Search Results (55)

Melanoma cells in the brain may use similar mechanisms for adapting to injury and/or disease (that is, through continued reallocation of energy, matter, and information) as other cell types do to create an environment in which cancer cells can grow and sustain themselves within the confines of the brain. These adaptable mechanisms include the ability to reactivate dormant neural crest-derived migration and communication pathways. Unlike some other types of cancers that invade neural tissue as a simple invasion, melanomas are capable of achieving limited molecular, metabolic, and electrical similarity to the neural circuitry of the brain. Melanomas achieve this limited similarity through both vascular co-optation and mimicking synaptic functions, as well as through their engagement of redox-coupled metabolic pathways and feedback-regulated signal transduction pathways. The result is the creation of a metastable tumor–host system, where the relationship between tumor and host is defined by the interaction of stabilizing and destabilizing forces; forces that define the degree of coherence, vulnerability, and persistence of the tumor–host system. In this review, we integrate molecular, electrophysiological, and anatomical data to develop a single unifying hypothesis for the functional integration of melanoma cells into the neural tissue of the brain. Additionally, we describe how neural crest-based regulatory pathways are reactivated in the adult brain and how tumor–host coherence is developed as a function of the shared thermodynamic and informational constraints placed on both tumor and host. We also describe how our proposed conceptual model allows for the understanding of therapeutic interventions as selective disruptions of the neural, metabolic, and immunological couplings that support metastatic adaptation. Full article

The processes responsible for high-grade disseminated gold mineralization remain poorly constrained, hindering effective exploration. This study integrates petrography, BPMA, and LA-ICP-MS analysis of magnetite from marble- and granite-hosted ores with contrasting gold grades, to constrain wall-rock-induced changes in the thermodynamic environment. BPMA results show distinct mineral assemblages: granite-hosted ores are characterized by quartz (52.31%)-K-feldspar (19.65%)-sericite (9.56%)-pyrite (8.36%), whereas marble-hosted ores feature pyrrhotite (33.90%)-chlorite (27.50%)-pyrite (15.22%)-magnetite (1.94%). The closed intergrowths of magnetite with gold and sulfides, along with the magnetite Ga-V (Grant-Vaughan) discrimination diagram, indicate a hydrothermal origin for magnetite formed during the mineralization stage. Geochemical data show that marble-hosted magnetite has lower V and chalcophile element (Co, Ni, Sn, Zn) concentrations than granite-hosted magnetite. Considering the partitioning behavior of these elements in magnetite, these differences indicate magnetite crystallization under increasing oxygen fugacity (fO₂) and decreasing sulfur fugacity (fS₂). Thermodynamic modeling results demonstrate that these changes in fO₂ and fS₂ destabilized gold-sulfur complexes in the ore-forming fluid, significantly enhancing gold precipitation efficiency and ultimately leading to the formation of high-grade ores in marble. Full article

Refractory gold and silver ores present significant challenges because precious metals are encapsulated within sulfide matrices, severely limiting extraction by conventional cyanidation. In this study, a pyritic concentrate from the Bacis Mine (Durango, Mexico) was characterized and subjected to two oxidative pretreatments—roasting and alkaline pressure oxidation—before cyanidation. X-ray diffraction confirmed pyrite to be the dominant phase, with quartz and minor carbonates contributing to the material’s refractory character. Roasting at 550 °C achieved gold and silver extraction of 80% and 70%, respectively, which improved to 89% Au and 74% Ag with the addition of hydrogen peroxide. In contrast, alkaline pressure oxidation at 150 °C and 1 MPa O₂ yielded the highest extraction of 92% for Au and 76% for Ag at 1 h. Thermodynamic analysis using the Fe–S Pourbaix diagram at 80 °C supported these experimental results, showing the destabilization of FeS₂ under oxidizing and moderately alkaline conditions. Overall, this study demonstrates that alkaline pressure oxidation is a technically efficient and environmentally favorable pretreatment for refractory gold ores. Full article

Polymeric micelles are widely studied as nanocarriers for hydrophobic drugs, yet their structural stability under physiological conditions remains a major limitation. This review provides a comparative evaluation of synthetic and natural polymeric micelles with a focus on their stability under dilution and in protein-rich environments. The discussion integrates thermodynamic and kinetic factors governing micelle integrity and examines how molecular composition, hydrophobic segment length, and core–shell modifications influence disintegration behavior. While synthetic micelles commonly collapse below their critical micelle concentration during intravenous administration, natural polymeric micelles, such as those derived from chitosan, alginate, or heparin, exhibit improved resistance to dilution but remain vulnerable to protein-induced destabilization. Strategies such as core or shell cross-linking, surface functionalization, and natural polymer coatings are reviewed as promising approaches to enhance circulation stability and controlled drug release. The work provides a framework for designing micellar systems with balanced biocompatibility, biodegradability, and robustness suitable for clinical drug-delivery applications. Full article

