Synthesis and computational evaluation of the antioxidant activity of pyrrolo[2,3-b]quinoxaline derivatives.

Pyrrolo[2,3-b]quinoxaline derivatives are known to possess antioxidant, anticancer, and antibacterial properties. Here we report the successful synthesis of five derivatives of 3-hydroxy-3-pyrroline-2-one through substitution. The 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay was employed to evaluate the antioxidant activity of the compounds. Out of these, ethyl 1,2-diphenyl-1H-pyrrolo[2,3-b]quinoxaline-3-carboxylate (3a) demonstrated the greatest potential as a radical scavenger. Thermodynamic and kinetic calculations of the radical scavenging activity indicated that 3a exhibited HO˙ radical scavenging activity with the overall rate constant of 8.56 × 108 M-1 s-1 in pentyl ethanoate; however, it was incapable of scavenging hydroperoxyl radicals in nonpolar media. In non-polar environments, the hydroxyl radical scavenging capability of 3a is fairly similar to that of reference antioxidants such as Trolox, melatonin, indole-3-carbinol, and gallic acid. Hence, in the physiological lipid environment, 3a holds promise as a scavenger of HO˙ radicals.

Evaluation of the Effectiveness of the Policy of Holding the Second Dose of Vaccination: Lessons from the Outbreak in Ho Chi Minh City.

The coronavirus disease 2019 (COVID-19) pandemic has caused a lot of ethical controversy in the equal provision of healthcare, including vaccination. Therefore, our study was designed to assess the impact of Ho Chi Minh City's policy to hold the second dose of the COVID-19 vaccine. Using a cross-sectional study design to assess low saturation of peripheral oxygen (SPO2) risk based on vaccination status, we included patients who were confirmed to have SARS-CoV-2 and were treated at home. The stepwise method was used to determine participants' low SPO2 risk-related factors. The average age of the 2836 respondents was 46.43 ± 17.33 (years). Research results have shown that seven factors are related to the low SPO2 status of participants, including age, sneezing, shortness of breath, coughing, and fainting as COVID-19 symptoms, the number of people living with COVID-19, and a history of lung disease. A statistically significant (p = 0.032) finding in this study was that fully vaccinated patients had a 6% lower risk of low SPO2 compared to the first dose less than 21 days group. This result was similar in the vaccine holder group (p < 0.001). Holding the second dose of the COVID-19 vaccine is associated with a lower SPO2 risk than that of fully vaccinated patients. Therefore, this approach should be considered by governments as it could bring a greater benefit to the community.

Experimental and theoretical studies on the synthesis of 1,4,5-trisubstituted pyrrolidine-2,3-diones.

Substituted 4-acetyl-3-hydroxy-3-pyrroline-2-ones have been prepared via three-component reactions and the tautomerism of these 3-pyrroline-2-ones is due to the slight difference of energy, and the significantly large rate constant of transformation between two tautomers. 1,4,5-Trisubstituted pyrrolidine-2,3-dione derivatives were prepared from the above mentioned 2-pyrrolidinone derivatives and aliphatic amines, which exist in enamine form and are stabilized by an intramolecular hydrogen bond. A possible reaction mechanism between 3-pyrroline-2-one and aliphatic amine (CH3NH2) was proposed based on computational results and the main product is formed favorably following the PES via the lowest ΔG # pathway in both the gas-phase and an ethanol solvent model. DFT calculations showed that kinetic selectivity is more significant than thermodynamic selectivity for forming main products.

Synthesis and evaluation of the antioxidant activity of 3-pyrroline-2-ones: experimental and theoretical insights.

The heterocyclic γ-lactam ring 2-pyrrolidinone has four carbon atoms and one nitrogen atom. Among the group of derivatives of 2-pyrrolidinones, 1,5-dihydro-2H-pyrrol-2-ones, also known as 3-pyrroline-2-ones, play a significant structural role in a variety of bioactive natural compounds. In this study, three-component reactions were used to successfully synthesize six polysubstituted 3-hydroxy-3-pyrroline-2-one derivatives. The antioxidant activity of the compounds was tested by the 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay, identifying 4-ethoxycarbonyl-3-hydroxy-5-(4-methylphenyl)-1-phenyl-3-pyrroline-2-one (4b) as the most promising radical scavenger. Quantum chemistry calculations of the thermodynamics and kinetics of the radical scavenging activity also suggest that 4b is an effective HO˙ radical scavenger, with k overall values of 2.05 × 109 and 1.54 × 1010 M-1 s-1 in pentyl ethanoate and water, respectively. On the other hand, 4b could not scavenge hydroperoxyl radicals in either media. The ability of 4b to scavenge hydroxyl radicals in polar and non-polar environments is comparable to that of conventional antioxidants such as melatonin, gallic acid, indole-3-carbinol, ramalin, or Trolox. Thus 4b may be classed as a promising HO˙ radical scavenger in the physiological environment.

