In the last decade,the rise of antibiotic resistance has heightened interest in antimicrobial peptides and lipopeptides as promising alternatives to conventional antibiotics because of their lower propensity to develo...In the last decade,the rise of antibiotic resistance has heightened interest in antimicrobial peptides and lipopeptides as promising alternatives to conventional antibiotics because of their lower propensity to develop resistance.However,lipopeptides often show undesired cytotoxicity due to their non-selective membrane disruptive effect,and their limited aqueous solubility represents a matter of concern from a pharmaceutical point of view.This study demonstrates a panel of ultrashort cationic lipopeptides(USCLs)consisting of a tetrapeptide(L1),originated from buforin II,coupled with saturated fatty acids of different lengths.Our results highlight that the 16-carbon fatty acid lipopeptide(Pal-L1)exhibits relevant antibacterial activity against multiresistant Staphylococcus aureus strain.However,the formation of heterogenic aggregates in cell culturemedium and toxic effects on human cells were also observed.Pal-L1 formulation with the randomly methylatedα-cyclodextrin(RAMEA)and the sulfobutylether-β-cyclodextrin(SBECD)has resulted in a production of ultralow-sized molecular dispersion systems and reduced lipopeptide toxicity without compromising its antimicrobial activity.With titration 1H-NMR,2D NMR experiments,together with molecular dynamics simulations,we described the size,structure,stoichiometry,and dissociation constant of the supramolecular complexes.Interactions of neutral and negatively chargedmodel liposomes with Pal-L1 lipopeptide in the presence or absence of cyclodextrins serve an explanation for the membrane selectivity,and based on the results,we proposed a potential mechanism of action for the Pal-L1+cyclodextrin complexes on different biological membranes.Overall,our model characterization points out that cyclodextrin formulation improves the therapeutical applicability of lipopeptides.展开更多
A T-shape tube hydraulic bulge test under axial feeding force is carried out to characterize the mechanical properties of EN AW 5049-O and 6060-O aluminium alloys.The punch displacement,T-branch height and axial compr...A T-shape tube hydraulic bulge test under axial feeding force is carried out to characterize the mechanical properties of EN AW 5049-O and 6060-O aluminium alloys.The punch displacement,T-branch height and axial compressive force are recorded online during the experiment.An intelligent inverse identification framework combining the finite element method and numerical optimization algorithm is developed to determine material parameters by fitting simulated results to the experimental data iteratively.The identified constitutive parameters using the inverse modelling technique are compared with those determined by the theoretical analysis and uniaxial tensile test.The comparison shows that the predicted bulge height and punch force based on the material parameters obtained by the three methods are different and the inverse strategy produces the smallest gap between numerical and experimental values.It is possible to conclude that the hydraulic bulge test can be applied to characterize the stress-strain curve of tubular materials at the large strain scope,and the automatic inverse framework is a more accurate post-processing procedure to identify material constitutive parameters compared with the classical analytical model.展开更多
基金The authors acknowledge the support of the Lendulet(Momentum)Programme of the Hungarian Academy of Sciences(Grant No.:LP2021-28)National Research,Development and Innovation Fund of Hungary(Grant Nos.:OTKA K142904,OTKA ANN 139484,KKP_22144180,TKP2021-EGA-31,and VEKOP-2.3.3-15-2016-00020)+2 种基金Marie-Skłodowska-Curie action(H2020-MSCA-ITN BactiVAX,grant agreement No.956758)CIBERES,an initiative of Instituto de Salud Carlos III(ISCIII,Madrid,Spain)Agencia Estatal Investigacion of Spain for the Severo Ochoa Center of Excellence Accreditation CEX2021-001136-S,funded by MCIN/AEI/10.13039/501100011033.
文摘In the last decade,the rise of antibiotic resistance has heightened interest in antimicrobial peptides and lipopeptides as promising alternatives to conventional antibiotics because of their lower propensity to develop resistance.However,lipopeptides often show undesired cytotoxicity due to their non-selective membrane disruptive effect,and their limited aqueous solubility represents a matter of concern from a pharmaceutical point of view.This study demonstrates a panel of ultrashort cationic lipopeptides(USCLs)consisting of a tetrapeptide(L1),originated from buforin II,coupled with saturated fatty acids of different lengths.Our results highlight that the 16-carbon fatty acid lipopeptide(Pal-L1)exhibits relevant antibacterial activity against multiresistant Staphylococcus aureus strain.However,the formation of heterogenic aggregates in cell culturemedium and toxic effects on human cells were also observed.Pal-L1 formulation with the randomly methylatedα-cyclodextrin(RAMEA)and the sulfobutylether-β-cyclodextrin(SBECD)has resulted in a production of ultralow-sized molecular dispersion systems and reduced lipopeptide toxicity without compromising its antimicrobial activity.With titration 1H-NMR,2D NMR experiments,together with molecular dynamics simulations,we described the size,structure,stoichiometry,and dissociation constant of the supramolecular complexes.Interactions of neutral and negatively chargedmodel liposomes with Pal-L1 lipopeptide in the presence or absence of cyclodextrins serve an explanation for the membrane selectivity,and based on the results,we proposed a potential mechanism of action for the Pal-L1+cyclodextrin complexes on different biological membranes.Overall,our model characterization points out that cyclodextrin formulation improves the therapeutical applicability of lipopeptides.
基金The first author was supported by China Scholarship Council(CSC)(201706080020)from the Ministry of Education of China and expresses his appreciation to CSC for their financial support。
文摘A T-shape tube hydraulic bulge test under axial feeding force is carried out to characterize the mechanical properties of EN AW 5049-O and 6060-O aluminium alloys.The punch displacement,T-branch height and axial compressive force are recorded online during the experiment.An intelligent inverse identification framework combining the finite element method and numerical optimization algorithm is developed to determine material parameters by fitting simulated results to the experimental data iteratively.The identified constitutive parameters using the inverse modelling technique are compared with those determined by the theoretical analysis and uniaxial tensile test.The comparison shows that the predicted bulge height and punch force based on the material parameters obtained by the three methods are different and the inverse strategy produces the smallest gap between numerical and experimental values.It is possible to conclude that the hydraulic bulge test can be applied to characterize the stress-strain curve of tubular materials at the large strain scope,and the automatic inverse framework is a more accurate post-processing procedure to identify material constitutive parameters compared with the classical analytical model.
