Search Results (641)

Chagas disease remains a significant neglected tropical disease that predominantly affects vulnerable populations in rural, low-income areas of Latin America. The management of this condition is severely hindered by the limitations of current therapies, which are characterized by substantial toxicity, diminished efficacy during the chronic phase, and the emergence of parasitic resistance. Given the promising activity of SB-83 (a 2-aminothiophenic derivative) against Leishmania spp., the present study sought to evaluate its trypanocidal activity against Trypanosoma cruzi. The results showed that SB-83 exhibited potent inhibitory effects on the epimastigote forms of T. cruzi (IC₅₀ = 6.23 ± 0.84 μM), trypomastigotes (EC₅₀ = 7.31 ± 0.52 μM) and intracellular amastigotes (EC₅₀ = 5.12 ± 0.49 μM). Furthermore, the cellular proliferation assay results indicated CC₅₀ values of 77.80 ± 2.05 µM for LLC-MK2 CCL-7 and 24.21 ± 1.2 µM for Vero CCL-87, with a selectivity index above 10 for LLC-MK2 cells. In addition, the compound increased TNF-α, IL-12, nitric oxide, and ROS while decreasing IL-10. Moreover, in silico and in vitro assays confirmed its binding to trypanothione reductase, disrupting redox balance. Flow cytometry further revealed apoptosis induction in trypomastigotes, whereas electron microscopy showed cellular disruption and organelle disorganization. Therefore, SB-83 demonstrated potent activity against the TcI-resistant strain linked to Chagas cardiomyopathy at non-toxic concentrations for host cells, supporting its potential as a therapeutic candidate. Full article

Emerging research indicates that neuronal activity is maintained by an architectural system of protons in a multi-scale fashion. Proton architecture is formed when organelles (such as mitochondria, endoplasmic reticulum, lysosomes, synaptic vesicles, etc.) are coupled together to produce dynamic energy domains. Techniques have been developed to visualize protons in neurons; recent advances include near-atomic structural imaging of organelle interfaces using cryo-tomography and nanoscale resolution imaging of organelle interfaces and proton tracking using ultra-fast spectroscopy. Results of these studies indicate that protons in neurons do not diffuse randomly throughout the neuron but instead exist in organized geometric configurations. The cristae of mitochondrial cells create oscillating proton micro-domains that are influenced by the curvature of the cristae, hydrogen bonding between molecules, and localized changes in dielectric properties that result in time-patterned proton signals that can be used to determine the metabolic load of the cell and the redox state of its mitochondria. These proton patterns also communicate to the rest of the cell via hydrated aligned proton-conductive pathways at the mitochon-dria-endoplasmic reticulum junctions, through acidic lipid regions, and through nano-tethered contact sites between mitochondria and other organelles, which are typically spaced approximately 10–25 nm apart. Other proton architectures exist in lysosomes, endosomes, and synaptic vesicles. In each of these organelles, the V-ATPase generates steep concentration gradients across their membranes, controlling the rate of cargo removal from the lumen of the organelle, recycling receptors from the surface of the membrane, and loading neurotransmitters into the vesicles. Recent super-resolution pH mapping has indicated that populations of synaptic vesicles contain significant heterogeneity in the amount of protons they contain, thereby influencing the amount of neurotransmitter released per vesicle, the probability of vesicle release, and the degree of post-synaptic receptor protonation. Additionally, proton gradients in each organelle interact with the cytoskeleton: the protonation status of actin and microtubules influences filament stiffness, protein–protein interactions, and organelle movement, resulting in the formation of localized spatial structures that may possess some type of computational significance. At multiple scales, it appears that neurons integrate the proton micro-domains with mechanical tension fields, dielectric nanodomains, and phase-state transitions to form distributed computing elements whose behavior is determined by the integration of energy flow, organelle geometry, and the organization of soft materials. Alterations to the proton landscape in neurons (e.g., due to alterations in cristae structure, drift in luminal pH, disruption in the hydration-structure of the cell, or imbalance in the protonation of cytoskeletal components) could disrupt the intracellular signaling network well before the onset of measurable electrical or biochemical pathologies. This article will summarize evidence indicating that proton–organelle interaction provides a previously unknown source of energetic substrate for neural computation. Using an integrated approach combining nanoscale proton energy, organelle interface geometry, cytoskeletal mechanics, and AI-based multiscale models, this article outlines current principles and unresolved questions related to the subject area as well as possible new approaches to early detection and precise intervention of pathological conditions related to altered intracellular energy flow. Full article

