The M1/M2 phenotypic shift of microglia after spinal cord injury plays an important role in the regulation of neuroinflammation during the secondary injury phase of spinal cord injury.Regulation of shifting microglia ...The M1/M2 phenotypic shift of microglia after spinal cord injury plays an important role in the regulation of neuroinflammation during the secondary injury phase of spinal cord injury.Regulation of shifting microglia polarization from M1(neurotoxic and proinflammatory type)to M2(neuroprotective and anti-inflammatory type)after spinal cord injury appears to be crucial.Tryptanthrin possesses an anti-inflammatory biological function.However,its roles and the underlying molecular mechanisms in spinal cord injury remain unknown.In this study,we found that tryptanthrin inhibited microglia-derived inflammation by promoting polarization to the M2 phenotype in vitro.Tryptanthrin promoted M2 polarization through inactivating the cGAS/STING/NF-κB pathway.Additionally,we found that targeting the cGAS/STING/NF-κB pathway with tryptanthrin shifted microglia from the M1 to M2 phenotype after spinal cord injury,inhibited neuronal loss,and promoted tissue repair and functional recovery in a mouse model of spinal cord injury.Finally,using a conditional co-culture system,we found that microglia treated with tryptanthrin suppressed endoplasmic reticulum stress-related neuronal apoptosis.Taken together,these results suggest that by targeting the cGAS/STING/NF-κB axis,tryptanthrin attenuates microglia-derived neuroinflammation and promotes functional recovery after spinal cord injury through shifting microglia polarization to the M2 phenotype.展开更多
In this work,the beneficial effect of Sn addition on the corrosion resistance mechanism of Cr-Mo low alloy steel was studied.Results demonstrated that Sn improves the corrosion resistance of the steel matrix mainly by...In this work,the beneficial effect of Sn addition on the corrosion resistance mechanism of Cr-Mo low alloy steel was studied.Results demonstrated that Sn improves the corrosion resistance of the steel matrix mainly by influencing the microstructural transformation.Sn addition and the synergistic effect of Sn,Cr,and Mo promote the formation of α-FeOOH,SnO_(2),SnO,Cr(OH)_(3),and molybdates,lead to the improved protection and stability of the rust layer.This synergistic effect also endows the inner rust layer with cation selectivity,preventing the further penetration of Cl-and inhibiting the localized corrosion of steel.展开更多
TANK-binding kinase 1(TBK1)is an essential protein kinase for activation of interferon regulatory factor 3(IRF3)and induction of the type I interferons(IFN-I).Although the biochemical regulation of TBK1 activation has...TANK-binding kinase 1(TBK1)is an essential protein kinase for activation of interferon regulatory factor 3(IRF3)and induction of the type I interferons(IFN-I).Although the biochemical regulation of TBK1 activation has been studied,little is known about how enterovirus 71(EV71)employs the deubiquitinases(DUBs)to regulate TBK1 activation for viral immune evasion.Here,we found that EV71 infection upregulated the expression of ubiquitinspecific protease 24(USP24).Further studies revealed that USP24 physically interacted with TBK1,and can reduce K63-linked polyubiquitination of TBK1.Knockdown of USP24 upregulated TBK1 K63-linked polyubiquitination,promoted the phosphorylation and nuclear translocation of IRF3,and in turn improved IFN-I production during EV71 infection.As a consequence,USP24 knockdown dramatically inhibited EV71 infection.This study revealed USP24 as a novel regulator of TBK1 activation,which promotes the understanding of immune evasion mechanisms of EV71 and could provide a potential strategy for treatment of EV71 infection.展开更多
