Eightfold Decrease Research Articles

Enhancing CFD solver with Machine Learning techniques

This study addresses the computational challenges in fluid flow simulations arising from demanding computational grids, required to capture the temporal and length scales involved. Our approach focuses on the pressure solver, as this is a resource-intensive component in Computational Fluid Dynamics (CFD) solvers. We achieve this by integrating a Machine Learning (ML) surrogate model with an incompressible fluid flow solver. We created two variants of an ML-enhanced CFD solver which were able to reduce the number of iterations required by the CFD pressure solver during unsteady flow simulations. Consequently, the simulations yielded comparable drag coefficients and Strouhal numbers, accompanied by an eightfold decrease in execution time. The performance enhancements are attributed to reduced computational effort per temporal iteration and early-stage forcing on the simulation dynamical behavior when using the ML-based surrogate models. This research introduces an approach to enhance the computational efficiency of fluid flow analyses by incorporating surrogate models to aid the pressure solver in CFD simulations. We propose a Hybrid CFD solver, ie. a physics-informed solver enhanced with data-driven surrogate models.

Comparison of the safety and efficacy of the wild-type and lpxL/lpxM mutant inactivated vaccine against the avian pathogenic Escherichia coli O1, O2, and O78 challenge

Avian pathogenic Escherichia coli (APEC) is primarily responsible for causing septicemia, pneumonitis, peritonitis, swollen head syndrome, and salpingitis in poultry, leading to significant losses in the poultry sector, particularly within the broiler industry. The removal of the lpxL and lpxM genes led to an eightfold decrease in the endotoxin levels of wild APEC strains. In this study, mutant strains of lpxL/lpxM and their O1, O2, and O78 wild-type strains were developed for an inactivated vaccine (referred to as the mutant vaccine and the wild-type vaccine, respectively), and the safety and effectiveness of these two prototype vaccines were assessed in white Leghorn chickens. Findings indicated that chickens immunized with the mutant vaccine showed a return of appetite sooner post-immunization and experienced earlier disappearance of nodules at the injection site compared to those immunized with the wild-type vaccine. Pathological examinations revealed that lesions were still present in the liver, lung, and injection site in chickens vaccinated with the wild-type vaccine 14 days post-vaccination (dpv), whereas no lesions were found in chickens vaccinated with the mutant vaccine at 14 dpv. There were no significant differences in antibody levels on the challenge day or in mortality or lesion scores between challenged birds immunized with either the mutant vaccine or the wild-type vaccine at the same dose. In this study, the safety of a single dose or overdose of the mutant vaccine and its efficacy at one dose were evaluated in broilers, and the results showed that the mutant vaccine had no adverse effects on or protected vaccinated broilers from challenge with the APEC O1, O2, or O78 strains. These results demonstrated that the mutant polyvalent inactivated vaccine is a competitive candidate against APEC O1, O2, and O78 infection compared to the wild-type vaccine.

Population Genomics of Domesticated Cucurbita ficifolia Reveals a Recent Bottleneck and Low Gene Flow with Wild Relatives

Cucurbita ficifolia is a squash grown from Mexico to Bolivia. Its ancestor is unknown, but it has limited compatibility with wild xerophytic Cucurbita from Mexico’s highlands. We assembled the reference genome of C. ficifolia and assessed the genetic diversity and historical demography of the crop in Mexico with 2524 nuclear single nucleotide polymorphisms (SNPs). We also evaluated the gene flow between C. ficifolia and xerophytic taxa with 6292 nuclear and 440 plastome SNPs from 142 individuals sampled in 58 sites across their area of sympatry. Demographic modelling of C. ficifolia supports an eight-fold decrease in effective population size at about 2409 generations ago (95% CI = 464–12,393), whereas plastome SNPs support the expansion of maternal lineages ca. 1906–3635 years ago. Our results suggest a recent spread of C. ficifolia in Mexico, with high genetic diversity (π = 0.225, FST = 0.074) and inbreeding (FIS = 0.233). Coalescent models suggest low rates of gene flow with C. radicans and C. pedatifolia, whereas ABBA-BABA tests did not detect significant gene flow with wild taxa. Despite the ecogeographic proximity of C. ficifolia and its relatives, this crop persists as a highly isolated lineage of puzzling origin.

