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In situ recovery (ISR) is the predominant method of uranium extraction in the United States. During ISR, uranium is leached from an ore body and extracted through ion exchange. The resultant production bleed water (PBW) contains contaminants such as arsenic and other heavy metals. Samples of PBW from an active ISR uranium facility were treated with cupric oxide nanoparticles (CuO-NPs). CuO-NP treatment of PBW reduced priority contaminants, including arsenic, selenium, uranium, and vanadium. Untreated and CuO-NP treated PBW was used as the liquid component of the cell growth media and changes in viability were determined by the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay in human embryonic kidney (HEK 293) and human hepatocellular carcinoma (Hep G2) cells. CuO-NP treatment was associated with improved HEK and HEP cell viability. Limitations of this method include dilution of the PBW by growth media components and during osmolality adjustment as well as necessary pH adjustment. This method is limited in its wider context due to dilution effects and changes in the pH of the PBW which is traditionally slightly acidic however; this method could have a broader use assessing CuO-NP treatment in more neutral waters.

Background Acute respiratory distress syndrome (ARDS) is the primary cause of mortality in critically ill subjects infected with the novel coronavirus (severe acute respiratory syndrome‐coronavirus‐2, or SARS‐CoV‐2). Given the elevated levels of circulating proinflammatory cytokines such as tumor necrosis factors (TNF)‐⍺ and interleukin (IL)‐6, it has been postulated that a “cytokine storm” is responsible for the COVID‐19 ARDS. A critical step in cytokine signaling is the shedding of membrane‐anchored cytokines and their receptors. Objective To determine the role of the metalloprotease/shreddase ADAM‐17 (A disinterring and metalloproteinase 17) in COVID‐19‐ mediated cytokine release from lung epithelial cells. We hypothesized pharmacological inhibition of ADAM‐17 attenuated COVID‐19‐induced release of TNF‐α in lung epithelial cells. Materials and Methods Human primary bronchial/tracheal epithelial cells (ATCC®, PS‐300‐010) were cultured to sub‐confluence and challenged with COVID‐19 Spike Coronavirus pseudovirus (SARS‐COV‐2 pseudo‐virus, MyBioSource), and phorbol‐12‐myristate‐13‐acetate (PMA, Sigma), which was used as a positive control in the presence or absence of the ADAM‐17 inhibitor TNF‐α Protease Inhibitor‐0 (TAPI‐0, Sigma). TNF‐α levels were determined in the cell media at different time points (2‐12h) following the challenge using an ELISA assay. Data are represented as mean ± SEM, and statistical significance was determined by using the Student’s t‐test. Results Treatment with both PMA (0.1 µM) and SARS‐COV‐2 pseudovirus (1x108pseudoviral particles), resulted in a robust increase of TNF‐α in the culture media 8 h post‐stimulation (3243.75± 55.3 and 1278.6 ± 357 pg/mL respectively, p <0.05, n = 4). Furthermore, treatment with TAPI‐0 resulted in a concentration‐dependent inhibition of the pseudovirus‐induced TNF‐α release by cultured bronchial epithelial cells, with a complete inhibition observed at 100 µM of TAPI‐0. Conclusion Targeting ADAM‐17 is a potential strategy to mitigated the cytokine storm associated with COVID‐19‐ARDS.

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