Programmed cell death occurs in browning explants of Fraxinus mandshurica during somatic embryogenesis, but the underlying mechanism is unclear. In this study, single cotyledons of zygotic embryos of F. mandshurica we...Programmed cell death occurs in browning explants of Fraxinus mandshurica during somatic embryogenesis, but the underlying mechanism is unclear. In this study, single cotyledons of zygotic embryos of F. mandshurica were used as explants. Mitochondrial structure and function, caspase-3-like protease activity, hydrogen peroxide metabolism, and nitric oxide accumulation induced by high concentrations of sucrose and plant growth regulators were studied. The results show that plant growth regulators induced somatic embryogenesis and also promoted explant browning. High sucrose concentrations had similar effects. High concentrations of sucrose and plant growth regulators led to the accumulation of hydrogen peroxide and nitric oxide which induced changes in mitochondrial structure and function such as modifications in mitochondrial morphology, increased membrane permeability, decreased membrane potential, and the release of cytochrome c into the cytoplasm. An increase in caspase-3-like protease activity triggered programmed cell death in some browning explant cells. During somatic embryogenesis there were increased activities of superoxide dismutase, peroxidase, and catalase, which are associated with hydrogen peroxide metabolism and jointly maintain reactive oxygen species levels. Intracellular nitric oxide synthase and nitrate reductase activities were not significantly correlated with nitric oxide content. Instead, intracellular nitric oxide may be derived from non-enzymatic reactions. Our results indicate that hydrogen peroxide and nitric oxide may function as signals, playing key roles in somatic embryogenesis and programmed cell death of explant cells of F. mandshurica. The interaction between nitric oxide and reactive oxygen species determines the occurrence of programmed cell death in explant cells;somatic embryogenesis and programmed cell death are positively regulated by hydrogen peroxide. However, the regulation of nitric oxide is complex.展开更多
A synergistic system of water falling film dielectric barrier discharge(DBD)plasma and persulfate(PS)was set up and used for oxidizing ciprofloxacin(CIP)in water.Results of reactive species formation in the DBD-only s...A synergistic system of water falling film dielectric barrier discharge(DBD)plasma and persulfate(PS)was set up and used for oxidizing ciprofloxacin(CIP)in water.Results of reactive species formation in the DBD-only system as well as the DBD–PS system verified the PS activation in the DBD system.Influencing factors on CIP degradation and the degradation process were also been studied.The obtained results showed that the presence of PS could greatly improve the degradation and mineralization of CIP and that the degradation efficiency could reach 97.73%after only 40 min treatment with 4 m M PS addition.The increase of PS concentration,the lower CIP concentration,the acidic solution p H and the addition of metal ions(Fe^(2+)and Cu^(2+))enhanced the CIP degradation,while the existence of Cl^(-)and HCO_(3)^(-)had a negative effect.The experiments related to scavenger addition confirmed the contribution of the main reactive species to the CIP oxidation.Three probable degradation pathways were proposed by analyzing the inorganic ions and organic byproducts formed during the CIP degradation.The toxicity evaluation results of the CIP and its intermediates confirmed the effectiveness of the DBD–PS synergistic system.展开更多
