Search Results (16)

Organ transplantation has significantly progressed since the 1950s, with notable advancements in surgical procedures and immunosuppression. However, current organ preservation techniques, mainly static cold storage, have not evolved at the same pace and remain insufficient to prevent ischemic and oxidative damage. This damage, primarily caused by the cessation of aerobic metabolism, limits organ viability and transplant outcomes. In this study, we investigated whether supplementing a storage solution with a hemoglobin-based oxygen carrier (HBOC) could improve the condition of ex vivo rabbit kidneys by maintaining oxygenation and supporting aerobic metabolism. In a paired, randomized design, contralateral rabbit kidneys were preserved either in a Krebs-Ringer-based solution enriched with the polymerized hemoglobin OxyVita^®C (15 g/L, p50 4–6 mmHg, MW ≈ 17 MDa, pH adjusted to 7.4) or in an HBOC-free control solution. Physicochemical characterization of OxyVita^®C included oxygen equilibrium curves, zeta potential, polydispersity index, and dynamic light scattering. Biochemical markers (AST, ALT, LDH, K⁺, pH) and histopathological assessments were used to evaluate tissue integrity over 24 h. Histology was additionally stratified according to rinsing protocols (unwashed, NaCl single flush, triple flush), and tubular necrosis was scored by blinded pathologists. Group comparisons were analyzed using ANOVA with Tukey’s HSD test. The HBOC-enriched solution showed improved tissue preservation, higher cell survivability, and better histomorphological profiles, with significantly reduced tubular necrosis scores compared to controls. These findings suggest that active oxygen delivery via HBOCs offers a promising strategy to mitigate ischemic damage during ex vivo kidney storage. Limitations include the lack of transplantation outcomes and direct ROS quantification, which will be addressed in future work integrating hypothermic and normothermic machine perfusion. Full article

Aflatoxins are toxic organic substances that are synthesized on the surfaces of seeds, nuts, and similar products by some fungi under elevated humidity. They decompose at temperatures well above 130 °C, so standard heating or autoclaving is an obsolete technique for the degradation of toxins on surfaces without significant modification of the treated material. Non-equilibrium plasma was used to degrade aflatoxins at low temperatures and determine the efficiency of O atoms. A commercial mixture of aflatoxins was deposited on smooth substrates, and the solvent was evaporated so that about a 3 nm thick film of dry toxins remained on the substrates. The samples were exposed to low-pressure oxygen plasma sustained by an inductively coupled radiofrequency (RF) discharge in either the E or H mode. The gas pressure was 20 Pa, the forward RF power was between 50 and 700 W, and the O-atom flux was between 1.2 × 10²³ and 1.5 × 10²⁴ m⁻² s⁻¹. Plasma treatment caused the rapid degradation of aflatoxins, whose concentration was deduced from the fluorescence signal at 455 nm upon excitation with a monochromatic source at 365 nm. The degradation was faster at higher discharge powers, but the degradation curves fitted well when plotted against the dose of O atoms. The experiments showed that the aflatoxin concentration dropped below the detection limit of the fluorescence probe after receiving the O-atom dose of just above 10²⁵ m⁻². This dose was achieved within 10 s of treatment in plasma in the H mode, and approximately a minute when plasma was in the E mode. The method provides a low-temperature solution for the efficient detoxification of agricultural products. Full article

