Enterovirus D68(EV-D68)and enterovirus A71(EV-A71)are two major types of enteroviruses that pose emerging challenges to public health and have the potential to cause outbreaks,yet their pathogenic mechanisms remain la...Enterovirus D68(EV-D68)and enterovirus A71(EV-A71)are two major types of enteroviruses that pose emerging challenges to public health and have the potential to cause outbreaks,yet their pathogenic mechanisms remain largely unexplored.Arrestin domain containing 3(ARRDC3)is a vital regulator of glucose metabolism,cancer development,and inflammation.Whether ARRDC3 contributes to innate antiviral immunity is undefined.Here,we found that enterovirus infection induces ARRDC3 expression at both the mRNA and protein levels,thereby inhibiting enterovirus replication.Moreover,we demonstrate that the expression of Yes-associated protein(YAP),a key effector of the Hippo pathway,is severely downregulated by ARRDC3 via lysosomal pathway.YAP facilitates enterovirus replication by suppressing the interferon pathway during the later stage of enterovirus infection,independent of its transcriptional activity.Finally,the ARRDC3-YAP pathway exhibits a broad-spectrum antiviral effect in various viral infections,including those caused by human parainfluenza virus type 3(HPIV3)and vesicular stomatitis virus(VSV).Collectively,our results identify the critical role of ARRDC3 and its negative regulatory effect on YAP in the innate antiviral response,suggesting a novel therapeutic strategy against virus infection.展开更多
Genome mining for the search and discovery of two new globin-like enzymes,TriB from Fusarium poae and TutaA from Schizophyllum commne,are involved in the synthesis of two linear terpenes tricinonoic acid(1)and 2-buten...Genome mining for the search and discovery of two new globin-like enzymes,TriB from Fusarium poae and TutaA from Schizophyllum commne,are involved in the synthesis of two linear terpenes tricinonoic acid(1)and 2-butenedioic acid(3).Both in vivo heterologous biosynthesis and in vitro biochemical assays showed that these two enzymes catalyzed the C-C double bond cleavage of a cyclic sesquiterpene precursor(-)-germacrene D(7)and a linear diterpene backbone schizostain(2),respectively.Our work presents an unusual formation mechanism of linear terpenes from fungi and expands the functional skills of globin-like enzymes in the synthesis of terpene compounds.展开更多
Damage to the skin causes physiological and functional issues.The most effective treatment approach is the use of wound dressings.Silk fibroin(SF)is a promising candidate biomaterial for regulating wound healing;howev...Damage to the skin causes physiological and functional issues.The most effective treatment approach is the use of wound dressings.Silk fibroin(SF)is a promising candidate biomaterial for regulating wound healing;however,its antibacterial properties and biological activity must be further improved.In this study,a photocrosslinking hydrogel was developed to treat full-thickness cutaneous wounds.The composite hydrogel(Ag-AV-SF hydrogel)was prepared by introducing the silver nanoparticles(AgNPs)and aloe vera(AV)as the modifiers.In vitro study exhibited great antibacterial ability,biocompatibility and cell-proliferation and-migration-promoting capacities.It also showed the pH-response releasing properties which release more AgNPs in a simulated chronic infection environment.The healing effect evaluation in vivo showed the healing-promoting ability of the Ag-AV-SF hydrogel was stronger than the single-modifiers groups,and the healing rate of it reached 97.02%on Day 21,higher than the commercial wound dressing,silver sulfadiazine(SS)cream on sale.Additionally,the histological and protein expression results showed that the Ag-AV-SF hydrogel has a greater effect on the pro-healing regenerative phenotype with M2 macrophages at the early stage,reconstructing the blood vessels networks and inhibiting the formation of scars.In summary,the Ag-AV-SF hydrogel developed in this study had good physical properties,overwhelming antibacterial properties,satisfactory biocompatibility and significantly promoting effect on cell proliferation,migration and wound healing.Overall,our results suggest that the Ag-AV-SF hydrogel we developed has great potential for improving the wound healing in clinical treatment.展开更多
