The thioredoxin system, comprising thioredoxin (Trx) and thioredoxin reductase (TrxR), is a central regulator of cellular redox homeostasis and plays essential roles in normal brain physiology and redox signaling. In glioblastoma (GBM), this system undergoes profound pathological rewiring, creating a redox dependency that represents a potential therapeutic vulnerability. The overexpression of Trx and TrxR in GBM promotes tumor proliferation, invasion, angiogenesis, and resistance to chemotherapy and radiotherapy, while the endogenous Trx inhibitor, thioredoxin-interacting protein (TXNIP), is frequently downregulated. This imbalance drives redox adaptation and sustains tumor survival under metabolic and therapeutic stress. Pharmacological modulation of the Trx system using synthetic inhibitors, such as auranofin, platinum-based compounds, and PX-12, as well as selected natural compounds including curcumin analogs and flavonoids, has shown efficacy in preclinical GBM models by inducing oxidative stress and enhancing sensitivity to standard therapies. Emerging evidence also suggests that Trx system targeting may modulate the tumor immune microenvironment, providing a rationale for combination strategies with immunomodulatory approaches. Overall, targeting the Trx system represents a promising precision oncology strategy for GBM. Future efforts should focus on the development of brain-penetrant inhibitors, rational combination therapies, and predictive biomarkers to facilitate clinical translation. Given the essential role of the Trx system in normal brain homeostasis, therapeutic targeting requires careful consideration of safety, therapeutic index, and tumor-selective vulnerabilities. This narrative review discusses current evidence on the physiological functions of the Trx system in the brain, its dysregulation in GBM, and its relevance as a precision therapeutic target.
Carbonic anhydrase isoforms I and II (hCA-I and hCA-II) are metalloenzymes involved in essential physiological processes and represent relevant therapeutic targets for disorders such as glaucoma and osteoporosis. Chalcones have emerged as promising scaffolds for carbonic anhydrase inhibition; however, their structure-activity relationships, particularly for non-sulfonamide derivatives, remain insufficiently explored from a computational point of view. In this study, a dataset of 118 chalcone derivatives has been analyzed by using a three-dimensional quantitative structure-activity relationship (3D-QSAR) modeling, which comprises Comparative Molecular Field Analysis (CoMFA) and Comparative Molecular Similarity Index Analysis (CoMSIA). The developed models exhibited strong internal consistency and predictive capability for both isoforms. For hCA-I, steric, electrostatic, hydrophobic, and hydrogen bond acceptor fields has been identified as key contributors to inhibitory activity, whereas for hCA-II, hydrogen bond donor features played a more prominent role. Molecular docking and molecular dynamics simulations have been employed as complementary approaches to analyze ligand-protein interactions and binding stability. In addition, quantum chemical descriptors, derived from density functional theory, that have been integrated with the 3D-QSAR analysis, reveal a consistent correspondence between contour map features and the distribution of frontier molecular orbitals and molecular electrostatic potential. Furthermore, ADME-based pharmacokinetic properties of the proposed compounds have been evaluated to assess their potential drug-likeness. Based on the integrated computational analysis, six new chalcone derivatives, with predicted inhibitory activity in the nanomolar range, are proposed. Overall, this study provides a consistent physicochemical framework for understanding the inhibitory activity of chalcone derivatives and highlights key molecular features that may guide the modulation of activity across hCA-I and hCA-II isoforms.
Lepton number violating meson decays, such as M-1(-) -> M-2(+) l(1)(-)l(2)(-), provide constraints on d = 9 Delta L = 2 operators. Renormalization group equation (RGE)-improved bounds on the Wilson coefficients of these operators have been presented in the literature, taking into account perturbative quantum chromodynamics (QCD) one-loop corrections and the corresponding operator mixing. Here, we present for the first time the contribution of connected diagrams to the hadronic matrix elements < M2 vertical bar Oh vertical bar M-1 >. These diagrams, usually overlooked under the assumption that < M2 vertical bar Oh|M-1 > similar to < M-2 vertical bar J(q3q4)vertical bar 0 > x < 0 vertical bar J(q1q2)vertical bar M-1 > >> < M-2 vertical bar J(q3q2) x J(q1q4 vertical bar)M(1 >), can give indeed a significant contribution to the matrix element. Including these connected diagrams is but the first step toward a full nonperturbative computation of the long-range QCD effects in these operators, that should be performed using lattice field theory techniques. However, connected diagrams represent the leading order in the 1/N-c expansion of the QCD nonperturbative effects and thus our work can be understood as a realistic, first approximation to a complete calculation of the long-range part of the matrix elements.
We investigate a cosmological model based on matter creation in a single-component universe, its late time behavior and observational constraints derived from observational data. Furthermore, we explore the equivalence between this framework and interacting dark sector models, which establishes a connection between the matter creation rate and cosmological interactions. We first focus on the case of a constant equation of state parameter, where both known and novel interaction terms naturally emerge from matter creation, numerous of them exhibiting a sign-changeable behavior. The analysis is then extended to a time-dependent equation of state by using dynamical systems techniques.
In fishes, mouth gape and body size constrain food acquisition, and morphology often changes throughout ontogeny, potentially leading to covariation between shape and trophic ecology. We tested this hypothesis in the spotted drunk blenny Scartichthys variolatus, an insular species from Robinson Crusoe Island (Southeast Pacific Ocean), by integrating geometric morphometrics and stable isotope analysis. Specimens (n = 90) range from 4.66 to 24.01 cm total length (mean ± SD: 12.14 ± 5.14 cm) and from 0.43 to 131.33 g (24.94 ± 29.55 g). The relative condition (Kn) was independent of size. Ontogenetic shape variation was characterised by a transition from individuals with relatively larger eyes, shorter snouts, and a relatively larger distance of dorsal fin insertion from the snout to specimens with smaller eyes relative to the head, vertically extended snouts, and more frontally inserted dorsal fins. The ontogenetic allometry was high (30.5