Selected Properties of the Surface Layer of C45 Steel Samples after Slide Burnishing.

This paper presents the experimental results of a study investigating the impact of the machining fluid type, the variable factor, used in slide burnishing on 2D and 3D surface roughness; surface topography; Abbott-Firestone curve shape; microhardness; and SFE (surface free energy). In the experiment, pre-ground, ringed samples of C45 steel were used. The results showed an over eight-fold decrease in the value of the Ra (arithmetical mean deviation) parameter and over a five-fold decrease in the Rt (total height of profile) parameter in relation to their values after grinding. The parameters Rpk (reduced peak height), Rk (core roughness depth), and Rvk (reduced valley depth) were also reduced. The Abbott-Firestone curve after slide burnishing changed its angle of inclination (it was more flattened), and the material ratio Smr increased. The reduction in the Rpk and Rk parameters and increased material ratio will most likely contribute to restoring the functionality of these surfaces (increased resistance to abrasive wear). After slide burnishing, the maximum 25% increase in microhardness was obtained compared to the value after grinding, while the layer thickness was 20 μm. The surface energy of elements subjected to slide burnishing using various machining fluids slightly increased, or its value was close to that of the ground surface. The most favourable properties of the surface layer in terms of mating between two elements were obtained for a part that was slide-burnished with a mixture of oil + polymethyl methacrylate (PMM) + molybdenum disulphide (MoS2).

In vitro activity of new combinations of β-lactam and β-lactamase inhibitors against the Mycobacterium tuberculosis complex.

As meropenem-clavulanic acid is recommended for the treatment of drug-resistant tuberculosis, the repurposing of new carbapenem combinations may provide new treatment options, including oral alternatives. Therefore, we studied the in vitro activities of meropenem-vaborbactam, meropenem-clavulanic acid, and tebipenem-clavulanic acid. One hundred nine Mycobacterium tuberculosis complex (MTBC) clinical isolates were tested, of which 69 were pan-susceptible and the remaining pyrazinamide- or multidrug-resistant. Broth microdilution MICs were determined using the EUCAST reference method. Meropenem and tebipenem were tested individually and in combination with vaborbactam 8 mg/L and clavulanic-acid 2 and 4 mg/L, respectively. Whole-genome sequencing was performed to explore resistance mechanisms. Clavulanic acid lowered the modal tebipenem MIC approximately 16-fold (from 16 to 1 mg/L). The modal meropenem MIC was reduced twofold by vaborbactam compared with an approximately eightfold decrease by clavulanic acid. The only previously described high-confidence carbapenem resistance mutation, crfA T62A, was shared by a subgroup of lineage 4.3.4.1 isolates and did not correlate with elevated MICs. The presence of a β-lactamase inhibitor reduced the MTBC MICs of tebipenem and meropenem. The resulting MIC distribution was lowest for the orally available drugs tebipenem-clavulanic acid. Whether this in vitro activity translates to similar or greater clinical efficacy of tebipenem-clavulanic acid compared with the currently WHO-endorsed meropenem-clavulanic acid requires clinical studies. IMPORTANCE Repurposing of already approved antibiotics, such as β-lactams in combination with β-lactamase inhibitors, may provide new treatment alternatives for drug-resistant tuberculosis. Meropenem-clavulanic acid was more active in vitro compared to meropenem-vaborbactam. Notably, tebipenem-clavulanic acid showed even better activity, raising the potential of an all-oral treatment option. Clinical data are needed to investigate whether the better in vitro activity of tebipenem-clavulanic acid correlates with greater clinical efficacy compared with the currently WHO-endorsed meropenem-clavulanic acid.