Objective:Arsenic trioxide(ATO or As2O3)has beneficial effects on suppressing neointimal hyperplasia and restenosis,but the mechanism is still unclear.The goal of this study is to further understand the mechanism of A...Objective:Arsenic trioxide(ATO or As2O3)has beneficial effects on suppressing neointimal hyperplasia and restenosis,but the mechanism is still unclear.The goal of this study is to further understand the mechanism of ATO's inhibitory effect on vascular smooth muscle cells(VSMCs).Methods and results:Through in vitro cell culture and in vivo stent implanting into the carotid arteries of rabbit,a synthetic-to-contractile phenotypic transition was induced and the proliferation of VSMCs was inhibited by ATO.F-actin filaments were clustered and the elasticity modulus was increased within the phenotypic modulation of VSMCs induced by ATO in vitro.Meanwhile,Yes-associated protein(YAP)nuclear translocation was inhibited by ATO both in vivo and in vitro.It was found that ROCK inhibitor or YAP inactivator could partially mask the phenotype modulation of ATO on VSMCs.Conclusions:The interaction of YAP with the ROCK pathway through ATO seems to mediate the contractile phenotype of VSMCs.This provides an indication of the clinical therapeutic mechanism for the beneficial bioactive effect of ATO-drug eluting stent(AES)on in-stent restenosis(ISR).展开更多
Atherosclerosis is a key mechanism underlying the pathogenesis of cardiovascular disease,which is associated with high morbidity and mortality.In the field of precision medicine for the treatment of atherosclerosis,na...Atherosclerosis is a key mechanism underlying the pathogenesis of cardiovascular disease,which is associated with high morbidity and mortality.In the field of precision medicine for the treatment of atherosclerosis,nanoparticle(NP)-mediated drug delivery systems have great potential,owing to their ability to release treatment locally.Cell-derived biomimetic NPs have attracted extensive attention at present due to their excellent targeting to atherosclerotic inflammatory sites,low immunogenicity and long blood circulation time.Here,we review the utility of cell-derived biomimetic NPs,including whole cells,cell membranes and extracellular vesicles,in the treatment of atherosclerosis.展开更多
The transport and metabolism of lipids in cerebrovascular endothelial cells(ECs)have been hypothesized to regulate blood-brain barrier(BBB)maturation and homeostasis.Long-chain polyunsaturated fatty acids(LCPUFAs)as t...The transport and metabolism of lipids in cerebrovascular endothelial cells(ECs)have been hypothesized to regulate blood-brain barrier(BBB)maturation and homeostasis.Long-chain polyunsaturated fatty acids(LCPUFAs)as the important lipids components of cell membranes are essential for the development and function of BBB,but the direct links of lipid metabolism and ECs barrier function remain to be established.Here,we comprehensively characterize the transcriptomic phenotype of developmental cerebrovascular ECs in single-cell resolution and firstly find that trans-2-enoyl-CoA reductase(Tecr),a verylong-chain fatty acid synthesis,is highly expressed during barriergenesis and decreased after BBB maturation.EC-specific knockout of Tecr compromises angiogenesis due to delayed vascular sprouting.Importantly,EC-specific deletion of Tecr loss restrictive quality of vascular permeability from neonatal stages to adulthood,with high levels of transcytosis,but maintains the vascular tight junctions.Moreover,lipidomic analysis shows that the expression of Tecr in ECs is associated with the containing of omega-3 fatty acids,which directly suppresses caveolae vesicles formation.These results reveal a protective role for Tecr in BBB integrity and suggest that Tecr as a novel therapeutic target in the central nervous system(CNS)diseases associated with BBB dysfunction.展开更多
