Relative reactivities of polyhalofluoroalkanes toward bromophilic or chlorophilic attacks have been evaluated for the first time by comparing the rates of halophilic attacks by a carbanion derived from the addition of...Relative reactivities of polyhalofluoroalkanes toward bromophilic or chlorophilic attacks have been evaluated for the first time by comparing the rates of halophilic attacks by a carbanion derived from the addition of a nucleophile to an olefin with the rate of β-elimination of the same carbanion intermediate. Relative reactivity orders of some polybromofluoroalkanes and polychlorofluoroalkanes are CF_2Br_2>CF_3CFBr_2 ～ CF_2BrCF_2Br>CF_3CBr_3, and CCl_4 > CF_3CCl_3 > CF_2ClCCl_3 > CFCl_3 > CFCl_2CFCl2 ～ CF_2ClCFCl_2. Early transition states for halophilic attacks are speculated.展开更多
It is generally recognized that the formation and accumulation of iron oxides on the surface of zero-valent iron(Fe^(0))resulting in significant decrease of contaminant degradation rates during the long-term reactions...It is generally recognized that the formation and accumulation of iron oxides on the surface of zero-valent iron(Fe^(0))resulting in significant decrease of contaminant degradation rates during the long-term reactions.However,in this study,we found that the removal efficiencies of p-nitrophenol(PNP)by micro zero-valent iron(mFe^(0))could maintain at the satisfactory level in the process of continuous reactions(20 cycles).The removal rate constant(0.1779 min^(-1))of the 5th cycle was 6.74 times higher than that of the 1streaction(0.0264 min^(-1)),even the 20th cycle(0.0371 min^(-1))was higher than that of the 1st reaction.Interestingly,almost no dissolved iron was detected in the solution,and the total iron concentrations decreased dramatically with the process of continuous reactions.The results of scanning electron microscope and energy dispersive spectrometry(SEM-EDS)and X-ray diffraction(XRD)revealed that the structure and composition of corrosion products change from amorphous to highly crystal with the increase of the number of cycles.The corrosion products were mainly magnetite(Fe_(3)O_(4))and a small part of maghemite(γ-Fe_(2)O_(3)),which were in the form of micro sphe res on the surface of mFe^(0).The formation of surface oxidation shell hindered the release of Fe^(2+).X-ray photoelectron spectroscopy(XPS)results illustrated that partial Fe3O_(4) could be converted into y-Fe_(2)O_(3).Electrochemical analysis proved that the electron transfer rate of mFe^(0) increased with the formation of the oxides shell.However,the consumption of iron core and thicker oxide film weakened the electron transfer rate.Besides,the quenching experiments indicated that the reaction activity of mFe^(0) could be enhanced with the addition of scavengers.This study deepened the understanding of the structural transformation and radical production of mFe^(0) in continuous reactions.展开更多
We have generated one possible active site structure of Oxyhemocyanin (Oxy-Hc) and two possible active site structures of Oxytyrosinase (Oxy-Ty) using the EHMO method. Oxy-Hc active site has a plane configuration, whi...We have generated one possible active site structure of Oxyhemocyanin (Oxy-Hc) and two possible active site structures of Oxytyrosinase (Oxy-Ty) using the EHMO method. Oxy-Hc active site has a plane configuration, while Oxy-Ty has boat configuration. When there exist water molecules, two water molecules are connected with the Oxy-Ty active site weakly. Calculations for the reactions of Oxy-Hc and Oxy-Ty (the water-off) with phenol demonstrate that the former reaction is thermodynamically forbidden, while the latter Is realizable.展开更多
Five Shenfu char samples were prepared from Shenfu raw coal at different temperatures （950, 1100, 1200, 1300 and 1400℃） using a muffle furnace. Demineralization of the char samples was performed by treating them wi...Five Shenfu char samples were prepared from Shenfu raw coal at different temperatures （950, 1100, 1200, 1300 and 1400℃） using a muffle furnace. Demineralization of the char samples was performed by treating them with 10% nitric acid for 10 min in a CEM Discover microwave reactor. The gasification of the chars, and corresponding demineralized chars, in a carbon dioxide （CO2） atmosphere was conducted in a Netzsch STA 409Cl31F tempera- ture-programmed thermogravimetry apparatus. The effects of charring temperature and demineralization on the gasification reactivity of chars were systematically investigated. The results show that a char formed at a lower temperature is more reactive except for demineralized char formed at 1100℃, which is less reactive than char formed at 1200℃. Demineralization decreases the char reactivities toward gasification with CO2 to a small extent.展开更多
Considerable efforts have been devoted to characterising the chemical components of vehicle exhaust.However,these components may not accurately reflect the contribution of vehicle exhaust to atmospheric reactivity bec...Considerable efforts have been devoted to characterising the chemical components of vehicle exhaust.However,these components may not accurately reflect the contribution of vehicle exhaust to atmospheric reactivity because of the presence of species not accounted for(“missing species”)given the limitations of analytical instruments.In this study,we improved the laser photolysis–laser-induced fluorescence(LP-LIF)technique and applied it to directly measure the total OH reactivity(TOR)in exhaust gas from light-duty gasoline vehicles in China.The TOR for China Ⅰ to Ⅵ-a vehicles was 15.6,16.3,8.4,2.6,1.5,and 1.6×10^(4) sec^(-1),respectively,reflecting a notable drop as emission standards were upgraded.The TOR was comparable between cold and warm starts.The missing OH reactivity(MOR)values for China Ⅰ to Ⅳ vehicles were close to zero with a cold start but were much higher with a warm start.The variations in oxygenated volatile organic compounds(OVOCs)under different emission standards and for the two start conditions were similar to those of the MOR,indicating that OVOCs and the missing species may have similar production processes.Online measurement revealed that the duration of the stable driving stage was the primary factor leading to the production of OVOCs and missing species.Our findings underscore the importance of direct measurement of TOR from vehicle exhaust and highlight the necessity of adding OVOCs and other organic reactive gases in future upgrades of emission standards,such that the vehicular contribution to atmospheric reactivity can be more effectively controlled.展开更多
