Reversing tumor stemness via orally targeted nanoparticles achieves efficient colon cancer treatment

The acquisition of stemness in colorectal cancer (CRC) attributed to the recurrence and metastasis in CRC treatment. Therefore, targeting the stemness of CRC forms a basis for the development of novel therapeutic approaches. However, the pain and systemic side effect from long-term of venipuncture injection remain great challenges to neoplastic treatment. Here, we introduce an oral drug delivery system for sustained release of BMI-1 inhibitor (PTC209) that reverse the stemness of CRC to over-come these obstacles. In this system, nanoparticles modified with hyaluronic acid (HA) showed high-affinity to CD44 / CD168 overexpressed-CRC cells, and efficiently targeted to tumor site in a metastatic orthotropic colon cancer mouse model by oral administration. Significantly, the observed tumor growth inhibition is accompanied by decreased expression of stemness markers in the tumor tissues. Furthermore, HA-NPs-PTC209 also significantly prevented metastasis to the gastrointestinal system, while failing to exhibit acute side effects. In summary, we have developed an orally active, easily synthesized nanomedicine that shows promise for the treatment of colon cancer

Suppression of Tumor Energy Supply by Liposomal Nanoparticle-Mediated Inhibition of Aerobic Glycolysis

Aerobic glycolysis enables cancer cells to rapidly take up nutrients (e.g., nucleotides, amino acids, and lipids) and incorporate them into the biomass needed to produce a new cell. In contrast to existing chemotherapy/radiotherapy strategies, inhibiting aerobic glycolysis to limit the adenosine 5′-triphosphate (ATP) yield is a highly efficient approach for suppressing tumor cell proliferation. However, most, if not all, current inhibitors of aerobic glycolysis cause significant adverse effects because of their nonspecific delivery and distribution to nondiseased organs, low bioavailability, and a narrow therapeutic window. New strategies to enhance the biosafety and efficacy of these inhibitors are needed for moving them into clinical applications. To address this need, we developed a liposomal nanocarrier functionalized with a well-validated tumor-targeting peptide to specifically deliver the aerobic glycolysis inhibitor 3-bromopyruvate (3-BP) into the tumor tissue. The nanoparticles effectively targeted tumors after systemic administration into tumor-bearing mice and suppressed tumor growth by locally releasing 3-BP to inhibit the ATP production of the tumor cells. No overt side effects were observed in the major organs. This report demonstrates the potential utility of the nanoparticle-enabled delivery of an aerobic glycolysis inhibitor as an anticancer therapeutic agent

Increasing the amylose content of maize through silencing of sbe2a genes

Improved amylose content in maize has been achieved by reducing the starch branching enzyme (SBE) activity via transgenic maize inbred line transformed by a high-efficient RNAi expression vector, which may provide the foundation for maize quality improvement. The sense and anti-sense fragments of maize SBE gene sbe2a were cloned by reverse transcript PCR and high efficient RNAi expression vector was constructed based on plant expression plasmid pCAMBIA1301. Then the reconstruct was introduced into maize inbred line Tie7922 by pollen tube pathway transformation. Four transgenic plants were obtained. The integration of interest gene sbe2a into maize genome has been confirmed by PCR amplification and Southern hybridization. The sbe2a transcription was suppressed obviously by the analyses of RT-PCR, SBE activity and amylase content on the four transgenic plants. The SBE activity was significantly less than that of wild type maize, and was at most reduced by 77.9%; the amylose content was at most increased by 87.8%. In conclusion, RNAi expression vector pRSBE2a containing sbe2a gene was successfully constructed. Through genetic transformation, RNAi technique efficiently silences endogenous sbe2a gene to reduce the SBE activity, and high-amylose maize linesare obtained.Keywords: Maize, starch branching enzyme gene sbe2a, RNA interference, genetic transformatio

Low ambient temperature and air pollution are associated with hospitalization incidence of coronary artery disease: Insights from a cross-sectional study in Northeast China

Previous studies have established a link between fluctuations in climate and increased mortality due to coronary artery disease (CAD). However, there remains a need to explore and clarify the evidence for associations between meteorological changes and hospitalization incidences related to CAD and its subtypes, especially in cold regions. This study aimed to systematically investigate the relationship between exposure to meteorological changes, air pollutants, and hospitalization for CAD in cold regions

convertingindustrialwastecontactmassesintoeffectivemulticomponentcopperbasedcatalystsfortherochowprocess

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Controllable wet synthesis of multicomponent copper-based catalysts for Rochow reaction

This work aims to provide a facile, low-cost and scalable method for the preparation of multicomponent Cu-Cu2O-CuO catalysts, which are of high interest to the organosilane industry. A series of submicrometer-sized and Cu-based catalysts containing CuO, Cu2O and Cu, or some combination of them, were synthesized by a simple low-temperature wet chemical method using CuSO4 center dot 5H(2)O as the precursor and N2H4 center dot H2O as a reducing agent. The samples were characterized by X-ray diffraction, thermogravimetric analysis, temperature-programmed reduction, X-ray photoelectron spectroscopy, transmission electron microscopy, and scanning electron microscopy techniques. It was observed that the composition of the samples could be tailored by varying the amount of reducing agent at a given reaction temperature and time. These catalysts were then tested in the Rochow reaction, using silicon powder and methyl chloride (MeCl) as reactants to produce dimethyldichlorosilane (M2), which is the most important organosilane monomer in the industry. Compared with bare CuO and Cu particles, the ternary CuO-Cu2O-Cu catalyst displayed much improved M2 selectivity and Si conversion, which can be attributed to the smaller copper particle size and the synergistic effect among the different components in the CuO-Cu2O-Cu catalyst. This catalyst preparation method is expected to yield efficient and low-cost copper catalysts for the organosilane industry.</p