Reverse electrodialysis (RED) enables the efficient conversion of the chemical potential difference between seawater and freshwater into electricity while simultaneously facilitating hydrogen production for integrated energy utilization. Nevertheless, the widespread deployment of RED remains constrained by the reliance on ruthenium–iridium-coated electrodes, which are expensive and resource-limited. This study proposes the adoption of titanium-based redox electrodes as a replacement for traditional precious metal electrodes and employs a novel spike structure to accelerate hydrogen bubble detachment. The electrochemical performance of titanium electrodes in an RED hydrogen production system was systematically evaluated experimentally. The influences of several parameters on the RED system performance were systematically examined under these operating conditions, including the ruthenium–iridium catalytic layer, operating temperature (15 to 45 °C), electrode rinse solution (ERS) concentration (0.1 to 0.7 M), and flow rate (50 to 130 mL·min⁻¹). Experimental results demonstrate that optimized titanium redox electrodes maintain high electrocatalytic activity while significantly reducing system costs. Under optimal conditions, the hydrogen yield of the Ti redox electrode reached 89.7% of that achieved with the mesh titanium plate coated oxide iridium and oxide ruthenium as electrodes, while the electrode cost was reduced by more than 60%. This is also one of the cost-cutting solutions adopted by RED for its development. Full article

Vanadium redox flow batteries (VRFBs) experience performance losses driven by electrode ageing, yet the underlying mechanisms remain poorly resolved under operational conditions. This work presents a novel application of dynamic electrochemical impedance spectroscopy (DEIS) in both full-cell and three-electrode configurations to monitor kinetic and transport processes throughout complete charge–discharge cycles. Carbon felt electrodes subjected to thermal activation, chemical degradation, and electrochemical ageing were systematically examined to capture a broad range of ageing-induced modifications. Complementary electrochemical impedance spectroscopy (EIS) measurements at selected states of charge were performed to highlight the substantial differences between spectra recorded under load and at open-circuit conditions. The results reveal that the impedance response of the full cell is dominated by processes occurring at the negative electrode, and that ageing leads to increased charge-transfer resistance and enhanced state of charge-dependent variation. X-ray photoelectron spectroscopy (XPS) analysis confirms significant modifications in surface chemistry, including variations in the sp²/sp³ carbon distribution and the enrichment of oxygen-containing functional groups, which correlate with the observed electrochemical behavior. Overall, this study demonstrates—for the first time under realistic VRFB cycling conditions—that DEIS provides unique diagnostic capabilities, enabling mechanistic insights into electrode ageing that are inaccessible to conventional impedance approaches. Full article

The power allocation in Vanadium Redox Flow Battery (VRB) energy storage systems faces a conflict between long-term lifespan and real-time power coupling. Using a single-layer optimization method to directly address multiple objectives simultaneously may lead to conflicts among these objectives. Therefore, this paper presents a multi-objective two-layer optimization allocation strategy. Its core is hierarchical scheduling for long/short-term goals to optimize multi-attribute objectives precisely. A two-layer model comprising an initial allocation layer and an operational optimization layer is constructed to ensure the prioritization of long-term lifespan objectives based on a predefined hierarchical structure. The initial allocation layer focuses on the long-term objective of energy storage capacity lifespan, by prioritizing minimal capacity degradation. A differential evolution algorithm is then applied to perform preliminary allocation of the total power demand. The operational optimization layer aims to achieve optimal State of Charge (SOC) balance across all units and minimize power losses. An Adaptive Multi-Objective Harris Hawks Optimizer (ASAMOHHO) based on adaptive simulated annealing is established to find the Pareto optimal solution set, and ultimately determining the real-time power allocation plan for each unit. Comparative simulations with conventional methods were conducted, and the results demonstrate that the proposed strategy provides an efficient and practical solution for efficient VRB scheduling. Full article

Vanadium redox flow batteries, as a key technology for energy storage systems, have gained application in recent years. Investigating the thermal behavior and performance of these batteries is crucial. This study establishes a three-dimensional model of a vanadium redox flow battery featuring a serpentine flow channel design. By adjusting key battery parameters, changes in ion concentration and uniformity are examined. The model integrates electrochemical, fluid dynamics, and Physico-Chemical Kinetics phenomena. Electrolyte flow velocity and current density are critical parameters. Results indicate that increasing the electrolyte inlet flow velocity leads to convergence in the battery’s charge/discharge cell voltage, ${\mathrm{VO}}_2^{+}{/\mathrm{VO}}^{2+}$, ${\mathrm{V}}^{2+}{/\mathrm{V}}^{3+}$ and concentration distribution across the carbon felt and flow channels. Coincidently, the uniformity of vanadium ions across all oxidation states improves. Furthermore, the observed ion uniformity and battery cell voltage are shown to be significantly modulated by the system’s State of Charge, which sets the baseline electrochemical environment for flow rate effects. Full article

