20 research outputs found

    Optimization of 4-( N -Cycloamino)phenylquinazolines as a Novel Class of Tubulin-Polymerization Inhibitors Targeting the Colchicine Site

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    The 6-methoxy-1,2,3,4-tetrahydroquinoline moiety in prior leads 2-chloro- and 2-methyl-4-(6-methoxy-3,4-dihydroquinolin-1(2H)-yl)quinazoline (1a and 1b) was modified to produce 4-(N-cycloamino)quinazolines (4a–c and 5a–m). The new compounds were evaluated in cytotoxicity and tubulin inhibition assays, resulting in the discovery of new tubulin-polymerization inhibitors. 7-Methoxy-4-(2-methylquinazolin-4-yl)-3,4-dihydroquinoxalin- 2(1H)-one (5f), the most potent compound, exhibited high in vitro cytotoxic activity (GI50 1.9–3.2 nM), significant potency against tubulin assembly (IC50 0.77 μM), and substantial inhibition of colchicine binding (99% at 5 μM). In mechanism studies, 5f caused cell arrest in G2/M phase, disrupted microtubule formation, and competed mostly at the colchicine site on tubulin. Compound 5f and N-methylated analogue 5g were evaluated in nude mouse MCF7 xenograft models to validate their antitumor activity. Compound 5g displayed significant in vivo activity (tumor inhibitory rate 51%) at a dose of 4 mg/kg without obvious toxicity, whereas 5f unexpectedly resulted in toxicity and death at the same dose

    The Magnetic Properties and Magnetocaloric Effect of Pr<sub>0.7</sub>Sr<sub>0.3</sub>MnO<sub>3</sub> Thin Film Grown on SrTiO<sub>3</sub> Substrate

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    The magnetic behaviors and magnetocaloric effect (MCE) of Pr0.7Sr0.3MnO3 (PSMO-7) film grown on a (001) SrTiO3 single-crystal substrate by a pulsed laser deposition (PLD) were studied in this paper. X-ray diffraction with a high resolution (HRXRD) measurement shows that PSMO-7 film is grown with a (001) single orientation. The magnetic properties and the MCE related to the ferromagnetic (FM) phase transition of the PSMO-7 film are investigated using the temperature dependence of magnetization M(T) and the magnetic field dependence of magnetization M(H). The M(T) data suggest that with decreasing temperatures, the PSMO-7 film goes through the transition from the paramagnetic (PM) state to the FM state at around the Curie temperature (TC). The TC (about 193 K) can be obtained by the linear fit of the Curie law. Magnetic hysteresis loop measurements show that the PSMO-7 film exhibits the FM feature at temperatures of 10, 100, and 150 K (low magnetic hysteresis can be found), while the film reveals the PM feature with the temperature increased up to 200 and/or 300 K. The research results of M(H) data are consistent with the M(T) data. Furthermore, the magnetic entropy change (−ΔSM) of the PSMO-7 film was studied. It was found that the maximum value of (−ΔSM) near TC reaches about 4.7 J/kg·K under the applied field change of 20 kOe, which is comparable to that of metal Gd (−ΔSM of 2.8 J/kg K under 10 kOe), indicating the potential applications of PSMO-7 film in the field of magnetic refrigeration

    Homogeneous and Stereoselective Copper(II)-Catalyzed Monohydration of Methylenemalononitriles to 2‑Cyanoacrylamides

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    A facile and efficient route for the homogeneous and highly stereoselective monohydration of substituted methylenemalononitriles to (<i>E</i>)-2-cyanoacrylamides catalyzed by copper­(II) acetate monohydrate in acetic acid containing 2% water is described, and a mechanism is proposed. The protocol has proved to be suitable for the monohydration of dicyanobenzenes and 2-substituted malononitriles

    Homogeneous and Stereoselective Copper(II)-Catalyzed Monohydration of Methylenemalononitriles to 2‑Cyanoacrylamides

    No full text
    A facile and efficient route for the homogeneous and highly stereoselective monohydration of substituted methylenemalononitriles to (<i>E</i>)-2-cyanoacrylamides catalyzed by copper­(II) acetate monohydrate in acetic acid containing 2% water is described, and a mechanism is proposed. The protocol has proved to be suitable for the monohydration of dicyanobenzenes and 2-substituted malononitriles

    Conservation Study of Imprinted Genes in Maize Triparental Heterozygotic Kernels

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    Genomic imprinting is a classic epigenetic phenomenon related to the uniparental expression of genes. Imprinting variability exists in seeds and can contribute to observed parent-of-origin effects on seed development. Here, we conducted allelic expression of the embryo and endosperm from four crosses at 11 days after pollination (DAP). First, the F1 progeny of B73(♀) × Mo17(♂) and the inducer line CAU5 were used as parents to obtain reciprocal crosses of BM-C/C-BM. Additionally, the F1 progeny of Mo17(♀) × B73(♂) and CAU5 were used as parents to obtain reciprocal crosses of MB-C/C-MB. In total, 192 and 181 imprinted genes were identified in the BM-C/C-BM and MB-C/C-MB crosses, respectively. Then, by comparing the allelic expression of these imprinted genes in the reciprocal crosses of B73 and CAU5 (BC/CB), fifty-one Mo17-added non-conserved genes were identified as exhibiting imprinting variability. Fifty-one B73-added non-conserved genes were also identified by comparing the allelic expression of imprinted genes identified in BM-C/C-BM, MB-C/C-MB and MC/CM crosses. Specific Gene Ontology (GO) terms were not enriched in B73-added/Mo17-added non-conserved genes. Interestingly, the imprinting status of these genes was less conserved across other species. The cis-element distribution, tissue expression and subcellular location were similar between the B73-added/Mo17-added conserved and B73-added/Mo17-added non-conserved imprinted genes. Finally, genotypic and phenotypic analysis of one non-conserved gene showed that the mutation and overexpression of this gene may affect embryo and kernel size, which indicates that these non-conserved genes may also play an important role in kernel development. The findings of this study will be helpful for elucidating the imprinting mechanism of genes involved in maize kernel development

