BACKGROUND C23,an oligo-peptide derived from cold-inducible RNA-binding protein(CIRP),has been reported to inhibit tissue inflammation,apoptosis and fibrosis by binding to the CIRP receptor;however,there are few repor...BACKGROUND C23,an oligo-peptide derived from cold-inducible RNA-binding protein(CIRP),has been reported to inhibit tissue inflammation,apoptosis and fibrosis by binding to the CIRP receptor;however,there are few reports on its role in liver fibrosis and the underlying mechanism is unknown.AIM To explore whether C23 plays a significant role in carbon tetrachloride(CCl4)-induced liver fibrosis.METHODS CCl4 was injected for 6 weeks to induce liver fibrosis and C23 was used beginning in the second week.Masson and Sirius red staining were used to examine changes in fiber levels.Inflammatory factors in the liver were detected and changes inα-smooth muscle actin(α-SMA)and collagen I expression were detected via immu-nohistochemical staining to evaluate the activation of hematopoietic stellate cells(HSCs).Western blotting was used to detect the activation status of the trans-forming growth factor-beta(TGF-β)/Smad3 axis after C23 treatment.RESULTS CCl4 successfully induced liver fibrosis in mice,while tumor necrosis factor-alpha(TNF-α),IL(interleukin)-1β,and IL-6 levels increased significantly and the IL-10 level decreased significantly.Interestingly,C23 inhibited this process.On the other hand,C23 significantly inhibited the activation of HSCs induced by CCl4,which inhibited the expression ofα-SMA and the synthesis of collagen I.In terms of mechanism,C23 can block Smad3 phosphorylation significantly and inhibits INTRODUCTION At present there is no specific and effective drug for treating liver fibrosis caused by acute or chronic injury.Although preclinical research has made breakthroughs,their suitability as clinical treatments is still unknown.The activation of hepatic stellate cells(HSCs)caused by chronic inflammation is a key process in the development of liver fibrosis and activated HSCs expressα-smooth muscle actin(α-SMA)and transdifferentiate into myofibroblasts with proliferation,migration and secretion abilities,synthesizing the extracellular matrix to deposit in the hepatocyte space and subse-quently forming liver fibrosis[1].Although therapeutic strategies have improved due to past few efforts there is no ideal treatment for hepatic fibrosis[2].Extracellular cold inducible RNA binding protein(CIRP)has been shown to play a role in various acute and chronic inflammatory diseases by promoting tissue inflammation and apoptosis and inducing fibrosis through its receptor Toll-like receptor 4(TLR4)[3].C23 is a recognized competitive inhibitor of CIRP that can competitively bind to CIRP receptors and reduce tissue damage in inflammatory diseases[4].C23 has been shown to significantly reduce serum tumor necrosis factor-alpha(TNF-α),IL(interleukin)-6 and IL-1βlevels.In addition,it can reduce tissue TLR4,TNF-α,IL-6 and IL-1βlevels and inhibit the colocalization of CIRP and TLR4,which plays a significant role in systemic inflammation[5].Re-search has shown that CIRP induces the inflammatory phenotype of lung fibroblasts in a TLR4-dependent manner[6].On the other hand,CIRP is associated with markers of fibrosis andα-SMA is significantly positively correlated with CIRP.Cirp-/-mice exhibit attenuated expression ofα-SMA and collagen(COL1A1 and COL3A1),decreased hydroxyproline content,decreased histological fibrosis scores,and improved pulmonary hypertension[7].C23 inhibited the release of TNF-α,the degradation of IκB and the nuclear translocation of NF-κB in CIRP-stimulated macrophages in a dose-dependent manner and C23 treatment significantly increased the serum levels of lactic dehydrogenase,alanine ami-notransferase,IL-6,TNF-αand IL-1βin septic CLP mice[8].Based on previous research we hypothesized that C23 might alleviate liver fibrosis by inhibiting acute and chronic inflammation.As a selective hepatotoxic chemical carbon tetrachloride(CCl4).can induce inflammation and activate HSCs,promoting liver fibrosis.This study reveals the role and mechanism of C23 in CCl4-induced liver fibrosis in mice.at room temperature for 30 minutes.The gray value of each group was calculated after chemiluminescence.展开更多
