The thermal simulation compression tests of near-β titanium alloy Ti-5Al-5Mo-5V-1Cr-1Fe were per-formed within the range of deformation temperatures of 710-860 ℃ and strain rates of 0.001-1 s^(-1).Based on electron ...The thermal simulation compression tests of near-β titanium alloy Ti-5Al-5Mo-5V-1Cr-1Fe were per-formed within the range of deformation temperatures of 710-860 ℃ and strain rates of 0.001-1 s^(-1).Based on electron backscatter diffraction(EBSD)characterization and analysis technology,the inter-action between dynamic phase transformation(DPT)of β-to-α and dynamic recrystallization(DRX)under thermal-mechanical coupling is deeply and systematically explored.We clarify the effects of temperatures and strain rates on the orientation relationship during dynamic precipitation of α-phase within β grain interiors possessing special orientation.The results show that the intragranular α-phase precipitated on the subgrain boundaries near {001}β with a high degree of dynamic recovery(DRV)deviates more from Burgers Orientation Relationship(BOR)than the α-phase that precipitates near{111}βas temperature increases.The proportion of α-phase precipitated by strain-induced on β recrys-tallized equiaxed grains for the deviating angle from BOR(θBoR)in the range of 20°-30° increases to 40%with the increase of strain rates below 800 ℃.In addition,the α-phase is dynamically precipitated on the grain boundaries with {110}β orientation,which undergoes continuous dynamic recrystallization(CDRX),exhibiting epitaxial recrystallization,namely {110}β//{0001 }α.Furthermore,the morphology of grain boundaries α phase(αGBs)precipitated by strain-induced phase transformation(SIPT)on specific types of β grain boundaries(βGBs),as well as the crystallographic orientation relationship and variant selection effect between adjacent α-variant within β grains are elucidated.The orientation relationships between α variants in {111}β grain are related with each other by 50°-60°/<-12-10>and 60°-70°/<-48-43>rotation.The"necklace"αGBs of recrystallization exhibit mainly the rotation of 50°-70° around the<2-310>zone axis,while the adjacent α-variant in the grain interiors is mainly 60° or 90°/<12-30>.In summary,the study has contributed to a deeper understanding of the deformation behavior and DPT laws of β-to-αp in near-β titanium alloy,which lays a foundation for the optimization of the hot deformation process and mechanical properties.展开更多
Rheumatoid arthritis(RA)is a prevalent autoimmune disease characterized by chronic inflammation and excessive proliferation of the synovium.Currently,treatment options focus on either reducing inflammation or inhibiti...Rheumatoid arthritis(RA)is a prevalent autoimmune disease characterized by chronic inflammation and excessive proliferation of the synovium.Currently,treatment options focus on either reducing inflammation or inhibiting synovial hyperplasia.However,these modalities are unsatisfactory in achieving the desired therapeutic outcomes.Halofuginone hydrobromide(HF),an herbal active ingredient,has demonstrated pharmacological effects of both anti-inflammation and inhibition of synovial hyperplasia proliferation.However,HF's medical efficacy is limited due to its poor water solubility,short half-life(t_(1/2)),and non-target toxicity.In the current study,by using the advantages of nanotechnology,we presented a novel dual-targeted nanocomplex,termed HA-M@P@HF NPs,which consisted of a hyaluronic acid(HA)-modified hybrid membrane(M)-camouflaged poly lactic-co-glycolic acid(PLGA)nanosystem for HF delivery.These nanocomplexes not only overcame the limitations of HF but also achieved simultaneous targeting of inflammatory macrophages and human fibroblast-like synoviocytes-RA(HFLS-RA).In vivo experiments demonstrated that these nanocomplexes effectively suppressed immune-mediated inflammation and synovial hyperplasia,safeguarding against bone destruction in rats with adjuvant-induced arthritis(AIA).Remarkable anti-arthritic effects of these nanocomplexes were accomplished through promoting repolarization of M1-to-M2 macrophages and apoptosis of HFLS-RA,thereby offering a promising therapeutic strategy for RA.展开更多
Staphylococcus aureus is a common cause of diverse infections,ranging from superficial to invasive,affecting both humans and animals.The widespread use of antibiotics in clinical treatments has led to the emergence of...Staphylococcus aureus is a common cause of diverse infections,ranging from superficial to invasive,affecting both humans and animals.The widespread use of antibiotics in clinical treatments has led to the emergence of antibiotic-resistant strains and small colony variants.This surge presents a significant challenge in eliminating infections and undermines the efficacy of available treatments.The bacterial Save Our Souls(Sos)response,triggered by genotoxic stressors,encompasses host immune defenses and antibiotics,playing a crucial role in bacterial survival,invasiveness,virulence,and drug resistance.Accumulating evidence underscores the pivotal role of the Sos response system in the pathogenicity of S.aureus.Inhibiting this system offers a promising approach for effective bactericidal treatments and curbing the evolution of antimicrobial re-sistance.Here,we provide a comprehensive review of the activation,impact,and key proteins associated with the Sos response in S.aureus.Additionally,perspectives on therapeutic strategies targeting the Sos response for S.aureus,both individually and in combination with traditional antibiotics are proposed.展开更多
