Ethylene glycol, glycerol, sorbitol, formamide, and urea were used as plasticizers for the preparation of thermoplastic starch(TPS) from corn starch. The properties of TPS were tested by analysis method. The results...Ethylene glycol, glycerol, sorbitol, formamide, and urea were used as plasticizers for the preparation of thermoplastic starch(TPS) from corn starch. The properties of TPS were tested by analysis method. The results showed that TPSs were more highly plasticized with amines than alcohols. For the same type of plasticizer, the degree of plasticization decreased as the molecular weight of plasticizer increased. The relationship between plasticization degree and TPS properties was characterized and described by mechanical properties and water absorption. The experimental results showed that when the degree of plasticization increased, the tensile strength decreased and the elongation at breakage and water absorption increased.展开更多
A plasticizer triethylene glycol maleate(TEG-MA) was synthesized. The dominated monoester of moderate hydrophobicity with apparent oil-water partition coefficient of 0.042 in the product was confirmed by acid value ...A plasticizer triethylene glycol maleate(TEG-MA) was synthesized. The dominated monoester of moderate hydrophobicity with apparent oil-water partition coefficient of 0.042 in the product was confirmed by acid value determination, HPLC and FTIR. Its plasticizing effect on oxidized starch was manifested by crystallization, aging behaviour, moisture absorption, and mechanical performance. X-ray diffraction data showed that the relative crystallinity of the plasticized starch decreased. Both the crystal and the crystallinity of starch films were rarely changed in aging. Moisture absorption relied on the ester content and relative humidity. The elongation at break increased significantly with plasticizer content more than 10% in the matrix.展开更多
The additives present in polyvinyl chloride(PVC)materials are the major source of organic by-products during PVC degradation.The thermal stabilizer and plasticizer are the main additives that endow PVC with the requir...The additives present in polyvinyl chloride(PVC)materials are the major source of organic by-products during PVC degradation.The thermal stabilizer and plasticizer are the main additives that endow PVC with the required properties during its processing.However,these two additives easily migrate when samples are obtained by physical mixing of the additives with PVC.This causes the reduction of PVC sample efficacy and the increase in the formation of organic by-products in the radiolysis process.In this work,two kinds of grafted PVC samples(tungoil derivative grafted PVC and Atz grafted PVC,abbreviated as P-GT4 and P-AZ3)were synthesized by chemical grafting of 3-amino-1,2,4-triazole(Atz)and tung-oil derivative on PVC,respectively.These two PVC samples were then blended at different mass ratios to obtain hybrid PVC materials with excellent plasticization,thermal stability and migration resistance ability.Differential scanning calorimetry(DSC),discoloration,Congo red test and thermogravimetric analysis(TGA)showed that when the mass ratio of P-GT4 to P-AZ3 in the mixed PVC resin was 1:3,the resulting P1:3-GT4-AZ3(P4)presented the best plasticization and thermal stability.The kinetics of thermal decomposition showed that the activation energy of P4 was much higher than that of the reference material[PVC/DOTP/CaSt2/ZnSt2,PVC/CZ41 for short]at mass lossα=20%and 80%.In addition,the leaching test showed that P4 material possessed excellent migration resistance ability.展开更多
Polylactide(PLA)films blended with poly(butylene adipate-co-terephthalate)(PBAT)were hot melted using a twin screw extruder with the addition of triethyl citrate(TEC)as a plasticizer and toluene diisocyanate(TDI)as a ...Polylactide(PLA)films blended with poly(butylene adipate-co-terephthalate)(PBAT)were hot melted using a twin screw extruder with the addition of triethyl citrate(TEC)as a plasticizer and toluene diisocyanate(TDI)as a compatibilizer.The synergistic effects of the two additives on the mechanical,thermal,and morphological properties of the PLA/PBAT blend films were investigated.The influence of TEC content on the plasticized PLA films and the effect of TDI’s presence on the PLA/PBAT blend films were also studied by comparing them with neat PLA.The results showed a pronounced increase in elongation at break of the plasticized PLA films with increasing TEC levels,but a slight reduction in thermal stability.Also,the addition of TEC and TDI to the blend system not only synergistically enhanced the tensile properties and tensile-impact strength of the PLA/PBAT blends,but also affected their crystallinity and cold crystallization rate,a result of the improvement of interfacial interaction between PLA and PBAT,including the enhancement of their chain mobility.The synergy of the plasticization and compatibilization processes led to the improvement of tensile properties,tensile-impact strength,and compatibility of the blends,accelerating cold crystallization without affecting crystallization.展开更多
Tributyl citrate (TBC) plasticizer has been selected to prepare the novel plasticized PC under different time and temperature. The TBC plasticization effect on PC T, mechanical properties and morphology has been inv...Tributyl citrate (TBC) plasticizer has been selected to prepare the novel plasticized PC under different time and temperature. The TBC plasticization effect on PC T, mechanical properties and morphology has been investigated by DMTA, DSC, tensile test and SEM. The results show that the TBC content in PC is controlled by plasticization time and temperature. The mass-loss test has conftnned a less lost rate of TBC in PC. The T declines gradually with increasing TBC content. The tensile modulus and strength of the plasticized PC also decrease with the increase of TBC content, and an approximate linear relationship is found to exist between the TBC content and the tensile modulus and strength. The SEM images show that significant changes have taken place on the surface and in the cross-section of plasticized thin PC sheet.展开更多
Pharmaceutical solid dosage forms are commonly coated to modify the release of drugs. Due to the disadvantages of coated single-unit dosage forms, such as occurrences of dose dumping and local irritation, coated multi...Pharmaceutical solid dosage forms are commonly coated to modify the release of drugs. Due to the disadvantages of coated single-unit dosage forms, such as occurrences of dose dumping and local irritation, coated multi-particulates are preferred.Coated multi-particulates can eventually be filled into capsules or compressed into tablets.展开更多
