Search Results (261)

TSGA10, a multifunctional protein critical for mitochondrial coupling and metabolic regulation, plays a paradoxical role in cancer progression and carcinogenesis. Here, we outline a potential mechanism by which TSGA10 mediates metabolism in oncogenesis and thermal modulation. Initially identified in spermatogenesis, TSGA10 interacts with mitochondrial Complex III: it directly binds cytochrome c1 (CytC1). In our model, TSGA10 optimizes electron transport to minimize reactive oxygen species (ROS) and heat production while enhancing Adenosine Triphosphate (ATP) synthesis. In cancer, TSGA10’s expression is context-dependent: Its downregulation in tumors like glioblastoma might disrupt mitochondrial coupling, promoting electron leakage, ROS accumulation, and genomic instability. This dysfunction would be predicted to contribute to a glycolytic shift, facilitating tumor survival under hypoxia. Conversely, TSGA10 overexpression in certain cancers suppresses HIF-1$\alpha$, inhibiting glycolysis and metastasis. TSGA10 and HIF-1$\alpha$ engage in mutual counter-regulation—TSGA10 represses HIF-1$\alpha$ to sustain oxidative phosphorylation (OXPHOS), while HIF-1$\alpha$ suppression of TSGA10 under hypoxia or thermal stress amplifies glycolytic dependency. This interplay is pivotal in tumors adapting to microenvironmental stressors, such as cold-induced mitochondrial uncoupling, which mimics brown adipose tissue thermogenesis to reduce ROS and sustain proliferation. Tissue-specific TSGA10 expression further modulates cancer susceptibility: high levels in the testes and brain may protect against thermal and oxidative damage, whereas low expression in the liver permits HIF-1$\alpha$-driven metabolic plasticity. Altogether, our model suggests that TSGA10 plays a central role in mitochondrial fidelity. We suggest that its crosstalk with oncogenic pathways position it as a metabolic rheostat, whose dysregulation fosters tumorigenesis through ROS-mediated mutagenesis, metabolic reprogramming, and microenvironmental remodeling. Targeting the hypothesized TSGA10-mediated mitochondrial coupling may offer therapeutic potential to disrupt cancer’s adaptive energetics and restore metabolic homeostasis. Full article

As the energy sector transitions toward decarbonisation, low-to-intermediate temperature geothermal resources in sedimentary basins—particularly repurposed oil and gas fields—have emerged as promising candidates for sustainable heat and power generation. Despite their widespread availability, the development of these systems is hindered by gaps in methodology, oversimplified modelling assumptions, and a lack of integrated analyses accounting for long-term reservoir and wellbore dynamics. This study presents a detailed, simulation-based framework to evaluate geothermal energy extraction from depleted petroleum reservoirs, with a focus on low-enthalpy resources (<150 °C). By examining coupling reservoir behaviour, wellbore heat loss, reinjection cooling, and surface energy conversion, the framework provides dynamic insights into system sustainability and net energy output. Through a series of parametric analyses—including production rate, doublet spacing, reservoir temperature, and field configuration—key performance indicators such as gross power, pumping requirements, and thermal breakthrough are quantified. The findings reveal that: (1) net energy output is maximised at optimal flow rate (~70 kg/s for a 90 °C reservoir), beyond which increased pumping offsets thermal gains; (2) doublet spacing has a non-linear impact on reinjection cooling, with larger distances reducing thermal interference and pumping energy; (3) reservoirs with higher temperatures (<120°C) offer significantly better thermodynamic and hydraulic performance, enabling pump-free or low-duty operations at higher flow rates; and (4) wellbore thermal losses and reinjection effects are critical in determining long-term viability, especially in low-permeability or shallow fields. This work demonstrates the importance of a coupled, site-specific modelling in assessing the geothermal viability of petroleum fields and provides a foundation for future techno-economic and sustainability assessments. The results inform optimal design strategies and highlight scenarios where the geothermal development of oil and gas fields can be both technically and energetically viable. Full article