Stroke is the leading cause of mortality globally,ultimately leading to severe,lifelong neurological impairments.Patients often suffer from a secondary cascade of damage,including neuroinflammation,cytotoxicity,oxidat...Stroke is the leading cause of mortality globally,ultimately leading to severe,lifelong neurological impairments.Patients often suffer from a secondary cascade of damage,including neuroinflammation,cytotoxicity,oxidative stress,and mitochondrial dysfunction.Regrettably,there is a paucity of clinically available therapeutics to address these issues.Emerging evidence underscores the pivotal roles of astrocytes,the most abundant glial cells in the brain,throughout the various stages of ischemic stroke.In this comprehensive review,we initially provide an overview of the fundamental physiological functions of astrocytes in the brain,emphasizing their critical role in modulating neuronal homeostasis,synaptic activity,and blood-brain barrier integrity.We then delve into the growing body of evidence that highlights the functional diversity and heterogeneity of astrocytes in the context of ischemic stroke.Their well-established contributions to energy provision,metabolic regulation,and neurotransmitter homeostasis,as well as their emerging roles in mitochondrial recovery,neuroinflammation regulation,and oxidative stress modulation following ischemic injury,are discussed in detail.We also explore the cellular and molecular mechanisms underpinning these functions,with particular emphasis on recently identified targets within astrocytes that offer promising prospects for therapeutic intervention.In the final section of this review,we offer a detailed overview of the current therapeutic strategies targeting astrocytes in the treatment of ischemic stroke.These astrocyte-targeting strategies are categorized into traditional small-molecule drugs,microRNAs(miRNAs),stem cell-based therapies,cellular reprogramming,hydrogels,and extracellular vesicles.By summarizing the current understanding of astrocyte functions and therapeutic targeting approaches,we aim to highlight the critical roles of astrocytes during and after stroke,particularly in the pathophysiological development in ischemic stroke.We also emphasize promising avenues for novel,astrocyte-targeted therapeutics that could become clinically available options,ultimately improving outcomes for patients with stroke.展开更多
Ischemia–reperfusion injury is a common pathophysiological mechanism in retinal degeneration.PANoptosis is a newly defined integral form of regulated cell death that combines the key features of pyroptosis,apoptosis,...Ischemia–reperfusion injury is a common pathophysiological mechanism in retinal degeneration.PANoptosis is a newly defined integral form of regulated cell death that combines the key features of pyroptosis,apoptosis,and necroptosis.Oligomerization of mitochondrial voltage-dependent anion channel 1 is an important pathological event in regulating cell death in retinal ischemia–reperfusion injury.However,its role in PANoptosis remains largely unknown.In this study,we demonstrated that voltage-dependent anion channel 1 oligomerization-mediated mitochondrial dysfunction was associated with PANoptosis in retinal ischemia–reperfusion injury.Inhibition of voltage-dependent anion channel 1 oligomerization suppressed mitochondrial dysfunction and PANoptosis in retinal cells subjected to ischemia–reperfusion injury.Mechanistically,mitochondria-derived reactive oxygen species played a central role in the voltagedependent anion channel 1-mediated regulation of PANoptosis by promoting PANoptosome assembly.Moreover,inhibiting voltage-dependent anion channel 1 oligomerization protected against PANoptosis in the retinas of rats subjected to ischemia–reperfusion injury.Overall,our findings reveal the critical role of voltage-dependent anion channel 1 oligomerization in regulating PANoptosis in retinal ischemia–reperfusion injury,highlighting voltage-dependent anion channel 1 as a promising therapeutic target.展开更多
Molten salt reactors,being the only reactor type among Generation Ⅳ advanced nuclear reactors that utilize liquid fuels,offer inherent safety,high-temperature,and low-pressure operation,as well as the capability for ...Molten salt reactors,being the only reactor type among Generation Ⅳ advanced nuclear reactors that utilize liquid fuels,offer inherent safety,high-temperature,and low-pressure operation,as well as the capability for online fuel reprocessing.However,the fuel-salt flow results in the decay of delayed neutron precursors(DNPs)outside the core,causing fluctuations in the effective delayed neutron fraction and consequently impacting the reactor reactivity.Particularly in accident scenarios—such as a combined pump shutdown and the inability to rapidly scram the reactor—the sole reliance on negative temperature feedback may cause a significant increase in core temperature,posing a threat to reactor safety.To address these problems,this paper introduces an innovative design for a passive fluid-driven suspended control rod(SCR)to dynamically compensate for reactivity fluctuations caused by DNPs flowing with the fuel.The control rod operates passively by leveraging the combined effects of gravity,buoyancy,and fluid dynamic forces,thereby eliminating the need for an external drive mechanism and enabling direct integration within the active region of the core.Using a 150 MWt thorium-based molten salt reactor as the reference design,we develop a mathematical model to systematically analyze the effects of key parameters—including the geometric dimensions and density of the SCR—on its performance.We examine its motion characteristics under different core flow conditions and assess its feasibility for the dynamic compensation of reactivity changes caused by fuel flow.The results of this study demonstrate that the SCR can effectively counteract reactivity fluctuations induced by fuel flow within molten salt reactors.A sensitivity analysis reveals that the SCR’s average density exerts a profound impact on its start-up flow threshold,channel flow rate,resistance to fuel density fluctuations,and response characteristics.This underscores the critical need to optimize this parameter.Moreover,by judiciously selecting the SCR’s length,number of deployed units,and the placement we can achieve the necessary reactivity control while maintaining a favorable balance between neutron economy and heat transfer performance.Ultimately,this paper provides an innovative solution for the passive reactivity control in molten salt reactors,offering significant potential for practical engineering applications.展开更多
Spared regions of the damaged central nervous system undergo dynamic remodelling and exhibit a remarkable potential for therapeutic exploitation1.Lesion-remote astrocytes(LRAs),which interact with viable neurons and g...Spared regions of the damaged central nervous system undergo dynamic remodelling and exhibit a remarkable potential for therapeutic exploitation1.Lesion-remote astrocytes(LRAs),which interact with viable neurons and glia,undergo reactive transformations whose molecular and functional properties are poorly understood2.Here,using multiple transcriptional profiling methods,we investigated LRAs from spared regions of mouse spinal cord following traumatic spinal cord injury.展开更多
BACKGROUND Ulcerative colitis(UC)is a chronic and debilitating inflammatory bowel disease.Cumulative evidence indicates that excess hydrogen peroxide,a potent neutrophilic chemotactic agent,produced by colonic epithel...BACKGROUND Ulcerative colitis(UC)is a chronic and debilitating inflammatory bowel disease.Cumulative evidence indicates that excess hydrogen peroxide,a potent neutrophilic chemotactic agent,produced by colonic epithelial cells has a causal role leading to infiltration of neutrophils into the colonic mucosa and subsequent development of UC.This evidence-based mechanism identifies hydrogen peroxide as a therapeutic target for reducing agents in the treatment of UC.CASE SUMMARY Presented is a 41-year-old female with a 26-year history of refractory UC.Having developed steroid dependence and never achieving complete remission on treatment by conventional and advanced therapies,she began treatment with oral R-dihydrolipoic acid(RDLA),a lipid-soluble reducing agent with intracellular site of action.Within a week,rectal bleeding ceased.She was asymptomatic for three years until a highly stressful experience,when she noticed blood in her stool.RDLA was discontinued,and she began treatment with oral sodium thiosulfate pentahydrate(STS),a reducing agent with extracellular site of action.After a week,rectal bleeding ceased,and she resumed oral RDLA and discontinued STS.To date,she remains asymptomatic with normal stool calprotectin while on RDLA.CONCLUSION STS and RDLA are reducing agents that serve as highly effective and safe therapy for the induction and maintenance of remission in UC,even in patients refractory or poorly controlled by conventional and advanced therapies.Should preliminary findings be validated by subsequent clinical trials,the use of reducing agents could potentially prevent thousands of colectomies and represent a paradigm shift in the treatment of UC.展开更多