The photodegradation of thin films of poly (4-chlorostyrene) and poly (4-bromostyrene) with 265 nm radiation in the presence of oxygen and as a function of irradiation time has been studied mainly using fluorescence, ...The photodegradation of thin films of poly (4-chlorostyrene) and poly (4-bromostyrene) with 265 nm radiation in the presence of oxygen and as a function of irradiation time has been studied mainly using fluorescence, FT-IR, and UV-VIS spectroscopic techniques. The influence of phthalate and terephthalate plasticizers on photo-oxidative degradation was also investigated. Phthalate and terephthalate-plasticizers were found to increase the photodegradation processes in polymeric chains. On the other hand, the intensity of absorption was also found to increase with irradiation time and in the intensity of a new absorption band at longer wavelength. The appearance of new fluorescence bands in the irradiated polymer films can well indicate a possibility of photodegradation of polymer films. In addition, the observed increase in the intensities of the carbonyl and hydroxyl regions of the FT-IR spectra, providing evidence for the photodegradation as well as the photo-oxidation of polymeric chains. The increase in the analyzed ranges was attributed to the formation of alcohols, aliphatic ketones and to the increase in the number of (C=C) that resulted from hydrogen abstraction during chains - scission.展开更多
Neuronal plasticity,the brain's ability to adapt structurally and functionally,is essential for learning,memory,and recovery from injuries.In neurodegenerative diseases such as Alzheimer's disease and Parkinso...Neuronal plasticity,the brain's ability to adapt structurally and functionally,is essential for learning,memory,and recovery from injuries.In neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease,this plasticity is disrupted,leading to cognitive and motor deficits.This review explores the mechanisms of neuronal plasticity and its effect on Alzheimer's disease and Parkinson's disease.Alzheimer's disease features amyloid-beta plaques and tau tangles that impair synaptic function,while Parkinson's disease involves the loss of dopaminergic neurons affecting motor control.Enhancing neuronal plasticity offers therapeutic potential for these diseases.A systematic literature review was conducted using databases such as PubMed,Scopus,and Google Scholar,focusing on studies of neuronal plasticity in Alzheimer's disease and Parkinson's disease.Data synthesis identified key themes such as synaptic mechanisms,neurogenesis,and therapeutic strategies,linking molecular insights to clinical applications.Results highlight that targeting synaptic plasticity mechanisms,such as long-term potentiation and long-term depression,shows promise.Neurotrophic factors,advanced imaging techniques,and molecular tools(e.g.,clustered regularly interspaced short palindromic repeats and optogenetics)are crucial in understanding and enhancing plasticity.Current therapies,including dopamine replacement,deep brain stimulation,and lifestyle interventions,demonstrate the potential to alleviate symptoms and improve outcomes.In conclusion,enhancing neuronal plasticity through targeted therapies holds significant promise for treating neurodegenerative diseases.Future research should integrate multidisciplinary approaches to fully harness the therapeutic potential of neuronal plasticity in Alzheimer's disease and Parkinson's disease.展开更多
With the increasing demand for the development of unconventional oil and gas resources,hydraulic fracturing has become a key technology for enhancing reservoir permeability.However,achieving controlled propagation of ...With the increasing demand for the development of unconventional oil and gas resources,hydraulic fracturing has become a key technology for enhancing reservoir permeability.However,achieving controlled propagation of fracture networks remains a significant challenge under complex geological conditions.This study integrates theoretical analysis and finite-discrete element method(FDEM)simulations to investigate mixed-mode mechanisms,plastic zone evolution at fracture tips,and anisotropic mechanical responses of shale.Modified fracture criteria-including a T-stress-integrated Mohr-Coulo mb criterion and maximum circumferential tensile stress criterion are derived and validated through uniaxial compression and Brazilian splitting tests on Longmaxi Formation shale.Results demonstrate that the modified Mohr-Coulomb criterion effectively predicts anisotropic fracture propagation by characterizing tensile-compressive strength differences,while the plastic zone evolution under maximum circumferential tensile stress is significantly influenced by T-stress:positive T-stress(45°-90°)expands the plastic zone,whereas negative T-stress(0°-45°)contracts it.Lower tensile-to-compressive strength ratios lead to larger plastic zones.An FDEM-based horizontal well fracturing model reveals vertical fracture propagation dominated by bedding plane and interbed fracture extension,forming complex networks,while horizontal fractures initially grow independently before deflecting and inte rconnecting under maximum principal stress.Sensitivity analysis of perforation spacing identifies 62.5 mm(16holes/m)as the optimal configuration,achieving ModeⅡ-dominated fracture networks with superior connectivity and stimulation efficiency.Larger spacings(71.4-83.3 mm)result in reduced efficiency or isolated fractures.By coupling stress interference and fluid pressure field dynamics,this study establishes a methodology to balance fracture network complexity and reservoir stimulation efficacy.The findings provide theoretical insights and engineering guidelines for optimizing hydraulic fracturing designs in anisotropic shale gas reservoirs through advanced fracture criteria and FDEM-based multiphysics simulations.展开更多
The work is conducted to uncover and simulate the dependence of the evolving anisotropic-asymmetric yield behavior on the temperature for an Mg-Gd-Y alloy.Experiments were carried out at 25~300℃,including uniaxial te...The work is conducted to uncover and simulate the dependence of the evolving anisotropic-asymmetric yield behavior on the temperature for an Mg-Gd-Y alloy.Experiments were carried out at 25~300℃,including uniaxial tension and compression.The strength is observed to decrease non-linearly as the temperature increases.Thermal softening effect is not significant when the temperature is lower than 200℃,but the strength decreases dramatically at high temperature than 250℃.Tension-compression asymmetry and anisotropy are observed to be strongly and nonlinearly dependent on strain and temperature.The temperature effect is taken into account in a combined Swift-Voce(SVT)model to predict the temperature-dependent strain hardening behavior with a higher accuracy than the traditional Johnson-Cook and Zerilli-Armstrong equations.An analytical Yoon2014(A-Yoon2014)yield function is established to capture the evolving anisotropicasymmetric behavior with respect to strain and temperature.The predicted force-stroke curves of the A-Yoon2014+SVT model are closer to the experimental results of the three-point bending process than the numerical results of the original Yoon2014+SVT model.Given its userfriendliness and high accuracy for the modeling of temperature-dependent anisotropic-asymmetric hardening behavior,the A-Yoon2014+SVT model is recommended to be utilized in the numerical simulation of plastic forming process for hexagonal close-packed metals.展开更多