Comparison of the condyle-fossa relationship and resorption between patients with and without Juvenile Idiopathic Arthritis (JIA).

PURPOSE: The purpose of this study was 1) to compare condyle - fossa relationships in the temporomandibular joint (TMJ), and 2) to score condylar resorption by using a TMJ indexing system in patients with JIA and without JIA. METHODS: The present retrospective cross-sectional study included cone-beam computed tomography (CBCT) images obtained from the sagittal, coronal, and axial slices. In the multidisciplinary Pediatric Rheumatology Outpatient Clinic at The University of Alabama at Birmingham (UAB) children with JIA are also examined by a group of orthodontists working in the same institute from October 2018 to July 2019. The predictor variable consists of patients with JIA and without JIA. The primary outcome variables are the depth of the mandibular fossa, joint spaces, axial angles, medio-lateral width, and condyle resorption. Other study variables were age and sex. In this study, the measurements obtained from 2 different groups (with JIA and without JIA) are compared using a t-test, where Tukey is utilized to adjust for multiple comparisons. The left and right joints are analyzed separately as the paired t test conducted showed a significant difference between the 2 joints (P < .05). RESULTS: The study was comprised of 34 patients diagnosed with JIA and 34 healthy subjects. The depth of the mandibular fossa, the anterior joint spaces, the axial angles, and the resorption index showed statistically significant differences between the JIA and healthy groups in both left and right sides (P < .05). However, there was no statistically significant difference in the posterior joint spaces and mediolateral width between JIA and healthy groups in both sides (P > .05). CONCLUSIONS: The results of our study presented the destructive potential of juvenile idiopathic arthritis by using CBCT. CBCT scanning is a helpful tool in the evaluation of the radiographic result of TMJ.

Remote sensing of vegetation conditions after post-fire mulch treatments.

Wildfires are becoming more prevalent and are impacting forests, watersheds and important resources. Hydrologic and geomorphic processes following wildfires can include erosion flooding, and degraded water quality. To mitigate these secondary impacts, post-fire restoration treatments can be applied to a burned area to stabilize the land surface or promote vegetative regrowth. This research focuses on wood and straw mulch treatment implemented after the 2012 Waldo Canyon Fire in Colorado (United States) and estimates the spatial and temporal changes in annual and seasonal vegetation after a fire with respect to geomorphic factors. This study highlights the use of satellite-based remote sensing products to investigate the impacts of post-fire rehabilitation treatments on vegetation. Using Enhanced Vegetation Index as a proxy for vegetative growth, vegetation conditions are evaluated with respect to slope, slope aspect, and burn severity to understand the impact of the ground cover treatments on vegetation for five years before and after the fire (2007-2016). Sixty-three burned and untreated sites, forty-nine burned sites treated with wood mulch, and twenty-eight burned sites treated with straw mulch were analyzed. These sites were also compared to two control sites that were unburned and untreated, Hunter's Run and Fountain Creek. Generally, post-fire conditions did not return to pre-fire levels, where average vegetation levels were lower. By the end of the study, burned and untreated sites had larger vegetative levels than burned and treated sites. The vegetation levels of the burned sites were statistically different (α = 0.05) from pre-fire conditions in all areas of treatment. Burned sites treated with wood and straw recovered to 69% and 73% of pre-fire conditions, respectively. This work demonstrates the novel use of remote sensing to observe vegetation after post-fire treatment applications to augment the number of sites and length of time that can be analyzed. The observed change in vegetation conditions also contributes to furthering our understanding of the impacts of post-fire restoration, which is important for post-fire management.

An anticholinergic reverses motor control and corticostriatal LTD deficits in Dyt1 ΔGAG knock-in mice.

DYT1 early-onset generalized torsion dystonia is an inherited movement disorder associated with mutations in DYT1 that codes for torsinA protein. The most common mutation seen in this gene is a trinucleotide deletion of GAG. We previously reported a motor control deficit on a beam-walking task in our Dyt1 ΔGAG knock-in heterozygous mice. In this report we show the reversal of this motor deficit with the anticholinergic trihexyphenidyl (THP), a drug commonly used to treat movement problems in dystonia patients. THP also restored the reduced corticostriatal long-term depression (LTD) observed in these mice. Corticostriatal LTD has long been known to be dependent on D2 receptor activation. In this mouse model, striatal D2 receptors were expressed at lower quantities in comparison to wild-type mice. Furthermore, the mice were also partially resistant to FPL64176, an agonist of L-type calcium channels that have been previously reported to cause severe dystonic-like symptoms in wild-type mice. Our findings collectively suggest that altered communication between cholinergic interneurons and medium spiny neurons is responsible for the LTD deficit and that this synaptic plasticity modification may be involved in the striatal motor control abnormalities in our mouse model of DYT1 dystonia.