Copper imbalance linked to oxidative stress and cell death during Zika virus infection in human astrocytes

The Zika virus (ZIKV) caused neurological abnormalities in more than 3500 Brazilian newborns between 2015 and 2020. Data have pointed to oxidative stress in astrocytes as well as to dysregulations in neural cell proliferation and cell cycle as important events accounting for the cell death and neurological complications observed in Congenital Zika Syndrome. Copper imbalance has been shown to induce similar alterations in other pathologies, and disturbances in copper homeostasis have already been described in viral infections. For this reason, we investigated copper homeostasis imbalance as a factor that could contribute to the cytotoxic effects of ZIKV infection in iPSC-derived human astrocytes. Our results show that ZIKV infection leads to a downregulation of one of the transporters mediating copper release, ATP7B protein. We also observed the activation of mechanisms that counteract high copper levels, including the synthesis of copper chaperones and the reduction of the copper importer protein CTR1. Finally, we show that chelator-mediated copper sequestration in ZIKV-infected astrocytes reduces the levels of reactive oxygen species and improves cell viability, but does not change the overall percentage of infected cells. In summary, our results show that copper homeostasis imbalance plays a role in the pathology of ZIKV in astrocytes, indicating that it may also be a factor accounting for the developmental abnormalities in the central nervous system following viral infection. Evaluating micronutrient levels and the use of copper chelators in pregnant women susceptible to ZIKV infection may be promising strategies to manage novel cases of congenital ZIKV syndrome.

Acute Toxicity of Cu-MOF Nanoparticles (nanoHKUST-1) towards Embryos and Adult Zebrafish

Metal-organic frameworks (MOFs) demonstrate unique properties, which are prospective for drug delivery, catalysis, and gas separation, but their biomedical applications might be limited due to their obscure interactions with the environment and humans. It is important to understand their toxic effect on nature before their wide practical application. In this study, HKUST-1 nanoparticles (Cu-nanoMOF, Cu3(btc)2, btc = benzene-1,3,5-tricarboxylate) were synthesized by the microwave (MW)-assisted ionothermal method and characterized by X-ray powder diffraction (XRD) and transmission electron microscopy (TEM) techniques. The embryotoxicity and acute toxicity of HKUST-1 towards embryos and adult zebrafish were investigated. To gain a better understanding of the effects of Cu-MOF particles towards Danio rerio (D. rerio) embryos were exposed to HKUST-1 nanoparticles (NPs) and Cu2+ ions (CuSO4). Cu2+ ions showed a higher toxic effect towards fish compared with Cu-MOF NPs for D. rerio. Both forms of fish were sensitive to the presence of HKUST-1 NPs. Estimated LC50 values were 2.132 mg/L and 1.500 mg/L for zebrafish embryos and adults, respectively. During 96 h of exposure, the release of copper ions in a stock solution and accumulation of copper after 96 h were measured in the internal organs of adult fishes. Uptake examination of the major internal organs did not show any concentration dependency. An increase in the number of copper ions in the test medium was found on the first day of exposure. Toxicity was largely restricted to copper release from HKUST-1 nanomaterials structure into solution.

Smartphone-powered efficient water disinfection at the point of use

Clean water free of bacteria is a precious resource in areas where no centralized water facilities are available. Conventional chlorine disinfection is limited by chemical transportation, storage, and the production of carcinogenic by-products. Here, a smartphone-powered disinfection system is developed for point-of-use (POU) bacterial inactivation. The integrated system uses the smartphone battery as a power source, and a customized on-the-go (OTG) hardware connected to the phone to realize the desired electrical output. Through a downloadable mobile application, the electrical output, either constant current (20–1000 µA) or voltage (0.7–2.1 V), can be configured easily through a user-friendly graphical interface on the screen. The disinfection device, a coaxial-electrode copper ionization cell (CECIC), inactivates bacteria by low levels of electrochemically generated copper with low energy consumption. The strategy of constant current control is applied in this study to solve the problem of uncontrollable copper release by previous constant voltage control. With the current control, a high inactivation efficiency of E. coli (~6 logs) is achieved with a low level of effluent Cu (~200 µg L−1) in the water samples within a range of salt concentration (0.2–1 mmol L−1). The smartphone-based power workstation provides a versatile and accurate electrical output with a simple graphical user interface. The disinfection device is robust, highly efficient, and does not require complex equipment. As smartphones are pervasive in modern life, the smartphone-powered CECIC system could provide an alternative decentralized water disinfection approach like rural areas and outdoor activities.

