Platelet Mitochondrial Bioenergetics Reprogramming in Patients with Urothelial Carcinoma

Mitochondrial bioenergetics reprogramming is an essential response of cells to stress. Platelets, an accessible source of mitochondria, have a crucial role in cancer development; however, the platelet mitochondrial function has not been studied in urothelial carcinoma (UC) patients. A total of 15 patients with UC and 15 healthy controls were included in the study. Parameters of platelet mitochondrial respiration were evaluated using the high-resolution respirometry method, and the selected antioxidant levels were determined by HPLC. In addition, oxidative stress was evaluated by the thiobarbituric acid reactive substances (TBARS) concentration in plasma. We demonstrated deficient platelet mitochondrial respiratory chain functions, oxidative phosphorylation (OXPHOS), and electron transfer (ET) capacity with complex I (CI)-linked substrates, and reduced the endogenous platelet coenzyme Q₁₀ (CoQ₁₀) concentration in UC patients. The activity of citrate synthase was decreased in UC patients vs. controls (p = 0.0191). γ-tocopherol, α-tocopherol in platelets, and β-carotene in plasma were significantly lower in UC patients (p = 0.0019; p = 0.02; p = 0.0387, respectively), whereas the plasma concentration of TBARS was increased (p = 0.0022) vs. controls. The changes in platelet mitochondrial bioenergetics are consistent with cell metabolism reprogramming in UC patients. We suppose that increased oxidative stress, decreased OXPHOS, and a reduced platelet endogenous CoQ₁₀ level can contribute to the reprogramming of platelet mitochondrial OXPHOS toward the activation of glycolysis. The impaired mitochondrial function can contribute to increased oxidative stress by triggering the reverse electron transport from the CoQ₁₀ cycle (Q-junction) to CI.     

The Role of Vitamin A in Retinal Diseases

Vitamin A is an essential fat-soluble vitamin that occurs in various chemical forms. It is essential for several physiological processes. Either hyper- or hypovitaminosis can be harmful. One of the most important vitamin A functions is its involvement in visual phototransduction, where it serves as the crucial part of photopigment, the first molecule in the process of transforming photons of light into electrical signals. In this process, large quantities of vitamin A in the form of 11-cis-retinal are being isomerized to all-trans-retinal and then quickly recycled back to 11-cis-retinal. Complex machinery of transporters and enzymes is involved in this process (i.e., the visual cycle). Any fault in the machinery may not only reduce the efficiency of visual detection but also cause the accumulation of toxic chemicals in the retina. This review provides a comprehensive overview of diseases that are directly or indirectly connected with vitamin A pathways in the retina. It includes the pathophysiological background and clinical presentation of each disease and summarizes the already existing therapeutic and prospective interventions.     

The grain-boundary resistance of CeO2 ceramics: A combined microscopy-spectroscopy-simulation study of a dilute solution

Weakly acceptor-doped ceria ceramics were characterized structurally and compositionally with advanced transmission electron microscopy (TEM) techniques and electrically with electrochemical impedance spectroscopy (EIS). The grain boundaries studied with TEM were found to be free of second phases. The impedance spectra, acquired in the range 703 ≤ T/K ≤ 893 in air, showed several arcs that were analyzed in terms of bulk, grain-boundary, and electrode responses. We ascribed the grain-boundary resistance to the presence of space-charge layers. Continuum-level simulations were used to calculate charge-carrier distributions (of acceptor cations, oxygen vacancies, and electrons) in these space-charge layers. The acceptor cations were assumed to be mobile at high (sintering) temperatures but immobile at the temperatures of the EIS measurements. Space-charge formation was assumed to be driven by the segregation of oxygen vacancies to the grain-boundary core. Comparisons of data from the simulations and from the EIS measurements yielded space-charge potentials and the segregation energy of vacancies to the grain-boundary core. The space-charge potentials from the simulations are compared with values obtained by applying the standard, analytical (Mott–Schottky and Gouy–Chapman) expressions. The importance of modelling space-charge layers from the thermodynamic level is demonstrated.     