Flexible electronic devices based on reversible bonds for self-curing capabilities arouses extensive interest.However,most of the composite conductive elastomers have the problems of poor mechanical properties and slo...Flexible electronic devices based on reversible bonds for self-curing capabilities arouses extensive interest.However,most of the composite conductive elastomers have the problems of poor mechanical properties and slow recovery of mechanical properties during multiple stretching,which hinder their stability in continuous operation.In this study,hyperbranched-MWCNTs/hyperbranched-PDMS self-healable conductive elastomers inspired by cephalopods were successfully developed.The prepared conductive elastomer exhibited good self-healing ability(91%)at room temperature excited by multiple reversible interactions.The prepared elastomer showed outstanding mechanical properties and anti-fatigue ability,so that it can cope with more arduous tasks.Moreover,the elastomer was sensitive to the change of stress states and can be used as a stable strain sensor.Therefore,the self-repairing conductive elastomer has potential practicability in the fields of human-computer interaction,motion monitoring,soft robot and so on.展开更多
The corrosion behavior of the as-received steel and the spheroidized steel in acidic chloride environment was investigated. The results indicate the corrosion mode and corrosion rate of two steels are diverse due to t...The corrosion behavior of the as-received steel and the spheroidized steel in acidic chloride environment was investigated. The results indicate the corrosion mode and corrosion rate of two steels are diverse due to their difference in microstructure. For as-received steel with ferrite-pearlite microstructure, severe localized corrosion happens on the pearlite regions, and plenty of cathodic cementite remains in the pits, further strengthening the micro-galvanic effect and accelerating the corrosion rate. While for spheroidized steel with tempered martensite microstructure, the nanosized cementite particles evenly distributed on the ferrite substrate are easy to fall off, which can significantly reduce the cementite accumulation on the steel surface, relieving the acceleration effect of micro-galvanic corrosion.展开更多
In this work,the corrosion behavior of medium-carbon steels(45,45 Cu and 45 Cuq steels)in acidic chloride environment was investigated.The results indicated that the micro-galvanic effect between the anodic ferrite ma...In this work,the corrosion behavior of medium-carbon steels(45,45 Cu and 45 Cuq steels)in acidic chloride environment was investigated.The results indicated that the micro-galvanic effect between the anodic ferrite matrix phase and the cathodic cementite secondary phase notably affected the corrosion resistance of the three steels.For 45 steel,serious pitting corrosion happened in and around the pearlite regions,and a large number of lamellar cementite was fixed in the corrosion pits.Meanwhile,the continuously increasing superficial area of cathodic cementite enhanced the micro-galvanic corrosion,resulting in a rapidly increase in corrosion rate with time.While for 45 Cu and 45 Cuq steels,macroscopic uniform corrosion occurred,and the cementite accumulation was markedly reduced as compared with 45 steel,thus the micro-galvanic effect was weakened and the corrosion rate was decreased accordingly.Among these,45 Cuq steel showed the most stable and excellent corrosion resistance during long-term corrosion,indicating the occurrence of a synergistic effect between cementite spheroidization and Cu alloying,thereby significantly improving the corrosion resistance of 45 steel.展开更多
Cancer vaccine efficacy relies on T cells eliciting tumor-specific adaptive immunity,with antigen-presenting cells,particularly dendritic cells(DCs),playing a crucial role.After capturing antigens,DCs migrate to lymph...Cancer vaccine efficacy relies on T cells eliciting tumor-specific adaptive immunity,with antigen-presenting cells,particularly dendritic cells(DCs),playing a crucial role.After capturing antigens,DCs migrate to lymph nodes,where they present antigens to naïve T cells and activate B and natural killer(NK)cells,thereby strengthening anti-tumor immune responses.However,limitations in immune adjuvants and insufficient antigen presentation hinder DCs migration,reducing vaccine effectiveness.This study introduces an outer membrane vesicle(OMV)-based platform engineered to express Vibrio vulnificus flagellin B(FlaB),a Toll-like receptor 5(TLR5)agonist.FlaB effectively activates DCs,enhances interactions with T cells,provides robust costimulatory signals,and promotes cytotoxic CD8^(+)T cell differentiation.Compared to unmodified OMV-Ag,the antigen-loaded OMV-FlaB-Ag nanovaccine significantly enhances DC function,eliciting potent antitumor responses and delaying tumor progression across multiple models.When combined with immune checkpoint inhibitors,it further amplifies antitumor immunity,markedly suppressing tumor growth and improving therapeutic outcomes.展开更多