The current single-atom catalysts(SACs)for medicine still suffer from the limited active site density.Here,we develop a synthetic method capable of increasing both the metal loading and mass-specific activity of SACs ...The current single-atom catalysts(SACs)for medicine still suffer from the limited active site density.Here,we develop a synthetic method capable of increasing both the metal loading and mass-specific activity of SACs by exchanging zinc with iron.The constructed iron SACs(h^(3)-FNC)with a high metal loading of 6.27 wt%and an optimized adjacent Fe distance of~4 A exhibit excellent oxidase-like catalytic performance without significant activity decay after being stored for six months and promising antibacterial effects.Attractively,a“density effect”has been found at a high-enough metal doping amount,at which individual active sites become close enough to interact with each other and alter the electronic structure,resulting in significantly boosted intrinsic activity of single-atomic iron sites in h^(3)-FNCs by 2.3 times compared to low-and medium-loading SACs.Consequently,the overall catalytic activity of h^(3)-FNC is highly improved,with mass activity and metal mass-specific activity that are,respectively,66 and 315 times higher than those of commercial Pt/C.In addition,h^(3)-FNCs demonstrate efficiently enhanced capability in catalyzing oxygen reduction into superoxide anion(O_(2)·^(−))and glutathione(GSH)depletion.Both in vitro and in vivo assays demonstrate the superior antibacterial efficacy of h^(3)-FNCs in promoting wound healing.This work presents an intriguing activity-enhancement effect in catalysts and exhibits impressive therapeutic efficacy in combating bacterial infections.展开更多
In the electrical discharge plasma process, various chemical and physical processes can participate in the removal of contaminants. In this paper, the chemical and physical processes that occur as a result of the elec...In the electrical discharge plasma process, various chemical and physical processes can participate in the removal of contaminants. In this paper, the chemical and physical processes that occur as a result of the electrical discharge plasma are reviewed, and their possible roles in the degradation of contaminants are discussed. Measurement methods for the quantification of important reactive species and their advantages and shortcomings are presented. Approaches on how to enhance the diffusion of the reactive species in solution are examined. In addition, the formation of typical reactive species in different electrical discharge plasma is compared.展开更多
Reactive oxygen species(ROS)plays important roles in living organisms.While ROS is a double-edged sword,which can eliminate drug-resistant bacteria,but excessive levels can cause oxidative damage to cells.A core–shel...Reactive oxygen species(ROS)plays important roles in living organisms.While ROS is a double-edged sword,which can eliminate drug-resistant bacteria,but excessive levels can cause oxidative damage to cells.A core–shell nanozyme,Ce O_(2)@ZIF-8/Au,has been crafted,spontaneously activating both ROS generating and scavenging functions,achieving the multifaceted functions of eliminating bacteria,reducing inflammation,and promoting wound healing.The Au Nanoparticles(NPs)on the shell exhibit high-efficiency peroxidase-like activity,producing ROS to kill bacteria.Meanwhile,the encapsulation of Ce O_(2) core within ZIF-8 provides a seal for temporarily limiting the superoxide dismutase and catalase-like activities of Ce O_(2) nanoparticles.Subsequently,as the ZIF-8 structure decomposes in the acidic microenvironment,the Ce O_(2) core is gradually released,exerting its ROS scavenging activity to eliminate excess ROS produced by the Au NPs.These two functions automatically and continuously regulate the balance of ROS levels,ultimately achieving the function of killing bacteria,reducing inflammation,and promoting wound healing.Such innovative ROS spontaneous regulators hold immense potential for revolutionizing the field of antibacterial agents and therapies.展开更多
