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In this study, a series of sphingosine-derived molecules with different structures were synthesized and their mechanism on increasing membrane permeability was elucidated in model lipid bilayers. [Display omitted] Sphingosine, an amphiphilic molecule, plays a pivotal role as the core structure of sphingolipids, essential constituents of cell membranes. Its unique capability to enhance the permeability of lipid membranes profoundly influences crucial life processes. The molecular structure of sphingosine dictates its mode of entry into lipid bilayers and governs its interactions with lipids, thereby determining membrane permeability. However, the incomplete elucidation of the relationship between the molecular structure of sphingosine and the permeability of lipid membranes persists due to challenges associated with synthesizing sphingosine molecules. A series of sphingosine-derived molecules, featuring diverse hydrophobic chain lengths and distinct headgroup structure, were meticulously designed and successfully synthesized. These molecules were employed to investigate the permeability of large unilamellar vesicles, functioning as model lipid bilayers. With a decrease in the hydrophobic chain length of sphingosine from C15 to C11, the transient leakage ratio of vesicle contents escalated from ∼ 13 % to ∼ 28 %. Although the presence of double bond did not exert a pronounced influence on transient leakage, it significantly affected the continuous leakage ratio. Conversely, modifying the chirality of the C-3 hydroxyl group gives the opposite result. Notably, methylation at the C-3 hydroxyl significantly elevates transient leakage while suppressing the continuous leakage ratio. Additionally, sphingosines that significantly affect vesicle permeability tend to have a more pronounced impact on cell viability. Throughout this leakage process, the charge state of sphingosine-derived molecule aggregates in the solution emerged as a pivotal factor influencing vesicle permeability. Fluorescence lifetime experiments further revealed discernible variations in the effect of sphingosine molecular structure on the mobility of hydrophobic regions within lipid bilayers. These observed distinctions emphasize the impact of molecular structure on intermolecular interactions, extending to the microscopic architecture of membranes, and underscore the significance of subtle alterations in molecular structure and their associated aggregation behaviors in governing membrane permeability. [ABSTRACT FROM AUTHOR]

In an effort to identify novel antibacterial agents, we presented two series of aminoguanidine derivatives that were designed by incorporating 1,2,4-triazol moieties. All compounds exhibited strong in vitro antibacterial activity against a variety of testing strains. Compound 5f was identified as a potent antibacterial agent with a minimum inhibitory concentration (MIC) of 2–8 µg/mL against S. aureus, E. coli, S. epidermidis, B. subtilis, C. albicans, multi-drug resistant Staphylococcus aureus and multi-drug resistant Escherichia coli and low toxicity (Hela > 100 µM). Membrane permeability and transmission electron microscopy (TEM) image studies demonstrated that compound 5f permeabilized bacterial membranes, resulting in irregular cell morphology and the rapid death of bacteria. The results of the present study suggested that aminoguanidine derivatives with 1,2,4-triazol moieties were the intriguing scaffolds for the development of bactericidal agents. [ABSTRACT FROM AUTHOR]

Cryopreservation of bovine oocytes and embryos is essential for long‐term preservation and widespread distribution of genetic material, particularly in bovine in vitro embryo production, which has witnessed substantial growth in the past decade due to advancements in reproductive biotechnologies. Among current cryopreservation methods, vitrification has emerged as the preferred cryopreservation technique over slow freezing for preserving oocytes and in vitro‐produced (IVP) embryos, as it effectively addresses membrane chilling injury and ice crystal formation. Nonetheless, challenges remain and a simple and robust vitrification protocol that guarantees the efficiency and viability after warming has not yet been developed. Furthermore, although slow cooling can easily be adapted for direct transfer, an easier and more practical vitrification protocol for IVP embryos is required to allow the transfer of IVP embryos on farms using in‐straw dilution. In addition, the susceptibility of bovine oocytes and embryos to cryoinjuries highlights the need for novel strategies to improve their cryotolerance. This manuscript examines various methodological approaches for increasing the viability of bovine oocytes and IVP embryos during vitrification. Strategies such as modifying lipid content or mitigating oxidative damage have shown promise in improving cryotolerance. Additionally, mathematical modelling of oocyte and embryo membrane permeability has facilitated the rational design of cryopreservation protocols, optimizing the exposure time and concentration of cryoprotectants to reduce cytotoxicity. [ABSTRACT FROM AUTHOR]

Background and Purpose: Demand for new antidepressants has resulted in a re‐evaluation of the therapeutic potential of psychedelic drugs. Several tryptamines found in psilocybin‐containing "magic" mushrooms share chemical similarities with psilocybin. Early work suggests they may share biological targets. However, few studies have explored their pharmacological and behavioural effects. Experimental Approach: We compared baeocystin, norbaeocystin and aeruginascin with psilocybin to determine if they are metabolized by the same enzymes, similarly penetrate the blood–brain barrier, serve as ligands for similar receptors and modulate behaviour in rodents similarly. We also assessed the stability and optimal storage and handling conditions for each compound. Key Results: In vitro enzyme kinetics assays found that all compounds had nearly identical rates of dephosphorylation via alkaline phosphatase and metabolism by monoamine oxidase. Further, we found that only the dephosphorylated products of baeocystin and norbaeocystin crossed a blood–brain barrier mimetic to a similar degree as the dephosphorylated form of psilocybin, psilocin. The dephosphorylated form of norbaeocystin was found to activate the 5‐HT2A receptor with similar efficacy to psilocin and norpsilocin in in vitro cell imaging assays. Behaviourally, only psilocybin induced head twitch responses in rats, a marker of 5‐HT2A‐mediated psychedelic effects and hallucinogenic potential. However, like psilocybin, norbaeocystin improved outcomes in the forced swim test. All compounds caused minimal changes to metrics of renal and hepatic health, suggesting innocuous safety profiles. Conclusions and Implications: Collectively, this work suggests that other naturally occurring tryptamines, especially norbaeocystin, may share overlapping therapeutic potential with psilocybin, but without causing hallucinations. [ABSTRACT FROM AUTHOR]

In this study, the effect of heat shock on the cell membrane was investigated using molecular dynamics (MD) simulations. Specifically, we examined the structural and dynamic behavior of a 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) lipid bilayer as it was exposed to increasing temperatures ranging from 310K to 340K. The results revealed a significant transition in membrane behavior as temperature increased, particularly at 330K and 340K, where the bilayer exhibited characteristics of a fluid disordered phase. This transition was marked by an increase in the area per lipid, a decrease in bilayer thickness, and a reduction in the deuterium order parameter (Scd), indicating increased molecular disorder and membrane fluidity. Additionally, the number of hydrogen bonds between lipid head groups and surrounding water molecules declined, weakening electrostatic interactions and promoting bilayer permeability. At 330K and 340K, these changes contributed to the formation of transient pores, which could facilitate molecular transport across the bilayer. The optimal temperature for maintaining membrane stability while enhancing molecular diffusion was found to be 320K, where the bilayer retained an ordered structure and displayed increased lipid mobility without significant disruption. These findings provide valuable insights into the thermal regulation of membrane behavior, which has critical implications for processes such as drug delivery, gene transfection, and thermal therapy. Molecular dynamics simulations at the atomistic level allow us to uncover intricate details of membrane phase transitions that are challenging to observe experimentally. [ABSTRACT FROM AUTHOR]

