Chemical genomic analysis reveals the interplay between iron chelation, zinc homeostasis, and retromer function in the bioactivity of an ethanol adduct of the feijoa fruit-derived ellagitannin vescalagin.

Nature has been a rich source of pharmaceutical compounds, producing 80% of our currently prescribed drugs. The feijoa plant, Acca sellowiana, is classified in the family Myrtaceae, native to South America, and currently grown worldwide to produce feijoa fruit. Feijoa is a rich source of bioactive compounds with anticancer, anti-inflammatory, antibacterial, and antifungal activities; however, the mechanism of action of these compounds is largely not known. Here, we used chemical genetic analyses in the model organism Saccharomyces cerevisiae to investigate the mechanism of action of a feijoa-derived ethanol adduct of vescalagin (EtOH-vescalagin). Genome-wide barcode sequencing analysis revealed yeast strains lacking genes in iron metabolism, zinc metabolism, retromer function, or mitochondrial function were hypersensitive to 0.3 µM EtOH-vescalagin. This treatment increased expression of iron uptake proteins at the plasma membrane, which was a compensatory response to reduced intracellular iron. Likewise, EtOH-vescalagin increased expression of the Cot1 protein in the vacuolar membrane that transports zinc into the vacuole to prevent cytoplasmic accumulation of zinc. Each individual subunit in the retromer complex was required for the iron homeostatic mechanism of EtOH-vescalagin, while only the cargo recognition component in the retromer complex was required for the zinc homeostatic mechanism. Overexpression of either retromer subunits or high-affinity iron transporters suppressed EtOH-vescalagin bioactivity in a zinc-replete condition, while overexpression of only retromer subunits increased EtOH-vescalagin bioactivity in a zinc-deficient condition. Together, these results indicate that EtOH-vescalagin bioactivity begins with extracellular iron chelation and proceeds with intracellular transport of zinc via the retromer complex. More broadly, this is the first report of a bioactive compound to further characterize the poorly understood interaction between zinc metabolism and retromer function.

Ozonation/UV irradiation of dispersed Ag/AgI nanoparticles in water resources: stability and aggregation.

Proliferation of nanoparticles (NPs) as aqueous pollutants is a matter of growing concern today. The aggregation kinetics of colloidal bare silver (Ag, 20.5 nm) and silver iodide (AgI, 15.3 nm) NPs were investigated during ozone/ultraviolet (O3/UV) oxidation. Dynamic light scattering was applied to monitor the aggregation of NPs, and the z-average of treated samples was considered aggregate diameter. The effect of temperature, pH, and initial concentration of NPs was investigated on the aggregation rate constant and stability ratio. At a short oxidation period of approximately 1 min, the lower stability ratio was achieved for Ag NPs (< 50) than AgI NPs (> 100). Under acidic conditions, the negative surface charge of both NPs was neutralized that resulted in faster aggregation. In contrast, the impact of temperature and initial concentration of NPs on the aggregation rate was different for both NPs, which was due to the type of O3/UV interaction with the surface of NPs and the thickness of the electrical double layer surrounding the NPs. The aggregation behavior of Ag NPs obeyed diffusion-limited regime, while an intermediate regime between diffusion- and reaction-limited was observed for AgI NP aggregation. The resulting aggregate morphologies showed that the clusters were ramified for Ag and compressed for AgI NPs. Applying the O3/UV oxidation process for water treatment purposes leads to a significant reduction in aggregation time for inherently unstable Ag and stable AgI toxic NPs from several hours or days to several minutes.

Assessment of aqueous phase ozonation on aggregation of polyvinylpyrrolidone-capped silver nanoparticles.

Due to the antibacterial characteristics, numerous-growing applications of silver nanoparticles (AgNPs) and its coated forms impact water treatment by ozone. The influence of ozone on the aggregation of bare AgNPs and polyvinylpyrrolidone-capped form (PVP-AgNPs) was investigated, as toxicity of NPs depends on particle aggregation/surface charge. Full factorial experimental design was employed to investigate the impact of pH, concentration of NPs' suspension, and ozonation time on bare and PVP-capped AgNPs. Z-Average, zeta potential, and polydispersity index (PdI) of NPs were measured as aggregation criteria. The most effective variables on aggregation of NPs were the coating layer (40-75.5% contribution), pH (14.1-29.6% contribution), and ozonation time (6.5-10.1% contribution), respectively. The aggregation rate increased with increasing ozonation time and decreased with pH. The aggregation of ozonated AgNPs (Z-average up to ~ 4000 nm) was much greater than that of ozonated PVP-AgNPs (Z-average up to ~ 450 nm) due to interaction of ozone-PVP stabilizing layer. During ozonation, the PVP-AgNPs' surface charge shifted from - 6.62 (steric repulsion) to - 29.17 mV (electrosteric repulsion) at pH 7.5, thereby requiring more treatment time to aggregate compared with AgNPs. Graphical abstract.