Photothermal and photodynamic therapies(PTT/PDT)hold promise for localized tumor treatment,yet their full potential is hampered by limitations such as the hypoxic tumor microenvironment and inadequate systemic immune ...Photothermal and photodynamic therapies(PTT/PDT)hold promise for localized tumor treatment,yet their full potential is hampered by limitations such as the hypoxic tumor microenvironment and inadequate systemic immune activation.Addressing these challenges,we present a novel near-infrared(NIR)-triggered RNS nanoreactor(PBNO-Ce6)to amplify the photodynamic and photothermal therapy efficacy against triple-negative breast cancer(TNBC).The designed PBNOCe6 combines sodium nitroprusside-doped Prussian Blue nanoparticles with Chlorin e6 to enable on-site RNS production through NIR-induced concurrent NO release and ROS generation.This not only enhances tumor cell eradication but also potentiates local and systemic antitumor immune responses,protecting mice from tumor rechallenge.Our in vivo evaluations revealed that treatment with PBNO-Ce6 leads to a remarkable 2.7-fold increase in cytotoxic T lymphocytes and a 62%decrease in regulatory T cells in comparison to the control PB-Ce6(Prussian Blue nanoparticles loaded with Chlorin e6),marking a substantial improvement over traditional PTT/PDT.As such,the PBNO-Ce6 nanoreactor represents a transformative approach for improving outcomes in TNBC and potentially other malignancies affected by similar barriers.展开更多
Superparamagnetic iron oxide nanoparticles （SPIONs） are one of the most versatile and safe nanoparticles in a wide variety of biomedical applications. In the past decades, considerable efforts have been made to inve...Superparamagnetic iron oxide nanoparticles （SPIONs） are one of the most versatile and safe nanoparticles in a wide variety of biomedical applications. In the past decades, considerable efforts have been made to investigate the potential adverse biological effects and safety issues associated with SPIONs, which is essential for the development of next-generation SPIONs and for continued progress in translational research. In this mini review, we summarize recent developments in toxicity studies on SPIONs, focusing on the relationship between the physicochemical properties of SPIONs and their induced toxic biological responses for a better toxicological understanding of SPIONs.展开更多
Objective To find out whether dexamethasone induces an uncoupling of the endothelial nitric oxide synthase （eNOS）. Methods ＆ Results A major cause of eNOS uncoupling is a deficiency of its cofactor tetrahydrobiopte...Objective To find out whether dexamethasone induces an uncoupling of the endothelial nitric oxide synthase （eNOS）. Methods ＆ Results A major cause of eNOS uncoupling is a deficiency of its cofactor tetrahydrobiopterin （BH4）. Treatment of human EA.hy 926 endothelial cells with dexamethasone decreased mRNA and protein expression of both BH4-synthesizing enzymes： GTP cyclobydrolase I and dihydrofolate reductase. Consistently, a concentration- and time-dependent reduction of BH4, dihydrobiopterin （BH2） as well as BH4：BH2 ratio was observed in dexamethasone-treated cells. Surprisingly, no evidence for eNOS uncoupling was found. We then analyzed the expression and phosphorylation of the eNOS enzyme. Dexamethasone treatment led to a down-regulation of eNOS protein and a reduction of eNOS phosphorylation at serine 1177. A reduction of eNOS expression may lead to a relatively normal BH4： eNOS molar ratio in dexamethasone-treated cells. Because the BH4-eNOS stoichiometry rather than the absolute BH4 amount is the key determinant of eNOS functionality （i.e., coupled or uncoupled）, the down-regulation of eNOS may represent an explanation for the absence of eNOS uncoupling. Phosphorylation of eNOS at serine 1177 is needed for both the NO-producing activity of the coupled eNOS and the superoxide-producing activity of the uncoupled eNOS. Thus, a reduction of serine 1177 phosphorylation may render a potentially uncoupled eNOS hardly detectable. Conclusions Although dexamethasone reduces BH4 levels in endothelial cells, eNOS uncoupling is not evident. The reduction of NO production in dexamethasone-treated endothelial cells is mainly attributable to reduced eNOS expression and decreased eNOS phosphorylation at serine 1177.展开更多