Photodynamic therapy is a noninvasive type of phototherapy with a high capacity to boost specific antitumor immunity by causing immunogenic cell death.However,the photodynamic therapeutic potency toward solid tumors i...Photodynamic therapy is a noninvasive type of phototherapy with a high capacity to boost specific antitumor immunity by causing immunogenic cell death.However,the photodynamic therapeutic potency toward solid tumors is dampened by tumor hypoxia that negatively impairs the generation of cytotoxic singlet oxygen and promotes the formation of tumor immunosuppression.Herein,fluorinated CaCO_(3)(CaF)nanoparticles are prepared with the addition of dopamine-conjugated perfluorosebacic acid and ferric chloride into a calcium chloride ethanol solution via an ammonium bicarbonate-mediated gas-diffusion process.After being coated with commercial lipids and hexadecylamin conjugated chlorin e6(hCe6)via a templated self-assembly process,the yielded PEGylated nanophotosensitizer(hCe6@CaF-PEG)exhibits an effective loading efficiency to perfluoro-15-crown-5-ether(PFCE),a model perfluorocarbon molecule,and thus oxygen molecules.Upon intravenous administration,the obtained PFCE/hCe6@CaF-PEG can alleviate tumor hypoxia by working as an oxygen nanoshuttle.Together with local light emitting diode light exposure,photodynamic treatment with PFCE/hCe6@CaF-PEG can suppress the growth of primary CT26 tumors and unirradiated distant tumors,particularly when synergized with anti-PD-1(aPD-1)immunotherapy to collectively reverse tumor immunosuppression.This work presents an effective strategy to potentiate photodynamic immunotherapy by concurrently reversing tumor hypoxia and immunosuppression.展开更多
A type of thiophene-bridged silica aerogel was prepared from tetraethyl orthosilicate(TEOS)and 2,5-divinyltrimethoxysilanethiophene(DVTHP)through a facile sol-gel reaction and ambient pressure drying process.DVTHP was...A type of thiophene-bridged silica aerogel was prepared from tetraethyl orthosilicate(TEOS)and 2,5-divinyltrimethoxysilanethiophene(DVTHP)through a facile sol-gel reaction and ambient pressure drying process.DVTHP was synthesized from vinyl trimethoxysilane and 2,5-dibromothiophene through the Heck reaction.FTIR and solid-state^(1)H CP/MAS NMR indicated that the thiophene units had been successfully introduced into the silica aerogel network.SEM showed a co-continuous porous structure and the Brunauer-Emmett-Teller(BET)measurements showed a mesoporous structure that had a high surface area of 834 m^(2)g^(-1),an average pore size of 17.84 nm and a large pore volume of 3.72 cm^(3)g^(-1).This thiophene-bridged silica aerogel had superhydrophobicity with a water contact angle(CA)exceeding 174°and a sliding angle of less than 3°.The silica aerogel had better selectivities for less polar or non-polar solvents than for polar solvents.The introduction of the thiophene unit could improve the adsorption properties.The adsorption capacities for n-hexane and gutter oil were calculated as 17 g g^(-1)and 16 g g^(-1),respectively.Moreover,the samples exhibited good recyclability for organic solvents even after recycling 10 times in adsorption/desorption tests and the adsorption capacities were nearly unchanged from the maximum uptake capacities.The results indicated that these materials could be flexibly utilized as adsorbent materials to selectively adsorb organic solvents for wastewater treatment.展开更多