Solubility parameter estimation and phase inversion modeling of bentonite-doped polymeric membrane systems

Effects of bentonite concentration on morphology and permeation characteristics of bentonite-doped polysulfone membranes were investigated. Solubility sphere for bentonite was constructed to estimate its solubility parameter. Thermodynamic modeling of phase inversion of this system was carried out using Flory–Huggins theory. The trade-off between thermodynamic and kinetic parameters was used to predict the membrane morphology for bentonite concentration varying from 0 to 5 wt %. The porosity of bentonite-doped membranes decreased up to 3 wt % that increased thereafter. Morphological analysis showed dense cross section with finger-like macrovoids at 3 wt % beyond which it changed to honeycomb structure with large circular voids. Permeability of 3 wt % membrane was the lowest (5.6 × 10⁻¹² m/Pa s) with 95% bovine serum albumin rejection. Contact angle of the membranes decreased from 83 to 66° with bentonite addition making the membrane more hydrophilic. © 2019 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2020 , 137, 48450.     

Interaction of Cucurbit[7]uril with Oxime K027, Atropine,and Paraoxon: Risky or Advantageous Delivery System?

Antidotes against organophosphates often possess physicochemical properties that mitigate their passage across the blood–brain barrier. Cucurbit[7]urils may be successfully used as a drug delivery system for bisquaternary oximes and improve central nervous system targeting. The main aim of these studies was to elucidate the relationship between cucurbit[7]uril, oxime K027, atropine, and paraoxon to define potential risks or advantages of this delivery system in a complex in vivo system. For this reason, in silico (molecular docking combined with umbrella sampling simulation) and in vivo (UHPLC—pharmacokinetics, toxicokinetics; acetylcholinesterase reactivation and functional observatory battery) methods were used. Based on our results, cucurbit[7]urils affect multiple factors in organophosphates poisoning and its therapy by (i) scavenging paraoxon and preventing free fraction of this toxin from entering the brain, (ii) enhancing the availability of atropine in the central nervous system and by (iii) increasing oxime passage into the brain. In conclusion, using cucurbit[7]urils with oximes might positively impact the overall treatment effectiveness and the benefits can outweigh the potential risks.     

Vortex characteristics due to nozzle clogging in water caster mould: modelling and validation

In continuous slab casting, clogging in the submerged entry nozzle (SEN) ports leads to flow asymmetry and vortex formation in the mould. Knowledge of vortexing and its influence on product quality is fundamental for defect-free production. In this study, the interconnected effects of nozzle clogging and SEN submergence depth, variation on flow asymmetry and vortex characteristics in a 0.4 scale water caster have been characterised by CFD investigation and validated with experimental results from the authors’ previous work. Mean flow velocities at the sub-meniscus and near the port exit predicted by the computational model are compared with the time-averaged values of the impeller probe velocity measurements and found to be in reasonable agreement. Three different clogging conditions (0, 33 and 66% in the left port of the SEN) for SEN submergence depth of 60?mm are studied and the 66% clogging produced vortices having largest diameter, which is consistent with the experimental observations. The effects of SEN submergence depth on flow asymmetry and vortexing are investigated with three different conditions – 40, 60 and 80?mm. It is found that the shallow SEN submergence depth (40?mm) produces vortices of largest diameter and the flow is most stable for a SEN submergence depth of 60?mm among the three cases. Vortex bending towards the SEN as noticed in the experimental observations is also observed in the computational study. This work illustrates the possibility of capturing features of vortexing using validated CFD model.     

Microbial and chemical assessment of regions within New Orleans, LA impacted by Hurricane Katrina

The city of New Orleans, LA was severely impacted by flooding and wind damage following landfall of Hurricane Katrina in August 2005. The city's drinking water infrastructure was severely compromised and massive amounts of sediment were redeposited throughout the flooded region. Thousands of homes were water-damaged resulting in the rapid growth of mold. In September and October 2005 a convenience sample of selected homes, tap water, surface water, and sediment within New Orleans was assessed for mold contamination, microbial contamination, and heavy metal concentrations. At selected sites, indoor mold spore concentrations were compared to outdoor concentrations. The purpose of this study was to conduct a baseline environmental assessment in an effort to identify public health threats caused by wind and flood damage. Surface waters contained high concentrations of bacterial indicators whereas no bacteria were detected in tap water, even from taps containing no chlorine residual. Sediment samples contained concentrations of lead and arsenic similarto pre-Katrina concentrations. Outdoor total spore (sp) concentrations ranged from >6500 to 84 713 sp/m(3). Indoor concentrations ranged from 6142 to 735 123 sp/m(3). For the 13 locations with matched indoor/ outdoor samples, the mean indoor/outdoor spore ratio was 4.11 (ranging from 0.27 to >11.44). Inside 5 of the 13 homes, total spore counts/m(3) exceeded 100 000, with measurements in the moldiest home exceeding 700 000 sp/ m(3). In conclusion, surface waters had high concentrations of bacterial contamination but no bacterial indicators were present in tap water. Sediment samples did not have appreciable increases in lead or arsenic. Flooded homes, however, contained substantial concentrations of mold which could present a public health exposure route to individuals repopulating and restoring the City of New Orleans.     