M23C6 chromium-rich carbides are common grain-boundary precipitations in Cr-containing steel.The presence of grain-boundary carbides often leads to intergranular brittleness and decreases mechanical properties.This st...M23C6 chromium-rich carbides are common grain-boundary precipitations in Cr-containing steel.The presence of grain-boundary carbides often leads to intergranular brittleness and decreases mechanical properties.This study proposes a deformation and aging technique to obtain a high-volume-fraction dispersion distribution of the hard nano-M23C6 phase by changing the nucleation sites from grain boundaries to deformation coherent twin boundaries produced during cold deformation.The M23C6 precipitation-strengthened austenitic stainless steel has a strength of up to 1.4 GPa but maintains favorable plasticity(>11%).This study provides a novel approach for the control of intergranular brittleness in metallic materials.展开更多
Transient liquid phase(TLP)bonding is a promising process for the joining and repairing of nickel-base superalloys.One of the most important parameters in TLP bonding is the bonding time required for suf-ficient isoth...Transient liquid phase(TLP)bonding is a promising process for the joining and repairing of nickel-base superalloys.One of the most important parameters in TLP bonding is the bonding time required for suf-ficient isothermal solidification which prevents the formation of undesirable precipitated phases.In the present work,the effect of bonding time on the microstructure,type,and evolution of precipitates in the non-isothermal solidified zone(NSZ)and their effect on micro-mechanical properties were systemat-ically investigated using multi-scale tests in TLP bonded Mar-M247 superalloy joints with Ni-15.2Cr-3.74B interlayer at 1230℃.For a bonding time of 5 min,dual-phase M_(23)(C,B)_(6)-γ/γ’(where M is a mix-ture of Hf,Ta,Cr,and Ni)with eutectic configuration was formed in NSZ.With the increase in bonding time,the evolution of NSZ microstructure can be summed up as eutectic M_(23)(C,B)_(6)-γ/γ’,semi-striping dual-phase M_(23)(C,B)_(6)-γ/γ’,discontinuously striping M_(23)(C,B)_(6)-γ/γ’,followed by the disintegration of NSZ.As the NSZ counterpart,the isothermal solidified zone(ISZ)is mainly composed ofγ/γ’.Ac-companied by the dissolution of M_(23)(C,B)_(6) in the centerline,the proportion of the ISZ increases greatly until the joints are completely occupied by ISZ.Finally,a bamboo-like structure with domain size of-100μm was formed in the joint centerline,along withγ’reorganized themselves all into cubic shapes and distributed homogeneously.Mechanical property tests demonstrated that in comparison to samples with longer bonding time,the NSZ of the shortest bonding time(5 min)has the highest strength and a subsequent decrease in strength was observed with prolonging the bonding time and post-bond heat treatment.Furthermore,possible solidification/transformation path,segregation behavior,and formation mechanism of NSZ/ISZ evolution were discussed.展开更多
Creep rupture of the reduced activation ferritic/martensitic(RAFM)steel and 316L steel dissimilar joint by friction stir welding was investigated.The creep rupture time of the dissimilar joint was 1941 h at 600℃/100 ...Creep rupture of the reduced activation ferritic/martensitic(RAFM)steel and 316L steel dissimilar joint by friction stir welding was investigated.The creep rupture time of the dissimilar joint was 1941 h at 600℃/100 MPa and 120 h at 650℃/100 MPa.The creep fracture occurred in heat affect zone(HAZ)of RAFM steel side where coarse Laves phase was detected.The formation and coarsening of the Laves phase particles in HAZ of RAFM steel side were the main reasons that caused the creep fracture of the dissimilar joint.The Laves phase particles nucleated adjacent to the large M_(23)C_(6) particles at the grain boundaries where W element segregated and grew fast during creep exposure.The large Laves phase would deteriorate the pinning effect of M_(23)C_(6) carbides and weaken the solid solution strengthening effect.Besides,the size of the Laves phase in HAZ of RAFM steel side was bigger than that in stir zone of RAFM steel side.These reasons explain the creep fracture in HAZ of RAFM steel side of dissimilar joint.展开更多
基金Supported by The Panzhihua Science and Technology Planning Project of China,No.2023ZD-S-57.
