Heavy metals are ubiquitous environmental pollutants that are extremely dangerous for public health, but the molecular mechanisms of their cytotoxic action are still not fully understood. In the ...present work, the possible contribution of the mitochondrial ATP-sensitive potassium channel (mK(ATP)), which is usually considered protective for the cell, to hepatotoxicity caused by heavy metals was investigated using polarography and swelling techniques as well as flow cytometry. Using isolated liver mitochondria from adult male Wistar rats and various potassium media containing or not containing penetrating anions (KNO3, KSCN, KAcet, KCl), we studied the effect of mK(ATP) modulators, namely its blockers (5-hydroxydecanoate, glibenclamide, ATP, ADP) and activators (diazoxide, malonate), on respiration and/or membrane permeability in the presence of hepatotoxins such as Cd2+, Hg2+, and Cu2+. It has been shown for the first time that, contrary to Hg2+ and depending on media used, the mK(ATP) modulators affect Cd2+- and/or Cu2+-induced alterations in mitochondrial swelling and respiration rates, although differently, nevertheless, in the ways compatible with mK(ATP) participation in both these cases. On rat AS-30D ascites hepatoma cells, it was found that, unlike Cd2+, an increase in the production of reactive oxygen species was observed with the simultaneous use of Cu2+ and diazoxide; in addition, there was no protective effect of diazoxide against cell death, which also occurred in the presence of Cu2+. In conclusion, the relationships (functional, structural and/or regulatory) between mK(ATP), components of the mitochondrial electron transport chain (CI, CII-CIII and/or ATP synthase, CV) and mitochondrial permeability transition pores were discussed, as well as the role of these molecular structures in the mechanisms of the cytotoxic action of heavy metals.
•mK(ATP) modulators (Diazo, 5-HD, Glib, Mg∙ATP, Mg∙ADP) affect heavy metals toxicity.•mK(ATP) participates in rat liver mitochondria dysfunction induced by Cu or Cd, but not Hg.•In case of Cu or Cd (appear to be IIQ inhibitors), CII is involved in mK(ATP) regulation.•ROS rise by Diazo in AS-30D rat hepatoma cells is increased by Cu and reduced by Cd.•mtETC, MPT pore and mK(ATP) are key players in cytotoxic action of heavy metals.
Square millimeters of free-standing graphene do not exist per se because of thermal fluctuations in two-dimensional crystals and their tendency to collapse during the detachment from the substrate. ...Here we form millimeter-scale freely suspended graphene by injecting an air bubble underneath a graphene monolayer floating at the water-air interface, which allowed us to measure the contact angle on fully free-standing non-contaminated graphene. A captive bubble measurement shows that free-standing clean graphene is hydrophilic with a contact angle of 42° ± 3°. The proposed design provides a simple tool to probe and explore the wettability of two-dimensional materials in free-standing geometries and will expand our perception of two-dimensional materials technologies from microscopic to now millimeter scales.
In this work, multiferroic cantilevers comprise a layer of a magnetoactive elastomer (MAE) and a commercially available piezoelectric polymer-based vibration sensor. The structures are fixed at one ...end in the horizontal plane and the magnetic field is applied vertically. First, the magnetoelectric (ME) response to uniform, triangle-wave magnetic fields with five different slew rates is investigated experimentally. Time and field dependences of the generated voltage, electric charge, and observed mechanical deflection are obtained and compared for four different thicknesses of the MAE layer. The ME responses to triangular and sinusoidal wave excitations are examined in contrast. Second, the ME response at low frequencies (≤3 Hz) is studied by the standard method of harmonic magnetic field modulation. The highest ME coupling coefficient is observed in the bias magnetic field strength of ≈73 kA/m and it is estimated to be about 3.3 ns/m (ME voltage coefficient ≈ 25 V/A) at theoretically vanishing modulation frequency (f→0 Hz). Presented results demonstrate that the investigated heterostructures are promising for applications as magnetic-field sensors and energy harvesting devices.
Interactions between water and graphene can be probed on a macroscopic level through wettability by measuring the water contact angle and on a microscopic level through water desorption kinetic ...studies using surface science methods. The contact angle studies of graphene pinpointed the critical role of sample preparation and measurement conditions in assessing the wettability of graphene. So far, studies of water desorption from graphene under the conditions of ultrahigh vacuum provided superior control over the environment but disregarded the importance of sample preparation. Here, we systematically examined the effect of the morphology of the growth substrate and of the transfer process on the macroscopic and microscopic wettability of graphene. Remarkably, the macroscopic wetting transparency of graphene does not always translate into microscopic wetting transparency, particularly in the case of an atomically defined Cu(111) substrate. Additionally, subtle differences in the type of substrates significantly alter the interactions between graphene and the first monolayer of adsorbed water but have a negligible effect on the apparent macroscopic wettability. This work looks into the correlations between the wetting properties of graphene, both on the macroscopic and microscopic scales, and highlights the importance of sample preparation in understanding the surface chemistry of graphene.
Theoretical simulations have predicted that a lipid bilayer forms a stable superstructure when a sheet of graphene is inserted in its hydrophobic core. We experimentally produced for the first time a ...lipid–graphene–lipid assembly by combining the Langmuir–Blodgett and the Langmuir–Schaefer methods. Graphene is sandwiched and remains flat within the hydrophobic core of the lipid bilayer. Using infrared spectroscopy, ellipsometry, and neutron reflectometry, we characterized the superstructure at every fabrication step. The hybrid superstructure is mechanically stable and graphene does not disturb the natural lipid bilayer structure.