基金supported by the National Natural Science Foundation of China,Nos.82071387(to HT),81971172(to YW)the Natural Science Foundation of Zhejiang Province,China,No.LY22H090012(to HT)the Basic Research Project of Wenzhou City,China,No.Y20220923(to MZ)。
文摘The M1/M2 phenotypic shift of microglia after spinal cord injury plays an important role in the regulation of neuroinflammation during the secondary injury phase of spinal cord injury.Regulation of shifting microglia polarization from M1(neurotoxic and proinflammatory type)to M2(neuroprotective and anti-inflammatory type)after spinal cord injury appears to be crucial.Tryptanthrin possesses an anti-inflammatory biological function.However,its roles and the underlying molecular mechanisms in spinal cord injury remain unknown.In this study,we found that tryptanthrin inhibited microglia-derived inflammation by promoting polarization to the M2 phenotype in vitro.Tryptanthrin promoted M2 polarization through inactivating the cGAS/STING/NF-κB pathway.Additionally,we found that targeting the cGAS/STING/NF-κB pathway with tryptanthrin shifted microglia from the M1 to M2 phenotype after spinal cord injury,inhibited neuronal loss,and promoted tissue repair and functional recovery in a mouse model of spinal cord injury.Finally,using a conditional co-culture system,we found that microglia treated with tryptanthrin suppressed endoplasmic reticulum stress-related neuronal apoptosis.Taken together,these results suggest that by targeting the cGAS/STING/NF-κB axis,tryptanthrin attenuates microglia-derived neuroinflammation and promotes functional recovery after spinal cord injury through shifting microglia polarization to the M2 phenotype.
基金This work was supported by National Key R&D Program of China(2017YFB0702100)the Fundamental Research Funds for the Central Universities(No.FRF-MP-18-002)。
文摘In this work,the beneficial effect of Sn addition on the corrosion resistance mechanism of Cr-Mo low alloy steel was studied.Results demonstrated that Sn improves the corrosion resistance of the steel matrix mainly by influencing the microstructural transformation.Sn addition and the synergistic effect of Sn,Cr,and Mo promote the formation of α-FeOOH,SnO_(2),SnO,Cr(OH)_(3),and molybdates,lead to the improved protection and stability of the rust layer.This synergistic effect also endows the inner rust layer with cation selectivity,preventing the further penetration of Cl-and inhibiting the localized corrosion of steel.
基金support was provided by the National Natural Science Foundation of China(81572052 and 82102473)Changzhou science and technology support plan(CE20225036,CJ20210141)Young Talent Development Plan of Changzhou Health Commission(2020-233).
文摘TANK-binding kinase 1(TBK1)is an essential protein kinase for activation of interferon regulatory factor 3(IRF3)and induction of the type I interferons(IFN-I).Although the biochemical regulation of TBK1 activation has been studied,little is known about how enterovirus 71(EV71)employs the deubiquitinases(DUBs)to regulate TBK1 activation for viral immune evasion.Here,we found that EV71 infection upregulated the expression of ubiquitinspecific protease 24(USP24).Further studies revealed that USP24 physically interacted with TBK1,and can reduce K63-linked polyubiquitination of TBK1.Knockdown of USP24 upregulated TBK1 K63-linked polyubiquitination,promoted the phosphorylation and nuclear translocation of IRF3,and in turn improved IFN-I production during EV71 infection.As a consequence,USP24 knockdown dramatically inhibited EV71 infection.This study revealed USP24 as a novel regulator of TBK1 activation,which promotes the understanding of immune evasion mechanisms of EV71 and could provide a potential strategy for treatment of EV71 infection.
基金This work was financially supported by Shandong Provincial Natural Science Foundation(No.ZR2019QB019)the National Natural Science Foundation of China(No.51872150)+1 种基金Shandong Provincial Natural Science Foundation(No.ZR2018MB034)Key Laboratory of Special Functional Aggregated Materials,Ministry of Education,P.R.China,“QingChuang Science and Technology Plan”Project of Colleges and Universities in Shandong Province(No.2020KJC005).