Nosodes are solutions prepared from pests, capable of controlling those same pests in crops. The use of these solutions in agriculture is an emerging technology for producing eco-friendly and inexpensive plant-based foods free from toxic compounds. The effects of applying nosodes to bean (Phaseolus vulgaris L.) crops before and after harvest were evaluated. The experiment was conducted in the field, with nosode 200CH applied once, three times, biweekly, and weekly from the flowering stage of the "Delgado" bean plant. The application of nosodes resulted in a 108% higher yield, 26% greater biomass, a 32% increase in root length, 34% more pods, and up to a 227% decrease in damaged pods compared to untreated plants. Furthermore, compared to the untreated plants, treated plants exhibited a 37% higher membrane stability and a phenolic content that was up to 27% higher in seeds and 22% higher in leaves. Plants under conventional management showed 61% less Diabrotica balteata (LeConte) incidence than nosode-treated ones. Seeds treated with nosodes exhibited a mortality in Zabrotes subfasciatus (Boh.) of up to 80%. This study highlights the use of nosodes in bean cultivation as an agronomic strategy to enhance seed production and quality, aiding producers in informed decision making about their application. [ABSTRACT FROM AUTHOR]

Abstract In an effort to identify novel antibacterial agents, we presented two series of aminoguanidine derivatives that were designed by incorporating 1,2,4-triazol moieties. All compounds exhibited strong in vitro antibacterial activity against a variety of testing strains. Compound 5f was identified as a potent antibacterial agent with a minimum inhibitory concentration (MIC) of 2–8 µg/mL against S. aureus, E. coli, S. epidermidis, B. subtilis, C. albicans, multi-drug resistant Staphylococcus aureus and multi-drug resistant Escherichia coli and low toxicity (Hela > 100 µM). Membrane permeability and transmission electron microscopy (TEM) image studies demonstrated that compound 5f permeabilized bacterial membranes, resulting in irregular cell morphology and the rapid death of bacteria. The results of the present study suggested that aminoguanidine derivatives with 1,2,4-triazol moieties were the intriguing scaffolds for the development of bactericidal agents.

Abstract Heavy metals stress particularly cadmium contamination is hotspot among researchers and considered highly destructive for both plants and human health. Iron is examined as most crucial element for plant development, but it is available in inadequate amount because they are present in insoluble Fe3+ form in soil. Fe3O4 have been recently found as growth promoting factor in plants. To understand, a sand pot experiment was conducted in completely randomized design (control, cadmium, 20 mg/L Fe3O4 nanoparticles,40 mg/L Fe3O4 nanoparticles, 20 mg/L Fe3O4 nanoparticles + cadmium, 40 mg/L Fe3O4 nanoparticles + cadmium) to study the mitigating role of Fe3O4 nanoparticles on cadmium stress in three Raphanus sativus cultivars namely i.e., MOL SANO, MOL HOL PARI, MOL DAQ WAL. The plant growth, physiological and biochemical parameters i.e.,shoot length, shoot fresh weight, shoot dry weight, root length, root fresh and dry weight, MDA content, soluble protein contents, APX, CAT, POD activities and ion concentrations, membrane permeability, chlorophyll a, chlorophyll b and anthocyanin content, respectively were studied. The results displayed that cadmium stress remarkably reduces all growth, physiological and biochemical parameters for allcultivars under investigation. However, Fe3O4 nanoparticles mitigated the adverse effect of cadmium by improving growth, biochemical and physiological attributes in all radish cultivars. While, 20 mg/L Fe3O4 nanoparticles have been proved to be more useful against cadmium stress. The outcome of present investigation displayed that Fe3O4 nanoparticles can be utilized for mitigating heavy metal stress.

Alternaria gansuensis, a seed-borne fungus of standing milkvetch (Astragalus adsurgens), is the most common pathogen of this plant species and causes yellow stunt and root rot. Although plant resistance to this disease has been identified, a better understanding of the nature of this resistance will help improve and optimize its implementation in standing milkvetch. The effects of A. gansuensis on the physiology of standing milkvetch were assessed in a 4-week study comparing a resistant plant variety, Shanxi, and a susceptible variety, Ningxia. In the first week, there was an obvious decrease in photosynthesis (P) in inoculated plants, especially in the susceptible variety, but there were no changes in stomatal conductance (Sc). From the second week on, P and Sc decreased progressively, and significant stem lesions were observed concomitantly. Water use efficiency (WUE) increased slightly in the second week but then decreased significantly from the third week. Physiological changes observed for the resistant variety of standing milkvetch were less dramatic than those of the susceptible variety. Hyphae were observed around inoculation lesions of the plants. Culture filtrate (CF) of A. gansuensis induced changes in extracellular pH and conductivity, especially in the susceptible variety samples. Tissue integrity changes in the plants correlated with the decrease in P. Secondary metabolite compounds were extracted from the plants and 21 types of compounds were identified. The composition and proportion of secondary metabolites were markedly altered by the pathogen, and these differences may indicate potential mechanisms of disease resistance to A. gansuensis in standing milkvetch. [ABSTRACT FROM AUTHOR]

Cyclic peptides are versatile therapeutic agents that boast high binding affinity, minimal toxicity, and the potential to engage challenging protein targets. However, the pharmaceutical utility of cyclic peptides is limited by their low membrane permeability—an essential indicator of oral bioavailability and intracellular targeting. Current machine learning-based models of cyclic peptide permeability show variable performance owing to the limitations of experimental data. Furthermore, these methods use features derived from the whole molecule that have traditionally been used to predict small molecules and ignore the unique structural properties of cyclic peptides. This study presents CycPeptMP: an accurate and efficient method to predict cyclic peptide membrane permeability. We designed features for cyclic peptides at the atom-, monomer-, and peptide-levels and seamlessly integrated these into a fusion model using deep learning technology. Additionally, we applied various data augmentation techniques to enhance model training efficiency using the latest data. The fusion model exhibited excellent prediction performance for the logarithm of permeability, with a mean absolute error of |$0.355$| and correlation coefficient of |$0.883$|⁠. Ablation studies demonstrated that all feature levels contributed and were relatively essential to predicting membrane permeability, confirming the effectiveness of augmentation to improve prediction accuracy. A comparison with a molecular dynamics-based method showed that CycPeptMP accurately predicted peptide permeability, which is otherwise difficult to predict using simulations. [ABSTRACT FROM AUTHOR]

