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
Oxygen carriers play a fundamental role in chemical looping combustion(CLC).Iron-based carriers have been extensively investigated owing to their abundance and environmentally friendly.However,the reactivity and separ...Oxygen carriers play a fundamental role in chemical looping combustion(CLC).Iron-based carriers have been extensively investigated owing to their abundance and environmentally friendly.However,the reactivity and separability of iron-based carriers require further enhancement.This study investigates the effect of the concentration of Mn doping on reactivity,elastic properties and magnetic properties based on density functional theory(DFT)calculations.Theoretical results demonstrate that Mn doping effectively enhances reactivity by reducing the oxygen vacancy formation energy(E_(vac))from 2.33 to 0.87 eV.However,Mn doping introduces HV/EV Ms lattice distortions that deteriorate elastic properties,thereby reducing wear resistance,as evidenced by a 54.54%decrease in the hardness-to-Young's modulus ratio(H_(v)/E_(v))forα-Fe_(2)O_(3)and an 83.33%reduction for Fe_(3)O_(4).Furthermore,Mn doping also modifies magnetic properties.The maximum of saturation magnetization(M_(s))of Fe_(3)O_(4)reaches 121.02 emu/g at 33.33%Mn doping concentration.Finally,systematic evaluation identifies 33.33%as the optimal Mn doping concentration,achieving a balance in enhanced reactivity,superior magnetic performance,and retained elastic stability.展开更多
The reactive materials filled structure(RMFS)is a structural penetrator that replaces high explosive(HE)with reactive materials,presenting a novel self-distributed initiation,multiple deflagrations behavior during pen...The reactive materials filled structure(RMFS)is a structural penetrator that replaces high explosive(HE)with reactive materials,presenting a novel self-distributed initiation,multiple deflagrations behavior during penetrating multi-layered plates,and generating a multipeak overpressure behind the plates.Here analytical models of RMFS self-distributed energy release and equivalent deflagration are developed.The multipeak overpressure formation model based on the single deflagration overpressure expression was promoted.The impact tests of RMFS on multi-layered plates at 584 m/s,616 m/s,and819 m/s were performed to validate the analytical model.Further,the influence of a single overpressure peak and time intervals versus impact velocity is discussed.The analysis results indicate that the deflagration happened within 20.68 mm behind the plate,the initial impact velocity and plate thickness are the crucial factors that dominate the self-distributed multipeak overpressure effect.Three formation patterns of multipeak overpressure are proposed.展开更多
Human health is seriously jeopardized by infections caused by pathogenic microorganisms.The current traditional disinfection technologies have many defects,such as producing harmful by-products,being affected by water...Human health is seriously jeopardized by infections caused by pathogenic microorganisms.The current traditional disinfection technologies have many defects,such as producing harmful by-products,being affected by water turbidity,and high energy consumption.The growing concern for microbial safety has brought non-thermal plasma(NTP)disinfection technology into the spotlight.NTP is a promising disinfection technology with advantages such as environmental protection,safety,room temperature disinfection,short disinfection cycle,and wide applicability.Researchers are continuously optimizing NTP reactions to improve disinfection efficiency.This paper provides an integrated analysis of both plasma disinfection in water and plasma-activated water(PAW)disinfection on object surfaces.NTP can directly treat bacterial contaminated water,and can also be employed to produce PAW as a disinfectant for treating bacteria on surfaces.This review introduces the fundamental concepts and commonly used equipment related to NTP technology,analyzes the influencing factors and mechanisms of disinfection,and concludes by outlining the future directions of NTP technology in the field of disinfection.We hope to provide a reference for the research and practice of bacterial pollution issues.展开更多
Elaidic acid(EA)is a typical trans fatty acid(TFA)that emerges during the processing of various fatty foods.In this study,we found that EA induced renal injury with necroptosis.Pretreatment with a reactive oxygen spec...Elaidic acid(EA)is a typical trans fatty acid(TFA)that emerges during the processing of various fatty foods.In this study,we found that EA induced renal injury with necroptosis.Pretreatment with a reactive oxygen species(ROS)inhibitor and a RIPK3 inhibitor alleviated EA-induced necroptosis.The data indicated that EA induced renal necroptosis through ROS/RIPK3/MLKL pathway.In mechanistic studies,we explored how EA induced ROS production.Results indicated that EA caused mitochondrial damage by testing MMP,MFN1,VDAC,and FIS1.Further,EA suppressed mitophagy by testing the levels of LC3,p62,PINK1,Parkin,colocalization of LC3 and Mito-Tracker Red.Mitophagy is a process of selective degradation of damaged mitochondria.A large number of damaged mitochondria couldn't be cleared by mitophagy in time,which increased ROS levels in renal cells.Pretreatment with a mitophagy activator decreased EA-induced ROS levels and mitochondrial damage.Taken together,our data identified that EA induced renal necroptosis by destroying mitochondria and inhibiting mitophagy,thereby activating the ROS/RIPK3/MLKL pathway.展开更多
