Objective:To study the effect of p53-targeted small molecular reactivator of p53 and induction of tumor apoptosis (RITA) combined with temozolomide (TMZ) on the glioma cell growth in vitro.Methods:Human glioma cell li...Objective:To study the effect of p53-targeted small molecular reactivator of p53 and induction of tumor apoptosis (RITA) combined with temozolomide (TMZ) on the glioma cell growth in vitro.Methods:Human glioma cell lines U87 were cultured and randomly divided into RITA+TMZ group (treated with 5 μmol/L RITA and 10 μmol/L TMZ), TMZ group (treated with 10 μmol/L TMZ) and control group (treated with drug-free DMEM). After 24 h of treatment, the expression of p53 downstream cell cycle molecules, apoptosis molecules and invasion molecules in cells were measured.Results:p21cip1, Per2, ATM and E-cadherin protein expression in RITA+TMZ group and TMZ group were significantly higher than those in control group while CDK4, CDK6, p-Rb, E2F, MDM2, c-myc, ILK, Snail and Slug protein expression were significantly lower than those in control group;p21cip1, Per2, ATM and E-cadherin protein expression in RITA+TMZ group were significantly higher than those in TMZ group while CDK4, CDK6, p-Rb, E2F, MDM2, c-myc, ILK, Snail and Slug protein expression were significantly lower than those in TMZ group.Conclusion:p53-targeted small molecular RITA combined with temozolomide treatment of glioma cells can induce p53-mediated cell cycle arrest, cell apoptosis activation and cell invasion inhibition.展开更多
An improved acetylcholinesterase liquid crystal(LC) biosensor has been developed for the identification of organophosphates(OPs) by using a reactivator. When the acetylcholinesterases(AChEs) inhibited by different kin...An improved acetylcholinesterase liquid crystal(LC) biosensor has been developed for the identification of organophosphates(OPs) by using a reactivator. When the acetylcholinesterases(AChEs) inhibited by different kinds of OPs are reactived by a reactivator, the catalytic activity of AChEs can be recovered with different activation efficiency because of the different phosphorylation structures formed in the inhibited AChEs. Accordingly, the reactived AChEs can catalyze the hydrolysis of acetylthiocholine to generate thiocholine product in different degrees, which will result in different catalytic growth of AuNPs and further form distinct orientational response of LCs. Based on such a reactivation mechanism, the AChE LC biosensor with a simple, rapid and visual procedure achieves an obvious identification of three OPs pesticides, methamidophos, trichlorfon and paraoxon, by using a pralidoxime reactivator.展开更多
Stroke is the leading cause of mortality globally,ultimately leading to severe,lifelong neurological impairments.Patients often suffer from a secondary cascade of damage,including neuroinflammation,cytotoxicity,oxidat...Stroke is the leading cause of mortality globally,ultimately leading to severe,lifelong neurological impairments.Patients often suffer from a secondary cascade of damage,including neuroinflammation,cytotoxicity,oxidative stress,and mitochondrial dysfunction.Regrettably,there is a paucity of clinically available therapeutics to address these issues.Emerging evidence underscores the pivotal roles of astrocytes,the most abundant glial cells in the brain,throughout the various stages of ischemic stroke.In this comprehensive review,we initially provide an overview of the fundamental physiological functions of astrocytes in the brain,emphasizing their critical role in modulating neuronal homeostasis,synaptic activity,and blood-brain barrier integrity.We then delve into the growing body of evidence that highlights the functional diversity and heterogeneity of astrocytes in the context of ischemic stroke.Their well-established contributions to energy provision,metabolic regulation,and neurotransmitter homeostasis,as well as their emerging roles in mitochondrial recovery,neuroinflammation regulation,and oxidative stress modulation following ischemic injury,are discussed in detail.We also explore the cellular and molecular mechanisms underpinning these functions,with particular emphasis on recently identified targets within astrocytes that offer promising prospects for therapeutic intervention.In the final section of this review,we offer a detailed overview of the current therapeutic strategies targeting astrocytes in the treatment of ischemic stroke.These astrocyte-targeting strategies are categorized into traditional small-molecule drugs,microRNAs(miRNAs),stem cell-based therapies,cellular reprogramming,hydrogels,and extracellular vesicles.By summarizing the current understanding of astrocyte functions and therapeutic targeting approaches,we aim to highlight the critical roles of astrocytes during and after stroke,particularly in the pathophysiological development in ischemic stroke.We also emphasize promising avenues for novel,astrocyte-targeted therapeutics that could become clinically available options,ultimately improving outcomes for patients with stroke.展开更多