The most common socioeconomic healthcare issues in clinical are burns,surgical incisions and other skin injuries.Skin lesion healing can be achieved with nanomedicines and other drug application techniques.This study ...The most common socioeconomic healthcare issues in clinical are burns,surgical incisions and other skin injuries.Skin lesion healing can be achieved with nanomedicines and other drug application techniques.This study developed a nano-spray based on cross-linked amorphous calcium peroxide(CaO_(2))nanoparticles of polyacrylic acid(PAA)for treating skin wounds(PAA-CaO_(2)nanoparticles).CaO_(2)serves as a‘drug’precursor,steadily and continuously releasing calcium ions(Ca^(2+))and hydrogen peroxide(H_(2)O_(2))under mildly acidic conditions,while PAA-CaO_(2)nanoparticles exhibited good spray behavior in aqueous form.Tests demonstrated that PAA-CaO_(2)nanoparticles exhibited low cytotoxicity and allowed L929 cells proliferation and migration in vitro.The effectiveness of PAA-CaO_(2)nanoparticles in promoting wound healing and inhibiting bacterial growth in vivo was assessed in SD rats using full-thickness skin defect and Staphylococcus aureus(S.aureus)-infected wound models based thereon.The results revealed that PAA-CaO_(2)nanoparticles demonstrated significant advantages in both aspects.Notably,the infected rats’skin defects healed in 12 days.The benefits are linked to the functional role of Ca^(2+)coalesces with H_(2)O_(2)as known antibacterial and healing-promoted agents.Therefore,we developed nanoscale PAA-CaO_(2)sprays to prevent bacterial development and heal skin lesions.展开更多
Complexing self-assembled DNA nanostructures with various functional vip species is the key to unlocking new and exciting biomedical applications.Cationic vip species not only induce magnesium-free DNA to self-ass...Complexing self-assembled DNA nanostructures with various functional vip species is the key to unlocking new and exciting biomedical applications.Cationic vip species not only induce magnesium-free DNA to self-assemble into defined structures but also endow the final complex nanomaterials with new properties.Herein,we propose a novel strategy that employs naturally occurring cationic amino acids to induce DNA self-assembly into defined nanostructures.Natural L-arginine and L-lysine can readily induce the assembly of tile-based DNA nanotubes and DNA origami sheets in a magnesium-free manner.The self-assembly processes are demonstrated to be pH-and concentration-dependent and are achieved at constant temperatures.Moreover,the assembled DNA/amino acid complex nanomaterials are stable at a physiological temperature of 37◦C.Substituting L-arginine with its D form enhances its serum stability.Further preliminary examination of this complex nanomaterial platform for biomedical applications indicates that DNA/amino acids exhibit distinct cellular uptake behaviors compared with their magnesium-assembled counterparts.The nanomaterial mainly clusters around the cell membrane and might be utilized to manipulate molecular events on the membrane.Our study suggests that the properties of DNA nanostructures can be tuned by complexing them with customized vip molecules for a designed application.The strategy proposed herein might be promising to advance the biomedical applications of DNA nanostructures.展开更多
Multiple signal strategies remarkably improve the accuracy and efficiency of electrochemiluminescence(ECL)immunoassays,but the lack of potential-resolved luminophore pairs and chemical cross talk hinders their develop...Multiple signal strategies remarkably improve the accuracy and efficiency of electrochemiluminescence(ECL)immunoassays,but the lack of potential-resolved luminophore pairs and chemical cross talk hinders their development.In this study,we synthesized a series of gold nanoparticles(AuNPs)/reduced graphene oxide(Au/rGO)composites as adjustable oxygen reduction reaction and oxygen evolution reaction catalysts to promote and modulate tris(2,2′-bipyridine)ruthenium(II)(Ru(bpy)_(3)^(2+))’s multisignal luminescence.With the increase in the diameter of AuNPs(3 to 30 nm),their ability to promote Ru(bpy)_(3)^(2+)’s anodic ECL was first impaired and then strengthened,and cathodic ECL was first enhanced and then weakened.Au/rGOs with medium-small and medium-large AuNP diameters remarkably increased Ru(bpy)_(3)^(2+)’s cathodic and anodic luminescence,respectively.Notably,the stimulation effects of