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Tilmicosin (TMC), a semi-synthetic macrolide antibiotic, is widely used in veterinary medicine due to its broad-spectrum, bacteriostatic properties. Frequently administered in various birds species, it is likely used off-label in geese as well. The study sought to investigate TMC's pharmacokinetics, tissue residues, in geese through in vivo experiments. The study involved longitudinal open studies on 15 healthy adult males, with three phases separated by one-month washout periods. Geese were administered TMC through intravenous (IV, 5 mg/kg), subcutaneous (SC, 10 mg/kg), and oral (PO, 25 mg/kg for five consecutive days) routes, with blood samples drawn at specific intervals. Tissue samples were also collected for subsequent analysis at pre-assigned times. TMC in goose plasma was quantified by a fully validated HPLC method. Plasma concentrations were quantified up to 4 hr for the PO and IV routes, and up to 10 hr in the SC route. Significant variations in bioavailability were observed between SC (87%) and PO (4%) routes. The body extraction ratio was low at 0.03, suggesting minimal ability of the liver and kidneys to eliminate TMC. Multiple oral doses showed no plasma accumulation, but tissue data revealed extensive distribution and prolonged residence, up to 120 h, suggesting a sustained therapeutic effect despite the brief plasma half-life. Regarding the multiple PO doses, provisional withdrawal times of 6, 7.5, and 8 days were suggested for the liver, muscles, and kidneys, respectively, according to the MRL set for these matrices in chickens by EMA. In conclusion, while the practical oral administration is discouraged at the population level, SC administration of TMC may be appropriate for geese, albeit impractical for flock therapy., (© 2024 John Wiley & Sons Ltd.)

Daptomycin, a lipopeptide comprising an N-decanoyl fatty acyl chain and a peptide core, is used clinically as an antimicrobial agent. The start condensation domain (dptC1) is an enzyme that catalyzes the lipoinitiation step of the daptomycin synthesis. In this study, we integrated enzymology, protein engineering, and computer simulation to study the substrate selectivity of the start condensation domain (dptC1) and to screen mutants with improved activity for decanoyl loading. Through molecular docking and computer simulation, the fatty acyl substrate channel and the protein-protein interaction interface of dptC1 are analyzed. Key residues at the protein-protein interface between dptC1 and the acyl carrier were mutated, and a single-point mutant showed more than three-folds improved catalytic efficiency of the target n-decanoyl substrate in comparing with the wild type. Moreover, molecular dynamics simulations suggested that mutants with increased catalytic activity may correlated with a more "open" and contracted substrate binding channel. Our work provides a new perspective for the elucidation of lipopeptide natural products biosynthesis, and also provides new resources to enrich its diversity and optimize the production of important components., (© 2024 Wiley‐VCH GmbH.)

Lanthanide hexaborides (LnB 6 ) have disparate and often anomalous properties, from structurally homogeneous mixed valency, to superconductivity, spectral anomalies, and unexplained phase transitions. It is unclear how such a diversity of properties may arise in the solids of identical crystal structures and seemingly very similar electronic structures. Building on our previous model for SmB 6 (mixed valent, with a peak in specific heat, and pressure induced magnetic phase transitions), we present a unifying dynamic bonding model for LnB 6 that explains simultaneously EuB 6 (possessing an anomalous peak in specific heat at low T, magnetic phase transitions, and no mixed valency), YbB 6 (mixed valent topological insulator), and rather ordinary LaB 6 . We show that Ln can engage in covalent bonding with boron, and, in some members of the LnB 6 family, also easily access alternative bonding states through the electron-phonon coupling. The accessibility, relative energetics, and bonding nature of the states involved dictate the properties., (© 2020 Wiley-VCH GmbH.)

Cyanobacteria are well recognised as producers of a wide range of natural compounds that are in turn recognised as toxins that have potential and useful applications in the future as pharmaceutical agents. The order Nostocales, which is largely overlooked in this regard, has become increasingly recognised as a source of toxin producers including Anabaena, Nostoc, Hapalosiphon, Fischerella, Anabaenopsis, Aphanizomenon, Gloeotrichia, Cylindrospermopsis, Scytonema, Raphidiopsis, Cuspidothrix, Nodularia, Stigonema, Calothrix, Cylindrospermum and Desmonostoc species. The toxin compounds (i.e., microcystins, nodularin, anatoxins, ambiguines, fischerindoles and welwitindolinones) and metabolites are about to have a destructive effect on both inland and aquatic environment aspects. The present review gives an overview of the various toxins that are extracted by the order Nostocales. The current research suggests that these compounds that are produced by cyanobacterial species have promising future considerations as potentially harmful algae and as promising leads for drug discovery., (© 2020 John Wiley & Sons, Ltd.)