Many drugs bind to and activate human pregnane X receptor (hPXR) to upregulate drug-metabolizing enzymes, resulting in decreased drug efficacy and increased resistance. This suggests that hPXR antagonists have therapeutic value. Here we report that SPA70 is a potent and selective hPXR antagonist. SPA70 inhibits hPXR in human hepatocytes and humanized mouse models and enhances the chemosensitivity of cancer cells, consistent with the role of hPXR in drug resistance. Unexpectedly, SJB7, a close analog of SPA70, is an hPXR agonist. X-ray crystallography reveals that SJB7 resides in the ligand-binding domain (LBD) of hPXR, interacting with the AF-2 helix to stabilize the LBD for coactivator binding. Differential hydrogen/deuterium exchange analysis demonstrates that SPA70 and SJB7 interact with the hPXR LBD. Docking studies suggest that the lack of the para-methoxy group in SPA70 compromises its interaction with the AF-2, thus explaining its antagonism. SPA70 is an hPXR antagonist and promising therapeutic tool.
Silk, one of the strongest natural biopolymers, was hybridized with Kevlar, one of the strongest synthetic polymers, through a biomimetic nanofibrous strategy. Regenerated silk materials have outstanding properties in transparency, biocompatibility, biodegradability and sustainability, and promising applications as diverse as in pharmaceutics, electronics, photonic devices and membranes. To compete with super mechanic properties of their natural counterpart, regenerated silk materials have been hybridized with inorganic fillers such as graphene and carbon nanotubes, but frequently lose essential mechanic flexibility. Inspired by the nanofibrous strategy of natural biomaterials (e.g., silk fibers, hemp and byssal threads of mussels) for fantastic mechanic properties, Kevlar was integrated in regenerated silk materials by combining nanometric fibrillation with proper hydrothermal treatments. The resultant hybrid films showed an ultimate stress and Young's modulus two times as high as those of pure regenerated SF films. This is not only because of the reinforcing effect of Kevlar nanofibrils, but also because of the increasing content of silk β-sheets. When introducing Kevlar nanofibrils into the membranes of silk nanofibrils assembled by regenerated silk fibroin, the improved mechanic properties further enabled potential applications as pressure-driven nanofiltration membranes and flexible substrates of electronic devices.
Quantum dot sensitized solar cells (QDSCs) have attracted considerable attention recently and become promising candidates for realizing a cost-effective solar cell. The design and synthesis of quantum dots (QDs) for achieving high photoelectric performance is an urgent need imposed on scientists. Here, we have succeeded in designing a QDSC with a high efficiency h of 6.33% based on Cd 0.8 Mn 0.2 Se quantum dots by facile chemical bath deposition (CBD). The effects of Mn 2+ ions on the physical, chemical, and photovoltaic properties of the QDSCs are investigated. The Mn 2+ ions doped into QDs can increase the light harvesting to produce more excitons. In addition, the Mn 2+ dopant also raises the conduction band of CdSe, accelerates the electron injection kinetics and reduces the charge recombination, improving the charge transfer and collection. The increase of the efficiencies of light-harvesting, charge-transfer and charge-collection results in the improvement of the quantum efficiency of the solar cells. The power conversion efficiency of the solar cell is increased to 6.33% (V oc ¼ 0.58 V, J sc ¼ 19.15 mA cm À2 , and FF ¼ 0.57).
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