using a multi-method approach. We aim to present a procedure that can guide and inspire clinicians that are going to work with dimensional models as presented in DSM-5 and ICD-11. Specifically, we show how questionnaire and interview data from multiple sources (i.e. patient and family) can be combined. The clinical case also illustrates how Criterion A (i.e. functioning) and B (i.e. traits) are interrelated, suggesting that the joint assessment of both Criterion A and B is necessary for a comprehensive and clinically relevant case formulation. It also highlights how multi-method information can enhance diagnostic formulations. Finally, we show how the AMPD model can serve treatment planning and provide suggestions for how patient feedback might be delivered. © 2020 John Wiley & Sons, Ltd.Several inorganic hosts such as SrB 4 O 7 or certain nitrides are known to intrinsically stabilize Eu 2+ even upon doping with a Eu 3+ -based precursor and no employment of any reducing conditions during synthesis. Although this somewhat alchemistic concept has already been known for a long time in the field of phosphor synthesis, the mechanistic details of the intrinsic reductive action of certain hosts are only scarcely understood. Herein, we aim to demonstrate first clear experimental evidence that trapped charge carriers such as color centers can also act as potential redox partners to stabilize certain oxidation states of activators taking Eu-activated CsMgCl 3 and CsMgBr 3 as a representative example. Upon intentional doping with EuCl 3 and without employment of any reducing conditions during the synthesis, yet dominant cyan or green luminescence related to the presence of Eu 2+ ions was observed instead, respectively. Photoluminescence spectroscopy at 10 K revealed that this intrinsically occurring reduction could be clearly correlated to the presence of impurity-localized color centers. Although defects are otherwise typically undesired in phosphors, this study demonstrates that their role may be underestimated and they could be used on purpose in the preparation of selected inorganic phosphors. © 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.A modular solid phase multicomponent reaction for the synthesis of 3-substituted isoindolinone derivatives has been carried out. A mixture of a chiral ß-keto lactam, an aldehyde, an isocyanide and a dienophile react to produce chiral 3-substituted isoindolinones in one pot. Modularity has been accomplished by using solid supported aldehydes and dienophiles. Optimization was achieved by using microwave as the source of energy. The reaction was also performed on a biologically relevant well-known programed cell death inducing peptide D(KLAKLAK)2 on solid phase. The molecules show significant fluorescence with large Stokes shifts and fast cell penetration. The chimeric peptides can be tracked under microscope proving the potential of the probes as cell sensors. They were efficiently internalized as compared to non-labeled peptide, with a concomitant induction of programed cell death proving their potential as drug carriers. © 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.INTRODUCTION Both beta-amyloid (Ab) deposition and decline in white matter integrity, are brain alterations observed in Alzheimer's disease (AD) and start to occur by the fourth and fifth decades. However, the association between both brain alterations in asymptomatic subjects is unclear. METHODS Amyloid positron emission tomography (PET) and diffusion tensor imaging (DTI) were obtained in 282 cognitively normal subjects (age 30-89 years). We assessed the interaction of age by abnormal amyloid PET status (Florbetapir F-18 PET >1.2 standard uptake value ratio [SUVR]) on regional mean diffusivity (MD) and global white matter hyperintensity (WMH) volume, controlled for sex, education, and hypertension. RESULTS Subjects with abnormal amyloid PET (n = 87) showed stronger age-related increase in global WMH and regional MD, particularly within the posterior parietal regions of the white matter. DISCUSSION Sporadic Aβ deposition is associated with white matter alterations in AD predilection areas in an age-dependent manner in cognitively normal individuals. © 2020 The Authors. Alzheimer's & Dementia published by Wiley Periodicals, Inc. on behalf of Alzheimer's Association.PURPOSE Pediatric oncology clinicians identify a need for increased sexual and reproductive health (SRH) education with adolescent and young adult (AYA) cancer patients. By surveying pediatric oncology fellowship directors, this study clarifies the state of current fellowship education about SRH for the AYA patient. METHODS A survey was sent to all pediatric oncology fellowship program directors (PDs) in the United States consisting of 13 questions pertaining to three primary SRH domains sexual health, fertility, and safe sex practices. Descriptive statistics and χ2 were used in data analyses. RESULTS Sixty-three PDs responded to the survey (91% response rate). Of these, 88% reported having formal instruction regarding fertility, 41% reported curriculum regarding contraception and 30% reported some education regarding sexual health. The curriculum "being too full" was identified as a barrier to education on fertility (29%), sexual health (40%), and safe sex practices (38%). Not being a required or expected part of the program was more likely to be endorsed as a barrier for sexual health (26%) and safe sex practices (30%) compared with fertility (8%) (P  less then  0.005). Lack of experts to teach was a more frequently endorsed barrier to education on sexual health (47%) compared with either fertility (23%) or safe sex practices (25%) (P  less then  0.005). CONCLUSIONS This study identifies important gaps in oncology fellow education about SRH. Future research must explore optimal education strategies that are feasible and acceptable by PDs and fellow learners, and effective in optimizing AYA SRH care. © 2020 Wiley Periodicals, Inc.AIM We sought to investigate whether the Geriatric Nutritional Risk Index is associated with systemic organ dysfunction among older patients who present with cholecystitis to the emergency department. METHODS This was an observational retrospective study among consecutive older patients with cholecystitis in the emergency department from 2012 to 2018. We collected baseline characteristics and laboratory data, and re-categorized the Geriatric Nutritional Risk Index into three risk groups. We carried out univariate and multivariate analyses to identify factors associated with systemic organ dysfunction. Logistic regression was used for statistical analysis. RESULTS A total of 303 patients were included in this study. The median age of participants was 74 years (interquartile range 68-79 years). The overall proportion of systemic organ dysfunction was 26.4%. The Geriatric Nutritional Risk Index was stratified as ≥98 (n = 183, systemic organ dysfunction 15.3%), 87 to less then 98 (n = 90, systemic organ dysfunction 38.