Architectured Cu–TNTZ Bilayered Coatings Showing Bacterial Inactivation under Indoor Light and Controllable Copper Release: Effect of the Microstructure on Copper Diffusion

A Ti–23Nb–0.7Ta–2Zr–1.2O alloy (at %), called “gum metal”, was deposited by direct-current magnetron sputtering (DCMS) on an under layer of copper. By varying the working pressure during the deposition, columnar TNTZ (Ti–Nb–Ta–Zr) nanoarchitectures were obtained. At low working pressures, the upper layer was dense with a coarse surface (Ra = 12 nm) with a maximum height of 163 nm; however, the other samples prepared at high working pressures showed columnar architectures with voids and an average roughness of 4 nm. The prepared coatings were characterized using atomic force microscopy (AFM) for surface topography, energy dispersive X-ray spectroscopy (EDX) for atomic mapping, scanning electron microscopy (SEM) for cross-section imaging, contact angle measurements for hydrophilic/hydrophobic balance of the prepared surfaces, and X-ray diffraction (XRD) for the crystallographic structures of the prepared coatings. The morphology and the density of the prepared coatings were seen to influence the hydrophilic properties of the surface. The antibacterial activity of the prepared coatings was tested in the dark and under low-intensity indoor light. Bacterial inactivation was seen to happen in the dark from samples presenting columnar nanoarchitectures. This was attributed to the diffusion of copper ions from the under layer. To verify the copper release from the prepared samples, an inductively coupled plasma mass spectrometer (ICP-MS) was used. Additionally, the atomic depth profiling of the elements was carried out by X-ray photoelectron spectroscopy (XPS) for the as-prepared samples and for the samples used for bacterial inactivation. The low amount of copper in the bulk of the TNTZ upper layer justifies its diffusion to the surface. Recycling of the antibacterial activity was also investigated and revealed a stable activity over cycles.

Effect of Chloride Ions on the Point-of-Use Drinking Water Disinfection Performance of Porous Ceramic Media Embedded with Metallic Silver and Copper

This study quantifies the effects of chloride ions on silver and copper release from porous ceramic cubes embedded with silver and copper and its effect on E. coli disinfection in drinking water. Log-reduction of E. coli by silver ions decreased after 4 h of contact time as the chloride ion concentration increased from 0 to 250 mg/L but, it was not changed by copper ions under the same conditions. For silver addition by silver-ceramic cubes, log reductions of E. coli decreased sharply from 7.2 to 1.6 after 12 h as the chloride concentration increased from 0 to 250 mg/L. For the silver-ceramic cube experiments, chloride ion also reduced the total silver concentration in solution. After 24 h, total silver concentrations in solution decreased from 61 µg/L to 20 µg/L for corresponding chloride ion concentrations. According to the MINTEQ equilibrium model analysis, the decrease in disinfection ability with silver embedded ceramic cubes could be the result of precipitation of silver ions as silver chloride. This suggests that AgCl was precipitating within the pore space of the ceramic. These results indicate that, although ionic silver is a highly effective disinfectant for E. coli, the presence of chloride ions can significantly reduce disinfection efficacy. For copper-ceramic cubes, log reductions of E. coli by copper embedded cubes increased from 1.2 to 1.5 when chloride ion concentration increased from 0 to 250 mg/L. Total copper concentrations in solution increased from 4 µg/L to 14 µg/L for corresponding chloride ion concentrations. These results point towards the synergistic effect of chloride ions on copper oxidation as an increased concentration of chloride enhances copper release.