OLAND(oxygen limited autotrophic nitrification and denitrification) nitrogen removal system was constructed by coupling with oxygen limited nitritation stage and anaerobic ammonium oxidation stage. Ammonia oxidizer, a...OLAND(oxygen limited autotrophic nitrification and denitrification) nitrogen removal system was constructed by coupling with oxygen limited nitritation stage and anaerobic ammonium oxidation stage. Ammonia oxidizer, as a kind of key bacteria in N cycle, plays an important role at the oxygen limited nitritation stage of OLAND nitrogen removal system. In this study, specific amplification of 16S rDNA fragment of ammonia oxidizer by nested PCR, separation of mixed PCR samples by denaturing gradient gel electrophoresis(DGGE), and the quantification of ammonia oxidizer by fluorescence in situ hybridization(FISH) were combined to investigate the shifts of community composition and quantity of ammonia oxidizer of the oxygen limited nitritation stage in OLAND system. It showed that the community composition of ammonia oxidizer changed drastically when dissolved oxygen was decreased gradually, and the dominant ammonia oxidizer of the steady nitrite accumulation stage were completely different from that of the early stage of oxygen limited nitritation identified by DGGE . It was concluded that the Nitrosomonas may be the dominant genus of ammonia oxidizer at the oxygen limited nitritation stage of OLAND system characterized by nested PCR-DGGE and FISH, and the percentage of Nitrosomonas was 72.5% ±0.8% of ammonia oxidizer at the steady nitrite accumulation stage detected by FISH.展开更多
Ammonium dinitramide(ADN)is considered as a potential substitute for ammonium perchlorate in energetic materials due to its high density,positive oxygen balance,and halogen-free characteristics.However,its application...Ammonium dinitramide(ADN)is considered as a potential substitute for ammonium perchlorate in energetic materials due to its high density,positive oxygen balance,and halogen-free characteristics.However,its application has been severely limited because of its strong hygroscopicity,difficult storage,and incompatibility with isocyanate curing agents.In order to better bloom the advantages of the highly energetic and environment-friendly ADN in the fields of energetic materials,an in-depth analysis of the current situation and discussion of key research points are particularly important.In this paper,a detailed overview on the synthesis,thermal decomposition,hygroscopic mechanism,and antihygroscopicity of ADN has been discussed,its application in powdes and explosives are also presented,and its future research directions are proposed.展开更多
Research and development of green oxidizers and green fuels as a possible replacement for ammonium perchlorate(NH4ClO4,AP) and hydrazine(N2H4) respectively has been increased considerably in the recent years.AP and hy...Research and development of green oxidizers and green fuels as a possible replacement for ammonium perchlorate(NH4ClO4,AP) and hydrazine(N2H4) respectively has been increased considerably in the recent years.AP and hydrazine are the oxidizer and fuel entities,and used in solid and liquid rocket motors respectively.AP is highly toxic and led to adverse health effects,while hydrazine is carcinogenic in nature.AP is in use from the last several decades for rocket and space shuttle propulsion,while hydrazine is used in upper stage liquid propelled rocket motors.It’s a tough task to replace AP with the currently available green oxidizers;since their ballistic properties are weaker when compared to AP and also they can’t be successfully deployed in a solid rocket motor at present Some important available solid green oxidizers are ammonium nitrate(AN),ammonium dinitramide(ADN),hydroxyl ammonium nitrate(HAN),and hydrazinium nitroformate(HNF).However,AN is one of the cheap and readily available oxidizer,and has great potential to use in solid/liquid rocket motors.Tremendous progress has been envisaged till now,and more progress will be there in the coming future over the development of AN based green energetic materials(GEM’s).A concise overview has been presented over the development of phase stabilized ammonium nitrate(PSAN) and AN/KDN based green oxidizers in the present review paper.展开更多
The experimental values of the enthalpy of formation of two isomeric 3,4-and 3,5-dinitro-1-(trinitromethyl)-1H-pyrazoles have been obtained(261.5±5.0and 246.4±6.7kJ/mol for crystalline 3,4-and 3,5-dinitro-1-...The experimental values of the enthalpy of formation of two isomeric 3,4-and 3,5-dinitro-1-(trinitromethyl)-1H-pyrazoles have been obtained(261.5±5.0and 246.4±6.7kJ/mol for crystalline 3,4-and 3,5-dinitro-1-(trinitromethyl)-1H-pyrazoles,respectively).The ballistic effectiveness of these potential oxidizers in composite solid propellants was studied.It is shown that these two oxidizers may be successfully applied in metal-free compositions or with a small content of metal.For the bottom stage 3,4-dinitro-1-(trinitromethyl)-1H-pyrazole is a bit better than 3,5-dinitro-1-(trinitromethyl)-1H-pyrazole,for the upper stage the both oxidizers show the equal ballistic parameters.These oxidizers allow to create metal-free solid composite propellants with the binder percentage not lower than 19%(volume fraction),with I3spequal to 256.5-257.0sat density equal to 1.72-1.74g/cm^3.展开更多
In this study, a porous inserted regenerative thermal oxidizer （PRTO） system was developed for a 125 kW industrial copper-melting furnace, due to its advantages of low NOr emissions and high radiant efficiency. Zirc...In this study, a porous inserted regenerative thermal oxidizer （PRTO） system was developed for a 125 kW industrial copper-melting furnace, due to its advantages of low NOr emissions and high radiant efficiency. Zirconium dioxide （ZrOz） ce- ramic foams were placed into the combustion zone of a regenerative thermal oxidizer （RTO）. Different performance characteris- tics of the RTO and PRTO systems, including pressure drop, temperature distribution, emissions, and energy efficiency, were evaluated to study the effects of the porous inserts on non-premixed CH4 combustion. It was found that the PRTO system achieved a significant reduction in the NOx emission level and a fuel saving of approximately 30% compared to the RTO system. It is most suitable for a lean combustion process at an equivalence ratio 〈0.4 with NOx and CO emission levels within 0.002%~）.003% and 0.001%q3.002%, respectively.展开更多
It is shown that it is not correct to estimate energetic characteristics of different compounds of solid composite propellants by evaluation of the specific impulse values of these components serving as an only compon...It is shown that it is not correct to estimate energetic characteristics of different compounds of solid composite propellants by evaluation of the specific impulse values of these components serving as an only component in the formulation.Such an approach may turn the researcher to a wrong conclusion.One has to compare compound′s potential in formulations close to real,e.g.at least with necessary amount of binders.Dependences of specific impulse upon element content of highenthalpy CHNO oxidizer,its enthalpy of formation,and kind of binder have been found.展开更多
Soil arsenic contamination is of great concern because of its toxicity to human,crops,and soil microorganisms.However,the impacts of arsenic on soil ammonia oxidizers communities remain unclear.Seven types of soil spi...Soil arsenic contamination is of great concern because of its toxicity to human,crops,and soil microorganisms.However,the impacts of arsenic on soil ammonia oxidizers communities remain unclear.Seven types of soil spiked with 0 or 100 mg arsenic per kg soil were incubated for 180 days and sampled at days 1,15,30,90 and 180.The changes in the community composition and abundance of ammonia oxidizing bacteria(AOB)and ammonia oxidizing archaea(AOA)were analyzed by terminal restriction fragment length polymorphism(TRFLP)analysis,clone library sequencing,and quantitative PCR(qPCR)targeting amoA gene.Results revealed considerable variations in the potential ammonia oxidation(PAO)rates in different soils,but soil PAO was not consistently significantly inhibited by arsenic,probably due to the low bioavailable arsenic contents or the existence of functional redundancy between AOB and AOA.The variations in AOB and AOA communities were closely associated with the changes in arsenic fractionations.The amoA gene abundances of AOA increased after arsenic addition,whereas AOB decreased,which corroborated the notion that AOA and AOB might occupy different niches in arsenic-contaminated soils.Phylogenetic analysis of amoA gene-encoded proteins revealed that all AOB clone sequences belonged to the genus Nitrosospira,among which those belonging to Nitrosospira cluster 3a were dominant.The main AOA sequence detected belonged to Thaumarchaeal Group 1.1b,which was considered to have a high ability to adapt to environmental changes.Our results provide new insights into the impacts of arsenic on the soil nitrogen cycling.展开更多