Ischemia–reperfusion injury is a common pathophysiological mechanism in retinal degeneration.PANoptosis is a newly defined integral form of regulated cell death that combines the key features of pyroptosis,apoptosis,...Ischemia–reperfusion injury is a common pathophysiological mechanism in retinal degeneration.PANoptosis is a newly defined integral form of regulated cell death that combines the key features of pyroptosis,apoptosis,and necroptosis.Oligomerization of mitochondrial voltage-dependent anion channel 1 is an important pathological event in regulating cell death in retinal ischemia–reperfusion injury.However,its role in PANoptosis remains largely unknown.In this study,we demonstrated that voltage-dependent anion channel 1 oligomerization-mediated mitochondrial dysfunction was associated with PANoptosis in retinal ischemia–reperfusion injury.Inhibition of voltage-dependent anion channel 1 oligomerization suppressed mitochondrial dysfunction and PANoptosis in retinal cells subjected to ischemia–reperfusion injury.Mechanistically,mitochondria-derived reactive oxygen species played a central role in the voltagedependent anion channel 1-mediated regulation of PANoptosis by promoting PANoptosome assembly.Moreover,inhibiting voltage-dependent anion channel 1 oligomerization protected against PANoptosis in the retinas of rats subjected to ischemia–reperfusion injury.Overall,our findings reveal the critical role of voltage-dependent anion channel 1 oligomerization in regulating PANoptosis in retinal ischemia–reperfusion injury,highlighting voltage-dependent anion channel 1 as a promising therapeutic target.展开更多
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 tertiary amine reactivators of acetylcholinesterase (AChE) have been consideredideal reactivators, but research on them has not been developed much for more than20 years for lack of an accurate guiding theory. Bed...The tertiary amine reactivators of acetylcholinesterase (AChE) have been consideredideal reactivators, but research on them has not been developed much for more than20 years for lack of an accurate guiding theory. Bedford reported a series ofnonquaternary reactivators in 1986. It is very important to decide the conformation ofthese reactivators,because it will be helpful in predicting the active site of AChE. Inthis note we shall explore the conformation of a typical reactivator (thedialkylaminoalkyl thioester of α-Keto thiohydroximic acid, shown as molecule 1).展开更多
After injury,bone tissue initiates a reparative response to restore its structure and function.The failure to initiate or delay this response could result in fracture nonunion.The molecular mechanisms underlying the o...After injury,bone tissue initiates a reparative response to restore its structure and function.The failure to initiate or delay this response could result in fracture nonunion.The molecular mechanisms underlying the occurrence of fracture nonunion are not yet established.We propose that hypoxia-triggered signaling pathways,mediated by reactive oxygen species(ROS)homeostasis,control Bmp2 expression and fracture healing initiation.The excessive ROS leads to oxidative stress and,ultimately,fracture nonunion.In this study,we silenced Apex1,the final ROS signaling transducer that mediates the activation of key transcription factors by their cysteines oxidoreduction,evaluating its role during endochondral ossification and fracture repair.Silencing Apex1 in limb bud mesenchyme results in transient metaphyseal dysplasia derived from impaired chondrocyte differentiation.During bone regeneration,Apex1 silencing induces a fracture nonunion phenotype,characterized by delayed fracture repair initiation,impaired periosteal response,and reduced chondrocyte and osteoblast differentiation.This compromised chondrocyte differentiation hampers callus vascularization and healing progression.Our findings highlight a critical mechanism where hypoxia-driven ROS signaling in mesenchymal progenitors through APEX1 is essential for fracture healing initiation.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