Lactate serves as a key energy metabolite in the central nervous system,facilitating essential brain functions,including energy supply,signaling,and epigenetic modulation.Moreover,it links epigenetic modifications wit...Lactate serves as a key energy metabolite in the central nervous system,facilitating essential brain functions,including energy supply,signaling,and epigenetic modulation.Moreover,it links epigenetic modifications with metabolic reprogramming.Nonetheless,the specific mechanisms and roles of this connection in astrocytes remain unclear.Therefore,this review aims to explore the role and specific mechanisms of lactate in the metabolic reprogramming of astrocytes in the central nervous system.The close relationship between epigenetic modifications and metabolic reprogramming was discussed.Therapeutic strategies for targeting metabolic reprogramming in astrocytes in the central nervous system were also outlined to guide future research in central nervous system diseases.In the nervous system,lactate plays an essential role.However,its mechanism of action as a bridge between metabolic reprogramming and epigenetic modifications in the nervous system requires future investigation.The involvement of lactate in epigenetic modifications is currently a hot research topic,especially in lactylation modification,a key determinant in this process.Lactate also indirectly regulates various epigenetic modifications,such as N6-methyladenosine,acetylation,ubiquitination,and phosphorylation modifications,which are closely linked to several neurological disorders.In addition,exploring the clinical applications and potential therapeutic strategies of lactic acid provides new insights for future neurological disease treatments.展开更多
A unique global strain approach based on the transition state theory was proposed to quantify the creep-recovery processes of metallic glasses,in which the structure of glasses is predominantly governed by the macrosc...A unique global strain approach based on the transition state theory was proposed to quantify the creep-recovery processes of metallic glasses,in which the structure of glasses is predominantly governed by the macroscopic strain.This methodology allows for the calculation of strain-dependent activation energy and activation volume for flow defects.The activation energy and volume of creep both increase linearly with the magnitude of strain.Upon the glass-to-liquid transition,they get large and strain-independent,which serves as a signature of the glass transition.During creep recovery,the cooperation of deformation units increases the activation volume but decreases activation energy due to the decrease in free volume.Notably,only a fraction of the anelasticity accumulated during creep persists in the recovery process;the rest is suppressed by structural relaxation.The results introduce physical insights into the deformation and relaxation of metastable solids that are not available in the usual rate-dependent theory developed for crystal plasticity.展开更多
This study presents a multi-scale modeling framework to describe the mechanical behavior of a 0.1 mm-thick commercially pure titanium(CP-Ti)sheet developed for fuel cell bipolar plates.Since standardized methods for c...This study presents a multi-scale modeling framework to describe the mechanical behavior of a 0.1 mm-thick commercially pure titanium(CP-Ti)sheet developed for fuel cell bipolar plates.Since standardized methods for characterizing ultra-thin sheets under complex stress states are lacking,a virtual modeling approach was employed.At the grain scale,a crystal plasticity finite element(CPFE)model was constructed to incorporate the relevant slip and twinning systems,enabling prediction of responses under diverse loading conditions.Extending to the continuum scale,the CPFE results,combined with tensile data,were used to calibrate an advanced constitutive model based on the evolutionary Yld2000-2d yield function,capable of capturing anisotropic behavior.Validation against independent limiting dome height tests confirmed the predictive accuracy of the framework.The proposed approach provides a basis for simulating the forming behavior of ultra-thin CP-Ti sheets and supports precise manufacturing of bipolar plates in fuel cell systems.展开更多
In rock engineering,natural cracks in rock masses subjected to external loads tend to initiate and propagate,leading to potential safety hazards.To investigate the effect of cracking behavior on the mechanical propert...In rock engineering,natural cracks in rock masses subjected to external loads tend to initiate and propagate,leading to potential safety hazards.To investigate the effect of cracking behavior on the mechanical properties of rocks,the cracking processes of pre-cracked rocks have been extensively studied using numerical modeling methods.The peridynamics(PD)exhibits advantages over other numerical methods due to the absence of the requirements for remeshing and external crack growth criterion.However,for modeling pre-cracked rock cracking processes under impact,current PD implementations lack generally applicable rock constitutive models and impact contact models,which leads to difficulties in determining rock material parameters and efficiently calculating impact loads.This paper proposes a non-ordinary state-based peridynamics(NOSBPD)modeling method integrating the Drucker-Prager(DP)plasticity model and an efficient contact model to address the above problems.In the proposed method,the Drucker-Prager plasticity model is integrated into the NOSBPD,thereby equipping NOSBPD with the capability to accurately characterize the nonlinear stress-strain relationship inherent in rocks.An efficient contact model between particles and meshes is designed to calculate the impact loads,which is essentially a coupling method of PD with the finite element method(FEM).The effectiveness of the proposed NOSBPD modeling method is verified by comparison with other numerical methods and experiments.Experimental results indicate that the proposed method can effectively and accurately predict the 3D cracking processes of pre-cracked cracks under impact loading,and the maximum principal stress is the key driver behind wing crack formation in pre-cracked rocks.展开更多
