der(1;7)(q10;p10).We observed that MDS patients with der(1;7) (q10;p10) present male predominance and have a better outcome than the -7/del(7q) group (Supplementary Table 4).Our findings revealed that the mutation spectrum of patients with der(1;7)(q10; p10) was different from that of MDS with -7/del(7q).We demonstrate for the first time, to our knowledge, that der(1;7) (q10;p10) is associated with a high frequency of mutations in RUNX1.Further studies are needed to clarify whether and how mutations of RUNX1 contribute to the pathogenesis of this subtype.
Background/Aims: Copper is an essential trace element for normal cellular function and contributes to critical physiological or pathological processes. The aim of the study was to investigate the effects of copper on vascular tone of rat mesenteric artery and compare the effects of copper on noradrenaline (NA) and high K+ induced vasoconstriction. Methods: The rat mesenteric arteries were isolated and the vessel tone was measured by using multi wire myograph system in vitro. Blood pressure of carotid artery in rabbits was measured by using physiological data acquisition and analysis system in vivo. Results: Copper dose-dependently blunted NA-induced vasoconstriction of rat mesenteric artery. Copper-induced vasorelaxation was inhibited when the vessels were pretreated with NG-nitro-L-arginine methyl ester (L-NAME). Copper did not blunt high K+-induced vasoconstriction. Copper preincubation inhibited NA-evoked vasoconstriction and the inhibition was not affected by the presence of L-NAME. Copper preincubation showed no effect on high K+-evoked vasoconstriction. Copper chelator diethyldithiocarbamate trihydrate (DTC) antagonized the vasoactivity induced by copper in rat mesenteric artery. In vivo experiments showed that copper injection (iv) significantly decreased blood pressure of rabbits and NA or DTC injection (iv) did not rescue the copper-induced hypotension and animal death. Conclusion: Copper blunted NA but not high K+-induced vasoconstriction of rat mesenteric artery. The acute effect of copper on NA-induced vasoconstriction was depended on nitric oxide (NO), but the effect of copper pretreatment on NA-induced vasoconstriction was independed on NO, suggesting that copper affected NA-induced vasoconstriction by two distinct mechanisms.
Inflammatory bowel disease (IBD) is a formidable disease due to its complex pathogenesis. Macrophages, as a major immune cell population in IBD, are crucial for gut homeostasis. However, it is still unveiled how macrophages modulate IBD. Here, we found that LIM domain only 7 (LMO7) was downregulated in pro-inflammatory macrophages, and that LMO7 directly degraded 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3) through K48-mediated ubiquitination in macrophages. As an enzyme that regulates glycolysis, PFKFB3 degradation led to the glycolytic process inhibition in macrophages, which in turn inhibited macrophage activation and ultimately attenuated murine colitis. Moreover, we demonstrated that PFKFB3 was required for histone demethylase Jumonji domain-containing protein 3 (JMJD3) expression, thereby inhibiting the protein level of trimethylation of histone H3 on lysine 27 (H3K27me3). Overall, our results indicated the LMO7/PFKFB3/JMJD3 axis is essential for modulating macrophage function and IBD pathogenesis. Targeting LMO7 or macrophage metabolism could potentially be an effective strategy for treating inflammatory diseases.
Cd1-xZnxTe:Cu Thin films were prepared by co-evaporation method. X-ray Fluorescence Spectrometry (XRF), scanning electron microscope(SEM), UV-Vis transmission spectra, thermal probe, four-probe method, step profiler and X-ray diffractometer (XRD) were used to investigate the composition, structure, morphology, optical and electrical properties of Cd1-x ZnxTe:Cu thin films with different doping concentration. The results show that the resistivity of 10% copper doped Cd1-x ZnxTe films increased several magnitude and the conductive type changed from p-type to n-type after annealing. The 20% cu-doped Cdl, Zn,Te films had not obvious change in conductive type and electrical resistivity after annealing and they exhibit good surface morphology. The transmissivity of 30% cu-doped Cd1-x, ZnxTe films decreased seriously below 10% after annealing, which indicate that they are not suitable to be the top cell materials in tandem structure. The 20% and 30% cu-doped Cd1-x Zn, Te films were both p-type conductivity.
Lung infections are major causes of acute lung injury (ALI), with limited effective treatment available. Tumor necrosis factor receptor-associated factor 6 (TRAF6) is an essential adaptor regulating Toll-like receptors (TLRs). We recently identified Cullin-5 (Cul-5) as a prominent component in the regulation of TRAF6 polyubiquitination, but its physiological significance in ALI has not been explored. In this study, we investigated the potential role of Cul-5 in regulating ALI using mice receiving intratracheal instillation of LPS. We observed that Cul-5-deficient mice displayed reduced lung injury compared with wild-type mice as evidenced by histological analysis, alveolar neutrophil infiltration, and lung liquid accumulation. In addition, inflammatory cytokine expression in bronchoalveolar lavage fluid and lung tissue was also markedly reduced in LPS-treated Cul-5-deficient mice. Interestingly, intratracheal adoptive transfer of Cul-5 +/− but not Cul-5 +/+ macrophages attenuated neutrophil recruitment, alveolar inflammation, and loss of barrier function in LPS-challenged wild-type mice. Finally, we demonstrated that Cul-5 neddylation following LPS exposure induced Cul-5 and TRAF6 interaction and, thereby, TFAR6 polyubiquitination, leading to NF-κB activation and generation of proinflammatory cytokines. Our data show that neural precursor cell expressed developmentally downregulated protein 8 (Nedd8) modification of Cul-5 is required for its interaction with TRAF6 and activation of the TLR4-TRAF6 signaling pathway in LPS-induced ALI, a feature that may be explored for therapeutic intervention.
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