Modern power systems increasingly depend on interconnected microgrids to enhance reliability and renewable energy utilization.However,the high penetration of intermittent renewable sources often causes frequency devia...Modern power systems increasingly depend on interconnected microgrids to enhance reliability and renewable energy utilization.However,the high penetration of intermittent renewable sources often causes frequency deviations,voltage fluctuations,and poor reactive power coordination,posing serious challenges to grid stability.Conventional Interconnection FlowControllers(IFCs)primarily regulate active power flowand fail to effectively handle dynamic frequency variations or reactive power sharing in multi-microgrid networks.To overcome these limitations,this study proposes an enhanced Interconnection Flow Controller(e-IFC)that integrates frequency response balancing and an Interconnection Reactive Power Flow Controller(IRFC)within a unified adaptive control structure.The proposed e-IFC is implemented and analyzed in DIgSILENT PowerFactory to evaluate its performance under various grid disturbances,including frequency drops,load changes,and reactive power fluctuations.Simulation results reveal that the e-IFC achieves 27.4% higher active power sharing accuracy,19.6% lower reactive power deviation,and 18.2% improved frequency stability compared to the conventional IFC.The adaptive controller ensures seamless transitions between grid-connected and islanded modes and maintains stable operation even under communication delays and data noise.Overall,the proposed e-IFCsignificantly enhances active-reactive power coordination and dynamic stability in renewable-integrated multi-microgrid systems.Future research will focus on coupling the e-IFC with tertiary-level optimization frameworks and conducting hardware-in-the-loop validation to enable its application in large-scale smart microgrid environments.展开更多
Background:Hepatocellular carcinoma(HCC)is one of the leading causes of cancer-related mortality worldwide.This study aimed to identify key genes involved in HCC development and elucidate their molecular mechanisms,wi...Background:Hepatocellular carcinoma(HCC)is one of the leading causes of cancer-related mortality worldwide.This study aimed to identify key genes involved in HCC development and elucidate their molecular mechanisms,with a particular focus on mitochondrial function and apoptosis.Methods:Differential expression analyses were performed across three datasets—The Cancer Genome Atlas(TCGA)-Liver Hepatocellular Carcinoma(LIHC),GSE36076,and GSE95698—to identify overlapping differentially expressed genes(DEGs).A prognostic risk model was then constructed.Cysteine/serine-rich nuclear protein 1(CSRNP1)expression levels in HCC cell lines were assessed via western blot(WB)and quantitative reverse transcription polymerase chain reaction(qRT-PCR).The effects of CSRNP1 knockdown or overexpression on cell proliferation,migration,and apoptosis were evaluated using cell counting-8(CCK-8)assays,Transwell assays,and flow cytometry.Mitochondrial ultrastructure was examined by transmission electron microscopy,and intracellular and mitochondrial reactive oxygen species(mROS)levels were measured using specific fluorescent probes.WB was used to assess activation of the c-Jun N-terminal kinase(JNK)/p38 mitogen-activated protein kinase(MAPK)pathway,and pathway dependence was examined using the ROS scavenger N-Acetylcysteine(NAC)and the JNK inhibitor SP600125.Results:A six-gene prognostic model was established,comprising downregulated genes(NR4A1 and CSRNP1)and upregulated genes(CENPQ,YAE1,FANCF,and POC5)in HCC.Functional experiments revealed that CSRNP1 knockdown promoted the proliferation of HCC cells and suppressed their apoptosis.Conversely,CSRNP1 overexpression impaired mitochondrial integrity,increased both mitochondrial and cytoplasmic ROS levels,and activated the JNK/p38 MAPK pathway.Notably,treatment with NAC or SP600125 attenuated CSRNP1-induced MAPK activation and apoptosis.Conclusion:CSRNP1 is a novel prognostic biomarker and tumor suppressor in HCC.It exerts anti-tumor effects by inducing oxidative stress and activating the JNK/p38 MAPK pathway in a ROS-dependent manner.These findings suggest that CSRNP1 may serve as a potential therapeutic target in the management of HCC.展开更多
Condensation of methyl 7-methylcoumarin-4-acetate(2)with primary amines and with an- thranilic acid gave 7-methyl-2-oxo-N-aryl-2H-[1]-benzopyran-4--acetamide(4a—d)and(7),respectively. Compound 7 underwent cyclization...Condensation of methyl 7-methylcoumarin-4-acetate(2)with primary amines and with an- thranilic acid gave 7-methyl-2-oxo-N-aryl-2H-[1]-benzopyran-4--acetamide(4a—d)and(7),respectively. Compound 7 underwent cyclization to give 2-(7-methyl-2-oxo-2H-[1]-benzopyran-4-yl)-methyl-4H-3,1- benzoxazin-4-one(3).The reaction of 3 with aromatic amines gave the corresponding quinazolone derivatives 5 which tautomerises to the thermodynamically more stable isomer 6,whereas its reaction with Grignard reagents and aromatic aldehydes gave 8a,8b,and 9a,9b,respectively.展开更多
The reduced form of the nicotinamide-adenine dinucleotide coenzyme(NAD(P)H)plays an important role in many bio-reductions by transferring a hydride ion or an electronto the surrounding substrate(see eq.(1),R represent...The reduced form of the nicotinamide-adenine dinucleotide coenzyme(NAD(P)H)plays an important role in many bio-reductions by transferring a hydride ion or an electronto the surrounding substrate(see eq.(1),R represents adenine dinucleotide).展开更多
The pathophysiology of Huntington's disease involves high levels of the neurotoxin quinolinic acid. Quinolinic acid accumulation results in oxidative stress, which leads to neurotoxicity. However, the molecular an...The pathophysiology of Huntington's disease involves high levels of the neurotoxin quinolinic acid. Quinolinic acid accumulation results in oxidative stress, which leads to neurotoxicity. However, the molecular and cellular mechanisms by which quinolinic acid contributes to Huntington's disease pathology remain unknown. In this study, we established in vitro and in vivo models of Huntington's disease by administering quinolinic acid to the PC12 neuronal cell line and the striatum of mice, respectively. We observed a decrease in the levels of hydrogen sulfide in both PC12 cells and mouse serum, which was accompanied by down-regulation of cystathionine β-synthase, an enzyme responsible for hydrogen sulfide production. However, treatment with NaHS(a hydrogen sulfide donor) increased hydrogen sulfide levels in the neurons and in mouse serum, as well as cystathionine β-synthase expression in the neurons and the mouse striatum, while also improving oxidative imbalance and mitochondrial dysfunction in PC12 cells and the mouse striatum. These beneficial effects correlated with upregulation of nuclear factor erythroid 2-related factor 2 expression. Finally, treatment with the nuclear factor erythroid 2-related factor 2inhibitor ML385 reversed the beneficial impact of exogenous hydrogen sulfide on quinolinic acid-induced oxidative stress. Taken together, our findings show that hydrogen sulfide reduces oxidative stress in Huntington's disease by activating nuclear factor erythroid 2-related factor 2,suggesting that hydrogen sulfide is a novel neuroprotective drug candidate for treating patients with Huntington's disease.展开更多