The fabrication of 304L stainless welding wires with a diameter 1.6 mm by using electrochemical cold drawing(ECD)of bars with a diameter of 5.6 mm was investigated,as well as that via traditional cold drawing(TCD)for ...The fabrication of 304L stainless welding wires with a diameter 1.6 mm by using electrochemical cold drawing(ECD)of bars with a diameter of 5.6 mm was investigated,as well as that via traditional cold drawing(TCD)for comparison.The results indicated that the dilute H2SO4aqueous solution was an appropriate electrolyte for ECD,and increasing the H2SO4concentration and current density within a range improved the corrosion rate and uniformity,leading to an easier and more coordinated deformation through uniformly distributing geometrically necessary dislocations and curved large-angle grain boundaries,and decreasing their density,and thus,an enhanced electrochemical plasticization(EP).Under the optimized electrochemical parameters(0.5 mol L-1H2SO4electrolyte and current density of 12.2 mA cm-2),the average cumulative reduction rate required for annealing was up to~34%,obviously higher than~20%of TCD due to the decreased work-hardening from the EP,so that the number of annealing was significantly reduced from 10 of TCD to 5,when the drawing pass was 23.In addition,the surface of the ECD wire was distinctly smoother and brighter than that of the TCD one.These findings confirm the large potential in engineering applications of the ECD technology based on the EP effect.展开更多
Microplastics(MPs)are ubiquitous and pose an environmental risk.This review examined MP pollution in terrestrial ecosystems from a myriad of poorly understood sources.Knowledge regarding the occurrence sources,migrati...Microplastics(MPs)are ubiquitous and pose an environmental risk.This review examined MP pollution in terrestrial ecosystems from a myriad of poorly understood sources.Knowledge regarding the occurrence sources,migration behaviors,ecotoxicology,absorption mechanisms,and effects of MPs has also been fully summarized.Microplastics interact with contaminants,such as antibiotics,pesticides,heavy metals,etc.,and may act as vectors for contaminant transfer in terrestrial ecosystems.The transportation and retention of MPs in soil are governed by interactions among their inherent properties,such as size,shape,surface charge,and density.Interestingly,MP migration into soil is lacking research.The MPs and nanoplastics were also found in edible fruits and vegetables.The MP contamination in soil affects ecosystems,causing soil structure changes,fertility reduction,and pollutant leaching into groundwater.The MP concentration lies in the range of 43-2443 and 40-43000 items kg-1in agricultural and urban soils,respectively.This review provides a comprehensive roadmap for future research and a framework for soil MP risk assessment.Future studies on the uptake,accumulation,and translocation of MPs and their associated toxins by plants are essential for evaluating their risks to food security and human health.Research on MPs in terrestrial habitats lacks comprehensive data on their long-term persistence,degradation pathways,and interactions with soil components under varying environmental conditions.Additionally,limited understanding exists regarding MP impacts on soil biodiversity,pollutant mobility,and plant uptake,highlighting the need for innovative detection methods and effective pollution abatement strategies.展开更多
The pervasive accumulation of plastic waste exacerbates environmental degradation and undermines resource circularity.Selective thermal catalysis emerges as a transformative pathway for valorizing waste plastics into ...The pervasive accumulation of plastic waste exacerbates environmental degradation and undermines resource circularity.Selective thermal catalysis emerges as a transformative pathway for valorizing waste plastics into value-added chemicals,yet persistent challenges in catalytic activity and product selectivity demand systematic resolution.This review decodes cutting-edge advances in thermal depolymerization by converging two critical dimensions:atomic-scale active site engineering-where rational design of coordination features and interfacial architectures regulates C-C cleavage energetics and intermediate adsorption-and macromolecular-scale manipulation of polymer transient states-leveraging nanoconfinement effects,chain folding dynamics,and thermal fragmentation to accelerate conversion kinetics.We further highlight breakthroughs in operando char-acterization techniques that resolve time-evolving reaction coordinates across catalytic systems.By establishing multiscale structure-activity relationships linking catalyst configurations to polymer dynamics,this analysis derives design paradigms for next-generation upcycling systems.These principles enable economically viable,industrially scalable plastic valorization while charting a strategic trajectory toward carbon-circular economies.展开更多
Chronic pain following a spinal cord injury refers to pain that persists or recurs after the injury.This pain can manifest as burning,stinging,or sensations similar to electric shocks.Recent studies have shown that sp...Chronic pain following a spinal cord injury refers to pain that persists or recurs after the injury.This pain can manifest as burning,stinging,or sensations similar to electric shocks.Recent studies have shown that spinal cord stimulation is an effective way to treat chronic pain after spinal cord injury.The purpose of this review is to introduce the technique of spinal cord stimulation,the clinical manifestations of spinal cord injury,and the role of spinal cord stimulation in the treatment of spinal cord injury.The mechanism and clinical application of spinal cord stimulation in the treatment of pain after spinal cord injury are discussed.The mechanism of spinal cord stimulation primarily involves three aspects:neuromodulation,neurochemical regulation,and anti-inflammatory effects,along with nerve repair.In terms of neuromodulation,spinal cord stimulation is based on the gate control theory of pain.It activates large-diameter amyloid-β nerve fibers to promote the release of inhibitory neurotransmitters by gamma-aminobutyric acidergic inhibitory interneurons in the spinal cord,thereby blocking the transmission of pain signals from small-diameter C fibers.Neurochemical studies indicate that spinal cord stimulation can regulate the balance of neurotransmitters within the spinal cord,increasing the release of inhibitory neurotransmitters such as gamma-aminobutyric acid,serotonin,and acetylcholine while reducing the levels of excitatory neurotransmitters.Additionally,spinal cord stimulation exhibits significant anti-inflammatory and neuroprotective effects,downregulating pro-inflammatory factor levels,upregulating anti-inflammatory factor expression,alleviating neuroinflammatory responses,and repairing damaged neural circuits by promoting the secretion of neurotrophic factors and axonal regeneration.Spinal cord stimulation have demonstrated remarkable efficacy in the clinical treatment of pain after spinal cord injury,but there are still limitations such as small sample size and high heterogeneity in clinical studies,as well as insufficient long-term efficacy data.Future research should conduct multi-center large-sample randomized controlled trials,and establish long-term follow-up mechanisms to improve evidence-based medical evidence.展开更多