The responses of soil ammonia-oxidizing archaea（AOA） and ammonia-oxidizing bacteria（AOB） to mercury（Hg） stress were investigated through a short-term incubation experiment.Treated with four different concentrati...The responses of soil ammonia-oxidizing archaea（AOA） and ammonia-oxidizing bacteria（AOB） to mercury（Hg） stress were investigated through a short-term incubation experiment.Treated with four different concentrations of Hg（CK,Hg25,Hg50,and Hg100,denoting 0,25,50,and 100 mg Hg/kg dry soil,respectively）,samples were harvested after 3,7,and 28 day incubation.Results showed that the soil potential nitrification rate（PNR） was significantly inhibited by Hg stress during the incubation.However,lower abundances of AOA（the highest in CK： 9.20 × 10~7 copies/g dry soil; the lowest in Hg50： 2.68 × 10~7 copies/g dry soil） and AOB（the highest in CK： 2.68 × 10~7 copies/g dry soil; the lowest in Hg50：7.49 × 10~6 copies/g dry soil） were observed only at day 28 of incubation（P 〈 0.05）.Moreover,only the community structure of soil AOB obviously shifted under Hg stress as seen through DGGE profiles,which revealed that 2-3 distinct AOB bands emerged in the Hg treatments at day 28.In summary,soil PNR might be a very useful parameter to assess acute Hg stress on soil ecosystems,and the community structure of soil AOB might be a realistic biological indicator for the assessment of heavy metal stress on soil ecosystems in the future.展开更多
The spatial distribution and diversity of archaeal and bacterial ammonia oxidizers （AOA and AOB） were evaluated targeting amoA genes in the gradient of a littoral buffer zone which has been identified as a hot spot ...The spatial distribution and diversity of archaeal and bacterial ammonia oxidizers （AOA and AOB） were evaluated targeting amoA genes in the gradient of a littoral buffer zone which has been identified as a hot spot for N cycling. Here we found high spatial heterogeneity in the nitrification rate and abundance of ammonia oxidizers in the five sampling sites. The bacterial amoA gene was numerically dominant in most of the surface soil but decreased dramatically in deep layers. Higher nitrification potentials were detected in two sites near the land/water interface at 4.4–6.1 μg NO2-N/（g dry weight soil·hr）, while only 1.0–1.7 μg NO2-N/（g dry weight soil·hr） was measured at other sites. The potential nitrification rates were proportional to the amoA gene abundance for AOB, but with no significant correlation with AOA. The NH4＋ concentration was the most determinative parameter for the abundance of AOB and potential nitrification rates in this study. Higher richness in the surface layer was found in the analysis of biodiversity. Phylogenetic analysis revealed that most of the bacterial amoA sequences in surface soil were affiliated with the genus of Nitrosopira while the archaeal sequences were almost equally affiliated with Candidatus ‘Nitrososphaera gargensis’ and Candidatus ‘Nitrosocaldus yellowstonii’. The spatial distribution of AOA and AOB indicated that bacteria may play a more important role in nitrification in the littoral buffer zone of a N-rich lake.展开更多
Excellent Heat Affected Zone Toughness Technology Improved by use of Strong Deoxidizers(ETISD Technology)has been developed by Baosteel.When deoxidation of molten steel is conducted at the precisely controlled oxygen ...Excellent Heat Affected Zone Toughness Technology Improved by use of Strong Deoxidizers(ETISD Technology)has been developed by Baosteel.When deoxidation of molten steel is conducted at the precisely controlled oxygen concentrations,the formation of the micro-meter inclusions and the nano-meter precipitates in the steel plate can be effectively controlled.During the welding process with high-heat input,the formation of acicular ferrite can be selectively promoted with the aid of micro-meter inclusions;the growth ofγgrain can also be selectively restrained by the pinning effect of nano-meter precipitates.After welding with high-heat input of 400 kJ/cm,excellent heat affected zone toughness can be obtained for the steel plates with both of the above microstructures,and the average absorbed energy is greater than 200 J for V notch Charpy impact test at-20℃.展开更多
Excellent heat affected zone(HAZ)toughness technology improved by strong deoxidizers(ETISI)technology has been developed by Baosteel.In the deoxidation process of molten steel by adding strong deoxidizers,the formatio...Excellent heat affected zone(HAZ)toughness technology improved by strong deoxidizers(ETISI)technology has been developed by Baosteel.In the deoxidation process of molten steel by adding strong deoxidizers,the formation of micrometer inclusions and nano-meter precipitates in steel plates can be effectively controlled by a precise control of oxygen concentration.In the welding process with a high-heat input,the formation of acicular ferrite can be selectively promoted with the aid of the micrometer inclusions;the growth ofγgrains can also be selectively restrained by the pinning effect of the nano-meter precipitates.After welding with a high-heat input of 400 kJ/cm,excellent HAZ toughness can be obtained in the steel plates with both of the above microstructures,and the average absorbed energy is greater than 200 J for the V-notch Charpy impact test at-20℃.展开更多
The mechanisms of oxide metallurgy include inducing the formation of intragranular acicular ferrite(IAF)using micron-sized inclusions and restricting the growth of prior austenite grains(PAGs)by nanosized particles du...The mechanisms of oxide metallurgy include inducing the formation of intragranular acicular ferrite(IAF)using micron-sized inclusions and restricting the growth of prior austenite grains(PAGs)by nanosized particles during welding.The chaotically oriented IAF and refined PAGs inhibit crack initiation and propagation in the steel,resulting in high impact toughness.This work summarizes the com-bined effect of deoxidizers and alloying elements,with the aim to provide a new perspective for the research and practice related to im-proving the impact toughness of the heat affected zone(HAZ)during the high heat input welding.Ti complex deoxidation with other strong deoxidants,such as Mg,Ca,Zr,and rare earth metals(REMs),can improve the toughness of the heat-affected zone(HAZ)by re-fining PAGs or increasing IAF contents.However,it is difficult to identify the specific phase responsible for IAF nucleation because ef-fective inclusions formed by complex deoxidation are usually multiphase.Increasing alloying elements,such as C,Si,Al,Nb,or Cr,con-tents can impair HAZ toughness.A high C content typically increases the number of coarse carbides and decreases the potency of IAF formation.Si,Cr,or Al addition leads to the formation of undesirable microstructures.Nb reduces the high-temperature stability of the precipitates.Mo,V,and B can enhance HAZ toughness.Mo-containing precipitates present good thermal stability.VN or V(C,N)is ef-fective in promoting IAF nucleation due to its good coherent crystallographic relationship with ferrite.The formation of the B-depleted zone around the inclusion promotes IAF formation.The interactions between alloying elements are complex,and the effect of adding dif-ferent alloying elements remains to be evaluated.In the future,the interactions between various alloying elements and their effects on ox-ide metallurgy,as well as the calculation of the nucleation effects of effective inclusions using first principles calculations will become the focus of oxide metallurgy.展开更多
