The atmospheric corrosion monitoring(ACM)technique has been widely employed to track the real-time corrosion behavior of metal materials.However,limited studies have applied ACM to the corrosion protection properties ...The atmospheric corrosion monitoring(ACM)technique has been widely employed to track the real-time corrosion behavior of metal materials.However,limited studies have applied ACM to the corrosion protection properties of organic coatings.This study compared a bare epoxy coating with one containing zinc phosphate corrosion inhibitors,both applied on ACM sensors,to observe their corrosion protection properties over time.Coatings with artificial damage via scratches were exposed to immersion and alternating dry and wet environments,which allowed for monitoring galvanic corrosion currents in real-time.Throughout the corrosion tests,the ACM currents of the zinc phosphate/epoxy coating were considerably lower than those of the blank epoxy coating.The trend in ACM current variations closely matched the results obtained from regular electrochemical tests and surface analysis.This alignment highlights the potential of the ACM technique in evaluating the corrosion protection capabilities of organic coatings.Compared with the blank epoxy coating,the zinc phosphate/epoxy coating showed much-decreased ACM current values that confirmed the effective inhibition of zinc phosphate against steel corrosion beneath the damaged coating.展开更多
Retinal neovascularization(RNV),a typical pathological manifestation involved in most neovascular diseases,causes retinal detachment,vision loss,and ultimately irreversible blindness.Repeated intravitreal injections o...Retinal neovascularization(RNV),a typical pathological manifestation involved in most neovascular diseases,causes retinal detachment,vision loss,and ultimately irreversible blindness.Repeated intravitreal injections of anti-VEGF drugs were developed against RNV,with limitations of incomplete responses and adverse effects.Therefore,a new treatment with a better curative effect and more prolonged dosage is demanding.Here,we induced macrophage polarization to anti-inflammatory M2 phenotype by inhibiting cGAS-STING signaling with an antagonist C176,appreciating the role of cGAS-STING signaling in the retina in pro-inflammatory M1 polarization.C176-loaded and phosphatidylserine-modified dendritic mesoporous silica nanoparticles were constructed and examined by a single intravitreal injection.The biosafe nanoparticles were phagocytosed by retinal macrophages through a phosphatidylserine-mediated“eat me”signal,which persistently release C176 to suppress STING signaling and thereby promote macrophage M2 polarization specifically.A single dosage can effectively alleviate pathological angiogenesis phenotypes in murine oxygen-induced retinopathy models.In conclusion,these C176-loaded nanoparticles with enhanced cell uptake and long-lasting STING inhibition effects might serve as a promising way for treating RNV.展开更多
Hydrogels are three-dimensional platforms that serve as substitutes for native extracellular matrix.These materials are starting to play important roles in regenerative medicine because of their similarities to native...Hydrogels are three-dimensional platforms that serve as substitutes for native extracellular matrix.These materials are starting to play important roles in regenerative medicine because of their similarities to native matrix in water content and flexibility.It would be very advantagoues for researchers to be able to regulate cell behavior and fate with specific hydrogels that have tunable mechanical properties as biophysical cues.Recent developments in dynamic chemistry have yielded designs of adaptable hydrogels that mimic dynamic nature of extracellular matrix.The current review provides a comprehensive overview for adaptable hydrogel in regenerative medicine as follows.First,we outline strategies to design adaptable hydrogel network with reversible linkages according to previous findings in supramolecular chemistry and dynamic covalent chemistry.Next,we describe the mechanism of dynamic mechanical microenvironment influence cell behaviors and fate,including how stress relaxation influences on cell behavior and how mechanosignals regulate matrix remodeling.Finally,we highlight techniques such as bioprinting which utilize adaptable hydrogel in regenerative medicine.We conclude by discussing the limitations and challenges for adaptable hydrogel,and we present perspectives for future studies.展开更多