Au/rGOs were superior to those of most existing Ru(bpy)_(3)^(2+)co-reactants.Moreover,we proposed a novel ratiometric immunosensor construction strategy using Ru(bpy)_(3)^(2+)’s luminescence promoter rather than luminophores as tags of antibodies to achieve signal resolution.This method avoids signal cross talk between luminophores and their respective co-reactants,which achieved a good linear range of 10−7 to 10−1 ng/ml and a limit of detection of 0.33 fg/ml for detecting carcinoembryonic antigen.This study addresses the previous scarcity of the macromolecular co-reactants of Ru(bpy)_(3)^(2+),broadening its application in biomaterial detection.Furthermore,the systematic clarification of the detailed mechanisms for converting the potential-resolved luminescence of Ru(bpy)_(3)^(2+)could facilitate an in-depth understanding of the ECL process and should inspire new designs of Ru(bpy)_(3)^(2+)luminescence enhancers or applications of Au/rGOs to other luminophores.This work removes some impediments to the development of multisignal ECL biodetection systems and provides vitality into their widespread applications.展开更多
The authors regret the publication of incorrect fund numbers in the acknowledgment section of the article.The number“cstc2019jcyj-zdxm0033”has been updated as“cstc2019jcyj-zdxmX0028”.The corrected acknowledgment s...The authors regret the publication of incorrect fund numbers in the acknowledgment section of the article.The number“cstc2019jcyj-zdxm0033”has been updated as“cstc2019jcyj-zdxmX0028”.The corrected acknowledgment section is as follows:This study was supported in part by grants from the National Natural Science Foundation,China(31971242,31701275),the Natural Science Foundation of Chongqing,China(cstc2020jcjy-msxmX0189),the Chongqing Research Program of Basic Research and Frontier Technology,China(cstc2019jcjy-dxmX0028),Open Fund for Key Laboratory of Biorheological Science and Technology,Ministry of Education,China(CQKLBST-2019-010),Innovation Talent Project of 2020 for Chongqing Primary and secondary School,China(CY200405)and the National Key R&D Program,China(2016YFC1102305).The support from the Chongqing Engineering Laboratory in Vascular Implants,China,the Public Experiment Centre of State Bioindustrial Base(Chongqing)and the National“111 Plan”,China(B06023)are gratefully acknowledged.展开更多
Nanoparticles(NPs)hold tremendous targeting potential in cardiovascular disease and regenerative medicine,and exciting clinical applications are coming into light.Vascular endothelial cells(ECs)exposure to different m...Nanoparticles(NPs)hold tremendous targeting potential in cardiovascular disease and regenerative medicine,and exciting clinical applications are coming into light.Vascular endothelial cells(ECs)exposure to different magnitudes and patterns of shear stress(SS)generated by blood flow could engulf NPs in the blood.However,an unclear understanding of the role of SS on NP uptake is hindering the progress in improving the targeting of NP therapies.Here,the temporal and spatial distribution of SS in vascular ECs and the effect of different SS on NP uptake in ECs are highlighted.The mechanism of SS affecting NP uptake through regulating the cellular ROS level,endothelial glycocalyx and membrane fluidity is summarized,and the molecules containing clathrin and caveolin in the engulfment process are elucidated.SS targeting NPs are expected to overcome the current bottlenecks and change the field of targeting nanomedicine.This assessment on how SS affects the cell uptake of NPs and the marginalization of NPs in blood vessels could guide future research in cell biology and vascular targeting drugs.展开更多
基金supported by the National Natural Science Foundation of China(31600139)the Chongqing Science and Technology Bureau(cstc2016jcyjA0020+3 种基金CSTB2024NSCQ-KJFZMSX0067)the Yuzhong District Science and Technology Commission(20190123)the Chongqing Municipal Education Commission(KJQN202300415)the Project of Undergraduates Innovating Experiment,and the Project of Tutorial System of Excellent Medical Undergraduates in the Lab Teaching and Management Center of Chongqing Medical University(S202410631068,LTMCMTS202458,LTMCMTS202459,LTMCMTS202460 and LTMCMTS202461).