Background/Objectives: Sickle cell disease (SCD) is caused by a β-globin gene mutation (βGlu6Val) that produces sickle hemoglobin (HbS). When deoxygenated, HbS polymerizes, leading to red blood cell (RBC) sickling; therefore, hemoglobin is a central therapeutic target for SCD. Current strategies include increasing the levels of oxygenated HbS (which cannot polymerize) and/or directly destabilizing the deoxygenated HbS polymer. This study aimed to design and synthesize next-generation Michael acceptor antisickling hemoglobin modifiers (MMA-206, MMA-207, MMA-208, and MMA-209) and evaluate their antisickling efficacy. Methods: Four Michael acceptor compounds (MMA-206 to MMA-209) were synthesized and characterized. Their pharmacologic activities and modes of action were assessed in vitro using disulfide exchange reaction with normal hemoglobin, sickling inhibition assays with sickle red blood cells, and hemoglobin oxygen equilibrium curve analysis with normal and sickle red blood cells. Results: MMA-206 exhibited the strongest antisickling activity, outperforming previously studied Michael acceptor antisickling agents. All four MMA analogues bound to hemoglobin at βCys93, destabilizing the low-oxygen-affinity T-state and thereby preventing deoxygenation-induced HbS polymerization and RBC sickling. In addition, they appeared to directly destabilize the HbS polymer, indicating a second mechanism of action. Furthermore, time-dependent oxygen equilibrium measurements confirmed that their pharmacologic effect was sustained over time in vitro. Conclusions: The new Michael acceptor compounds, particularly MMA-206, demonstrated potent antisickling effects via dual mechanisms and showed sustained activity. These findings highlight Michael acceptor compounds’ promise as hemoglobin oxygen-affinity modulators for the treatment of SCD. Full article

We prepared a rhodamine (RB)–perylene (Pery) compact electron donor/acceptor dyad (RB–Pery) to study the spin-orbit charge-transfer intersystem crossing (SOCT–ISC). The UV–vis absorption spectrum indicates a negligible electronic interaction between the donor and acceptor at ground state. However, the fluorescence of both the RB and Pery units are quenched in the dyad, which is attributed to the photoinduced electron transfer, supported by the electrochemical studies. Nanosecond transient absorption (ns-TA) spectra show delocalized triplet states, i.e., there is an excited-state equilibrium between Pery and the RB triplet states. The triplet state lifetime was determined as 109.8 μs. With intermolecular triplet–triplet energy transfer, monitored using ns-TA spectra, the triplet-state energy balance between RB and Pery in RB–Pery was confirmed. The proposed cascade photophysical processes of the dyad are ¹RB*-Pery→RB–Pery^+•→[³RB*-Pery↔RB-³Pery*]. Moreover, long-lived rhodamine radical cation (in milliseconds) was detected in both deaerated/aerated non-polar or low-polarity solvents (i.e., p-xylene, toluene). The potential energy curve of the dyad against the variation in the dihedral angle between the two units indicates large torsional freedom (53°~128°) in RB–Pery, which leads to inefficient SOCT–ISC; consequently, low singlet-oxygen quantum yields (Φ_Δ = 2~8%) were observed. Full article

Sickle cell disease (SCD) is caused by a single-point mutation, and the ensuing deoxygenation-induced polymerization of sickle hemoglobin (HbS), and reduction in bioavailability of vascular nitric oxide (NO), contribute to the pathogenesis of the disease. In a proof-of-concept study, we successfully incorporated nitrate ester groups onto two previously studied potent antisickling aromatic aldehydes, TD7 and VZHE039, to form TD7-NO and VZHE039-NO hybrids, respectively. These compounds are stable in buffer but demonstrated the expected release of NO in whole blood in vitro and in mice. The more promising VZHE039-NO retained the functional and antisickling activities of the parent VZHE039 molecule. Moreover, VZHE039-NO, unlike VZHE039, significantly attenuated RBC adhesion to laminin, suggesting this compound has potential in vivo RBC anti-adhesion properties relevant to vaso-occlusive events. Crystallographic studies show that, as with VZHE039, VZHE039-NO also binds to liganded Hb to make similar protein interactions. The knowledge gained during these investigations provides a unique opportunity to generate a superior candidate drug in SCD with enhanced benefits. Full article

This paper reviews the near-equilibrium ammonothermal (NEAT) growth of bulk gallium nitride (GaN) crystals and reports the evaluation of 2″ GaN substrates and 100 mmbulk GaN crystal grown in our pilot production reactor. Recent progress in oxygen reduction enabled growing NEAT GaN substrates with lower residual oxygen, coloration, and optical absorption. The oxygen concentration was approximately 2 × 10¹⁸ cm⁻², and the optical absorption coefficient was 1.3 cm⁻¹ at 450 nm. Maps of full-width half maximum (FWHM) of X-ray diffraction rocking curveswere generated for grown crystals and finished wafers. The X-ray rocking curve maps confirmed high-quality and uniform microstructure across the entire surface of the bulk crystals and substrates. The average FWHM of the 50 best bulk crystals from the recent batch was 28 ± 4 arcsec for the 002 diffraction and 34 ± 5 arcsec for the 201 diffraction, with an average radius of curvature of 20 m. X-ray topography measured on both sides of the bulk crystals implied that the density of dislocations wasreduced by one order of magnitude during the NEAT growth. A typical NEAT GaN substrate shows dislocation density of about 2 × 10⁵ cm⁻². Full article