The development of highly active functionalized ionic liquids(ILs)as both extractants and catalysts for use in achieving deep desulfurization continues to pose challenges.In this study,a highly efficient oxidative des...The development of highly active functionalized ionic liquids(ILs)as both extractants and catalysts for use in achieving deep desulfurization continues to pose challenges.In this study,a highly efficient oxidative desulfurization system was constructed,composed of dual-acidic ionic liquids(DILs)and H_(2)O_(2)-AcOH.The investigation results of four DILs prepared from different metal chlorides([HSO_(3)C_(3)NEt_(3)]Cl-MnCl_(n),MnCl_(n)=AlCl_(3),ZnCl_(2),CuCl_(2),FeCl_(3))in oxidative desulfurization showed that[HSO_(3)C_(3)NEt_(3)]Cl-AlCl_(3)had an outstanding catalytic effect and significantly promoted the oxidation of sulfides.With a 0.2 g[HSO_(3)C_(3)NEt_(3)]Cl-AlCl_(3),the removal rate of dibenzothiophene(DBT)reached 100%in 10 mL model oil under mild conditions at 55℃for 20 min.The key is its ability to induce the dismutation of su-peroxide anions(·O_(2)^(-)),which facilitates the generation of singlet oxygen(1 O_(2)).The efficient oxidation of DBT is accomplished through a predominantly^(1)O_(2)-mediated_(n)on-radical mechanism.[HSO_(3)C_(3)NEt_(3)]Cl-AlCl_(3)serves as a favorable medium for contact to be made between^(1)O_(2)and sulfides,which indicates an efficient catalytic-adsorption synergy.展开更多
Background: Cerebral ischemia-reperfusion injury(CIRI) refers to a secondary brain injury that can occur when the blood supply to the ischemic brain tissue is restored. However, the mechanism underlying such injury re...Background: Cerebral ischemia-reperfusion injury(CIRI) refers to a secondary brain injury that can occur when the blood supply to the ischemic brain tissue is restored. However, the mechanism underlying such injury remains elusive.Methods: The 150 male C57 mice underwent middle cerebral artery occlusion(MCAO) for 1 h and reperfusion for 24 h,Among them, 50 MCAO mice were further treated with Mitochondrial division inhibitor 1(Mdivi-1) and 50 MCAO mice were further treated with N-acetylcysteine(NAC). SH-SY5Y cells were cultured in a low-glucose culture medium for 4 h under hypoxic conditions and then transferred to normal conditions for 12 h. Then, cerebral blood flow, mitochondrial structure, mitochondrial DNA(mtDNA) copy number, intracellular and mitochondrial reactive oxygen species(ROS),autophagic flux, aggresome and exosome expression profiles, cardiac tissue structure, mitochondrial length and cristae density, mtDNA and ROS content, as well as the expression of Drp1-Ser616/Drp1, RIP1/RIP3, LC3 II/I, TNF-α,IL-1β, etc., were detected under normal or Drp1 interference conditions.Results: The mtDNA content, ROS levels, and Drp1-Ser616/Drp1 were elevated by 2.2, 1.7 and 2.7 times after CIRI(P<0.05). However, the high cytoplasmic LC3 II/I ratio and increased aggregation of p62 could be reversed by 44%and 88% by Drp1 short hairpin RNA(shRNA)(P<0.05). The low fluorescence intensity of autophagic flux and the increased phosphorylation of RIP3 induced by CIRI could be attenuated by ROS scavenger, NAC(P<0.05). RIP1/RIP3inhibitor Necrostatin-1(Nec-1) restored 75% to a low LC3 II/I ratio and enhanced 2 times to a high RFP-LC3 after Drp1 activation(P<0.05). In addition, although CIRI-induced ROS production caused no considerable accumulation of autophagosomes(P>0.05), it increased the packaging and extracellular secretion of exosomes containing p62 by 4–5 times, which could be decreased by Mdivi-1, Drp1 shRNA, and Nec-1(P<0.05). Furthermore, TNF-α and IL-1βincreased in CIRI-derived exosomes could increase RIP3 phosphorylation in normal or oxygen–glucose deprivation/reoxygenation(OGD/R) conditions(P<0.05).Conclusions: CIRI activated Drp1 and accelerated the p62-mediated formation of autophagosomes while inhibiting the transition of autophagosomes to autolysosomes via the RIP1/RIP3 pathway activation. Undegraded autophagosomes were secreted extracellularly in the form of exosomes, leading to inflammatory cascades that further damaged mitochondria, resulting in excessive ROS generation and the blockage of autophagosome degradation,triggering a vicious cycle.展开更多
基金This work was supported by the Fundamental Research Funds for the Central Universities(2572018BW02)the Innovation Project of State Key Laboratory of Tree Genetics and Breeding(2016C01)+1 种基金the National Key R&D Program of China(2017YFD0600600)the National Natural Science Foundation of China(31400535 and 31570596).