Thought processes in the brain occur as it continually modifies its use of energy. This review integrates research findings from molecular neurology, vascular physiology and non-equilibrium thermodynamics to create a comprehensive perspective on thinking as a coordinated energy process. Data shows that there is a relationship between the processing of information and metabolism throughout all scales, from the mitochondria’s electron transport chain to the rhythmic changes in the microvasculature. Through the cellular level of organization, mitochondrial networks, calcium (Ca²⁺) signals from astrocytes and the adaptive control of capillaries work together to maintain a state of balance between order and dissipation that maintains function while also maintaining the ability to be flexible. The longer-term regulatory mechanisms including redox plasticity, epigenetic programs and organelle remodeling may convert short-lived states of metabolism into long-lasting physiological “memory”. As well, data indicates that the cortical networks of the brain appear to be operating close to their critical regimes, which will allow them to respond to stimuli but prevent the brain from reaching an unstable energetic state. It is suggested that cognition occurs as the result of the brain’s ability to coordinate energy supply with neural activity over both time and space. Providing a perspective of the functional aspects of neurons as a continuous thermodynamic process creates a framework for making predictive statements that will guide future studies to measure coherence as a key link between energy flow, perception, memory and cognition. Full article

Microbial electrolysis cells (MECs) are bioreactors that utilize electroactive microorganisms to catalyze the oxidation of organic substrates in wastewater, generating electron flow for hydrogen production. Despite the concept, a persistent performance gap exists where metabolically active anodic biofilms frequently fail to achieve expected current densities by the flow of electrons to produce hydrogen. This review examines the multiple causes that lead to the disconnect between robust biofilm development, electron transfer, and hydrogen production. Factors affecting biofilm generation (formation, substrate selection, thickness, conductivity, and heterogeneity) are discussed. Moreover, factors affecting electron transfer (electrode configuration, mass transfer constraints, key electroactive species, and metabolic pathways) are discussed. Also, substrate diffusion limitations, proton accumulation causing inhibitory pH gradients in stratified biofilms, elevated internal resistance, electron diversion to competing processes like hydrogenotrophic methanogenesis consuming H₂, and detrimental biofilm aging, impacting hydrogen production, are studied. The critical roles of electrode materials, reactor configuration, and biofilm electroactivity are analyzed, emphasizing advanced electrochemical (CV, EIS, LSV), imaging (CLSM, SEM, AFM), and omics (metagenomics, transcriptomics, proteomics) techniques essential for diagnosing bottlenecks. Strategies to enhance extracellular electron transfer (EET) (advanced nanomaterials, redox mediators, conductive polymers, bioaugmentation, and pulsed electrical operation) are evaluated for bridging this performance gap and improving energy recovery. The review presents an integrated framework connecting biofilm electroactivity, EET kinetics, and hydrogen evolution efficiency. It highlights that conventional biofilm metrics may not reflect actual electron flow. Combining electrochemical, microelectrode, and omics insights allows precise evaluation of EET efficiency and supports sustainable MEC optimization for enhanced hydrogen generation. Full article

An asymmetric four-chamber redox flow desalination cell was developed to enhance ion transport and energy efficiency by controlling chamber geometry, applied voltage, and electrolyte flow rate. The design integrates thick outer redox chambers with thin desalination chambers to promote uniform redox reactions and stable mass transfer. The system operated stably for 12 h and achieved a high salt removal rate of approximately 1226 mmol·m⁻²·h⁻¹ at 1.0 V with low specific energy consumption of about 99.74 kJ·mol⁻¹, demonstrating both durable operation and highly promising desalination performance. Electrochemical impedance analysis further confirmed that increased electrolyte flow reduces charge-transfer and diffusion resistances, enabling faster ionic transport. These findings highlight the originality of the chamber-asymmetric design and its promise for compact, low-voltage redox flow systems. This work provides design guidelines for next-generation flow-based desalination systems and suggests future research directions in scaling the architecture, optimizing flow-channel geometry, and integrating higher-stability redox electrolytes for long-term practical operation. Full article