5-hydroxyfurfural (5HMF), an allosteric effector of hemoglobin (Hb) with an ability to increase Hb affinity for oxygen has been studied extensively for its antisickling effect in vitro and in vivo, and in humans for the treatment of sickle cell disease (SCD). One of the downstream pathophysiologies of SCD is nitric oxide (NO) deficiency, therefore increasing NO (bio)availability is known to mitigate the severity of SCD symptoms. We report the synthesis of an NO-releasing prodrug of 5HMF (5HMF-NO), which in vivo, is expected to be bio-transformed into 5HMF and NO, with concomitant therapeutic activities. In vitro studies showed that when incubated with whole blood, 5HMF-NO releases NO, as anticipated. When incubated with sickle blood, 5HMF-NO formed Schiff base adduct with Hb, increased Hb affinity for oxygen, and prevented hypoxia-induced erythrocyte sickling, which at 1 mM concentration were 16%, 10% and 27%, respectively, compared to 21%, 18% and 21% for 5HMF. Crystal structures of 5HMF-NO with Hb showed 5HMF-NO bound to unliganded (deoxygenated) Hb, while the hydrolyzed product, 5HMF bound to liganded (carbonmonoxy-ligated) Hb. Our findings from this proof-of-concept study suggest that the incorporation of NO donor group to 5HMF and analogous molecules could be a novel beneficial strategy to treat SCD and warrants further detailed in vivo studies. Full article

Antimony (Sb) traces in water pose a serious threat to human health due to their negative effects. In this work, nanoscale zero-valent iron (Fe⁰) supported on activated carbon (nZVI) was employed for eliminating Sb(V) from the drinking water. To better understand the overall process, the effects of several experimental variables, including pH, dissolved oxygen (DO), coexisting ions, and adsorption kinetics on the removal of Sb(V) from the SW were investigated by employing fixed-bed column runs or batch-adsorption methods. A pH of 4.5 and 72 h of equilibrium time were found to be the ideal conditions for drinking water. The presence of phosphate (${\mathrm{PO}}_4^{3-}$), silicate (${\mathrm{SiO}}_4^{2-}$), chromate (${\mathrm{CrO}}_4^{2-}$) and arsenate (${\mathrm{AsO}}_4^{3-}$) significantly decreased the rate of Sb(V) removal, while humic acid and other anions exhibited a negligible effect. The capacity for Sb(V) uptake decreased from 6.665 to 2.433 mg when the flow rate was increased from 5 to 10 mL·min⁻¹. The dynamic adsorption penetration curves of Sb(V) were 116.4% and 144.1% with the weak magnetic field (WMF) in fixed-bed column runs. Considering the removal rate of Sb(V), reusability, operability, no release of Sb(V) after being incorporated into the iron (hydr)oxides structure, it can be concluded that WMF coupled with ZVI would be an effective Sb(V) immobilization technology for drinking water. Full article

