The electrically assisted(EA)deformation process has received considerable attention in recent years,ac-companied by research on current-induced deformation mechanisms.However,there are still challenges in eliminating...The electrically assisted(EA)deformation process has received considerable attention in recent years,ac-companied by research on current-induced deformation mechanisms.However,there are still challenges in eliminating thermal effects,which have prevented a comprehensive understanding of the underlying current-induced mechanisms.Opting for a single crystal(SC)in research provides advantages in decou-pling the nonthermal effect of electric current at smaller scales and eliminating the complex interactions that exist in polycrystalline materials.Therefore,the innovation of this work lies in decoupling the non-thermal effect of electric current and conducting a comprehensive analysis of anisotropic deformation and mechanisms within a Ni-based SC with different crystallographic axes and various current directions dur-ing electrically assisted tensile simulation.A significant tension axis direction in the SC during EA tension was induced by the combination of a higher current direction factor(|cosθ|)and a dimensionless factor for the current density(|J^(α)/J_(0)^(α)|)along the[100]axis.The stress drop within the SC due to the nonthermal effect of electric current generally increased with increasing current direction.This was attributed to the increased dislocation density differences and decreased temperature.The increased stress anisotropy of the SC at a current direction of 45°was attributed to fewer activated(111)slip systems and the pinning effect of more dislocations within these systems.This study advances our understanding of the thermal and nonthermal effects of electric current and offers valuable insights for the informed application of EA deformations in industrial and aerospace settings with SC superalloys.展开更多
Human adenoviruses type 26(HAdV26)and type 35(HAdV35)have increasingly become the choice of adenovirus vectors for vaccine application.However,the population pre-existing immunity to these two adenoviruses in China,wh...Human adenoviruses type 26(HAdV26)and type 35(HAdV35)have increasingly become the choice of adenovirus vectors for vaccine application.However,the population pre-existing immunity to these two adenoviruses in China,which may reduce vaccine efficacy,remains largely unknown.Here,we established micro-neutralizing(MN)assays to investigate the seroprevalence of neutralizing antibodies(nAbs)against HAdV26 and HAdV35 in the general population of Guangdong and Shandong provinces,China.A total of 1184 serum samples were collected,47.0%and 15.8%of which showed HAdV26 and HAdV35 nAb activity,respectively.HAdV26-seropositive individuals tended to have more moderate nAbs titers(201-1000),while HAdV35-seropositive individuals appeared to have more low nAbs titers(72-200).The seropositive rates of HAdV26 and HAdV35 in individuals younger than 20 years old were very low.The seropositive rates of HAdV26 increased with age before 70 years old and decreased thereafter,while HAdV35 seropositive rates did not show similar characteristics.Notably,the seropositive rates and nAb levels of both HAdV26 and HAdV35 were higher in Guangdong Province than in Shandong Province,but did not exert significant differences between males and females.The seroprevalence between HAdV26 and HAdV35 showed little correlation,and no significant cross-neutralizing activity was detected.These results clarified the characteristics of the herd immunity against HAdV26 and HAdV35,and provided information for the rational development and application of HAdV26 and HAdV35 as vaccine vectors in China.展开更多
Gradient distributions of temperature and deformation(GDTD)are crucial for achieving dual-performance discs of titanium alloys which is required by the service environment of aeroengine.However,heating,cooling and def...Gradient distributions of temperature and deformation(GDTD)are crucial for achieving dual-performance discs of titanium alloys which is required by the service environment of aeroengine.However,heating,cooling and deforming sequence in the whole process of the titanium disc forming,which leads to difficulties for achieving GDTD due to a lot of parameters.To solve this problem,a whole-process model of the titanium disc forming for GDTD has been established.In the model,heating and cooling via heat radiation,conduction