Increased Expression of Efflux Pump norA Drives the Rapid Evolutionary Trajectory from Tolerance to Resistance against Ciprofloxacin in Staphylococcus aureus.

The intensively intermittent use of antibiotics promotes the rapid evolution of tolerance, which may lead to resistance acquisition in the following evolutionary trajectory. In addition to directly exporting antibiotics as an instant resistance strategy, efflux pumps are overexpressed in tolerant strains. To investigate how efflux pumps participate in resistance development from tolerance to resistance, we performed in vitro evolutional experiments against the antibiotic ciprofloxacin in norA efflux pump mutants of Staphylococcus aureus. These experiments demonstrated that overexpression of norA rapidly facilitated the development of ciprofloxacin resistance from tolerance to resistance through elevated spontaneous mutations. The generated resistance mutations were further fixed in the population by increasing survival ability. The observed Ser80Phe and Glu84Lys mutations in the topoisomerase IV ParC (GrlA in S. aureus) may be responsible for tolerant strains to develop resistance to ciprofloxacin since it has been reported that such mutations disrupt the water-metal ion bridge between quinolones and ParC. MepA and Sav1866 are related to the same antibiotic (ciprofloxacin) susceptibility as NorA, and they also contributed to resistance development against ciprofloxacin. MgrA positively regulated NorA expression and the development of ciprofloxacin resistance. Importantly, blocking the evolutionary pathway by coadministering ciprofloxacin with the efflux pump inhibitor reserpine effectively delayed the resistance acquisition in an in vitro experiment. This study illustrated the role of efflux pumps in the evolutionary trajectory from tolerance to resistance. The delayed resistance development caused by the efflux pump inhibitor illuminates a possible strategy for postponing the resistance acquisition from tolerance to resistance by disrupting efflux pumps.

Apoptotic effect of sodium acetate on a human gastric adenocarcinoma epithelial cell line.

The objective of this study was to investigate the effect of sodium acetate on the viability of the human gastric adenocarcinoma (AGS) epithelial cell line. AGS cells were exposed to a range of concentrations of sodium acetate for different periods of time, and the sodium acetate-induced cytotoxic effects, including cell viability, DNA fragmentation, apoptotic gene expression, and caspase activity, were assessed. The changes in these phenotypes were quantified by performing a lactate dehydrogenase cell viability assay, annexin V staining, terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL), and several caspase activity assays. In vitro studies demonstrated that the cytotoxicity of sodium acetate on the AGS cell line were dose- and time-dependent manners. No differences were found between the negative control and sodium acetate-treated cells stained with annexin V and subjected to the TUNEL assay. However, caspase-3 activity was increased in AGS cells exposed to sodium acetate. Overall, it was concluded that sodium acetate exerted an apoptotic effect in AGS cells via a caspase-dependent apoptotic pathway.

Acupuncture improve proteinuria in diabetic kidney disease rats by inhibiting ferroptosis and epithelial-mesenchymal transition.

Objective: To explore the mechanism of acupuncture to relieve diabetic proteinuria in Diabetic Kidney Disease (DKD). Methods: A total of 10 male Sprague-Dawley rats were randomly selected as the negative control group (NC), and a further 30 rats were fed a high-fat diet (HFD) and intraperitoneal streptozotocin (STZ). The DKD model rats in the model group (DKD) and the acupuncture group (DKD + Acu) were randomly assigned. After 4 weeks of intervention, collected urine, peripheral blood, and renal tissues from all rats, and assessed blood urea nitrogen, serum creatinine, triglyceride, 24-h urine protein quantification, and blood glucose, left kidney weight, kidney body ratio index, then observe changes in renal histology in the rats. The renal cortex tissues of three rats from each group were sent for transcriptomic analysis. According to the results of transcriptomic analysis, various kits were used to detect SOD, MDA, GSH, GSH-px, and iron concentration. The expression levels of GPX4 and System Xc-, members of the antioxidative stress pathway, and TfR 1, SLC39A14, FTH 1, and SLC40A1, involved in iron metabolism, in the kidney tissues were measured by western blotting and reverse transcription-quantitative PCR. The expression of mesenchymal phenotype markers and podocyte-specific markers were evaluated by immunofluorescence. Results: Acupuncture promoted the levels of GSH, GSH-px, and SOD, decreased the level of MDA (P < 0.05), promoted the expression of GPX4 and System Xc- (P < 0.05), decreased the expression of TfR1 and SLC39A14 (P < 0.01), and increased the expression of FTH 1 and SLC40A1 (P < 0.05), inhibited the expression of TGF-ß1, desmin, FSP-1, and α-SMA (P < 0.05), promoted the expression of Nephrin, Podocin, and CD2AP (P < 0.05). Conclusion: Improving the ability of podocytes to prevent oxidative stress and restoring iron ion homeostasis, can improve Ferroptosis and block epithelial-mesenchymal transition, improve podocyte injury, restore filtration function, and reduce proteinuria in DKD rats.