文摘Enterovirus D68(EV-D68)and enterovirus A71(EV-A71)are two major types of enteroviruses that pose emerging challenges to public health and have the potential to cause outbreaks,yet their pathogenic mechanisms remain largely unexplored.Arrestin domain containing 3(ARRDC3)is a vital regulator of glucose metabolism,cancer development,and inflammation.Whether ARRDC3 contributes to innate antiviral immunity is undefined.Here,we found that enterovirus infection induces ARRDC3 expression at both the mRNA and protein levels,thereby inhibiting enterovirus replication.Moreover,we demonstrate that the expression of Yes-associated protein(YAP),a key effector of the Hippo pathway,is severely downregulated by ARRDC3 via lysosomal pathway.YAP facilitates enterovirus replication by suppressing the interferon pathway during the later stage of enterovirus infection,independent of its transcriptional activity.Finally,the ARRDC3-YAP pathway exhibits a broad-spectrum antiviral effect in various viral infections,including those caused by human parainfluenza virus type 3(HPIV3)and vesicular stomatitis virus(VSV).Collectively,our results identify the critical role of ARRDC3 and its negative regulatory effect on YAP in the innate antiviral response,suggesting a novel therapeutic strategy against virus infection.
基金supported by the National Natural Science Foundation of China(No.31870022)Chongqing Science Funds for Distinguished Young Scientists(No.cstc2020jcyjjqX0005)。
文摘Genome mining for the search and discovery of two new globin-like enzymes,TriB from Fusarium poae and TutaA from Schizophyllum commne,are involved in the synthesis of two linear terpenes tricinonoic acid(1)and 2-butenedioic acid(3).Both in vivo heterologous biosynthesis and in vitro biochemical assays showed that these two enzymes catalyzed the C-C double bond cleavage of a cyclic sesquiterpene precursor(-)-germacrene D(7)and a linear diterpene backbone schizostain(2),respectively.Our work presents an unusual formation mechanism of linear terpenes from fungi and expands the functional skills of globin-like enzymes in the synthesis of terpene compounds.
基金supported by the National Natural Science Foundation of China(12032007,31971242)the Natural Science Foundation of Chongqing(cstc2020jcyj-msxmX0330)+3 种基金the Project of Science and Technology of Chongqing Yuzhong District(20170119,20170113)the Project of Tutorial System of Medical Undergraduate in Lab Teaching&Management Center in Chongqing Medical University(LTMCMTS202003)the National Project of University Students Innovation and Entrepreneurship Training Program(201910631002)the Project of‘Ying Yao Program’for College Student in School of Basic Medical Sciences in ChongqingMedical University(JCYY202003).
文摘Damage to the skin causes physiological and functional issues.The most effective treatment approach is the use of wound dressings.Silk fibroin(SF)is a promising candidate biomaterial for regulating wound healing;however,its antibacterial properties and biological activity must be further improved.In this study,a photocrosslinking hydrogel was developed to treat full-thickness cutaneous wounds.The composite hydrogel(Ag-AV-SF hydrogel)was prepared by introducing the silver nanoparticles(AgNPs)and aloe vera(AV)as the modifiers.In vitro study exhibited great antibacterial ability,biocompatibility and cell-proliferation and-migration-promoting capacities.It also showed the pH-response releasing properties which release more AgNPs in a simulated chronic infection environment.The healing effect evaluation in vivo showed the healing-promoting ability of the Ag-AV-SF hydrogel was stronger than the single-modifiers groups,and the healing rate of it reached 97.02%on Day 21,higher than the commercial wound dressing,silver sulfadiazine(SS)cream on sale.Additionally,the histological and protein expression results showed that the Ag-AV-SF hydrogel has a greater effect on the pro-healing regenerative phenotype with M2 macrophages at the early stage,reconstructing the blood vessels networks and inhibiting the formation of scars.In summary,the Ag-AV-SF hydrogel developed in this study had good physical properties,overwhelming antibacterial properties,satisfactory biocompatibility and significantly promoting effect on cell proliferation,migration and wound healing.Overall,our results suggest that the Ag-AV-SF hydrogel we developed has great potential for improving the wound healing in clinical treatment.
基金This study was supported in part by grants from the National Natural Science Foundation of China,China(31971242,31701275)the National Science Foundation of Chongqing,China(cstc2020jcjymsxmX0189)+4 种基金the Chongqing Research Program of Basic Research and Frontier Technology,China(CSTC2019JCYJ-ZDXM0033)Open Fund for Key Laboratory of Biorheological Science and Technology,Ministry of Education,China(CQKLBST-2019-010)Innovation Talent Project of 2020 for Chongqing Primary and secondary School,China(CY200405)the National Key R&D Program,China(2016YFC1102305)The support from the Chongqing Engineering Laboratory in Vascular Implants,China,the Public Experiment Centre of State Bioindustrial Base(Chongqing)and the National“111 Plan”,China(B06023)are gratefully acknowledged.