and convection,and deforming by local loading with mold chilling are all considered.Experiments on heating and cooling as well as deforming were carried out by using a furnace and the Gleeble-3500 machine.The experimental data are used to determine thermal parameters and constitutive relations of the IMI834 titanium alloy,and then to verify the reliability of the model.Then the model was used to simulate the evolution rules of temperature and deformation of the titanium disc.The results show that the heating surface,furnace temperature,billet profile and loading rate play the core role for the control of GDTD,and thus a set of parameters were determined.Therefore,this work provides a base for developing a new forming technology of the dual-performance titanium discs with the approach of local heating and local loading.展开更多
Despite demonstrating significant anti-tumor potential as an artemisinin derivative,artesunate faces delivery efficiency challenges due to low water solubility and insufficient targeting specificity.To improve the del...Despite demonstrating significant anti-tumor potential as an artemisinin derivative,artesunate faces delivery efficiency challenges due to low water solubility and insufficient targeting specificity.To improve the delivery efficiency,we engineered three artesunate(ART) derivatives,AC_(15)-L(linear),AC_(15)-B(branched),and AC_(15)-C(cyclic) with distinct aliphatic chain architectures.Unexpectedly,we observed that AC_(15)-C exhibited superior cytotoxicity against 4T1 breast cancer cells,and had the highest binding affinity for Lon protease 1(LONP1)(-72.6 kcal/mol).Subsequently,disulfide bond-containing lipid-PEG(DSPESS-PEG2K) modified chain architecture-engineered ART derivatives nanoassemblies(NAs) were developed to mitigate solubility-related limitations while enhancing targeting precision.Molecular docking and experimental validation demonstrated that ART derivatives inhibited LONP1 through hydrophobic interactions while preserved Fe^(2+)-mediated Fenton-like reaction activity.In vitro and in vivo evaluations demonstrated that AC_(15)-C NAs outperformed free ART and other NAs,suppressing 4T1 tumor growth via dual action:LONP1-directed mitochondrial proteostasis collapse and reactive oxygen species(ROS) amplification through Fe^(2+)-ART interactions.This study elucidated a novel anti-tumor mechanism of ART through the rational design of derivatives with spatially configured aliphatic chains,and developed reductionresponsive NAs to provide an advanced delivery strategy.展开更多
Oxaliplatin(OXA)has shown excellent potential in inducing immunogenic cell death and enhancing immunotherapy.However,the poor physicochemical properties of oxaliplatin make it difficult to achieve efficient synchronou...Oxaliplatin(OXA)has shown excellent potential in inducing immunogenic cell death and enhancing immunotherapy.However,the poor physicochemical properties of oxaliplatin make it difficult to achieve efficient synchronous delivery and synergistic immunotherapy with immune checkpoint inhibitors.To address this,we designed structurally optimized dual-wing butterfly prodrugs:oxaliplatin prodrug(POP)that enhances immunogenicity and reducible NLG919 homodimer(NSSN)that mitigates immunosuppression.Structural optimization of dual-wing butterfly prodrugs significantly enhanced lipid solubility compared to the parent drugs.It is worth noting that we assembled two dual-wing butterfly prodrugs,POP and NSSN,together into hybrid nanoassemblies(NAs),achieving advantages such as stable assembly,flexible dosing,and collaborative therapy.Dual-wing butterfly prodrug-driven hybrid NAs demonstrated enhanced antitumor efficacy and metastasis control in experimental models,with biocompatibility confirmed through biosafety evaluations.This work proposes a co-delivery strategy based on dual-wing butterfly prodrugs as a clinically translatable candidate.展开更多
