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15. Characterization of naphthoquinones as inhibitors of glutathione reductase and inducers of intracellular oxidative stress.

Author

Chen, Xiaowan, Ma, Yan, Yang, Ziming, Shen, Dingjie, Li, Xia, Ni, Maowei, Xu, Xiaoling, and Chen, Wei

Subjects
*GLUTATHIONE reductase, *CANCER cell growth, *ENDOENZYMES, *REACTIVE oxygen species, *MEMBRANE proteins
Abstract

Glutathione reductase (GR), one of the most important antioxidant enzymes in maintaining intracellular redox homeostasis, has become a novel target to suppress cancer cell growth and metastasis. In this work, we evaluated a series of naphthoquinones (NQs) as potential GR inhibitors and elucidated the mechanism of inhibition. NQ-6, one of the most potent compounds among this series, inhibited GR in vitro and in vivo and was identified as a competitive and irreversible inhibitor. The Ki and kinact values of NQ-6 were determined to be 17.30 ± 3.63 μM and 0.0136 ± 0.0005 min-1, respectively. The tandem mass spectrometric analysis revealed that the two substrate binding sites Cys61 and Cys66 of yeast GR were modified simultaneously through arylation or only Cys66 was covalently modified by NQ-6. Intracellular reactive oxygen species, collapsing of mitochondrial membrane potential and protein S-glutathionylation elevation were induced by NQ-6. NQs can be valuable compounds in GR inhibition and oxidative stress-related research. [ABSTRACT FROM AUTHOR]

Published
2024
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31. Bending-shear interaction buckling of stainless steel plate girders: numerical investigation and design method

Author

Universitat Politècnica de Catalunya. Departament d'Enginyeria Civil i Ambiental, Universitat Politècnica de Catalunya. ATEM - Anàlisi i Tecnologia d'Estructures i Materials, Chen, Xiaowan, Yuan, Huanxin, Real Saladrigas, Esther, Universitat Politècnica de Catalunya. Departament d'Enginyeria Civil i Ambiental, Universitat Politècnica de Catalunya. ATEM - Anàlisi i Tecnologia d'Estructures i Materials, Chen, Xiaowan, Yuan, Huanxin, and Real Saladrigas, Esther

Abstract

A comprehensive numerical investigation of transversely stiffened stainless steel plate girders under combined bending and shear was carried out in this paper. By using the finite element (FE) software package ABAQUS, numerical models with incorporation of material nonlinearity, initial geometric imperfections and welding residual stresses were developed, and were used to replicate previously obtained test results. The validated numerical models were employed to perform parametric studies to generate structural data points for stainless steel plate girders over a broad range of cross-sectional properties, involving various combinations of bending moment and shear force. The summarised test and FE results were compared with the predicted strengths determined according to European code EN 1993-1-5 and proposals of Jáger et al., Chinese code GB 50017-2017, and American specification ANSI/AISC 370-21, highlighting that the applicability of existing design methods in predicting the ultimate resistances of stainless steel plate girders under combined bending moment and shear force was limited. By referring to the design methods in GB 50017-2017 and ANSI/AISC 370-21, two separate design recommendations were proposed, respectively. Further reliability analyses were performed to verify the applicability of the abovementioned design methods., Peer Reviewed, Postprint (author's final draft)

Published
2023

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