Single-atom catalysts for alkyne semi-hydrogenation have been extensively investigated due to their high metal utilization and improved olefin selectivity.However,their reactivity is hindered by the sluggish activatio...Single-atom catalysts for alkyne semi-hydrogenation have been extensively investigated due to their high metal utilization and improved olefin selectivity.However,their reactivity is hindered by the sluggish activation of reactants on isolated sites.Herein,a non-precise metal catalyst consisting of Ni-Cu hetero-diatomic pairs was prepared using a sequential deposition method.The diatomic sites catalyst exhibited an unprecedented activity among non-precious catalysts with over 98%conversion and 77 mol_(C2H2) mol_(metal)^(-1) h^(-1) at 180℃,whereas the single-atom catalysts of Cu/C and Ni/C were almost inert under the same conditions.Experimental and theoretical results revealed the crucial diatomic synergy between the Ni-Cu pairs,wherein acetylene was adsorbed on Ni sites and hydrogen was adsorbed on Cu sites,and the diatomic site enabled spontaneous desorption of ethylene.The superior activity of the diatomic catalyst was observed,resulting from the enhanced dominance of d-electrons of Ni near the Fermi level.The research demonstrates an approach to designing non-precise metal catalysts with extraordinary catalytic performance for alkyne hydrogenation.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
Reactive oxygen species(ROS)act as early messengers in plants exposed to drought,salinity,heat and other environmental challenges.Their timely removal is crucial.Unchecked ROS injure membranes,macromolecules and photo...Reactive oxygen species(ROS)act as early messengers in plants exposed to drought,salinity,heat and other environmental challenges.Their timely removal is crucial.Unchecked ROS injure membranes,macromolecules and photosynthetic systems,ultimately curbing growth or causing cell death.While mitochondria possess inhouse antioxidant machinery,how non-mitochondrial systems contribute to mitochondrial redox homeostasis has remained unresolved.Laura F.DiGiovanni et al.demonstrate that peroxisomes directly protect mitochondria through contact-mediated ROS shuttling.This discovery extends the concept of organelle crosstalk beyond metabolic exchange to contact-mediated ROS flux,adding a system-level buffer against oxidative stress.Deep understanding and regulation of this pathway are highly significant for exploring how ROS coordinate plant stress responses,enhancing crop stress resistance and reducing extreme environment-induced oxidative damage.This may provide breeders and agronomists with a novel approach to develop stress-resistant traits.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
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
BACKGROUND:The central nervous system is a critical target of severe heatstroke,with oxidative stress and multi-organelle damage being the key pathogenic mechanisms.However,research on endogenous antioxidant defense r...BACKGROUND:The central nervous system is a critical target of severe heatstroke,with oxidative stress and multi-organelle damage being the key pathogenic mechanisms.However,research on endogenous antioxidant defense remains limited.In this study,we aimed to characterize neuronal oxidative damage as a key heatstroke pathological mechanism and assess the neuroprotective effects of nuclear factor E2-related factor 2(NRF2).METHODS:After developing in vivo and in vitro heatstroke models,we employed histological staining,cell viability and apoptosis assays,oxidative stress indicators determination,organelle ultrastructural observation,and molecular expression analysis to investigate the mechanisms of brain injury and changes in the NRF2 pathway following heatstroke.We pretreated mice and SH-SY5Y cells with tert-butylhydroquinone(TBHQ) to activate NRF2 expression.Furthermore,we utilized NRF2 knockout(KO) mice and NRF2 siRNA transfection to suppress NRF2 expression,thereby examining the effects of NRF2 both in vivo and in vitro.RESULTS:We found that heatstroke induced neuronal damage,elevated oxidative stress levels,and caused structural damage to both the mitochondria and the endoplasmic reticulum(ER).Notably,NRF2 activation was insufficient post-heatstroke.Pretreatment with TBHQ effectively activated the NRF2 signaling pathway and mitigated the resulting damage.In contrast,these injuries were exacerbated in NRF2 KO mice and SH-SY5Y cells transfected with NRF2 siRNA.CONCLUSION:This preliminary research shows that the NRF2 antioxidant signaling pathway exerts a protective effect against oxidative stress,mitigating both mitochondrial and ER structural damage in neuronal cells during heatstroke.Therefore,targeting the NRF2 pathway is a promising therapeutic strategy for heatstroke-induced neuronal injury.展开更多
