Search

• A modified plasticity-creep superposition model was developed to predict the lifetime. • The effects of creep-ratcheting evolution, anelastic recovery and PCR were discussed. • The proposed model can well simulate the evolution of stress–strain during the whole lifetime. The creep-ratcheting behavior of advanced 9–12 % Cr ferritic steel at 600 °C under peak holding time of 0 min, 2 min, 5 min, 10 min, 20 min and 30 min were investigated and a creep-ratcheting constitutive model was developed. Results present that the anelastic strain during the whole creep-fatigue life for various holding time approximately keep constant. However, it decreases rapidly during the last several cycles. Moreover, the primary creep regeneration (PCR) behavior during repeated loading and unloading process was observed. It keeps almost the same with increasing number of cycles and changes slightly for different peak holding time under the same stress amplitude and stress ratio. Additionally, a modified plasticity-creep superposition model was established considering the combination effects of creep damage, ratcheting evolution, anelastic recovery and PCR. The comparison between tested and predicted data shows that the proposed model has high accuracy for the prediction of both creep-ratcheting strain and creep-fatigue lifetime. It is of interest that the proposed model can also well simulate the evolution of stress–strain during the whole lifetime, especially for the reproduction of anelastic creep recovery and PCR along the load history. [ABSTRACT FROM AUTHOR]

Abstract: Toll-like receptor 2 (TLR2) is involved in phagocytosis and autophagy to enhance host innate immune response to bacterial infection. TLR2 has been reported to participate in the recognition of Staphylococcus aureus (S. aureus). However, the role of TLR2 in phagocytosis and autophagy in S. aureus-stimulated macrophages and the underlying mechanisms as yet remain unclear. In the present study, stimulation of mouse macrophage cell line RAW264.7 with S. aureus activated multiple signaling pathways including mitogen-activated protein kinases (MAPKs), myeloid differentiation factor 88 (MyD88), phosphatidylinositide 3-kinase (PI3K) and Rac1 and triggered autophagy process. Knockdown of TLR2 by siRNA significantly reduced phagocytosis and autophagy of macrophages upon S. aureus infection. Interestingly, TLR2 siRNA markedly attenuated S. aureus-induced phosphorylation of c-Jun N-terminal kinase (JNK) but not p38 or extracellular regulated protein kinase (ERK) in macrophages. Similarly, SP600125, a JNK inhibitor, also down-regulated phagocytosis and autophagy in S. aureus-stimulated macrophages. Furthermore, TLR2 siRNA and SP600125 simultaneous treatment showed similar phagocytosis and autophagy compared to that in TLR2 siRNA treatment alone. Collectively, our results indicate that TLR2 may be critical for phagocytosis and autophagy through JNK signaling pathway, and provide an underlying mechanistic link between innate immune receptor and induction of phagocytosis and autophagy in S. aureus-stimulated macrophages. [Copyright &y& Elsevier]

Activation of toll-like receptor (TLR) signaling that initiates an innate immune response to pathogens must be strictly regulated to prevent excessive inflammatory damage in the host. Here, we demonstrate that Mer receptor tyrosine kinase (MerTK) is a negative regulatory molecule in the lipoteichoic acid (LTA)-induced inflammatory response. LTA that activated TLR2 signaling concomitantly induced activation of MerTK signaling in RAW264.7 macrophages, including phosphoinositide 3-kinase (PI3K)/Akt and suppressor of cytokine signaling 3 (SOCS3). Moreover, LTA induced MerTK activation in a time-dependent manner, and LTA-induced MerTK activation was dependent on the ligand Gas6. Additionally, pretreatment with a specific Mer-blocking antibody significantly inhibited LTA-induced phosphorylation of MerTK, while further enhancing LTA-induced phosphorylation of IκB-α and NF-κBp65 as well as production of TNF-α and IL-6. Meanwhile, the antibody blockade of MerTK markedly prevented LTA-induced Akt phosphorylation and SOCS3 expression, both of which were crucial for the inhibition of TLR2-mediated immune response. Collectively, these results suggest, for the first time, that MerTK is an intracellular negative feedback regulator that inhibits the inflammatory response of LTA-stimulated macrophages through the PI3K/Akt pathway and SOCS3 protein. [ABSTRACT FROM AUTHOR]

Abstract: Aims: Glucocorticoids (GCs) are frequently used to treat various pulmonary diseases, which are typically accompanied by hypoxia. Whether hypoxia influences the effects of GCs on human airway cells remains unclear. The aim of the present study was to characterize changes in the expression levels of two isoforms of the glucocorticoid receptor (GR) and to evaluate the anti-inflammatory actions of GCs under hypoxic conditions in A549 cells. Main methods: A549 cells were exposed to normoxic or hypoxic conditions for 24, 48 and 72 h. Morphological alterations of cells were captured using a differential interference contrast microscope (DIC), and cell cycle distribution was estimated by flow cytometry. Real-time quantitative polymerase chain reaction and western blot were used to determine the mRNA and protein expression levels of GRα and GRβ. Radioimmunoassay (RIA) for interleukin (IL)-8 was used to assess the anti-inflammatory actions of GCs after cells were stimulated with lipopolysaccharide (LPS). Key findings: After cells were exposed to hypoxic conditions for 48 h, visible morphological alterations in the cells were observed. Cell cycle analysis showed that the number of cells in G1 phase increased significantly under hypoxia compared to the normoxic conditions. Hypoxia caused a time-dependent decrease in both mRNA and protein expression levels for GRα, but not GRβ. Furthermore, when exposed to hypoxia for 48 h, the inhibitory effects of dexamethasone on LPS-stimulated IL-8 release were attenuated. Significance: These results indicate that hypoxia impairs the anti-inflammatory actions of GCs in A549 cells, which could be attributed to down-regulation of GRα expression under hypoxic conditions. [Copyright &y& Elsevier]