Cardiac arrest can lead to severe neurological impairment as a result of inflammation,mitochondrial dysfunction,and post-cardiopulmonary resuscitation neurological damage.Hypoxic preconditioning has been shown to impr...Cardiac arrest can lead to severe neurological impairment as a result of inflammation,mitochondrial dysfunction,and post-cardiopulmonary resuscitation neurological damage.Hypoxic preconditioning has been shown to improve migration and survival of bone marrow–derived mesenchymal stem cells and reduce pyroptosis after cardiac arrest,but the specific mechanisms by which hypoxia-preconditioned bone marrow–derived mesenchymal stem cells protect against brain injury after cardiac arrest are unknown.To this end,we established an in vitro co-culture model of bone marrow–derived mesenchymal stem cells and oxygen–glucose deprived primary neurons and found that hypoxic preconditioning enhanced the protective effect of bone marrow stromal stem cells against neuronal pyroptosis,possibly through inhibition of the MAPK and nuclear factor κB pathways.Subsequently,we transplanted hypoxia-preconditioned bone marrow–derived mesenchymal stem cells into the lateral ventricle after the return of spontaneous circulation in an 8-minute cardiac arrest rat model induced by asphyxia.The results showed that hypoxia-preconditioned bone marrow–derived mesenchymal stem cells significantly reduced cardiac arrest–induced neuronal pyroptosis,oxidative stress,and mitochondrial damage,whereas knockdown of the liver isoform of phosphofructokinase in bone marrow–derived mesenchymal stem cells inhibited these effects.To conclude,hypoxia-preconditioned bone marrow–derived mesenchymal stem cells offer a promising therapeutic approach for neuronal injury following cardiac arrest,and their beneficial effects are potentially associated with increased expression of the liver isoform of phosphofructokinase following hypoxic preconditioning.展开更多
Astrocytes are the most abundant type of glial cell in the central nervous system.Upon injury and inflammation,astrocytes become reactive and undergo morphological and functional changes.Depending on their phenotypic ...Astrocytes are the most abundant type of glial cell in the central nervous system.Upon injury and inflammation,astrocytes become reactive and undergo morphological and functional changes.Depending on their phenotypic classification as A1 or A2,reactive astrocytes contribute to both neurotoxic and neuroprotective responses,respectively.However,this binary classification does not fully capture the diversity of astrocyte responses observed across different diseases and injuries.Transcriptomic analysis has revealed that reactive astrocytes have a complex landscape of gene expression profiles,which emphasizes the heterogeneous nature of their reactivity.Astrocytes actively participate in regulating central nervous system inflammation by interacting with microglia and other cell types,releasing cytokines,and influencing the immune response.The phosphoinositide 3-kinase(PI3K)/protein kinase B(AKT)signaling pathway is a central player in astrocyte reactivity and impacts various aspects of astrocyte behavior,as evidenced by in silico,in vitro,and in vivo results.In astrocytes,inflammatory cues trigger a cascade of molecular events,where nuclear factor-κB serves as a central mediator of the pro-inflammatory responses.Here,we review the heterogeneity of reactive astrocytes and the molecular mechanisms underlying their activation.We highlight the involvement of various signaling pathways that regulate astrocyte reactivity,including the PI3K/AKT/mammalian target of rapamycin(mTOR),αvβ3 integrin/PI3K/AKT/connexin 43,and Notch/PI3K/AKT pathways.While targeting the inactivation of the PI3K/AKT cellular signaling pathway to control reactive astrocytes and prevent central nervous system damage,evidence suggests that activating this pathway could also yield beneficial outcomes.This dual function of the PI3K/AKT pathway underscores its complexity in astrocyte reactivity and brain function modulation.The review emphasizes the importance of employing astrocyte-exclusive models to understand their functions accurately and these models are essential for clarifying astrocyte behavior.The findings should then be validated using in vivo models to ensure real-life relevance.The review also highlights the significance of PI3K/AKT pathway modulation in preventing central nervous system damage,although further studies are required to fully comprehend its role due to varying factors such as different cell types,astrocyte responses to inflammation,and disease contexts.Specific strategies are clearly necessary to address these variables effectively.展开更多
Nitric oxide(NO)is a gaseous molecule produced by 3 different NO synthase(NOS)isoforms:Neural/brain NOS(nNOS/bNOS,type 1),endothelial NOS(eNOS,type 3)and inducible NOS(type 2).Type 1 and 3 NOS are constitutively expre...Nitric oxide(NO)is a gaseous molecule produced by 3 different NO synthase(NOS)isoforms:Neural/brain NOS(nNOS/bNOS,type 1),endothelial NOS(eNOS,type 3)and inducible NOS(type 2).Type 1 and 3 NOS are constitutively expressed.NO can serve different purposes:As a vasoactive molecule,as a neurotransmitter or as an immunomodulator.It plays a key role in cerebral ischemia/reperfusion injury(CIRI).Hypoxic episodes simulate the production of oxygen free radicals,leading to mitochondrial and phospholipid damage.Upon reperfusion,increased levels of oxygen trigger oxide synthases;whose products are associated with neuronal damage by promoting lipid peroxidation,nitrosylation and excitotoxicity.Molecular pathways in CIRI can be altered by NOS.Neuroprotective effects are observed with eNOS activity.While nNOS interplay is prone to endothelial inflammation,oxidative stress and apoptosis.Therefore,nNOS appears to be detrimental.The interaction between NO and other free radicals develops peroxynitrite;which is a cytotoxic agent.It plays a main role in the likelihood of hemorrhagic events by tissue plasminogen activator(t-PA).Peroxynitrite scavengers are currently being studied as potential targets to prevent hemorrhagic transformation in CIRI.展开更多
文摘Relative reactivities of polyhalofluoroalkanes toward bromophilic or chlorophilic attacks have been evaluated for the first time by comparing the rates of halophilic attacks by a carbanion derived from the addition of a nucleophile to an olefin with the rate of β-elimination of the same carbanion intermediate. Relative reactivity orders of some polybromofluoroalkanes and polychlorofluoroalkanes are CF_2Br_2>CF_3CFBr_2 ～ CF_2BrCF_2Br>CF_3CBr_3, and CCl_4 > CF_3CCl_3 > CF_2ClCCl_3 > CFCl_3 > CFCl_2CFCl2 ～ CF_2ClCFCl_2. Early transition states for halophilic attacks are speculated.