The electrochemical CO₂ reduction reaction (eCO₂RR), driven by renewable energy, represents a promising strategy for mitigating atmospheric CO₂ levels while generating valuable fuels and chemicals. Its practical implementation hinges on the development of highly efficient electrocatalysts. In this study, a novel dual-metal atomic catalyst (DAC), composed of niobium and palladium single atoms anchored on a ferroelectric α-In₂Se₃ monolayer (Nb-Pd@In₂Se₃), is proposed based on density functional theory (DFT) calculations. The investigation encompassed analyses of structural and electronic characteristics, CO₂ adsorption configurations, transition-state energetics, and Gibbs free energy changes during the eCO₂RR process, elucidating a synergistic catalytic mechanism. The Nb-Pd@In₂Se₃ DAC system demonstrates enhanced CO₂ activation compared to single-atom counterparts, which is attributed to the complementary roles of Nb and Pd sites. Specifically, Nb atoms primarily drive carbon reduction, while neighboring Pd atoms facilitate oxygen species removal through proton-coupled electron transfer. This dual-site interaction lowers the overall reaction barrier, promoting efficient CO₂ conversion. Notably, the polarization switching of the In₂Se₃ substrate dynamically modulates energy barriers and reaction pathways, thereby influencing product selectivity. Our work provides theoretical guidance for designing ferroelectric-supported DACs for the eCO₂RR. Full article

Burnout syndrome, which significantly impacts both individual and societal quality of life, is primarily characterized by three key criteria: depersonalization, emotional exhaustion, and low personal accomplishment, all linked to work-related stress. Purpose: Comparative evaluation of urine metabolite patterns that may discriminate the burnout levels and the effects of night shifts on healthcare professionals. The Maslach Burnout Inventory survey was administered to 64 physicians and nurses working day and night shifts, with scores for each criterion recorded. Methods: Urine samples were collected, and metabolomic patterns were analyzed using UHPLC-QTOF-ESI+-MS technology. This analysis employed both untargeted and semi-targeted metabolomics, coupled with multivariate and ANOVA statistics, utilizing the online Metaboanalyst 6.0 platform. Partial Least Squares Discriminant Analysis (PLSDA) was performed, along with VIP values, Random Forest graphs, and heatmaps based on 79 identified metabolites. These were further complemented by biomarker analysis (AUC ranking) and pathway analysis of metabolic networks. Results: The findings highlighted the biochemical effects of night shifts and their correlation with burnout scores from each dimension. Conclusions: This study demonstrated the involvement of three major metabolic pathways in diagnosing burnout: lipid metabolism, particularly related to steroid hormones (cortisol, cortisone, and androsterone metabolites); energetic metabolism, involving long-chain acylated carnitines as transporters of free fatty acids, which play a role in burnout control; and a third pathway affecting catecholamine metabolism (neurotransmitters derived from tyrosine, such as dopamine, adrenaline, and noradrenaline), as well as tryptophan metabolism (serotonin and melatonin metabolites) and amino acid metabolism (including aspartate, arginine, and valine). Full article

We investigate the time evolution of the quark condensate toward a chiral symmetry broken phase in hot and dense quark matter using a field-theoretic quark model with nonlocal chiral-invariant four-fermion coupling. By purposely selecting a parameter set in which inhomogeneous phases are energetically disfavored, we nonetheless observe the emergence of metastable patterned configurations that appear to persist for remarkably long timescales. These findings suggest that even when not fully stable, inhomogeneous phases may play a significant role in the dynamics of chiral symmetry breaking and restoration. To gain deeper insight into these phenomena, we also analyze the impact of the dimensionality of coordinate space on both the formation and stability of inhomogeneous chiral condensates. Full article

The production of Fischer–Tropsch liquid biofuels from the supercritical water gasification (SCWG) of lignocellulosic biomass is energetically and environmentally assessed by coupling process modelling with Life-Cycle Assessment. A conceptual process model has been developed comprising the following stages: (a) the thermochemical conversion of lignocellulosic biomass in a supercritical water gasification (SCWG) reactor, (b) syngas upgrade through dry reforming (DRR), (c) liquid biofuel production from Fischer–Tropsch synthesis (FTS) and (d) FT product upgrade and refinement, so that diesel-like (FT—Diesel), gasoline-like (FT—Gasoline), and jet fuel-like (FT Jet Fuel) yields are predicted. Parametric studies have been performed, highlighting the effect of biomass concentration and SCWG temperature on end-product yields. Furthermore, alternative scenarios have been examined with respect to: (a) maximizing FT liquid biofuel yields and (b) minimizing heat requirements to potentially achieve a thermally self-sustained process. The results of the simulated process, including liquid biofuel yield and heat-demand predictions, are used as inputs in the inventories compiled for the Life-Cycle Assessment of the overall process. Agricultural and feedstock transportation stages have also been considered. Energetic and environmental benefits and challenges are highlighted through the quantification of Global Warming Potential (GWP), while special importance is assigned to following the REDII sustainability methodology and reference data. Full article