文摘Flexible electronic devices based on reversible bonds for self-curing capabilities arouses extensive interest.However,most of the composite conductive elastomers have the problems of poor mechanical properties and slow recovery of mechanical properties during multiple stretching,which hinder their stability in continuous operation.In this study,hyperbranched-MWCNTs/hyperbranched-PDMS self-healable conductive elastomers inspired by cephalopods were successfully developed.The prepared conductive elastomer exhibited good self-healing ability(91%)at room temperature excited by multiple reversible interactions.The prepared elastomer showed outstanding mechanical properties and anti-fatigue ability,so that it can cope with more arduous tasks.Moreover,the elastomer was sensitive to the change of stress states and can be used as a stable strain sensor.Therefore,the self-repairing conductive elastomer has potential practicability in the fields of human-computer interaction,motion monitoring,soft robot and so on.
基金financial support of the Natural Science Foundation of Liaoning Province,China(2019JH3/30100037)the National Natural Science Foundation of China(No.U1867216)the State Key Laboratory of Metal Material for Marine Equipment and Application(No.SKLMEA-K201907)。
文摘The corrosion behavior of the as-received steel and the spheroidized steel in acidic chloride environment was investigated. The results indicate the corrosion mode and corrosion rate of two steels are diverse due to their difference in microstructure. For as-received steel with ferrite-pearlite microstructure, severe localized corrosion happens on the pearlite regions, and plenty of cathodic cementite remains in the pits, further strengthening the micro-galvanic effect and accelerating the corrosion rate. While for spheroidized steel with tempered martensite microstructure, the nanosized cementite particles evenly distributed on the ferrite substrate are easy to fall off, which can significantly reduce the cementite accumulation on the steel surface, relieving the acceleration effect of micro-galvanic corrosion.
基金financially supported by the Natural Science Foundation of Liaoning Province,China(No.2019JH3/30100037)National Natural Science Foundation of China(Nos.U1867216,51701222)State Key Laboratory of Metal Material for Marine Equipment and Application(No.SKLMEA-K201907)。
文摘In this work,the corrosion behavior of medium-carbon steels(45,45 Cu and 45 Cuq steels)in acidic chloride environment was investigated.The results indicated that the micro-galvanic effect between the anodic ferrite matrix phase and the cathodic cementite secondary phase notably affected the corrosion resistance of the three steels.For 45 steel,serious pitting corrosion happened in and around the pearlite regions,and a large number of lamellar cementite was fixed in the corrosion pits.Meanwhile,the continuously increasing superficial area of cathodic cementite enhanced the micro-galvanic corrosion,resulting in a rapidly increase in corrosion rate with time.While for 45 Cu and 45 Cuq steels,macroscopic uniform corrosion occurred,and the cementite accumulation was markedly reduced as compared with 45 steel,thus the micro-galvanic effect was weakened and the corrosion rate was decreased accordingly.Among these,45 Cuq steel showed the most stable and excellent corrosion resistance during long-term corrosion,indicating the occurrence of a synergistic effect between cementite spheroidization and Cu alloying,thereby significantly improving the corrosion resistance of 45 steel.
基金supported by the National Natural Science Foundation of China(Nos.U24A20765 and T2321005)Jiangsu Provincial Science and Technology Plan Special Fund(No.BM2023003)+1 种基金Jiangsu Provincial Medical Key Discipline(No.ZDXK202247)the Priority Academic Program Development of the Jiangsu Higher Education Institutes.
文摘Cancer vaccine efficacy relies on T cells eliciting tumor-specific adaptive immunity,with antigen-presenting cells,particularly dendritic cells(DCs),playing a crucial role.After capturing antigens,DCs migrate to lymph nodes,where they present antigens to naïve T cells and activate B and natural killer(NK)cells,thereby strengthening anti-tumor immune responses.However,limitations in immune adjuvants and insufficient antigen presentation hinder DCs migration,reducing vaccine effectiveness.This study introduces an outer membrane vesicle(OMV)-based platform engineered to express Vibrio vulnificus flagellin B(FlaB),a Toll-like receptor 5(TLR5)agonist.FlaB effectively activates DCs,enhances interactions with T cells,provides robust costimulatory signals,and promotes cytotoxic CD8^(+)T cell differentiation.Compared to unmodified OMV-Ag,the antigen-loaded OMV-FlaB-Ag nanovaccine significantly enhances DC function,eliciting potent antitumor responses and delaying tumor progression across multiple models.When combined with immune checkpoint inhibitors,it further amplifies antitumor immunity,markedly suppressing tumor growth and improving therapeutic outcomes.
