Dual EGFR/erbB2 inhibition is an attractive therapeutic strategy for epithelial tumors, as ligand-induced erbB2/EGFR heterodimerization triggers potent proliferative and survival signals. Here we show that a small molecule, GW572016, potently inhibits both EGFR and erbB2 tyrosine kinases leading to growth arrest and/or apoptosis in EGFR and erbB2-dependent tumor cell lines. GW572016 markedly reduced tyrosine phosphorylation of EGFR and erbB2, and inhibited activation of Erk1/2 and AKT, downstream effectors of proliferation and cell survival, respectively. Complete inhibition of activated AKT in erbB2 overexpressing cells correlated with a 23-fold increase in apoptosis compared with vehicle controls. EGF, often elevated in cancer patients, did not reverse the inhibitory effects of GW572016. These observations were reproduced in vivo, where GW572016 treatment inhibited activation of EGFR, erbB2, Erk1/2 and AKT in human tumor xenografts. Erk1/2 and AKT represent potential biomarkers to assess the clinical activity of GW572016. Inhibition of activated AKT in EGFR or erbB2-dependent tumors by GW572016 may lead to tumor regressions when used as a monotherapy, or may enhance the anti-tumor activity of chemotherapeutics, since constitutive activation of AKT has been linked to chemo-resistance.
Worldwide regulatory frameworks for the assessment and remediation of contaminated soils have moved towards a risk-based approach, taking contaminant bioavailability into consideration. However, there is much debate on the precise definition of bioavailability and on the standardization of methods for the measurement of bioavailability so that it can be reliably applied as a tool for risk assessment. Therefore, in this paper, we reviewed the existing definitions of heavy metal bioavailability in relation to plant uptake (phytoavailability), in order to better understand both the conceptual and operational aspects of bioavailability. The related concepts of specific and non-specific adsorption, as well as complex formation and organic ligand affinity were also intensively discussed to explain the variations of heavy metal solubility and mobility in soils. Further, the most frequently used methods to measure bioavailable metal soil fractions based on both chemical extractions and mechanistic geochemical models were reviewed. For relatively highly mobile metals (Cd, Ni, and Zn), a neutral salt solution such as 0.01 M CaCl2 or 1 M NH4NO3 was recommended, whereas a strong acid or chelating solution such as 0.43 M HNO3 or 0.05 M DTPA was recommended for strongly soil-adsorbed and less mobile metals (Cu, Cr, and Pb). While methods which assessed the free metal ion activity in the pore water such as DGT and DMT or WHAM/Model VI, NICA-Donnan model, and TBLM are advantageous for providing a more direct measure of bioavailability, few of these models have to date been properly validated.
A wide variety of veterinary antibiotics (VAs) has been detected in environmental water samples, and this is of potential environmental concern due to their adverse effects. In particular, the potential for development of antibiotic-resistant bacteria has raised social concerns leading to intensive investigation regarding the influence of antibiotics on human and ecosystem health. One of the main sources of antibiotic effluence to the environment is livestock manures that often contain elevated levels of VAs that survive normal digestive procedures following medication in animal husbandry because unlike human waste, waste generated on farms does not undergo tertiary wastewater treatment, and consequently, the concentration of antibiotics entering the environment is expected to be larger from farming practices. Animal feed is often supplemented with VAs to promote growth and parasite resistance in the medicated animals, and this practice typically resulted in higher use of VAs and consequential excretion from livestock through urine and feces. The excretion rate varied depending on the type of VA used with around 75, 90, and 50-100% being excreted for chlortetracycline, sulfamethazine, and tyolsin, respectively. The excreted VAs that initially present in livestock manures were degraded more than 90% when proper composting practice was used, and hence, this can be employed as a management strategy to decrease VA environmental loads. The reduction of VA concentrations during composting was mainly attributed to abiotic processes rather than biotic degradation. The VAs released to soils by the application of manure and manure-based composts can be degraded or inactivated to various degrees through abiotic process such as adsorption to soil components. Depending on the antibiotic species and soil properties, residues can be transferred to groundwater and surface water through leaching and runoff and can potentially be taken up by plants.
Solar-steam generation is one of the most promising technologies to mitigate the issue of clean water shortage using sustainable solar energy. Photothermal aerogels, especially the three-dimensional (3D) graphene-based aerogels, have shown unique merits for solar-steam generation, such as lightweight, high flexibility, and superior evaporation rate and energy efficiency. However, 3D aerogels require much more raw materials of graphene, which limits their large-scale applications. In this study, 3D photothermal aerogels composed of reduced graphene oxide (RGO) nanosheets, rice-straw-derived cellulose fibers, and sodium alginate (SA) are prepared for solar-steam generation. The use of rice straw fibers as skeletal support significantly reduces the need for the more expensive RGO by 43.5%, turning the rice straw biomass waste into value-added materials. The integration of rice straw fibers and RGO significantly enhances the flexibility and mechanical stability of the obtained photothermal RGO−SA−cellulose aerogel. The photothermal aerogel shows a strong broad-band light absorption of 96−97%. During solar-steam generation, the 3D photothermal aerogel effectively decreases the radiation and convection energy loss while enhancing energy harvesting from the environment, leading to an extremely high evaporation rate of 2.25 kg m −2 h −1 , corresponding to an energy conversion efficiency of 88.9% under 1.0 sun irradiation. The salinity of clean water collected during the evaporation of real seawater is only 0.37 ppm. The materials are environmentally friendly and cost-effective, showing great potential for real-world desalination applications.
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