Hydrogen peroxide (H₂O₂) plays a crucial role in cell signaling in response to physiological and environmental perturbations. H₂O₂ can oxidize typical 2-Cys peroxiredoxin (PRX) first into a sulfenic acid, which resolves into a disulfide that can be reduced by thioredoxin (TRX)/TRX reductase (TR). At high levels, H₂O₂ can also hyperoxidize sulfenylated PRX into a sulfinic acid that can be reduced by sulfiredoxin (SRX). Therefore, PRX, TRX, TR, and SRX (abbreviated as PTRS system here) constitute the coupled sulfenylation and sulfinylation cycle (CSSC), where certain oxidized PRX and TRX forms also function as redox signaling intermediates. Earlier studies have revealed that the PTRS system is capable of rich signaling dynamics, including linearity, ultrasensitivity/switch-like response, nonmonotonicity, circadian oscillation, and possibly, bistability. However, the origins of ultrasensitivity, which is fundamentally required for redox signal amplification, have not been adequately characterized, and their roles in enabling complex nonlinear dynamics of the PTRS system remain to be determined. Through in-depth mathematical modeling analyses, here we revealed multiple sources of ultrasensitivity that are intrinsic to the CSSC, including zero-order kinetic cycles, multistep H₂O₂ signaling, and a mechanism arising from diminished H₂O₂ removal at high PRX hyperoxidation state. The CSSC, structurally a positive feedback loop, is capable of bistability under certain parameter conditions, which requires embedding multiple sources of ultrasensitivity identified. Forming a negative feedback loop with cytosolic SRX as previously observed in energetically active cells, the mitochondrial PTRS system (where PRX3 is expressed) can produce sustained circadian oscillations through supercritical Hopf bifurcations. In conclusion, our study provided novel quantitative insights into the dynamical complexity of the PTRS system and improved appreciation of intracellular redox signaling. Full article

The substitution of aluminum powder with highly reactive ultrafine aluminum-based metal fuels has a significant impact on the energy release of aluminum-containing energetic materials because of their excellent energy density and combustion performances. A series of ultrafine spherical Al-Mg alloy fuels with different contents of magnesium were prepared by close-coupled gas atomization technology. The properties of Al-Mg alloy powders of 13~15 μm were tested by SEM, TG-DSC, and laser ignition experiments. Results show that alloying with magnesium can significantly enhance thermal oxidation and combustion performance, leading to more oxidation weight gains and higher combustion heat release. HMX-based castable explosives with the same content of Al and the novel Al-Mg alloy were made and tested. Results show that the detonation performances of HMX/Al-Mg alloy/HTPB are better than HMX/Al/HTPB. Compared to the HMX/Al/HTPB explosive, the detonation heat of HMX/ Al-Mg alloy/HTPB was increased by 200 kJ/kg, the energy release efficiency was enhanced from 80.55% to 83.19%, the detonation velocity was increased by 114 m/s, and the shock wave overpressure at 5 m was increased by 83%. This research provides a new type of composite metal fuel for improving the combustion performance of Al powder. Full article

Prolyl cis/trans isomerization is a rate-limiting step in protein folding, often coupling directly to the acquisition of native structure. Here, we investigated the interplay between folding and prolyl isomerization in the N2 domain of the gene-3-protein from filamentous phage fd, which adopts a native-state cis/trans equilibrium at Pro161. Using mutational and Φ-value analysis, we identified a discrete folding nucleus encompassing the β-strands surrounding Pro161. These native-like interactions form early in the folding pathway and provide the energy to shift the cis/trans equilibrium toward the cis form. Variations distant from the Pro161-loop have minimal impact on the cis/trans ratio, underscoring the spatial specificity and localized control of the isomerization process. Using NMR spectroscopy, we determined the structures for both native N2 forms. The cis- and trans-Pro161 conformations are overall identical and exhibit only slight differences around the Pro161-loop. The cis-conformation adopts a more compact structure with improved backbone hydrogen bonding, explaining the approximately 10 kJ·mol⁻¹ stability increase of the cis state. Our findings highlight that prolyl isomerization in the N2 domain is governed by a localized folding nucleus rather than global stability changes. This localized energetic coupling ensures that proline isomerization is not simply a passive, slow step but an integral component of the folding landscape, optimizing both the formation of native structure and the establishment of the cis-conformation. Full article