Klebsiella pneumoniae , a highly prevalent Gram-negative bacterium, is widely known for causing nosocomial infections, leading to various diseases including systemic infections and fever. In traditional medicine, Launaea nudicaulis (L.) Hook. f. (Asteraceae), is often used to alleviate fever caused by bacterial infections. This study aimed to assess the antibacterial efficacy of the key phytochemicals present in the extract of L. nudicaulis against a panel of K. pneumoniae isolates. Three main constituents were isolated from this plant: cichorin (1), methyl-3,5-di- O -caffeoylquinate (syn. macranthoin G) (2), and cynaroside (3). Among these compounds, macranthoin G demonstrated notable antibacterial activity, with minimum inhibitory concentrations ranging from 64 to 256 µg/mL. It was found to inhibit the growth of the tested isolates and significantly affect the integrity of their cell membranes in 65.2 % of cases. Moreover, it increased the permeability of both the inner and outer membranes in 60.87 % and 52.17 % of K. pneumoniae isolates, respectively. Docking studies revealed that it exhibited strong binding scores to LpxC and FabI enzymes, with significant interactions occurring with key amino acids in their active sites. Based on these findings, macranthoin G shows promise as a potential antimicrobial drug, warranting further research to validate its antimicrobial and pharmacokinetic properties. [Display omitted] • Three main components were isolated from Launaea naudicaulis. • The isolated compounds are cichorin, macranthoin G, and cynaroside. • Macranthoin G exhibited notable antibacterial action. • It impaired the inner and outer membrane integrity of Klebsiella pneumoniae. • It showed significant docking scores and interactions with LpxC and FabI enzymes. [ABSTRACT FROM AUTHOR]

The characterization of phospholipid membrane permeability for small molecules is crucial for many applications in drug discovery and biomedical research in general. Here, chemosensor‐laden vesicles offer an attractive platform for permeability assays. In this work, the stability of immobilized chemosensor‐filled vesicles is explored on anti‐fouling polymer brush surfaces for potential use in monitoring small molecule membrane permeability. The study focuses on the development of a method for immobilizing sensor‐loaded vesicles into arbitrary patterns on surfaces and characterizing their stability under changing temperatures and compositions. As substrate to enable intact, long‐term stable vesicle immobilization reactive polymer brushes with anti‐fouling properties are used. Utilizing microchannel cantilever spotting, biotin moieties are introduced on the polymer brush surface, enabling stable tethering of vesicles through streptavidin‐biotin interactions. The immobilized vesicles are monitored through fluorescence microscopy for their response to analytes under changing environmental parameters and vesicle composition. A higher stability of immobilized vesicles compared to free‐floating ones is observed, with permeability only at elevated temperatures. By tuning vesicle compositions, permeability at lower temperatures can be raised again. Overall, the study provides insights into a novel approach for vesicle immobilization, showcasing the potential of surface‐bound vesicles for applications in microfluidic systems and as biosensors in various assays. [ABSTRACT FROM AUTHOR]

Heavy metals stress particularly cadmium contamination is hotspot among researchers and considered highly destructive for both plants and human health. Iron is examined as most crucial element for plant development, but it is available in inadequate amount because they are present in insoluble Fe3+ form in soil. Fe3O4 have been recently found as growth promoting factor in plants. To understand, a sand pot experiment was conducted in completely randomized design (control, cadmium, 20 mg/L Fe3O4 nanoparticles,40 mg/L Fe3O4 nanoparticles, 20 mg/L Fe3O4 nanoparticles + cadmium, 40 mg/L Fe3O4 nanoparticles + cadmium) to study the mitigating role of Fe3O4 nanoparticles on cadmium stress in three Raphanus sativus cultivars namely i.e., MOL SANO, MOL HOL PARI, MOL DAQ WAL. The plant growth, physiological and biochemical parameters i.e.,shoot length, shoot fresh weight, shoot dry weight, root length, root fresh and dry weight, MDA content, soluble protein contents, APX, CAT, POD activities and ion concentrations, membrane permeability, chlorophyll a, chlorophyll b and anthocyanin content, respectively were studied. The results displayed that cadmium stress remarkably reduces all growth, physiological and biochemical parameters for allcultivars under investigation. However, Fe3O4 nanoparticles mitigated the adverse effect of cadmium by improving growth, biochemical and physiological attributes in all radish cultivars. While, 20 mg/L Fe3O4 nanoparticles have been proved to be more useful against cadmium stress. The outcome of present investigation displayed that Fe3O4 nanoparticles can be utilized for mitigating heavy metal stress. [ABSTRACT FROM AUTHOR]

Electroporation techniques have emerged as attractive tools for intracellular delivery, rendering promising prospects towards clinical therapies. Transient disruption of membrane permeability is the critical process for efficient electroporation‐based cargo delivery. However, smart nanotools for precise characterization of transient membrane changes induced by strong electric pulses are extremely limited. Herein, multivalent membrane‐anchored fluorescent nanoprobes (MMFNPs) that take advantages of flexible functionalization and spatial arrangement of DNA frameworks are developed for in situ evaluation of electric field‐induced membrane permeability during reversible electroporation. Single‐molecule fluorescence imaging techniques are adopted to precisely verify the excellent analytical performance of the engineered MMFNPs. Benefited from tight membrane anchoring and sensitive adenosine triphosphate (ATP) profiling, varying degrees of membrane disturbances are visually exhibited under different intensities of the microsecond pulse electric field (µsPEF). Significantly, the dynamic process of membrane repair during reversible electroporation is well demonstrated via ATP fluctuations monitored by the designed MMFNPs. Furthermore, molecular dynamics (MD) simulations are performed for accurate verification of electroporation‐driven dynamic cargo entry via membrane nanopores. This work provides an avenue for effectively capturing transient fluctuations of membrane permeability under external stimuli, offering valuable guidance for developing efficient and safe electroporation‐driven delivery strategies for clinical diagnosis and therapeutics. [ABSTRACT FROM AUTHOR]

Background: This study aimed to investigate the potential relationship between bone morphogenetic protein 7 (BMP-7) and peritoneal permeability, as well as clinical outcomes. Methods: We conducted a cross-sectional study involving 67 peritoneal dialysis (PD) patients who had been on PD for at least 1 year. We measured BMP-7 levels in both plasma and PD effluent fluid. Two peritoneal equilibration tests, the first and last ones, were compared to assess alterations in peritoneal membrane permeability. Dialysate to plasma ratio for creatinine (DPRC) was used to define membrane permeability. BMP-7 level was measured concurrently in both plasma and PD effluent. Results: Among the patients, 81% (n = 51) were on ambulatory PD, while 19% (n = 12) were on automated PD. The average PD duration was 58.9 months. Increased DPRC was determined in 61.9% of the patients. There was a positive correlation between plasma BMP-7 levels and the change in DPRC (r = 0.323, P = .004). No correlation was determined between effluent BMP-7 levels and changes in DPRC. A statistically significant negative correlation was determined between plasma BMP-7 levels and serum albumin levels (r = -0.274, P = .02). Plasma BMP-7 levels independently predicted changes in DPRC (P = .02), while effluent BMP-7 levels did not (P = .212). Conclusion: We identified a correlation between plasma BMP-7 level and changes in peritoneal membrane permeability. However, we did not find any relationship with the PD clinical outcomes. Plasma BMP-7 levels can serve as a parameter for predicting alterations in permeability. [ABSTRACT FROM AUTHOR]