Alzheimer's disease is typified by amyloid-beta oligomer-mediated synaptic disruption,neuroinflammation,and mitochondrial loss of function,culminating in cognitive decline.Recent evidence points toward the β2-...Alzheimer's disease is typified by amyloid-beta oligomer-mediated synaptic disruption,neuroinflammation,and mitochondrial loss of function,culminating in cognitive decline.Recent evidence points toward the β2-adrenergic receptor as a target through its regulation of synaptic plasticity,neuroinflammation,and epigenetic control.Activation of β2-adrenergic receptor potentiates long-term potentiation,reverses amyloid-beta-mediated synaptic loss,and stimulates neuroprotective gene expression through cyclic adenosine monophosphateprotein kinase A-cyclic AMP response element-binding protein.Moreover,β2-adrenergic receptor suppression of histone deacetylase 2/3 promotes transcriptional reprogramming,supporting synaptic function.Beyond synaptic maintenance,activation of β2-adrenergic receptor prevents neuroinflammation by polarizing microglia toward an anti-inflammatory phenotype and augmenting amyloid-beta degradation.Additionally,mitochondrial metabolism is regulated by β2-adrenergic receptor,diminishing oxidative stress and allowing for bioenergetic resilience.Enriched environments mediate their neuroprotective effects through,in part,activation of β2-adrenergic receptor,supporting its role in promoting synaptic resilience.Pharmacological activation of β2-adrenergic receptor with specific agonists such as formoterol and clenbuterol has shown promise in preclinical models of Alzheimer's disease by restoring cognitive function and synaptic integrity.In this review,the molecular mechanisms of β2-adrenergic receptor-mediated neuroprotection are examined,with specific emphasis on its regulation of synaptic plasticity,neuroinflammation,mitochondrial function,and epigenetic control.Due to its multi-faceted action for maintenance of neuronal health,activation of β2-adrenergic receptor is an appealing therapy for Alzheimer's disease.Future research needs to target optimizing brain-penetrant β2-adrenergic receptor agonists and determining their longterm effects on Alzheimer's disease pathology.展开更多
The dentate gyrus of the hippocampus is a plastic structure that displays modifications at different levels in response to positive stimuli as well as to negative conditions such as brain damage.The latter involves gl...The dentate gyrus of the hippocampus is a plastic structure that displays modifications at different levels in response to positive stimuli as well as to negative conditions such as brain damage.The latter involves global alterations,making understanding plastic responses triggered by local damage difficult.One key feature of the dentate gyrus is that it contains a well-defined neurogenic niche,the subgranular zone,and beyond neurogenesis,newly born granule cells may maintain a“young”phenotype throughout life,adding to the plastic nature of the structure.Here,we present a novel experimental model of local brain damage in organotypic entorhino-hippocampal cultures that results in the activation of adjacent newly born granule cells.A small piece of filter paper was placed on the surface of the granule cell layer of the dentate gyrus,which evoked a foreign body reaction of astrocytes,along with the activation of local young neurons expressing doublecortin.Forty-eight hours after foreign body placement,the number of doublecortin-immunoreactive cells increased in the subgranular zone in the direct vicinity of the foreign body,whereas overall increased doublecortin immunoreactivity was observed in the granule cell layer and molecular layer of the dentate gyrus.Foreign body placement in the pyramidal layer of the CA1 region evoked a comparable local astroglial reaction but did not lead to an increase in doublecortin-immunoreactive in either the CA1 region or the adjacent dentate gyrus.Seven days after foreign body placement in the dentate gyrus,the increase in doublecortin-immunoreactivity was no longer observed,indicating the transient activation of young cells.However,7 days after foreign body placement,the number of doublecortin-immunoreactive granule cells coimmunoreactive for calbindin was lower than that under the control conditions.As calbindin is a marker for mature granule cells,this result suggests that activated young cells remain at a more immature stage following foreign body placement.Live imaging of retrovirally green fluorescent protein-labeled newly born granule cells revealed the orientation and growth of their dendrites toward the foreign body placement.This novel experimental model of foreign body placement in organotypic entorhino-hippocampal cultures could serve as a valuable tool for studying both glial reactivity and neuronal plasticity,specifically of newly born neurons under controlled in vitro conditions.展开更多
基金Funded by the Fundamental Research Funds for the Central Universities(DL13CB13)the China Postdoctoral Science Foundation Funded Project(No.2014M550178)the National Natural Science Foundation of China(No.31200442)
摘要Ethylene glycol, glycerol, sorbitol, formamide, and urea were used as plasticizers for the preparation of thermoplastic starch(TPS) from corn starch. The properties of TPS were tested by analysis method. The results showed that TPSs were more highly plasticized with amines than alcohols. For the same type of plasticizer, the degree of plasticization decreased as the molecular weight of plasticizer increased. The relationship between plasticization degree and TPS properties was characterized and described by mechanical properties and water absorption. The experimental results showed that when the degree of plasticization increased, the tensile strength decreased and the elongation at breakage and water absorption increased.
基金Funded by Science and Technology Support Project of Sichuan Province(Nos.2014GZ0136 and 2015GZ0176)National Natural Science Foundation of China(No.51603134)
摘要A plasticizer triethylene glycol maleate(TEG-MA) was synthesized. The dominated monoester of moderate hydrophobicity with apparent oil-water partition coefficient of 0.042 in the product was confirmed by acid value determination, HPLC and FTIR. Its plasticizing effect on oxidized starch was manifested by crystallization, aging behaviour, moisture absorption, and mechanical performance. X-ray diffraction data showed that the relative crystallinity of the plasticized starch decreased. Both the crystal and the crystallinity of starch films were rarely changed in aging. Moisture absorption relied on the ester content and relative humidity. The elongation at break increased significantly with plasticizer content more than 10% in the matrix.
基金the National Natural Science Foundation of China(21905117)Guangxi Key Laboratory of Chemistry and Engineering of Forest Products(GXFK2203)and the Natural Science Foundation of Jiangsu Province(BK20201128)the Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD).