Impact of Salinity, Elevated Temperature, and Their Interaction with the Photosynthetic Efficiency of Halophyte Crop Chenopodium quinoa Willd

Chenopodium quinoa is a genetically diverse crop that can adapt to a wide range of environments, including temperatures and salinities. However, only a few studies have assessed the combined effects of two or more environmental factors on C. quinoa. Here, we investigated the effects of salinity (300 mM NaCl), elevated temperature (35 °C), and their interaction with growth, water–salt balance, the efficiency of photosystem II (PSII), the activity of cyclic electron transport (CET) around photosystem I (PSI), Rubisco and PEPC enzyme content, and the expression of photosynthetic genes. We found that elevated temperature did not decrease the biomass but caused a significant increase in the water and potassium content of C. quinoa leaves. The decrease in PSII efficiency under elevated temperature was accompanied by an increase in the expression of genes encoding the components of PSII (psbA) and linear electron transport (FDI), as well as the main photosynthetic protein Rubisco (rbcL). Moreover, the strongest effect was induced by the combined effect of elevated temperature and salinity, which induced high oxidative stress (a threefold increase in MDA), a threefold decrease in the biomass, a twofold decrease in PSII efficiency, and a two- to eightfold decrease in the expression of the photosynthetic genes psbA, FDI, and rbcL. PSI was more tolerant to all forms of stress; however, the combined effect of elevated temperature and salinity downregulated the expression of PGR5 and FNR1, which may diminish the role of PGR5/PGRL1-dependent CET in favor of the NDH-dependent CET of PSI. The obtained data on the functioning of photosystems and the expression of photosynthetic genes under combined stress (elevated temperature and salinity) can make a significant contribution to understanding the mechanisms of tolerance of C. quinoa to multiple stresses under climate change conditions.

Doping of Transparent Electrode Based on Oriented Networks of Nickel in Poly(3,4-Ethylenedioxythiophene) Polystyrene Sulfonate Matrix with P-Toluenesulfonic Acid

This work aimed to obtain an optically transparent electrode based on the oriented nanonetworks of nickel in poly(3,4-ethylenedioxythiophene) polystyrene sulfonate matrix. Optically transparent electrodes are used in many modern devices. Therefore, the search for new inexpensive and environmentally friendly materials for them remains an urgent task. We have previously developed a material for optically transparent electrodes based on oriented platinum nanonetworks. This technique was upgraded to obtain a cheaper option from oriented nickel networks. The study was carried out to find the optimal electrical conductivity and optical transparency values of the developed coating, and the dependence of these values on the amount of nickel used was investigated. The figure of merit (FoM) was used as a criterion for the quality of the material in terms of finding the optimal characteristics. It was shown that doping PEDOT: PSS with p-toluenesulfonic acid in the design of an optically transparent electroconductive composite coating based on oriented nickel networks in a polymer matrix is expedient. It was found that the addition of p-toluenesulfonic acid to an aqueous dispersion of PEDOT: PSS with a concentration of 0.5% led to an eight-fold decrease in the surface resistance of the resulting coating.

The Synergistic Effect of Theranekron and Cisplatin on the Neuroblastoma (SH-SY5Y) Cell Line.

Neuroblastoma (NB), a pediatric tumor with high prevalence and mortality rates, was the focus of this investigation. This study aimed to assess the combined antitumor potential of theranekron (Trn) and cisplatin in this cell line. The interaction between theranekron (10-100 µM) and cisplatin (40 µM) was examined. The cytotoxicity of theranekron was evaluated using MTT assays, cell volume analyses, apoptosis assessments, and measurements of mitochondrial membrane potential. These evaluations were conducted over a 24-hour incubation period. The coadministration of 100 µM theranekron with cisplatin exhibited a cytotoxic effect of approximately 60%. Furthermore, it led to a reduction of up to 38% in cell volume. Notably, SH-SY5Y cells demonstrated an early apoptosis rate of 34.4%, accompanied by an eightfold decrease in mitochondrial membrane potential compared to the control group. Theranekron demonstrated synergism and significantly enhanced the efficacy of cisplatin (P 0.001). Nevertheless, further in-depth investigations are necessary to elucidate the intricacies of these synergistic effects.

Sequential Delivery of Novel Triple Drug Combination via Crosslinked Alginate/Lactoferrin Nanohybrids for Enhanced Breast Cancer Treatment.