Ultrasonic-mediated plasmid transformation is a promising microbial transformation strategy with broad application prospects that has attracted interest across various fields. Limited research exists on developing a quantitative model to understand the relationship between transformation efficiency and ultrasonic power. Within the ultrasonic range that did not damage plasmids, the maximum transformation efficiency reached at 4.84 × 105 CFU/μg DNA. A kinetic model based on changes in membrane permeability was utilized to determine the membrane permeability at different power levels. The results indicated a linear correlation between ultrasonic power, transformation efficiency, and membrane permeability within a specific range. A quantitative relationship model was established based on ultrasonic power and transformation efficiency in E. coli. Electron microscopy revealed that E. coli cells subjected to ultrasonic treatment exhibited pore formation and cellular expansion. Furthermore, the integrity of the bacterial membrane was compromised as ultrasonic power increased. Nine genes associated with the functional terms of cell membrane components and transmembrane transport were identified in E. coli DH5α. According to qRT-PCR results, genes with these functions (including cusC, uidC, tolQ, tolA, ompC, yaiY) play crucial roles in ultrasound-mediated transformation of E. coli DH5α. This study suggested that ultrasound-mediated transformation in E. coli DH5α is not a simple physical–chemical process but rather involves the regulation of responsive membrane-related genes. This research establishes the groundwork for future comprehensive investigations into the molecular mechanism of ultrasound-mediated transformation and provides insights for the application of ultrasound technology in genetic engineering and related fields.

Background: Atractylodin and β-eudesmol are the major constituents of Atractylodes lancea (Thunb.) D.C. (AL) which have been demonstrated potential activities against cholangiocarcinoma in a series of in vitro and in vivo studies. Purpose: The study investigated their membrane permeability properties and effects on the efflux transporter P-glycoprotein (P-gp) using a Caco-2 cell monolayer. Methods: The transport and modulatory effects of both compounds on the expression of MDR-1 mRNA and protein, including P-gp function were investigated using the Caco-2 cells, RT-PCR, western blot analysis, and Rhodamine 123 (R123) assay, respectively. Results: The efflux ratio of atractylodin and β-eudesmol (50–200 µM) was higher than 2, indicating the predominant efflux transport of both compounds compared with the influx transport. However, neither of the compounds were P-gp inhibitors nor modulators of the expression of MDR-1 mRNA, and P-gp function. Only a slight inhibitory effect was observed with atractylodin exposure at 160 µM for 24 hrs. Conclusion: The low permeability of both compounds across the Caco-2 cell monolayer in both directions may lead to inadequate concentrations in the target cells, which may limit the clinical use of AL in cholangiocarcinoma treatment. Concurrent administration of both compounds and substrates of P-gp is not a clinical concern since neither compound is an inhibitor of P-gp in Caco-2 monolayers.

Antibiotic-resistant strains of Staphylococcus aureus are being viewed as a serious threat by various public health agencies. Identifying novel targets in this important pathogen is crucial to the development of new effective antibacterial formulations. We investigated the antibacterial effect of a colloidal nanosilver formulation, Silversol®, against an antibiotic-resistant strain of S. aureus using appropriate in vitro assays. Moreover, we deciphered the molecular mechanisms underlying this formulation's anti-S. aureus activity using whole transcriptome analysis. Lower concentrations of the test formulation exerted a bacteriostatic effect against this pathogen, and higher concentrations exerted a bactericidal effect. Silversol® at sub-lethal concentration was found to disturb multiple physiological traits of S. aureus such as growth, antibiotic susceptibility, membrane permeability, efflux, protein synthesis and export, biofilm and exopolysaccharide production, etc. Transcriptome data revealed that the genes coding for transcriptional regulators, efflux machinery, transferases, β-lactam resistance, oxidoreductases, metal homeostasis, virulence factors, and arginine biosynthesis are expressed differently under the influence of the test formulation. Genes (argG and argH) involved in arginine biosynthesis emerged among the major targets of Silversol®'s antibacterial activity against S. aureus. [ABSTRACT FROM AUTHOR]

The root dielectric response was measured on a minute scale to assess its efficiency for monitoring short-term cadmium (Cd) toxicity non-destructively. Electrical capacitance (CR), dissipation factor (DR) and electrical conductance (GR) were detected during the 24 to 168 h after Cd treatment (0, 20, 50 mg Cd2+ kg–1 substrate) in potted maize, cucumber and pea. Stress was also evaluated by measuring leaf chlorophyll content, Fv/Fm and stomatal conductance (gs) in situ, and shoot and root mass and total root length after harvest. CR showed a clear diurnal pattern, reflecting the water uptake rate, and decreased significantly in response to excessive Cd due to impeded root growth, the reduced tissue permittivity caused by accelerated lignification, and root ageing. Cd exposure markedly increased DR, indicating greater conductive energy loss due to oxidative membrane damage and enhanced electrolyte leakage. GR, which was coupled with root hydraulic conductance and varied diurnally, was increased transiently by Cd toxicity due to enhanced membrane permeability, but declined thereafter owing to stress-induced leaf senescence and transpiration loss. The time series of impedance components indicated the comparatively high Cd tolerance of the applied maize and the sensitivity of pea cultivar, which was confirmed by visible shoot symptoms, repeated physiological investigations and biomass measurements. The results demonstrated the potential of single-frequency dielectric measurements to follow certain aspects of the stress response of different species on a fine timescale without plant injury. The approach can be combined with widely used plant physiological methods and could contribute to breeding crop genotypes with improved stress tolerance. [ABSTRACT FROM AUTHOR]

Summary: In developing countries, fresh fruit juices are prepared and sold without ongoing assessment of the quality and safety of mulberry and carrot juices. Therefore, most fruit juices offered for consumption had high microbial content. This investigation was performed to indicate the efficacy of low concentrations of Cinnamomum verum essential oils (CEO) in the inactivation of E. faecalis and S. aureus in carrot juice and white mulberry juice and the impact on the sensorial characteristics of the juices. CEO antimicrobial activity can prevent the growth of Staphylococcus aureus and Enterococcus faecalis at 12 and 4 °C in juices. For the MIC and MBC concentrations, CEO exhibited higher antibacterial effects against S. aureus and E. faecalis. A higher number of pathogens were inactivated at 12 °C than at 4 °C. Cytoplasmic membrane permeability plays a vital role in the CEO bactericidal action. CEO can be recommended to extend the shelf‐life of juices by retaining the sensorial quality and inactivating pathogenic microorganisms, which provides a reference for practical production and application. [ABSTRACT FROM AUTHOR]

Abstract The characterization of phospholipid membrane permeability for small molecules is crucial for many applications in drug discovery and biomedical research in general. Here, chemosensor‐laden vesicles offer an attractive platform for permeability assays. In this work, the stability of immobilized chemosensor‐filled vesicles is explored on anti‐fouling polymer brush surfaces for potential use in monitoring small molecule membrane permeability. The study focuses on the development of a method for immobilizing sensor‐loaded vesicles into arbitrary patterns on surfaces and characterizing their stability under changing temperatures and compositions. As substrate to enable intact, long‐term stable vesicle immobilization reactive polymer brushes with anti‐fouling properties are used. Utilizing microchannel cantilever spotting, biotin moieties are introduced on the polymer brush surface, enabling stable tethering of vesicles through streptavidin‐biotin interactions. The immobilized vesicles are monitored through fluorescence microscopy for their response to analytes under changing environmental parameters and vesicle composition. A higher stability of immobilized vesicles compared to free‐floating ones is observed, with permeability only at elevated temperatures. By tuning vesicle compositions, permeability at lower temperatures can be raised again. Overall, the study provides insights into a novel approach for vesicle immobilization, showcasing the potential of surface‐bound vesicles for applications in microfluidic systems and as biosensors in various assays.