文摘BACKGROUND C23,an oligo-peptide derived from cold-inducible RNA-binding protein(CIRP),has been reported to inhibit tissue inflammation,apoptosis and fibrosis by binding to the CIRP receptor;however,there are few reports on its role in liver fibrosis and the underlying mechanism is unknown.AIM To explore whether C23 plays a significant role in carbon tetrachloride(CCl4)-induced liver fibrosis.METHODS CCl4 was injected for 6 weeks to induce liver fibrosis and C23 was used beginning in the second week.Masson and Sirius red staining were used to examine changes in fiber levels.Inflammatory factors in the liver were detected and changes inα-smooth muscle actin(α-SMA)and collagen I expression were detected via immu-nohistochemical staining to evaluate the activation of hematopoietic stellate cells(HSCs).Western blotting was used to detect the activation status of the trans-forming growth factor-beta(TGF-β)/Smad3 axis after C23 treatment.RESULTS CCl4 successfully induced liver fibrosis in mice,while tumor necrosis factor-alpha(TNF-α),IL(interleukin)-1β,and IL-6 levels increased significantly and the IL-10 level decreased significantly.Interestingly,C23 inhibited this process.On the other hand,C23 significantly inhibited the activation of HSCs induced by CCl4,which inhibited the expression ofα-SMA and the synthesis of collagen I.In terms of mechanism,C23 can block Smad3 phosphorylation significantly and inhibits INTRODUCTION At present there is no specific and effective drug for treating liver fibrosis caused by acute or chronic injury.Although preclinical research has made breakthroughs,their suitability as clinical treatments is still unknown.The activation of hepatic stellate cells(HSCs)caused by chronic inflammation is a key process in the development of liver fibrosis and activated HSCs expressα-smooth muscle actin(α-SMA)and transdifferentiate into myofibroblasts with proliferation,migration and secretion abilities,synthesizing the extracellular matrix to deposit in the hepatocyte space and subse-quently forming liver fibrosis[1].Although therapeutic strategies have improved due to past few efforts there is no ideal treatment for hepatic fibrosis[2].Extracellular cold inducible RNA binding protein(CIRP)has been shown to play a role in various acute and chronic inflammatory diseases by promoting tissue inflammation and apoptosis and inducing fibrosis through its receptor Toll-like receptor 4(TLR4)[3].C23 is a recognized competitive inhibitor of CIRP that can competitively bind to CIRP receptors and reduce tissue damage in inflammatory diseases[4].C23 has been shown to significantly reduce serum tumor necrosis factor-alpha(TNF-α),IL(interleukin)-6 and IL-1βlevels.In addition,it can reduce tissue TLR4,TNF-α,IL-6 and IL-1βlevels and inhibit the colocalization of CIRP and TLR4,which plays a significant role in systemic inflammation[5].Re-search has shown that CIRP induces the inflammatory phenotype of lung fibroblasts in a TLR4-dependent manner[6].On the other hand,CIRP is associated with markers of fibrosis andα-SMA is significantly positively correlated with CIRP.Cirp-/-mice exhibit attenuated expression ofα-SMA and collagen(COL1A1 and COL3A1),decreased hydroxyproline content,decreased histological fibrosis scores,and improved pulmonary hypertension[7].C23 inhibited the release of TNF-α,the degradation of IκB and the nuclear translocation of NF-κB in CIRP-stimulated macrophages in a dose-dependent manner and C23 treatment significantly increased the serum levels of lactic dehydrogenase,alanine ami-notransferase,IL-6,TNF-αand IL-1βin septic CLP mice[8].Based on previous research we hypothesized that C23 might alleviate liver fibrosis by inhibiting acute and chronic inflammation.As a selective hepatotoxic chemical carbon tetrachloride(CCl4).can induce inflammation and activate HSCs,promoting liver fibrosis.This study reveals the role and mechanism of C23 in CCl4-induced liver fibrosis in mice.at room temperature for 30 minutes.The gray value of each group was calculated after chemiluminescence.