It is difficult to stimulate coal reservoirs in physical approaches,and the recovery factor of coalbed methane(CBM)can be enhanced by applying strong oxidizers through oxidation to stimulate coal reservoirs.At present...It is difficult to stimulate coal reservoirs in physical approaches,and the recovery factor of coalbed methane(CBM)can be enhanced by applying strong oxidizers through oxidation to stimulate coal reservoirs.At present,however,there have been very few studies on the oxidation of CBM and fewer experimental studies for systematically evaluating the effect of oxidation on the seepage capacity of coal reservoirs.In this paper,the coal samples taken from coal seams of the Jurassic Xishanyao Formation in the Heishan Coal Mine,Toksun,Xinjiang,were selected as the study objects.Hydrogen peroxide solution immersion experiments were carried out on columnar and powdered coal samples,respectively to measure the permeability of columnar coal samples,the dissolution rate of powdered coal samples and the property parameters of hydrogen peroxide solution.Then,the reaction mechanisms between coal samples and hydrogen peroxide and the mechanisms to improve the seepage capacity of coal reservoirs were analyzed by means of X-ray diffraction(XRD),scanning electron microscope(SEM),infrared spectrum and wetting angle measurement.Finally,the stimulation effect of oxidation was compared with that of acidification.The following research results were obtained.(1)The permeability of coal samples is increased significantly after oxidation to 1.4–3.2 times the original permeability.(2)A large number of micro-fractures and dissolved pores are formed in the coal samples after oxidation,and consequently pore connectivity is improved greatly.Thus,the amount of associative hydroxyl and carboxyl functional groups on the surface of the coal samples increases,and the water wettability on the surface reduces.(3)Organic matters and pyrites are oxidized and consumed easily,and the generated H+and micro-molecular aliphatic acids further dissolve inorganic mineral components.(4)Oxidation also has the advantage of acidification for dissolving inorganic mineral components,so there is a low and controllable probability of generating coal powder.In conclusion,applying strong oxidizers has the potential to become a new technology for coal reservoir stimulation.展开更多
Regenerative catalytic oxidizers(RCO)are widely used to remove volatile organic compounds(VOCs)due to their energy-saving and stability.In this study,a multi-component catalytic reaction model was constructed to numer...Regenerative catalytic oxidizers(RCO)are widely used to remove volatile organic compounds(VOCs)due to their energy-saving and stability.In this study,a multi-component catalytic reaction model was constructed to numerically investigate the reaction process of hydrocarbon-containing VOCs in RCO using computational fluid dynamics(CFD)simulation.To obtain the conversion characteristics of multi-component hydrocarbons,the effects of intake load,equivalence ratio,and the composition of multi-component hydrocarbons on the flow,heat transfer,and conversion rate of the reactor were analyzed.A feasibility study plan targeting the hard-to-convert components was also proposed.The results indicated that as the load increases,the conversion rates of the various components decrease,while the reaction rates increase.Moreover,increasing the flow velocity intensifies turbulence and enhances the collision frequency between the gas and the wall surfaces.This,in turn,amplifies the resistance effect of the porous medium.As the equivalence ratio of VOCs to oxygen increases,the oxygen-deficient condition leads to a decrease in the molecular weight of the hydrocarbons involved in the reaction.The reaction temperature also shows a downward trend.A comparative analysis of the catalytic combustion characteristics of multi-component VOCs and single-component gases reveals that adding ethane and propane can facilitate methane oxidation.展开更多
Polynitro compounds play indispensable roles as high-energy oxidizers in solid propellants and space exploration.Generally,the number of nitro groups governs the energy and stability of these oxidizers:the more the pr...Polynitro compounds play indispensable roles as high-energy oxidizers in solid propellants and space exploration.Generally,the number of nitro groups governs the energy and stability of these oxidizers:the more the presence of nitro groups,the higher the energy,and the lower the stability.Maximizing the number of nitro groups while maintaining good stability is,therefore,challenging.Here,we exploited the synergy between the weak repulsion among groups and the uniform charge distribution to design and synthesize a new polynitro compound,2,2′,5,5′-tetra(trinitromethyl)-3,3′-bi-1,2,4-triazole(BITE-202).This compound not only had 12 nitro groups,which were the most among all small molecules but also exhibited exceptional stability(thermal decomposition at 164℃,stability at 70℃,nonhygroscopic in air,and stable in water).BITE-202 had an ultrahigh oxygen balance of+34.96%,which,in combination with a high density of 1.976 g cm−3,allowed formulations thereof to deliver an exceptionally high specific impulse of 275.2 s,far higher than that of the state-of-the-art ammonium dinitramide(ADN)of 271.6 s.Our findings subvert the long-held concept of“more nitro,lower stability,”and offer a practical approach for constructing ultrahigh-energy oxidizers with superior stability,which undoubtedlyprovides a huge impetus for thedevelopment of nitro chemistry.展开更多
Ischemic stroke is a major cause of neurological deficits and high disability rate.As the primary immune cells of the central nervous system,microglia play dual roles in neuroinflammation and tissue repair following a...Ischemic stroke is a major cause of neurological deficits and high disability rate.As the primary immune cells of the central nervous system,microglia play dual roles in neuroinflammation and tissue repair following a stroke.Their dynamic activation and polarization states are key factors that influence the disease process and treatment outcomes.This review article investigates the role of microglia in ischemic stroke and explores potential intervention strategies.Microglia exhibit a dynamic functional state,transitioning between pro-inflammatory(M1)and anti-inflammatory(M2)phenotypes.This duality is crucial in ischemic stroke,as it maintains a balance between neuroinflammation and tissue repair.Activated microglia contribute to neuroinflammation through cytokine release and disruption of the blood-brain barrier,while simultaneously promoting tissue repair through anti-inflammatory responses and regeneration.Key pathways influencing microglial activation include Toll-like receptor 4/nuclear factor kappa B,mitogen-activated protein kinases,Janus kinase/signal transducer and activator of transcription,and phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin pathways.These pathways are targets for various experimental therapies aimed at promoting M2 polarization and mitigating damage.Potential therapeutic agents include natural compounds found in drugs such as minocycline,as well as traditional Chinese medicines.Drugs that target these regulatory mechanisms,such as small molecule inhibitors and components of traditional Chinese medicines,along with emerging technologies such as single-cell RNA sequencing and spatial transcriptomics,offer new therapeutic strategies and clinical translational potential for ischemic stroke.展开更多