Knowing the precise relationship between fuel loading and reactivity is essential for guiding reactor criticality extrapolation and online refueling in molten salt reactors(MSRs).This study aims to explore and explain...Knowing the precise relationship between fuel loading and reactivity is essential for guiding reactor criticality extrapolation and online refueling in molten salt reactors(MSRs).This study aims to explore and explain the linear relationship between reactivity and the reciprocal of uranium concentration in thermal-spectrum MSRs.By applying neutron balance theory,we analyzed the neutron absorption cross sections of various nuclides in single-lattice models with varying fuel concentrations.Our findings reveal a simple linear correlation between reactivity and the reciprocal of uranium concentration,which can be explained from the perspective of nuclear reaction cross sections that adhere to the 1/v law in the thermal neutron spectrum.Furthermore,we identified that the neutron absorption single-group cross sections of structural materials and carrier salts exhibit an approximately linear relationship with the fission single-group cross section of ^(235) U;similarly,the reciprocal of ^(235)U’s fission cross section exhibits an approximately linear relationship with uranium concentration.This linear relationship deviates as the volume fraction of molten salt increases,due to a greater proportion of neutrons being captured in the resonance energy spectrum.However,it remains valid for molten salt volume fractions up to 25%and demonstrates broad applicability in the physical design and operation of thermal molten salt reactors.展开更多
Overproduction of reactive oxygen species(ROS) following ischemic injury triggers an inflammatory response,significantly impeding neurological functional recovery.Nanozymes with potent antioxidative and anti-inflammat...Overproduction of reactive oxygen species(ROS) following ischemic injury triggers an inflammatory response,significantly impeding neurological functional recovery.Nanozymes with potent antioxidative and anti-inflammatory effects thus offer great potential for ischemic stroke treatment.In this study,we developed an ischemia-homing nanozyme by combining melatonin(MT)-loaded honeycomb manganese dioxide(MnO_(2)) nanoflowers with M2-type microglia membranes to rescue the ischemic penumbra.The surface-engineered M2-type microglia membranes provided intrinsic ischemia-homing and blood-brain barrier(BBB)-crossing properties to the biomimetic nanozymes.This nanozyme can not only transforms harmfulsuperoxide anion radicals(^(·)O^(2-)) and hydrogen peroxide(H_(2)O_(2)) into harmless water and oxygen but also scavenges highly toxic hydroxyl radicals(^(·)OH),dramatically lowering intracellular ROS levels.More importantly,the biomimetic nanoparticles reduce cerebral infarct areas and provide significant neuroprotection against ischemic stroke by lowering oxidative stress,inhibiting cell apoptosis,and decreasing inflammation.This study may offer a viable approach for the use of nanozymes in treating ischemic stroke.展开更多
Vacuum-ultraviolet(VUV)radiation is high-energy UV radiation with a wavelength of 100-200 nm capable of decomposing/mineralizing hazardous emerging organic pollutants(EPs)in water through direct photolysis and/or by g...Vacuum-ultraviolet(VUV)radiation is high-energy UV radiation with a wavelength of 100-200 nm capable of decomposing/mineralizing hazardous emerging organic pollutants(EPs)in water through direct photolysis and/or by generating reactive free radicals(RFRs)during photolysis.However,due to the unsatisfactory photoelectric conversion rate,strong absorption by oxygen and water molecules,and other characteristics of VUV radiation,its application and development are hindered,leading to misconceptions regarding high energy consumption and insufficient free radical yield.The objectives of our assessment in this review are as follows:The illumination of the photochemical characteristics of VUV and the reactivity of aqueous solutions.Summarization of accurate UV dose and energy evaluation criteria.Comparison and analysis of the photochemical mechanisms and reaction kinetics of different types of EPs via VUV direct photolysis,as well as the interference origins of typical substrates in water for VUV decontamination.We found that quantities typically reported in VUV photochemical reactions of engineered systems are underreported in low-pressure mercury lamp(LPUV)photochemical reactions,especially a quantitative indicator of the species or energy that induces a chemical reaction.The absence of these quantities has made it difficult to assess the fundamental performance of VUV photolysis fully compared with that of UV-C.Some studies have sought to optimize VUV-advanced reduction processes(VUV-ARP)or VUV reactor treatment of these contaminants;however,an abundant evaluation of the reaction origins and processes between VUV-derived main RFRs and reactants(H_(2)O,O_(2),organic matter,inorganic ions,etc.)is essential,cause these scientific elements will provide the possibility to break the application gap for VUV in the field of EPs treating.Overall,the data compilation,analysis,and research recommendations provided in this review will form the basis for all photochemical reactions initiated by VUV radiation with water as the backing agent.展开更多
