In engineering practice, tubular X-joints have been widely used in offshore structures. The fatigue failure of tubular X-joints in offshore engineering is mainly caused by axial tensile stress. In this study, the stre...In engineering practice, tubular X-joints have been widely used in offshore structures. The fatigue failure of tubular X-joints in offshore engineering is mainly caused by axial tensile stress. In this study, the stress concentration factor distribution along the weld toe in the hot spot stress region for tubular X-joints subject to axial loads have been analyzed by use of finite element method. Through numerical analysis, it has been found that the peak stress concentration factor is located at the saddle position. Thereafter, 80 models have been analyzed, and the effect of the geometric parameters of a tubular X-joint on the stress concentration factor has been investigated. Based on the experimental values of the numerical stress concentration factor, a parametric equation to calculate the stress concentration factor of tubular X-joints has been proposed. The accuracy of this equation has been verified against the requirement of the Fatigue Guidance Review Panel, and the proposed equation is found capable of producing reasonably accurate stress concentration factor values for tubular X-joints subject to axial loads.展开更多
The mesencephalic astrocyte-derived neurotrophic factor(MANF)has been recently identified as a neurotrophic factor,but its role in hepatic fibrosis is unknown.Here,we found that MANF was upregulated in the fibrotic li...The mesencephalic astrocyte-derived neurotrophic factor(MANF)has been recently identified as a neurotrophic factor,but its role in hepatic fibrosis is unknown.Here,we found that MANF was upregulated in the fibrotic liver tissues of the patients with chronic liver diseases and of mice treated with CCl4.MANF deficiency in either hepatocytes or hepatic mono-macrophages,particularly in hepatic mono-macrophages,clearly exacerbated hepatic fibrosis.Myeloid-specific MANF knockout increased the population of hepatic Ly6C^(high)macrophages and promoted HSCs activation.Furthermore,MANF-sufficient macrophages(from WT mice)transfusion ameliorated CCl4-induced hepatic fibrosis in myeloid cells-specific MANF knockout(MKO)mice.Mechanistically,MANF interacted with S100A8 to competitively block S100A8/A9 heterodimer formation and inhibited S100A8/A9-mediated TLR4-NF-κB signal activation.Pharmacologically,systemic administration of recombinant human MANF significantly alleviated CCl_(4)-induced hepatic fibrosis in both WT and hepatocytes-specific MANF knockout(HKO)mice.This study reveals a mechanism by which MANF targets S100A8/A9-TLR4 as a“brake”on the upstream of NF-κB pathway,which exerts an impact on macrophage differentiation and shed light on hepatic fibrosis treatment.展开更多
基金The research work was financially supported by the National Natural Scientice Foundation of China(Grant No.10142001)by the Shandong Provincial Natural Scientice Foundation(Grant No.Y2006F46)
文摘In engineering practice, tubular X-joints have been widely used in offshore structures. The fatigue failure of tubular X-joints in offshore engineering is mainly caused by axial tensile stress. In this study, the stress concentration factor distribution along the weld toe in the hot spot stress region for tubular X-joints subject to axial loads have been analyzed by use of finite element method. Through numerical analysis, it has been found that the peak stress concentration factor is located at the saddle position. Thereafter, 80 models have been analyzed, and the effect of the geometric parameters of a tubular X-joint on the stress concentration factor has been investigated. Based on the experimental values of the numerical stress concentration factor, a parametric equation to calculate the stress concentration factor of tubular X-joints has been proposed. The accuracy of this equation has been verified against the requirement of the Fatigue Guidance Review Panel, and the proposed equation is found capable of producing reasonably accurate stress concentration factor values for tubular X-joints subject to axial loads.
基金supported by the National Natural Science Foundation of China(81973336)the Joint Fund of the National Natural Science Foundation of China(U21A20345)。
文摘The mesencephalic astrocyte-derived neurotrophic factor(MANF)has been recently identified as a neurotrophic factor,but its role in hepatic fibrosis is unknown.Here,we found that MANF was upregulated in the fibrotic liver tissues of the patients with chronic liver diseases and of mice treated with CCl4.MANF deficiency in either hepatocytes or hepatic mono-macrophages,particularly in hepatic mono-macrophages,clearly exacerbated hepatic fibrosis.Myeloid-specific MANF knockout increased the population of hepatic Ly6C^(high)macrophages and promoted HSCs activation.Furthermore,MANF-sufficient macrophages(from WT mice)transfusion ameliorated CCl4-induced hepatic fibrosis in myeloid cells-specific MANF knockout(MKO)mice.Mechanistically,MANF interacted with S100A8 to competitively block S100A8/A9 heterodimer formation and inhibited S100A8/A9-mediated TLR4-NF-κB signal activation.Pharmacologically,systemic administration of recombinant human MANF significantly alleviated CCl_(4)-induced hepatic fibrosis in both WT and hepatocytes-specific MANF knockout(HKO)mice.This study reveals a mechanism by which MANF targets S100A8/A9-TLR4 as a“brake”on the upstream of NF-κB pathway,which exerts an impact on macrophage differentiation and shed light on hepatic fibrosis treatment.
