2,363 research outputs found

    Mitochondria-targeted spin-labelled luminescent iridium anticancer complexes

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    Mitochondria generate energy but malfunction in many cancer cells, hence targeting mitochondrial metabolism is a promising approach for cancer therapy. Here we have designed cyclometallated iridium(III) complexes, containing one TEMPO (2,2,6,6-tetramethylpiperidine-1-oxyl) spin label [C43H43N6O2Ir1·PF6]˙ (Ir-TEMPO1) and two TEMPO spin labels [C52H58N8O4Ir1·PF6]˙ (Ir-TEMPO2). Electron paramagnetic resonance (EPR) spectroscopy revealed spin–spin interactions between the TEMPO units in Ir-TEMPO2. Both Ir-TEMPO1 and Ir-TEMPO2 showed bright luminescence with long lifetimes (ca. 35–160 ns); while Ir-TEMPO1 displayed monoexponential decay kinetics, the biexponential decays measured for Ir-TEMPO2 indicated the presence of more than one energetically-accessible conformation. This observation was further supported by density functional theory (DFT) calculations. The antiproliferative activity of Ir-TEMPO2 towards a range of cancer cells was much greater than that of Ir-TEMPO1, and also the antioxidant activity of Ir-TEMPO2 is much higher against A2780 ovarian cancer cells when compared with Ir-TEMPO1. Most notably Ir-TEMPO2 was particularly potent towards PC3 human prostate cancer cells (IC50 = 0.53 μM), being ca. 8× more active than the clinical drug cisplatin, and ca. 15× more selective towards cancer cells versus normal cells. Confocal microscopy showed that both Ir-TEMPO1 and Ir-TEMPO2 localise in the mitochondria of cancer cells

    The expression profile of microRNAs in a model of 7,12-dimethyl-benz[a]anthrance-induced oral carcinogenesis in Syrian hamster

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    <p>Abstract</p> <p>Background</p> <p>Non-coding RNA molecules, such as microRNAs, may play an important role in carcinogenesis. Recent studies have indicated that microRNAs are involved in initiation and progression of various malignancies. However, little work has been done to compare the microRNA expression patterns in oral cancer. In this study, we constructed an animal model of oral squamous cell carcinoma to investigate expression profiles of microRNAs in oral carcinogenesis.</p> <p>Methods</p> <p>The animal model of oral squamous cell carcinoma was conducted by tri-weekly (Monday, Wednesday, and Friday) painting with 5% DMBA in acetone. Six Syrian hamsters, including three from the treated group and three from the control group, were used as a training group for microRNA microarray analysis. All microarray data were analyzed by Significance Analysis of Microarrays (SAM) and CLUSTER 3.0 software, and this result was further confirmed by qRT-PCR assay.</p> <p>Results</p> <p>Seventeen microRNAs were differentially expressed in oral squamous cell carcinoma. Five microRNAs (hsa-miR-21, hsa-miR-200b, hsa-miR-221, hsa-miR-338, and mmu-miR-762) were significantly upregulated and twelve microRNAs (hsa-miR-16, hsa-miR-26a, hsa-miR-29a, hsa-miR-124a, hsa-miR-125b, mmu-miR-126-5p, hsa-miR-143, hsa-miR-145, hsa-miR-148b, hsa-miR-155, hsa-miR-199a, and hsa-miR-203) were down-regulated in cancer tissues. The expression levels of hsa-miR-21 and hsa-miR-16 seen with Stem-loop qRT-PCR were also seen in microarray analysis in all samples.</p> <p>Conclusion</p> <p>Our findings identified specific microRNA expression in oral squamous cell carcinoma and suggested that microRNAs have a role in oral carcinogenesis.</p

    Mineralization age and genesis of the makeng-style iron deposits in the Paleo-Pacific tectonic domain of South China: In situ LA-ICPMS garnet U-Pb chronological and geochemical constraints

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    To reveal the genesis of Makeng-style iron polymetallic deposits from SE China in the paleo-Pacific tectonic domain, a new analytical method of LA-ICPMS garnet U-Pb dating and rare Earth element analysis was conducted for the Makeng, Luoyang, Dapai and Pantian deposits. The U-Pb dating results of nine garnet skarn samples from these deposits suggested that the Makeng-style iron polymetallic deposits mainly formed during 137–130 Ma, which is consistent with the zircon U-Pb and molybdenite Re-Os ages. This study provides more direct evidence of the mineralization age and the relationship between mineralization and granite, compared with previous studies on the zircon U-Pb dating for granites in the ore fields. Rare Earth element (REE) analysis results and REE patterns of four representative garnet samples from the Makeng, Luoyang, Dapai and Pantian deposits show that they are similar to typical skarn deposits, but obvious differences in the REE distribution types indicate that the ore-forming process may be distinct due to different mineralizing fluid for these Makeng-style deposits. Our new garnet U-Pb dating and rare Earth element analysis result not only provides new evidence for the mineralization age and genesis of the Makeng-style deposits but is also of great significance to promote the application of U-Pb dating methods to research skarn type deposits

    In Situ Synthesis of Reduced Graphene Oxide-Reinforced Silicone-Acrylate Resin Composite Films Applied in Erosion Resistance

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    The reduced graphene oxide reinforced silicone-acrylate resin composite films (rGO/SAR composite films) were prepared by in situ synthesis method. The structure of rGO/SAR composite films was characterized by Raman spectrum, atomic force microscope, scanning electron microscopy, and thermogravimetric analyzer. The results showed that the rGO were uniformly dispersed in silicone-acrylate resin matrix. Furthermore, the effect of rGO loading on mechanical properties of composite films was investigated by bulge test. A significant enhancement (ca. 290% and 320%) in Young’s modulus and yield stress was obtained by adding the rGO to silicone-acrylate resin. At the same time, the adhesive energy between the composite films and metal substrate was also improved to be about 200%. Moreover, the erosion resistance of the composite films was also investigated as function of rGO loading. The rGO had great effect on the erosion resistance of the composite films, in which the Rcorr (ca. 0.8 mm/year) of composite film was far lower than that (28.7 mm/year) of pure silicone-acrylate resin film. Thus, this approach provides a novel route to investigate mechanical stability of polymer composite films and improve erosion resistance of polymer coating, which are very important to be used in mechanical-corrosion coupling environments

    Superconductivity emerged from density-wave order in a kagome bad metal

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    Unconventional superconductivity (USC) in a highly correlated kagome system has been theoretically proposed for years, yet the experimental realization is hard to achieve. The recently discovered vanadium-based kagome materials, which exhibit both superconductivity and charge density wave (CDW) orders, are nonmagnetic and weakly correlated, thus unlikely host USC as theories proposed. Here we report the discovery of a chromium-based kagome bad metal, CsCr3_3Sb5_5, which is contrastingly characterised by significant electron correlations and frustrated magnetism. Successive phase transitions at \sim54 K with stripe-like 4a04a_0 structural modulations are observed, probably associated with CDW and antiferromagnetic spin-density-wave (SDW) orderings. Under moderately high pressures of 4-8 GPa, these density-wave orders are suppressed and, remarkably, superconductivity emerges with a maximum TcT_\mathrm{c} of 6.4 K. A quantum critical point at PcP_\mathrm{c}\approx 4 GPa is revealed, by which non-Fermi-liquid behaviours show up, reminiscent of USC in iron-based superconductors. The electronic structure calculations indicate that the electron filling is close to the characteristic flat bands of the kagome lattice. Our work offers an unprecedented platform for investigating the mechanism of USC in a correlated kagome system.Comment: 26 pages, 10 figure
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