Aroma profiles of five basil (Ocimum basilicum L.) cultivars grown under conventional and organic conditions

A headspace solid-phase microextraction (HS-SPME) method coupled to gas chromatography–ion trap mass spectrometry (GC–ITMS) has been developed and applied for profiling of volatile compounds released from five Ocimum basilicum L. cultivars grown under both organic and conventional conditions. Comprehensive two-dimensional gas chromatography coupled to time-of-flight mass spectrometry (GC×GC–TOFMS) was employed for confirmation of identity of volatiles extracted from the basil headspace by SPME.     

Emulsifying properties of β-lactoglobulin and Quillaja bark saponin mixtures: Effects of number of homogenization passes,pH, and NaCl concentration

The effects of number of homogenization passes, pH, and NaCl concentration on the formation and stability of oil-in-water emulsions comprising a mixture of a biosurfactant (Quillaja bark saponin) and a globular protein (β-lactoglobulin) were investigated. The emulsions were characterized as to visual appearance, droplet size, droplet surface charge, and rheology. The emulsions obtained by different conditions (4, 6, or 8 passes; pH 7, 8, or 9; and 0, 100, or 200 mmol L^?1 of NaCl) were polydisperse, presented relatively small average droplet sizes (z-average < 323 nm) as well as negative droplet charge (between –20 and –79.6 mV) in all evaluated conditions. Regardless of the number of homogenization passes, the emulsions exhibited low apparent viscosity and pseudoplastic behavior with small yield stress. Viscoelastic behavior was also observed, thus the emulsions were characterized as weak gels. Four homogenization passes were enough to obtain small droplets in the evaluated conditions. Droplet size was not significantly affected by NaCl concentration and pH (p > 0.05). On the other hand, the absolute ζ-potential values significantly decreased and increased upon increased NaCl content and pH, respectively. Regardless of the tested conditions, all emulsions had good stability against phase separation and droplet aggregation, since no significant changes in average droplet size were observed throughout storage (p > 0.05). In the presence of NaCl, in which droplet charge significantly decreased, emulsion was also stable. Thus, we can conclude that electrostatic repulsion as well as steric repulsion was responsible for stabilization.     

Impact of electrically formed interfacial layer and improved memory characteristics of IrOx/high-κx/W structures containing AlOx,GdOx, HfOx,and TaOx switching materials

Improved switching characteristics were obtained from high-κ oxides AlO_x, GdO_x, HfO_x, and TaO_x in IrO_x/high-κ_x/W structures because of a layer that formed at the IrO_x/high-κ_x interface under external positive bias. The surface roughness and morphology of the bottom electrode in these devices were observed by atomic force microscopy. Device size was investigated using high-resolution transmission electron microscopy. More than 100 repeatable consecutive switching cycles were observed for positive-formatted memory devices compared with that of the negative-formatted devices (only five unstable cycles) because it contained an electrically formed interfacial layer that controlled ‘SET/RESET’ current overshoot. This phenomenon was independent of the switching material in the device. The electrically formed oxygen-rich interfacial layer at the IrO_x/high-κ_x interface improved switching in both via-hole and cross-point structures. The switching mechanism was attributed to filamentary conduction and oxygen ion migration. Using the positive-formatted design approach, cross-point memory in an IrO_x/AlO_x/W structure was fabricated. This cross-point memory exhibited forming-free, uniform switching for >1,000 consecutive dc cycles with a small voltage/current operation of ±2 V/200 μA and high yield of >95% switchable with a large resistance ratio of >100. These properties make this cross-point memory particularly promising for high-density applications. Furthermore, this memory device also showed multilevel capability with a switching current as low as 10 μA and a RESET current of 137 μA, good pulse read endurance of each level (>10⁵ cycles), and data retention of >10⁴ s at a low current compliance of 50 μA at 85°C. Our improvement of the switching characteristics of this resistive memory device will aid in the design of memory stacks for practical applications.