Ischemic stroke is an acute and serious cerebral vascular disease,which greatly affects people’s health and brings huge economic burden to society.Microglia,as important innate immune components in central nervous sy...Ischemic stroke is an acute and serious cerebral vascular disease,which greatly affects people’s health and brings huge economic burden to society.Microglia,as important innate immune components in central nervous system(CNS),are double-edged swords in the battle of nerve injury,considering their polarization between pro-inflammatory M1 or anti-inflammatory M2 phenotypes.High mobility group box 1(HMGB1)is one of the potent pro-inflammatory mediators that promotes the M1 polarization of microglia.18β-glycyrrhetinic acid(GA)is an effective intracellular inhibitor of HMGB1,but of poor water solubility and dose-dependent toxicity.To overcome the shortcomings of GA delivery and to improve the efficacy of cerebral ischemia therapy,herein,we designed reactive oxygen species(ROS)responsive polymer-drug conjugate nanoparticles(DGA)to manipulate microglia polarization by suppressing the translocation of nuclear HMGB1.DGA presented excellent therapeutic efficacy in stroke mice,as evidenced by the reduction of infarct volume,recovery of motor function,suppressed of M1 microglia activation and enhanced M2 activation,and induction of neurogenesis.Altogether,our work demonstrates a close association between HMGB1 and microglia polarization,suggesting potential strategies for coping with inflammatory microglia-related diseases.展开更多
The neuroinflammatory responses following ischemic stroke cause irreversible nerve cell death.Cell free-double strand DNA(dsDNA)segments from ischemic tissue debris are engulfed by microglia and sensed by their cyclic...The neuroinflammatory responses following ischemic stroke cause irreversible nerve cell death.Cell free-double strand DNA(dsDNA)segments from ischemic tissue debris are engulfed by microglia and sensed by their cyclic GMP-AMP synthase(cGAS),which triggers robust activation of the innate immune stimulator of interferon genes(STING)pathway and initiate the chronic inflammatory cascade.The decomposition of immunogenic dsDNA and inhibition of the innate immune STING are synergistic immunologic targets for ameliorating neuroinflammation.To combine the anti-inflammatory strategies of STING inhibition and dsDNA elimination,we constructed a DNase-mimetic artificial enzyme loaded with C-176.Nanoparticles are self-assembled by amphiphilic copolymers(P[CL35-b-(OEGMA20.7-co-NTAMA14.3)]),C-176,and Ce^(4+)which is coordinated with nitrilotriacetic acid(NTA)group to form corresponding catalytic structures.Our work developed a new nano-drug that balances the cGAS-STING axis to enhance the therapeutic impact of stroke by combining the DNase-memetic Ce^(4+)enzyme and STING inhibitor synergistically.In conclusion,it is a novel approach to modulating central nervus system(CNS)inflammatory signaling pathways and improving stroke prognosis.展开更多
Rheumatoid arthritis(RA)is a common autoimmune disease leading to pain,disability,and even death.Although studies have revealed that aberrant activation of STING was implicated in various autoimmune diseases,the role ...Rheumatoid arthritis(RA)is a common autoimmune disease leading to pain,disability,and even death.Although studies have revealed that aberrant activation of STING was implicated in various autoimmune diseases,the role of STING in RA remains unclear.In the current study,we demonstrated that STING activation was pivotal in RA pathogenesis.As the accumulation of dsDNA,a specific stimulus for STING,is a feature of RA,we developed a spherical polyethyleneimine-coated mesoporous polydopamine nanoparticles loaded with STING antagonist C-176(PEI-PDA@C-176 NPs)for treating RA.The fabricated NPs with biocompatibility had high DNA adsorption ability and could effectively inhibit the STING pathway and inflammation in macrophages.Intra-articular administration of PEI-PDA@C-176 NPs could effectively reduce joint damage in mice models of dsDNA-induced arthritis and collagen-induced arthritis by inhibiting STING pathway.We concluded that materials with synergistic effects of STING inhibition might be an efficacious strategy to treat RA.展开更多
基金financially supported by the National Natural Science Foundation of China(No.52371049)the Young Elite Scientists Sponsorship Program by the China Association for Science and Technology(YESS,No.2020QNRC001)the National Science and Technology Resources Investigation Program of China(Nos.2021FY100603 and 2019FY101404)。
文摘The atmospheric corrosion monitoring(ACM)technique has been widely employed to track the real-time corrosion behavior of metal materials.However,limited studies have applied ACM to the corrosion protection properties of organic coatings.This study compared a bare epoxy coating with one containing zinc phosphate corrosion inhibitors,both applied on ACM sensors,to observe their corrosion protection properties over time.Coatings with artificial damage via scratches were exposed to immersion and alternating dry and wet environments,which allowed for monitoring galvanic corrosion currents in real-time.Throughout the corrosion tests,the ACM currents of the zinc phosphate/epoxy coating were considerably lower than those of the blank epoxy coating.The trend in ACM current variations closely matched the results obtained from regular electrochemical tests and surface analysis.This alignment highlights the potential of the ACM technique in evaluating the corrosion protection capabilities of organic coatings.Compared with the blank epoxy coating,the zinc phosphate/epoxy coating showed much-decreased ACM current values that confirmed the effective inhibition of zinc phosphate against steel corrosion beneath the damaged coating.