To study the antifungal effect and mechanism of linalool against Fusarium oxysporum FOX-1, the causative agent of ginger Fusarium wilt, the damaging effects of different concentrations of linalool on the mycelial growth, spore germination and cell membrane of F. oxysporum FOX-1, and its control effect on ginger Fusarium wilt were systemically investigated. The results showed that linalool could significantly inhibit the mycelial growth of F. oxysporum FOX-1 in a concentration-dependent manner, and the half maximal effective concentration (EC50) and the minimum inhibitory concentration (MICs) were 1.183 and 2 g/L, respectively. The spore concentration of F. oxysporum FOX-1 treated with linalool at MIC for 6 h was (1.43 ± 0.12) × 104 spores/mL, which was significantly lower than that of the control group ((5.79 ± 0.19) × 104 spores/mL) (P < 0.05), and the spore germination rate of F. oxysporum FOX-1 treated with linalool at MIC for 12 h was (5.83 ± 2.16)%, which was significantly lower than that of the control group ((95.12 ± 3.78)%) (P < 0.05). Treatment with linalool at 1/2 MIC and MIC damaged the integrity of the cell membrane, resulting in a significant increase in relative electrical conductivity and nucleic acid leakage in the mycelial suspension and malondialdehyde (MDA) content in the mycelium, and a significant decrease in ergosterol content, finally weakening the pathogenicity of the fungus. No lesions appeared on ginger pieces after treatment with linalool at MIC for 3 days. In conclusion, linalool affects the normal physiological function of F. oxysporum FOX-1 by inhibiting its spore germination and mycelial growth and destroying its cellular structure. This study provides a new direction for the effective control of Fusarium wilt.

Abstract Membrane permeability is an in vitro parameter that represents the apparent permeability (Papp) of a compound, and is a key absorption, distribution, metabolism, and excretion parameter in drug development. Although the Caco-2 cell lines are the most used cell lines to measure Papp, other cell lines, such as the Madin-Darby Canine Kidney (MDCK), LLC-Pig Kidney 1 (LLC-PK1), and Ralph Russ Canine Kidney (RRCK) cell lines, can also be used to estimate Papp. Therefore, constructing in silico models for Papp estimation using the MDCK, LLC-PK1, and RRCK cell lines requires collecting extensive amounts of in vitro Papp data. An open database offers extensive measurements of various compounds covering a vast chemical space; however, concerns were reported on the use of data published in open databases without the appropriate accuracy and quality checks. Ensuring the quality of datasets for training in silico models is critical because artificial intelligence (AI, including deep learning) was used to develop models to predict various pharmacokinetic properties, and data quality affects the performance of these models. Hence, careful curation of the collected data is imperative. Herein, we developed a new workflow that supports automatic curation of Papp data measured in the MDCK, LLC-PK1, and RRCK cell lines collected from ChEMBL using KNIME. The workflow consisted of four main phases. Data were extracted from ChEMBL and filtered to identify the target protocols. A total of 1661 high-quality entries were retained after checking 436 articles. The workflow is freely available, can be updated, and has high reusability. Our study provides a novel approach for data quality analysis and accelerates the development of helpful in silico models for effective drug discovery. Scientific Contribution: The cost of building highly accurate predictive models can be significantly reduced by automating the collection of reliable measurement data. Our tool reduces the time and effort required for data collection and will enable researchers to focus on constructing high-performance in silico models for other types of analysis. To the best of our knowledge, no such tool is available in the literature.

This study explores the combined toxic effect of Mn(II) and resorcinol (0.01 n and 0.2 n) on duckweed (Lemna minor). During the acute experiments, the plants released electrolytes into the aquatic environment after 30 min of exposure to the toxicants, indicating a disruption of tissue permeability as a test response. The experiments showed that the toxicity of the equinormal mixtures of resorcinol and Mn(II) (0.2 n each) increased relative to their single solutions. This was observed both in the freshly prepared solutions and in the solutions stored for 20 h prior to the experiments. The change in the UV absorption spectra indicates that there was complexation or other interaction between resorcinol and Mn(II) at equinormal concentrations (0.01 n). At the Mn(II) : resorcinol ratio of 1:20 (0.01 n Mn(II) and 0.2 n resorcinol), the toxicity of the system to duckweed decreased compared to the separate effects of these substances. The results obtained highlight the importance of considering the interactions between heavy metals and phenolic compounds when assessing the quality of aquatic environments.

This paper reports the development of a highly crosslinked hyper-branched polyglycerol (HPG) polymer bound to elastin-like proteins (ELPs) to create a membrane that undergoes a distinct closed-to-open permeation transition at 32 °C. The crosslinked HPG forms a robust, mesoporous structure (150–300 nm pores), suitable for selective filtration. The membranes were characterized by FTIR, UV–visible spectroscopy, SEM, and AFM, revealing their structural and morphological properties. Incorporating a synthetic polypeptide introduced thermo-responsive behavior, with the membrane transitioning from impermeable to permeable above the lower critical solution temperature (LCST) of 32 °C. Permeation studies using crystal violet (CV) demonstrated selective transport, where CV permeated only above 32 °C, while water permeated at all temperatures. This hybrid HPG-ELP membrane system, acting as a molecular switch, offers potential for applications in drug delivery, bioseparations, and smart filtration systems, where permeability can be controlled by temperature.

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Stenotrophomonas maltophilia are ubiquitous Gram-negative bacteria found in both natural and clinical environments. It is a remarkably adaptable species capable of thriving in various environments, thanks to the plasticity of its genome and a diverse array of genes that encode a wide range of functions. Among these functions, one notable trait is its remarkable ability to resist various antimicrobial agents, primarily through mechanisms that regulate the diffusion across cell membranes. We have investigated the Mla ABC transport system of S. maltophilia, which in other Gram-negative bacteria is known to transport phospholipids across the periplasmand is involved inmaintaining outer membrane homeostasis. First, we structurally and functionally characterized the periplasmic substrate-binding protein MlaC, which determines the specificity of this system. The predicted structure of the S. maltophilia MlaC protein revealed a hydrophobic cavity of sufficient size to accommodate the phospholipids commonly found in this species. Moreover, recombinant MlaC produced heterologously demonstrated the ability to bind phospholipids. Gene knockout experiments in S. maltophilia K279a revealed that the Mla system is involved in baseline resistance to antimicrobial and antibiofilm agents, especially those with divalent-cation chelating activity. Co-culture experiments with Pseudomonas aeruginosa also showed a significant contribution of this system to the cooperation between both species in the formation of polymicrobial biofilms. As suggested for other Gram-negative pathogenic microorganisms, this system emerges as an appealing target for potential combined antimicrobial therapies. [ABSTRACT FROM AUTHOR]