Conventional treatments for non-small cell lung cancer(NSCLC)suffer from low remission rates,high drug resistance,and severe adverse effects.To leverage the therapeutic potential of reactive oxygen species(ROS),nanoca...Conventional treatments for non-small cell lung cancer(NSCLC)suffer from low remission rates,high drug resistance,and severe adverse effects.To leverage the therapeutic potential of reactive oxygen species(ROS),nanocatalytic medicine utilizes nanomaterials to generate ROS specifically within tumor sites,enabling efficient and targeted cancer treatment.In this study,hyaluronic acid(HA)-modified copper-N,N-dimethyl-Nphenylsulfonylbisamine(DMSA)-assembled nanoparticles(Cu-DMSA-HA NPs)are developed with tumor-targeting capability and efficiently catalyze ROS production via coordination chemistry.Targeted delivery is facilitated by HA surface modification through recognition of overexpressed cluster of differentiation 44 receptors on cancer cells,which enhances nanoparticle uptake.Once internalized,intracellular glutathione is depleted by the NPs,followed by a Fenton-like reaction that sustains ROS production.Both in vitro and in vivo studies demonstrate that this catalytic strategy effectively inhibits DNA replication,prevents cell cycle progression,downregulates glutathione peroxidase 4 expression,induces ferroptosis,and ultimately suppresses NSCLC progression.Overall,the readily prepared Cu-DMSA-HA NPs exhibit robust catalytic activity and tumor specificity,highlighting their strong potential for clinical translation in nanocatalytic cancer therapy.展开更多
Heterogeneous catalysis is a complex,multiscale phenomenon in which reactions occur at dynamically evolving surfaces.A longstanding goal is to probe these processes to distill design rules for novel catalytic material...Heterogeneous catalysis is a complex,multiscale phenomenon in which reactions occur at dynamically evolving surfaces.A longstanding goal is to probe these processes to distill design rules for novel catalytic materials,a capability that is essential to the transition toward a sustainable future[1–3].展开更多
We are sorry for the mistakes of Affiliation,"a State Key Laboratory of Advanced Fiber Materials,Center for Advanced Low-Dimension Materials,Donghua University,Shanghai 201620,China"should be replaced by&quo...We are sorry for the mistakes of Affiliation,"a State Key Laboratory of Advanced Fiber Materials,Center for Advanced Low-Dimension Materials,Donghua University,Shanghai 201620,China"should be replaced by"a State Key Laboratory of Advanced Fiber Materials,Center for Advanced Low-Dimension Materials,College of Materials Science and Engineering,Donghua University,Shanghai 201620,China".We apologized for the inconvenience caused by this error.展开更多
Supramolecular catalysis uses noncovalent interactions,such as hydrogen bonding,π-π stacking,and host-vip recognition,to control reactivity and selectivity in chemical reactions [1,2].Unlike traditional covalent c...Supramolecular catalysis uses noncovalent interactions,such as hydrogen bonding,π-π stacking,and host-vip recognition,to control reactivity and selectivity in chemical reactions [1,2].Unlike traditional covalent catalysis,supramolecular systems can create dynamic and adaptable microenvironments tailored to specific substrates,similar to how enzymes work.This strategy has shown great promise in asymmetric catalysis,cascade reactions,and green chemistry applications.Recent advances focus on leveraging less conventional noncovalent forces to expand the toolbox of supramolecular strategies in catalysis.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
While injection-induced seismicity has been widely studied,its implications for CO_(2)geological storage require reevaluation due to distinct fluid-rock interactions.This study develops a coupled hydromechanical model...While injection-induced seismicity has been widely studied,its implications for CO_(2)geological storage require reevaluation due to distinct fluid-rock interactions.This study develops a coupled hydromechanical model incorporating rate-and-state friction laws to investigate fault reactivation mechanisms during early-stage CO_(2)injection.The competing effects of pore pressure diffusion and fluid pressurization are systematically investigated,considering three key factors:permeability variations within fault damage zones,normal stress variation coefficients,and injection parameters.Numerical simulations reveal that slower CO_(2)migration causes limited pressure perturbation(<0.3 MPa over 15 d)compared to single-phase fluid injection.Fluid pressurization enhances fault strength and delays reactivation,though this stabilizing effect diminishes in low-permeability damage zones.Highly permeable damage zones promote larger rupture areas despite strengthening from pressurization,as reduced effective stress accelerates failure.Paradoxically,while fluid pressurization increases fault strength,it simultaneously elevates seismic risk through amplified stress drops during slip events.Temporal analysis shows that fluid pressurization dominates initial fault response,while sustained pore pressure diffusion ultimately drives reactivation.Increased normal stress variation coefficients and injection rates accelerate localized rupture initiation but restrict propagation due to non-critically stressed states.This discrepancy demonstrates that regions with positive Coulomb failure stress changes do not correlate well with actual slip zones.These findings highlight the critical interplay between transient pressurization effects and progressive pressure diffusion during early CO_(2)injection phases,providing crucial insights for seismic risk management in CO_(2)storage projects.展开更多
