Activity of polymyxin B combined with cefepime-avibactam against the biofilms of polymyxin B-resistant Pseudomonas aeruginosa and Klebsiella pneumoniae in in vitro and in vivo models.

Bacterial biofilms, often forming on medical devices, can lead to treatment failure due to their increased antimicrobial resistance. Cefepime-avibactam (CFP-AVI) exhibits potent activities against Pseudomonas aeruginosa (P. aeruginosa) and Klebsiella pneumoniae (K. pneumoniae) when used with polymyxin B (PMB). However, its efficacy in biofilm-related infections is unknown. The present study aimed to evaluate the activity of PMB combined with CFP-AVI against the biofilms of PMB-resistant Gram-negative bacteria. Five K. pneumoniae strains and three P. aeruginosa strains known to be PMB-resistant and prone to biofilm formation were selected and evaluated. Antimicrobial susceptibility assays demonstrated that the minimal biofilm inhibitory and eradication concentrations of PMB and CFP-AVI for biofilms formed by the eight strains were significantly higher than the minimal inhibitory concentrations of the antibiotics for planktonic cells. The biofilm formation inhibition and eradication assays showed that PMB combined with CFP-AVI cannot only suppress the formation of biofilm but also effectively eradicate the preformed mature biofilms. In a modified in vitro pharmacokinetic/pharmacodynamic biofilm model, CFP-AVI monotherapy exhibited a bacteriostatic or effective activity against the biofilms of seven strains, whereas PMB monotherapy did not have any activity at 72 h. However, PMB combined with CFP-AVI demonstrated bactericidal activity against the biofilms of all strains at 72 h. In an in vivo Galleria mellonella infection model, the 7-day survival rates of larvae infected with biofilm implants of K. pneumoniae or P. aeruginosa were 0-6.7%, 40.0-63.3%, and 46.7-90.0%, respectively, for PMB alone, CFP-AVI alone, and PMB combined with CFP-AVI; the combination therapy increased the rate by 6.7-33.3% (P < 0.05, n = 6), compared to CFP-AVI monotherapy. It is concluded that PMB combined with CFP-AVI exhibits effective anti-biofilm activities against PMB-resistant K. pneumoniae and P. aeruginosa both in vitro and in vivo, and thus may be a promising therapeutic strategy to treat biofilm-related infections.

Chromatographic Determination of the Mycotoxin Patulin in 219 Chinese Tea Samples and Implications for Human Health.

Patulin (PAT) is a mycotoxin, with several acute, chronic, and cellular level toxic effects, produced by various fungi. A limit for PAT in food of has been set by authorities to guarantee food safety. Research on PAT in tea has been very limited although tea is the second largest beverage in the world. In this paper, HPLC-DAD and GC-MS methods for analysis of PAT in different tea products, such as non-fermented (green tea), partially fermented (oolong tea, white tea, yellow tea), completely fermented (black tea), and post-fermented (dark tea and Pu-erh tea) teas were developed. The methods showed good selectivity with regard to tea pigments and 5-hydroxymethylfurfural (5-HMF) and a recovery of 90-102% for PAT at a 10-100 ppb spiking level. Limit of detection (LOD) and limit of quantification (LOQ) in tea were 1.5 ng/g and 5.0 ng/g for HPLC-UV, and 0.25 ng/g and 0.83 ng/g for GC-MS. HPLC was simpler and more robust, while GC-MS showed higher sensitivity and selectivity. GC-MS was used to validate the HPLC-UV method and prove its accuracy. The PAT content of 219 Chinese tea samples was investigated. Most tea samples contained less than 10 ng/g, ten more than 10 ng/g and two more than 50 ng/g. The results imply that tea products in China are safe with regard to their PAT content. Even an extreme daily consumption of 25 g of the tea with the highest PAT content (124 ng/g), translates to an intake of only 3 µg/person/day, which is still an order of magnitude below the maximum allowed daily intake of 30 µg for an adult.

Electrochemical sensor based on an electrode modified with porous graphitic carbon nitride nanosheets (C3N4) embedded in graphene oxide for simultaneous determination of ascorbic acid, dopamine and uric acid.

Two-dimensional porous graphitic carbon nitride (g-C3N4) nanosheets were synthesized by low-cost and direct thermal oxidation. Porous g-C3N4 assembled with graphene oxide (GO) was immobilized on a glassy carbon electrode. The sensor was applied to simultaneous determination of ascorbic acid (AA), dopamine (DA) and uric acid (UA) with high performance. Cyclic voltammetry and differential pulse voltammetry were used to investigate electrochemical and electrocatalytic properties. The results indicate that the electrochemical sensor possesses high specific surface area, hierarchical pore structure and excellent signal response to AA, DA and UA. The oxidation potentials are well separated at around 0.15, 0.34 and 0.46 V for AA, DA and UA respectively. The determination limits for AA, DA and UA are 3.7 µM, 0.07 µM and 0.43 µM, respectively. The sensor was applied to tracking the three analytes in spiked serum samples with recovery 95.1~105.5% and relation standard deviations of less than 5%. Graphical abstract Schematic representation of porous graphitic carbon nitride nanosheet embedded in graphene oxide for simultaneous determination of ascorbic acid, dopamine and uric acid.

The Associations of Erythrocyte Fatty Acids with Whole Blood Mineral Elements in Children.

Background. Minerals play important biological roles in lipid metabolism. The primary aim of this study was to examine the relationships between erythrocyte fatty acids (FAs) levels with whole blood mineral elements concentrations among Chinese children. Methods. A cross-sectional study was conducted. A total of 435 children aged 4−7 years were recruited. Whole blood mineral elements were determined by atomic absorption spectrometry and erythrocyte FAs composition by gas chromatography-mass spectrometer. Results. There were direct correlations between Zn and C18:2n-6 (FDR corrected p = 0.019), total n-6 PUFAs (FDR corrected p = 0.034), and total PUFAs (FDR corrected p = 0.034). Direct correlations were found between whole blood Zn and C18:1n-9 (FDR corrected p = 0.035), C24:1n-9 (FDR corrected p = 0.023), total MUFAs (FDR corrected p = 0.023), and C18:2n-6 (FDR corrected p = 0.048) in the Cu < P50 group. In the Cu ≥ P50 group, Mg was inversely related to most FAs (All FDR corrected p < 0.05). In the Zn < P50 group, Cu was directly related to C24:1n-9, total MUFAs, C20:5n-3, C22:6n-3, total n-3 PUFAs, C20:4n-6, total n-6 PUFAs, total PUFAs, and total FAs (All FDR corrected p < 0.05). Conclusions. Whole blood Cu and Zn levels were directly linked to several FAs levels in the erythrocytes of children. The interactions of Mg, Cu, and Zn with fatty acids may affect FA metabolism, in which Mg influences FA absorption.