文摘Objective:Arsenic trioxide(ATO or As2O3)has beneficial effects on suppressing neointimal hyperplasia and restenosis,but the mechanism is still unclear.The goal of this study is to further understand the mechanism of ATO's inhibitory effect on vascular smooth muscle cells(VSMCs).Methods and results:Through in vitro cell culture and in vivo stent implanting into the carotid arteries of rabbit,a synthetic-to-contractile phenotypic transition was induced and the proliferation of VSMCs was inhibited by ATO.F-actin filaments were clustered and the elasticity modulus was increased within the phenotypic modulation of VSMCs induced by ATO in vitro.Meanwhile,Yes-associated protein(YAP)nuclear translocation was inhibited by ATO both in vivo and in vitro.It was found that ROCK inhibitor or YAP inactivator could partially mask the phenotype modulation of ATO on VSMCs.Conclusions:The interaction of YAP with the ROCK pathway through ATO seems to mediate the contractile phenotype of VSMCs.This provides an indication of the clinical therapeutic mechanism for the beneficial bioactive effect of ATO-drug eluting stent(AES)on in-stent restenosis(ISR).
基金supported in part by grants from the Open Fund for Key Laboratory of Biorheological Science and Technology,Ministry of Education(CQKLBST-2019-010)The Project of Tutorial System of Medical Undergraduate in Lab Teaching&Management Center in Chongqing Medical University(LTMCMTS201905)Undergraduate Scientific Research and Innovation Laboratory Project of Chongqing Medical University(201965)。
文摘Atherosclerosis is a key mechanism underlying the pathogenesis of cardiovascular disease,which is associated with high morbidity and mortality.In the field of precision medicine for the treatment of atherosclerosis,nanoparticle(NP)-mediated drug delivery systems have great potential,owing to their ability to release treatment locally.Cell-derived biomimetic NPs have attracted extensive attention at present due to their excellent targeting to atherosclerotic inflammatory sites,low immunogenicity and long blood circulation time.Here,we review the utility of cell-derived biomimetic NPs,including whole cells,cell membranes and extracellular vesicles,in the treatment of atherosclerosis.
基金the National Natural Science Foundation of China(12032007,31971242)to Guixue Wangthe Chongqing Science and Technology Bureau(cstc2019jcyj-zdxmX0028)to Guixue WangChongqing Municipal Education Commission,China(KYYJ202001)to Guixue Wang。
文摘The transport and metabolism of lipids in cerebrovascular endothelial cells(ECs)have been hypothesized to regulate blood-brain barrier(BBB)maturation and homeostasis.Long-chain polyunsaturated fatty acids(LCPUFAs)as the important lipids components of cell membranes are essential for the development and function of BBB,but the direct links of lipid metabolism and ECs barrier function remain to be established.Here,we comprehensively characterize the transcriptomic phenotype of developmental cerebrovascular ECs in single-cell resolution and firstly find that trans-2-enoyl-CoA reductase(Tecr),a verylong-chain fatty acid synthesis,is highly expressed during barriergenesis and decreased after BBB maturation.EC-specific knockout of Tecr compromises angiogenesis due to delayed vascular sprouting.Importantly,EC-specific deletion of Tecr loss restrictive quality of vascular permeability from neonatal stages to adulthood,with high levels of transcytosis,but maintains the vascular tight junctions.Moreover,lipidomic analysis shows that the expression of Tecr in ECs is associated with the containing of omega-3 fatty acids,which directly suppresses caveolae vesicles formation.These results reveal a protective role for Tecr in BBB integrity and suggest that Tecr as a novel therapeutic target in the central nervous system(CNS)diseases associated with BBB dysfunction.
基金supported by grants from the Natural Science Foundation of Chongqing(cstc2020jcyj-msxmX0330,cstc2021jsyjyzysbA0057)the National Natural Science Foundation of China(31971242,12032007)+1 种基金the Science and Technology Innovation Project of Jinfeng Laboratory,Chongqing,China(jfkyjf202203001)the Project of Tutorial System of Medical Undergraduate in Lab Teaching&Management Center in Chongqing Medical University(LTMCMTS202107).