I-motifs are non-canonical, cytosine-rich DNA structures stabilized by hemiprotonated C•C⁺ base pairs, whose formation is highly pH-dependent. While certain chemical modifications can enhance i-motif stability, modifications at the sugar moiety often disrupt essential inter-strand contacts. In this study, we examine the structural and thermodynamic impact of incorporating 2′-fluoro-ribocytidine (2′F-riboC) into i-motif-forming sequences derived from d(TCCCCC). Using a combination of UV, ¹H NMR, and ¹⁹F NMR spectroscopy, we demonstrate that full substitution with 2′F-riboC strongly destabilizes i-motif, whereas partial substitutions (one or two substitutions per strand) support well-folded structures at acidic pH (pH 5). High-resolution NMR structures reveal well-defined i-motif architectures with conserved C•C⁺ pairing and characteristic interstrand NOEs. Sugar conformational analysis reveals a predominant North pucker for cytosines, which directs the fluorine substituent toward the minor groove of the i-motif. ¹⁹F NMR further confirms slow exchange between folded and unfolded species, enabling the simultaneous detection of both under identical experimental conditions and, consequently, highlighting the utility of fluorine at the 2′ sugar position as a spectroscopic probe. These findings provide insights into fluorine-mediated modulation of i-motif stability and further extend the utility of ¹⁹F NMR in nucleic acid research. Full article

Methods such as AlphaFold have revolutionized protein structure prediction, making quantitative prediction of the thermodynamic stability of individual proteins and their complexes one of the next frontiers in computational protein modeling. Here, we develop methods for using protein language models (PLMs) with protein mutational datasets related to protein tertiary and quaternary stability. First, we demonstrate that fine-tuning of a ProtT5 PLM enables accurate prediction of the largest protein mutant stability dataset available. Next, we show that mutational impacts on protein function can be captured by fine-tuning PLMs, using green fluorescent protein (GFP) brightness as a readout of folding and stability. In our final case study, we observe that PLMs can also be extended to protein complexes by identifying mutations that are stabilizing or destabilizing. Finally, we confirmed that state-of-the-art simulation methods (free energy perturbation) can refine the accuracy of predictions made by PLMs. This study highlights the versatility of PLMs and demonstrates their application towards the prediction of protein and complex stability. Full article

When developing deep subsurface infrastructure in areas with intense geothermal activity, the significant temperature gradient inevitably leads to low-temperature contraction and high-temperature expansion of the rock body, resulting in changes in the rock’s mechanical properties. These thermodynamic effects can easily lead to the destabilization and subsequent collapse of the rock. There exists a pressing necessity to methodically evaluate the surrounding rock stability encountered in deep underground engineering under the action of thermal-solid coupling. This study constructed a multi-physical field coupling nonlinear calculation model based on a high-precision three-dimensional finite difference method, systematically analyzed the interdependent effects between the original rock temperature and excavation-induced disturbance, and then analyzed the dynamic changes in temperature, stress, and displacement fields along with plastic zone of surrounding rock of the deep underground engineering under thermal-solid coupling. The results indicate that the closer to the excavation contour surface, the lower the surrounding rock temperature, while the temperature gradient increased correspondingly. The farther away from the excavation contour face, the closer the temperature was to the original rock temperature. As the original rock temperature climbed from 30 °C to 90 °C, the increment of vault displacement was 2.45 times that of arch bottom displacement, and the influence of temperature change on vault deformation was more significant. The horizontal displacement magnitudes at the different original temperatures followed the following order: sidewall > spandrel > skewback, and at an original rock temperature of 90 °C, the sidewall horizontal displacement reached 15.31 cm. With the elevation of the original rock temperature, the distribution range and concentration degree of the maximum and minimum principal stresses increased obviously, and both were compression-dominated. The types of plastic zones in the surrounding rock were mainly characterized by shear stress-induced yielding and tensile stress-induced damage failure. When the original rock temperature increased to 90 °C, the rock mass extending up to 1.5 m from the excavation contour surface formed a large area of damage zone. The closer the working face was to the monitoring section, the faster the temperature dropped, and the displacement changed in the monitoring section. The findings offer a theoretical basis for engineering practice, and it is of great significance to ensure the safety of the project. Full article

