Quercetin attenuates Pseudomonas aeruginosa-induced acute lung inflammation by inhibiting PI3K/AKT/NF-κB signaling pathway.

Pseudomonas aeruginosa is an opportunistic pathogen that commonly causes infections in immunocompromised individuals with significant morbidity and mortality. Quercetin is a natural flavonoid abundantly present in fruits and vegetables, exerting potent anti-inflammatory effects in treatment of various diseases. However, the molecular mechanisms of quercetin in treatment of P. aeruginosa-induced acute lung inflammation are unclear. In this study, we exploited network pharmacology- and molecular docking-based approach to explore the potential mechanisms of quercetin against P. aeruginosa pneumonia, which was further validated via in vivo and in vitro experiments. The in vivo experiments demonstrated that quercetin alleviated the P. aeruginosa-induced lung injury by diminishing neutrophil infiltration and production of proinflammatory cytokines (IL-1ß, IL-6, and TNF), which was associated with decreased mortality. Moreover, the quercetin-treated mice displayed decreased phosphorylation levels of PI3K, AKT, IκBα, and NF-κB p65 in lung tissues compared to non-drug-treated mice. Similarly, the in vitro study showed that the phosphorylation of these regulatory proteins and production of the proinflammatory cytokines were impaired in the quercetin-pretreated macrophages upon P. aeruginosa infection. Altogether, this study suggested that quercetin reduced the P. aeruginosa-induced acute lung inflammation by suppressing PI3K/AKT/NF-κB signaling pathway.

Synthesis of Butadiynyl-Strapped Corona[6]arenes and Their Selective Anion Binding Properties.

A number of butadiynylene-strapped O6-corona[6]arenes were synthesized straightforwardly through intramolecular oxidative homocoupling of O6-corona[6]arenes, which contained at least two N-propargyl-phthalimide segments. The mono-macrocyclic reactants were prepared from the reaction between 3,6-dichlorotetrazine and N-propargyl-3,6-dihydroxyphthalimide and another 1,4-dihydroxybenzene derivative with roughly a 3:2:1.3-1.5 ratio in a one-pot reaction manner. The synthesized butadiynylene-strapped corona[3]arene[3]tetrazines acted as highly selective electron-deficient macrocyclic hosts to form 1:1 complexes with thiocyanate in solution, and the association constant (Ka) was up to 1390 M-1. The anion-π noncovalent interactions provided the driving force for host-guest complexation.

Synthesis and anion binding properties of phthalimide-containing corona[6]arenes.

Functionalized O6-corona[3]arene[3]tetrazines were synthesized efficiently and conveniently by means of a macrocyclic condensation reaction between N-functionalized 3,6-dihydroxyphthalimides and 3,6-dichlorotetrazine under mild conditions in a one-pot reaction manner. The novel macrocycles exist as a mixture of rapidly interconvertible conformers in solution while in the solid state they adopt the conformation in which three phthalimide units are cis,trans-orientated. Acting as electron-deficient macrocyclic hosts, the synthesized O6-corona[3]arene[3]tetrazines self-regulated conformational structures to complex anions in the gas phase and in the solid state owing to the anion-π noncovalent interactions between anions and the tetrazine rings.

Pseudomonas aeruginosa in Cancer Therapy: Current Knowledge, Challenges and Future Perspectives.

Drug resistance, undesirable toxicity and lack of selectivity are the major challenges of conventional cancer therapies, which cause poor clinical outcomes and high mortality in many cancer patients. Development of alternative cancer therapeutics are highly required for the patients who are resistant to the conventional cancer therapies, including radiotherapy and chemotherapy. The success of a new cancer therapy depends on its high specificity to cancer cells and low toxicity to normal cells. Utilization of bacteria has emerged as a promising strategy for cancer treatment. Attenuated or genetically modified bacteria were used to inhibit tumor growth, modulate host immunity, or deliver anti-tumor agents. The bacteria-derived immunotoxins were capable of destructing tumors with high specificity. These bacteria-based strategies for cancer treatment have shown potent anti-tumor effects both in vivo and in vitro, and some of them have proceeded to clinical trials. Pseudomonas aeruginosa, a Gram-negative bacterial pathogen, is one of the common bacteria used in development of bacteria-based cancer therapy, particularly known for the Pseudomonas exotoxin A-based immunotoxins, which have shown remarkable anti-tumor efficacy and specificity. This review concisely summarizes the current knowledge regarding the utilization of P. aeruginosa in cancer treatment, and discusses the challenges and future perspectives of the P. aeruginosa-based therapeutic strategies.

Risk Assessment of Deep Coal and Gas Outbursts Based on IQPSO-SVM.

Coal and gas outbursts seriously threaten the mining safety of deep coal mines. The evaluation of the risk grade of these events can effectively prevent the occurrence of safety accidents in deep coal mines. Characterized as a high-dimensional, nonlinear, and small-sample problem, a risk evaluation method for deep coal and gas outbursts based on an improved quantum particle swarm optimization support vector machine (IQPSO-SVM) was constructed by leveraging the unique advantages of a support vector machine (SVM) in solving small-sample, high-dimension, and nonlinear problems. Improved quantum particle swarm optimization (IQPSO) is used to optimize the penalty and kernel function parameters of SVM, which can solve the optimal local risk and premature convergence problems of particle swarm optimization (PSO) and quantum particle swarm optimization (QPSO) in the training process. The proposed algorithm can also balance the relationship between the global search and local search in the algorithm design to improve the parallelism, stability, robustness, global optimum, and model generalization ability of data fitting. The experimental results prove that, compared with the test results of the standard SVM, particle swarm optimization support vector machine (PSO-SVM), and quantum particle swarm optimization support vector machine (QPSO-SVM) models, IQPSO-SVM significantly improves the risk assessment accuracy of coal and gas outbursts in deep coal mines. Therefore, this study provides a new idea for the prevention of deep coal and gas outburst accidents based on risk prediction and also provides an essential reference for the scientific evaluation of other high-dimensional and nonlinear problems in other fields. This study can also provide a theoretical basis for preventing coal and gas outburst accidents in deep coal mines and help coal mining enterprises improve their safety management ability.

Au(I)-thiolate nanostructures fabricated by chemical exfoliation and their transformation to gold nanoparticle assemblies.

Chemical exfoliation method was applied to transform bulky assemblies of Au(I)-3-mercaptopropionate (MPA) coordination polymer (CP) to nanosheets and nanostrings using sodium citrate as an exfoliator. The exfoliation process and the structural characteristics of the Au(I)-MPA nanosheets and nanostrings were fully investigated by transmission electron microscopy, atomic force microscopy, UV-vis absorption spectroscopy, X-ray photoelectron spectroscopy and so on. As the structural rigidity and stability of the obtained Au(I)-MPA nanosheets, they are ideal precursors for fabrication of water soluble gold nanoparticle assemblies through progressive pyrolysis. This work provides a significant strategy toward the morphology regulation of CP nanostructures and will inspire further development of this research area.