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        O-GlcNAc transferase regulates intervertebral disc degeneration by targeting FAM134B-mediated ER-phagy

        Luo Rongjin,Li Gaocai,Zhang Weifei,Liang Huaizhen,Lu Saideng,Cheung Jason Pui Yin,Zhang Teng,Tu Ji,Liu Hui,Liao Zhiwei,Ke Wencan,Wang Bingjin,Song Yu,Yang Cao 생화학분자생물학회 2022 Experimental and molecular medicine Vol.54 No.-

        Both O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) and endoplasmic reticulum-phagy (ER-phagy) are well-characterized conserved adaptive regulatory mechanisms that maintain cellular homeostasis and function in response to various stress conditions. Abnormalities in O-GlcNAcylation and ER-phagy have been documented in a wide variety of human pathologies. However, whether O-GlcNAcylation or ER-phagy is involved in the pathogenesis of intervertebral disc degeneration (IDD) is largely unknown. In this study, we investigated the function of O-GlcNAcylation and ER-phagy and the related underlying mechanisms in IDD. We found that the expression profiles of O-GlcNAcylation and O-GlcNAc transferase (OGT) were notably increased in degenerated NP tissues and nutrient-deprived nucleus pulposus (NP) cells. By modulating the O-GlcNAc level through genetic manipulation and specific pharmacological intervention, we revealed that increasing O-GlcNAcylation abundance substantially enhanced cell function and facilitated cell survival under nutrient deprivation (ND) conditions. Moreover, FAM134B-mediated ER-phagy activation was regulated by O-GlcNAcylation, and suppression of ER-phagy by FAM134B knockdown considerably counteracted the protective effects of amplified O-GlcNAcylation. Mechanistically, FAM134B was determined to be a potential target of OGT, and O-GlcNAcylation of FAM134B notably reduced FAM134B ubiquitination-mediated degradation. Correspondingly, the protection conferred by modulating O-GlcNAcylation homeostasis was verified in a rat IDD model. Our data demonstrated that OGT directly associates with and stabilizes FAM134B and subsequently enhances FAM134B-mediated ER-phagy to enhance the adaptive capability of cells in response to nutrient deficiency. These findings may provide a new option for O-GlcNAcylation-based therapeutics in IDD prevention.

      • KCI등재

        Value range optimization of ply parameter for composite wind turbine blades based on sensitivity analysis

        Pengwen Sun,Yin Zhang,Lanting Zhang,Weifei Hu 대한기계학회 2022 JOURNAL OF MECHANICAL SCIENCE AND TECHNOLOGY Vol.36 No.3

        Blade ply parameters are important design factors that influence the performances of wind turbine blades. This paper proposes a sensitivity analysis method of the blade ply parameters that fuses the relative sensitivity analysis of multi-parameters and the interval sensitivity analysis of single-parameters. A method for identifying the stability region of the sensitive parameters is presented. Coupled mathematical models of the blade static strength and the blade stiffness as a function of the blade ply parameters are established by incorporating experimental design, finite element analysis, and multiple nonlinear regression. The moment independent sensitivity analysis method based on the cumulative distribution function is used to analyze the multi-parameter relative sensitivity, and the direct derivative method was used to analyze single-parameter interval sensitivity. The sensitive and insensitive ply parameters are identified, and the initial stability and instability regions of the ply parameters are determined. A case study of a 1.5 MW blade shows that the ply angle and the ply thickness are sensitive parameters, and the ply stacking sequence is an insensitive parameter. The optimal and stability value ranges of the ply angle and the ±x° ply thickness ratio are [44°, 45°] and [44 %, 48 %], respectively. Hence, the validity and reliability of the proposed method is verified.

      • KCI등재

        A discrete material optimization method with a patch strategy based on stiffness matrix interpolation

        Pengwen Sun,Jie Zhang,Penghui Wu,Jiandong Li,Lanting Zhang,Weifei Hu 대한기계학회 2022 JOURNAL OF MECHANICAL SCIENCE AND TECHNOLOGY Vol.36 No.2

        A discrete material optimization method with a patch strategy based on the stiffness matrix interpolation is proposed, and a comprehensive technical process of patch discrete material optimization using existing finite element software was developed. This method employs the stiffness matrix instead of the constitutive matrix for material interpolation, which facilitates the optimization process integrated with the existing finite element software. The element stiffness matrix can be derived directly from the finite element analysis, which can not only ensure the correctness of the data, but also reduce the programming work of solving the numerical integration of the composite constitutive matrix. The mathematical model of the patch discrete material optimization is established, which takes the artificial density as the design variable, the minimum compliance as the objective function, and the sequential quadratic programming (SQP) algorithm as the optimization solver. Numerical examples show that by seeking a balance between the number of regions and practical production, the performance of the composite could be further improved using the discrete material optimization method with a patch strategy. Besides, the convergence rate of the optimization is increased by introducing the sum constraints of the design variables and the value functions. The effectiveness and the feasibility of the method were verified.

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