Assessment of wastes recycling for deinking purposes in ozone assisted green process.

This study investigates techno-economic aspects of wastepaper recycling to optimize process efficiency and operating cost. The deinking was carried out using pulping followed by froth flotation. The development of a waste management process was achieved employing refinery wastewater to provide chemical reagents in pulping. Ozone was also used as a gas media in flotation to improve brightness and number of ink-spot and to reduce chemical oxygen demand (COD) simultaneously. An enhancement in the brightness was observed from 50.1 to 64.1% ISO that was superior to the brightness of virgin newspaper before printing (61.0% ISO). It was equivalent to a reduction of 55% (from > 100,000 to 45,058) in number of ink-spot. The quality of flotation effluent was assessed by measuring the COD and phthalocyanine concentration. The COD reduction of 67% (from 3250 to 1072 mg/L) and phthalocyanine reduction of 85% (from 2 to 0.3 mg/L) were achieved after 30 min ozonation. According to the obtained results, approximately 67% of the direct (variable) cost reduced while the wastewater was used in pulping because of saving NaOH and water consumption. Associating the refinery and paper recycling wastewater treatment units, while taking into account the environmental and economic benefits of ozone, results in a quality paper and significantly preserves the environment.

Linear and nonlinear analyses of femoral fractures: Computational/experimental study.

This paper describes two new methods for computational fracture analysis of human femur using Quantitative Computed Tomography (QCT) voxel-based finite element (FE) simulation. The paper also reports comprehensive mechanical testing for validation of the methods and evaluation of the required material properties. The analyses and tests were carried out on 15 human femurs under 11 different stance-type loading orientations. Several classical forms of subcapital, transcervical, basicervical, and intertrochanteric fractures plus a specific type of subtrochanteric fracture were created and analyzed. A new procedure was developed for prediction of the strengths and the fracture initiation patterns using a FE-based linear scheme. The predicted and observed fracture patterns were in correspondence, and the FE predictions of the fracture loads were in very good agreement with the experimental results. Moreover, the crack initiation and growth behaviors of two subtrochanteric fractures were successfully simulated through a novel implementation of the cohesive zone model (CZM) within a nonlinear FE analysis scheme. The CZM parameters were obtained through a series of experimental tests on different types of specimens and determination of a variety of material properties for different anatomic regions and orientations. The presented results indicated that the locations and patterns of crack initiation, the sequences of crack growth on different paths, and the compatibility of growth increments agreed very well with the observed specifications. Also, very good agreements were achieved between the measured and simulated fracture loads.

Metabolic engineering of Saccharomyces cerevisiae for linalool production.

OBJECTIVES: To engineer the yeast Saccharomyces cerevisiae for the heterologous production of linalool. RESULTS: Expression of linalool synthase gene from Lavandula angustifolia enabled heterologous production of linalool in S. cerevisiae. Downregulation of ERG9 gene, that encodes squalene synthase, by replacing its native promoter with the repressible MET3 promoter in the presence of methionine resulted in accumulation of 78 µg linalool l(-1) in the culture medium. This was more than twice that produced by the control strain. The highest linalool titer was obtained by combined repression of ERG9 and overexpression of tHMG1. The yeast strain harboring both modifications produced 95 µg linalool l(-1). CONCLUSIONS: Although overexpression of tHMG1 and downregulation of ERG9 enhanced linalool titers threefold in the engineered yeast strain, alleviating linalool toxicity is necessary for further improvement of linalool biosynthesis in yeast.

QCT-based failure analysis of proximal femurs under various loading orientations.

In this paper, the variations of the failure strength and pattern of human proximal femur with loading orientation were analysed using a novel quantitative computed tomography (QCT)-based linear finite element (FE) method. The QCT images of 4 fresh-frozen femurs were directly converted into voxel-based finite element models for the analyses of the failure loads and patterns. A new geometrical reference system was used for the alignment of the mechanical loads on the femoral head. A new method was used for recognition and assortment of the high-risk elements using a strain energy-based measure. The FE results were validated with the experimental results of the same specimens and the results of similar case studies reported in the literature. The validated models were used for the computational investigation of the failure loads and patterns under 15 different loading conditions. A consistent variation of the failure loads and patterns was found for the 60 different analysed cases. Finally, it was shown that the proposed procedure can be used as a reliable tool for the failure analysis of proximal femurs, e.g. identification of the relevant loading directions for specific failure patterns, or determination of the loading conditions under which the proximal femurs are failure-prone.