文摘Programmed cell death occurs in browning explants of Fraxinus mandshurica during somatic embryogenesis, but the underlying mechanism is unclear. In this study, single cotyledons of zygotic embryos of F. mandshurica were used as explants. Mitochondrial structure and function, caspase-3-like protease activity, hydrogen peroxide metabolism, and nitric oxide accumulation induced by high concentrations of sucrose and plant growth regulators were studied. The results show that plant growth regulators induced somatic embryogenesis and also promoted explant browning. High sucrose concentrations had similar effects. High concentrations of sucrose and plant growth regulators led to the accumulation of hydrogen peroxide and nitric oxide which induced changes in mitochondrial structure and function such as modifications in mitochondrial morphology, increased membrane permeability, decreased membrane potential, and the release of cytochrome c into the cytoplasm. An increase in caspase-3-like protease activity triggered programmed cell death in some browning explant cells. During somatic embryogenesis there were increased activities of superoxide dismutase, peroxidase, and catalase, which are associated with hydrogen peroxide metabolism and jointly maintain reactive oxygen species levels. Intracellular nitric oxide synthase and nitrate reductase activities were not significantly correlated with nitric oxide content. Instead, intracellular nitric oxide may be derived from non-enzymatic reactions. Our results indicate that hydrogen peroxide and nitric oxide may function as signals, playing key roles in somatic embryogenesis and programmed cell death of explant cells of F. mandshurica. The interaction between nitric oxide and reactive oxygen species determines the occurrence of programmed cell death in explant cells;somatic embryogenesis and programmed cell death are positively regulated by hydrogen peroxide. However, the regulation of nitric oxide is complex.
基金National Natural Science Foundation of China(No.21876070)for their support of this study.
文摘A synergistic system of water falling film dielectric barrier discharge(DBD)plasma and persulfate(PS)was set up and used for oxidizing ciprofloxacin(CIP)in water.Results of reactive species formation in the DBD-only system as well as the DBD–PS system verified the PS activation in the DBD system.Influencing factors on CIP degradation and the degradation process were also been studied.The obtained results showed that the presence of PS could greatly improve the degradation and mineralization of CIP and that the degradation efficiency could reach 97.73%after only 40 min treatment with 4 m M PS addition.The increase of PS concentration,the lower CIP concentration,the acidic solution p H and the addition of metal ions(Fe^(2+)and Cu^(2+))enhanced the CIP degradation,while the existence of Cl^(-)and HCO_(3)^(-)had a negative effect.The experiments related to scavenger addition confirmed the contribution of the main reactive species to the CIP oxidation.Three probable degradation pathways were proposed by analyzing the inorganic ions and organic byproducts formed during the CIP degradation.The toxicity evaluation results of the CIP and its intermediates confirmed the effectiveness of the DBD–PS synergistic system.
基金supported by the National Key Research and Development Program of China(Grant No.2022YFB3804500)the National Natural Science Foundation of China(Grant No.52202352,22335006)+4 种基金the Shanghai Municipal Health Commission(Grant No.20224Y0010)the CAMS Innovation Fund for Medical Sciences(Grant No.2021-I2M-5-012)the Basic Research Program of Shanghai Municipal Government(Grant No.21JC1406000)the Fundamental Research Funds for the Central Universities(Grant No.22120230237,2023-3-YB-11,22120220618)the Basic Research Program of Shanghai Municipal Government(23DX1900200).
