Synergistic and Additive Effects of Menadione in Combination with Antibiotics on Multidrug-Resistant Staphylococcus aureus: Insights from Structure-Function Analysis of Naphthoquinones.

Antimicrobial resistance (AMR) interferes with the effective treatment of infections and increases the risk of microbial spread and infection-related illness and death. The synergistic activities of combinations of antimicrobial compounds offer satisfactory approaches to some extent. Structurally diverse naphthoquinones (NQs) including menadione (-CH3 group at C2) exhibit substantial antimicrobial activities against multidrug-resistant (MDR) pathogens. We explored the combinations of menadione with antibiotic ciprofloxacin or ampicillin against Staphylococcus aureus and its biofilms. We found an additive (0.590 %) were also observed. However, preformed biofilms were not affected. Dent formation was also evident in S. aureus treated with the test compounds. The structure-function relationship (SFR) of NQs was used to determine and predict their activity pattern against pathogens. Analysis of 10 structurally distinct NQs revealed that the compounds with -Cl, -Br, -CH3 , or -OH groups displayed the lowest MICs (32-256 µg/mL). Furthermore, 1,4-NQs possessing a halogen or -CH3 moiety showed elevated ROS activity, whereas molecules with an -OH group affected cell integrity. Improved activity of antimicrobial combinations and SFR approaches are significant in antimicrobial therapies.

How Structure-Function Relationships of 1,4-Naphthoquinones Combat Antimicrobial Resistance in Multidrug-Resistant (MDR) Pathogens.

Antimicrobial resistance (AMR) is one of the top ten health-related threats worldwide. Among several antimicrobial agents, naphthoquinones (NQs) of plant/chemical origin possess enormous structural and functional diversity and are effective against multidrug-resistant (MDR) pathogens. 1,4-NQs possess alkyl, hydroxyl, halide, and metal groups as side chains on their double-ring structure, predominantly at the C-2, C-3, C-5, and C-8 positions. Among 1,4-NQs, hydroxyl groups at either C-2 or C-5 exhibit significant antibacterial activity against Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Enterobacter spp. (ESKAPE) and MDR categories. 1,4-NQs exhibit antibacterial activities like plasmids curing, reactive oxygen species generation, efflux pumps inhibition, anti-DNA gyrase activity, membrane permeabilization, and biofilm inhibition. This review emphasizes the structure-function relationships of 1,4-NQs against ESKAPE and MDR pathogens based on a literature review of studies published in the last 15 years. Overall, 1,4-NQs have great potential for counteracting the antimicrobial resistance of MDR pathogens.

Biosurfactants' multifarious functional potential for sustainable agricultural practices.

Increasing food demand by the ever-growing population imposes an extra burden on the agricultural and food industries. Chemical-based pesticides, fungicides, fertilizers, and high-breeding crop varieties are typically employed to enhance crop productivity. Overexploitation of chemicals and their persistence in the environment, however, has detrimental effects on soil, water, and air which consequently disturb the food chain and the ecosystem. The lower aqueous solubility and higher hydrophobicity of agrochemicals, pesticides, metals, and hydrocarbons allow them to adhere to soil particles and, therefore, continue in the environment. Chemical pesticides, viz., organophosphate, organochlorine, and carbamate, are used regularly to protect agriculture produce. Hydrophobic pollutants strongly adhered to soil particles can be solubilized or desorbed through the usage of biosurfactant/s (BSs) or BS-producing and pesticide-degrading microorganisms. Among different types of BSs, rhamnolipids (RL), surfactin, mannosylerythritol lipids (MELs), and sophorolipids (SL) have been explored extensively due to their broad-spectrum antimicrobial activities against several phytopathogens. Different isoforms of lipopeptide, viz., iturin, fengycin, and surfactin, have also been reported against phytopathogens. The key role of BSs in designing and developing biopesticide formulations is to protect crops and our environment. Various functional properties such as wetting, spreading, penetration ability, and retention period are improved in surfactant-based formulations. This review emphasizes the use of diverse types of BSs and their source microorganisms to challenge phytopathogens. Extensive efforts seem to be focused on discovering the innovative antimicrobial potential of BSs to combat phytopathogens. We discussed the effectiveness of BSs in solubilizing pesticides to reduce their toxicity and contamination effects in the soil environment. Thus, we have shed some light on the use of BSs as an alternative to chemical pesticides and other agrochemicals as sparse literature discusses their interactions with pesticides. Life cycle assessment (LCA) and life cycle sustainability analysis (LCSA) quantifying their impact on human activities/interventions are also included. Nanoencapsulation of pesticide formulations is an innovative approach in minimizing pesticide doses and ultimately reducing their direct exposures to humans and animals. Some of the established big players and new entrants in the global BS market are providing promising solutions for agricultural practices. In conclusion, a better understanding of the role of BSs in pesticide solubilization and/or degradation by microorganisms represents a valuable approach to reducing their negative impact and maintaining sustainable agricultural practices.

Force balance of hydrogen bubbles growing and oscillating on a microelectrode.