文摘The most common socioeconomic healthcare issues in clinical are burns,surgical incisions and other skin injuries.Skin lesion healing can be achieved with nanomedicines and other drug application techniques.This study developed a nano-spray based on cross-linked amorphous calcium peroxide(CaO_(2))nanoparticles of polyacrylic acid(PAA)for treating skin wounds(PAA-CaO_(2)nanoparticles).CaO_(2)serves as a‘drug’precursor,steadily and continuously releasing calcium ions(Ca^(2+))and hydrogen peroxide(H_(2)O_(2))under mildly acidic conditions,while PAA-CaO_(2)nanoparticles exhibited good spray behavior in aqueous form.Tests demonstrated that PAA-CaO_(2)nanoparticles exhibited low cytotoxicity and allowed L929 cells proliferation and migration in vitro.The effectiveness of PAA-CaO_(2)nanoparticles in promoting wound healing and inhibiting bacterial growth in vivo was assessed in SD rats using full-thickness skin defect and Staphylococcus aureus(S.aureus)-infected wound models based thereon.The results revealed that PAA-CaO_(2)nanoparticles demonstrated significant advantages in both aspects.Notably,the infected rats’skin defects healed in 12 days.The benefits are linked to the functional role of Ca^(2+)coalesces with H_(2)O_(2)as known antibacterial and healing-promoted agents.Therefore,we developed nanoscale PAA-CaO_(2)sprays to prevent bacterial development and heal skin lesions.
基金This work was supported by the National Natural Science Foundation of China(32071379,81670047,and 81873422)the Natural Science Foundation of Chongqing,China(No.cstc2020jcyj-msxmX0622)+1 种基金the Project Foundation of Chongqing Municipal Education Committee(KJQN201900405)the NUS Cross Faculty Grant(R279000502133).
文摘Complexing self-assembled DNA nanostructures with various functional vip species is the key to unlocking new and exciting biomedical applications.Cationic vip species not only induce magnesium-free DNA to self-assemble into defined structures but also endow the final complex nanomaterials with new properties.Herein,we propose a novel strategy that employs naturally occurring cationic amino acids to induce DNA self-assembly into defined nanostructures.Natural L-arginine and L-lysine can readily induce the assembly of tile-based DNA nanotubes and DNA origami sheets in a magnesium-free manner.The self-assembly processes are demonstrated to be pH-and concentration-dependent and are achieved at constant temperatures.Moreover,the assembled DNA/amino acid complex nanomaterials are stable at a physiological temperature of 37◦C.Substituting L-arginine with its D form enhances its serum stability.Further preliminary examination of this complex nanomaterial platform for biomedical applications indicates that DNA/amino acids exhibit distinct cellular uptake behaviors compared with their magnesium-assembled counterparts.The nanomaterial mainly clusters around the cell membrane and might be utilized to manipulate molecular events on the membrane.Our study suggests that the properties of DNA nanostructures can be tuned by complexing them with customized vip molecules for a designed application.The strategy proposed herein might be promising to advance the biomedical applications of DNA nanostructures.
基金This work was supported by grants from the Natural Science Foundation of Chongqing(cstc2020jcyj-msxmX0330,cstc2021jsyj-yzysbA0057,and cstc2019jcyj-zdxmX0028)the National Natural Science Foundation of China(31971242 and 12032007)+4 种基金the Project of Tutorial System of Medical Undergraduate in Lab Teaching&Management Center in Chongqing Medical University(LTMCMTS202005 and LTMCMTS202110)the JinFeng Laboratory Foundation of Chongqing(jfkyjf202203001)the Scientific and Technological Research Program of Chongqing Municipal Education Commission(KJQN202200426)the Scientific Research,the CQMU Program for Youth Innovation in Future Medicine(W0015)the Innovation Experimental Project of Chongqing Medical University(SRIEP202105).