文摘The current single-atom catalysts(SACs)for medicine still suffer from the limited active site density.Here,we develop a synthetic method capable of increasing both the metal loading and mass-specific activity of SACs by exchanging zinc with iron.The constructed iron SACs(h^(3)-FNC)with a high metal loading of 6.27 wt%and an optimized adjacent Fe distance of~4 A exhibit excellent oxidase-like catalytic performance without significant activity decay after being stored for six months and promising antibacterial effects.Attractively,a“density effect”has been found at a high-enough metal doping amount,at which individual active sites become close enough to interact with each other and alter the electronic structure,resulting in significantly boosted intrinsic activity of single-atomic iron sites in h^(3)-FNCs by 2.3 times compared to low-and medium-loading SACs.Consequently,the overall catalytic activity of h^(3)-FNC is highly improved,with mass activity and metal mass-specific activity that are,respectively,66 and 315 times higher than those of commercial Pt/C.In addition,h^(3)-FNCs demonstrate efficiently enhanced capability in catalyzing oxygen reduction into superoxide anion(O_(2)·^(−))and glutathione(GSH)depletion.Both in vitro and in vivo assays demonstrate the superior antibacterial efficacy of h^(3)-FNCs in promoting wound healing.This work presents an intriguing activity-enhancement effect in catalysts and exhibits impressive therapeutic efficacy in combating bacterial infections.
基金funded by National Natural Science Foundation of China (Nos. 51608448 and 21737003)Young Talent Cultivation Scheme Funding of Northwest A&F University (No. Z109021802)the Fundamental Research Funds for the Central Universities (No. Z109021617) for their financial support in this research
文摘In the electrical discharge plasma process, various chemical and physical processes can participate in the removal of contaminants. In this paper, the chemical and physical processes that occur as a result of the electrical discharge plasma are reviewed, and their possible roles in the degradation of contaminants are discussed. Measurement methods for the quantification of important reactive species and their advantages and shortcomings are presented. Approaches on how to enhance the diffusion of the reactive species in solution are examined. In addition, the formation of typical reactive species in different electrical discharge plasma is compared.
基金supported by the Natural Science Foundation of Fujian Province of China(No.2022J01043)China Scholarship Council(201806315005 and 201703170071).
文摘Reactive oxygen species(ROS)plays important roles in living organisms.While ROS is a double-edged sword,which can eliminate drug-resistant bacteria,but excessive levels can cause oxidative damage to cells.A core–shell nanozyme,Ce O_(2)@ZIF-8/Au,has been crafted,spontaneously activating both ROS generating and scavenging functions,achieving the multifaceted functions of eliminating bacteria,reducing inflammation,and promoting wound healing.The Au Nanoparticles(NPs)on the shell exhibit high-efficiency peroxidase-like activity,producing ROS to kill bacteria.Meanwhile,the encapsulation of Ce O_(2) core within ZIF-8 provides a seal for temporarily limiting the superoxide dismutase and catalase-like activities of Ce O_(2) nanoparticles.Subsequently,as the ZIF-8 structure decomposes in the acidic microenvironment,the Ce O_(2) core is gradually released,exerting its ROS scavenging activity to eliminate excess ROS produced by the Au NPs.These two functions automatically and continuously regulate the balance of ROS levels,ultimately achieving the function of killing bacteria,reducing inflammation,and promoting wound healing.Such innovative ROS spontaneous regulators hold immense potential for revolutionizing the field of antibacterial agents and therapies.
基金the financial support from the National Natural Science Foundation of China (No. 82372019, 82022034, 82173327)Jiangsu Province Natural Science Foundation of China (BK20200032)Double First Class Foundation of China Pharmaceutical University(CPUQNJC22_03)
文摘Photothermal and photodynamic therapies(PTT/PDT)hold promise for localized tumor treatment,yet their full potential is hampered by limitations such as the hypoxic tumor microenvironment and inadequate systemic immune activation.Addressing these challenges,we present a novel near-infrared(NIR)-triggered RNS nanoreactor(PBNO-Ce6)to amplify the photodynamic and photothermal therapy efficacy against triple-negative breast cancer(TNBC).The designed PBNOCe6 combines sodium nitroprusside-doped Prussian Blue nanoparticles with Chlorin e6 to enable on-site RNS production through NIR-induced concurrent NO release and ROS generation.This not only enhances tumor cell eradication but also potentiates local and systemic antitumor immune responses,protecting mice from tumor rechallenge.Our in vivo evaluations revealed that treatment with PBNO-Ce6 leads to a remarkable 2.7-fold increase in cytotoxic T lymphocytes and a 62%decrease in regulatory T cells in comparison to the control PB-Ce6(Prussian Blue nanoparticles loaded with Chlorin e6),marking a substantial improvement over traditional PTT/PDT.As such,the PBNO-Ce6 nanoreactor represents a transformative approach for improving outcomes in TNBC and potentially other malignancies affected by similar barriers.