While breast cancer remains a global health concern, the elaboration of rationally designed drug combinations coupled with advanced biocompatible delivery systems offers new promising treatment venues. Herein, we repurposed rosuvastatin (RST) based on its selective tumor apoptotic effect and combined it with the antimetabolite pemetrexed (PMT) and the tumor-sensitizing polyphenol honokiol (HK). This synergistic three-drug combination was incorporated into protein polysaccharide nanohybrids fabricated by utilizing sodium alginate (ALG) and lactoferrin (LF), inspired by the stealth property of the former and the cancer cell targeting capability of the latter. ALG was conjugated to PMT and then coupled with LF which was conjugated to RST, forming core shell nanohybrids into which HK was physically loaded, followed by cross linking using genipin. The crosslinked HK-loaded PMT-ALG/LF-RST nanohybrids exhibited a fair drug loading of 7.86, 5.24 and 6.11% for RST, PMT and HK, respectively. It demonstrated an eight-fold decrease in the IC50 compared to the free drug combination, in addition to showing an enhanced cellular uptake by MCF-7 cells. The in vivo antitumor efficacy in a breast cancer-bearing mouse model confirmed the superiority of the triple cocktail-loaded nanohybrids. Conclusively, our rationally designed triple drug-loaded protein/polysaccharide nanohybrids offer a promising, biocompatible approach for an effective breast tumor suppression.

Entropy-Driven Inclusion of Natural Protoberberine Alkaloids in Sulfobutylether-β-Cyclodextrin.

The understanding of the relationship between molecular structure and the thermodynamics of host-guest binding is essential for the rational design of the applications of inclusion complexes. To obtain insight into the factors governing the driving force of complex formation in aqueous solutions, the encapsulation of five pharmaceutically important protoberberine alkaloids was studied in sulfobutylether-β-cyclodextrin having on average 6.4 degrees of substitution (SBE6.4βCD). Spectrophotometric, fluorescence spectroscopic, and isothermal calorimetric measurements showed 1:1 complexation in dilute solutions. From 1.92 × 104 M−1, about an eight-fold decrease of the association constant was observed in the series of berberine ≈ coptisine >> palmatine > epiberberine > dehydrocorydaline. The embedment of these alkaloids in the SBE6.4βCD cavity was entropy-controlled with mildly negative enthalpy contributions. These findings suggest that the stabilization of the examined complexes arises primarily from the hydrophobic interaction between the constituents. The more than three orders of magnitude smaller association constants of protoberberine alkaloids with SBE6.4βCD than with cucurbit[7]uril, a host having similar cavity size, originates from the much smaller exothermicity of the confinement in the former macrocycle.

Developing Porous Ortho- and Pyrophosphate-Containing Glass Microspheres; Structural and Cytocompatibility Characterisation.

Phosphate-based glasses (PBGs) are promising materials for bone repair and regeneration as they can be formulated to be compositionally similar to the inorganic components of bone. Alterations to the PBG formulation can be used to tailor their degradation rates and subsequent release of biotherapeutic ions to induce cellular responses, such as osteogenesis. In this work, novel invert-PBGs in the series xP2O5·(56 - x)CaO·24MgO·20Na2O (mol%), where x is 40, 35, 32.5 and 30 were formulated to contain pyro (Q1) and orthophosphate (Q0) species. These PBGs were processed into highly porous microspheres (PMS) via flame spheroidisation, with ~68% to 75% porosity levels. Compositional and structural analysis using EDX and 31P-MAS NMR revealed that significant depolymerisation occurred with reducing phosphate content which increased further when PBGs were processed into PMS. A decrease from 50% to 0% in Q2 species and an increase from 6% to 35% in Q0 species was observed for the PMS when the phosphate content decreased from 40 to 30 mol%. Ion release studies also revealed up to a four-fold decrease in cations and an eight-fold decrease in phosphate anions released with decreasing phosphate content. In vitro bioactivity studies revealed that the orthophosphate-rich PMS had favourable bioactivity responses after 28 days of immersion in simulated body fluid (SBF). Indirect and direct cell culture studies confirmed that the PMS were cytocompatible and supported cell growth and proliferation over 7 days of culture. The P30 PMS with ~65% pyro and ~35% ortho phosphate content revealed the most favourable properties and is suggested to be highly suitable for bone repair and regeneration, especially for orthobiologic applications owing to their highly porous morphology.

Demonstration of the efficacy of curcumin on carbapenem-resistant Pseudomonas aeruginosa with Galleria mellonella larvae model.