Rare-earth oxide (REO) nanoparticles (NPs)—such as cerium (CeO₂), samarium (Sm₂O₃), neodymium (Nd₂O₃), terbium (Tb₄O₇), and praseodymium (Pr₂O₃)—have demonstrated strong antimicrobial activity against multidrug-resistant bacteria. Their effectiveness is attributed to unique physicochemical properties, including oxygen vacancies and redox cycling, which facilitate the generation of reactive oxygen species (ROS) that damage microbial membranes and biomolecules. Additionally, electrostatic interactions with microbial surfaces and sustained ion release contribute to membrane disruption and long-term antimicrobial effects. REOs also inhibit bacterial enzymes, DNA, and protein synthesis, providing broad-spectrum activity against Gram-positive, Gram-negative, and fungal pathogens. However, dose-dependent cytotoxicity to mammalian cells—primarily due to excessive ROS generation—and nanoparticle aggregation in biological media remain challenges. Surface functionalization with polymers, peptides, or metal dopants (e.g., Ag, Zn, and Cu) can mitigate cytotoxicity and enhance selectivity. Scalable and sustainable synthesis remains a challenge due to high synthesis costs and scalability issues in industrial production. Green and biogenic routes using plant or microbial extracts can produce REOs at lower cost and with improved safety. Advanced continuous flow and microwave-assisted synthesis offer improved particle uniformity and production yields. Biomedical applications include antimicrobial coatings, wound dressings, and hybrid nanozyme systems for oxidative disinfection. However, comprehensive and intensive toxicological evaluations, along with regulatory frameworks, are required before clinical deployment. Full article

The EU’s green transition hinges on secure access to critical raw materials; vanadium is pivotal for microalloyed steels and emerging long-duration energy storage (VRFBs). Methods: We combine a market and technology review with PESTEL and Porter-5+2 analyses, complemented by a value-chain assessment and a SWOT-to-CAME strategy for the EU. Results: Vanadium supply is highly concentrated (VTM-derived, largely in CN/RU/ZA), prices are volatile, and >85% of demand remains tied to steel; yet VRFBs could shift demand shares by 2030 if costs—dominated by electrolyte—are mitigated. EU weaknesses include lack of primary mining and refining capacity; strengths include research leadership, regulatory frameworks and circularity potential (slag/catalyst recovery, electrolyte reuse). Conclusions: A resilient EU strategy should prioritize circular supply, selective upstream partnerships, battery-grade refining hubs, and targeted instruments (strategic stocks, offtake/price-stabilization, LDES-ready regulation) to de-risk vanadium for grid storage and low-carbon infrastructure. This study also discusses supply chain concentration and price volatility, and outline circular-economy pathways and decarbonization policy levers relevant to the EU’s green energy transition. Full article

Sexual dimorphism significantly influences the epidemiology of thyroid disorders, with females exhibiting higher incidence of thyroid diseases. Estrogens and their hydroxylated metabolites are key regulators of cellular redox balance and may contribute to sex-specific susceptibility through pro-oxidative mechanisms. However, the impact of individual estrogen metabolites on oxidative stress in thyroid follicular cells remains poorly defined. Here, we investigated the pro-oxidative effects of 17β-estradiol (E2) and its hydroxylated metabolites—2-hydroxyestradiol (2-OHE2), 4-hydroxyestradiol (4-OHE2), and 16α-hydroxyestrone (16α-OHE1)—in primary porcine thyroid cell cultures from males and females. Primary follicular thyroid cells were isolated from six male and six female pigs. Cells were exposed to E2 (100 nM) or its metabolites (1 μM), with or without Fenton reaction substrates (Fe²⁺ and H₂O₂), for 24 h. Lipid peroxidation (an index of oxidative damage to lipids) was quantified using BODIPY^® 581/591 C11 fluorescence via flow cytometry. Basal lipid peroxidation did not differ between sexes. 2-OHE2 increased lipid peroxidation in both male and female thyroid cells, with a more pronounced effect observed in males. In contrast, 4-OHE2 selectively enhanced lipid peroxidation only in female cells. 16α-OHE1 elevated lipid peroxidation in both sexes. E2 significantly increased lipid peroxidation in both male and female cells. Among all compounds tested, E2 exhibited the most potent pro-oxidative activity, particularly in female-derived cells. These findings provide novel insights into the redox-modulating effects of estrogen metabolism in the thyroid and suggest a potential molecular basis for sex-related susceptibility to thyroid dysfunction. While based on an in vitro porcine model, the study increases our understanding of the mechanisms by which estrogenic compounds may influence thyroid pathophysiology, possibly including early events in thyroid disease development or oncogenesis. Full article