Ischemic stroke is a severe neurological disease with high global mortality and disability rates.Atherosclerosis has been identified as the primary cause of ischemic stroke,while abnormal lipid levels are significant ...Ischemic stroke is a severe neurological disease with high global mortality and disability rates.Atherosclerosis has been identified as the primary cause of ischemic stroke,while abnormal lipid levels are significant contributors to the development of this condition.Multiple pro-apoptotic mechanisms are involved in ischemic stroke caused by lipid metabolism disorders,while various lipids have a strong causal relationship with neuronal apoptosis.However,studies to date have focused on the individual roles of lipid metabolism and apoptosis in ischemic stroke,and an overview of how impaired lipid metabolism leads to apoptosis in ischemic stroke is still lacking in the literature.In this review,we summarize current research on lipids in ischemic stroke.We discuss the role of lipid metabolism in accelerating apoptosis in ischemic stroke as well as the associated mechanisms.Additionally,we highlight advances in drug development and the treatment of stroke,focusing on lipid metabolism.The purpose is to provide novel ideas and strategies for the treatment and prevention of ischemic stroke.展开更多
In real industrial microgrids(MGs),the length of the primary delivery feeder to the connection point of the main substation is sometimes long.This reduces the power factor and increases reactive power absorption along...In real industrial microgrids(MGs),the length of the primary delivery feeder to the connection point of the main substation is sometimes long.This reduces the power factor and increases reactive power absorption along the primary delivery feeder from the external network.Besides,the giant induction electro-motors as the working horse of industries requires remarkable amounts of reactive power for electro-mechanical energy conversions.To reduce power losses and operating costs of the MG as well as to improve the voltage quality,this study aims at providing an insightful model for optimal placement and sizing of reactive power compensation capacitors in an industrial MG.In the presented model,the objective function considers voltage profile and network power factor improvement at the MG connection point.Also,it realizes power flow equations within which all operational security constraints are considered.Various reactive power compensation strategies including distributed group compensation,centralized compensation at the main substation,and distributed compensation along the primary delivery feeder are scrutinized.A real industrial MG,say as Urmia Petrochemical plant,is considered in numerical validations.The obtained results in each scenario are discussed in depth.As seen,the best performance is obtained when the optimal location and sizing of capacitors are simultaneously determined at the main buses of the industrial plants,at the main substation of the MG,and alongside the primary delivery feeder.In this way,74.81%improvement in power losses reduction,1.3%lower active power import from the main grid,23.5%improvement in power factor,and 37.5%improvement in network voltage deviation summation are seen in this case compared to the base case.展开更多
Epilepsy is a prevalent neurological disorder in which hippocampal neuronal damage,particularly ferroptosis,plays a critical role.Previous studies have shown that hypoxia-inducible factor 1αis considered an important...Epilepsy is a prevalent neurological disorder in which hippocampal neuronal damage,particularly ferroptosis,plays a critical role.Previous studies have shown that hypoxia-inducible factor 1αis considered an important regulator of cellular stress responses and has been confirmed to play a critical role in the occurrence of various diseases.However,the mechanisms by which hypoxia-inducible factor 1αis related to epilepsy and neuronal ferroptosis remain unclear.In this study,we used a pentylentetrazole-induced chronic epilepsy mouse model and treated the mice with intraperitoneal administration of PX-478,a hypoxia-inducible factor-1αinhibitor.Our results showed that PX-478 significantly prolonged the latency of epilepsy,reduced seizure severity,and shortened seizure duration.PX-478 also alleviated neuronal damage in the hippocampal CA1 and CA2 regions,reduced levels of reactive oxygen species and malondialdehyde,and increased levels of superoxide dismutase,catalase,and glutathione peroxidase.Transmission electron microscopy showed that PX-478 treatment reduced mitochondrial damage in the hippocampal neurons of epileptic mice,and significantly improved mitochondrial length and area.Additionally,PX-478 preferentially reduced Fe^(2+)levels and the expression of cyclooxygenase-2,ferritin heavy chain 1 and transferrin in the hippocampus of epileptic mice.It also inhibited the activity of the hypoxia-inducible factor 1α/heme oxygenase-1 pathway.In summary,these findings suggest that PX-478 has the potential to treat epilepsy by inhibiting the hypoxia-inducible factor 1α/heme oxygenase-1 pathway,alleviating oxidative stress,and reducing ferroptosis in hippocampal neurons.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