基金Project supported by the Major State Basic Research Development Program of China(Grant Nos.2013CB733802 and 2014CB744503)the National Natural Science Foundation of China(Grant Nos.81101101 and 51273165)+1 种基金the Key Project of Chinese Ministry of Education(Grant No.212149)the Fundamental Research Funds for the Central Universities,China(Grant Nos.2013121039 and ZK1002)
文摘Superparamagnetic iron oxide nanoparticles （SPIONs） are one of the most versatile and safe nanoparticles in a wide variety of biomedical applications. In the past decades, considerable efforts have been made to investigate the potential adverse biological effects and safety issues associated with SPIONs, which is essential for the development of next-generation SPIONs and for continued progress in translational research. In this mini review, we summarize recent developments in toxicity studies on SPIONs, focusing on the relationship between the physicochemical properties of SPIONs and their induced toxic biological responses for a better toxicological understanding of SPIONs.
文摘Objective To find out whether dexamethasone induces an uncoupling of the endothelial nitric oxide synthase （eNOS）. Methods ＆ Results A major cause of eNOS uncoupling is a deficiency of its cofactor tetrahydrobiopterin （BH4）. Treatment of human EA.hy 926 endothelial cells with dexamethasone decreased mRNA and protein expression of both BH4-synthesizing enzymes： GTP cyclobydrolase I and dihydrofolate reductase. Consistently, a concentration- and time-dependent reduction of BH4, dihydrobiopterin （BH2） as well as BH4：BH2 ratio was observed in dexamethasone-treated cells. Surprisingly, no evidence for eNOS uncoupling was found. We then analyzed the expression and phosphorylation of the eNOS enzyme. Dexamethasone treatment led to a down-regulation of eNOS protein and a reduction of eNOS phosphorylation at serine 1177. A reduction of eNOS expression may lead to a relatively normal BH4： eNOS molar ratio in dexamethasone-treated cells. Because the BH4-eNOS stoichiometry rather than the absolute BH4 amount is the key determinant of eNOS functionality （i.e., coupled or uncoupled）, the down-regulation of eNOS may represent an explanation for the absence of eNOS uncoupling. Phosphorylation of eNOS at serine 1177 is needed for both the NO-producing activity of the coupled eNOS and the superoxide-producing activity of the uncoupled eNOS. Thus, a reduction of serine 1177 phosphorylation may render a potentially uncoupled eNOS hardly detectable. Conclusions Although dexamethasone reduces BH4 levels in endothelial cells, eNOS uncoupling is not evident. The reduction of NO production in dexamethasone-treated endothelial cells is mainly attributable to reduced eNOS expression and decreased eNOS phosphorylation at serine 1177.
基金support provided by South Africa National Research Foundation(UID 95983,113648,137947)Foundation for Innovative Research Groups of the Natural Science Foundation of Hebei Province(no.B2021208005).