文摘Multiple signal strategies remarkably improve the accuracy and efficiency of electrochemiluminescence(ECL)immunoassays,but the lack of potential-resolved luminophore pairs and chemical cross talk hinders their development.In this study,we synthesized a series of gold nanoparticles(AuNPs)/reduced graphene oxide(Au/rGO)composites as adjustable oxygen reduction reaction and oxygen evolution reaction catalysts to promote and modulate tris(2,2′-bipyridine)ruthenium(II)(Ru(bpy)_(3)^(2+))’s multisignal luminescence.With the increase in the diameter of AuNPs(3 to 30 nm),their ability to promote Ru(bpy)_(3)^(2+)’s anodic ECL was first impaired and then strengthened,and cathodic ECL was first enhanced and then weakened.Au/rGOs with medium-small and medium-large AuNP diameters remarkably increased Ru(bpy)_(3)^(2+)’s cathodic and anodic luminescence,respectively.Notably,the stimulation effects of Au/rGOs were superior to those of most existing Ru(bpy)_(3)^(2+)co-reactants.Moreover,we proposed a novel ratiometric immunosensor construction strategy using Ru(bpy)_(3)^(2+)’s luminescence promoter rather than luminophores as tags of antibodies to achieve signal resolution.This method avoids signal cross talk between luminophores and their respective co-reactants,which achieved a good linear range of 10−7 to 10−1 ng/ml and a limit of detection of 0.33 fg/ml for detecting carcinoembryonic antigen.This study addresses the previous scarcity of the macromolecular co-reactants of Ru(bpy)_(3)^(2+),broadening its application in biomaterial detection.Furthermore,the systematic clarification of the detailed mechanisms for converting the potential-resolved luminescence of Ru(bpy)_(3)^(2+)could facilitate an in-depth understanding of the ECL process and should inspire new designs of Ru(bpy)_(3)^(2+)luminescence enhancers or applications of Au/rGOs to other luminophores.This work removes some impediments to the development of multisignal ECL biodetection systems and provides vitality into their widespread applications.
文摘The authors regret the publication of incorrect fund numbers in the acknowledgment section of the article.The number“cstc2019jcyj-zdxm0033”has been updated as“cstc2019jcyj-zdxmX0028”.The corrected acknowledgment section is as follows:This study was supported in part by grants from the National Natural Science Foundation,China(31971242,31701275),the Natural Science Foundation of Chongqing,China(cstc2020jcjy-msxmX0189),the Chongqing Research Program of Basic Research and Frontier Technology,China(cstc2019jcjy-dxmX0028),Open Fund for Key Laboratory of Biorheological Science and Technology,Ministry of Education,China(CQKLBST-2019-010),Innovation Talent Project of 2020 for Chongqing Primary and secondary School,China(CY200405)and the National Key R&D Program,China(2016YFC1102305).The support from the Chongqing Engineering Laboratory in Vascular Implants,China,the Public Experiment Centre of State Bioindustrial Base(Chongqing)and the National“111 Plan”,China(B06023)are gratefully acknowledged.
基金supported by the National Natural Science Foundation of China(12032007,31971242)to G.W.the Chongqing Science and Technology Bureau(cstc2019jcyj-zdxmX0028)to G.W.JinFeng Laboratory,Chongqing,China(jfkyjf202203001)to G.W.
文摘Nanoparticles(NPs)hold tremendous targeting potential in cardiovascular disease and regenerative medicine,and exciting clinical applications are coming into light.Vascular endothelial cells(ECs)exposure to different magnitudes and patterns of shear stress(SS)generated by blood flow could engulf NPs in the blood.However,an unclear understanding of the role of SS on NP uptake is hindering the progress in improving the targeting of NP therapies.Here,the temporal and spatial distribution of SS in vascular ECs and the effect of different SS on NP uptake in ECs are highlighted.The mechanism of SS affecting NP uptake through regulating the cellular ROS level,endothelial glycocalyx and membrane fluidity is summarized,and the molecules containing clathrin and caveolin in the engulfment process are elucidated.SS targeting NPs are expected to overcome the current bottlenecks and change the field of targeting nanomedicine.This assessment on how SS affects the cell uptake of NPs and the marginalization of NPs in blood vessels could guide future research in cell biology and vascular targeting drugs.