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 National Natural Science Foundation of China(50976032,51776070)。
文摘Oxygen carriers play a fundamental role in chemical looping combustion(CLC).Iron-based carriers have been extensively investigated owing to their abundance and environmentally friendly.However,the reactivity and separability of iron-based carriers require further enhancement.This study investigates the effect of the concentration of Mn doping on reactivity,elastic properties and magnetic properties based on density functional theory(DFT)calculations.Theoretical results demonstrate that Mn doping effectively enhances reactivity by reducing the oxygen vacancy formation energy(E_(vac))from 2.33 to 0.87 eV.However,Mn doping introduces HV/EV Ms lattice distortions that deteriorate elastic properties,thereby reducing wear resistance,as evidenced by a 54.54%decrease in the hardness-to-Young's modulus ratio(H_(v)/E_(v))forα-Fe_(2)O_(3)and an 83.33%reduction for Fe_(3)O_(4).Furthermore,Mn doping also modifies magnetic properties.The maximum of saturation magnetization(M_(s))of Fe_(3)O_(4)reaches 121.02 emu/g at 33.33%Mn doping concentration.Finally,systematic evaluation identifies 33.33%as the optimal Mn doping concentration,achieving a balance in enhanced reactivity,superior magnetic performance,and retained elastic stability.
基金the support received from the National Natural Science Foundation of China(Grant No.12302460)the State Key Laboratory of Explosion Science and Safety Protection(Grant No.YBKT24-02)。
文摘The reactive materials filled structure(RMFS)is a structural penetrator that replaces high explosive(HE)with reactive materials,presenting a novel self-distributed initiation,multiple deflagrations behavior during penetrating multi-layered plates,and generating a multipeak overpressure behind the plates.Here analytical models of RMFS self-distributed energy release and equivalent deflagration are developed.The multipeak overpressure formation model based on the single deflagration overpressure expression was promoted.The impact tests of RMFS on multi-layered plates at 584 m/s,616 m/s,and819 m/s were performed to validate the analytical model.Further,the influence of a single overpressure peak and time intervals versus impact velocity is discussed.The analysis results indicate that the deflagration happened within 20.68 mm behind the plate,the initial impact velocity and plate thickness are the crucial factors that dominate the self-distributed multipeak overpressure effect.Three formation patterns of multipeak overpressure are proposed.
基金support by National Natural Science Foundation of China(No.22006069)Natural Science Foundation of Jiangsu Province in China(No.BK20200801)Jiangsu Special Foundation on Technology Innovation of Carbon Dioxide Peaking and Carbon Neutrality(No.BK20220016).
文摘Human health is seriously jeopardized by infections caused by pathogenic microorganisms.The current traditional disinfection technologies have many defects,such as producing harmful by-products,being affected by water turbidity,and high energy consumption.The growing concern for microbial safety has brought non-thermal plasma(NTP)disinfection technology into the spotlight.NTP is a promising disinfection technology with advantages such as environmental protection,safety,room temperature disinfection,short disinfection cycle,and wide applicability.Researchers are continuously optimizing NTP reactions to improve disinfection efficiency.This paper provides an integrated analysis of both plasma disinfection in water and plasma-activated water(PAW)disinfection on object surfaces.NTP can directly treat bacterial contaminated water,and can also be employed to produce PAW as a disinfectant for treating bacteria on surfaces.This review introduces the fundamental concepts and commonly used equipment related to NTP technology,analyzes the influencing factors and mechanisms of disinfection,and concludes by outlining the future directions of NTP technology in the field of disinfection.We hope to provide a reference for the research and practice of bacterial pollution issues.
基金supported by National Key Research and Development Program of China(2023YFD1800902).
文摘Elaidic acid(EA)is a typical trans fatty acid(TFA)that emerges during the processing of various fatty foods.In this study,we found that EA induced renal injury with necroptosis.Pretreatment with a reactive oxygen species(ROS)inhibitor and a RIPK3 inhibitor alleviated EA-induced necroptosis.The data indicated that EA induced renal necroptosis through ROS/RIPK3/MLKL pathway.In mechanistic studies,we explored how EA induced ROS production.Results indicated that EA caused mitochondrial damage by testing MMP,MFN1,VDAC,and FIS1.Further,EA suppressed mitophagy by testing the levels of LC3,p62,PINK1,Parkin,colocalization of LC3 and Mito-Tracker Red.Mitophagy is a process of selective degradation of damaged mitochondria.A large number of damaged mitochondria couldn't be cleared by mitophagy in time,which increased ROS levels in renal cells.Pretreatment with a mitophagy activator decreased EA-induced ROS levels and mitochondrial damage.Taken together,our data identified that EA induced renal necroptosis by destroying mitochondria and inhibiting mitophagy,thereby activating the ROS/RIPK3/MLKL pathway.
