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Purpose: Vortioxetine an anti-depressant FDA-drug recently reported showing better in vitro efficacy against SARS-CoV-2. Methods: In this study, we have synthesized ten new derivatives having alkenes, alkynes, benzyl, aryl, and mixed carbamate at the N-terminal of vortioxetine. Then the binding energy and interactions with the crucial amino acid residues in the binding pocket of main protease (Mpro) of SARS-CoV-2, of reported and ten newly synthesized vortioxetine derivatives (total thirty-one) in comparison with remdesivir are analyzed and presented in this paper. Results: Based on the docking scores predicted by ADV and AD, most vortioxetine derivatives showed better binding efficiency towards Mpro of SARS-CoV-2 in comparison with remdesivir (an EUA approved drug against SARS-CoV-2 Mpro) and vortioxetine. Conclusion: This study shows that some vortioxetine derivatives can be developed into promising drugs for COVID-19 treatment. [ABSTRACT FROM AUTHOR]

This paper presents the largest cohort to date of infants under 1 year of age treated with mebendazole. We evaluated the occurrence of mebendazole-associated clinical and laboratory toxicity as safety data in this age group are currently lacking. [ABSTRACT FROM AUTHOR]

Desmodium canum (Strong back) commonly consumed as a tea or tonic is believed to possess hypoglycaemic activity. This paper sets out to isolate potential hypoglycaemic compounds present within the plant and investigate their synergistic effects on blood glucose levels in euglycaemic Sprague Dawley rats. The milled plant was sequentially extracted using hexane, ethyl acetate and methanol. The ethyl acetate extract was subjected to column chromatography yielding seven major fractions and were subsequently bioassayed using the Oral Glucose Tolerance Test (OGTT). Further chromatographic separation and analysis using Gas Chromatography–Mass Spectroscopy and Fourier Transform Infrared Spectroscopy enabled the identification of two hypoglycaemic compounds, oleic acid (OA) and succinic acid (SA). These were bioassayed individually and as a cocktail to determine the synergistic effects using OGTT. Intravenous administration of these compounds individually indicated both are very potent in retarding blood glucose levels. However, the most significant activity was observed on synergistic administration. The cocktail (1 : 1) displayed significant hypoglycaemic activity throughout the entire study. It also significantly differed from OA at the 120 min interval (3.43 ± 0.22 mmol/L vs. 4.98 ± 0.19 mmol/L, resp., p = 4.29 × 10 − 7 ) and significantly differed from SA at 30 min (3.95 ± 0.43 mmol/L vs. 5.17 ± 0.32 mmol/L, resp., p = 0.003), 90 min (4.35 ± 0.36 mmol/L vs. 5.49 ± 0.69 mmol/L, resp., p = 0.04), and 120 min intervals (3.43 ± 0.22 mmol/L vs. 4.94 ± 0.31, resp., p = 1.54 × 10 − 5 ). Oral administration of the cocktail showed comparable potency to that of metformin (p > 0.05) throughout the OGTT curve. The synergistic effects of the naturally isolated compounds yielded higher potency levels than individual administration and when administered orally, the hypoglycaemic effect was similar to that of metformin. This may assist in paving a way to attempt a novel method in approaching antidiabetic therapy. [ABSTRACT FROM AUTHOR]

Background: Bisphenol A (BPA) is a ubiquitous, endocrine-disrupting environmental contaminant that increases risk of some adverse developmental effects. Thus, it is important to characterize BPA levels, metabolic fate and sources of exposure in pregnant women.Methods: We used an improved liquid chromatography-tandem mass spectrometry (LC-MS/MS) analytic method to directly and simultaneously measure unconjugated BPA (uBPA), BPA glucuronide and BPA sulfate in the urine of a population of ethnically and racially diverse, and predominately low-income pregnant women (n = 112) in their second trimester. We also administered a questionnaire on dietary and non-dietary sources of exposure to BPA.Results: We found universal and high exposure to uBPA and its metabolites: median concentrations were 0.25, 4.67, and 0.31 μg/g creatinine for uBPA, BPA glucuronide, and BPA sulfate, respectively. The median Total BPA (uBPA + BPA in glucuronide and sulfate forms) level was more than twice that measured in U.S. pregnant women in NHANES 2005-2006, while 30 % of the women had Total BPA levels above the 95th percentile. On average, Total BPA consisted of 71 % BPA in glucuronide form, 15 % BPA in sulfate form and 14 % uBPA, however the proportion of BPA in sulfate form increased and the proportion of uBPA decreased with Total BPA levels. Occupational and non-occupational contact with paper receipts was positively associated with BPA in conjugated (glucuronidated + sulfated) form after adjustment for demographic characteristics. Recent consumption of foods and beverages likely to be contaminated with BPA was infrequent among participants and we did not observe any positive associations with BPA analyte levels.Conclusion: The high levels of BPA analytes found in our study population may be attributable to the low-income status of the majority of participants and/or our direct analytic method, which yields a more complete evaluation of BPA exposure. We observed near-universal exposure to BPA among pregnant women, as well as substantial variability in BPA metabolic clearance, raising additional concerns for effects on fetal development. Our results are consistent with studies showing thermal paper receipts to be an important source of exposure, point to the difficulty pregnant women have avoiding BPA exposure on an individual level, and therefore underscore the need for changes in BPA regulation and commerce. [ABSTRACT FROM AUTHOR]

