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The potential use of Ligilactobacillus salivarius -derived bacteriocin for the control of L. monocytogenes was investigated. The purpose of the study was to explore the antibacterial action mode of crude bacteriocin C2-1 from Ligilactobacillus salivarius C2-1 against Listeria monocytogenes CICC 21633. The inhibition zone diameter of crude bacteriocin C2-1 was 27.82 ± 0.3 mm against L. monocytogenes CICC 21633, and the minimum inhibitory concentration (MIC) of bacteriocin C2-1was 13.98 μg/mL. Bacteriocin C2-1 significantly inhibited the normal growth of L. monocytogenes CICC21633, is sensitive to proteinase K, trypsin, and pepsin, and has good thermal stability and acid tolerance. The antibacterial mode of bacteriocin C2-1 against L. monocytogenes CICC 21633 was discussed based on changes in cell membrane permeability, integrity, and morphological structure of L. monocytogenes CICC 21633 by measuring the conductivity, UV-absorbing substance content and the observation via scanning electron microscopy, respectively. These results demonstrated that bacteriocin C2-1 affected the cell membrane permeability and integrity of L. monocytogenes CICC 21633, resulting in intracellular material leakage. Furthermore, bacteriocin-producing genes were identified in the genome sequence using antiSMASH and BAGEL4 assays. Bacteriocin C2-1 might be a good biological food preservative to prevent L. monocytogenes infestation. • Bacteriocin C2-1 has antimicrobial activity against Listeria monocytogenes CICC 21633. • Bacteriocin C2-1 can strongly inhibit the normal growth of Listeria monocytogenes CICC 21633. • High heat stability, pH tolerance, and protease sensitivity are all characteristics of bacteriocin C2-1. • The antibacterial action mode of bacteriocin C2-1 was studied against Listeria monocytogenes CICC 21633. • Whole-genome sequencing analysis revealed the presence of bacteriocin biosynthetic gene clusters in Lb. salivarius C2-1. [ABSTRACT FROM AUTHOR]

Values of cell membranes permeability coefficients for water and molecules of cryoprotective agents (CPAs) are the necessary characteristics for developing physical-mathematical models describing mass transfer processes through cell membranes in order to predict optimal cell cooling rates. We carried out a comparative analysis of the permeability coefficients of mouse oocyte membranes for molecules of water, ethylene glycol (EG), propane-1,2-diol (1,2-PD) and dimethyl sulfoxide (Me 2 SO), determined by applying the classical Kedem-Katchalsky model, which considers only the penetration of non-electrolyte molecules (water and CPA) through the membrane, and the model developed by us, which takes into account the transmembrane transfer of ions and the associated changes in the transmembrane electric potential. We shown that calculations based on the developed modified model provide lower values of the permeability coefficients of the oocyte membrane for water and CPA molecules. What is important that the obtained by our modified model permeability coefficients for water molecules do not depend on the type of cryoprotectant, while the application of the classical model both in our studies and works of other authors always gave different values of these coefficients in solutions with different cryoprotectants. Our modified model also makes it possible to determine the dynamics of the transmembrane electric potential of the cell under the conditions of transmembrane mass transfer and the duration of the membrane being influenced by the changes in electric potential, that is a parameter that can directly affect the viability of cells. • The physical-mathematical model for determining of cell's permeability coefficients considering transmembrane ion transfer. • Modified model makes it possible to determine the dynamics of the transmembrane potential during cryoprotectant penetration. • Maximum change in the transmembrane potential depend on the rate of the cryoprotectant penetration into the cell. • Our model provides values of permeability coefficients for water that do not depend on the type of cryoprotectant. [ABSTRACT FROM AUTHOR]