Photoreceptor degeneration is a major cause of vision impairment in retinal diseases,for which no effective treatment currently exists.Previous research by our team demonstrated that Lycium barbarum glycopeptide and l...Photoreceptor degeneration is a major cause of vision impairment in retinal diseases,for which no effective treatment currently exists.Previous research by our team demonstrated that Lycium barbarum glycopeptide and luteolin can independently promote photoreceptor survival and function in degenerated mouse retinas,although with limited efficacy.This study evaluated whether a combination of Lycium barbarum glycopeptide and luteolin provides enhanced therapeutic benefits compared with either compound alone.Wild-type mice received a daily oral gavage of Lycium barbarum glycopeptide and luteolin for 7 days prior to intraperitoneal injection of N-nitroso-N-methylurea to induce photoreceptor damage.The treatment continued for an additional week after injury.Retinal structure and function were subsequently assessed using electroretinogram recordings,visual behavior testing,and immunostaining.Western blot analysis was conducted to investigate the underlying protective mechanisms.The results showed that the Lycium barbarum glycopeptide-luteolin mixture significantly increased photoreceptor survival,improved retinal light response,and enhanced visual behavior.Importantly,the combination outperformed either compound alone in protective efficacy.Mechanistic analysis indicated that the mixture suppressed retinal inflammation and modulated the extracellular signal-regulated kinase and Bcl-2-associated X protein/B-cell lymphoma 2 signaling pathways.These findings suggest that the combination of Lycium barbarum glycopeptide and luteolin represents a promising therapeutic strategy for photoreceptor degeneration.展开更多
文摘Objective:To study the effect of p53-targeted small molecular reactivator of p53 and induction of tumor apoptosis (RITA) combined with temozolomide (TMZ) on the glioma cell growth in vitro.Methods:Human glioma cell lines U87 were cultured and randomly divided into RITA+TMZ group (treated with 5 μmol/L RITA and 10 μmol/L TMZ), TMZ group (treated with 10 μmol/L TMZ) and control group (treated with drug-free DMEM). After 24 h of treatment, the expression of p53 downstream cell cycle molecules, apoptosis molecules and invasion molecules in cells were measured.Results:p21cip1, Per2, ATM and E-cadherin protein expression in RITA+TMZ group and TMZ group were significantly higher than those in control group while CDK4, CDK6, p-Rb, E2F, MDM2, c-myc, ILK, Snail and Slug protein expression were significantly lower than those in control group;p21cip1, Per2, ATM and E-cadherin protein expression in RITA+TMZ group were significantly higher than those in TMZ group while CDK4, CDK6, p-Rb, E2F, MDM2, c-myc, ILK, Snail and Slug protein expression were significantly lower than those in TMZ group.Conclusion:p53-targeted small molecular RITA combined with temozolomide treatment of glioma cells can induce p53-mediated cell cycle arrest, cell apoptosis activation and cell invasion inhibition.
基金supported by the International Scientific and Technological Cooperation Projects of China(2012DFR40480)the National Natural Science Foundation of China(21175037,21277042 and J1210040)
文摘An improved acetylcholinesterase liquid crystal(LC) biosensor has been developed for the identification of organophosphates(OPs) by using a reactivator. When the acetylcholinesterases(AChEs) inhibited by different kinds of OPs are reactived by a reactivator, the catalytic activity of AChEs can be recovered with different activation efficiency because of the different phosphorylation structures formed in the inhibited AChEs. Accordingly, the reactived AChEs can catalyze the hydrolysis of acetylthiocholine to generate thiocholine product in different degrees, which will result in different catalytic growth of AuNPs and further form distinct orientational response of LCs. Based on such a reactivation mechanism, the AChE LC biosensor with a simple, rapid and visual procedure achieves an obvious identification of three OPs pesticides, methamidophos, trichlorfon and paraoxon, by using a pralidoxime reactivator.
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.