Due to increasing antimicrobial resistance, studies where new treatment options are investigated along with the synergistic effects of natural products with antibiotics have arisen. Pseudomonas aeruginosa (P. aeruginosa) is an opportunistic pathogen and infection with multi-drug resistant (MDR) P. aeruginosa poses a critical problem during treatment. Curcumin (CUR) is listed in the literature as one of the promising natural ingredients with its strong antimicrobial activity. In our study, our aim was to investigate the in vitro synergistic effect of CUR with imipenem (IMP) and Colistin (CST) in MDR P. aeruginosa isolates and in vivo activity on Galleria mellonella (G. mellonella) larvae. Three clinical isolates of MDR P. aeruginosa, which were determined to be phenotypically resistant to carbapenems, were used, and KPC and OXA48 resistance genes were determined by PCR method. The synergistic effect of CUR with antibiotics were investigated by the checkerboard method. Larval survival and bacterial load were compared with the in vivo study. In this study, IMP MIC values were significantly reduced (two to eight-fold decrease) in the presence of CUR, and partial synergy was observed. For CST, this value decreased two-fold. Bacterial load was evaluated to investigate the effect of antimicrobials during infection. While the CFUs increased over time in non-treated larvae as compared to the initial inoculum, bacterial load was significantly decreased for the groups treated with CUR, IMP and CST compared to the untreated group (p < 0.05). It was concluded CUR-antibiotic combinations can provide an alternative approach in the treatment of infections with MDR bacteria.

Current state of building demolition and potential for selective dismantling in Vietnam

In Vietnam, an increase in construction activities together with the absence of recycling-oriented demolition techniques is giving rise to an alarming generation of construction and demolition waste. This study scrutinized the current state of building demolition approaches in Hanoi, Vietnam and evaluated the potential for the selective dismantling, or deconstruction, of reinforced-concrete (RC) houses. Site observations, direct measurement, and interviews were conducted to obtain information on technical, environmental, and economic characteristics of three residential housing sites, each representing a typical current demolition technique (manual, hybrid, and mechanical demolition). A selective dismantling site is proposed based on the collected survey data and published case studies. Our findings confirmed the unsustainability of RC-building demolition practices in Hanoi, which have an average reuse/recycling rate of roughly 3%. The application of selective dismantling will boost the recycling rate to a remarkable 90%, associated with a 55% decrease in greenhouse gas emissions. Even though selective dismantling is more time-consuming and therefore more costly, it results in double the resale value and an eight-fold decrease in disposal costs. The results of a sensitivity analysis indicate that increasing the current disposal fee will significantly improve the feasibility of selective dismantling, suggesting a need for stricter disposal charging mechanisms along with other interventions such as the development of recycling facilities to promote the introduction of this building removal alternative in Vietnam.

Design and characterization of Ca-Fe(III) pyrophosphate salts with tunable pH-dependent solubility for dual-fortification of foods

• Characterization of designed mixed salts: Ca 2(1-x) Fe 4x (P 2 O 7 ) (1+2x) (0 < x < 1). • Homogeneous distribution of Ca and Fe in salts was observed for 0.14 ≤ x ≤ 0.35. • Mixed pyrophosphate salts showed enhanced iron solubility in the gastric pH range. • Ca-Fe(III) pyrophosphate salt is a potential delivery system for dual-fortification. Food-fortification using poorly water-soluble mineral-containing compounds is a common approach to deliver iron. However, it comes with the challenge of ensuring iron bio-accessibility and limiting iron-phenolic interactions that can change organoleptic properties. Mixed Ca-Fe(III) pyrophosphate salts with the general formula Ca 2(1-x) Fe 4x (P 2 O 7 ) (1+2x) were designed as a system for simultaneous delivery of iron and calcium. The salts were synthesized via a co-precipitation method and characterized by TEM-EDX, XRD, and FT-IR. All mixed salts with 0.14 ≤ x ≤ 0.35 yielded homogenous amorphous particles. The iron dissolution from these mixed salts showed a fourfold increase at gastric pH compared to Fe(III) pyrophosphate. In the food-relevant pH range, the salts with x ≤ 0.15 showed up to an eight-fold decrease in iron solubility. Despite this, reactivity of the mixed salts in tea was similar to that of FePP. Our results indicate that these mixed salts are potential dual-fortificants with tunable iron content and solubility.