摘要The additives present in polyvinyl chloride(PVC)materials are the major source of organic by-products during PVC degradation.The thermal stabilizer and plasticizer are the main additives that endow PVC with the required properties during its processing.However,these two additives easily migrate when samples are obtained by physical mixing of the additives with PVC.This causes the reduction of PVC sample efficacy and the increase in the formation of organic by-products in the radiolysis process.In this work,two kinds of grafted PVC samples(tungoil derivative grafted PVC and Atz grafted PVC,abbreviated as P-GT4 and P-AZ3)were synthesized by chemical grafting of 3-amino-1,2,4-triazole(Atz)and tung-oil derivative on PVC,respectively.These two PVC samples were then blended at different mass ratios to obtain hybrid PVC materials with excellent plasticization,thermal stability and migration resistance ability.Differential scanning calorimetry(DSC),discoloration,Congo red test and thermogravimetric analysis(TGA)showed that when the mass ratio of P-GT4 to P-AZ3 in the mixed PVC resin was 1:3,the resulting P1:3-GT4-AZ3(P4)presented the best plasticization and thermal stability.The kinetics of thermal decomposition showed that the activation energy of P4 was much higher than that of the reference material[PVC/DOTP/CaSt2/ZnSt2,PVC/CZ41 for short]at mass lossα=20%and 80%.In addition,the leaching test showed that P4 material possessed excellent migration resistance ability.
基金financially supported by Development and Promotion of Science and Technology Talents (DPST) (No. 013/2559)
摘要Polylactide(PLA)films blended with poly(butylene adipate-co-terephthalate)(PBAT)were hot melted using a twin screw extruder with the addition of triethyl citrate(TEC)as a plasticizer and toluene diisocyanate(TDI)as a compatibilizer.The synergistic effects of the two additives on the mechanical,thermal,and morphological properties of the PLA/PBAT blend films were investigated.The influence of TEC content on the plasticized PLA films and the effect of TDI’s presence on the PLA/PBAT blend films were also studied by comparing them with neat PLA.The results showed a pronounced increase in elongation at break of the plasticized PLA films with increasing TEC levels,but a slight reduction in thermal stability.Also,the addition of TEC and TDI to the blend system not only synergistically enhanced the tensile properties and tensile-impact strength of the PLA/PBAT blends,but also affected their crystallinity and cold crystallization rate,a result of the improvement of interfacial interaction between PLA and PBAT,including the enhancement of their chain mobility.The synergy of the plasticization and compatibilization processes led to the improvement of tensile properties,tensile-impact strength,and compatibility of the blends,accelerating cold crystallization without affecting crystallization.
基金Funded by the Natural Science Foundation of Hubei Province(No.2010CDB04604)
摘要Tributyl citrate (TBC) plasticizer has been selected to prepare the novel plasticized PC under different time and temperature. The TBC plasticization effect on PC T, mechanical properties and morphology has been investigated by DMTA, DSC, tensile test and SEM. The results show that the TBC content in PC is controlled by plasticization time and temperature. The mass-loss test has conftnned a less lost rate of TBC in PC. The T declines gradually with increasing TBC content. The tensile modulus and strength of the plasticized PC also decrease with the increase of TBC content, and an approximate linear relationship is found to exist between the TBC content and the tensile modulus and strength. The SEM images show that significant changes have taken place on the surface and in the cross-section of plasticized thin PC sheet.
摘要Pharmaceutical solid dosage forms are commonly coated to modify the release of drugs. Due to the disadvantages of coated single-unit dosage forms, such as occurrences of dose dumping and local irritation, coated multi-particulates are preferred.Coated multi-particulates can eventually be filled into capsules or compressed into tablets.
摘要The photodegradation of thin films of poly (4-chlorostyrene) and poly (4-bromostyrene) with 265 nm radiation in the presence of oxygen and as a function of irradiation time has been studied mainly using fluorescence, FT-IR, and UV-VIS spectroscopic techniques. The influence of phthalate and terephthalate plasticizers on photo-oxidative degradation was also investigated. Phthalate and terephthalate-plasticizers were found to increase the photodegradation processes in polymeric chains. On the other hand, the intensity of absorption was also found to increase with irradiation time and in the intensity of a new absorption band at longer wavelength. The appearance of new fluorescence bands in the irradiated polymer films can well indicate a possibility of photodegradation of polymer films. In addition, the observed increase in the intensities of the carbonyl and hydroxyl regions of the FT-IR spectra, providing evidence for the photodegradation as well as the photo-oxidation of polymeric chains. The increase in the analyzed ranges was attributed to the formation of alcohols, aliphatic ketones and to the increase in the number of (C=C) that resulted from hydrogen abstraction during chains - scission.
基金financially supported by King Abdulaziz University,Deanship of Scientific Research(DSR)。
摘要Neuronal plasticity,the brain's ability to adapt structurally and functionally,is essential for learning,memory,and recovery from injuries.In neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease,this plasticity is disrupted,leading to cognitive and motor deficits.This review explores the mechanisms of neuronal plasticity and its effect on Alzheimer's disease and Parkinson's disease.Alzheimer's disease features amyloid-beta plaques and tau tangles that impair synaptic function,while Parkinson's disease involves the loss of dopaminergic neurons affecting motor control.Enhancing neuronal plasticity offers therapeutic potential for these diseases.A systematic literature review was conducted using databases such as PubMed,Scopus,and Google Scholar,focusing on studies of neuronal plasticity in Alzheimer's disease and Parkinson's disease.Data synthesis identified key themes such as synaptic mechanisms,neurogenesis,and therapeutic strategies,linking molecular insights to clinical applications.Results highlight that targeting synaptic plasticity mechanisms,such as long-term potentiation and long-term depression,shows promise.Neurotrophic factors,advanced imaging techniques,and molecular tools(e.g.,clustered regularly interspaced short palindromic repeats and optogenetics)are crucial in understanding and enhancing plasticity.Current therapies,including dopamine replacement,deep brain stimulation,and lifestyle interventions,demonstrate the potential to alleviate symptoms and improve outcomes.In conclusion,enhancing neuronal plasticity through targeted therapies holds significant promise for treating neurodegenerative diseases.Future research should integrate multidisciplinary approaches to fully harness the therapeutic potential of neuronal plasticity in Alzheimer's disease and Parkinson's disease.