文摘Knowing the precise relationship between fuel loading and reactivity is essential for guiding reactor criticality extrapolation and online refueling in molten salt reactors(MSRs).This study aims to explore and explain the linear relationship between reactivity and the reciprocal of uranium concentration in thermal-spectrum MSRs.By applying neutron balance theory,we analyzed the neutron absorption cross sections of various nuclides in single-lattice models with varying fuel concentrations.Our findings reveal a simple linear correlation between reactivity and the reciprocal of uranium concentration,which can be explained from the perspective of nuclear reaction cross sections that adhere to the 1/v law in the thermal neutron spectrum.Furthermore,we identified that the neutron absorption single-group cross sections of structural materials and carrier salts exhibit an approximately linear relationship with the fission single-group cross section of ^(235) U;similarly,the reciprocal of ^(235)U’s fission cross section exhibits an approximately linear relationship with uranium concentration.This linear relationship deviates as the volume fraction of molten salt increases,due to a greater proportion of neutrons being captured in the resonance energy spectrum.However,it remains valid for molten salt volume fractions up to 25%and demonstrates broad applicability in the physical design and operation of thermal molten salt reactors.
基金supported by National Key R&D Program of China (No.2022YFC3501700)National Natural Science Foundation of China (No.82274059)+3 种基金Naval Military Medical University,Far East Talent Project (No.SL-33)Talent Project established by Chinese Pharmaceutical Association Hospital Pharmacy department (No.CPA-Z05-ZC-2024-003)Shanghai Oriental Talent Plan Youth Program (formerly Shanghai Young Top-Notch Talent) (2023)the Baoshan District Medical Key Science (Specialty) and Specialty Brand Construction Project (No.BSZK-2023-A12)。
文摘Overproduction of reactive oxygen species(ROS) following ischemic injury triggers an inflammatory response,significantly impeding neurological functional recovery.Nanozymes with potent antioxidative and anti-inflammatory effects thus offer great potential for ischemic stroke treatment.In this study,we developed an ischemia-homing nanozyme by combining melatonin(MT)-loaded honeycomb manganese dioxide(MnO_(2)) nanoflowers with M2-type microglia membranes to rescue the ischemic penumbra.The surface-engineered M2-type microglia membranes provided intrinsic ischemia-homing and blood-brain barrier(BBB)-crossing properties to the biomimetic nanozymes.This nanozyme can not only transforms harmfulsuperoxide anion radicals(^(·)O^(2-)) and hydrogen peroxide(H_(2)O_(2)) into harmless water and oxygen but also scavenges highly toxic hydroxyl radicals(^(·)OH),dramatically lowering intracellular ROS levels.More importantly,the biomimetic nanoparticles reduce cerebral infarct areas and provide significant neuroprotection against ischemic stroke by lowering oxidative stress,inhibiting cell apoptosis,and decreasing inflammation.This study may offer a viable approach for the use of nanozymes in treating ischemic stroke.
基金supported by the National Key R&D Program of China(No.2023YFC3210100).
文摘Vacuum-ultraviolet(VUV)radiation is high-energy UV radiation with a wavelength of 100-200 nm capable of decomposing/mineralizing hazardous emerging organic pollutants(EPs)in water through direct photolysis and/or by generating reactive free radicals(RFRs)during photolysis.However,due to the unsatisfactory photoelectric conversion rate,strong absorption by oxygen and water molecules,and other characteristics of VUV radiation,its application and development are hindered,leading to misconceptions regarding high energy consumption and insufficient free radical yield.The objectives of our assessment in this review are as follows:The illumination of the photochemical characteristics of VUV and the reactivity of aqueous solutions.Summarization of accurate UV dose and energy evaluation criteria.Comparison and analysis of the photochemical mechanisms and reaction kinetics of different types of EPs via VUV direct photolysis,as well as the interference origins of typical substrates in water for VUV decontamination.We found that quantities typically reported in VUV photochemical reactions of engineered systems are underreported in low-pressure mercury lamp(LPUV)photochemical reactions,especially a quantitative indicator of the species or energy that induces a chemical reaction.The absence of these quantities has made it difficult to assess the fundamental performance of VUV photolysis fully compared with that of UV-C.Some studies have sought to optimize VUV-advanced reduction processes(VUV-ARP)or VUV reactor treatment of these contaminants;however,an abundant evaluation of the reaction origins and processes between VUV-derived main RFRs and reactants(H_(2)O,O_(2),organic matter,inorganic ions,etc.)is essential,cause these scientific elements will provide the possibility to break the application gap for VUV in the field of EPs treating.Overall,the data compilation,analysis,and research recommendations provided in this review will form the basis for all photochemical reactions initiated by VUV radiation with water as the backing agent.
