No abstract
In this communication, we show that ultrathin Au nanowires (NWs) with dominant edge sites on their surface are active and selective for electrochemical reduction of CO2 to CO. We first develop a facile seed-mediated growth method to synthesize these ultrathin (2 nm wide) Au NWs in high yield (95%) by reducing HAuCl4 in the presence of 2 nm Au nanoparticles (NPs). These NWs catalyze CO2 reduction to CO in aqueous 0.5 M KHCO3 at an onset potential of -0.2 V (vs reversible hydrogen electrode). At -0.35 V, the reduction Faradaic efficiency (FE) reaches 94% (mass activity 1.84 A/g Au) and stays at this level for 6 h without any noticeable activity change. Density functional theory (DFT) calculations suggest that the excellent catalytic performance of these Au NWs is attributed both to their high mass density of reactive edge sites (≥16%) and to the weak CO binding on these sites. These ultrathin Au NWs are the most efficient nanocatalyst ever reported for electrochemical reduction of CO2 to CO.
Epithelial-mesenchymal transition (EMT) contributes to tumor invasion and metastasis in many cancers and correlates highly with the acquisition of cancer stem cell (CSC) characteristics. EMT also correlates with changes in specific microRNAs (miRNAs) that have already been integrated into tumorigenic programs as either oncogenes or tumor suppressor genes. Here, we show that miR-7, which was downregulated in breast CSCs (BCSCs) isolated from the human MCF-7 and MDA-MB-231 cell lines, inhibited cell invasion and metastasis, decreased the BCSC population and partially reversed EMT in MDA-MB-231 cells by directly targeting the oncogene, SETDB1. The conspicuous epigenetic transition induced by miR-7 overexpression was found not only in MDA-MB-231 cells but also in BCSC xenograft tumors. MiR-7 inhibited the metastasis of BCSCs in lungs, kidneys, and adrenal glands of NOD/SCID mice. ChIP-polymerase chain reaction result suggested that the SETDB1 induced STAT3 expression by binding to the promoter of STAT3. MiR-7-mediated downregulation of SETDB1 resulted in the suppression of STAT3, which led to the downregulation of c-myc, twist, and mir-9. In addition, the downregulation of miR-7 in BCSCs may be indirectly attributed to lincRNA HOTAIR by modulating the expression of HoxD10 that promotes the expression of miR-7. These findings demonstrate that miR-7 was a tumor suppressor and that the overexpression of miR-7 might serve as a good strategy for treating highly invasive breast cancer.
Oscillons are extremely long-lived, spatially-localized field configurations in real-valued scalar field theories that slowly lose energy via radiation of scalar waves. Before their eventual demise, oscillons can pass through (one or more) exceptionally stable field configurations where their decay rate is highly suppressed. We provide an improved calculation of the non-trivial behavior of the decay rates, and lifetimes of oscillons. In particular, our calculation correctly captures the existence (or absence) of the exceptionally long-lived states for large amplitude oscillons in a broad class of potentials, including non-polynomial potentials that flatten at large field values. The key underlying reason for the improved (by many orders of magnitude in some cases) calculation is the systematic inclusion of a spacetime-dependent effective mass term in the equation describing the radiation emitted by oscillons (in addition to a source term). Our results for the exceptionally stable configurations, decay rates, and lifetime of large amplitude oscillons (in some cases 10 8 oscillations) in such flattened potentials might be relevant for cosmological applications.
Due to its simplicity, versatility, and high efficiency, the clustered regularly interspaced short palindromic repeat (CRISPR)/Cas9 technology has emerged as one of the most promising approaches for treatment of a variety of genetic diseases, including human cancers. However, further translation of CRISPR/Cas9 for cancer gene therapy requires development of safe approaches for efficient, highly specific delivery of both Cas9 and single guide RNA to tumors. Here, novel core–shell nanostructure, liposome-templated hydrogel nanoparticles (LHNPs) that are optimized for efficient codelivery of Cas9 protein and nucleic acids is reported. It is demonstrated that, when coupled with the minicircle DNA technology, LHNPs deliver CRISPR/Cas9 with efficiency greater than commercial agent Lipofectamine 2000 in cell culture and can be engineered for targeted inhibition of genes in tumors, including tumors the brain. When CRISPR/Cas9 targeting a model therapeutic gene, polo-like kinase 1 (PLK1), is delivered, LHNPs effectively inhibit tumor growth and improve tumor-bearing mouse survival. The results suggest LHNPs as versatile CRISPR/Cas9-delivery tool that can be adapted for experimentally studying the biology of cancer as well as for clinically translating cancer gene therapy.
Here we present a routine and efficient protocol for year-round production of fertile transgenic maize plants. Type II callus derived from maize Hi II immature zygotic embryos was transformed using the PDS 1000/He biolistic gun and selected on bialaphos. In an effort to improve the transformation protocol, the effects of gold particle size and callus morphology on transformation efficiency were investigated. Reducing gold particle size from 1.0 mm or 0.6 mm resulted in a significant increase in the rate of recovery of bialaphos-resistant clones from Type II callus. The average transformation efficiency of pre-embryogenic, early embryogenic and late embryogenic callus did not vary significantly. Rates of transformation, regeneration and fertility achieved for Type II callus are summarized and compared to those achieved for greenhouse-and field-derived immature zygotic embryos.
Purpose With recent approval of inhibitors of PD-1 in melanoma, non-small cell lung cancer (NSCLC) and renal cell carcinoma (RCC), extensive efforts are underway to develop biomarkers predictive of response. PD-L1 expression has been most widely studied, and is more predictive in NSCLC than RCC or melanoma. We therefore studied differences in expression patterns across tumor types. Experimental Design We employed tissue microarrays with tumors from NSCLC, RCC or melanoma and a panel of cell lines to study differences between tumor types. Predictive studies were conducted on samples from 65 melanoma patients treated with PD-1 inhibitors alone or with CTLA-4 inhibitors, characterized for outcome. PD-L1 expression was studied by quantitative immunofluorescence using two well-validated antibodies. Results PD-L1 expression was higher in NSCLC specimens than RCC, and lowest in melanoma (P=0.001), and this finding was confirmed in a panel of cell lines. In melanoma tumors, PD-L1 was expressed either on tumor cells or immune-infiltrating cells. The association between PD-L1 expression in immune-infiltrating cells and progression-free or overall-survival in melanoma patients treated with ipilimumab and nivolumab was stronger than PD-L1 expression in tumor cells, and remained significant on multi-variable analysis. Conclusions PD-L1 expression in melanoma tumor cells is lower than NSCLC or RCC cells. The higher response rate in melanoma patients treated with PD-1 inhibitors is likely related to PD-L1 in tumor-associated inflammatory cells. Further studies are warranted to validate the predictive role of inflammatory cell PD-L1 expression in melanoma and determine its biological significance.
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