Microwave-assisted rapid synthesis of γ-cyclodextrin metal-organic 2 frameworks for size control and efficient drug loading 3 4

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Liquid-crystalline blue phases (BPs) have sparked an enormous interest due to their exotic optical properties, exhibiting no birefringence but selective refl ection of circularly polarized light, and potential for advanced applications in a wide variety of fi elds including self-assembling tunable photonic crystals and fast-response display. [ 1 ] BPs are made up of double-twist cylinders arranged in a highly fl uid self-assembled cubic lattice with periods of ∼ 100 nm, which is stabilized by a network of topological -1/2 disclination lines. The competition between the chiral forces and the packing topology leads to at least three different lattice structures, labeled as blue phase III (BPIII), blue phase II (BPII), and blue phase I (BPI) upon decreasing the temperature from the isotropic (I) to the chiral nematic phase. [ 2 ] The packing structures are macroscopically amorphous, simple cubic, and body-centered cubic, respectively. [ 3 ] As is known, the main obstacles to the potential applications of the BPs are the narrow temperature range as well as the instability of cubic structure against an electric fi eld. [ 4 ] Recent developments that introduce BPs with an extended temperature range [ 5 ] make them more attractive for applications. However, the stability of cubic structures against an electric fi eld, such as heavy hysteresis or irreversible switching, is still a big challenge on the road toward practical applications.Theoretical investigations of the BP switching dynamics in presence of an electric fi eld have shown that cubic structure (especially, BPI) is unstable and diffi cult to be reversibly switched in the strong fi eld region. [ 6 ] It has been experimentally demonstrated that serious hysteresis was observed in the pure BPs, which may be due to the fi eld induced phase transition from BP to a chiral nematic phase. [ 7 ] Interestingly, polymer-stabilized BPs (PSBP) could be reversibly switched with microsecond response time, [ 5 ] but the driving voltage of these system is relatively high due to the doping of ∼ 10.0 wt% monomers, and the long-term stability of polymer network is a remaining technical challenge. [ 1 , 8 ] Moreover, BPIII could also undergo a reversible switching with an AC fi eld of less than 10.0 V μ m − 1 but the response speed is relatively slow (about several millisecond) due to the fact that BPIII with wide temperature range is usually observed in the systems with high chirality or viscosity. [ 9 ] Therefore, there is an urgent need to explore a novel strategy to solve the instability of cubic BPs against an electric fi eld and develop the BP composites without hysteresis, with fast response speed, and with low driving voltage.Liquid-crystal nanoscience has attracted special attention in recent years due to the potential applications in developing new composite materials with exciting optical as well as electro-optical properties. [ 10 ] Doping nematic liquid crystals (LC) with nanoparticles (NPs) has lead to many promising LC electro-optical characteristics including low ...

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Background:Mesothelioma is a notoriously chemotherapy-resistant neoplasm, as is evident in the dismal overall survival for patients with those of asbestos-associated disease. We previously demonstrated co-activation of multiple receptor tyrosine kinases (RTKs), including epidermal growth factor receptor (EGFR), MET, and AXL in mesothelioma cell lines, suggesting that these kinases could serve as novel therapeutic targets. Although clinical trials have not shown activity for EGFR inhibitors in mesothelioma, concurrent inhibition of various activated RTKs has pro-apoptotic and anti-proliferative effects in mesothelioma cell lines. Thus, we hypothesised that a coordinated network of multi-RTK activation contributes to mesothelioma tumorigenesis.Methods:Activation of PI3K/AKT/mTOR, Raf/MAPK, and co-activation of RTKs were evaluated in mesotheliomas. Effects of RTK and downstream inhibitors/shRNAs were assessed by measuring mesothelioma cell viability/growth, apoptosis, activation of signalling intermediates, expression of cell-cycle checkpoints, and cell-cycle alterations.Results:We demonstrate activation of the PI3K/AKT/p70S6K and RAF/MEK/MAPK pathways in mesothelioma, but not in non-neoplastic mesothelial cells. The AKT activation, but not MAPK activation, was dependent on coordinated activation of RTKs EGFR, MET, and AXL. In addition, PI3K/AKT/mTOR pathway inhibition recapitulated the anti-proliferative effects of concurrent inhibition of EGFR, MET, and AXL. Dual targeting of PI3K/mTOR by BEZ235 or a combination of RAD001 and AKT knockdown had a greater effect on mesothelioma proliferation and viability than inhibition of individual activated RTKs or downstream signalling intermediates. Inhibition of PI3K/AKT was also associated with MDM2-p53 cell-cycle regulation.Conclusions:These findings show that PI3K/AKT/mTOR is a crucial survival pathway downstream of multiple activated RTKs in mesothelioma, underscoring that PI3K/mTOR is a compelling target for therapeutic intervention.

To acquire materials of higher specific stiffness and strength, stretching dominated lattice materials reinforced by carbon fibers were designed and manufactured. The mechanical behaviors were predicted and experimented. The imperfections of lattice materials, such as the waviness of the struts, non-circular crosssections and cantilever ribs, greatly influenced their performance. The bending effects of the imperfections were predicted and compared with the experiment results. Although influenced by the imperfections, carbon reinforced lattice materials are still much stiffer and stronger than foams and honeycombs.

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Protein stability plays an extremely important role not only in its biological function but also in medical science and protein engineering. Osmolytes provide a general method to protect proteins from the unfolding and aggregation induced by extreme environmental stress. In this study, the effect of glycerol on protection of the model enzyme creatine kinase (CK) against heat stress was investigated by a combination of spectroscopic method and thermodynamic analysis. Glycerol could prevent CK from thermal inactivation and aggregation in a concentration-dependent manner. The spectroscopic measurements suggested that the protective effect of glycerol was a result of enhancing the structural stability of native CK. A further thermodynamic analysis using the activated-complex theory suggested that the effect of glycerol on preventing CK against aggregation was consistent with those previously established mechanisms in reversible systems. The osmophobic effect of glycerol, which preferentially raised the free energy of the activated complex, shifted the equilibrium between the native state and the activated complex in favor of the native state. A comparison of the inactivation rate and the denaturation rate suggested that the protection of enzyme activity by glycerol should be attributed to the enhancement of the structural stability of the whole protein rather than the flexible active site.