Occurrence of Fusarium mycotoxins in freshly harvested highland barley (qingke) grains from Tibet, China.

Highland barley, also called "qingke" in Tibetan, is mainly cultivated in the Tibetan Plateau of China and has been used as a major staple food for Tibetans. Recently, Fusarium head blight (FHB) of qingke was frequently observed around the Brahmaputra River in Tibet. Considering the importance of qingke for Tibetans, the assessment of Fusarium mycotoxin contamination is essential for food safety. In this study, a total of 150 freshly harvested qingke grain samples were obtained from three regions around the Brahmaputra River in Tibet (China) in 2020. The samples were investigated for the occurrence of 20 Fusarium mycotoxins using high-performance liquid chromatography-tandem mass spectrometry (HPLC‒MS/MS). The most frequently occurring mycotoxin was enniatin B (ENB) (46%), followed by enniatin B1 (ENB1) (14.7%), zearalenone (ZEN) (6.0%), enniatin A1 (ENA1) (3.3%), enniatin A (ENA) (1.3%), beauvericin (BEA) (0.7%), and nivalenol (NIV) (0.7%). Due to the increase in altitude, the cumulative precipitation level and average temperature decreased from the downstream to the upstream of the Brahmaputra River; this directly correlated to the contamination level of ENB in qingke, which gradually decreased from downstream to upstream. In addition, the level of ENB in qingke obtained from qingke-rape rotation was significantly lower than that from qingke-wheat and qingke-qingke rotations (p < 0.05). These results disseminated the occurrence of Fusarium mycotoxins and provided further understanding of the effect of environmental factors and crop rotation on Fusarium mycotoxins.

Controllable energy transfer in fluorescence upconversion of NdF3 and NaNdF4 nanocrystals.

The synthesized Nd fluoride nanocrystals exhibited different upconversion behaviors as dispersed and aggregated samples due to the different energy transfer mechanisms. When they were dispersed in water, the NaNdF(4) nanocrystals exhibited approximately 400 times stronger upconversion fluorescence than the NdF(3) nanocrystals. Remarkable upconversion behaviors were found when the nanocrystals were aggregated in the films. For the NdF(3) nanocrystals, the energy transfer processes (4)I(13/2)<--(4)F(3/2)-->(4)G(7/2) in the films generated avalanche upconversion emissions with a high slope of approximately 12.0, which could be due to the large avalanche cross relaxation rates and spectral broadening effect. In contrast, the spectral broadening effect in the NaNdF(4) NCs films increased the energy transfer (4)I(15/2)<--(4)F(3/2)-->(4)G(5/2) of the Nd(3+) ions, and induced a new upconversion emission at approximately 680 nm with the slope increased from 1.0 to 3.2.

Different plantar interface effects on dynamics of the lower limb.

The moments acting on the lower limb joints influence the life of the arthrosis. These loads may depend on the footwear and action style. The footwear factor was studied with three-dimensional gait measure system. Five young women in their 20s, wear 7 cm high-heeled shoes and sneakers, and walked in 10 m gait laboratory walkway. Inversed dynamics was used to analysis the torques at the ankle, knee and hip. Results showed that peak adduction moments at the knee and ankle increased and flexion/extension moments at hip increased with high-heel shoes compared with the sneakers. The high-heeled shoes result in greater load in lower limb joints especial to the knee and hip.

A health survey of workers in the pentachlorophenol section of a chemical manufacturing plant.

During 1968 to 1985, 109 workers who had been engaged in the production of pentachlorophenol, using non-gamma isomers of hexachloroclohexane (BHC) as the raw material, were surveyed. Endemic chloracne among them had been noted since 1974. The prevalence of chloracne was 73.4% (80/109) in total and 95.2% (20/21) in a trichlorobenzene (TCB) tank area where dioxin and dibenzofurans levels were thousands of ppm. To our knowledge, PCDDs and PCDFs have not previously been reported from thermal decomposition of BHC. Urinary porphyrins were significantly higher among exposed workers than among the controls but there was no significant difference between the workers with chloracne and those without. The conduction velocities of the median motor nerves were much slower among the workers in the TCB tank area where the highest PCDDs contamination appeared. The mortality study cohort was relatively young. Based on the three deaths observed during the follow-up, no association could be drawn.