Psoriasis is a long-lasting and recurrent autoimmune disease which is incurable so far.Dead Sea water(DSW)therapy is an effective approach to help control the symptoms of psoriasis due to the abundant mineral ions in ...Psoriasis is a long-lasting and recurrent autoimmune disease which is incurable so far.Dead Sea water(DSW)therapy is an effective approach to help control the symptoms of psoriasis due to the abundant mineral ions in DSW,which inspired the material formulation in this study.Rubidium–Sodium alginate/Polyacrylamide hydrogels(Rb-SA/PAAm gels)composed of sodium alginate and polyacrylamide interpenetrating network structure with different concentrations of rubidium and certain magnesium and zinc content were prepared for the treatment of psoriasis.The obtained results suggest the good mechanical properties of the Rb-SA/PAAm gels including toughness and swelling performance.In terms of in vitro tests,the Rb-SA/PAAm gels not only show nontoxicity to human keratinocyte cell line(Hacats)but also inhibits the activity against inflammatory NF-κβ signaling pathway.Meanwhile,they can release Rb+which enable the Rb-SA/PAAm gels have better antibacterial ability to Streptococcus and Escherichia coli.The results obtained from in vivo tests indicate that these hydrogels could alleviate the symptoms of psoriasis caused by Imiquimod(IMQ)in mice by reducing the inflammatory factor in STAT3 pathway and therefore reduce the immune stimulation of the spleen.In conclusion,the 100Rb-SA/PAAm gel has demonstrated great potential to be a topical wettable dressing for psoriasis treatment.展开更多
This article has been retracted:please see Elsevier Policy on Article Withdrawal(https://www.elsevier.com/about/our-business/policies/article-withdrawal).This article has been retracted at the request of all the Autho...This article has been retracted:please see Elsevier Policy on Article Withdrawal(https://www.elsevier.com/about/our-business/policies/article-withdrawal).This article has been retracted at the request of all the Authors,the Editor-in-Chief and the owner of the journal.The article has been retracted because of the authors recently re-conducted partly the experiments and found that the anti-bacteria behavior of Rb+was not reproducible.As shown in Fig.1(see enclosed file),at a centration as high as 200 mM,the addition of single Rb+does not show anti-bacteria effect.In Fig.2(see enclosed file),the authors prepared a mixed solution containing Rb+,Mg2+and Zn2+with concentrations close to those(12 h)in the article,and found that the mixed solution does not show anti-bacterial effect either.The two figures indicate that the anti-bacteria effect of Rb+is not conclusive,which seriously impairs the rigidity of the paper.Considering complex factors influencing the experiments with hydrogels,there might be other effects on the anti-bacteria behavior.However,since the anti-bacteria effect of Rb+is incorrect,the authors would like to retract the published article.展开更多
基金National Science Fund for Distinguished Young Scholars(No.52225505)the National Sci-ence and Technology Major Project(No.J2019-VII-0014-0154)+1 种基金the National Natural Science Foundation of China(No.52005412)the Tianjin Natural Science Foundation of China-Multi-input key projects(No.22JCZDJC00650)for financial supports given to this research.
文摘The electrically assisted(EA)deformation process has received considerable attention in recent years,ac-companied by research on current-induced deformation mechanisms.However,there are still challenges in eliminating thermal effects,which have prevented a comprehensive understanding of the underlying current-induced mechanisms.Opting for a single crystal(SC)in research provides advantages in decou-pling the nonthermal effect of electric current at smaller scales and eliminating the complex interactions that exist in polycrystalline materials.Therefore,the innovation of this work lies in decoupling the non-thermal effect of electric current and conducting a comprehensive analysis of anisotropic deformation and mechanisms within a Ni-based SC with different crystallographic axes and various current directions dur-ing electrically assisted tensile simulation.A significant tension axis direction in the SC during EA tension was induced by the combination of a higher current direction factor(|cosθ|)and a dimensionless factor for the current density(|J^(α)/J_(0)^(α)|)along the[100]axis.The stress drop within the SC due to the nonthermal effect of electric current generally increased with increasing current direction.This was attributed to the increased dislocation density differences and decreased temperature.The increased stress anisotropy of the SC at a current direction of 45°was attributed to fewer activated(111)slip systems and the pinning effect of more dislocations within these systems.This study advances our understanding of the thermal and nonthermal effects of electric current and offers valuable insights for the informed application of EA deformations in industrial and aerospace settings with SC superalloys.