Hydrogen evolution in acidic aqueous electrolytes was recently found to be characterized by a carpet of microbubbles covering the microelectrode and feeding the growth of the main bubbles by coalescence. Besides this, oscillatory behavior of the main bubbles was observed prior to departure. Extending earlier studies, this work delivers the forces acting on the main bubble more accurately by taking into account further geometric and electrochemical details measured during experiments. Combining simulation work and measurements makes it possible to confirm the role of an attractive electrical (Coulomb) force caused by the adsorption of hydrogen ions at the bubble interface and to obtain a better understanding of the bubble dynamics observed.

On the growth regimes of hydrogen bubbles at microelectrodes.

The growth of single hydrogen bubbles at micro-electrodes is studied in an acidic electrolyte over a wide range of concentrations and cathodic potentials. New bubble growth regimes have been identified which differ in terms of whether the bubble evolution proceeds in the presence of a monotonic or oscillatory variation in the electric current and a carpet of microbubbles underneath the bubble. Key features such as the growth law of the bubble radius, the dynamics of the microbubble carpet, the onset time of the oscillations and the oscillation frequencies have been characterized as a function of the concentration and electric potential. Furthermore, the system's response to jumps in the cathodic potential has been studied. Based on the analysis of the forces involved and their scaling with the concentration, potential and electric current, a sound hypothesis is formulated regarding the mechanisms underlying the micro-bubble carpet and oscillations.

Dynamics of single hydrogen bubbles at Pt microelectrodes in microgravity.

The dynamics of single hydrogen bubbles electrogenerated in acidic electrolytes at a Pt microelectrode under potentiostatic conditions is investigated in microgravity during parabolic flights. Three bubble evolution scenarios have been identified depending on the electric potential applied and the acid concentration. The dominant scenario, characterized by lateral detachment of the grown bubble, is studied in detail. For that purpose, the evolution of the bubble radius, electric current and bubble trajectories, as well as the bubble lifetime are comprehensively addressed for different potentials and electrolyte concentrations. We focus particularly on analyzing bubble-bubble coalescence events which are responsible for reversals of the direction of bubble motion. Finally, as parabolic flights also permit hypergravity conditions, a detailed comparison of the characteristic bubble phenomena at various levels of gravity is drawn.

Oscillating Hydrogen Bubbles at Pt Microelectrodes.

The dynamics of hydrogen bubbles produced via electrolysis in acidic electrolytes is studied in a combination of experiments and numerical simulations. A transition from monotonic to oscillatory bubble growth is observed after 2/3 of the bubble lifetime, if the electric potential exceeds -3 V. This work analyzes characteristic features of the oscillations in terms of bubble geometry, the thickness of the microbubble carpet, and the oscillation frequency. An explanation of the oscillation mechanisms is provided by the competition between buoyancy and electric force, the magnitude of which depends on the carpet thickness. Both the critical carpet thickness at detachment and the oscillation frequencies of the bubble as predicted by the model agree well with the experiment.

Ionic size dependent electroviscous effects in ion-selective nanopores.

Pressure-driven flows of aqueous ionic liquids are characterized by electroviscosity-an increase in the effective (apparent) viscosity because of an induced back electric field termed streaming potential. In this work, we investigate the electrokinetic phenomenon of streaming potential mediated flows in ion-selective nanopores. We report a dramatic augmentation in the effective viscosity as attributable to the finite size effect of the ionic species in counterion-only systems. The underlying physics involves complex interaction between the concerned electrochemical phenomena and hydrodynamic transport in a confined fluidic environment, which we capture through a modified continuum based approach and validate using molecular dynamics simulations. We obtain an expression for the ionic-size dependent streaming potential pertinent to the physical situation being addressed. The corresponding estimations of effective viscosity implicate that the classical paradigm of point sized ions can give rise to gross underestimations of the flow resistance in counterion-only systems especially for negligible surface (Stern layer) conductivity and large fluidic slip at the surface.

Autophagic cell death is induced by acetone and ethyl acetate extracts from Eupatorium odoratum in vitro: effects on MCF-7 and vero cell lines.

Eupatorium odoratum (EO) contains many biologically active compounds, the anticancer effects of which are not well documented. This study evaluates the cytotoxic effects and mechanism of action of EO extracts on MCF-7 and Vero cell lines. Evaluation of the cytotoxic activity using MTT assay, morphological alterations, and apoptosis were carried out. Autophagy was evaluated by LC3-A protein expression. Cytotoxic activity, membrane blebbing and ballooning at 24 hours, replacement by mass vacuolation, and double membrane vesicles mimicking autophagy and cell death were observed in the cancer cells. No apoptosis was observed by DNA fragmentation assay. Overexpression of LC3-A protein indicated autophagic cell death. Cell cycle analysis showed G0 and G2/M arrest. The Vero cells did not show significant cell death at concentrations <100 µg/mL. These results thus suggest that acetone and ethyl acetate extracts of EO induce cell death through induction of autophagy and hold potential for development as potential anticancer drugs.