Aluminum nanoparticles (Al NPs) are interesting for energetic and plasmonic applications due to their enhanced size-dependent properties. Passivating the surface of these particles is necessary to avoid forming a native oxide layer, which can degrade energetic and optical characteristics. This work utilized a radiofrequency (RF)-driven capacitively coupled argon/hydrogen plasma to form surface-modified Al NPs from aluminum trichloride (AlCl₃) vapor and 5% silane in argon (dilute SiH₄). Varying the power and dilute SiH₄ flow rate in the afterglow of the plasma led to the formation of varying nanoparticle morphologies: Al–SiO₂ core–shell, Si–Al₂O₃ core–shell, and Al–Si Janus particles. Scanning transmission electron microscopy with a high-angle annular dark-field detector (STEM-HAADF) and energy-dispersive X-ray spectroscopy (EDS) were employed for characterization. The surfaces of the nanoparticles and sample composition were characterized and found to be sensitive to changes in RF power input and dilute SiH₄ flow rate. This work demonstrates a tunable range of Al–SiO₂ core–shell nanoparticles where the Al-to-Si ratio could be varied by changing the plasma parameters. Thermal analysis measurements performed on plasma-synthesized Al, crystalline Si, and Al–SiO₂ samples are compared to those from a commercially available 80 nm Al nanopowder. Core–shell particles exhibit an increase in oxidation temperature from 535 °C for Al to 585 °C for Al–SiO₂. This all-gas-phase synthesis approach offers a simple preparation method to produce high-purity heterostructured Al NPs. Full article

Diapause, a survival strategy utilized by many insects under severe environmental conditions, can generate costs that potentially affect post-diapause development and reproduction. The willow leaf beetle, Plagiodera versicolora, overwinters as an adult. This study investigated the cold hardiness-hardiness and energy utilization of female P. versicolora, and their impact on post-diapause reproductive fitness. The supercooling point exhibited seasonal temperature variation, with the lowest points occurring in January and February, coinciding with the relatively lower ambient temperatures. Lipid content demonstrated a pronounced decline at the onset of diapause (from November to December) and stabilized from December to March. Glycogen content also showed a sharp decrease from November to January, subsequently stabilizing at relatively constant levels. In addition, trehalose content increased significantly when temperatures dropped (from November to January) and then decreased as temperatures rose (from January to March). There were no significant differences in the time from pairing to successful mating for post-diapause females compared with non-diapause females. However, mating duration and the pre-oviposition period for post-diapause individuals relative to non-diapause individuals increased, coupled with a reduction in the oviposition period, total number of eggs, number of egg clutches, and number of eggs per clutch; however, most importantly, there was no notable change in egg-hatching success. These results suggest that the cold-hardiness strategy of P. versicolora falls within the freeze-avoidance category, with energy usage predominantly reliant on lipids and carbohydrates during diapause initiation. Our findings also highlight that, although post-diapause females are capable of nutrient replenishment, the energetic demands of diapause result in considerable negative impacts on post-diapause female reproductive fitness. Full article

Environmental changes, such as applied medication, nutrient depletion, and accumulation of metabolic residues, affect cell culture activity. The combination of these factors reflects on the local temperature distribution and local oxygen concentration towards the cell culture scaffold. However, determining the temporal variation of local temperature, independent of local oxygen concentration changes in biological specimens, remains a significant technological challenge. The process of triplet–triplet annihilation upconversion (TTA-UC), performed in a nanoconfined environment with a continuous aqueous phase, appears to be a possible solution to these severe sensing problems. This process generates two optical signals (delayed emitter fluorescence (dF) and residual sensitizer phosphorescence (rPh)) in response to a single external stimulus (local temperature), allowing the application of the ratiometric-type sensing procedure. The ability to incorporate large amounts of sacrificial singlet oxygen scavenging materials, without altering the temperature sensitivity, allows long-term protection against photo-oxidative damage to the sensing moieties. Translucent agarose/silk fibroin hydrogels embedding non-ionic micellar systems containing energetically optimized annihilation couples simultaneously fulfill two critical functions: first, to serve as mechanical support (for further application as a cell culture scaffold); second, to allow tuning of the material response window to achieve a maximum temperature sensitivity better than 0.5 K for the physiologically important region around 36 °C. Full article