Stroke,particularly ischemic stroke,is the leading cause of long-term disability and mortality worldwide.It occurs due to the occlusion of the cerebral arteries,which significantly reduces the delivery of blood,oxygen...Stroke,particularly ischemic stroke,is the leading cause of long-term disability and mortality worldwide.It occurs due to the occlusion of the cerebral arteries,which significantly reduces the delivery of blood,oxygen,and essential nutrients to brain tissues.This deprivation triggers a cascade of cellular events that ultimately leads to neuronal death.Recent studies have clarified the multifactorial pathogenesis of ischemic stroke,highlighting the roles of energy failure,excitotoxicity,oxidative stress,neuroinflammation,and apoptosis.This review aimed to provide a comprehensive insight into the fundamental mechanisms driving neuronal death triggered by ischemia and to examine the progress of neuroprotective therapeutic approaches designed to mitigate neuronal loss and promote neurological recovery after a stroke.Additionally,we explored widely accepted findings regarding the potential pathways implicated in neuronal death during ischemic stroke,including the interplay of apoptosis,autophagy,pyroptosis,ferroptosis,and necrosis,which collectively influence neuronal fate.We also discussed advancements in neuroprotective therapeutics,encompassing a range of interventions from pharmacological modulation to stem cell-based therapies,aimed at reducing neuronal injury and enhancing functional recovery following ischemic stroke.Despite these advancements,challenges remain in translating mechanistic insights into effective clinical therapies.Although neuroprotective strategies have shown promise in preclinical models,their efficacy in human trials has been inconsistent,often due to the complex pathology of ischemic stroke and the timing of interventions.In conclusion,this review synthesizes mechanistic insights into the intricate interplay of molecular and cellular pathways driving neuronal death post-ischemia.It sheds light on cutting-edge advancements in potential neuroprotective therapeutics,underscores the promise of regenerative medicine,and offers a forward-looking perspective on potential clinical breakthroughs.The ongoing evolution of precision-targeted interventions is expected to significantly enhance preventative strategies and improve clinical outcomes.展开更多
The cure rate for chronic neurodegenerative diseases remains low,creating an urgent need for improved intervention methods.Recent studies have shown that enhancing mitochondrial function can mitigate the effects of th...The cure rate for chronic neurodegenerative diseases remains low,creating an urgent need for improved intervention methods.Recent studies have shown that enhancing mitochondrial function can mitigate the effects of these diseases.This paper comprehensively reviews the relationship between mitochondrial dysfunction and chronic neurodegenerative diseases,aiming to uncover the potential use of targeted mitochondrial interventions as viable therapeutic options.We detail five targeted mitochondrial intervention strategies for chronic neurodegenerative diseases that act by promoting mitophagy,inhibiting mitochondrial fission,enhancing mitochondrial biogenesis,applying mitochondria-targeting antioxidants,and transplanting mitochondria.Each method has unique advantages and potential limitations,making them suitable for various therapeutic situations.Therapies that promote mitophagy or inhibit mitochondrial fission could be particularly effective in slowing disease progression,especially in the early stages.In contrast,those that enhance mitochondrial biogenesis and apply mitochondria-targeting antioxidants may offer great benefits during the middle stages of the disease by improving cellular antioxidant capacity and energy metabolism.Mitochondrial transplantation,while still experimental,holds great promise for restoring the function of damaged cells.Future research should focus on exploring the mechanisms and effects of these intervention strategies,particularly regarding their safety and efficacy in clinical settings.Additionally,the development of innovative mitochondria-targeting approaches,such as gene editing and nanotechnology,may provide new solutions for treating chronic neurodegenerative diseases.Implementing combined therapeutic strategies that integrate multiple intervention methods could also enhance treatment outcomes.展开更多
Stroke is a major cause of death and disability worldwide.It is characterized by a highly interconnected and multiphasic neuropathological cascade of events,in which an intense and protracted inflammatory response pla...Stroke is a major cause of death and disability worldwide.It is characterized by a highly interconnected and multiphasic neuropathological cascade of events,in which an intense and protracted inflammatory response plays a crucial role in worsening brain injury.Neuroinflammation,a key player in the pathophysiology of stroke,has a dual role.In the acute phase of stroke,neuroinflammation exacerbates brain injury,contributing to neuronal damage and blood–brain barrier disruption.This aspect of neuroinflammation is associated with poor neurological outcomes.Conversely,in the recovery phase following stroke,neuroinflammation facilitates brain repair processes,including neurogenesis,angiogenesis,and synaptic plasticity.The transition of neuroinflammation from a harmful to a reparative role is not well understood.Therefore,this review seeks to explore the mechanisms underlying this transition,with the goal of informing the development of therapeutic interventions that are both time-and context-specific.This review aims to elucidate the complex and dual role of neuroinflammation in stroke,highlighting the main actors,biomarkers of the disease,and potential therapeutic approaches.展开更多
Neuronal cell death is a common outcome of multiple pathophysiological processes and a key factor in neurological dysfunction after subarachnoid hemorrhage.Neuronal ferroptosis in particular plays an important role in...Neuronal cell death is a common outcome of multiple pathophysiological processes and a key factor in neurological dysfunction after subarachnoid hemorrhage.Neuronal ferroptosis in particular plays an important role in early brain injury.Bromodomain-containing protein 4,a member of the bromo and extraterminal domain family of proteins,participated in multiple cell death pathways,but the mechanisms by which it regulates ferroptosis remain unclear.The primary aim of this study was to investigate how bromodomain-containing protein 4 affects neuronal ferroptosis following subarachnoid hemorrhage in vivo and in vitro.Our findings revealed that endogenous bromodomain-containing protein 4 co-localized with neurons,and its expression was decreased 48 hours after subarachnoid hemorrhage of the cerebral cortex in vivo.In addition,ferroptosis-related pathways were activated in vivo and in vitro after subarachnoid hemorrhage.Targeted inhibition of bromodomain-containing protein 4 in neurons increased lipid peroxidation and intracellular ferrous iron accumulation via ferritinophagy and ultimately led to neuronal ferroptosis.Using cleavage under targets and tagmentation analysis,we found that bromodomain-containing protein 4 enrichment in the Raf-1 promoter region decreased following oxyhemoglobin stimulation in vitro.Furthermore,treating bromodomain-containing protein 4-knockdown HT-22 cell lines with GW5074,a Raf-1 inhibitor,exacerbated neuronal ferroptosis by suppressing the Raf-1/ERK1/2 signaling pathway.Moreover,targeted inhibition of neuronal bromodomain-containing protein 4 exacerbated early and long-term neurological function deficits after subarachnoid hemorrhage.Our findings suggest that bromodomain-containing protein 4 may have neuroprotective effects after subarachnoid hemorrhage,and that inhibiting ferroptosis could help treat subarachnoid hemorrhage.展开更多
文摘OLAND(oxygen limited autotrophic nitrification and denitrification) nitrogen removal system was constructed by coupling with oxygen limited nitritation stage and anaerobic ammonium oxidation stage. Ammonia oxidizer, as a kind of key bacteria in N cycle, plays an important role at the oxygen limited nitritation stage of OLAND nitrogen removal system. In this study, specific amplification of 16S rDNA fragment of ammonia oxidizer by nested PCR, separation of mixed PCR samples by denaturing gradient gel electrophoresis(DGGE), and the quantification of ammonia oxidizer by fluorescence in situ hybridization(FISH) were combined to investigate the shifts of community composition and quantity of ammonia oxidizer of the oxygen limited nitritation stage in OLAND system. It showed that the community composition of ammonia oxidizer changed drastically when dissolved oxygen was decreased gradually, and the dominant ammonia oxidizer of the steady nitrite accumulation stage were completely different from that of the early stage of oxygen limited nitritation identified by DGGE . It was concluded that the Nitrosomonas may be the dominant genus of ammonia oxidizer at the oxygen limited nitritation stage of OLAND system characterized by nested PCR-DGGE and FISH, and the percentage of Nitrosomonas was 72.5% ±0.8% of ammonia oxidizer at the steady nitrite accumulation stage detected by FISH.
