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In this study, ultra-small nickel nanoparticles on NiFe 2 O 4 (Ni@NiFe 2 O 4) and Ni@NiFe 2 O 4 /ZnO magnetic nanocomposites were synthesized and utilized for the solar light-driven photocatalytic degradation of cefadroxil. The drug cefadroxil is widely used to treat bacterial infections and cefadroxil is a non-biodegradable pharmaceutical compound detected in the groundwater sources because of its low removal efficiency. The Raman active phonon at 540 cm−1 confirms the presence of Ni nanoparticles at the surface of NiFe 2 O 4 /ZnO. DR-UV-Vis analysis exhibited surface plasmon resonance at 350 nm for ultra-small nickel nanoparticles. The observed optical bandgap values for Ni@NiFe 2 O 4 and NiFe 2 O 4 /ZnO are 1.2 eV and 2.43 eV, respectively. Which indicates that these magnetic nanocomposites can be utilized for the mineralization of cefadroxil (β-lactam antibiotic) under ambient environmental conditions. The efficiency was determined by the direct solar light driven photocatalytic oxidation of cefadroxil in the presence and absence of peroxymonosulphate (PMS). The experimental findings exhibits that ∼95 % of cefadroxil (CDL) was eliminated by the ultra-small Ni@NiFe 2 O 4 /ZnO within 60 min (k = 7.5 × 10−4 s−1) of direct solar light irradiation. Further, the addition of PMS enhanced the photodegradation to achieve 100 % cefadroxil oxidation within 40 min (k = 25 × 10−4 s−1) of direct sunlight. The efficiency of the nanocatalyst was compared with controlled experiments and was found to be Fe 2 O 3 < ZnO < TiO 2 (P25) < Ni@NiFe 2 O 4 < Ni@NiFe 2 O 4 /ZnO under absence and presence of PMS. Moreover, ultra-small Ni@NiFe 2 O 4 /ZnO nanophotocatalyst were stable up to 3 consecutive cycles. [ABSTRACT FROM AUTHOR]

Methicillin-resistant Staphylococcus aureus (MRSA) mastitis poses a significant threat to dairy herds worldwide, given its resistance to methicillin and other β-lactam antibiotics, which often leads to treatment failure. Consequently, there is an urgent need for safe and effective alternative therapeutic approaches. Recent investigations have highlighted the potential of baicalein, a natural flavonoid known for its potent anti-inflammatory and antibacterial properties, especially its synergistic effects with β-lactam antibiotics against MRSA. However, the limited solubility and bioavailability of baicalein hinder its biomedical utility. The present study assessed the therapeutic efficacy of encapsulated baicalein in chitosan, forming a tricomplex with a β-lactam antibiotic, using a murine model of MRSA-induced mastitis. The experimental design comprised seven groups, each consisting of six mice. We evaluated the ability of various treatment regimens to mitigate histopathological alterations and bacterial burden induced by MRSA infection, aiming to elucidate underlying mechanisms. Our results revealed that tricomplex treatment significantly reduced bacterial load in mammary tissue and preserved tissue integrity, resulting in decreased inflammatory responses post-MRSA inoculation. In addition, tricomplex treatment markedly reduced mean leukocyte and neutrophil counts in blood and suppressed the matrix metalloproteinase-9 (MMP-9) concentration and C-reactive protein (CRP) response. Notably, the synergistic interaction between baicalein and amoxicillin was particularly pronounced. Our findings suggest that chitosan-encapsulated baicalein combined with a β-lactam antibiotic holds promise as a therapeutic option for MRSA-induced mastitis. Further investigations, particularly in target animal species, are warranted to comprehensively evaluate its clinical feasibility.

Nonribosomal peptide synthetases (NRPSs) are responsible for the production of important biologically active peptides. The large, multidomain NRPSs operate through an assembly line strategy in which the growing peptide is tethered to carrier domains that deliver the intermediates to neighboring catalytic domains. While most NRPS domains catalyze standard chemistry of amino acid activation, peptide bond formation, and product release, some canonical NRPS catalytic domains promote unexpected chemistry. The paradigm monobactam antibiotic sulfazecin is produced through the activity of a terminal thioesterase domain of SulM, which catalyzes an unusual β-lactam-forming reaction in which the nitrogen of the C-terminal N-sulfo-2,3-diaminopropionate residue attacks its thioester tether to release the monobactam product. We have determined the structure of the thioesterase domain as both a free-standing domain and a didomain complex with the upstream holo peptidyl-carrier domain. The position of variant lid helices results in an active site pocket that is quite constrained, a feature that is likely necessary to orient the substrate properly for β-lactam formation. Modeling of a sulfazecin tripeptide into the active site identifies a plausible binding mode identifying potential interactions for the sulfamate and the peptide backbone with Arg2849 and Asn2819, respectively. The overall structure is similar to the β-lactone-forming thioesterase domain that is responsible for similar ring closure in the production of obafluorin. We further use these insights to enable bioinformatic analysis to identify additional, uncharacterized β-lactam-forming biosynthetic gene clusters by genome mining., Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

• PEI-modified HNTs-based hybrid silica monolith was prepared. • The monolith showed a large adsorption capacity of hydrophilic cefoperazone. • The monolith was used as a sorbent for spin tip solid-phase extraction. • The tip effectively purified sulbactam, cefoperazone and cefuroxime in whole blood. • The determination of the analytes was accurate, reproducible and sensitive. In this study, we proposed a novel method utilizing polyethyleneimine (PEI)-modified halloysite nanotubes (HNTs)-based hybrid silica monolithic spin tip to analyze hydrophilic β-lactam antibiotics and β-lactamases inhibitors in whole blood samples for the first time. HNTs were incorporated directly into the hybrid silica monolith via a sol-gel method, which improved the hydrophilicity of the matrix. The as-prepared monolith was further modified with PEI by glutaraldehyde coupling reaction. It was found that the PEI-modified HNTs-based hybrid silica monolith enabled a large adsorption capacity of cefoperazone at 35.7 mg g−1. The monolithic spin tip-based purification method greatly reduced the matrix effect of whole blood samples and had a detection limit as low as 0.1 − 0.2 ng mL−1. In addition, the spiked recoveries of sulbactam, cefuroxime, and cefoperazone in blank whole blood were in the range of 89.3–105.4 % for intra-day and 90.6–103.5 % for inter-day, with low relative standard deviations of 1.3–7.2 % and 4.9–10.5 %, respectively. This study introduces a new strategy for preparing nanoparticles incorporated in a hybrid silica monolith with a high adsorption capacity. Moreover, it offers a valuable tool to monitor sulbactam, cefoperazone, and cefuroxime in whole blood from pregnant women with the final aim of guiding their administration. [ABSTRACT FROM AUTHOR]