The tetrameric protein transthyretin (TTR) transports the hormone thyroxine in plasma and cerebrospinal fluid. Certain point mutations of TTR, including the Val122Ile mutation investigated here, destabilize the tetramer leading to its dissociation, misfolding, aggregation, and the eventual buildup of amyloid fibrils in the myocardium. Cioffi et al. reported the design and synthesis of a novel TTR kinetic stabilizing ligand, referred to here as TKS14, that inhibited TTR dissociation and amyloid fibril formation. In this study, molecular dynamics simulations were used to investigate the binding of TKS14 and eight TSK14 derivatives to the Val122Ile TTR mutant. For each complex, the ligand’s solvent accessible surface area (SASA), ligand–receptor hydrogen-bonding interactions, and the free energy of ligand-binding to TTR were investigated. The goal of this study was to identify the TSK14 functional groups that contributed to TTR stabilization. TKS14 was found to form a stable, two-point interaction with TTR by hydrogen bonding to Ser-117 residues in the inner receptor binding pocket and interacting through hydrogen bonds and electrostatically with Lys-15 residues near the receptor’s surface. The free energy of TKS14-TTR binding was −18.0 kcal mol⁻¹ and the ligand’s average SASA value decreased by over 80% upon binding to the receptor. The thermodynamic favorability of TTR binding decreased when TKS14 derivatives contained either methyl ester, amide, tetrazole, or N-methyl functional groups that disrupted the above two-point interaction. One derivative in which a tetrazole ring was added to TKS14 was found to form hydrogen bonds with Thr-106, Thr-119, Ser-117, and Lys-15 residues. This derivative had a free energy of TTR binding of −21.4 kcal mol⁻¹. Overall, the molecular dynamics simulations showed that the functional groups within the TKS14 structural template can be tuned to optimize the thermodynamic favorability of ligand binding. Full article

Lithium borohydride (LiBH₄) has emerged as a promising hydrogen storage material due to its exceptional theoretical hydrogen capacity (18.5 wt.%). However, its practical application is hindered by high dehydrogenation temperature (>400 °C), sluggish kinetics, and limited reversibility due to stable intermediate formation. This review critically analyzes recent advances in LiBH₄ modification through three primary strategies: catalytic enhancement, nanostructure engineering, and reactive composite design. Advanced carbon architectures and metal oxide catalysts demonstrate significant improvements in reaction kinetics and cycling stability through interface engineering and electronic modification. Sophisticated nanostructuring approaches, including mechanochemical processing and infiltration techniques, enable precise control over material architecture and phase distribution, effectively modifying thermodynamic and kinetic properties. The development of reactive hydride composites, particularly LiBH₄-MgH₂ systems, provides promising pathways for thermodynamic destabilization while maintaining high capacity. Despite these advances, challenges persist in maintaining engineered structures and suppressing intermediate phases during cycling. Future developments require integrated approaches combining multiple modification strategies while addressing practical implementation requirements. Full article

Effective formation and stabilisation of emulsions while meeting high consumer requirements, including the so-called green label, is still a technological challenge. This is related to the multitude of emulsion destabilization mechanisms and the vastness of methods used to study them, which implies the need to develop an understanding of the phenomena occurring in emulsions. Commercial starch preparations obtained by physical and chemical modification were used to prepare model emulsions that were studied in terms of their stability. Native potato starch was the reference material. The analytical methods used included rheology, low field nuclear magnetic resonance (LF NMR), size exclusion chromatography with triple detection (SEC), and surface/interfacial tension measurements. The results showed that chemical and physical modification improved the functionality of starch in emulsions. This is due to not only chemical but also physical modifications, i.e., pregelatinization causes changes in the molecular structure of starch, including an increase in the molecular weight and the degree of branching. As a consequence, the conformation of starch macromolecules changes, which results in a change of the dynamics of protons in the continuous phase of the emulsion and the thermodynamics of starch adsorption at the water/oil interface. Full article

GdmCl and NaSCN are two strong chaotropic salts commonly used in protein folding and stability studies, but their microscopic mechanisms remain enigmatic. Here, by CD and NMR, we investigated their effects on conformations, stability, binding and backbone dynamics on ps-ns and µs-ms time scales of a 39-residue but well-folded WW4 domain at salt concentrations ≤200 mM. Up to 200 mM, both denaturants did not alter the tertiary packing of WW4, but GdmCl exerted more severe destabilization than NaSCN. Intriguingly, GdmCl had only weak binding to amide protons, while NaSCN showed extensive binding to both hydrophobic side chains and amide protons. Neither denaturant significantly affected the overall ps-ns backbone dynamics, but they distinctively altered µs-ms backbone dynamics. This study unveils that GdmCl and NaSCN destabilize a protein before the global unfolding occurs with differential binding properties and µs-ms backbone dynamics, implying the absence of a simple correlation between thermodynamic stability and backbone dynamics of WW4 at both ps-ns and µs-ms time scales. Full article