The utility of measuring whole-animal performance to frame the metabolic response to environmental hypoxia is well established. Progressively reducing ambient oxygen (O₂) will initially limit maximum metabolic rate as a result of a hypoxemic state and ultimately lead to a time-limited, tolerance state supported by substrate-level phosphorylation when the O₂ supply can no longer meet basic needs (standard metabolic rate, SMR). The metabolic consequences of declining ambient O₂ were conceptually framed for fishes initially by Fry’s hypoxic performance curve, which characterizes the hypoxemic state and its consequences to absolute aerobic scope (AAS), and Hochachka’s concept of scope for hypoxic survival, which characterizes time-limited life when SMR cannot be supported by O₂ supply. Yet, despite these two conceptual frameworks, the toolbox to assess whole-animal metabolic performance remains rather limited. Here, we briefly review the ongoing debate concerning the need to standardize the most commonly used assessments of respiratory performance in hypoxic fishes, namely critical O₂ (the ambient O₂ level below which maintenance metabolism cannot be sustained) and the incipient lethal O₂ (the ambient O₂ level at which a fish loses the ability to maintain upright equilibrium), and then we advance the idea that the most useful addition to the toolbox will be the limiting-O₂ concentration (LOC) performance curve. Using Fry & Hart’s (1948) hypoxia performance curve concept, an LOC curve was subsequently developed as an eco-physiological framework by Neil et al. and derived for a group of fish during a progressive hypoxia trial by Claireaux and Lagardère (1999). In the present review, we show how only minor modifications to available respirometry tools and techniques are needed to generate an LOC curve for individual fish. This individual approach to the LOC curve determination then increases its statistical robustness and importantly opens up the possibility of examining individual variability. Moreover, if peak aerobic performance at a given ambient O₂ level of each individual is expressed as a percentage of its AAS, the water dissolved O₂ that supports 50% of the individual’s AAS (DO_AAS-50) can be interpolated much like the P₅₀ for an O₂ hemoglobin dissociation curve (when hemoglobin is 50% saturated with O₂). Thus, critical O₂, incipient lethal O₂, DO_AAS-50 and P₅₀ and can be directly compared within and across species. While an LOC curve for individual fish represents a start to an ongoing need to seamlessly integrate aerobic to anaerobic capacity assessments in a single, multiplexed respirometry trial, we close with a comparative exploration of some of the known whole-organism anaerobic and aerobic capacity traits to examine for correlations among them and guide the next steps. Full article

The main objective of the present paper is to evaluate by thermal (cooling curve) analysis the solidification pattern and the occurrence of the layer of degenerate graphite at the surface of ductile iron castings (3.15% Si, typically as 450-18 grade, ISO 1563/2011), with or without a mold coating, including S or O, and different agents (carbonic material, iron powder), supposed to act to block their diffusion into the iron melt. It is found that the mold coating materials temperately influence the parameters of the solidification cooling curves and, more visibly, the occurrence and the thickness of the undesired skin layer. Different graphite morphologies comparable to the casting body are present, at a large range of thicknesses, from 50 up to 200 µm. The sulfur presence in the mold coating will promote a higher skin thickness compared to oxygen (up to 50% by oxygen and 2.5–3.3 times for sulfur action), despite the fact that in the casting body, the graphite nodularity undergoes a limited decrease (from 85% up to 82%–83% level). Carbonic material or iron powder supplementary addition decreases these undesired effects, but the solidification undercooling compared to the equilibrium system is increased. It is found that carbonic material is more efficient at limiting oxygen than iron powder is at limiting the negative effects of sulfur on the casting skin thickness. More experiments are necessary to quantify their capacity to block the oxygen or sulfur transfer into the iron melt. Full article

Due to their high hemocompatibility and gas permeation capacity, bi-soft segment polyurethane/polycaprolactone (PU/PCL) polymers are promising materials for use in membrane blood oxygenators. In this work, both nonporous symmetric and integral asymmetric PU/PCL membranes were synthesized, and the permeation properties of the atmospheric gases N₂, O₂, and CO₂ through these membranes were experimentally determined using a new custom-built gas permeation apparatus. Permeate pressure vs. time curves were obtained at 37.0 °C and gas feed pressures up to 5 bar. Fluxes, permeances, and permeability coefficients were determined from the steady-state part of the curves, and the diffusion and sorption coefficients were estimated from the analysis of the transient state using the time-lag method. Independent measurements of the sorption coefficients of the three gases were performed, under equilibrium conditions, in order to validate the new setup and procedure. This work shows that the gas sorption in the PU/PCL polymers is the dominant factor for the permeation properties of the atmospheric gases in these membranes. Full article