Bacillus thuringiensis Vip3 toxins form a tetrameric structure crucial for their insecticidal activity. Each Vip3Aa monomer comprises five domains. Interaction of the first four α-helices in domain I with the target cellular membrane was proposed to be a key step before pore formation. In this study, four N-terminal α-helix-deleted truncations of Vip3Aa were produced and, it was found that they lost both liposome permeability and insecticidal activity against Spodoptera litura. To further probe the role of domain I in membrane permeation, the full-length domain I and the fragments of N-terminal α-helix-truncated domain I were fused to green fluorescent protein (GFP), respectively. Only the fusion carrying the full-length domain I exhibited permeability against artificial liposomes. In addition, seven Vip3Aa-Cry1Ac fusions were also constructed by combination of α-helices from Vip3Aa domains I and II with the domains II and III of Cry1Ac. Five of the seven combinations were determined to show membrane permeability in artificial liposomes. However, none of the Vip3Aa-Cry1Ac combinations exhibited insecticidal activity due to the significant reduction in proteolytic stability. These results indicated that the N-terminal helix α1 in the Vip3Aa domain I is essential for both insecticidal activity and liposome permeability and that domain I of Vip3Aa preserved a high liposome permeability independently from domains II–V. [ABSTRACT FROM AUTHOR]

Aims We aimed to analyze the behavior of cellular glutathione of Streptococcus thermophilus strain YIT 2001 (ST-1) in the gastrointestinal environment to understand how orally administered glutathione in ST-1 cells is delivered stably to the intestine in a reactive form, which is essential for its systemic bioavailability against lipid peroxidation. Methods and results Intracellular glutathione was labeled with L-cysteine-containing stable isotopes. ST-1 cells from fresh culture or lyophilized powder were treated with simulated gastric and intestinal juices for 60 min each. The release of intracellular glutathione in digestive juices was quantified via LC–MS/MS. Most of the cellular glutathione was retained in the gastric environment and released in response to exposure to the gastrointestinal environment. During digestion, the membrane permeability of propidium iodide increased significantly, especially when cells were exposed to cholate, without change in the cell wall state. Conclusions ST-1 cells act as vehicles to protect intracellular reactive components, such as glutathione, from digestive stress, and release them in the upper intestine owing to the disruption of membrane integrity induced by bile acid. [ABSTRACT FROM AUTHOR]

Membrane distillation (MD) is a separation technology for many industries including desalination, pharmaceuticals, and food processing. However, MD technology readiness has not reached the required level to penetrate the desalination and water treatment market. One of the challenges to commercialization is the limited development and inaccurate assessment of MD-specific membranes. In fact, measuring the performance of MD membranes is challenging because it is dependent on process parameters, making it difficult to separate the individual influences of the process operating conditions and the membranes’ intrinsic properties. These shortcomings drive the need for a standardized methodology to compare and report membrane performance independently of the process parameters. In this work, we propose a standardized methodology for measuring the permeance of MD membranes using a reduced scale direct contact membrane distillation (DCMD) setup. This methodology has the potential to streamline membrane assessment and support ongoing efforts in MD membrane development and process scale-up.

Abstract Background There is a global need to develop new therapies to treat infectious diseases and tackle the rise in antimicrobial resistance. To date, the larvae of the Black Solider Fly, Hermetia illucens, have the largest repertoire of antimicrobial peptides derived from insects. Antimicrobial peptides are of particular interest in the exploration of alternative antimicrobials due to their potent action and reduced propensity to induce resistance compared with more traditional antibiotics. Results The predicted attacin from H. illucens, Hill_BB_C10074, was first identified in the transcriptome of H. illucens populations that had been fed a plant-oil based diet. In this study, recombinant Hill_BB_C10074 (500 µg/mL), was found to possess potent antimicrobial activity against the serious Gram-negative pathogen, Pseudomonas aeruginosa. Sequence and structural homology modelling predicted that Hill_BB_C10074 formed a homotrimeric complex that may form pores in the Gram-negative bacterial outer membrane. In vitro experiments defined the antimicrobial action of Hill_BB_C10074 against P. aeruginosa and transmission electron microscopy and electrochemical impedance spectroscopy confirmed the outer membrane disruptive power of Hill_BB_C10074 which was greater than the clinically relevant antibiotic, polymyxin B. Conclusions Combining predictive tools with in vitro approaches, we have characterised Hill_BB_C10074 as an important insect antimicrobial peptide and promising candidate for the future development of clinical antimicrobials.

Listeria monocytogenes is a foodborne human pathogen responsible for severe listeriosis and poses a great threat to human health. Hence, controlling the growth of L. monocytogenes plays an important role in the prevention of food contamination. Listeria innocua is often studied experimentally as a substitute strain for L. monocytogenes. In order to better maintain the sensory properties and nutrients of foods and extend their shelf life, this study explored the antimicrobial effect and possible mechanism of high pressure processing (HPP) combined with lauroyl arginate ethyl ester hydrochloride (LAE) on L. innocua. The feasibility of applying the combined treatment as a preservative was also investigated in ham. The results showed that 12 mg/L LAE treatment for 60 minutes had a potent antimicrobial effect on L. innocua, achieving a bacterial reduction of 3.12 (lg (CFU/mL)). Under the combined action of HPP and LAE, the surface morphology of bacterial cells became more wrinkled and sunken, and intracellular contents leaked out, suggesting a severe change in cell membrane permeability. The combined treatment of HPP at 350 MPa for 5 min with 12 mg/L LAE reduced L. innocua count by 4.87 (lg (CFU/mL)), which was 3.25 and 3.54 (lg (CFU/mL)) higher than that achieved using HPP and LAE treatments alone, respectively, suggesting a synergistic antimicrobial effect. Such synergistic antimicrobial effect was also observed on ham inoculated with L. innocua. This study could provide a theoretical reference for controlling the contamination of foodborne pathogens in ready-to-eat meat products.

Curcumin (Cur) nanoparticles were prepared by subcritical water (SBCW) method and its membrane permeability was evaluated. The processing conditions for the preparation of curcumin nanoparticles were investigated in terms of its particle size distribution, polydispersity index (PDI) and zeta potential, and the prepared nanoparticles were characterized and evaluated for in vitro membrane permeability. The results showed that nanoparticles with a diameter of 166 nm and a drug loading of 70.2% were obtained under the conditions: SBCW temperature 120 ℃, receiving solvent temperature 0 ℃, subcritical water/receiving solution ratio 1:3 (V/V), 0.04 g/100 mL lactose as stabilizing agent, and 30% (V/V) ethanol as entrainer. Fourier transform infrared (FTIR) spectroscopy showed no structural changes in Cur. Scanning electron microscopy (SEM) showed that Cur nanoparticles were uniformly spherical in shape. Differential scanning calorimetry (DSC) analysis showed a decrease in the crystallinity of the nanoparticles. Cur nanoparticles exhibited excellent membrane permeability in vitro, and the permeation rate in the first two hours was 25 folds higher than that of free Cur. Furthermore, Cur nanoparticles exhibited good transmembrane capacity in rabbits and significantly enhanced the bioavailability of Cur. The preparation of Cur nanoparticles using subcritical water method has the advantages of high drug loading, good membrane permeability, no need for carriers, simple process, and green environmental protection.