基金supported by the Strategic Priority Research Program of the Chinese Academy of Sciences (XDB29050701)the Emergency Key Program of Guangzhou (EKPG21-20)+2 种基金the China Evergrande Group funding for SARS-Co V-2 (2020GIRHHMS22)the Zhongnanshan Medical Foundation of Guangdong Province (ZNSA-2022009)the China Postdoctoral Science Foundation (2020M682942)
文摘Human adenoviruses type 26(HAdV26)and type 35(HAdV35)have increasingly become the choice of adenovirus vectors for vaccine application.However,the population pre-existing immunity to these two adenoviruses in China,which may reduce vaccine efficacy,remains largely unknown.Here,we established micro-neutralizing(MN)assays to investigate the seroprevalence of neutralizing antibodies(nAbs)against HAdV26 and HAdV35 in the general population of Guangdong and Shandong provinces,China.A total of 1184 serum samples were collected,47.0%and 15.8%of which showed HAdV26 and HAdV35 nAb activity,respectively.HAdV26-seropositive individuals tended to have more moderate nAbs titers(201-1000),while HAdV35-seropositive individuals appeared to have more low nAbs titers(72-200).The seropositive rates of HAdV26 and HAdV35 in individuals younger than 20 years old were very low.The seropositive rates of HAdV26 increased with age before 70 years old and decreased thereafter,while HAdV35 seropositive rates did not show similar characteristics.Notably,the seropositive rates and nAb levels of both HAdV26 and HAdV35 were higher in Guangdong Province than in Shandong Province,but did not exert significant differences between males and females.The seroprevalence between HAdV26 and HAdV35 showed little correlation,and no significant cross-neutralizing activity was detected.These results clarified the characteristics of the herd immunity against HAdV26 and HAdV35,and provided information for the rational development and application of HAdV26 and HAdV35 as vaccine vectors in China.
基金the National Natural Science Foundation of China(No.51675433)the Natural Science Foundation for Distinguished Young Scholars of Shaanxi Province(No.2019JC-09)for financial supports given to this research。
文摘Gradient distributions of temperature and deformation(GDTD)are crucial for achieving dual-performance discs of titanium alloys which is required by the service environment of aeroengine.However,heating,cooling and deforming sequence in the whole process of the titanium disc forming,which leads to difficulties for achieving GDTD due to a lot of parameters.To solve this problem,a whole-process model of the titanium disc forming for GDTD has been established.In the model,heating and cooling via heat radiation,conduction and convection,and deforming by local loading with mold chilling are all considered.Experiments on heating and cooling as well as deforming were carried out by using a furnace and the Gleeble-3500 machine.The experimental data are used to determine thermal parameters and constitutive relations of the IMI834 titanium alloy,and then to verify the reliability of the model.Then the model was used to simulate the evolution rules of temperature and deformation of the titanium disc.The results show that the heating surface,furnace temperature,billet profile and loading rate play the core role for the control of GDTD,and thus a set of parameters were determined.Therefore,this work provides a base for developing a new forming technology of the dual-performance titanium discs with the approach of local heating and local loading.
基金financially supported by the Liaoning Revitalization Talents Program (No.XLYC2403107)the Excellent Youth Science Foundation of Liaoning Province (No.2024JH3/10200046)the Basic Scientific Research Project of Liaoning Provincial Department of Education (No.LJ212410163015)。
文摘Despite demonstrating significant anti-tumor potential as an artemisinin derivative,artesunate faces delivery efficiency challenges due to low water solubility and insufficient targeting specificity.To improve the delivery efficiency,we engineered three artesunate(ART) derivatives,AC_(15)-L(linear),AC_(15)-B(branched),and AC_(15)-C(cyclic) with distinct aliphatic chain architectures.Unexpectedly,we observed that AC_(15)-C exhibited superior cytotoxicity against 4T1 breast cancer cells,and had the highest binding affinity for Lon protease 1(LONP1)(-72.6 kcal/mol).Subsequently,disulfide bond-containing lipid-PEG(DSPESS-PEG2K) modified chain architecture-engineered ART derivatives nanoassemblies(NAs) were developed to mitigate solubility-related limitations while enhancing targeting precision.Molecular docking and experimental validation demonstrated that ART derivatives inhibited LONP1 through hydrophobic interactions while preserved Fe^(2+)-mediated Fenton-like reaction activity.In vitro and in vivo evaluations demonstrated that AC_(15)-C NAs outperformed free ART and other NAs,suppressing 4T1 tumor growth via dual action:LONP1-directed mitochondrial proteostasis collapse and reactive oxygen species(ROS) amplification through Fe^(2+)-ART interactions.This study elucidated a novel anti-tumor mechanism of ART through the rational design of derivatives with spatially configured aliphatic chains,and developed reductionresponsive NAs to provide an advanced delivery strategy.