    Homogeneous and Stereoselective Copper(II)-Catalyzed Monohydration of Methylenemalononitriles to 2‑Cyanoacrylamides

    No full text
    A facile and efficient route for the homogeneous and highly stereoselective monohydration of substituted methylenemalononitriles to (<i>E</i>)-2-cyanoacrylamides catalyzed by copper­(II) acetate monohydrate in acetic acid containing 2% water is described, and a mechanism is proposed. The protocol has proved to be suitable for the monohydration of dicyanobenzenes and 2-substituted malononitriles

    POCl<sub>3</sub>‑Mediated Reaction of 1‑Acyl-1-carbamoyl Oximes: A New Entry to Cyanoformamides

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    A facile and efficient one-pot synthesis of cyanoformamides was developed from readily available 1-acyl-1-carbamoyl oximes mediated by phosphoryl­trichloride (POCl<sub>3</sub>) under mild conditions in good to high yields

    A State-Level Socioeconomic Data Collection of the United States for COVID-19 Research

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    The outbreak of COVID-19 from late 2019 not only threatens the health and lives of humankind but impacts public policies, economic activities, and human behavior patterns significantly. To understand the impact and better prepare for future outbreaks, socioeconomic factors play significant roles in (1) determinant analysis with health care, environmental exposure and health behavior; (2) human mobility analyses driven by policies; (3) economic pressure and recovery analyses for decision making; and (4) short to long term social impact analysis for equity, justice and diversity. To support these analyses for rapid impact responses, state level socioeconomic factors for the United States of America (USA) are collected and integrated into topic-based indicators, including (1) the daily quantitative policy stringency index; (2) dynamic economic indices with multiple time frequency of GDP, international trade, personal income, employment, the housing market, and others; (3) the socioeconomic determinant baseline of the demographic, housing financial situation and medical resources. This paper introduces the measurements and metadata of relevant socioeconomic data collection, along with the sharing platform, data warehouse framework and quality control strategies. Different from existing COVID-19 related data products, this collection recognized the geospatial and dynamic factor as essential dimensions of epidemiologic research and scaled down the spatial resolution of socioeconomic data collection from country level to state level of the USA with a standard data format and high quality

    Black Phosphorus Quantum Dots Enhance the Radiosensitivity of Human Renal Cell Carcinoma Cells through Inhibition of DNA-PKcs Kinase

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    Renal cell carcinoma (RCC) is one of the most aggressive urological malignancies and has a poor prognosis, especially in patients with metastasis. Although RCC is traditionally considered to be radioresistant, radiotherapy (RT) is still a common treatment for palliative management of metastatic RCC. Novel approaches are urgently needed to overcome radioresistance of RCC. Black phosphorus quantum dots (BPQDs) have recently received great attention due to their unique physicochemical properties and good biocompatibility. In the present study, we found that BPQDs enhance ionizing radiation (IR)-induced apoptotic cell death of RCC cells. BPQDs treatment significantly increases IR-induced DNA double-strand breaks (DSBs), as indicated by the neutral comet assay and the DSBs biomarkers &gamma;H2AX and 53BP1. Mechanistically, BPQDs can interact with purified DNA&ndash;protein kinase catalytic subunit (DNA-PKcs) and promote its kinase activity in vitro. BPQDs impair the autophosphorylation of DNA-PKcs at S2056, and this site phosphorylation is essential for efficient DNA DSBs repair and the release of DNA-PKcs from the damage sites. Consistent with this, BPQDs suppress nonhomologous end-joining (NHEJ) repair and lead to sustained high levels of autophosphorylated DNA-PKcs on the damaged sites. Moreover, animal experiments indicate that the combined approach with both BPQDs and IR displays better efficacy than monotreatment. These findings demonstrate that BPQDs have potential applications in radiosensitizing RCC cells

    Pavement Temperature Forecasts Based on Model Output Statistics: Experiments for Highways in Jiangsu, China

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    Forecasts on transportation meteorology, such as pavement temperature, are becoming increasingly important in the face of global warming and frequent disruptions from extreme weather and climate events. In this study, we propose a pavement temperature forecast model based on stepwise regression—model output statistics (SRMOS) at the short-term timescale, using highways in Jiangsu, China, as examples. Experiments demonstrate that the SRMOS model effectively calibrates against the benchmark of the linear regression model based on surface air temperature (LRT). The SRMOS model shows a reduction in mean absolute errors by 0.7–1.6 °C, with larger magnitudes observed for larger biases in the LRT forecasts. Both forecasts exhibit higher accuracy in predicting minimum nighttime temperatures compared to maximum daytime temperatures. Additionally, it overall shows increasing biases from the north to the south, and the SRMOS superiority is greater over the south with larger initial LRT biases. Predictor importance analysis indicates that temperature, moisture, and larger-scale background are basically the key predictors in the SRMOS model for pavement temperature forecasts, of which the air temperature is the most crucial factor in the model’s construction. Although larger-scale circulation backgrounds are generally characterized by relatively low importance, their significance increases with longer lead times. The presented results demonstrate the considerable skill of the SRMOS model in predicting pavement temperatures, highlighting its potential in disaster prevention for extreme transportation meteorology events
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