基金the financial support from China Postdoctoral Science Foundation(No.2019T120843)Sichuan Science and Technology Program(No.2019YJ0091)。
文摘It is generally recognized that the formation and accumulation of iron oxides on the surface of zero-valent iron(Fe^(0))resulting in significant decrease of contaminant degradation rates during the long-term reactions.However,in this study,we found that the removal efficiencies of p-nitrophenol(PNP)by micro zero-valent iron(mFe^(0))could maintain at the satisfactory level in the process of continuous reactions(20 cycles).The removal rate constant(0.1779 min^(-1))of the 5th cycle was 6.74 times higher than that of the 1streaction(0.0264 min^(-1)),even the 20th cycle(0.0371 min^(-1))was higher than that of the 1st reaction.Interestingly,almost no dissolved iron was detected in the solution,and the total iron concentrations decreased dramatically with the process of continuous reactions.The results of scanning electron microscope and energy dispersive spectrometry(SEM-EDS)and X-ray diffraction(XRD)revealed that the structure and composition of corrosion products change from amorphous to highly crystal with the increase of the number of cycles.The corrosion products were mainly magnetite(Fe_(3)O_(4))and a small part of maghemite(γ-Fe_(2)O_(3)),which were in the form of micro sphe res on the surface of mFe^(0).The formation of surface oxidation shell hindered the release of Fe^(2+).X-ray photoelectron spectroscopy(XPS)results illustrated that partial Fe3O_(4) could be converted into y-Fe_(2)O_(3).Electrochemical analysis proved that the electron transfer rate of mFe^(0) increased with the formation of the oxides shell.However,the consumption of iron core and thicker oxide film weakened the electron transfer rate.Besides,the quenching experiments indicated that the reaction activity of mFe^(0) could be enhanced with the addition of scavengers.This study deepened the understanding of the structural transformation and radical production of mFe^(0) in continuous reactions.
文摘We have generated one possible active site structure of Oxyhemocyanin (Oxy-Hc) and two possible active site structures of Oxytyrosinase (Oxy-Ty) using the EHMO method. Oxy-Hc active site has a plane configuration, while Oxy-Ty has boat configuration. When there exist water molecules, two water molecules are connected with the Oxy-Ty active site weakly. Calculations for the reactions of Oxy-Hc and Oxy-Ty (the water-off) with phenol demonstrate that the former reaction is thermodynamically forbidden, while the latter Is realizable.
基金Projects 2004CB217704 supported by the Special Fund for Major State Basic Research Project, 104031 by the Key Project of Chinese Ministry of Education JHB05-33 by the Program of the Universities in Jiangsu Province for Development of High-Tech Industries
文摘Five Shenfu char samples were prepared from Shenfu raw coal at different temperatures （950, 1100, 1200, 1300 and 1400℃） using a muffle furnace. Demineralization of the char samples was performed by treating them with 10% nitric acid for 10 min in a CEM Discover microwave reactor. The gasification of the chars, and corresponding demineralized chars, in a carbon dioxide （CO2） atmosphere was conducted in a Netzsch STA 409Cl31F tempera- ture-programmed thermogravimetry apparatus. The effects of charring temperature and demineralization on the gasification reactivity of chars were systematically investigated. The results show that a char formed at a lower temperature is more reactive except for demineralized char formed at 1100℃, which is less reactive than char formed at 1200℃. Demineralization decreases the char reactivities toward gasification with CO2 to a small extent.
基金supported by the National Natural Science Foundation of China(Nos.91644221 and 41627809)the National Key Research and Development Program of China(Nos.2016YFC0202201 and 2018YFC0213904)the Key-Area Research and Development Program of Guangdong Province(No.2019B110206001).
文摘Considerable efforts have been devoted to characterising the chemical components of vehicle exhaust.However,these components may not accurately reflect the contribution of vehicle exhaust to atmospheric reactivity because of the presence of species not accounted for(“missing species”)given the limitations of analytical instruments.In this study,we improved the laser photolysis–laser-induced fluorescence(LP-LIF)technique and applied it to directly measure the total OH reactivity(TOR)in exhaust gas from light-duty gasoline vehicles in China.The TOR for China Ⅰ to Ⅵ-a vehicles was 15.6,16.3,8.4,2.6,1.5,and 1.6×10^(4) sec^(-1),respectively,reflecting a notable drop as emission standards were upgraded.The TOR was comparable between cold and warm starts.The missing OH reactivity(MOR)values for China Ⅰ to Ⅳ vehicles were close to zero with a cold start but were much higher with a warm start.The variations in oxygenated volatile organic compounds(OVOCs)under different emission standards and for the two start conditions were similar to those of the MOR,indicating that OVOCs and the missing species may have similar production processes.Online measurement revealed that the duration of the stable driving stage was the primary factor leading to the production of OVOCs and missing species.Our findings underscore the importance of direct measurement of TOR from vehicle exhaust and highlight the necessity of adding OVOCs and other organic reactive gases in future upgrades of emission standards,such that the vehicular contribution to atmospheric reactivity can be more effectively controlled.
基金supported by the National Natural Science Foundation of China,No.82001325Visiting Scholar Foundation of Shandong Province,No.20236-01(both to CS).