基金financially supported by the National Natural Science Foundation of China(No.82204317)the Liaoning Revitalization Talents Program(No.XLYC2403107)+1 种基金the Excellent Youth Science Foundation of Liaoning Province(No.2024JH3/10200046)the Basic Scientific Research Project of Liaoning Provincial Department of Education(No.LJ212410163015).
文摘Oxaliplatin(OXA)has shown excellent potential in inducing immunogenic cell death and enhancing immunotherapy.However,the poor physicochemical properties of oxaliplatin make it difficult to achieve efficient synchronous delivery and synergistic immunotherapy with immune checkpoint inhibitors.To address this,we designed structurally optimized dual-wing butterfly prodrugs:oxaliplatin prodrug(POP)that enhances immunogenicity and reducible NLG919 homodimer(NSSN)that mitigates immunosuppression.Structural optimization of dual-wing butterfly prodrugs significantly enhanced lipid solubility compared to the parent drugs.It is worth noting that we assembled two dual-wing butterfly prodrugs,POP and NSSN,together into hybrid nanoassemblies(NAs),achieving advantages such as stable assembly,flexible dosing,and collaborative therapy.Dual-wing butterfly prodrug-driven hybrid NAs demonstrated enhanced antitumor efficacy and metastasis control in experimental models,with biocompatibility confirmed through biosafety evaluations.This work proposes a co-delivery strategy based on dual-wing butterfly prodrugs as a clinically translatable candidate.
基金The authors would like to thank the financial support by National Natural Science Funds for Distinguished Young Scholar of China(51625404)China Scholarship Council(202006370330)State Key Laboratory of Powder Metallurgy,Central South University,Changsha,China.
文摘Psoriasis is a long-lasting and recurrent autoimmune disease which is incurable so far.Dead Sea water(DSW)therapy is an effective approach to help control the symptoms of psoriasis due to the abundant mineral ions in DSW,which inspired the material formulation in this study.Rubidium–Sodium alginate/Polyacrylamide hydrogels(Rb-SA/PAAm gels)composed of sodium alginate and polyacrylamide interpenetrating network structure with different concentrations of rubidium and certain magnesium and zinc content were prepared for the treatment of psoriasis.The obtained results suggest the good mechanical properties of the Rb-SA/PAAm gels including toughness and swelling performance.In terms of in vitro tests,the Rb-SA/PAAm gels not only show nontoxicity to human keratinocyte cell line(Hacats)but also inhibits the activity against inflammatory NF-κβ signaling pathway.Meanwhile,they can release Rb+which enable the Rb-SA/PAAm gels have better antibacterial ability to Streptococcus and Escherichia coli.The results obtained from in vivo tests indicate that these hydrogels could alleviate the symptoms of psoriasis caused by Imiquimod(IMQ)in mice by reducing the inflammatory factor in STAT3 pathway and therefore reduce the immune stimulation of the spleen.In conclusion,the 100Rb-SA/PAAm gel has demonstrated great potential to be a topical wettable dressing for psoriasis treatment.
文摘This article has been retracted:please see Elsevier Policy on Article Withdrawal(https://www.elsevier.com/about/our-business/policies/article-withdrawal).This article has been retracted at the request of all the Authors,the Editor-in-Chief and the owner of the journal.The article has been retracted because of the authors recently re-conducted partly the experiments and found that the anti-bacteria behavior of Rb+was not reproducible.As shown in Fig.1(see enclosed file),at a centration as high as 200 mM,the addition of single Rb+does not show anti-bacteria effect.In Fig.2(see enclosed file),the authors prepared a mixed solution containing Rb+,Mg2+and Zn2+with concentrations close to those(12 h)in the article,and found that the mixed solution does not show anti-bacterial effect either.The two figures indicate that the anti-bacteria effect of Rb+is not conclusive,which seriously impairs the rigidity of the paper.Considering complex factors influencing the experiments with hydrogels,there might be other effects on the anti-bacteria behavior.However,since the anti-bacteria effect of Rb+is incorrect,the authors would like to retract the published article.