文摘The thermal simulation compression tests of near-β titanium alloy Ti-5Al-5Mo-5V-1Cr-1Fe were per-formed within the range of deformation temperatures of 710-860 ℃ and strain rates of 0.001-1 s^(-1).Based on electron backscatter diffraction(EBSD)characterization and analysis technology,the inter-action between dynamic phase transformation(DPT)of β-to-α and dynamic recrystallization(DRX)under thermal-mechanical coupling is deeply and systematically explored.We clarify the effects of temperatures and strain rates on the orientation relationship during dynamic precipitation of α-phase within β grain interiors possessing special orientation.The results show that the intragranular α-phase precipitated on the subgrain boundaries near {001}β with a high degree of dynamic recovery(DRV)deviates more from Burgers Orientation Relationship(BOR)than the α-phase that precipitates near{111}βas temperature increases.The proportion of α-phase precipitated by strain-induced on β recrys-tallized equiaxed grains for the deviating angle from BOR(θBoR)in the range of 20°-30° increases to 40%with the increase of strain rates below 800 ℃.In addition,the α-phase is dynamically precipitated on the grain boundaries with {110}β orientation,which undergoes continuous dynamic recrystallization(CDRX),exhibiting epitaxial recrystallization,namely {110}β//{0001 }α.Furthermore,the morphology of grain boundaries α phase(αGBs)precipitated by strain-induced phase transformation(SIPT)on specific types of β grain boundaries(βGBs),as well as the crystallographic orientation relationship and variant selection effect between adjacent α-variant within β grains are elucidated.The orientation relationships between α variants in {111}β grain are related with each other by 50°-60°/<-12-10>and 60°-70°/<-48-43>rotation.The"necklace"αGBs of recrystallization exhibit mainly the rotation of 50°-70° around the<2-310>zone axis,while the adjacent α-variant in the grain interiors is mainly 60° or 90°/<12-30>.In summary,the study has contributed to a deeper understanding of the deformation behavior and DPT laws of β-to-αp in near-β titanium alloy,which lays a foundation for the optimization of the hot deformation process and mechanical properties.
基金funded by grants from the National Natural Science Foundation of China(Grant No.:82274506)the China Postdoctoral Science Foundation(Grant No.:2022M721128)+6 种基金the Science and Technology Innovation Program of Hunan,China(Grant No.:2021RC4035)the Natural Science Foundation of Hunan,China(Grant No.:2023JJ40477)the Open-competing Disciple Construction Project of Hunan University of Chinese Medicine(HNUCM),China(Grant No.:22JBZ003)was financially supported by the Furong Distinguished Scholar Program of Hunan,China(Program No.:XJT[2020]58)the 121 Training Project for Innovative Talents of Hunan,China(Project No.:XRSH[2019]192)the Chinese Academy of Engineering Academician Liang Liu's Workstation Project,China(Project No.:KH[2023]3-23YS001)the World First-class Discipline Incubation Project of HNUCM,China(Project No.:XJF[2022]57)。
文摘Rheumatoid arthritis(RA)is a prevalent autoimmune disease characterized by chronic inflammation and excessive proliferation of the synovium.Currently,treatment options focus on either reducing inflammation or inhibiting synovial hyperplasia.However,these modalities are unsatisfactory in achieving the desired therapeutic outcomes.Halofuginone hydrobromide(HF),an herbal active ingredient,has demonstrated pharmacological effects of both anti-inflammation and inhibition of synovial hyperplasia proliferation.However,HF's medical efficacy is limited due to its poor water solubility,short half-life(t_(1/2)),and non-target toxicity.In the current study,by using the advantages of nanotechnology,we presented a novel dual-targeted nanocomplex,termed HA-M@P@HF NPs,which consisted of a hyaluronic acid(HA)-modified hybrid membrane(M)-camouflaged poly lactic-co-glycolic acid(PLGA)nanosystem for HF delivery.These nanocomplexes not only overcame the limitations of HF but also achieved simultaneous targeting of inflammatory macrophages and human fibroblast-like synoviocytes-RA(HFLS-RA).In vivo experiments demonstrated that these nanocomplexes effectively suppressed immune-mediated inflammation and synovial hyperplasia,safeguarding against bone destruction in rats with adjuvant-induced arthritis(AIA).Remarkable anti-arthritic effects of these nanocomplexes were accomplished through promoting repolarization of M1-to-M2 macrophages and apoptosis of HFLS-RA,thereby offering a promising therapeutic strategy for RA.
基金This work was supported by the National Natural Science Foundation of China(32270043 and 32100017)the Natural Science Foundation of Zhejiang Province(LQ22C050002)+2 种基金the State Key Laboratory Foundation for Diagnosis and Treatment of Infectious Diseases to KC(zz202309)the Hangzhou Youth Innovation Team Project(TD2023020)the Scientific Research Foundation for Scholars of HZNU(4125C50221204040).
文摘Staphylococcus aureus is a common cause of diverse infections,ranging from superficial to invasive,affecting both humans and animals.The widespread use of antibiotics in clinical treatments has led to the emergence of antibiotic-resistant strains and small colony variants.This surge presents a significant challenge in eliminating infections and undermines the efficacy of available treatments.The bacterial Save Our Souls(Sos)response,triggered by genotoxic stressors,encompasses host immune defenses and antibiotics,playing a crucial role in bacterial survival,invasiveness,virulence,and drug resistance.Accumulating evidence underscores the pivotal role of the Sos response system in the pathogenicity of S.aureus.Inhibiting this system offers a promising approach for effective bactericidal treatments and curbing the evolution of antimicrobial re-sistance.Here,we provide a comprehensive review of the activation,impact,and key proteins associated with the Sos response in S.aureus.Additionally,perspectives on therapeutic strategies targeting the Sos response for S.aureus,both individually and in combination with traditional antibiotics are proposed.