基金This work was partially supported by the National Natural Science Foundation of China(No.22077093)the National Research Programs from Ministry of Science and Technology(MOST)of China(Nos.2021YFF0701800 and 2022YFF0706500)+1 种基金the Natural Science Foundation of Jiangsu Province(No.BK20220110)the Collaborative Innovation Center of Suzhou Nano Science and Technology,the Suzhou Key Laboratory of Nanotechnology and Biomedicine,and the 111 Program from the Ministry of Education of China。
文摘Photodynamic therapy is a noninvasive type of phototherapy with a high capacity to boost specific antitumor immunity by causing immunogenic cell death.However,the photodynamic therapeutic potency toward solid tumors is dampened by tumor hypoxia that negatively impairs the generation of cytotoxic singlet oxygen and promotes the formation of tumor immunosuppression.Herein,fluorinated CaCO_(3)(CaF)nanoparticles are prepared with the addition of dopamine-conjugated perfluorosebacic acid and ferric chloride into a calcium chloride ethanol solution via an ammonium bicarbonate-mediated gas-diffusion process.After being coated with commercial lipids and hexadecylamin conjugated chlorin e6(hCe6)via a templated self-assembly process,the yielded PEGylated nanophotosensitizer(hCe6@CaF-PEG)exhibits an effective loading efficiency to perfluoro-15-crown-5-ether(PFCE),a model perfluorocarbon molecule,and thus oxygen molecules.Upon intravenous administration,the obtained PFCE/hCe6@CaF-PEG can alleviate tumor hypoxia by working as an oxygen nanoshuttle.Together with local light emitting diode light exposure,photodynamic treatment with PFCE/hCe6@CaF-PEG can suppress the growth of primary CT26 tumors and unirradiated distant tumors,particularly when synergized with anti-PD-1(aPD-1)immunotherapy to collectively reverse tumor immunosuppression.This work presents an effective strategy to potentiate photodynamic immunotherapy by concurrently reversing tumor hypoxia and immunosuppression.
基金supported by the Key Research and Development Project of Shandong Province(2018GGX102006)the Major Science and Technology Innovation Project of Shandong Province(2017CXGC1104)the Shandong Provincial Natural Science Foundation,China(ZR2018MB034).
文摘A type of thiophene-bridged silica aerogel was prepared from tetraethyl orthosilicate(TEOS)and 2,5-divinyltrimethoxysilanethiophene(DVTHP)through a facile sol-gel reaction and ambient pressure drying process.DVTHP was synthesized from vinyl trimethoxysilane and 2,5-dibromothiophene through the Heck reaction.FTIR and solid-state^(1)H CP/MAS NMR indicated that the thiophene units had been successfully introduced into the silica aerogel network.SEM showed a co-continuous porous structure and the Brunauer-Emmett-Teller(BET)measurements showed a mesoporous structure that had a high surface area of 834 m^(2)g^(-1),an average pore size of 17.84 nm and a large pore volume of 3.72 cm^(3)g^(-1).This thiophene-bridged silica aerogel had superhydrophobicity with a water contact angle(CA)exceeding 174°and a sliding angle of less than 3°.The silica aerogel had better selectivities for less polar or non-polar solvents than for polar solvents.The introduction of the thiophene unit could improve the adsorption properties.The adsorption capacities for n-hexane and gutter oil were calculated as 17 g g^(-1)and 16 g g^(-1),respectively.Moreover,the samples exhibited good recyclability for organic solvents even after recycling 10 times in adsorption/desorption tests and the adsorption capacities were nearly unchanged from the maximum uptake capacities.The results indicated that these materials could be flexibly utilized as adsorbent materials to selectively adsorb organic solvents for wastewater treatment.