Background: Cystathione beta-synthase (CBS) T236N is a novel mutation associated with pyridoxine non-responsiveness, which presents a significant difficulty in the medical treatment of homocystinuria. Reported severe phenotypes in homocystinuria patients highlight the urgent requirement to comprehend the molecular mechanisms underlying mutation pathogenicity for the advancement of the disease. Methodology: In this study, we used a multidisciplinary approach to investigate the molecular properties of bacterially expressed and purified recombinant CBS^T236N protein, which we directly compared to those of the wild-type (CBS^WT) protein. Results: Our data revealed a profound impact of the p.T236N mutation on CBS enzymatic activity, with a dramatic reduction of ~96% compared to the CBS^WT protein. Circular dichroism (CD) experiments indicated that the p.T236N mutation did not significantly alter the secondary structure of the protein. However, CD spectra unveiled distinct differences in the thermal stability of CBS^WT and CBS^T236N mutant protein species. In addition, chemical denaturation experiments further highlighted that the CBS^WT protein exhibited greater thermodynamic stability than the CBS^T236N mutant, suggesting a destabilizing effect of this mutation. Conclusions: Our findings provide an explanation of the pathogenicity of the p.T236N mutation, shedding light on its role in severe homocystinuria phenotypes. This study contributes to a deeper understanding of CBS deficiency and may improve the development of targeted therapeutic strategies for affected individuals. Full article

Surface charges of catalysts have important influences on the thermodynamics and kinetics of electrochemical reactions. Herein, we develop a modified version of the grand-canonical potential kinetics (GCP-K) method based on density functional theory (DFT) calculations to explore the effect of surface charges on reaction thermodynamics and kinetics. Using the hydrogen evolution reaction (HER) on the Pt(111) surface as an example, we show how to track the change of surface charge in a reaction and how to analyze its influence on the kinetics. Grand-canonical calculations demonstrate that the optimum hydrogen adsorption energy on Pt under the standard hydrogen electrode condition (SHE) is around −0.2 eV, rather than 0 eV established under the canonical ensemble, due to the high density of surface negative charges. By separating the surface charges that can freely exchange with the external electron reservoir, we obtain a Tafel barrier that is in good agreement with the experimental result. During the Tafel reaction, the net electron inflow into the catalyst leads to a stabilization of canonical energy and a destabilization of the charge-dependent grand-canonical component. This study provides a practical method for obtaining accurate grand-canonical reaction energetics and analyzing the surface charge induced changes. Full article

The nonstructural proteins 7 and 8 (nsp7 and nsp8) of SARS-CoV-2 are highly important proteins involved in the RNA-dependent polymerase (RdRp) protein replication complex. In this study, we analyzed the global mutation of nsp7 and nsp8 in 2022 and 2023 and analyzed the effects of mutation on the viral replication protein complex using bio-chemoinformatics. Frequently occurring variants are found to be single amino acid mutations for both nsp7 and nsp8. The most frequently occurring mutations for nsp7 which include L56F, L71F, S25L, M3I, D77N, V33I and T83I are predicted to cause destabilizing effects, whereas those in nsp8 are predicted to cause stabilizing effects, with the threonine to isoleucine mutation (T89I, T145I, T123I, T148I, T187I) being a frequent mutation. A conserved domain database analysis generated critical interaction residues for nsp7 (Lys-7, His-36 and Asn-37) and nsp8 (Lys-58, Pro-183 and Arg-190), which, according to thermodynamic calculations, are prone to destabilization. Trp-29, Phe-49 of nsp7 and Trp-154, Tyr-135 and Phe-15 of nsp8 cause greater destabilizing effects to the protein complex based on a computational alanine scan suggesting them as possible new target sites. This study provides an intensive analysis of the mutations of nsp7 and nsp8 and their possible implications for viral complex stability. Full article

High-entropy alloys (HEAs) are a promising class of materials that can grant remarkable functional performances for a large range of applications due to their highly tunable composition. Among these applications, recently, bcc HEAs capable of forming fcc hydrides have been proposed as high-capacity hydrogen storage materials with improved thermodynamics compared to classical metal hydrides. In this context, a single-phase bcc (TiVNb)_0.90Cr_0.05Mn_0.05 HEA was prepared by arc melting to evaluate the effect of combined Cr/Mn addition in the ternary TiVNb. A thermodynamic destabilization of the fcc hydride phase was found in the HEA compared to the initial TiVNb. In situ neutron and synchrotron X-ray diffraction experiments put forward a fcc → bcc phase transition of the metallic subnetwork in the temperature range of 260–350 °C, whereas the H/D subnetwork underwent an order → disorder transition at 180 °C. The absorption/desorption cycling demonstrated very fast absorption kinetics at room temperature in less than 1 min with a remarkable total capacity (2.8 wt.%) without phase segregation. Therefore, the design strategy consisting of small additions of non-hydride-forming elements into refractory HEAs allows for materials with promising properties for solid-state hydrogen storage to be obtained. Full article