基金supported by National Natural Science Foundation of China(82272943)Shanghai Municipal Science and Technology Commission(21Y11913400)Fundamental Research Funds for the Central Universities and National Key Research and Development Program of China(2022YFC2407405).
文摘Conventional treatments for non-small cell lung cancer(NSCLC)suffer from low remission rates,high drug resistance,and severe adverse effects.To leverage the therapeutic potential of reactive oxygen species(ROS),nanocatalytic medicine utilizes nanomaterials to generate ROS specifically within tumor sites,enabling efficient and targeted cancer treatment.In this study,hyaluronic acid(HA)-modified copper-N,N-dimethyl-Nphenylsulfonylbisamine(DMSA)-assembled nanoparticles(Cu-DMSA-HA NPs)are developed with tumor-targeting capability and efficiently catalyze ROS production via coordination chemistry.Targeted delivery is facilitated by HA surface modification through recognition of overexpressed cluster of differentiation 44 receptors on cancer cells,which enhances nanoparticle uptake.Once internalized,intracellular glutathione is depleted by the NPs,followed by a Fenton-like reaction that sustains ROS production.Both in vitro and in vivo studies demonstrate that this catalytic strategy effectively inhibits DNA replication,prevents cell cycle progression,downregulates glutathione peroxidase 4 expression,induces ferroptosis,and ultimately suppresses NSCLC progression.Overall,the readily prepared Cu-DMSA-HA NPs exhibit robust catalytic activity and tumor specificity,highlighting their strong potential for clinical translation in nanocatalytic cancer therapy.
文摘Heterogeneous catalysis is a complex,multiscale phenomenon in which reactions occur at dynamically evolving surfaces.A longstanding goal is to probe these processes to distill design rules for novel catalytic materials,a capability that is essential to the transition toward a sustainable future[1–3].
文摘We are sorry for the mistakes of Affiliation,"a State Key Laboratory of Advanced Fiber Materials,Center for Advanced Low-Dimension Materials,Donghua University,Shanghai 201620,China"should be replaced by"a State Key Laboratory of Advanced Fiber Materials,Center for Advanced Low-Dimension Materials,College of Materials Science and Engineering,Donghua University,Shanghai 201620,China".We apologized for the inconvenience caused by this error.
文摘Supramolecular catalysis uses noncovalent interactions,such as hydrogen bonding,π-π stacking,and host-vip recognition,to control reactivity and selectivity in chemical reactions [1,2].Unlike traditional covalent catalysis,supramolecular systems can create dynamic and adaptable microenvironments tailored to specific substrates,similar to how enzymes work.This strategy has shown great promise in asymmetric catalysis,cascade reactions,and green chemistry applications.Recent advances focus on leveraging less conventional noncovalent forces to expand the toolbox of supramolecular strategies in catalysis.
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.
基金funded by Joint Funds of the National Natural Science Foundation of China(Grant No.U23A20671)the Major Project of Inner Mongolia Science and Technology(Grant No.2021ZD0034)the Creative Groups of Natural Science Foundation of Hubei Province,China(Grant No.2021CFA030).
文摘While injection-induced seismicity has been widely studied,its implications for CO_(2)geological storage require reevaluation due to distinct fluid-rock interactions.This study develops a coupled hydromechanical model incorporating rate-and-state friction laws to investigate fault reactivation mechanisms during early-stage CO_(2)injection.The competing effects of pore pressure diffusion and fluid pressurization are systematically investigated,considering three key factors:permeability variations within fault damage zones,normal stress variation coefficients,and injection parameters.Numerical simulations reveal that slower CO_(2)migration causes limited pressure perturbation(<0.3 MPa over 15 d)compared to single-phase fluid injection.Fluid pressurization enhances fault strength and delays reactivation,though this stabilizing effect diminishes in low-permeability damage zones.Highly permeable damage zones promote larger rupture areas despite strengthening from pressurization,as reduced effective stress accelerates failure.Paradoxically,while fluid pressurization increases fault strength,it simultaneously elevates seismic risk through amplified stress drops during slip events.Temporal analysis shows that fluid pressurization dominates initial fault response,while sustained pore pressure diffusion ultimately drives reactivation.Increased normal stress variation coefficients and injection rates accelerate localized rupture initiation but restrict propagation due to non-critically stressed states.This discrepancy demonstrates that regions with positive Coulomb failure stress changes do not correlate well with actual slip zones.These findings highlight the critical interplay between transient pressurization effects and progressive pressure diffusion during early CO_(2)injection phases,providing crucial insights for seismic risk management in CO_(2)storage projects.