基金supported by the National Natural Science Foundation of China(No.52250130).
文摘M23C6 chromium-rich carbides are common grain-boundary precipitations in Cr-containing steel.The presence of grain-boundary carbides often leads to intergranular brittleness and decreases mechanical properties.This study proposes a deformation and aging technique to obtain a high-volume-fraction dispersion distribution of the hard nano-M23C6 phase by changing the nucleation sites from grain boundaries to deformation coherent twin boundaries produced during cold deformation.The M23C6 precipitation-strengthened austenitic stainless steel has a strength of up to 1.4 GPa but maintains favorable plasticity(>11%).This study provides a novel approach for the control of intergranular brittleness in metallic materials.
基金supported by the National Natural Science Foundation of China(No.52125101)the Basic and Applied Basic Research Major Program of Guangdong Province,China(Grant No.2021B0301030003)the Jihua Laboratory(Project No.X210141TL210).
文摘Transient liquid phase(TLP)bonding is a promising process for the joining and repairing of nickel-base superalloys.One of the most important parameters in TLP bonding is the bonding time required for suf-ficient isothermal solidification which prevents the formation of undesirable precipitated phases.In the present work,the effect of bonding time on the microstructure,type,and evolution of precipitates in the non-isothermal solidified zone(NSZ)and their effect on micro-mechanical properties were systemat-ically investigated using multi-scale tests in TLP bonded Mar-M247 superalloy joints with Ni-15.2Cr-3.74B interlayer at 1230℃.For a bonding time of 5 min,dual-phase M_(23)(C,B)_(6)-γ/γ’(where M is a mix-ture of Hf,Ta,Cr,and Ni)with eutectic configuration was formed in NSZ.With the increase in bonding time,the evolution of NSZ microstructure can be summed up as eutectic M_(23)(C,B)_(6)-γ/γ’,semi-striping dual-phase M_(23)(C,B)_(6)-γ/γ’,discontinuously striping M_(23)(C,B)_(6)-γ/γ’,followed by the disintegration of NSZ.As the NSZ counterpart,the isothermal solidified zone(ISZ)is mainly composed ofγ/γ’.Ac-companied by the dissolution of M_(23)(C,B)_(6) in the centerline,the proportion of the ISZ increases greatly until the joints are completely occupied by ISZ.Finally,a bamboo-like structure with domain size of-100μm was formed in the joint centerline,along withγ’reorganized themselves all into cubic shapes and distributed homogeneously.Mechanical property tests demonstrated that in comparison to samples with longer bonding time,the NSZ of the shortest bonding time(5 min)has the highest strength and a subsequent decrease in strength was observed with prolonging the bonding time and post-bond heat treatment.Furthermore,possible solidification/transformation path,segregation behavior,and formation mechanism of NSZ/ISZ evolution were discussed.
基金supported by the National Natural Science Foundation of China(52034004).
文摘Creep rupture of the reduced activation ferritic/martensitic(RAFM)steel and 316L steel dissimilar joint by friction stir welding was investigated.The creep rupture time of the dissimilar joint was 1941 h at 600℃/100 MPa and 120 h at 650℃/100 MPa.The creep fracture occurred in heat affect zone(HAZ)of RAFM steel side where coarse Laves phase was detected.The formation and coarsening of the Laves phase particles in HAZ of RAFM steel side were the main reasons that caused the creep fracture of the dissimilar joint.The Laves phase particles nucleated adjacent to the large M_(23)C_(6) particles at the grain boundaries where W element segregated and grew fast during creep exposure.The large Laves phase would deteriorate the pinning effect of M_(23)C_(6) carbides and weaken the solid solution strengthening effect.Besides,the size of the Laves phase in HAZ of RAFM steel side was bigger than that in stir zone of RAFM steel side.These reasons explain the creep fracture in HAZ of RAFM steel side of dissimilar joint.