基金financially supported by the First-Class Discipline Collaborative Innovation Program of Heilongjiang Province(Grant No.LJGXCG2024-F02)the Key Research and Development Program of Heilongjiang Province(Grant No.2024ZX09C01)+1 种基金The Postdoctoral Special Funding of Heilongjiang Province(LBH-TZ2301)supported by Heilongjiang Provincial Natural Science Foundation of China(LH2022E020)。
摘要With the increasing demand for the development of unconventional oil and gas resources,hydraulic fracturing has become a key technology for enhancing reservoir permeability.However,achieving controlled propagation of fracture networks remains a significant challenge under complex geological conditions.This study integrates theoretical analysis and finite-discrete element method(FDEM)simulations to investigate mixed-mode mechanisms,plastic zone evolution at fracture tips,and anisotropic mechanical responses of shale.Modified fracture criteria-including a T-stress-integrated Mohr-Coulo mb criterion and maximum circumferential tensile stress criterion are derived and validated through uniaxial compression and Brazilian splitting tests on Longmaxi Formation shale.Results demonstrate that the modified Mohr-Coulomb criterion effectively predicts anisotropic fracture propagation by characterizing tensile-compressive strength differences,while the plastic zone evolution under maximum circumferential tensile stress is significantly influenced by T-stress:positive T-stress(45°-90°)expands the plastic zone,whereas negative T-stress(0°-45°)contracts it.Lower tensile-to-compressive strength ratios lead to larger plastic zones.An FDEM-based horizontal well fracturing model reveals vertical fracture propagation dominated by bedding plane and interbed fracture extension,forming complex networks,while horizontal fractures initially grow independently before deflecting and inte rconnecting under maximum principal stress.Sensitivity analysis of perforation spacing identifies 62.5 mm(16holes/m)as the optimal configuration,achieving ModeⅡ-dominated fracture networks with superior connectivity and stimulation efficiency.Larger spacings(71.4-83.3 mm)result in reduced efficiency or isolated fractures.By coupling stress interference and fluid pressure field dynamics,this study establishes a methodology to balance fracture network complexity and reservoir stimulation efficacy.The findings provide theoretical insights and engineering guidelines for optimizing hydraulic fracturing designs in anisotropic shale gas reservoirs through advanced fracture criteria and FDEM-based multiphysics simulations.
基金support by the National Natural Science Foundation of China(Grant No.52075423,U2141214)National Science and Technology Major Project of China(No.J2019-III-0008-0051)Taiyuan University of Science and Technology Scientific Research Initial Funding(Grant No.20242119).
摘要The work is conducted to uncover and simulate the dependence of the evolving anisotropic-asymmetric yield behavior on the temperature for an Mg-Gd-Y alloy.Experiments were carried out at 25~300℃,including uniaxial tension and compression.The strength is observed to decrease non-linearly as the temperature increases.Thermal softening effect is not significant when the temperature is lower than 200℃,but the strength decreases dramatically at high temperature than 250℃.Tension-compression asymmetry and anisotropy are observed to be strongly and nonlinearly dependent on strain and temperature.The temperature effect is taken into account in a combined Swift-Voce(SVT)model to predict the temperature-dependent strain hardening behavior with a higher accuracy than the traditional Johnson-Cook and Zerilli-Armstrong equations.An analytical Yoon2014(A-Yoon2014)yield function is established to capture the evolving anisotropicasymmetric behavior with respect to strain and temperature.The predicted force-stroke curves of the A-Yoon2014+SVT model are closer to the experimental results of the three-point bending process than the numerical results of the original Yoon2014+SVT model.Given its userfriendliness and high accuracy for the modeling of temperature-dependent anisotropic-asymmetric hardening behavior,the A-Yoon2014+SVT model is recommended to be utilized in the numerical simulation of plastic forming process for hexagonal close-packed metals.
基金supported by the National Natural Science Foundation of China,Nos.82071383,82371392(to BN)the Natural Science Foundation of Shandong Province of China(Key Project),No.ZR2020KH007(to BN)+1 种基金“Taishan Scholar Distinguished Expert Program”of Shandong Province,No.tstp20231257(to BN)Health Commission Science and Technology Plan Project of Jinan,No.2023-1-8(to YZ).
摘要Lactate serves as a key energy metabolite in the central nervous system,facilitating essential brain functions,including energy supply,signaling,and epigenetic modulation.Moreover,it links epigenetic modifications with metabolic reprogramming.Nonetheless,the specific mechanisms and roles of this connection in astrocytes remain unclear.Therefore,this review aims to explore the role and specific mechanisms of lactate in the metabolic reprogramming of astrocytes in the central nervous system.The close relationship between epigenetic modifications and metabolic reprogramming was discussed.Therapeutic strategies for targeting metabolic reprogramming in astrocytes in the central nervous system were also outlined to guide future research in central nervous system diseases.In the nervous system,lactate plays an essential role.However,its mechanism of action as a bridge between metabolic reprogramming and epigenetic modifications in the nervous system requires future investigation.The involvement of lactate in epigenetic modifications is currently a hot research topic,especially in lactylation modification,a key determinant in this process.Lactate also indirectly regulates various epigenetic modifications,such as N6-methyladenosine,acetylation,ubiquitination,and phosphorylation modifications,which are closely linked to several neurological disorders.In addition,exploring the clinical applications and potential therapeutic strategies of lactic acid provides new insights for future neurological disease treatments.
基金supported by the National Natural Science Foundation of China(NSFC)(Grant Nos.52271153 and 12472112)the Strategic Priority Research Program(Grants Nos.XDB0620103 and XDB0510301)+5 种基金the Youth Innovation Promotion Association of Chinese Academy of SciencesResearch Grant Council(RGC)the Hong Kong government through the General Research Fund(GRF)(Grant Nos.CityU11200719 and CityU11213118)MICIU/AEI/10.13039/501100011033(Grant No.PID2023-146623NB-I00)Maria de Maeztu Units of Excellence Programme(Grant No.CEX2023-001300-M)Generalitat de Catalunya/AGAUR(Grant No.2021-SGR-00343).
摘要A unique global strain approach based on the transition state theory was proposed to quantify the creep-recovery processes of metallic glasses,in which the structure of glasses is predominantly governed by the macroscopic strain.This methodology allows for the calculation of strain-dependent activation energy and activation volume for flow defects.The activation energy and volume of creep both increase linearly with the magnitude of strain.Upon the glass-to-liquid transition,they get large and strain-independent,which serves as a signature of the glass transition.During creep recovery,the cooperation of deformation units increases the activation volume but decreases activation energy due to the decrease in free volume.Notably,only a fraction of the anelasticity accumulated during creep persists in the recovery process;the rest is suppressed by structural relaxation.The results introduce physical insights into the deformation and relaxation of metastable solids that are not available in the usual rate-dependent theory developed for crystal plasticity.
