Meropenem-vaborbactam resistance in Klebsiella pneumoniae isolates is associated with loss-of-function mutations in the OmpK35 and OmpK36 porins. We identify two previously unknown loss-of-function mutations that confer cefuroxime resistance in K. pneumoniae isolates. The proteins lost were NlpD and KvrA; the latter is a transcriptional repressor that controls capsule production. We demonstrate that KvrA loss reduces OmpK35 and OmpK36 porin production, which confers reduced susceptibility to meropenem-vaborbactam in a KPC-3-producing K. pneumoniae isolate.
Benzeneboronate of catecholic carboxyl methyl esters, N-acetyldopamine, coumarin and catechol estrogens were prepared as crystalline derivatives in high yield. Related catechol compounds with extra polar functional group(s) (OH, NH2) do not form or only partially form unstable cyclic boronate derivatives.
Boronic acids have been widely investigated for their potential use as glucose sensors in glucose responsive polymeric insulin delivery systems. Interactions between cyclic diols and boronic acids, anchored to polymeric delivery systems, may result in swelling of the delivery system, releasing the drug. In this study, 4-formylphenylboronic acid conjugated chitosan was formulated into insulin containing nanoparticles via polyelectrolyte complexation. The nanoparticles had an average diameter of 140 ± 12.8 nm, polydispersity index of 0.17 ± 0.1, zeta potential of +19.1 ± 0.69 mV, encapsulation efficiency of 81% ± 1.2%, and an insulin loading capacity of 46% ± 1.8% w/w. Changes in size of the nanoparticles and release of insulin were type of sugar- and concentration-dependent. High concentration of diols resulted in a sustained release of insulin due to crosslink formation with boronic acid moieties within the nanoparticles. The formulation has potential to be developed into a self-regulated insulin delivery system for the treatment of diabetes.
Cross-linked resin-captured palladium (XL-QPPd) was readily prepared by simple physical adsorption onto the high loading QuadraPure macroporous resin and a subsequent reduction process. To enhance the mechanical stability, entrapped palladium nanocatalysts were cross-linked with succinyl chloride. Both transmission electron microscopy images and X-ray diffraction analysis revealed that the palladium nanoparticles were well dispersed with diameters ranging in 4-10 nm. The catalyst performed good catalytic activity in microwave-promoted Suzuki cross-coupling reactions in water under aerobic condition with mild condition by using various aryl halides and phenylboronic acid. In addition, the catalyst showed an excellent recyclability without significant loss of catalytic activity.
An investigation was conducted on the usage of a single-step extraction procedure involving the retention of a phenylboronate-salbutamol complex on an end-capped C18 solid-phase sorbent to determine the level of salbutamol in human plasma samples. Propranolol, a beta-blocker, was chosen as the internal standard for this assay. In this solid-phase clean-up method, 50 mM sodium carbonate buffer, pH 9.60, was used for conditioning the column as well as washing the endogenous interference. Under the optimal conditions, the recovery of salbutamol from spiked plasma samples was found to be high and reproducible with mean recoveries (n = 3) of more than 90% after elution by using 50% 1 M trifluoroacetic acid in methanol. This sample clean-up step was effectively analyzed under reversed-phase high-performance liquid chromatography with fluorimetric detection. The method was successfully applied to the routine measurement of salbutamol in human plasma from the bioequivalence study on the different administration route of salbutamol. Quantification of salbutamol was convincingly reported with the correlation of coefficient of 0.9980 for the concentration range from 0 to 1000 ng ml(-1). An adequate precision was achieved with both between- and within-day precisions of less than 10% (n = 6) for 100 and 1000 ng ml(-1) and less than 15% (n = 6) for 10 ng ml(-1).
The principal challenge for the use of boronic acids (BA) as glucose sensors is their lack of specificity for glucose. We examined the selectivity of and insulin release from two boronic acids- (2-formyl-3-thienylboronic acid (FTBA) and 4-formylphenylboronic acid (FPBA)) conjugated chitosan scaffolds to glucose and fructose. Adsorption of glucose to BA: chitosan conjugates was dose-dependent up to 1:1 at 35 and 42% for FPBA and FTBA respectively but the FTBA conjugates adsorbed more glucose and fructose at respective FPBA ratios. The affinity of both BA conjugates to glucose decreased with increase in BA ratio. On the other hand, the affinity of both BA conjugates for fructose decreased from ratio 1:1 to 2:1 then rose again at 3:1. Insulin release from FPBA nanoparticles (FPBAINP) and FTBA nanoparticles (FTBAINP) were both concentration-dependent within glyceamically relevant values (1-3 mg/ml glucose and 0.002 mg/ml fructose). Furthermore, the total amounts of insulin released from FPBAINP in both the media were higher than from FTBAINP. Both FPBAINP and FTBAINP have the potential for development as a glucose-selective insulin delivery system in physiological settings.
Recent advances and applications of biomolecule-responsive hydrogels, namely, glucose-responsive hydrogels, protein-responsive hydrogels, and nucleic-acid-responsive hydrogels are highlighted. However, achieving the ultimate purpose of using biomolecule-responsive hydrogels in preclinical and clinical areas is still at the very early stage and calls for more novel designing concepts and advance ideas. On the way toward the real/clinical application of biomolecule-responsive hydrogels, plenty of factors should be extensively studied and examined under both in vitro and in vivo conditions. For example, biocompatibility, biointegration, and toxicity of biomolecule-responsive hydrogels should be carefully evaluated. From the living body's point of view, biocompatibility is seriously depended on the interactions at the tissue/polymer interface. These interactions are influenced by physical nature, chemical structure, surface properties, and degradation of the materials. In addition, the developments of advanced hydrogels with tunable biological and mechanical properties which cause no/low side effects are of great importance.
Background: Complicated urinary tract infections are a significant cause of morbidity, hospitalization, and elevated hospital costs associated with kidney transplantations. The treatment of complicated urinary tract infections is very challenging, due to varying severities of infection and lower cure rates. The available drug options for treating these infections are limited, each with different mechanisms of action, efficacy, and safety profiles, making drug selection more difficult for healthcare professionals. Objectives: A systematic review was conducted to evaluate the safety and efficacy of drugs approved by the United States Food and Drug Administration for the treatment of complicated urinary tract infections between 2016 and 2023. The primary endpoint for all drugs used in treating complicated urinary tract infections was the cure rate. Results: Among the drugs used for treating complicated urinary tract infections, meropenem had the highest cure rate at 91.4%, followed by plazomicin at 88% and cefiderocol at 73% when used as monotherapy. In combination therapy, meropenem-vaborbactam had the highest cure rate at 98.4%, followed by piperacillin-tazobactam at 94%, and ceftazidime-avibactam at 87.5%. The safety profiles of the drugs indicated that almost all drugs caused gastrointestinal symptoms, with imipenem-relebactam and colistin-imipenem combinations having the most serious adverse events. Cefiderocol had a low magnitude of adverse events, with most side effects being mild gastrointestinal symptoms. Conclusion: The study concludes that appropriate drug selection and treatment adherence are crucial for preventing complicated urinary tract infections and improving health outcomes.