Radioluminescence Imaging of Drug Elution from Biomedical Implants

AbstractA method to noninvasively measure the concentration of radiolabeled pharmaceuticals on modified drug‐eluting biomedical implant surfaces is described. The implants are coated with microphosphors and radiolabeled pharmaceuticals in a polyurethane film. The drug molecules emit radiation which excites radioluminescence in nearby phosphors; for drug released from the film the radiation is absorbed by the surrounding media and generates no light. The technique is applied to measure beta‐emitting tritium‐labeled vancomycin (3H‐vancomycin) concentration on the surface of an orthopedic plate. Bacteria can coat orthopedic implant surfaces and form biofilms which are resistant to antibiotics and the host's immune system. Antibiotic eluting implant coatings are thus promising candidates for infection prevention and treatment. Radioluminescence imaging permits surface‐specific, noninvasive measurement of drug concentration on implant surfaces, which is an important metric for developing effective drug eluting coatings. The radioluminescence signal increases linearly with 3H‐vancomycin concentration, with a limit of detection (LOD) of 9.6 nCi (3.5 pmol) without tissue. Biomedically relevant drug release concentrations are monitored through 5 mm of porcine tissue slices (38.7 nmol LOD). Despite light scattering, and an eightfold signal decrease through 5 mm of tissue, drug release and reference regions are resolvable for non‐invasive quantification.

Estimating cardiac active tension from wall motion-An inverse problem of cardiac biomechanics.

The contraction of the human heart is a complex process as a consequence of the interaction of internal and external forces. In current clinical routine, the resulting deformation can be imaged during an entire heart beat. However, the active tension development cannot be measured in vivo but may provide valuable diagnostic information. In this work, we present a novel numerical method for solving an inverse problem of cardiac biomechanics-estimating the dynamic active tension field, provided the motion of the myocardial wall is known. This ill-posed non-linear problem is solved using second order Tikhonov regularization in space and time. We conducted a sensitivity analysis by varying the fiber orientation in the range of measurement accuracy. To achieve RMSE <20% of the maximal tension, the fiber orientation needs to be provided with an accuracy of 10°. Also, variation was added to the deformation data in the range of segmentation accuracy. Here, imposing temporal regularization led to an eightfold decrease in the error down to 12%. Furthermore, non-contracting regions representing myocardial infarct scars were introduced in the left ventricle and could be identified accurately in the inverse solution (sensitivity >0.95). The results obtained with non-matching input data are promising and indicate directions for further improvement of the method. In future, this method will be extended to estimate the active tension field based on motion data from clinical images, which could provide important insights in terms of a new diagnostic tool for the identification and treatment of diseased heart tissue.

Multiscale Simulations Examining Glycan Shield Effects on Drug Binding to Influenza Neuraminidase

Influenza neuraminidase is an important drug target. Glycans are present on neuraminidase and are generally considered to inhibit antibody binding via their glycan shield. In this work, we studied the effect of glycans on the binding kinetics of antiviral drugs to the influenza neuraminidase. We created all-atom in silico systems of influenza neuraminidase with experimentally derived glycoprofiles consisting of four systems with different glycan conformations and one system without glycans. Using Brownian dynamics simulations, we observe a two- to eightfold decrease in the rate of ligand binding to the primary binding site of neuraminidase due to the presence of glycans. These glycans are capable of covering much of the surface area of neuraminidase, and the ligand binding inhibition is derived from glycans sterically occluding the primary binding site on a neighboring monomer. Our work also indicates that drugs preferentially bind to the primary binding site (i.e., the active site) over the secondary binding site, and we propose a binding mechanism illustrating this. These results help illuminate the complex interplay between glycans and ligand binding on the influenza membrane protein neuraminidase.

Antibacterial and Cytotoxic Activities of Ten Commercially Available Essential Oils.