基金supported by Key Program of the National Natural Science Foundation of China(82330032)Natural Science Foundation of China(82201195)+1 种基金National Natural Science Foundation Regional Innovation and Development Joint Fund(U20A20386)Key Research and Development Program of Zhejiang Province(2024C03204).
文摘Retinal neovascularization(RNV),a typical pathological manifestation involved in most neovascular diseases,causes retinal detachment,vision loss,and ultimately irreversible blindness.Repeated intravitreal injections of anti-VEGF drugs were developed against RNV,with limitations of incomplete responses and adverse effects.Therefore,a new treatment with a better curative effect and more prolonged dosage is demanding.Here,we induced macrophage polarization to anti-inflammatory M2 phenotype by inhibiting cGAS-STING signaling with an antagonist C176,appreciating the role of cGAS-STING signaling in the retina in pro-inflammatory M1 polarization.C176-loaded and phosphatidylserine-modified dendritic mesoporous silica nanoparticles were constructed and examined by a single intravitreal injection.The biosafe nanoparticles were phagocytosed by retinal macrophages through a phosphatidylserine-mediated“eat me”signal,which persistently release C176 to suppress STING signaling and thereby promote macrophage M2 polarization specifically.A single dosage can effectively alleviate pathological angiogenesis phenotypes in murine oxygen-induced retinopathy models.In conclusion,these C176-loaded nanoparticles with enhanced cell uptake and long-lasting STING inhibition effects might serve as a promising way for treating RNV.
基金support of the National Key Research and Development Program of China(2016YFE0132700)National Natural Science Foundation of China(51822306,51673171)+1 种基金Science Technology Department of Zhejiang Province(2020C03042)the Fundamental Research Funds for the Central Universities of China.
文摘Hydrogels are three-dimensional platforms that serve as substitutes for native extracellular matrix.These materials are starting to play important roles in regenerative medicine because of their similarities to native matrix in water content and flexibility.It would be very advantagoues for researchers to be able to regulate cell behavior and fate with specific hydrogels that have tunable mechanical properties as biophysical cues.Recent developments in dynamic chemistry have yielded designs of adaptable hydrogels that mimic dynamic nature of extracellular matrix.The current review provides a comprehensive overview for adaptable hydrogel in regenerative medicine as follows.First,we outline strategies to design adaptable hydrogel network with reversible linkages according to previous findings in supramolecular chemistry and dynamic covalent chemistry.Next,we describe the mechanism of dynamic mechanical microenvironment influence cell behaviors and fate,including how stress relaxation influences on cell behavior and how mechanosignals regulate matrix remodeling.Finally,we highlight techniques such as bioprinting which utilize adaptable hydrogel in regenerative medicine.We conclude by discussing the limitations and challenges for adaptable hydrogel,and we present perspectives for future studies.
基金support of the National Natural Science Foundation of China(No.22161132027,51822306)Key Research and Development Program of Zhejiang Province(No.2020C03042)the Starry Night Science Fund of Zhejiang University Shanghai Institute for Advanced Study(SN-ZJU-SIAS-006).
