Ericksonwinkler5182

77) for a measurement time of 2 seconds. Using the same reconstruction in the patients with chronic obstructive pulmonary disease, the Dice coefficient of defect volumes was 0.86 ± 0.05, the mean difference in volume defect percentage was -1.0 ± 1.7 percentage points, and the overlap percentage was 87% ± 2% for a measurement time of 6 seconds. Between volume defect percentage of 19 F and 129 Xe, a linear correlation (r = 0.75; P = .03) was found, with 19 F volume defect percentage being significantly higher (mean difference = 11%; P = .04). CONCLUSION 1 H-guided reconstruction of pulmonary 19 F gas MRI enables reduction of acquisition time while maintaining image quality and robustness of functional parameters. © 2020 The Authors. Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine.The use of synthetic bridges as surrogates for disulfide bonds has emerged as a practical strategy to obviate the poor stability of some disulfide-containing peptides. However, peptides incorporating large-span synthetic bridges are still beyond the reach of existing methods. GSK3787 chemical structure Here we report a native chemical ligation (NCL)-assisted diaminodiacid (DADA) strategy that enables the robust generation of disulfide surrogate peptides incorporating surrogate bridges up to 50 amino acids in length. This strategy provides access, for this first time, to some highly desirable but otherwise impossible-to-obtain disulfide surrogates of bioactive peptides, including μ-conotoxin KIIIA, a potent inhibitor of voltage-gated sodium channels. The bioactivities and structures of the synthetic disulfide surrogates were verified by voltage clamp assays, NMR, and X-ray crystallography; and stability studies established that the disulfide replacements effectively overcame the problems of disulfide reduction and scrambling that often plague these pharmacologically important peptides. By expanding access to structurally more diverse disulfide surrogate peptides, the NCL-assisted DADA strategy is expected to facilitate the development of peptide-based diagnostic and therapeutic agents. © 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.The roles of cancer-associated fibroblasts (CAF) in the progression of various types of cancers are well established. CAF promote cancer progression through pleiotropic mechanisms, including the secretion of soluble factors and extracellular matrix, physical interactions with cancer cells, and the regulation of angiogenesis, immunity and metabolism. Their contribution to therapeutic resistance is also well appreciated. Therefore, CAF have been considered as a therapeutic target in cancer. However, recent studies in autochthonous pancreatic cancer models suggest that specific subset(s) of CAF exhibit cancer-restraining roles, indicating that CAF are functionally and molecularly heterogeneous, which is supported by recent single-cell transcriptome analyses. While cancer-promoting CAF (pCAF) have been extensively studied, the nature and specific marker(s) of cancer-restraining CAF (rCAF) have remained uncharacterized. Interestingly, a recent study provided insight into the nature of rCAF and suggested that they may share molecular properties with pancreatic stellate cells (PSC) and mesenchymal stem/stromal cells (MSC). Complicating this finding is that PSC and MSC have been shown to promote the formation of a tumor-permissive and tumor-promoting environment in xenograft tumor models. However, these cells undergo significant transcriptional and epigenetic changes during ex vivo culture, which confounds the interpretation of experimental results based on the use of cultured cells. In this short review, we describe recent studies and hypotheses on the identity of rCAF and discuss their analogy to fibroblasts that suppress fibrosis in fibrotic diseases. Finally, we discuss how these findings can be exploited to develop novel anticancer therapies in the future. © 2020 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.Structural alterations of NUTM1 were originally thought to be restricted to poorly differentiated carcinomas with variable squamous differentiation originating in the midline organs of children and adolescents. Termed NUT carcinomas (NCs), they were defined by a t(15;19) chromosomal rearrangement that was found to result in a BRD4-NUTM1 gene fusion. However, the use of DNA and RNA-based next-generation sequencing has recently revealed a multitude of new NUTM1 fusion partners in a diverse array of neoplasms including sarcoma-like tumors, poromas, and acute lymphoblastic leukemias (ALLs) that we propose to call NUTM1-rearranged neoplasms (NRNs). Intriguingly, the nosology of NRNs often correlates with the functional classification of the fusion partner, suggesting different oncogenic mechanisms within each NRN division. Indeed, whereas NCs are characterized by their aggressiveness and intransigence to standard therapeutic measures, the more positive clinical outcomes seen in some sarcoma and ALL NRNs may reflect these mechanistic differences. Here we provide a broad overview of the molecular, nosological, and clinical features in these newly discovered neoplastic entities. We describe how aberrant expression of NUTM1 due to fusion with an N-terminal DNA/chromatin-binding protein can generate a potentially powerful chromatin modifier that can give rise to oncogenic transformation in numerous cellular contexts. We also conclude that classification, clinical behavior, and therapeutic options may be best defined by the NUTM1 fusion partner rather than by tumor morphology or immunohistochemical profile. © 2020 Wiley Periodicals, Inc.Emerging evidence highlights the role of the long noncoding RNA (lncRNA) KCNQ1OT1 in fracture healing. Osteoblast proliferation, migration, and survival are pivotal during this process. In this study, we aimed to improve our understanding of the regulatory role of lncRNA KCNQ1OT1 during osteoblast proliferation, migration, and survival. We searched the gene expression omnibus databases and LncBase Experimental V.2 to identify key microRNAs (miRNAs) targets of KCNQ1OT1. MiR-701-3p was selected as a differentially expressed miRNA and RNA immunoprecipitation assays were performed to verify its interaction with KCNQ1OT1. Fibroblast growth factor receptor 3 (FGFR3) was also identified as a target of miR-701-3p. We further identified KCNQ1OT1 as a competing endogenous RNA of miR-701-3p that could influence osteoblast proliferation, migration, and apoptosis in vitro and in vivo. Taken together, our results indicate that the KCNQ1OT1/miR-701-3p/FGFR3 axis is an important regulator of osteoblast proliferation, migration, and apoptosis, and provide a new therapeutic avenue for fracture healing.