基金supported by the National Natural Science Foundation of China,Nos.31871169(to YT),32471179(to AW)the Natural Science Foundation of Hunan Province,No.2021JJ30601(to AW)Key Program of Education Department of Hunan Province,No.21A0274(to AW).
文摘Ischemic stroke is a severe neurological disease with high global mortality and disability rates.Atherosclerosis has been identified as the primary cause of ischemic stroke,while abnormal lipid levels are significant contributors to the development of this condition.Multiple pro-apoptotic mechanisms are involved in ischemic stroke caused by lipid metabolism disorders,while various lipids have a strong causal relationship with neuronal apoptosis.However,studies to date have focused on the individual roles of lipid metabolism and apoptosis in ischemic stroke,and an overview of how impaired lipid metabolism leads to apoptosis in ischemic stroke is still lacking in the literature.In this review,we summarize current research on lipids in ischemic stroke.We discuss the role of lipid metabolism in accelerating apoptosis in ischemic stroke as well as the associated mechanisms.Additionally,we highlight advances in drug development and the treatment of stroke,focusing on lipid metabolism.The purpose is to provide novel ideas and strategies for the treatment and prevention of ischemic stroke.
文摘In real industrial microgrids(MGs),the length of the primary delivery feeder to the connection point of the main substation is sometimes long.This reduces the power factor and increases reactive power absorption along the primary delivery feeder from the external network.Besides,the giant induction electro-motors as the working horse of industries requires remarkable amounts of reactive power for electro-mechanical energy conversions.To reduce power losses and operating costs of the MG as well as to improve the voltage quality,this study aims at providing an insightful model for optimal placement and sizing of reactive power compensation capacitors in an industrial MG.In the presented model,the objective function considers voltage profile and network power factor improvement at the MG connection point.Also,it realizes power flow equations within which all operational security constraints are considered.Various reactive power compensation strategies including distributed group compensation,centralized compensation at the main substation,and distributed compensation along the primary delivery feeder are scrutinized.A real industrial MG,say as Urmia Petrochemical plant,is considered in numerical validations.The obtained results in each scenario are discussed in depth.As seen,the best performance is obtained when the optimal location and sizing of capacitors are simultaneously determined at the main buses of the industrial plants,at the main substation of the MG,and alongside the primary delivery feeder.In this way,74.81%improvement in power losses reduction,1.3%lower active power import from the main grid,23.5%improvement in power factor,and 37.5%improvement in network voltage deviation summation are seen in this case compared to the base case.
基金supported by the Science and Technology Development Plan Project of Jilin Province,No.YDZJ202401157ZYTS(to SL).
文摘Epilepsy is a prevalent neurological disorder in which hippocampal neuronal damage,particularly ferroptosis,plays a critical role.Previous studies have shown that hypoxia-inducible factor 1αis considered an important regulator of cellular stress responses and has been confirmed to play a critical role in the occurrence of various diseases.However,the mechanisms by which hypoxia-inducible factor 1αis related to epilepsy and neuronal ferroptosis remain unclear.In this study,we used a pentylentetrazole-induced chronic epilepsy mouse model and treated the mice with intraperitoneal administration of PX-478,a hypoxia-inducible factor-1αinhibitor.Our results showed that PX-478 significantly prolonged the latency of epilepsy,reduced seizure severity,and shortened seizure duration.PX-478 also alleviated neuronal damage in the hippocampal CA1 and CA2 regions,reduced levels of reactive oxygen species and malondialdehyde,and increased levels of superoxide dismutase,catalase,and glutathione peroxidase.Transmission electron microscopy showed that PX-478 treatment reduced mitochondrial damage in the hippocampal neurons of epileptic mice,and significantly improved mitochondrial length and area.Additionally,PX-478 preferentially reduced Fe^(2+)levels and the expression of cyclooxygenase-2,ferritin heavy chain 1 and transferrin in the hippocampus of epileptic mice.It also inhibited the activity of the hypoxia-inducible factor 1α/heme oxygenase-1 pathway.In summary,these findings suggest that PX-478 has the potential to treat epilepsy by inhibiting the hypoxia-inducible factor 1α/heme oxygenase-1 pathway,alleviating oxidative stress,and reducing ferroptosis in hippocampal neurons.
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.