文摘Ischemic stroke is an acute and serious cerebral vascular disease,which greatly affects people’s health and brings huge economic burden to society.Microglia,as important innate immune components in central nervous system(CNS),are double-edged swords in the battle of nerve injury,considering their polarization between pro-inflammatory M1 or anti-inflammatory M2 phenotypes.High mobility group box 1(HMGB1)is one of the potent pro-inflammatory mediators that promotes the M1 polarization of microglia.18β-glycyrrhetinic acid(GA)is an effective intracellular inhibitor of HMGB1,but of poor water solubility and dose-dependent toxicity.To overcome the shortcomings of GA delivery and to improve the efficacy of cerebral ischemia therapy,herein,we designed reactive oxygen species(ROS)responsive polymer-drug conjugate nanoparticles(DGA)to manipulate microglia polarization by suppressing the translocation of nuclear HMGB1.DGA presented excellent therapeutic efficacy in stroke mice,as evidenced by the reduction of infarct volume,recovery of motor function,suppressed of M1 microglia activation and enhanced M2 activation,and induction of neurogenesis.Altogether,our work demonstrates a close association between HMGB1 and microglia polarization,suggesting potential strategies for coping with inflammatory microglia-related diseases.
基金the National Natural Science Foundation of China(No.22161132027,82272465,and 52273152)Zhejiang Provincial Natural Science Foundation of China(LY20H060008)+2 种基金the Starry Night Science Fund of Zhejiang University Shanghai Institute for Advanced Study(SN-ZJU-SIAS-006)‘Open Competition to Select the Best Candidates’Key Technology Program for Nucleic Acid Drugs of NCTIB(Grant No.NCTIB2022HS02006)Zhejiang High-Level Young Talent Special Support Plan for Dr.Zhengwei Mao.
文摘The neuroinflammatory responses following ischemic stroke cause irreversible nerve cell death.Cell free-double strand DNA(dsDNA)segments from ischemic tissue debris are engulfed by microglia and sensed by their cyclic GMP-AMP synthase(cGAS),which triggers robust activation of the innate immune stimulator of interferon genes(STING)pathway and initiate the chronic inflammatory cascade.The decomposition of immunogenic dsDNA and inhibition of the innate immune STING are synergistic immunologic targets for ameliorating neuroinflammation.To combine the anti-inflammatory strategies of STING inhibition and dsDNA elimination,we constructed a DNase-mimetic artificial enzyme loaded with C-176.Nanoparticles are self-assembled by amphiphilic copolymers(P[CL35-b-(OEGMA20.7-co-NTAMA14.3)]),C-176,and Ce^(4+)which is coordinated with nitrilotriacetic acid(NTA)group to form corresponding catalytic structures.Our work developed a new nano-drug that balances the cGAS-STING axis to enhance the therapeutic impact of stroke by combining the DNase-memetic Ce^(4+)enzyme and STING inhibitor synergistically.In conclusion,it is a novel approach to modulating central nervus system(CNS)inflammatory signaling pathways and improving stroke prognosis.
基金supported by the National Natural Science Foundation of China(81772382,22161132027 and 82102599)the Key Research Program in Zhejiang Province,Science Technology Department of Zhejiang Province(2020C03042)the Starry Night Science Fund of Zhejiang University Shanghai Institute for Advanced Study(SN-ZJU-SIAS-006).
文摘Rheumatoid arthritis(RA)is a common autoimmune disease leading to pain,disability,and even death.Although studies have revealed that aberrant activation of STING was implicated in various autoimmune diseases,the role of STING in RA remains unclear.In the current study,we demonstrated that STING activation was pivotal in RA pathogenesis.As the accumulation of dsDNA,a specific stimulus for STING,is a feature of RA,we developed a spherical polyethyleneimine-coated mesoporous polydopamine nanoparticles loaded with STING antagonist C-176(PEI-PDA@C-176 NPs)for treating RA.The fabricated NPs with biocompatibility had high DNA adsorption ability and could effectively inhibit the STING pathway and inflammation in macrophages.Intra-articular administration of PEI-PDA@C-176 NPs could effectively reduce joint damage in mice models of dsDNA-induced arthritis and collagen-induced arthritis by inhibiting STING pathway.We concluded that materials with synergistic effects of STING inhibition might be an efficacious strategy to treat RA.