文摘Stroke is the leading cause of mortality globally,ultimately leading to severe,lifelong neurological impairments.Patients often suffer from a secondary cascade of damage,including neuroinflammation,cytotoxicity,oxidative stress,and mitochondrial dysfunction.Regrettably,there is a paucity of clinically available therapeutics to address these issues.Emerging evidence underscores the pivotal roles of astrocytes,the most abundant glial cells in the brain,throughout the various stages of ischemic stroke.In this comprehensive review,we initially provide an overview of the fundamental physiological functions of astrocytes in the brain,emphasizing their critical role in modulating neuronal homeostasis,synaptic activity,and blood-brain barrier integrity.We then delve into the growing body of evidence that highlights the functional diversity and heterogeneity of astrocytes in the context of ischemic stroke.Their well-established contributions to energy provision,metabolic regulation,and neurotransmitter homeostasis,as well as their emerging roles in mitochondrial recovery,neuroinflammation regulation,and oxidative stress modulation following ischemic injury,are discussed in detail.We also explore the cellular and molecular mechanisms underpinning these functions,with particular emphasis on recently identified targets within astrocytes that offer promising prospects for therapeutic intervention.In the final section of this review,we offer a detailed overview of the current therapeutic strategies targeting astrocytes in the treatment of ischemic stroke.These astrocyte-targeting strategies are categorized into traditional small-molecule drugs,microRNAs(miRNAs),stem cell-based therapies,cellular reprogramming,hydrogels,and extracellular vesicles.By summarizing the current understanding of astrocyte functions and therapeutic targeting approaches,we aim to highlight the critical roles of astrocytes during and after stroke,particularly in the pathophysiological development in ischemic stroke.We also emphasize promising avenues for novel,astrocyte-targeted therapeutics that could become clinically available options,ultimately improving outcomes for patients with stroke.
基金supported by the National Natural Science Foundation of China,Nos.82172196(to KX),82372507(to KX)the Natural Science Foundation of Hunan Province,China,No.2023JJ40804(to QZ)the Key Laboratory of Emergency and Trauma(Hainan Medical University)of the Ministry of Education,China,No.KLET-202210(to QZ)。
文摘Ischemia–reperfusion injury is a common pathophysiological mechanism in retinal degeneration.PANoptosis is a newly defined integral form of regulated cell death that combines the key features of pyroptosis,apoptosis,and necroptosis.Oligomerization of mitochondrial voltage-dependent anion channel 1 is an important pathological event in regulating cell death in retinal ischemia–reperfusion injury.However,its role in PANoptosis remains largely unknown.In this study,we demonstrated that voltage-dependent anion channel 1 oligomerization-mediated mitochondrial dysfunction was associated with PANoptosis in retinal ischemia–reperfusion injury.Inhibition of voltage-dependent anion channel 1 oligomerization suppressed mitochondrial dysfunction and PANoptosis in retinal cells subjected to ischemia–reperfusion injury.Mechanistically,mitochondria-derived reactive oxygen species played a central role in the voltagedependent anion channel 1-mediated regulation of PANoptosis by promoting PANoptosome assembly.Moreover,inhibiting voltage-dependent anion channel 1 oligomerization protected against PANoptosis in the retinas of rats subjected to ischemia–reperfusion injury.Overall,our findings reveal the critical role of voltage-dependent anion channel 1 oligomerization in regulating PANoptosis in retinal ischemia–reperfusion injury,highlighting voltage-dependent anion channel 1 as a promising therapeutic target.
基金supported by Youth Innovation Promotion Association of Chinese Academy of Sciences(No.2020261)Strategic Priority Research Program of Chinese Academy of Sciences(No.XDA02010000)the Young Potential Program of Shanghai Institute of Applied Physics,Chinese Academy of Sciences(No.SINAP-YXJH-202412).
文摘Molten salt reactors,being the only reactor type among Generation Ⅳ advanced nuclear reactors that utilize liquid fuels,offer inherent safety,high-temperature,and low-pressure operation,as well as the capability for online fuel reprocessing.However,the fuel-salt flow results in the decay of delayed neutron precursors(DNPs)outside the core,causing fluctuations in the effective delayed neutron fraction and consequently impacting the reactor reactivity.Particularly in accident scenarios—such as a combined pump shutdown and the inability to rapidly scram the reactor—the sole reliance on negative temperature feedback may cause a significant increase in core temperature,posing a threat to reactor safety.To address these problems,this paper introduces an innovative design for a passive fluid-driven suspended control rod(SCR)to dynamically compensate for reactivity fluctuations caused by DNPs flowing with the fuel.The control rod operates passively by leveraging the combined effects of gravity,buoyancy,and fluid dynamic forces,thereby eliminating the need for an external drive mechanism and enabling direct integration within the active region of the core.Using a 150 MWt thorium-based molten salt reactor as the reference design,we develop a mathematical model to systematically analyze the effects of key parameters—including the geometric dimensions and density of the SCR—on its performance.We examine its motion characteristics under different core flow conditions and assess its feasibility for the dynamic compensation of reactivity changes caused by fuel flow.The results of this study demonstrate that the SCR can effectively counteract reactivity fluctuations induced by fuel flow within molten salt reactors.A sensitivity analysis reveals that the SCR’s average density exerts a profound impact on its start-up flow threshold,channel flow rate,resistance to fuel density fluctuations,and response characteristics.This underscores the critical need to optimize this parameter.Moreover,by judiciously selecting the SCR’s length,number of deployed units,and the placement we can achieve the necessary reactivity control while maintaining a favorable balance between neutron economy and heat transfer performance.Ultimately,this paper provides an innovative solution for the passive reactivity control in molten salt reactors,offering significant potential for practical engineering applications.
文摘Spared regions of the damaged central nervous system undergo dynamic remodelling and exhibit a remarkable potential for therapeutic exploitation1.Lesion-remote astrocytes(LRAs),which interact with viable neurons and glia,undergo reactive transformations whose molecular and functional properties are poorly understood2.Here,using multiple transcriptional profiling methods,we investigated LRAs from spared regions of mouse spinal cord following traumatic spinal cord injury.