基金financially supported by the National Natural Science Foundation of China (Project No. 21805139, 12102194, 22005144 and 22005145)the Joint Funds of the National Natural Science Foundation of China (No. U2141202)+1 种基金Natural Science Foundation of Jiangsu Province (No. BK20200471)the Fundamental Research Funds for the Central Universities (No. 30920041106, 30921011203)
文摘Ammonium dinitramide(ADN)is considered as a potential substitute for ammonium perchlorate in energetic materials due to its high density,positive oxygen balance,and halogen-free characteristics.However,its application has been severely limited because of its strong hygroscopicity,difficult storage,and incompatibility with isocyanate curing agents.In order to better bloom the advantages of the highly energetic and environment-friendly ADN in the fields of energetic materials,an in-depth analysis of the current situation and discussion of key research points are particularly important.In this paper,a detailed overview on the synthesis,thermal decomposition,hygroscopic mechanism,and antihygroscopicity of ADN has been discussed,its application in powdes and explosives are also presented,and its future research directions are proposed.
文摘Research and development of green oxidizers and green fuels as a possible replacement for ammonium perchlorate(NH4ClO4,AP) and hydrazine(N2H4) respectively has been increased considerably in the recent years.AP and hydrazine are the oxidizer and fuel entities,and used in solid and liquid rocket motors respectively.AP is highly toxic and led to adverse health effects,while hydrazine is carcinogenic in nature.AP is in use from the last several decades for rocket and space shuttle propulsion,while hydrazine is used in upper stage liquid propelled rocket motors.It’s a tough task to replace AP with the currently available green oxidizers;since their ballistic properties are weaker when compared to AP and also they can’t be successfully deployed in a solid rocket motor at present Some important available solid green oxidizers are ammonium nitrate(AN),ammonium dinitramide(ADN),hydroxyl ammonium nitrate(HAN),and hydrazinium nitroformate(HNF).However,AN is one of the cheap and readily available oxidizer,and has great potential to use in solid/liquid rocket motors.Tremendous progress has been envisaged till now,and more progress will be there in the coming future over the development of AN based green energetic materials(GEM’s).A concise overview has been presented over the development of phase stabilized ammonium nitrate(PSAN) and AN/KDN based green oxidizers in the present review paper.
基金Ministry of Education and Science of the Russian Federation(14.613.21.0043)
文摘The experimental values of the enthalpy of formation of two isomeric 3,4-and 3,5-dinitro-1-(trinitromethyl)-1H-pyrazoles have been obtained(261.5±5.0and 246.4±6.7kJ/mol for crystalline 3,4-and 3,5-dinitro-1-(trinitromethyl)-1H-pyrazoles,respectively).The ballistic effectiveness of these potential oxidizers in composite solid propellants was studied.It is shown that these two oxidizers may be successfully applied in metal-free compositions or with a small content of metal.For the bottom stage 3,4-dinitro-1-(trinitromethyl)-1H-pyrazole is a bit better than 3,5-dinitro-1-(trinitromethyl)-1H-pyrazole,for the upper stage the both oxidizers show the equal ballistic parameters.These oxidizers allow to create metal-free solid composite propellants with the binder percentage not lower than 19%(volume fraction),with I3spequal to 256.5-257.0sat density equal to 1.72-1.74g/cm^3.
文摘In this study, a porous inserted regenerative thermal oxidizer （PRTO） system was developed for a 125 kW industrial copper-melting furnace, due to its advantages of low NOr emissions and high radiant efficiency. Zirconium dioxide （ZrOz） ce- ramic foams were placed into the combustion zone of a regenerative thermal oxidizer （RTO）. Different performance characteris- tics of the RTO and PRTO systems, including pressure drop, temperature distribution, emissions, and energy efficiency, were evaluated to study the effects of the porous inserts on non-premixed CH4 combustion. It was found that the PRTO system achieved a significant reduction in the NOx emission level and a fuel saving of approximately 30% compared to the RTO system. It is most suitable for a lean combustion process at an equivalence ratio 〈0.4 with NOx and CO emission levels within 0.002%~）.003% and 0.001%q3.002%, respectively.
文摘It is shown that it is not correct to estimate energetic characteristics of different compounds of solid composite propellants by evaluation of the specific impulse values of these components serving as an only component in the formulation.Such an approach may turn the researcher to a wrong conclusion.One has to compare compound′s potential in formulations close to real,e.g.at least with necessary amount of binders.Dependences of specific impulse upon element content of highenthalpy CHNO oxidizer,its enthalpy of formation,and kind of binder have been found.
基金supported by the National Natural Science Foundation of China(Nos.41877061,41671308)Central Public-interest Scientific Institution Basal Research Fund(No.BSRF202101)the Agricultural Science and Technology Innovation Program of the Chinese Academy of Agricultural Sciences(No.CAAS-ASTIP-2016-IEDA).
