Radiation-induced gastrointestinal injury is a dose-limiting complication of abdominal and pelvic radiotherapy, marked by epithelial loss, inflammation, and impaired regeneration. Glycogen synthase kinase-3β (GSK-3β), a negative regulator of canonical Wnt/β-catenin signaling, is central to intestinal stem cell maintenance and mucosal repair. Here, we evaluated valproic acid (VPA) as a modulator of GSK-3β using in silico docking and molecular dynamics, network biology, and in vivo irradiation models. Molecular docking analysis revealed favorable binding of VPA within the ATP-binding pocket of GSK-3β (binding free energy: -4.7 kcal/mol; estimated Ki: 0.36 mM). Notably, the predicted Ki falls within the clinically achievable therapeutic concentration range of VPA, supporting the potential for biologically relevant GSK-3β modulation in vivo. VPA interacted with residues implicated in ATP coordination, forming hydrogen bonds with Val139 and hydrophobic contacts with Gly67, Lys89, Asp137, and Tyr138. A 200-ns MD trajectory showed a stable VPA-GSK-3β complex and persistent hydrogen bonding, supporting electrostatic stabilization. MM/PBSA binding energies for VPA (-34.16 kcal/mol) was more favorable than the native ligand and known inhibitor (native: -33.9673 kcal/mol, known inhibitor: -31.273 kcal/mol). Principal component analysis revealed ligand-dependent shifts in conformational sampling, suggesting altered active-site dynamics rather than full blockade. PPI network analysis connected GSK-3β modulation to stabilization of β-catenin and attenuation of NF-κB-driven inflammation. In vivo, VPA (100 mg/kg.b.wt) increased survival after whole-body irradiation (66% vs. 33%) and preserved colon length following abdominal irradiation. Together, these results support a model in which VPA exerts moderate, indirect inhibition of GSK-3β that favors Wnt-mediated regeneration and reduces inflammatory responses in irradiated intestine.
This study investigates the steam oxidation resistance of a TiN/TiAlN bilayer coating deposited on Zircaloy-4 (Zr-4) using cylindrical magnetron sputtering. The coated samples were characterized by X-ray diffraction (XRD), Scanning Electron Microscopy (SEM), Raman Spectroscopy, X-ray Photon Spectroscopy (XPS), and weight gain measurements before and after exposure to a steam environment at 400 °C and 10 MPa for 72 h. Post oxidation, the TiN/TiAlN bilayer developed a surface layer of anatase TiO2, while maintaining the structural integrity of the underlying coating. Cross-sectional SEM analysis confirmed the formation of a thin and compact TiO2 layer ( 250 nm) on the TiN/TiAlN coating surface. XPS results revealed surface hydroxylation and the presence of sub-stoichiometric TiOx on the outer layer. Notable, nitrogen depletion was also observed, evidenced by the absence of N 1s peak, and the Ti 2p envelopes were dominated by Ti–O bonds. Wettability tests revealed a significant difference between the uncoated and coated samples. Post oxidation, the uncoated Zr-4 exhibited a hydrophilic response for, whereas the TiN/TiAlN bilayer retained its hydrophobicity. Weight gain measurements after steam oxidation at 400 °C, 10 MPa, 72 h showed a nearly four-fold reduction for coated samples ( 5.3 mg·dm− 2) compared to the uncoated Zr-4 ( 19.5 mg·dm− 2). Further, high temperature steam oxidation behavior of coated samples was evaluated at 600 °C and 700 °C to assess its suitability for accident tolerant fuel (ATF) application. Superior oxidation resistance of TiN/TiAlN bilayer showcased enhanced protection, supporting its suitability under high temperature steam (up to 600 °C) for Zr-4 fuel cladding tubes.
The STAR Collaboration reports measurements of acoplanarity using semi-inclusive distributions of charged-particle jets recoiling from direct photon and pi(0) triggers, in central Au-Au and pp collisions at root s(NN) = 200 GeV. Significant medium-induced acoplanarity broadening is observed for large but not small recoil jet resolution parameter, corresponding to recoil jet yield enhancement up to a factor of approximate to 20 for trigger-recoil azimuthal separation far from pi. This phenomenology is indicative of the response of the quark-gluon plasma to excitation, but not the scattering of jets off of its quasiparticles. The measurements are not well described by current theoretical models which incorporate jet quenching.
The Carroll group arises in the vanishing speed of light limit of the Poincaré group and was initially discarded as just a mathematical curiosity. However, recent developments have proved otherwise. Carroll and conformal Carroll symmetries are now ubiquitous, appearing in diverse physical phenomena starting from condensed matter physics to quantum gravity. This review aims to provide the reader a gateway into this fast-developing field. After an introduction and setting the stage with basics of the symmetry in question, we detail the construction of Carrollian and Carrollian Conformal field theories (CCFT). We then focus on applications. By far the most popular of these applications is in the context of the construction of holography in asymptotically flat spacetimes (AFS) in terms of a co-dimension one dual CCFT. We review the early work on AFS _3 /CCFT _2 before delving into an in-depth analysis for the construction of the dual to 4D AFS. Two other important sets of applications are in hydrodynamics and in condensed matter physics, which we discuss in detail. Carroll hydrodynamics is introduced as the c→ 0 limit of relativistic hydrodynamics first and then reconstructed from a symmetry based approach. Relations to ultrarelativistic flows and connections to the quark-gluon plasma are discussed with concrete examples of the Bjorken and Gubser flow models. In condensed matter applications, we cover connections to fractons, flat bands, and phase separation in Luttinger liquid models. To conclude, we give very brief outlines of other topics of interest including string theory and black hole horizons.
In the nuclear industry, achieving high-quality welds requires careful study of the formation of the fusion zone (FZ) and heat-affected zone (HAZ), as these regions play a critical role in determining the joint’s metallurgical and mechanical properties. Accurate characterisation of the FZ and HAZ depends on understanding the transient temperature distribution during welding. In this work, a multiphysics finite element model incorporating a moving heat source was developed to efficiently simulate the Tungsten inert gas welding process. The influence of welding current, arc distance and rotational speed on thermal profiles was systematically investigated. The simulations predicted that the FZ and HAZ lengths varied from 0.6 to 2.0 mm and from 2.95 to 5.4 mm, respectively, depending on the welding parameters. These predictions showed good agreement with experimental measurements, with deviations within 10