文摘BACKGROUND Ulcerative colitis(UC)is a chronic and debilitating inflammatory bowel disease.Cumulative evidence indicates that excess hydrogen peroxide,a potent neutrophilic chemotactic agent,produced by colonic epithelial cells has a causal role leading to infiltration of neutrophils into the colonic mucosa and subsequent development of UC.This evidence-based mechanism identifies hydrogen peroxide as a therapeutic target for reducing agents in the treatment of UC.CASE SUMMARY Presented is a 41-year-old female with a 26-year history of refractory UC.Having developed steroid dependence and never achieving complete remission on treatment by conventional and advanced therapies,she began treatment with oral R-dihydrolipoic acid(RDLA),a lipid-soluble reducing agent with intracellular site of action.Within a week,rectal bleeding ceased.She was asymptomatic for three years until a highly stressful experience,when she noticed blood in her stool.RDLA was discontinued,and she began treatment with oral sodium thiosulfate pentahydrate(STS),a reducing agent with extracellular site of action.After a week,rectal bleeding ceased,and she resumed oral RDLA and discontinued STS.To date,she remains asymptomatic with normal stool calprotectin while on RDLA.CONCLUSION STS and RDLA are reducing agents that serve as highly effective and safe therapy for the induction and maintenance of remission in UC,even in patients refractory or poorly controlled by conventional and advanced therapies.Should preliminary findings be validated by subsequent clinical trials,the use of reducing agents could potentially prevent thousands of colectomies and represent a paradigm shift in the treatment of UC.
基金the Deanship of Scientific Research at Northern Border University,Arar,Saudi Arabia,for funding this research work through the project number“NBU-FFR-2025-3623-11”.
文摘Modern power systems increasingly depend on interconnected microgrids to enhance reliability and renewable energy utilization.However,the high penetration of intermittent renewable sources often causes frequency deviations,voltage fluctuations,and poor reactive power coordination,posing serious challenges to grid stability.Conventional Interconnection FlowControllers(IFCs)primarily regulate active power flowand fail to effectively handle dynamic frequency variations or reactive power sharing in multi-microgrid networks.To overcome these limitations,this study proposes an enhanced Interconnection Flow Controller(e-IFC)that integrates frequency response balancing and an Interconnection Reactive Power Flow Controller(IRFC)within a unified adaptive control structure.The proposed e-IFC is implemented and analyzed in DIgSILENT PowerFactory to evaluate its performance under various grid disturbances,including frequency drops,load changes,and reactive power fluctuations.Simulation results reveal that the e-IFC achieves 27.4% higher active power sharing accuracy,19.6% lower reactive power deviation,and 18.2% improved frequency stability compared to the conventional IFC.The adaptive controller ensures seamless transitions between grid-connected and islanded modes and maintains stable operation even under communication delays and data noise.Overall,the proposed e-IFCsignificantly enhances active-reactive power coordination and dynamic stability in renewable-integrated multi-microgrid systems.Future research will focus on coupling the e-IFC with tertiary-level optimization frameworks and conducting hardware-in-the-loop validation to enable its application in large-scale smart microgrid environments.
基金funded by Shanghai Yangpu District Science and Technology Commission(Grant No.YPQ202303(Xuejing Lin))Shanghai Yangpu Hospital Foundation(Grant No.Se1202420(Wenchao Wang)and Ye1202423(Juan Huang)).
文摘Background:Hepatocellular carcinoma(HCC)is one of the leading causes of cancer-related mortality worldwide.This study aimed to identify key genes involved in HCC development and elucidate their molecular mechanisms,with a particular focus on mitochondrial function and apoptosis.Methods:Differential expression analyses were performed across three datasets—The Cancer Genome Atlas(TCGA)-Liver Hepatocellular Carcinoma(LIHC),GSE36076,and GSE95698—to identify overlapping differentially expressed genes(DEGs).A prognostic risk model was then constructed.Cysteine/serine-rich nuclear protein 1(CSRNP1)expression levels in HCC cell lines were assessed via western blot(WB)and quantitative reverse transcription polymerase chain reaction(qRT-PCR).The effects of CSRNP1 knockdown or overexpression on cell proliferation,migration,and apoptosis were evaluated using cell counting-8(CCK-8)assays,Transwell assays,and flow cytometry.Mitochondrial ultrastructure was examined by transmission electron microscopy,and intracellular and mitochondrial reactive oxygen species(mROS)levels were measured using specific fluorescent probes.WB was used to assess activation of the c-Jun N-terminal kinase(JNK)/p38 mitogen-activated protein kinase(MAPK)pathway,and pathway dependence was examined using the ROS scavenger N-Acetylcysteine(NAC)and the JNK inhibitor SP600125.Results:A six-gene prognostic model was established,comprising downregulated genes(NR4A1 and CSRNP1)and upregulated genes(CENPQ,YAE1,FANCF,and POC5)in HCC.Functional experiments revealed that CSRNP1 knockdown promoted the proliferation of HCC cells and suppressed their apoptosis.Conversely,CSRNP1 overexpression impaired mitochondrial integrity,increased both mitochondrial and cytoplasmic ROS levels,and activated the JNK/p38 MAPK pathway.Notably,treatment with NAC or SP600125 attenuated CSRNP1-induced MAPK activation and apoptosis.Conclusion:CSRNP1 is a novel prognostic biomarker and tumor suppressor in HCC.It exerts anti-tumor effects by inducing oxidative stress and activating the JNK/p38 MAPK pathway in a ROS-dependent manner.These findings suggest that CSRNP1 may serve as a potential therapeutic target in the management of HCC.
文摘Condensation of methyl 7-methylcoumarin-4-acetate(2)with primary amines and with an- thranilic acid gave 7-methyl-2-oxo-N-aryl-2H-[1]-benzopyran-4--acetamide(4a—d)and(7),respectively. Compound 7 underwent cyclization to give 2-(7-methyl-2-oxo-2H-[1]-benzopyran-4-yl)-methyl-4H-3,1- benzoxazin-4-one(3).The reaction of 3 with aromatic amines gave the corresponding quinazolone derivatives 5 which tautomerises to the thermodynamically more stable isomer 6,whereas its reaction with Grignard reagents and aromatic aldehydes gave 8a,8b,and 9a,9b,respectively.
文摘The reduced form of the nicotinamide-adenine dinucleotide coenzyme(NAD(P)H)plays an important role in many bio-reductions by transferring a hydride ion or an electronto the surrounding substrate(see eq.(1),R represents adenine dinucleotide).