Significant deformations of bodies made from compliant magnetoactive elastomers (MAE) in magnetic fields make these materials promising for applications in magnetically controlled actuators for soft ...robotics. Reported experimental research in this context was devoted to the behaviour in the quasi-static magnetic field, but the transient dynamics are of great practical importance. This paper presents an experimental study of the transient response of apparent longitudinal and transverse strains of a family of isotropic and anisotropic MAE cylinders with six different aspect ratios in time-varying uniform magnetic fields. The time dependence of the magnetic field has a trapezoidal form, where the rate of both legs is varied between 52 and 757 kA/(s·m) and the maximum magnetic field takes three values between 153 and 505 kA/m. It is proposed to introduce four characteristic times: two for the delay of the transient response during increasing and decreasing magnetic field, as well as two for rise and fall times. To facilitate the comparison between different magnetic field rates, these characteristic times are further normalized on the rise time of the magnetic field ramp. The dependence of the normalized characteristic times on the aspect ratio, the magnetic field slew rate, maximum magnetic field values, initial internal structure (isotropic versus anisotropic specimens) and weight fraction of the soft-magnetic filler are obtained and discussed in detail. The normalized magnetostrictive hysteresis loop is introduced, and used to explain why the normalized delay times vary with changing experimental parameters.
The voltage response to pulsed uniform magnetic fields and the accompanying bending deformations of laminated cantilever structures are investigated experimentally in detail. The structures comprise ...a magnetoactive elastomer (MAE) slab and a commercially available piezoelectric polymer multilayer. The magnetic field is applied vertically and the laminated structures are customarily fixed in the horizontal plane or, alternatively, slightly tilted upwards or downwards. Six different MAE compositions incorporating three concentrations of carbonyl iron particles (70 wt%, 75 wt% and 80 wt%) and two elastomer matrices of different stiffness are used. The dependences of the generated voltage and the cantilever’s deflection on the composition of the MAE layer and its thickness are obtained. The appearance of the voltage between the electrodes of a piezoelectric material upon application of a magnetic field is considered as a manifestation of the direct magnetoelectric (ME) effect in a composite laminated structure. The ME voltage response increases with the increasing total quantity of the soft-magnetic filler in the MAE layer. The relationship between the generated voltage and the cantilever’s deflection is established. The highest observed peak voltage around 5.5 V is about 8.5-fold higher than previously reported values. The quasi-static ME voltage coefficient for this type of ME heterostructures is about 50 V/A in the magnetic field of ≈100 kA/m, obtained for the first time. The results could be useful for the development of magnetic field sensors and energy harvesting devices relying on these novel polymer composites.
The effect of mature pine and birch trees on the mosaic pattern of the soil and vegetation cover of northern taiga pine forests exposed to long-term atmospheric emissions from the copper-nickel plant ...(the town of Monchegorsk, Murmansk oblast) is considered. In the background area, the biomass stock of live ground cover increases and the mortmass stock concentrated in plant and forest litter decreases from the near-trunk to intercrown zones; the differences in the trends of both the pine and birch tesserae are leveled off under the effect of aerotechnogenic pollution. The edificator roles of pine and birch trees are approximately the same. The high level of toxicity of the forest litter prevents the beginning of the recovery of ground cover in the impact zone.
Myeloproliferative neoplasms (MPNs) often carry JAK2(V617F), MPL(W515L), or CALR(del52) mutations. Current treatment options for MPNs include cytoreduction by hydroxyurea and JAK1/2 inhibition by ...ruxolitinib, both of which are not curative. We show here that cell lines expressing JAK2(V617F), MPL(W515L), or CALR(del52) accumulated reactive oxygen species–induced DNA double-strand breaks (DSBs) and were modestly sensitive to poly-ADP-ribose polymerase (PARP) inhibitors olaparib and BMN673. At the same time, primary MPN cell samples from individual patients displayed a high degree of variability in sensitivity to these drugs. Ruxolitinib inhibited 2 major DSB repair mechanisms, BRCA-mediated homologous recombination and DNA-dependent protein kinase–mediated nonhomologous end-joining, and, when combined with olaparib, caused abundant accumulation of toxic DSBs resulting in enhanced elimination of MPN primary cells, including the disease-initiating cells from the majority of patients. Moreover, the combination of BMN673, ruxolitinib, and hydroxyurea was highly effective in vivo against JAK2(V617F)+ murine MPN-like disease and also against JAK2(V617F)+, CALR(del52)+, and MPL(W515L)+ primary MPN xenografts. In conclusion, we postulate that ruxolitinib-induced deficiencies in DSB repair pathways sensitized MPN cells to synthetic lethality triggered by PARP inhibitors.
•Ruxolitinib caused DNA repair defects and sensitized MPN stem and progenitor cells to PARP inhibitors.•Quiescent and proliferating MPN cells were eliminated by ruxolitinib and olaparib plus or minus hydroxyurea.
Solid substrates often induce non-uniform strain and doping in graphene monolayer, therefore altering the intrinsic properties of graphene, reducing its charge carrier mobilities and, consequently, ...the overall electrical performance. Here, we exploit confocal Raman spectroscopy to study graphene directly free-floating on the surface of water, and show that liquid supports relief the preexisting strain, have negligible doping effect and restore the uniformity of the properties throughout the graphene sheet. Such an effect originates from the structural adaptability and flexibility, lesser contamination and weaker intermolecular bonding of liquids compared to solid supports, independently of the chemical nature of the liquid. Moreover, we demonstrate that water provides a platform to study and distinguish chemical defects from substrate-induced defects, in the particular case of hydrogenated graphene. Liquid supports, thus, are advantageous over solid supports for a range of applications, particularly for monitoring changes in the graphene structure upon chemical modification.
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