Tension energies for acyclic and cyclic assemblies of adamantane units sharing hexagons of carbon atoms converge in a size-extensive manner for large numbers n of adamantane units. In most cases the convergence features diagrams of strain energy per adamantane unit E (n-1) versus n-2 for cyclic aggregates and versus n-1 for acyclic aggregates having linear dependence with slopes of opposite signs. However, we found two exceptions which are discussed in the present paper, with convergence involving linear dependence with slopes of the same sign. [ABSTRACT FROM AUTHOR]

1-Deoxynojirimycin (DNJ), the main hypoglycemic constituent in mulberry (Morus alba) latex, has been extensively researched. Although there is considerable interest in the biological effects of DNJ, the roles of 1-deoxynojirimycin (DNJ) in glycometabolism and energy metabolism in insects have received little attention. In this paper, 1H nuclear magnetic resonance (1H NMR) based metabonomic was performed to study the effects of the oral supplementation of 0.25% DNJ, 0.5% DNJ, latex, and the mixture of 0.5% DNJ and latex (1 : 1) on the fat body glycometabolism and energy metabolism of the fourth-instar larvae of Eri silkworms, Samia cynthia ricini. Metabolic pattern recognition analysis (partial least square-discriminant analysis, PLS-DA) of fat body extracts indicated that the groups of 0.25% DNJ, 0.5% DNJ, latex, and the mixture of 0.5% DNJ and latex (1 : 1) were significantly different from the control group. Further, compared to the control group, the metabolites levels of lactate, trehalose, succinate, malate, and fumarate were remarkably changed in experimental groups, which were involved in glycolysis, hydrolysis of trehalose, and tricarboxylic acid (TCA) cycle. Our results indicate that DNJ has a positive impact on the reverse energy metabolism of Eri silkworms and metabonomic analysis based on NMR can be used as a tool to identify potential biomarkers. [ABSTRACT FROM AUTHOR]

Abstract: Mixed culture fermentation of Bacillus megaterium and Gluconobacter oxydans is widely used to produce 2-keto-l-gulonic acid (2-KGA), a key precursor for l-ascorbic acid synthesis. For such mixed cultivation, kinetic modelling is difficult because the interactions between the two strains are not well known yet. In this paper, data-driven prediction of the product formation is presented for the purpose of better process monitoring. A rolling learning-prediction approach based on neural networks is practiced to predict 2-KGA formation. Techniques associated with the approach, such as the data pretreatment and the rolling learning-prediction mechanism, are given in more detail. The validation results by using the data from commercial scale 2-KGA cultivation indicate that the prediction error is less than 5% in the later phase of fermentation and the reliable prediction time span is 8h. The robustness of the prediction approach is further tested by adding extra noises to the process variables. [Copyright &y& Elsevier]

Abstract: Process intensification (PI) has the potential to improve existing processes or create new process options, which are needed in order to produce products using more sustainable methods. In principle, an enormous number of process options can be generated but where and how the process should be intensified for the biggest improvement is difficult to identify. In this paper the development of a systematic computer aided model-based synthesis and design methodology incorporating PI is presented. In order to manage the complexities involved, the methodology employs a decomposition-based solution approach. Starting from an analysis of existing processes, the methodology generates a set of process options and reduces their number through several screening steps until from the remaining options, the optimal is found. The application of the methodology is highlighted through a case study involving the chemo-enzymatic synthesis of N-acetyl-d-neuraminic acid (Neu5Ac). [Copyright &y& Elsevier]