基金supported by the National Natural Science Foundation of China,Nos.82271327 (to ZW),82072535 (to ZW),81873768 (to ZW),and 82001253 (to TL)。
文摘The pathophysiology of Huntington's disease involves high levels of the neurotoxin quinolinic acid. Quinolinic acid accumulation results in oxidative stress, which leads to neurotoxicity. However, the molecular and cellular mechanisms by which quinolinic acid contributes to Huntington's disease pathology remain unknown. In this study, we established in vitro and in vivo models of Huntington's disease by administering quinolinic acid to the PC12 neuronal cell line and the striatum of mice, respectively. We observed a decrease in the levels of hydrogen sulfide in both PC12 cells and mouse serum, which was accompanied by down-regulation of cystathionine β-synthase, an enzyme responsible for hydrogen sulfide production. However, treatment with NaHS(a hydrogen sulfide donor) increased hydrogen sulfide levels in the neurons and in mouse serum, as well as cystathionine β-synthase expression in the neurons and the mouse striatum, while also improving oxidative imbalance and mitochondrial dysfunction in PC12 cells and the mouse striatum. These beneficial effects correlated with upregulation of nuclear factor erythroid 2-related factor 2 expression. Finally, treatment with the nuclear factor erythroid 2-related factor 2inhibitor ML385 reversed the beneficial impact of exogenous hydrogen sulfide on quinolinic acid-induced oxidative stress. Taken together, our findings show that hydrogen sulfide reduces oxidative stress in Huntington's disease by activating nuclear factor erythroid 2-related factor 2,suggesting that hydrogen sulfide is a novel neuroprotective drug candidate for treating patients with Huntington's disease.
基金supported by the Natural Science Fund of Fujian Province,No.2020J011058(to JK)the Project of Fujian Provincial Hospital for High-level Hospital Construction,No.2020HSJJ12(to JK)+1 种基金the Fujian Provincial Finance Department Special Fund,No.(2021)848(to FC)the Fujian Provincial Major Scientific and Technological Special Projects on Health,No.2022ZD01008(to FC).
文摘Cardiac arrest can lead to severe neurological impairment as a result of inflammation,mitochondrial dysfunction,and post-cardiopulmonary resuscitation neurological damage.Hypoxic preconditioning has been shown to improve migration and survival of bone marrow–derived mesenchymal stem cells and reduce pyroptosis after cardiac arrest,but the specific mechanisms by which hypoxia-preconditioned bone marrow–derived mesenchymal stem cells protect against brain injury after cardiac arrest are unknown.To this end,we established an in vitro co-culture model of bone marrow–derived mesenchymal stem cells and oxygen–glucose deprived primary neurons and found that hypoxic preconditioning enhanced the protective effect of bone marrow stromal stem cells against neuronal pyroptosis,possibly through inhibition of the MAPK and nuclear factor κB pathways.Subsequently,we transplanted hypoxia-preconditioned bone marrow–derived mesenchymal stem cells into the lateral ventricle after the return of spontaneous circulation in an 8-minute cardiac arrest rat model induced by asphyxia.The results showed that hypoxia-preconditioned bone marrow–derived mesenchymal stem cells significantly reduced cardiac arrest–induced neuronal pyroptosis,oxidative stress,and mitochondrial damage,whereas knockdown of the liver isoform of phosphofructokinase in bone marrow–derived mesenchymal stem cells inhibited these effects.To conclude,hypoxia-preconditioned bone marrow–derived mesenchymal stem cells offer a promising therapeutic approach for neuronal injury following cardiac arrest,and their beneficial effects are potentially associated with increased expression of the liver isoform of phosphofructokinase following hypoxic preconditioning.
基金supported by Fondo Nacional de Desarrollo Científico y Tecnológico(FONDECYT)#1200836,#1210644,and#1240888,and Agencia Nacional de Investigación y Desarrollo(ANID)-FONDAP#15130011(to LL)FONDECYT#3230227(to MFG).
文摘Astrocytes are the most abundant type of glial cell in the central nervous system.Upon injury and inflammation,astrocytes become reactive and undergo morphological and functional changes.Depending on their phenotypic classification as A1 or A2,reactive astrocytes contribute to both neurotoxic and neuroprotective responses,respectively.However,this binary classification does not fully capture the diversity of astrocyte responses observed across different diseases and injuries.Transcriptomic analysis has revealed that reactive astrocytes have a complex landscape of gene expression profiles,which emphasizes the heterogeneous nature of their reactivity.Astrocytes actively participate in regulating central nervous system inflammation by interacting with microglia and other cell types,releasing cytokines,and influencing the immune response.The phosphoinositide 3-kinase(PI3K)/protein kinase B(AKT)signaling pathway is a central player in astrocyte reactivity and impacts various aspects of astrocyte behavior,as evidenced by in silico,in vitro,and in vivo results.In astrocytes,inflammatory cues trigger a cascade of molecular events,where nuclear factor-κB serves as a central mediator of the pro-inflammatory responses.Here,we review the heterogeneity of reactive astrocytes and the molecular mechanisms underlying their activation.We highlight the involvement of various signaling pathways that regulate astrocyte reactivity,including the PI3K/AKT/mammalian target of rapamycin(mTOR),αvβ3 integrin/PI3K/AKT/connexin 43,and Notch/PI3K/AKT pathways.While targeting the inactivation of the PI3K/AKT cellular signaling pathway to control reactive astrocytes and prevent central nervous system damage,evidence suggests that activating this pathway could also yield beneficial outcomes.This dual function of the PI3K/AKT pathway underscores its complexity in astrocyte reactivity and brain function modulation.The review emphasizes the importance of employing astrocyte-exclusive models to understand their functions accurately and these models are essential for clarifying astrocyte behavior.The findings should then be validated using in vivo models to ensure real-life relevance.The review also highlights the significance of PI3K/AKT pathway modulation in preventing central nervous system damage,although further studies are required to fully comprehend its role due to varying factors such as different cell types,astrocyte responses to inflammation,and disease contexts.Specific strategies are clearly necessary to address these variables effectively.
文摘Nitric oxide(NO)is a gaseous molecule produced by 3 different NO synthase(NOS)isoforms:Neural/brain NOS(nNOS/bNOS,type 1),endothelial NOS(eNOS,type 3)and inducible NOS(type 2).Type 1 and 3 NOS are constitutively expressed.NO can serve different purposes:As a vasoactive molecule,as a neurotransmitter or as an immunomodulator.It plays a key role in cerebral ischemia/reperfusion injury(CIRI).Hypoxic episodes simulate the production of oxygen free radicals,leading to mitochondrial and phospholipid damage.Upon reperfusion,increased levels of oxygen trigger oxide synthases;whose products are associated with neuronal damage by promoting lipid peroxidation,nitrosylation and excitotoxicity.Molecular pathways in CIRI can be altered by NOS.Neuroprotective effects are observed with eNOS activity.While nNOS interplay is prone to endothelial inflammation,oxidative stress and apoptosis.Therefore,nNOS appears to be detrimental.The interaction between NO and other free radicals develops peroxynitrite;which is a cytotoxic agent.It plays a main role in the likelihood of hemorrhagic events by tissue plasminogen activator(t-PA).Peroxynitrite scavengers are currently being studied as potential targets to prevent hemorrhagic transformation in CIRI.
