As a kind of biologically important reactive oxygen species (ROS), hypochlorite (ClO-) plays a crucial role in many physiological processes. As such, endogenous ClO- is a powerful antibacterial agent during pathogen invasion. Nonetheless, excessive endogenous ClO- could pose a health threat to mammalian animals including humans. However, the detection of endogenous ClO- by bioluminescence probes in vivo remains a considerable challenge. Herein, based on a caged strategy, we developed a turn-on bioluminescent probe 1 for the highly selective detection of ClO-in vitro and imaging endogenous ClO- in a mouse inflammation model. We anticipate that such a probe could help us understand the role of endogenous ClO- in a variety of physiological and pathological processes.
Along with the rapid development of international metropolis, China's urbanization is developing faster and faster. In the process of China's urbanization development, mountain mounding with construction waste is one of the most direct, effective and economical means to deal with construction waste, not only that, but also, one of the important methods for ecological restoration project of landscape gardening, this method has several advantages such as green construction, green low carbon, energy saving and carbon reduction, etc. It also improves the utilization rate of resources, has high economic and environmental benefits, and also has high High research value and social significance.Since there are differences in the mechanical properties of the original soil and the mounded hill materials in the process of construction waste mounding, as well as, differences in the soil quality in different regions, it is necessary to study the stability of the hill. In this paper, the following research results are obtained through actual case studies of typical landscape projects: first, geomechanical tests are conducted on the raw soil and construction waste mound hill materials to obtain the particle size ratios, maximum dry density and optimum moisture content, and compression modulus of specific mixes, and the triaxial shear test proves that each stress-strain curve basically conforms to the Duncan-Zhang hyperbolic relationship assumption before the peak occurs.Finally, numerical simulations were carried out for different working conditions in combination with the three-dimensional calculation model, and the calculation and analysis of the Bishop consolidation theory were used to obtain the settlement displacement, horizontal displacement development and pore pressure dissipation process of the calculation model. The landslide stability of the slope is calculated and the minimum safety coefficient under normal conditions and the minimum safety coefficient under seismic conditions are both calculated by Swedish method and Bishop method respectively, both of which meet the requirements and determine the technical feasibility and reasonableness of the scheme. In the conclusion part of this paper, the problems and handling measures in the construction process are summarized to provide valuable experience for similar projects.
Two series of novel coelenterazine analogues (alkynes and triazoles) with imidazopyrazinone C-6 extended substitution have been designed and synthesized successfully for the extension of bioluminescent substrates. After extensive evaluation, some compounds display excellent bioluminescence properties compared with DeepBlueC in cellulo, thus becoming potential molecules for bioluminescence techniques.
To enhance the efficiency of firefly luciferase/luciferin bioluminescence imaging, a series of N-cycloalkylaminoluciferins (cyaLucs) were developed by introducing lipophilic N-cycloalkylated substitutions. The experimental results demonstrate that these cyaLucs are effective substrates for native firefly luciferase (Fluc) and can produce elevated bioluminescent signals in vitro, in cellulo, and in vivo. It should be noted that, in animal studies, N-cyclobutylaminoluciferin (cybLuc) at 10 μM (0.1 mL), which is 0.01% of the standard dose of d-luciferin (dLuc) used in mouse imaging, can radiate 20-fold more bioluminescent light than d-luciferin (dLuc) or aminoluciferin (aLuc) at the same concentration. Longer in vivo emission imaging using cybLuc suggests that it can be used for long-time observation. Regarding the mechanism of cybLuc, our cocrystal structure data from firefly luciferase with oxidized cybLuc suggested that oxidized cybLuc fits into the same pocket as oxyluciferin. Most interestingly, our results demonstrate that the sensitivity of cybLuc in brain tumor imaging contributes to its extended application in deep tissues.
High-throughput screening (HTS) of ligand library to find new active molecules for G protein-coupled receptors is still a major interest, as well as an actual challenge. Fluorescence polarization (FP) assay portrays an essential role in HTS; however, in many cases, it was restricted by the absence of FP probes, the narrow measurement window, and low signal-to-noise (S/N) ratio. Herein, based on the modification of our previous probe 1 (QFL), we discovered an FP probe 3 (QGGFL) for α1-adrenergic receptors (α1-ARs), which has satisfactory fluorescence intensity, specific binding ability to receptors, and suitable fluorescence properties that were compatible with the filters in the FP system. Meanwhile, an "ELISA-like" strategy was designed for FP-based HTS assay in which proteins were adhered into a solid phase to improve the measurement window and S/N ratio. With fluorescent antagonist QGGFL and the ELISA strategy, we succeeded in establishing the first competitive binding FP assay for α1-AR antagonists as the alternative of the radioligand binding assay.
A series of 2-phenylnaphthalenes as firefly luciferase inhibitors are reported. The most potent compound 5 showed good systemic inhibition in transgenic mice. Kinetic assay indicated 5 is competitive for aminoluciferin and noncompetitive for ATP.
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