Adverse drug reactions (ADRs) restrict the maximum doses applicable in chemotherapy, which leads to failure in cancer treatment. Various approaches, including nano-drug and prodrug strategies aimed at reducing ADRs, have been developed, but these strategies have their own pitfalls. A renovated strategy for ADR reduction is urgently needed. Here, we employ an enzymatic supramolecular self-assembly process to accumulate a bioorthogonal decaging reaction trigger inside targeted cancer cells, enabling spatiotemporally controlled, synergistic prodrug activation. The bioorthogonally activated prodrug exhibits significantly enhanced potency against cancer cells compared with normal cells. This prodrug activation strategy further demonstrates high tumour inhibition efficacy with satisfactory biocompatibility, pharmacokinetics, and safety in vivo. We envision that integration of enzymatic and bioorthogonal reactions will serve as a general small-molecule-based strategy for alleviation of ADRs in chemotherapy.
There are more than 30,000 biomass-and fossil-fuel-burning power plants now operating worldwide, reflecting a tremendously diverse infrastructure, which ranges in capacity from less than a megawatt to more than a gigawatt. In 2010, 68.7% of electricity generated globally came from these power plants, compared with 64.2% in 1990. Although the electricity generated by this infrastructure is vital to economic activity worldwide, it also produces more CO2 and air pollutant emissions than infrastructure from any other industrial sector. Here, we assess fuel-and region-specific opportunities for reducing undesirable air pollutant emissions using a newly developed emission dataset at the level of individual generating units. For example, we find that retiring or installing emission control technologies on units representing 0.8% of the global coal-fired power plant capacity could reduce levels of PM2.5 emissions by 7.7-14.2%. In India and China, retiring coal-fired plants representing 1.8% and 0.8% of total capacity can reduce total PM2.5 emissions from coal-fired plants by 13.2% and 16.0%, respectively. Our results therefore suggest that policies targeting a relatively small number of 'super-polluting' units could substantially reduce pollutant emissions and thus the related impacts on both human health and global climate.
A terahertz (THz) Brewster vacuum window has been developed for the newly emerged ultrabroadband gyrotron application. In the simulation, the influences of the slant angle, the thickness, and the dielectric constant of the window plate on the results were systematically analyzed. In the experimental measurement, two THz high-directivity horn antennas were used to produce and collect a quasi-plane wave that travels through the window. The measurement shows that the window transmission coefficient between 0.33 and 0.50 THz is higher than -1 dB. A conventional Brewster window uses an elliptical window plate, resulting in the asymmetrical stress distribution. In this letter, a novel circular symmetrical ceramic-Kovar brazing scheme is applied to mitigate the challenging asymmetrical stress distribution. This Brewster window would promote the development of the broadband THz gyrotron and other high-power THz systems.
Recently emerged multimode gyrotron, a high-power broadband terahertz radiator, encounters the challenge of efficiently converting a series of operating whispering-gallery modes (WGMs) into free-space Gaussian beams. To this demand, we propose a frequency- and mode-insensitive antenna capable of broadband multimode converting. For a single mode, to achieve broadband operation, special reflector configuration and large-radius launcher guarantee the system high robustness to frequency-induced wave number variation. Furthermore, for a series of operating WGMs, in order to achieve multimode operation, high-order mode indices guarantees familiar field patterns and ray trajectories. In particular, high-purity Gaussian beams are simultaneously achieved in different WGMs of broad continuous bands, including 351–361 GHz for TE11,2 mode, 375–385 GHz for TE12,2 mode, and 398–410 GHz for TE13,2 mode. The results are verified by both the vector diffraction theory and the method of momentum. This kind of mode converter will promote the development of multimode gyrotrons and other antenna-feeder systems for high-power terahertz applications.
A pair of uranyl complexes incorporating tetrahydrosalen and N,N-dimethyltetrahydrosalen ligands are synthesized and studied. These new ligands, with saturated secondary and tertiary amines, exhibit higher chemostability than the prototype Schiff base (salen) structure, especially under acidic conditions. As shown by X-ray diffraction crystallography, the coordination geometry of uranium in these new complexes is a distorted pentagonal bipyramid. Interestingly, UO2([H-4]-salen), comprising the tetrahydrosalen ligand, forms a dimeric structure in the crystals, with two subunits held together by sharing one of the two phenoxy oxygen atoms from each subunit, whereas UO2([H2Me2]-salen) with the N,N-dimethyltetrahydrosalen ligand is in the monomer state, with a solvent molecule coordinated to uranium to complete the penta-coordination configuration. Moreover, as revealed by UV/Vis spectroscopy using the colorimetry method, these hydrogenated salen ligands exhibit comparable, or even higher, binding affinities toward uranyl than the prototype Schiff base salen ligand in weakly basic solution.
In this paper, thermodynamic phase behaviour and miscibility of confined pure and mixing fluids in nanopores are studied. First, a semi-analytical equation of state (EOS) is developed, based on which two correlations are modified to predict the shifts of critical temperature and pressure. Second, the thermodynamic free energy of mixing and solubility parameter are derived, quantitatively calculated, and applied to study the conditions and characteristics of the fluid miscibility in nanopores. Third, an improved EOS model with the modified correlations is proposed and used to calculate the phase properties and miscibility-associated quantities of three mixing fluids. The critical temperature and pressure of confined fluids are always decreased by reducing the pore radius. The negative pressure state is validated for a confined liquid, whose upper temperature limit is quantitatively determined and found to be lowered with the reduction of pore radius. The liquid–gas miscibility is beneficial from the pore radius reduction and the intermediate hydrocarbons (e.g., C2, C3, i- and n-C4) perform more miscible with the liquid C8 in comparison with the lean gas (e.g., N2 and CH4). Moreover, the molecular diameter of single liquid molecule is determined to be the bottom limit, the pore radius above which is concluded as a necessary condition for the liquid–gas miscibility. The calculated phase behaviour and minimum miscibility pressures (MMPs) of the three mixing fluids agree well with the literature results, which reveals that the shifts of critical properties dominate the phase behaviour and miscibility changes of confined fluids from bulk phase to nanopores.