文摘The development of highly active functionalized ionic liquids(ILs)as both extractants and catalysts for use in achieving deep desulfurization continues to pose challenges.In this study,a highly efficient oxidative desulfurization system was constructed,composed of dual-acidic ionic liquids(DILs)and H_(2)O_(2)-AcOH.The investigation results of four DILs prepared from different metal chlorides([HSO_(3)C_(3)NEt_(3)]Cl-MnCl_(n),MnCl_(n)=AlCl_(3),ZnCl_(2),CuCl_(2),FeCl_(3))in oxidative desulfurization showed that[HSO_(3)C_(3)NEt_(3)]Cl-AlCl_(3)had an outstanding catalytic effect and significantly promoted the oxidation of sulfides.With a 0.2 g[HSO_(3)C_(3)NEt_(3)]Cl-AlCl_(3),the removal rate of dibenzothiophene(DBT)reached 100%in 10 mL model oil under mild conditions at 55℃for 20 min.The key is its ability to induce the dismutation of su-peroxide anions(·O_(2)^(-)),which facilitates the generation of singlet oxygen(1 O_(2)).The efficient oxidation of DBT is accomplished through a predominantly^(1)O_(2)-mediated_(n)on-radical mechanism.[HSO_(3)C_(3)NEt_(3)]Cl-AlCl_(3)serves as a favorable medium for contact to be made between^(1)O_(2)and sulfides,which indicates an efficient catalytic-adsorption synergy.
基金supported by the National Natural Science Foundation of China (81700429)the China Postdoctoral Science Foundation (2021MD703924)+1 种基金the Chongqing Postdoctoral Innovative Talents Support Program (CQBX2021018)the Kuanren Talents Program of the second affiliated hospital of Chongqing Medical University。
文摘Background: Cerebral ischemia-reperfusion injury(CIRI) refers to a secondary brain injury that can occur when the blood supply to the ischemic brain tissue is restored. However, the mechanism underlying such injury remains elusive.Methods: The 150 male C57 mice underwent middle cerebral artery occlusion(MCAO) for 1 h and reperfusion for 24 h,Among them, 50 MCAO mice were further treated with Mitochondrial division inhibitor 1(Mdivi-1) and 50 MCAO mice were further treated with N-acetylcysteine(NAC). SH-SY5Y cells were cultured in a low-glucose culture medium for 4 h under hypoxic conditions and then transferred to normal conditions for 12 h. Then, cerebral blood flow, mitochondrial structure, mitochondrial DNA(mtDNA) copy number, intracellular and mitochondrial reactive oxygen species(ROS),autophagic flux, aggresome and exosome expression profiles, cardiac tissue structure, mitochondrial length and cristae density, mtDNA and ROS content, as well as the expression of Drp1-Ser616/Drp1, RIP1/RIP3, LC3 II/I, TNF-α,IL-1β, etc., were detected under normal or Drp1 interference conditions.Results: The mtDNA content, ROS levels, and Drp1-Ser616/Drp1 were elevated by 2.2, 1.7 and 2.7 times after CIRI(P<0.05). However, the high cytoplasmic LC3 II/I ratio and increased aggregation of p62 could be reversed by 44%and 88% by Drp1 short hairpin RNA(shRNA)(P<0.05). The low fluorescence intensity of autophagic flux and the increased phosphorylation of RIP3 induced by CIRI could be attenuated by ROS scavenger, NAC(P<0.05). RIP1/RIP3inhibitor Necrostatin-1(Nec-1) restored 75% to a low LC3 II/I ratio and enhanced 2 times to a high RFP-LC3 after Drp1 activation(P<0.05). In addition, although CIRI-induced ROS production caused no considerable accumulation of autophagosomes(P>0.05), it increased the packaging and extracellular secretion of exosomes containing p62 by 4–5 times, which could be decreased by Mdivi-1, Drp1 shRNA, and Nec-1(P<0.05). Furthermore, TNF-α and IL-1βincreased in CIRI-derived exosomes could increase RIP3 phosphorylation in normal or oxygen–glucose deprivation/reoxygenation(OGD/R) conditions(P<0.05).Conclusions: CIRI activated Drp1 and accelerated the p62-mediated formation of autophagosomes while inhibiting the transition of autophagosomes to autolysosomes via the RIP1/RIP3 pathway activation. Undegraded autophagosomes were secreted extracellularly in the form of exosomes, leading to inflammatory cascades that further damaged mitochondria, resulting in excessive ROS generation and the blockage of autophagosome degradation,triggering a vicious cycle.