文摘Soil arsenic contamination is of great concern because of its toxicity to human,crops,and soil microorganisms.However,the impacts of arsenic on soil ammonia oxidizers communities remain unclear.Seven types of soil spiked with 0 or 100 mg arsenic per kg soil were incubated for 180 days and sampled at days 1,15,30,90 and 180.The changes in the community composition and abundance of ammonia oxidizing bacteria(AOB)and ammonia oxidizing archaea(AOA)were analyzed by terminal restriction fragment length polymorphism(TRFLP)analysis,clone library sequencing,and quantitative PCR(qPCR)targeting amoA gene.Results revealed considerable variations in the potential ammonia oxidation(PAO)rates in different soils,but soil PAO was not consistently significantly inhibited by arsenic,probably due to the low bioavailable arsenic contents or the existence of functional redundancy between AOB and AOA.The variations in AOB and AOA communities were closely associated with the changes in arsenic fractionations.The amoA gene abundances of AOA increased after arsenic addition,whereas AOB decreased,which corroborated the notion that AOA and AOB might occupy different niches in arsenic-contaminated soils.Phylogenetic analysis of amoA gene-encoded proteins revealed that all AOB clone sequences belonged to the genus Nitrosospira,among which those belonging to Nitrosospira cluster 3a were dominant.The main AOA sequence detected belonged to Thaumarchaeal Group 1.1b,which was considered to have a high ability to adapt to environmental changes.Our results provide new insights into the impacts of arsenic on the soil nitrogen cycling.
基金supported by the Natural Science Foundation of China (Nos.41371477,41071163)the National Key Technology R&D Program (No.2014BAD14B01)the Fundamental Research Funds for the Central Universities (No.XDJK2014B047)
文摘The responses of soil ammonia-oxidizing archaea（AOA） and ammonia-oxidizing bacteria（AOB） to mercury（Hg） stress were investigated through a short-term incubation experiment.Treated with four different concentrations of Hg（CK,Hg25,Hg50,and Hg100,denoting 0,25,50,and 100 mg Hg/kg dry soil,respectively）,samples were harvested after 3,7,and 28 day incubation.Results showed that the soil potential nitrification rate（PNR） was significantly inhibited by Hg stress during the incubation.However,lower abundances of AOA（the highest in CK： 9.20 × 10~7 copies/g dry soil; the lowest in Hg50： 2.68 × 10~7 copies/g dry soil） and AOB（the highest in CK： 2.68 × 10~7 copies/g dry soil; the lowest in Hg50：7.49 × 10~6 copies/g dry soil） were observed only at day 28 of incubation（P 〈 0.05）.Moreover,only the community structure of soil AOB obviously shifted under Hg stress as seen through DGGE profiles,which revealed that 2-3 distinct AOB bands emerged in the Hg treatments at day 28.In summary,soil PNR might be a very useful parameter to assess acute Hg stress on soil ecosystems,and the community structure of soil AOB might be a realistic biological indicator for the assessment of heavy metal stress on soil ecosystems in the future.
基金supported by the National Natural Science Foundation of China (No. 20877086 21077119)+5 种基金the National Basic Research Program (973) of China (No. 2009CB421103)the National Water Project of China (No. 2009ZX07209-005 2008ZX07421-001 2008ZX07209-006-02)the support of Beijing Nova Program (No. 2011104)K. C. Wong Education Foundation, Hong Kong
文摘The spatial distribution and diversity of archaeal and bacterial ammonia oxidizers （AOA and AOB） were evaluated targeting amoA genes in the gradient of a littoral buffer zone which has been identified as a hot spot for N cycling. Here we found high spatial heterogeneity in the nitrification rate and abundance of ammonia oxidizers in the five sampling sites. The bacterial amoA gene was numerically dominant in most of the surface soil but decreased dramatically in deep layers. Higher nitrification potentials were detected in two sites near the land/water interface at 4.4–6.1 μg NO2-N/（g dry weight soil·hr）, while only 1.0–1.7 μg NO2-N/（g dry weight soil·hr） was measured at other sites. The potential nitrification rates were proportional to the amoA gene abundance for AOB, but with no significant correlation with AOA. The NH4＋ concentration was the most determinative parameter for the abundance of AOB and potential nitrification rates in this study. Higher richness in the surface layer was found in the analysis of biodiversity. Phylogenetic analysis revealed that most of the bacterial amoA sequences in surface soil were affiliated with the genus of Nitrosopira while the archaeal sequences were almost equally affiliated with Candidatus ‘Nitrososphaera gargensis’ and Candidatus ‘Nitrosocaldus yellowstonii’. The spatial distribution of AOA and AOB indicated that bacteria may play a more important role in nitrification in the littoral buffer zone of a N-rich lake.
文摘Excellent Heat Affected Zone Toughness Technology Improved by use of Strong Deoxidizers(ETISD Technology)has been developed by Baosteel.When deoxidation of molten steel is conducted at the precisely controlled oxygen concentrations,the formation of the micro-meter inclusions and the nano-meter precipitates in the steel plate can be effectively controlled.During the welding process with high-heat input,the formation of acicular ferrite can be selectively promoted with the aid of micro-meter inclusions;the growth ofγgrain can also be selectively restrained by the pinning effect of nano-meter precipitates.After welding with high-heat input of 400 kJ/cm,excellent heat affected zone toughness can be obtained for the steel plates with both of the above microstructures,and the average absorbed energy is greater than 200 J for V notch Charpy impact test at-20℃.
文摘Excellent heat affected zone(HAZ)toughness technology improved by strong deoxidizers(ETISI)technology has been developed by Baosteel.In the deoxidation process of molten steel by adding strong deoxidizers,the formation of micrometer inclusions and nano-meter precipitates in steel plates can be effectively controlled by a precise control of oxygen concentration.In the welding process with a high-heat input,the formation of acicular ferrite can be selectively promoted with the aid of the micrometer inclusions;the growth ofγgrains can also be selectively restrained by the pinning effect of the nano-meter precipitates.After welding with a high-heat input of 400 kJ/cm,excellent HAZ toughness can be obtained in the steel plates with both of the above microstructures,and the average absorbed energy is greater than 200 J for the V-notch Charpy impact test at-20℃.
基金supported by the National Natural Science Foundation of China(No.U1960202).
文摘The mechanisms of oxide metallurgy include inducing the formation of intragranular acicular ferrite(IAF)using micron-sized inclusions and restricting the growth of prior austenite grains(PAGs)by nanosized particles during welding.The chaotically oriented IAF and refined PAGs inhibit crack initiation and propagation in the steel,resulting in high impact toughness.This work summarizes the com-bined effect of deoxidizers and alloying elements,with the aim to provide a new perspective for the research and practice related to im-proving the impact toughness of the heat affected zone(HAZ)during the high heat input welding.Ti complex deoxidation with other strong deoxidants,such as Mg,Ca,Zr,and rare earth metals(REMs),can improve the toughness of the heat-affected zone(HAZ)by re-fining PAGs or increasing IAF contents.However,it is difficult to identify the specific phase responsible for IAF nucleation because ef-fective inclusions formed by complex deoxidation are usually multiphase.Increasing alloying elements,such as C,Si,Al,Nb,or Cr,con-tents can impair HAZ toughness.A high C content typically increases the number of coarse carbides and decreases the potency of IAF formation.Si,Cr,or Al addition leads to the formation of undesirable microstructures.Nb reduces the high-temperature stability of the precipitates.Mo,V,and B can enhance HAZ toughness.Mo-containing precipitates present good thermal stability.VN or V(C,N)is ef-fective in promoting IAF nucleation due to its good coherent crystallographic relationship with ferrite.The formation of the B-depleted zone around the inclusion promotes IAF formation.The interactions between alloying elements are complex,and the effect of adding dif-ferent alloying elements remains to be evaluated.In the future,the interactions between various alloying elements and their effects on ox-ide metallurgy,as well as the calculation of the nucleation effects of effective inclusions using first principles calculations will become the focus of oxide metallurgy.