文摘The tertiary amine reactivators of acetylcholinesterase (AChE) have been consideredideal reactivators, but research on them has not been developed much for more than20 years for lack of an accurate guiding theory. Bedford reported a series ofnonquaternary reactivators in 1986. It is very important to decide the conformation ofthese reactivators,because it will be helpful in predicting the active site of AChE. Inthis note we shall explore the conformation of a typical reactivator (thedialkylaminoalkyl thioester of α-Keto thiohydroximic acid, shown as molecule 1).
文摘After injury,bone tissue initiates a reparative response to restore its structure and function.The failure to initiate or delay this response could result in fracture nonunion.The molecular mechanisms underlying the occurrence of fracture nonunion are not yet established.We propose that hypoxia-triggered signaling pathways,mediated by reactive oxygen species(ROS)homeostasis,control Bmp2 expression and fracture healing initiation.The excessive ROS leads to oxidative stress and,ultimately,fracture nonunion.In this study,we silenced Apex1,the final ROS signaling transducer that mediates the activation of key transcription factors by their cysteines oxidoreduction,evaluating its role during endochondral ossification and fracture repair.Silencing Apex1 in limb bud mesenchyme results in transient metaphyseal dysplasia derived from impaired chondrocyte differentiation.During bone regeneration,Apex1 silencing induces a fracture nonunion phenotype,characterized by delayed fracture repair initiation,impaired periosteal response,and reduced chondrocyte and osteoblast differentiation.This compromised chondrocyte differentiation hampers callus vascularization and healing progression.Our findings highlight a critical mechanism where hypoxia-driven ROS signaling in mesenchymal progenitors through APEX1 is essential for fracture healing initiation.
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 the National Key R&D Program of China(Grant No.2021YFA1501803)the National Natural Science Foundation of China(NSFC,Grant No.21978148&52206156)。
文摘Single-atom catalysts for alkyne semi-hydrogenation have been extensively investigated due to their high metal utilization and improved olefin selectivity.However,their reactivity is hindered by the sluggish activation of reactants on isolated sites.Herein,a non-precise metal catalyst consisting of Ni-Cu hetero-diatomic pairs was prepared using a sequential deposition method.The diatomic sites catalyst exhibited an unprecedented activity among non-precious catalysts with over 98%conversion and 77 mol_(C2H2) mol_(metal)^(-1) h^(-1) at 180℃,whereas the single-atom catalysts of Cu/C and Ni/C were almost inert under the same conditions.Experimental and theoretical results revealed the crucial diatomic synergy between the Ni-Cu pairs,wherein acetylene was adsorbed on Ni sites and hydrogen was adsorbed on Cu sites,and the diatomic site enabled spontaneous desorption of ethylene.The superior activity of the diatomic catalyst was observed,resulting from the enhanced dominance of d-electrons of Ni near the Fermi level.The research demonstrates an approach to designing non-precise metal catalysts with extraordinary catalytic performance for alkyne hydrogenation.
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.
基金supported by the Youth Innovation Promotion Association of the Chinese Academy of Sciences(No.2020261)the Strategic Priority Research Program of the Chinese Academy of Sciences(No.XDA02010000)the Young Potential Program of the Shanghai Institute of Applied Physics,Chinese Academy of Sciences(No.SINAP-YXJH-202412)。
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funded from the Natural Science Foundation of Heilongjiang Province(LH2024C095,YQ2023B001)the China Postdoctoral Science Foundation(2024M751241)+3 种基金the National Key Laboratory of Green Pesticides(Central China Normal University)the earmarked fund for China Agricultural Research System(CARS170503)Heilongjiang Province Agriculture Research SystemEcological Agriculture 20231197Heilongjiang Province“Double First Class”Discipline Collaborative Innovation Achievement Project(LJGXCG2023-036).
文摘Reactive oxygen species(ROS)act as early messengers in plants exposed to drought,salinity,heat and other environmental challenges.Their timely removal is crucial.Unchecked ROS injure membranes,macromolecules and photosynthetic systems,ultimately curbing growth or causing cell death.While mitochondria possess inhouse antioxidant machinery,how non-mitochondrial systems contribute to mitochondrial redox homeostasis has remained unresolved.Laura F.DiGiovanni et al.demonstrate that peroxisomes directly protect mitochondria through contact-mediated ROS shuttling.This discovery extends the concept of organelle crosstalk beyond metabolic exchange to contact-mediated ROS flux,adding a system-level buffer against oxidative stress.Deep understanding and regulation of this pathway are highly significant for exploring how ROS coordinate plant stress responses,enhancing crop stress resistance and reducing extreme environment-induced oxidative damage.This may provide breeders and agronomists with a novel approach to develop stress-resistant traits.