The design of the chemical structure of ion-conductive membranes is critical to enhance proton/vanadium ion selectivity and the performance of vanadium redox flow batteries (VRFBs). Herein, camphorsulfonic acid is proposed as a novel proton-conductive group and grafted on polybenzimidazole (PBICa). The pendant sulfonic acid group on the end of the grafted side chains is flexible to promote the aggregation of ionic clusters at even a relatively low ion-exchange capacity (IEC) of 2.14 mmol g⁻¹. The formation of these high-quality clusters underscores the remarkable efficacy of this structural strategy in driving nanoscale phase separation, which is a prerequisite for creating efficient proton-conducting pathways. The bulky and non-coplanar architecture of the camphorsulfonic acid group helps to increase the proportion of free volume compared with the conventional sulfonated polybenzimidazole, which not only promotes water uptake to facilitate proton transport but also exerts a sieving effect to effectively block vanadium ion permeation. The well-formed ionic clusters, together with the expanded free volume architecture, endow the membrane with both high proton conductivity (30.5 mS cm⁻¹) and low vanadium ion permeability (0.15 × 10⁻⁷ cm² s⁻¹), achieving excellent proton/vanadium ion selectivity of 9.85 × 10⁹ mS s cm⁻³, which is about 5.6-fold that of a Nafion 212 membrane. Operating at 200 mA cm⁻², the PBICa-based VRFB achieves an energy efficiency of 78.4% and a discharge capacity decay rate of 0.32% per cycle, outperforming the Nafion 212-based battery (EE of 76.9%, capacity decay of 0.79% per cycle). Full article

Accurate and real-time state of charge (SOC) monitoring is critical for the safe, efficient, and stable long-term operation of vanadium redox flow batteries (VRFBs). Traditional monitoring methods are susceptible to errors arising from side reactions, cumulative drift, and electrolyte imbalance. This study develops a non-invasive optical sensor module for the negative electrolyte (anolyte), utilizing the favorable spectral properties of V(II)/V(III) ions at 850 nm for real-time SOC tracking. A fifth-order polynomial model was employed for calibration, successfully managing the non-linear optical response of highly concentrated electrolytes and achieving exceptional accuracy (adjusted R² > 0.9999). The optical sensor reliably tracked capacity degradation over 50 galvanostatic cycles, yielding a degradation curve that showed a high correlation with the conventional coulomb counting method, thus confirming its feasibility for assessing battery’s state of health. Contrary to initial expectations, operating at higher current densities resulted in a lower capacity degradation rate (CDR). This phenomenon is primarily attributed to the time-dependent nature of parasitic side reactions. Higher current densities reduce the cycle duration, thereby minimizing the temporal exposure of active species to degradation mechanisms and mitigating cumulative ion imbalance. This mechanism was corroborated by physicochemical analysis via UV-Vis spectroscopy, which revealed a strong correlation between the severity of spectral deviation and the CDR ranking. This non-invasive optical technology offers a low-cost and effective solution for precise VRFB management and preventative maintenance. Full article

Background: Breast cancer is the most prevalent cancer among women worldwide, and therapeutic resistance represents a major clinical challenge. Mitochondria are key regulators of cancer metabolism, redox homeostasis, and apoptosis, making them potential therapeutic targets. Aim: This study aimed to evaluate the effects of combined Akt and PARP inhibition on mitochondrial metabolic function, energy production, and apoptosis in breast cancer cells. Methodology: The SRB assay was used to compare the viability of MDA-MB-231 and MCF7 cells. A colony formation assay was conducted to assess the capacity of individual cells to develop colonies, and ROS production was quantified using DHR123. Flow cytometric analysis was performed to evaluate cell death, and the Seahorse Mito stress test was used to measure ATP production and essential mitochondrial parameters. Results: The combination of Akt and PARP inhibitors impaired oxidative phosphorylation without inducing a compensatory shift to glycolysis, leading to reduced ATP production, increased ROS generation, and apoptotic cell death in breast cancer cells compared to monotherapy. Conclusions and Recommendations: These findings indicate that the combination of olaparib and capivasterib is a promising therapeutic strategy for breast cancer. Furthermore, evaluation of in vivo toxicity and antitumor effectiveness is essential to validate its potential. Full article