基金supported by National Natural Science Foundation of China-General Program“Study on acceleration of gas transmission by enhancing permeability through organic-rich shale fracturing due to oxidation”(No.:51674209).
文摘It is difficult to stimulate coal reservoirs in physical approaches,and the recovery factor of coalbed methane(CBM)can be enhanced by applying strong oxidizers through oxidation to stimulate coal reservoirs.At present,however,there have been very few studies on the oxidation of CBM and fewer experimental studies for systematically evaluating the effect of oxidation on the seepage capacity of coal reservoirs.In this paper,the coal samples taken from coal seams of the Jurassic Xishanyao Formation in the Heishan Coal Mine,Toksun,Xinjiang,were selected as the study objects.Hydrogen peroxide solution immersion experiments were carried out on columnar and powdered coal samples,respectively to measure the permeability of columnar coal samples,the dissolution rate of powdered coal samples and the property parameters of hydrogen peroxide solution.Then,the reaction mechanisms between coal samples and hydrogen peroxide and the mechanisms to improve the seepage capacity of coal reservoirs were analyzed by means of X-ray diffraction(XRD),scanning electron microscope(SEM),infrared spectrum and wetting angle measurement.Finally,the stimulation effect of oxidation was compared with that of acidification.The following research results were obtained.(1)The permeability of coal samples is increased significantly after oxidation to 1.4–3.2 times the original permeability.(2)A large number of micro-fractures and dissolved pores are formed in the coal samples after oxidation,and consequently pore connectivity is improved greatly.Thus,the amount of associative hydroxyl and carboxyl functional groups on the surface of the coal samples increases,and the water wettability on the surface reduces.(3)Organic matters and pyrites are oxidized and consumed easily,and the generated H+and micro-molecular aliphatic acids further dissolve inorganic mineral components.(4)Oxidation also has the advantage of acidification for dissolving inorganic mineral components,so there is a low and controllable probability of generating coal powder.In conclusion,applying strong oxidizers has the potential to become a new technology for coal reservoir stimulation.
基金supported by National Key Research&Development Program of China(2022YFB4101500).
文摘Regenerative catalytic oxidizers(RCO)are widely used to remove volatile organic compounds(VOCs)due to their energy-saving and stability.In this study,a multi-component catalytic reaction model was constructed to numerically investigate the reaction process of hydrocarbon-containing VOCs in RCO using computational fluid dynamics(CFD)simulation.To obtain the conversion characteristics of multi-component hydrocarbons,the effects of intake load,equivalence ratio,and the composition of multi-component hydrocarbons on the flow,heat transfer,and conversion rate of the reactor were analyzed.A feasibility study plan targeting the hard-to-convert components was also proposed.The results indicated that as the load increases,the conversion rates of the various components decrease,while the reaction rates increase.Moreover,increasing the flow velocity intensifies turbulence and enhances the collision frequency between the gas and the wall surfaces.This,in turn,amplifies the resistance effect of the porous medium.As the equivalence ratio of VOCs to oxygen increases,the oxygen-deficient condition leads to a decrease in the molecular weight of the hydrocarbons involved in the reaction.The reaction temperature also shows a downward trend.A comparative analysis of the catalytic combustion characteristics of multi-component VOCs and single-component gases reveals that adding ethane and propane can facilitate methane oxidation.
基金supported by the National Natural Science Foundation of China(grant nos.21875021,22075024,22305020,and 22375022)Beijing Institute of Technology Research Fund Program for Young Scholars,China(grant no.6120230044).
文摘Polynitro compounds play indispensable roles as high-energy oxidizers in solid propellants and space exploration.Generally,the number of nitro groups governs the energy and stability of these oxidizers:the more the presence of nitro groups,the higher the energy,and the lower the stability.Maximizing the number of nitro groups while maintaining good stability is,therefore,challenging.Here,we exploited the synergy between the weak repulsion among groups and the uniform charge distribution to design and synthesize a new polynitro compound,2,2′,5,5′-tetra(trinitromethyl)-3,3′-bi-1,2,4-triazole(BITE-202).This compound not only had 12 nitro groups,which were the most among all small molecules but also exhibited exceptional stability(thermal decomposition at 164℃,stability at 70℃,nonhygroscopic in air,and stable in water).BITE-202 had an ultrahigh oxygen balance of+34.96%,which,in combination with a high density of 1.976 g cm−3,allowed formulations thereof to deliver an exceptionally high specific impulse of 275.2 s,far higher than that of the state-of-the-art ammonium dinitramide(ADN)of 271.6 s.Our findings subvert the long-held concept of“more nitro,lower stability,”and offer a practical approach for constructing ultrahigh-energy oxidizers with superior stability,which undoubtedlyprovides a huge impetus for thedevelopment of nitro chemistry.
基金supported by the National Natural Science Foundation of China,82471345(to LC)the Key Research and Development Program for Social Development by the Jiangsu Provincial Department of Science and Technology.No.BE2022668(to LC).
文摘Ischemic stroke is a major cause of neurological deficits and high disability rate.As the primary immune cells of the central nervous system,microglia play dual roles in neuroinflammation and tissue repair following a stroke.Their dynamic activation and polarization states are key factors that influence the disease process and treatment outcomes.This review article investigates the role of microglia in ischemic stroke and explores potential intervention strategies.Microglia exhibit a dynamic functional state,transitioning between pro-inflammatory(M1)and anti-inflammatory(M2)phenotypes.This duality is crucial in ischemic stroke,as it maintains a balance between neuroinflammation and tissue repair.Activated microglia contribute to neuroinflammation through cytokine release and disruption of the blood-brain barrier,while simultaneously promoting tissue repair through anti-inflammatory responses and regeneration.Key pathways influencing microglial activation include Toll-like receptor 4/nuclear factor kappa B,mitogen-activated protein kinases,Janus kinase/signal transducer and activator of transcription,and phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin pathways.These pathways are targets for various experimental therapies aimed at promoting M2 polarization and mitigating damage.Potential therapeutic agents include natural compounds found in drugs such as minocycline,as well as traditional Chinese medicines.Drugs that target these regulatory mechanisms,such as small molecule inhibitors and components of traditional Chinese medicines,along with emerging technologies such as single-cell RNA sequencing and spatial transcriptomics,offer new therapeutic strategies and clinical translational potential for ischemic stroke.
基金supported by the National Natural Science Foundation of China,Nos.82171387 and 31830111(both to SL).