Nano-magnesia is the intermediate product during the growth of magnesia inclusion in Mg-deoxidized steel. Understanding the thermodynamics on nano-magnesia is important to explore the relationship between magnesia product size and deoxidation reaction in molten steel. In this work, a thermodynamic modeling is developed to study the Mg-deoxidation reaction between nano-magnesia inclusions and liquid iron. The thermodynamic results based on the first principle method show that the Gibbs free energy change for the forming magnesia product decrease gradually with the increasing nano-magnesia size in liquid iron. The published experimental data about Mg-deoxidation equilibria in liquid iron are scattered across the region between the thermodynamic curves of 2 nm magnesia and bulk-magnesia. It is suggested that these scattered experimental data of Mg-deoxidized liquid iron are in different thermodynamic states. Some of these experiments are in equilibrium with bulk-magnesia, while most of these experiments do not reach the equilibrium state between bulk magnesia and liquid iron, but in quasi-equilibria between nano-magnesia and liquid iron. This is the reason that different researchers gave different equilibrium constants. Furthermore, the behavior of the metastable magnesia is one of the most important reasons for the supersaturation ratio or the excess oxygen for MgO formation in liquid iron. Full article

The Noble–Abel Stiffened-Gas (NASG) equation of state (Le Métayer, O. and Saurel, R. proposed in 2016) is extended to variable attractive and repulsive effects to improve the liquid phase accuracy when large temperature and pressure variation ranges are under consideration. The transition from pure phase to supercritical state is of interest as well. The gas phase is considered through the ideal gas assumption with variable specific heat rendering the formulation valid for high temperatures. The liquid equation-of-state constants are determined through the saturation curves making the formulation suitable for two-phase mixtures at thermodynamic equilibrium. The overall formulation is compared to experimental characteristic curves of the phase diagram showing good agreement for various fluids (water, oxygen). Compared to existing cubic equations of state, the present one is convex, a key feature for computations with hyperbolic flow models. Full article

Hemoglobin (Hb) modifiers that stereospecifically inhibit sickle hemoglobin polymer formation and/or allosterically increase Hb affinity for oxygen have been shown to prevent the primary pathophysiology of sickle cell disease (SCD), specifically, Hb polymerization and red blood cell sickling. Several such compounds are currently being clinically studied for the treatment of SCD. Based on the previously reported non-covalent Hb binding characteristics of substituted aryloxyalkanoic acids that exhibited antisickling properties, we designed, synthesized and evaluated 18 new compounds (KAUS II series) for enhanced antisickling activities. Surprisingly, select test compounds showed no antisickling effects or promoted erythrocyte sickling. Additionally, the compounds showed no significant effect on Hb oxygen affinity (or in some cases, even decreased the affinity for oxygen). The X-ray structure of deoxygenated Hb in complex with a prototype compound, KAUS-23, revealed that the effector bound in the central water cavity of the protein, providing atomic level explanations for the observed functional and biological activities. Although the structural modification did not lead to the anticipated biological effects, the findings provide important direction for designing candidate antisickling agents, as well as a framework for novel Hb allosteric effectors that conversely, decrease the protein affinity for oxygen for potential therapeutic use for hypoxic- and/or ischemic-related diseases. Full article

A new white-light-emitting molecule (1) was synthesized and characterized by NMR spectroscopy, high resolution mass spectrometry, and single-crystal X-ray diffraction. Compound 1 crystallizes in the orthorhombic space group Pnma, with a = 12.6814(6), b = 7.0824(4), c = 17.4628(9) Å, α = 90°, β = 90°, γ = 90°. In the crystal, molecules are linked by weak intermolecular C-H···O hydrogen bonds, forming an infinite chain along [100], generating a C(10) motif. Compound 1 possesses an intramolecular six-membered-ring hydrogen bond, from which excited-state intramolecular proton transfer (ESIPT) takes place from the phenolic proton to the carbonyl oxygen, resulting in a tautomer that is in equilibrium with the normal species, exhibiting a dual emission that covers almost all of the visible spectrum and consequently generates white light. It exhibits one irreversible one-electron oxidation and two irreversible one-electron reductions in dichloromethane at modest potentials. Furthermore, the geometric structures, frontier molecular orbitals (MOs), and the potential energy curves (PECs) for 1 in the ground and the first singlet excited state were fully rationalized by density functional theory (DFT) and time-dependent DFT calculations. The results demonstrate that the forward and backward ESIPT may happen on a similar timescale, enabling the excited-state equilibrium to be established. Full article