There is a huge concern in the medical field concerning the emergence of bacterial resistance to antibiotics. Essential oils are a source of antibacterial compounds that can overcome this problem. Ten essential oils that are commercially available were investigated in the present study: ajowan, basil, German chamomile, Chinese cinnamon, coriander, clove, lemongrass, Spanish lavender, oregano and palmarosa. Their direct, synergistic and indirect antibacterial activities were evaluated against different human pathogenic Gram-positive and Gram-negative strains. To evaluate their possible use in clinics, the cytotoxicity of these essential oils was also tested on keratinocyte and epithelial cell lines. Except for the Chinese cinnamon, coriander and lemongrass, all other essential oils presented no cytotoxicity at 32 and 16 μg/mL. The highest indirect antibacterial activities were observed with the palmarosa and Spanish lavender in association with penicillin V. These two associations presented a 64-fold decrease against a resistant strain of Staphylococcus aureus, however, at a cytotoxic concentration. It can also be highlighted that when tested at a non-cytotoxic concentration, the activity of oregano in association with penicillin V presented an eight-fold decrease. These results show the interest to use essential oils in combination with antibiotics to reduce their concentrations inside drugs.

Strain-specific anti-biofilm and antibiotic-potentiating activity of 3\u2032,4\u2032-difluoroquercetin

Antibacterial properties of 3′,4′-difluoroquercetin (di-F-Q), a fluorine-substituted stable quercetin derivative, were investigated. Even though di-F-Q itself did not show interesting antibacterial activity, treatment of the Staphylococcus aureus strains with di-F-Q resulted in a dose-dependent reduction in biofilm formation with IC50 values of 1.8 ~ 5.3 mg/L. Also, the antibacterial activity of ceftazidime (CAZ) against carbapenem-resistant Pseudomonas aeruginosa (CRPA) showed eightfold decrease upon combination with di-F-Q. Assessment of the antimicrobial activity of CAZ in combination with di-F-Q against 50 clinical isolates of P. aeruginosa confirmed 15.7% increase in the percentages of susceptible P. aeruginosa isolates upon addition of di-F-Q to CAZ. Further mechanistic studies revealed that di-F-Q affected the antibiotics efflux system in CRPA but not the β-lactamase activity. Thus, di-F-Q was almost equally effective as carbonyl cyanide m-chlorophenyl hydrazine in inhibiting antibiotic efflux by P. aeruginosa. In vivo evaluation of the therapeutic efficacy of CAZ-(di-F-Q) combination against P. aeruginosa showed 20% of the mice treated with CAZ-(di-F-Q) survived after 7 days in IMP carbapenemase-producing multidrug-resistant P. aeruginosa infection group while no mice treated with CAZ alone survived after 2 days. Taken together, di-F-Q demonstrated unique strain-specific antimicrobial properties including anti-biofilm and antibiotic-potentiating activity against S. aureus and P. aeruginosa, respectively.

Inhibitory effects of aptamer targeted teicoplanin encapsulated PLGA nanoparticles for Staphylococcus aureus strains.

Emergence of resistance to traditional antibiotic treatments necessitates alternative delivery systems. Teicoplanin is a glycopeptide antibiotic used in the treatments of serious infections caused by Gram-positive bacteria, including Methicillin Resistant Staphylococcus aureus (MRSA). One strategy to keep up with antibiotic resistance development is to limit dose and amount during treatments. Targeted delivery systems of antibiotics have been suggested as a mechanism to slow-down the evolution of resistance and to increase efficiency of the antimicrobials on already resistant pathogens. In this study, we report teicoplanin delivery nanoparticles of Poly Lactic-co-Glycolic Acid (PLGA), which are functionalized with S. aureus specific aptamers. A 32-fold decrease in minimum inhibitory concentration (MIC) values of teicoplanin for S. aureus was demonstrated for susceptible strains and about 64-fold decline in MIC value was achieved for moderately resistant clinical isolates of MRSA upon teicoplanin treatment with aptamer-PLGA nanoparticles. Although teicoplanin delivery in PLGA nanoparticles without targeting demonstrated eightfold decrease in MIC of susceptible strains of S. aureus and S. epidermidis and twofold in MIC of resistant strains, the aptamer targeting specifically decreased MIC for S. aureus, but not for S. epidermidis. Therefore, aptamer-targeted PLGA delivery of antibiotic can be an attractive alternative to combat with some of the multi-drug resistant bacterial pathogens.