The aims of this study were to use metagenomics to reveal the fates of antibiotic resistance genes (ARGs) during composting under the regulation of peroxydisulfate and clarify the relationship between ARGs and cell membrane permeability. Results showed that peroxydisulfate increased cell membrane permeability by effectively regulating the expression of outer membrane protein and lipopolysaccharide related genes. Besides, it reduced polysaccharides and proteins in extracellular polymer substances by 36% and 58%, respectively, making it easier for intracellular ARGs (i-ARGs) to reach the extracellular environment, among which the absolute intracellular abundance of mphK , Erm(31) , and tet(44) decreased to 1.2, 1.0, and 0.89 fold of the control, respectively. Finally, variation partitioning analysis showed that i-ARGs dominated the removal of ARGs. These results revealed that the removal of i-ARGs by activated peroxydisulfate was the key to the removal of ARGs and increased cell membrane permeability played a key role for peroxydisulfate to remove i-ARGs during composting. [Display omitted] • The fates of ARGs in response to peroxydisulfate were revealed by metagenomics. • Peroxydisulfate promoted the degradation of extracellular polymeric substances. • Peroxydisulfate increased the permeability of cell membranes. • Increased membrane permeability led to more i-ARGs to extracellular environment. • The removal of i-ARGs dominated the removal of ARGs. [ABSTRACT FROM AUTHOR]

The interaction between Ras and SOS1 is an attractive and promising target in discovering candidate drugs for the Ras-driven cancers. Synthesized hydrocarbon-stapled peptides simulate αH helix structure of SOS1, improve proteolytical stability and enhance cell permeability. SSOSH-5 inhibited the proliferation of pan-Ras-mutated cancer cells and induce cell apoptosis. SSOSH-5 could regulate downstream signaling pathway, such as Ras-RAF-MEK-ERK and Ras-PI3K-AKT-mTOR. [Display omitted] • Ras is the most frequently mutated gene family in numerous cancers. • The interaction between Ras and SOS1 is an attractive and promising target in discovering candidate drugs for the Ras-driven cancers. • Synthesized hydrocarbon-stapled peptides simulate αH helix structure of SOS1, improve proteolytical stability and enhance cell permeability. • SSOSH-5 inhibited the proliferation of pan-Ras-mutated cancer cells and induce cell apoptosis. • SSOSH-5 could regulate downstream signaling pathway, such as Ras-RAF-MEK-ERK and Ras-P110-AKT-mTOR. Blocking the interaction between Ras and Son of Sevenless homolog 1 (SOS1) has been an attractive therapeutic strategy for treating cancers involving oncogenic Ras mutations. K-Ras mutation is the most common in Ras-driven cancers, accounting for 86%, with N -Ras mutation and H-Ras mutation accounting for 11% and 3%, respectively. Here, we report the design and synthesis of a series of hydrocarbon-stapled peptides to mimic the alpha-helix of SOS1 as pan-Ras inhibitors. Among these stapled peptides, SSOSH-5 was identified to maintain a well-constrained alpha-helical structure and bind to H-Ras with high affinity. SSOSH-5 was furthermore validated to bind with Ras similarly to the parent linear peptide through structural modeling analysis. This optimized stapled peptide was proven to be capable of effectively inhibiting the proliferation of pan-Ras–mutated cancer cells and inducing apoptosis in a dose-dependent manner by modulating downstream kinase signaling. Of note, SSOSH-5 exhibited a high capability of crossing cell membranes and strong proteolytic resistance. We demonstrated that the peptide stapling strategy is a feasible approach for developing peptide-based pan-Ras inhibitors. Furthermore, we expect that SSOSH-5 can be further characterized and optimized for the treatment of Ras-driven cancers. [ABSTRACT FROM AUTHOR]

It is well established that lipid aldehydes (LAs) are able to increase the permeability of cell membranes and induce their rupture. However, it is not yet clear how LAs are distributed in phase-separated membranes (PSMs), which are responsible for the transport of selected molecules and intracellular signaling. Thus, we investigate here the distribution of LAs in a PSM by coarse-grained molecular dynamics simulations. Our results reveal that LAs derived from mono-unsaturated lipids tend to accumulate at the interface between the liquid-ordered/liquid-disordered domains, whereas those derived from poly-unsaturated lipids remain in the liquid-disordered domain. These results are important for understanding the effects caused by oxidized lipids in membrane structure, properties and organization. [Display omitted] • Liquid-ordered (Lo) and liquid-disordered (Ld) phases coexist in cell membranes (lipid rafts). • The interface between the Lo/Ld domains is more susceptible to pore formation. • Lipid aldehydes (LAs) derived from mono-unsaturated lipids tend to accumulate at the interface between the Lo/Ld domains. • LAs derived from poly-unsaturated lipids remains in the Ld domain. [ABSTRACT FROM AUTHOR]