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)+1 种基金Fundamental Research Funds for the Central UniversitiesNational 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 the National Natural Science Foundation of China (No.82202432)the Guangzhou Science and Technology Plan Project (No.2023A04J2059,2024A03J0242)。
文摘BACKGROUND:The central nervous system is a critical target of severe heatstroke,with oxidative stress and multi-organelle damage being the key pathogenic mechanisms.However,research on endogenous antioxidant defense remains limited.In this study,we aimed to characterize neuronal oxidative damage as a key heatstroke pathological mechanism and assess the neuroprotective effects of nuclear factor E2-related factor 2(NRF2).METHODS:After developing in vivo and in vitro heatstroke models,we employed histological staining,cell viability and apoptosis assays,oxidative stress indicators determination,organelle ultrastructural observation,and molecular expression analysis to investigate the mechanisms of brain injury and changes in the NRF2 pathway following heatstroke.We pretreated mice and SH-SY5Y cells with tert-butylhydroquinone(TBHQ) to activate NRF2 expression.Furthermore,we utilized NRF2 knockout(KO) mice and NRF2 siRNA transfection to suppress NRF2 expression,thereby examining the effects of NRF2 both in vivo and in vitro.RESULTS:We found that heatstroke induced neuronal damage,elevated oxidative stress levels,and caused structural damage to both the mitochondria and the endoplasmic reticulum(ER).Notably,NRF2 activation was insufficient post-heatstroke.Pretreatment with TBHQ effectively activated the NRF2 signaling pathway and mitigated the resulting damage.In contrast,these injuries were exacerbated in NRF2 KO mice and SH-SY5Y cells transfected with NRF2 siRNA.CONCLUSION:This preliminary research shows that the NRF2 antioxidant signaling pathway exerts a protective effect against oxidative stress,mitigating both mitochondrial and ER structural damage in neuronal cells during heatstroke.Therefore,targeting the NRF2 pathway is a promising therapeutic strategy for heatstroke-induced neuronal injury.
基金Natural Science Foundation of Guangdong Province,No.2023A1515012397(to YX)the National Natural Science Foundation of China,No.82074169(to XM)+2 种基金the Guangdong Basic and Applied Basic Research Foundation,No.2021A1515012473(to XM)and Project of Administration of Traditional Chinese Medicine of Guangdong Province,No.20202045(to XM)Aier Eye Hospital Group,No.AF2019001(to ST,KFS,YX,and XM).
文摘Photoreceptor degeneration is a major cause of vision impairment in retinal diseases,for which no effective treatment currently exists.Previous research by our team demonstrated that Lycium barbarum glycopeptide and luteolin can independently promote photoreceptor survival and function in degenerated mouse retinas,although with limited efficacy.This study evaluated whether a combination of Lycium barbarum glycopeptide and luteolin provides enhanced therapeutic benefits compared with either compound alone.Wild-type mice received a daily oral gavage of Lycium barbarum glycopeptide and luteolin for 7 days prior to intraperitoneal injection of N-nitroso-N-methylurea to induce photoreceptor damage.The treatment continued for an additional week after injury.Retinal structure and function were subsequently assessed using electroretinogram recordings,visual behavior testing,and immunostaining.Western blot analysis was conducted to investigate the underlying protective mechanisms.The results showed that the Lycium barbarum glycopeptide-luteolin mixture significantly increased photoreceptor survival,improved retinal light response,and enhanced visual behavior.Importantly,the combination outperformed either compound alone in protective efficacy.Mechanistic analysis indicated that the mixture suppressed retinal inflammation and modulated the extracellular signal-regulated kinase and Bcl-2-associated X protein/B-cell lymphoma 2 signaling pathways.These findings suggest that the combination of Lycium barbarum glycopeptide and luteolin represents a promising therapeutic strategy for photoreceptor degeneration.