Converting industrial waste contact masses into effective multicomponent copper-based catalysts for the Rochow process

In this work, we report a simple and inexpensive approach to synthesize effective multicomponent Cu-Cu2O-CuO catalysts for the Rochow process from industrial waste contact masses (WCMs). WCMs from the organosilane industry were treated with acid followed by reduction with metallic iron powder. The obtained copper powder was then subjected to controlled oxidation in air at different temperatures, followed by ball milling. The orthogonal array approach was applied to optimize this process, and the stirring speed and pH were found to significantly affect the leaching ratio and copper yield, respectively. When used for the Rochow process, the optimized ternary Cu-Cu2O-CuO catalyst greatly enhanced the dimethyldichlorosilane selectivity and Si conversion compared with Cu-Cu2O-CuO catalysts prepared without ball milling, bare Cu catalysts, and Cu-Cu2O-CuO catalysts with different compositions. This could be attributed to their small particle size and the strong synergistic effect among the multiple components in the catalyst with the optimized composition. (C) 2017 Chinese Society of Particuology and Institute of Process Engineering, Chinese Academy of Sciences. Published by Elsevier B.V. All rights reserved.</p

RSC Adv.

The metallic Cu flakes prepared by milling metallic Cu powder were controllably oxidized in air at different temperatures to obtain the Cu-based catalysts containing multicomponents of Cu, Cu2O, and CuO. These catalysts are explored in the Rochow reaction using silicon powder and methyl chloride (MeCl) as reactants to produce dimethyldichlorosilane (M2), which is the most important organosilane monomer in the industry. The samples were characterized by X-ray diffraction, temperature-programmed reduction, thermogravimetric analysis, oxidimetry analysis, particle size analysis, transmission electron microscopy, and scanning electron microscopy. Compared to the metallic Cu powder and Cu flakes, the controllably oxidized Cu flakes containing Cu, Cu2O, and CuO species show much higher M2 selectivity and silicon conversion in the Rochow reaction. The enhanced catalytic performance may stem from the larger interfacial contact among the gas MeCl, solid Si particles, and solid Cu-based catalyst flakes, as well as the synergistic effect among the different Cu species. The work would be helpful to the development of novel Cu-based catalysts for organosilane synthesis.The metallic Cu flakes prepared by milling metallic Cu powder were controllably oxidized in air at different temperatures to obtain the Cu-based catalysts containing multicomponents of Cu, Cu2O, and CuO. These catalysts are explored in the Rochow reaction using silicon powder and methyl chloride (MeCl) as reactants to produce dimethyldichlorosilane (M2), which is the most important organosilane monomer in the industry. The samples were characterized by X-ray diffraction, temperature-programmed reduction, thermogravimetric analysis, oxidimetry analysis, particle size analysis, transmission electron microscopy, and scanning electron microscopy. Compared to the metallic Cu powder and Cu flakes, the controllably oxidized Cu flakes containing Cu, Cu2O, and CuO species show much higher M2 selectivity and silicon conversion in the Rochow reaction. The enhanced catalytic performance may stem from the larger interfacial contact among the gas MeCl, solid Si particles, and solid Cu-based catalyst flakes, as well as the synergistic effect among the different Cu species. The work would be helpful to the development of novel Cu-based catalysts for organosilane synthesis

Honeycomb-like CuO/ZnO hybrid nanocatalysts prepared from solid waste generated in the organosilane industry

We report the preparation of honeycomb-like CuO/ZnO (CZx/y) nanocatalysts with CuO nanospheres (NSs) adhered with ZnO nanoparticles (NPs) for the Rochow reaction. The synthesis was carried out via adsorption of Cu2+/Zn2+ ions on carbon black (CB) which acted as both the agglomeration inhibitor and the hard template, and followed by calcination in air. The low cost Cu2+/Zn2+ ions were recovered from the solid waste generated in the organosilane industry via a simple ammonia leaching treatment. The samples were characterized by X-ray diffraction, transmission electron microscopy, scanning electron microscopy, X-ray photoelectron spectroscopy, and temperature-programmed reduction. The as-obtained CZx/y nanohybrids had a honeycomb-like structure with large voids and openings among the CuO NSs. When re-used as a Cu-based catalyst for the Rochow reaction, the CZx/y NPs sample with an optimized ratio showed significantly improved dimethyldichlorosilane (M2) selectivity and silicon (Si) conversion as compared with the CuO/ZnO NPs prepared in the absence of CB, discrete CuO or ZnO NPs and the CuO/ZnO NPs with different compositions, mainly due to the unique honeycomb-like structure, smaller crystal size and synergistic electronic effect at the interface between Cu and ZnO in CZx/y NPs