文摘Stroke,particularly ischemic stroke,is the leading cause of long-term disability and mortality worldwide.It occurs due to the occlusion of the cerebral arteries,which significantly reduces the delivery of blood,oxygen,and essential nutrients to brain tissues.This deprivation triggers a cascade of cellular events that ultimately leads to neuronal death.Recent studies have clarified the multifactorial pathogenesis of ischemic stroke,highlighting the roles of energy failure,excitotoxicity,oxidative stress,neuroinflammation,and apoptosis.This review aimed to provide a comprehensive insight into the fundamental mechanisms driving neuronal death triggered by ischemia and to examine the progress of neuroprotective therapeutic approaches designed to mitigate neuronal loss and promote neurological recovery after a stroke.Additionally,we explored widely accepted findings regarding the potential pathways implicated in neuronal death during ischemic stroke,including the interplay of apoptosis,autophagy,pyroptosis,ferroptosis,and necrosis,which collectively influence neuronal fate.We also discussed advancements in neuroprotective therapeutics,encompassing a range of interventions from pharmacological modulation to stem cell-based therapies,aimed at reducing neuronal injury and enhancing functional recovery following ischemic stroke.Despite these advancements,challenges remain in translating mechanistic insights into effective clinical therapies.Although neuroprotective strategies have shown promise in preclinical models,their efficacy in human trials has been inconsistent,often due to the complex pathology of ischemic stroke and the timing of interventions.In conclusion,this review synthesizes mechanistic insights into the intricate interplay of molecular and cellular pathways driving neuronal death post-ischemia.It sheds light on cutting-edge advancements in potential neuroprotective therapeutics,underscores the promise of regenerative medicine,and offers a forward-looking perspective on potential clinical breakthroughs.The ongoing evolution of precision-targeted interventions is expected to significantly enhance preventative strategies and improve clinical outcomes.
基金partly supported by the Yan’an University Qin Chuanyuan“Scientist+Engineer”Team Special Fund,No.2023KXJ-012(to YL)Yan’an University Transformation of Scientific and Technological Achievements Fund,No.2023CGZH-001(to YL)+2 种基金College Students Innovation and Entrepreneurship Training Program,Nos.D2023158,202410719056(to XS,JM)Yan’an University Production and Cultivation Project,No.CXY202001(to YL)Kweichow Moutai Hospital Research and Talent Development Fund Project,No.MTyk2022-25(to XO)。
文摘The cure rate for chronic neurodegenerative diseases remains low,creating an urgent need for improved intervention methods.Recent studies have shown that enhancing mitochondrial function can mitigate the effects of these diseases.This paper comprehensively reviews the relationship between mitochondrial dysfunction and chronic neurodegenerative diseases,aiming to uncover the potential use of targeted mitochondrial interventions as viable therapeutic options.We detail five targeted mitochondrial intervention strategies for chronic neurodegenerative diseases that act by promoting mitophagy,inhibiting mitochondrial fission,enhancing mitochondrial biogenesis,applying mitochondria-targeting antioxidants,and transplanting mitochondria.Each method has unique advantages and potential limitations,making them suitable for various therapeutic situations.Therapies that promote mitophagy or inhibit mitochondrial fission could be particularly effective in slowing disease progression,especially in the early stages.In contrast,those that enhance mitochondrial biogenesis and apply mitochondria-targeting antioxidants may offer great benefits during the middle stages of the disease by improving cellular antioxidant capacity and energy metabolism.Mitochondrial transplantation,while still experimental,holds great promise for restoring the function of damaged cells.Future research should focus on exploring the mechanisms and effects of these intervention strategies,particularly regarding their safety and efficacy in clinical settings.Additionally,the development of innovative mitochondria-targeting approaches,such as gene editing and nanotechnology,may provide new solutions for treating chronic neurodegenerative diseases.Implementing combined therapeutic strategies that integrate multiple intervention methods could also enhance treatment outcomes.
基金supported by European Union-NextGeneration EU under the Italian University and Research(MUR)National Innovation Ecosystem grant ECS00000041-VITALITY-CUP E13C22001060006(to MdA)。
文摘Stroke is a major cause of death and disability worldwide.It is characterized by a highly interconnected and multiphasic neuropathological cascade of events,in which an intense and protracted inflammatory response plays a crucial role in worsening brain injury.Neuroinflammation,a key player in the pathophysiology of stroke,has a dual role.In the acute phase of stroke,neuroinflammation exacerbates brain injury,contributing to neuronal damage and blood–brain barrier disruption.This aspect of neuroinflammation is associated with poor neurological outcomes.Conversely,in the recovery phase following stroke,neuroinflammation facilitates brain repair processes,including neurogenesis,angiogenesis,and synaptic plasticity.The transition of neuroinflammation from a harmful to a reparative role is not well understood.Therefore,this review seeks to explore the mechanisms underlying this transition,with the goal of informing the development of therapeutic interventions that are both time-and context-specific.This review aims to elucidate the complex and dual role of neuroinflammation in stroke,highlighting the main actors,biomarkers of the disease,and potential therapeutic approaches.
基金supported by the National Natural Science Foundation of China,Nos.82371310(to YJ),82271306(to JP)the Sichuan Science and Technology Support Program,Nos.2023YFH0069(to JP),2023NSFSC0028(to YJ),2023NSFSC1559(to YJ),2022YFS0615(to JP),2022NSFSC1421(to JP)+1 种基金Scientific Research Project of Sichuan Provincial Health Commission,No.23LCYJ040(to YJ)Youth Foundation of Southwestern Medical University and Southwest Medical University Project,Nos.2020ZRQNA038(to JP),2021ZKZD013(to JP),2021LZXNYD-P01(to YJ),2023QN014(to JP).
文摘Neuronal cell death is a common outcome of multiple pathophysiological processes and a key factor in neurological dysfunction after subarachnoid hemorrhage.Neuronal ferroptosis in particular plays an important role in early brain injury.Bromodomain-containing protein 4,a member of the bromo and extraterminal domain family of proteins,participated in multiple cell death pathways,but the mechanisms by which it regulates ferroptosis remain unclear.The primary aim of this study was to investigate how bromodomain-containing protein 4 affects neuronal ferroptosis following subarachnoid hemorrhage in vivo and in vitro.Our findings revealed that endogenous bromodomain-containing protein 4 co-localized with neurons,and its expression was decreased 48 hours after subarachnoid hemorrhage of the cerebral cortex in vivo.In addition,ferroptosis-related pathways were activated in vivo and in vitro after subarachnoid hemorrhage.Targeted inhibition of bromodomain-containing protein 4 in neurons increased lipid peroxidation and intracellular ferrous iron accumulation via ferritinophagy and ultimately led to neuronal ferroptosis.Using cleavage under targets and tagmentation analysis,we found that bromodomain-containing protein 4 enrichment in the Raf-1 promoter region decreased following oxyhemoglobin stimulation in vitro.Furthermore,treating bromodomain-containing protein 4-knockdown HT-22 cell lines with GW5074,a Raf-1 inhibitor,exacerbated neuronal ferroptosis by suppressing the Raf-1/ERK1/2 signaling pathway.Moreover,targeted inhibition of neuronal bromodomain-containing protein 4 exacerbated early and long-term neurological function deficits after subarachnoid hemorrhage.Our findings suggest that bromodomain-containing protein 4 may have neuroprotective effects after subarachnoid hemorrhage,and that inhibiting ferroptosis could help treat subarachnoid hemorrhage.