Cyclodextrins (CDs) are known for their ability to extract lipid components from synthetic and biological membranes and therefore to induce an increase of membrane permeability. However, the effect of cholesterol (CHOL) content in the membrane on the CD permeabilizing effect was not considered yet. Given that an increase in CHOL content reduces the membrane permeability, the aim of this work was to reveal how CHOL would modulate the CDs effect on the membrane. Hence, liposomes made of dipalmitoyl phosphatidylcholine (DPPC) and various CHOL contents (DPPC/CHOL 100:10, 100:25, 100:50, and 100:100) encapsulating the hydrophilic fluorophore, sulforhodamine B (SRB), were prepared and exposed to the native CDs (α-CD, β-CD, γ-CD) and four β-CD derivatives: the randomly methylated-β-CD (RAMEB), the low methylated-β-CD (CRYSMEB), the hydroxypropyl-β-CD (HP-β-CD) and the sulfobutyl ether-β-CD (SBE-β-CD) at different CD/DPPC molar ratios (1:1, 10:1, and 100:1). The membrane permeability was monitored following the release of SRB with time. The results demonstrated that the CDs effect on the membrane depends on the CD type, CD concentration, and membrane CHOL content. The investigated CDs exhibited an instantaneous permeabilizing effect promoting vesicle leakage of SRB from the various membranes; this effect increased with CDs concentration. Among the studied CDs, α-CD, β-CD, and RAMEB were the most permeabilizing CDs on the different membranes. Similar modifications of SRB release from the various liposomal formulations were obtained with HP-β-CD, CRYSMEB, and SBE-β-CD. γ-CD was the less potent CD in affecting the membrane permeability. The CDs effect also depended on the CHOL content: at the CD/DPPC molar ratio (100:1), RAMEB and β-CD considerably permeabilized the membrane of high CHOL content (50%, 100%) while the remaining CDs showed a decreasing permeabilizing effect upon CHOL content membrane increase.

Nosodes are solutions prepared from pests, capable of controlling those same pests in crops. The use of these solutions in agriculture is an emerging technology for producing eco-friendly and inexpensive plant-based foods free from toxic compounds. The effects of applying nosodes to bean (Phaseolus vulgaris L.) crops before and after harvest were evaluated. The experiment was conducted in the field, with nosode 200CH applied once, three times, biweekly, and weekly from the flowering stage of the “Delgado” bean plant. The application of nosodes resulted in a 108% higher yield, 26% greater biomass, a 32% increase in root length, 34% more pods, and up to a 227% decrease in damaged pods compared to untreated plants. Furthermore, compared to the untreated plants, treated plants exhibited a 37% higher membrane stability and a phenolic content that was up to 27% higher in seeds and 22% higher in leaves. Plants under conventional management showed 61% less Diabrotica balteata (LeConte) incidence than nosode-treated ones. Seeds treated with nosodes exhibited a mortality in Zabrotes subfasciatus (Boh.) of up to 80%. This study highlights the use of nosodes in bean cultivation as an agronomic strategy to enhance seed production and quality, aiding producers in informed decision making about their application.

Alternaria gansuensis, a seed-borne fungus of standing milkvetch (Astragalus adsurgens), is the most common pathogen of this plant species and causes yellow stunt and root rot. Although plant resistance to this disease has been identified, a better understanding of the nature of this resistance will help improve and optimize its implementation in standing milkvetch. The effects of A. gansuensis on the physiology of standing milkvetch were assessed in a 4-week study comparing a resistant plant variety, Shanxi, and a susceptible variety, Ningxia. In the first week, there was an obvious decrease in photosynthesis (P) in inoculated plants, especially in the susceptible variety, but there were no changes in stomatal conductance (Sc). From the second week on, P and Sc decreased progressively, and significant stem lesions were observed concomitantly. Water use efficiency (WUE) increased slightly in the second week but then decreased significantly from the third week. Physiological changes observed for the resistant variety of standing milkvetch were less dramatic than those of the susceptible variety. Hyphae were observed around inoculation lesions of the plants. Culture filtrate (CF) of A. gansuensis induced changes in extracellular pH and conductivity, especially in the susceptible variety samples. Tissue integrity changes in the plants correlated with the decrease in P. Secondary metabolite compounds were extracted from the plants and 21 types of compounds were identified. The composition and proportion of secondary metabolites were markedly altered by the pathogen, and these differences may indicate potential mechanisms of disease resistance to A. gansuensis in standing milkvetch.

Abstract Background Recent achievements in cancer therapy are the use of alternating electrical fields at intermediate frequencies (100–300 kHz) and low intensities (1–3 V/cm), which specifically target cell proliferation while affecting different cellular activities depending on the frequency used. Methods In this article, we examine the effect of electric fields on spherical suspended cells and propose the combination of Daunorubicin, a chemotherapy agent widely used in the treatment of acute myeloid leukemia, with electric field exposure. U937 cells were subjected to an electric field with a frequency of 200 kHz and an intensity of 0.75 V/cm, or to a combination of Daunorubicin and electric field exposure, resulting in a significant reduction in cell proliferation. Furthermore, the application of an electric field to U937 cells increased Daunorubicin uptake. Results Apoptosis and DNA damage were induced by the electric field or in conjunction with Daunorubicin. Notably, normal cells exposed to an electric field did not show significant damage, indicating a selective effect on dividing cancer cells (U937). Moreover, the electric field affects the U937 cell line either alone or in combination with Daunorubicin. This effect may be due to increased membrane permeability. Conclusions Our findings suggest that the use of electric fields at intermediate frequencies and low intensities, either alone or in combination with Daunorubicin, has potential as a selective anti-cancer therapy for dividing cancer cells, particularly in the treatment of acute myeloid leukemia. Further research is needed to fully understand the underlying mechanisms and to optimize the use of this therapy.

The routes by which foreign objects enter cells is well studied; however, their fate following uptake has not been explored extensively. Following exposure to synchrotron-sourced (SS) terahertz (THz) radiation, reversible membrane permeability has been demonstrated in eukaryotic cells by the uptake of nanospheres; nonetheless, cellular localization of the nanospheres remained unclear. This study utilized silica core-shell gold nanospheres (AuSi NS) of diameter 50 ± 5 nm to investigate the fate of nanospheres inside pheochromocytoma (PC 12) cells following SS THz exposure. Fluorescence microscopy was used to confirm nanosphere internalization following 10 min of SS THz exposure in the range 0.5–20 THz. Transmission electron microscopy followed by scanning transmission electron microscopy energy-dispersive spectroscopic (STEM-EDS) analysis was used to confirm the presence of AuSi NS in the cytoplasm or membrane, as single NS or in clusters (22% and 52%, respectively), with the remainder (26%) sequestered in vacuoles. Cellular uptake of NS in response to SS THz radiation could have suitable applications in a vast number of biomedical applications, regenerative medicine, vaccines, cancer therapy, gene and drug delivery.

