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Methazolamide is a carbonic anhydrase (CA) inhibitor with satisfactory safety. Our previous studies have demonstrated the elevation of CA1 expression and the therapeutic effect of Methazolamide in Ankylosing spondylitis (AS). In this study, we explored the pathogenic role of CA1 and the pharmacological mechanism of Methazolamide in AS through Gene Set Enrichment Analysis (GSEA) and network pharmacology. Seven out of twelve CA1 related gene sets were enriched in AS group. CA1 was core enriched in above seven gene sets involving zinc ion binding, arylesterase activity and one carbon metabolic process. Functional analysis of the candidate target genes obtained from the intersection of AS associated genes and Methazolamide target genes indicated that Methazolamide exerts therapeutic effects on AS mainly through inflammatory pathways which regulate the production of tumor necrosis factor, IL-6 and nitric oxide. PTGS2, ESR1, GSK3β, JAK2, NOS2 and CA1 were selected as therapeutic targets of Methazolamide in AS. Molecular docking and molecular dynamics simulations were performed successfully. In addition, we innovatively obtained the intersection of Gene Ontology (GO)/Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses and GSEA results, and found that 18 GO terms and 5 KEGG terms were indicated in the pharmacological mechanism of Methazolamide in AS, involving bone mineralization, angiogenesis, inflammation, and chemokine signaling pathways. Nevertheless, validation for these mechanisms is needed in vivo/vitro experiments. [ABSTRACT FROM AUTHOR]

The coupling between structural phase transformations and dislocations induces challenges in understanding the deformation behavior of metallic cerium at the nanoscale. In the present work, we elucidate the underlying mechanism of cerium under ultra-precision diamond cutting by means of molecular dynamics modeling and simulations. The molecular dynamics model of diamond cutting of cerium is established by assigning empirical potentials to describe atomic interactions and evaluating properties of two face-centered cubic cerium phases. Subsequent molecular dynamics simulations reveal that dislocation slip dominates the plastic deformation of cerium under the cutting process. In addition, the analysis based on atomic radial distribution functions demonstrates that there are trivial phase transformations from the γ-Ce to the δ-Ce occurred in both machined surface and formed chip. Following investigations on machining parameter dependence reveal the optimal machining conditions for achieving high quality of machined surface of cerium. [ABSTRACT FROM AUTHOR]

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Detwinning is a unique deformation mechanism of nanotwinned metals with twin lamellae thickness down to a few nanometers. In this work we investigate the impact of detwinning mechanism on the tensile ductility of twinned Cu nanowires containing high density of parallel twin boundaries by means of molecular dynamics simulations. Simulation results show that the fracture strain of twinned Cu nanowires has a strong dependence on twin boundary spacing, resulting from the competition between individual deformation modes. Particularly for the twinned Cu nanowires containing the thinnest twin lamellaes, the dominant detwinning mechanism leads to a significant reduction in the tensile ductility. It is found that detwinning originates from twin boundary migration, which is a result of the glide of lattice partial dislocations on the twin planes. This work advances our fundamental understanding of the twin boundary-related mechanical properties of twinned metallic nanowires. [ABSTRACT FROM AUTHOR]

Interfaces play key roles in determining mechanical properties of materials. In current work we perform molecular dynamics simulations of diffusion bonding to evaluate the effect of temperature on the morphology of the Ni/Al interface and the strength of the diffusion bonded Ni/Al nanowires. The centro-symmetry parameter is adopted to identify defect atoms generated. Simulation results show that the thickness of the Ni/Al interface has strong dependence on the temperature of diffusion bonding. Following uniaxial tension tests indicate that the yield strength of Ni/Al nanowires is smaller than both the single crystalline Ni and Al nanowires, because of the Ni/Al interface acting as dislocation source and the mobilization of pre-existing dislocations at high temperature. It is shown that the mechanical properties of diffusion bonded Ni/Al nanowires strongly depend on the temperature. [ABSTRACT FROM AUTHOR]