Background/Objectives: Pyruvate kinase M2, a central regulator of cancer cell metabolism, has garnered significant attention as a promising target for disrupting the metabolic adaptability of tumor cells. This study explores the potential of the Mannich base derived from lawsone (MB-6a) to interfere with PKM2 enzymatic activity both in vitro and in silico. Methods: The antiproliferative potential of MB-6a was tested using MTT assay in various cell lines, including SCC-9, Hep-G2, HT-29, B16-F10, and normal human gingival fibroblast (HGF). The inhibition of PKM2 mediated by MB-6a was assessed using an LDH-coupled assay and by measuring ATP production. Docking studies and molecular dynamics calculations were performed using Autodock 4 and GROMACS, respectively, on the tetrameric PKM2 crystallographic structure. Results: The Mannich base 6a demonstrated selective cytotoxicity against all cancer cell lines tested without affecting cell migration, with the highest selectivity index (SI) of 4.63 in SCC-9, followed by B16-F10 (SI = 3.9), Hep-G2 (SI = 3.4), and HT-29 (SI = 2.03). The compound effectively inhibited PKM2 glycolytic activity, leading to a reduction of ATP production both in the enzymatic reaction and in cells treated with this naphthoquinone derivative. MB-6a showed favorable binding to PKM2 in the ATP-bound monomers through docking studies (PDB ID: 4FXF; binding affinity scores ranging from −6.94 to −9.79 kcal/mol) and MD simulations, revealing binding affinities stabilized by key interactions including hydrogen bonds, halogen bonds, and hydrophobic contacts. Conclusions: The findings suggest that MB-6a exerts its antiproliferative activity by disrupting cell glucose metabolism, consequently reducing ATP production and triggering energetic collapse in cancer cells. This study highlights the potential of MB-6a as a lead compound targeting PKM2 and warrants further investigation into its mechanism of action and potential clinical applications. Full article

Myocardial cells and the extracellular matrix achieve their functions through the availability of energy. In fact, the mechanical and electrical properties of the heart are heavily dependent on the balance between energy production and consumption. The energy produced is utilized in various forms, including kinetic, dynamic, and thermal energy. Although total energy remains nearly constant, the contribution of each form changes over time. Thermal energy increases, while dynamic and kinetic energy decrease, ultimately becoming insufficient to adequately support cardiac function. As a result, toxic byproducts, unfolded or misfolded proteins, free radicals, and other harmful substances accumulate within the myocardium. This leads to the failure of crucial processes such as myocardial contraction–relaxation coupling, ion exchange, cell growth, and regulation of apoptosis and necrosis. Consequently, both the micro- and macro-architecture of the heart are altered. Energy production and consumption depend on the heart’s metabolic resources and the functional state of the cardiac structure, including cardiomyocytes, non-cardiomyocyte cells, and their metabolic and energetic behavior. Mitochondria, which are intracellular organelles that produce more than 95% of ATP, play a critical role in fulfilling all these requirements. Therefore, it is essential to gain a deeper understanding of their anatomy, function, and homeostatic properties. Full article

In order to reach climate protection goals at national or international levels, new forms of combined heating and cooling networks with ultra-low network temperatures (5GDHC) are viable alternatives to conventional heating networks. This paper presents a simulation library for 5GDHC networks as sustainable shared energy systems, developed in the object-oriented simulation framework OpenModelica. It comprises sub-models for residential buildings acting as prosumers in the network, with additional roof-mounted thermal systems, dynamic thermo-hydraulic representations of distribution pipes and storage, time-series-based sources for heating and cooling, and weather conditions adjustable to user-specified locations. A detailed insight into an in-house development of a sub-model for horizontal ground heat collectors is given. This sub-model is directly coupled with thermo-hydraulic network simulations. The simulation results of energy balances and energetic efficiencies for an example district are described. Findings from this study show that decentralised roof-mounted solar thermal systems coupled to the network can contribute 21% to the total source heat provided in the network while annual thermal gains from the distribution pipes add up to more than 18% within the described settings. The presented simulation library can support conceptual and advanced planning phases for renewable heating and cooling supply structures based on environmental sources. Full article