Stenotrophomonas maltophilia are ubiquitous Gram-negative bacteria found in both natural and clinical environments. It is a remarkably adaptable species capable of thriving in various environments, thanks to the plasticity of its genome and a diverse array of genes that encode a wide range of functions. Among these functions, one notable trait is its remarkable ability to resist various antimicrobial agents, primarily through mechanisms that regulate the diffusion across cell membranes. We have investigated the Mla ABC transport system of S. maltophilia, which in other Gram-negative bacteria is known to transport phospholipids across the periplasm and is involved in maintaining outer membrane homeostasis. First, we structurally and functionally characterized the periplasmic substrate-binding protein MlaC, which determines the specificity of this system. The predicted structure of the S. maltophilia MlaC protein revealed a hydrophobic cavity of sufficient size to accommodate the phospholipids commonly found in this species. Moreover, recombinant MlaC produced heterologously demonstrated the ability to bind phospholipids. Gene knockout experiments in S. maltophilia K279a revealed that the Mla system is involved in baseline resistance to antimicrobial and antibiofilm agents, especially those with divalent-cation chelating activity. Co-culture experiments with Pseudomonas aeruginosa also showed a significant contribution of this system to the cooperation between both species in the formation of polymicrobial biofilms. As suggested for other Gram-negative pathogenic microorganisms, this system emerges as an appealing target for potential combined antimicrobial therapies.

IntroductionMultidrug resistance in bacteria is a pressing concern, particularly among clinical isolates. Gram-negative bacteria like Salmonella employ various strategies, such as altering membrane properties, to resist treatment. Their two-membrane structure affects susceptibility to antibiotics, whereas specific proteins and the peptidoglycan layer maintain envelope integrity. Disruptions can compromise stability and resistance profile toward xenobiotics. In this study, we investigated the unexplored protein SanA’s role in modifying bacterial membranes, impacting antibiotic resistance, and intracellular replication within host cells.MethodsWe generated a sanA deletion mutant and complemented it in trans to assess its biological function. High-throughput phenotypic profiling with Biolog Phenotype microarrays was conducted using 240 xenobiotics. Membrane properties and permeability were analyzed via cytochrome c binding, hexadecane adhesion, nile red, and ethidium bromide uptake assays, respectively. For intracellular replication analysis, primary bone marrow macrophages served as a host cells model.ResultsOur findings demonstrated that the absence of sanA increased membrane permeability, hydrophilicity, and positive charge, resulting in enhanced resistance to certain antibiotics that target peptidoglycan synthesis. Furthermore, the sanA deletion mutant demonstrated enhanced replication rates within primary macrophages, highlighting its ability to evade the bactericidal effects of the immune system. Taking together, we provide valuable insights into a poorly known SanA protein, highlighting the complex interplay among bacterial genetics, membrane physiology, and antibiotic resistance, underscoring its significance in understanding Salmonella pathogenicity.

Copyright of Shipin Kexue/ Food Science is the property of Food Science Editorial Department and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Pre-exposure prophylaxis (PrEP) prevents HIV infection through the daily administration of anti-HIV drugs, such as Truvada combination tablets (a combination of emtricitabine (FTC) and tenofovir disoproxil fumarate (TDF)). However, since PrEP is not approved in Japan, generic drugs sold overseas are imported and used by individuals. Then, the present study investigated the pharmaceutical equivalence of two generic drugs of Truvada (Generic A and Generic B). Tablet properties were examined by X-ray diffraction and differential scanning calorimetry. The dissolution behaviors and membrane permeabilities of FTC and TDF were assessed by the dissolution test using the paddle method and a membrane permeation experiment using Caco-2 cell monolayers, respectively. The dissolution behaviors of FTC and TDF differed between Truvada and its generic drugs. Furthermore, the membrane permeation rates of FTC and TDF in Generic B were slower than those in Truvada, and the AUC of FTC in Generic B was significantly smaller than that in Truvada. Differences were observed in the dissolution behaviors and membrane permeabilities of FTC and TDF in generic drugs (particularly Generic B) from those in Truvada. Since there are concerns regarding the clinical implications of these results, further studies, including in vivo experiments, are needed to ensure the safety of generic drugs. [ABSTRACT FROM AUTHOR]

Chagas disease (CD) is a worldwide public health problem, and the drugs available for its treatment have severe limitations. Red propolis is a natural extract known for its high content of phenolic compounds and for having activity against T. cruzi. The aim of this study was to investigate the trypanocidal potential of red propolis to isolate, identify, and indicate the mode of action of the bioactive compounds. The results revealed that the total phenolic content was 15.4 mg GAE/g, and flavonoids were 7.2 mg QE/g. The extract was fractionated through liquid–liquid partitioning, and the trypanocidal potential of the samples was evaluated using the epimastigote forms of the Y strain of T. cruzi. In this process, one compound was characterized by MS, 1H, and 13C NMR and identified as vestitol. Cytotoxicity was evaluated employing MRC-5 fibroblasts and H9C2 cardiomyocytes, showing cytotoxic concentrations above 15.62 μg/mL and 31.25 μg/mL, respectively. In silico analyses were applied, and the data suggested that the substance had a membrane-permeation-enhancing effect, which was confirmed through an in vitro assay. Finally, a molecular docking analysis revealed a higher affinity of vestitol with farnesyl diphosphate synthase (FPPS). The identified isoflavan appears to be a promising lead compound for further development to treat Chagas disease. [ABSTRACT FROM AUTHOR]

Copyright of Shipin Kexue/ Food Science is the property of Food Science Editorial Department and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: There is a global need to develop new therapies to treat infectious diseases and tackle the rise in antimicrobial resistance. To date, the larvae of the Black Solider Fly, Hermetia illucens, have the largest repertoire of antimicrobial peptides derived from insects. Antimicrobial peptides are of particular interest in the exploration of alternative antimicrobials due to their potent action and reduced propensity to induce resistance compared with more traditional antibiotics. Results: The predicted attacin from H. illucens, Hill_BB_C10074, was first identified in the transcriptome of H. illucens populations that had been fed a plant-oil based diet. In this study, recombinant Hill_BB_C10074 (500 µg/mL), was found to possess potent antimicrobial activity against the serious Gram-negative pathogen, Pseudomonas aeruginosa. Sequence and structural homology modelling predicted that Hill_BB_C10074 formed a homotrimeric complex that may form pores in the Gram-negative bacterial outer membrane. In vitro experiments defined the antimicrobial action of Hill_BB_C10074 against P. aeruginosa and transmission electron microscopy and electrochemical impedance spectroscopy confirmed the outer membrane disruptive power of Hill_BB_C10074 which was greater than the clinically relevant antibiotic, polymyxin B. Conclusions: Combining predictive tools with in vitro approaches, we have characterised Hill_BB_C10074 as an important insect antimicrobial peptide and promising candidate for the future development of clinical antimicrobials. [ABSTRACT FROM AUTHOR]