基金supported by the National Research Foundation of Korea(NRF)grant funded by the Korea government(MSIT)(No.RS-2024-00338965)financial support from the Fundamental Research Program of the Korea Institute of Materials Science(No.PNKA300/PNKA730)。
摘要This study presents a multi-scale modeling framework to describe the mechanical behavior of a 0.1 mm-thick commercially pure titanium(CP-Ti)sheet developed for fuel cell bipolar plates.Since standardized methods for characterizing ultra-thin sheets under complex stress states are lacking,a virtual modeling approach was employed.At the grain scale,a crystal plasticity finite element(CPFE)model was constructed to incorporate the relevant slip and twinning systems,enabling prediction of responses under diverse loading conditions.Extending to the continuum scale,the CPFE results,combined with tensile data,were used to calibrate an advanced constitutive model based on the evolutionary Yld2000-2d yield function,capable of capturing anisotropic behavior.Validation against independent limiting dome height tests confirmed the predictive accuracy of the framework.The proposed approach provides a basis for simulating the forming behavior of ultra-thin CP-Ti sheets and supports precise manufacturing of bipolar plates in fuel cell systems.
基金support from the National Natural Science Foundation of China(Grant Nos.42277161 and 42230709).
摘要In rock engineering,natural cracks in rock masses subjected to external loads tend to initiate and propagate,leading to potential safety hazards.To investigate the effect of cracking behavior on the mechanical properties of rocks,the cracking processes of pre-cracked rocks have been extensively studied using numerical modeling methods.The peridynamics(PD)exhibits advantages over other numerical methods due to the absence of the requirements for remeshing and external crack growth criterion.However,for modeling pre-cracked rock cracking processes under impact,current PD implementations lack generally applicable rock constitutive models and impact contact models,which leads to difficulties in determining rock material parameters and efficiently calculating impact loads.This paper proposes a non-ordinary state-based peridynamics(NOSBPD)modeling method integrating the Drucker-Prager(DP)plasticity model and an efficient contact model to address the above problems.In the proposed method,the Drucker-Prager plasticity model is integrated into the NOSBPD,thereby equipping NOSBPD with the capability to accurately characterize the nonlinear stress-strain relationship inherent in rocks.An efficient contact model between particles and meshes is designed to calculate the impact loads,which is essentially a coupling method of PD with the finite element method(FEM).The effectiveness of the proposed NOSBPD modeling method is verified by comparison with other numerical methods and experiments.Experimental results indicate that the proposed method can effectively and accurately predict the 3D cracking processes of pre-cracked cracks under impact loading,and the maximum principal stress is the key driver behind wing crack formation in pre-cracked rocks.
基金supported by Major Science and Technology Project of Gansu Province(Grant No.23ZDGA010)National Natural Science Foundation of China(Grant No.51971105).
摘要The fabrication of 304L stainless welding wires with a diameter 1.6 mm by using electrochemical cold drawing(ECD)of bars with a diameter of 5.6 mm was investigated,as well as that via traditional cold drawing(TCD)for comparison.The results indicated that the dilute H2SO4aqueous solution was an appropriate electrolyte for ECD,and increasing the H2SO4concentration and current density within a range improved the corrosion rate and uniformity,leading to an easier and more coordinated deformation through uniformly distributing geometrically necessary dislocations and curved large-angle grain boundaries,and decreasing their density,and thus,an enhanced electrochemical plasticization(EP).Under the optimized electrochemical parameters(0.5 mol L-1H2SO4electrolyte and current density of 12.2 mA cm-2),the average cumulative reduction rate required for annealing was up to~34%,obviously higher than~20%of TCD due to the decreased work-hardening from the EP,so that the number of annealing was significantly reduced from 10 of TCD to 5,when the drawing pass was 23.In addition,the surface of the ECD wire was distinctly smoother and brighter than that of the TCD one.These findings confirm the large potential in engineering applications of the ECD technology based on the EP effect.
摘要Microplastics(MPs)are ubiquitous and pose an environmental risk.This review examined MP pollution in terrestrial ecosystems from a myriad of poorly understood sources.Knowledge regarding the occurrence sources,migration behaviors,ecotoxicology,absorption mechanisms,and effects of MPs has also been fully summarized.Microplastics interact with contaminants,such as antibiotics,pesticides,heavy metals,etc.,and may act as vectors for contaminant transfer in terrestrial ecosystems.The transportation and retention of MPs in soil are governed by interactions among their inherent properties,such as size,shape,surface charge,and density.Interestingly,MP migration into soil is lacking research.The MPs and nanoplastics were also found in edible fruits and vegetables.The MP contamination in soil affects ecosystems,causing soil structure changes,fertility reduction,and pollutant leaching into groundwater.The MP concentration lies in the range of 43-2443 and 40-43000 items kg-1in agricultural and urban soils,respectively.This review provides a comprehensive roadmap for future research and a framework for soil MP risk assessment.Future studies on the uptake,accumulation,and translocation of MPs and their associated toxins by plants are essential for evaluating their risks to food security and human health.Research on MPs in terrestrial habitats lacks comprehensive data on their long-term persistence,degradation pathways,and interactions with soil components under varying environmental conditions.Additionally,limited understanding exists regarding MP impacts on soil biodiversity,pollutant mobility,and plant uptake,highlighting the need for innovative detection methods and effective pollution abatement strategies.
基金supported by the Key Technologies Research and Development Program(2024YFC2909605)Black Soil Project of Shenyang Science and Technology Program(24-216-2-07)Fundamental Research Funds for the Central Universities(NO.N25BSS006).
摘要The pervasive accumulation of plastic waste exacerbates environmental degradation and undermines resource circularity.Selective thermal catalysis emerges as a transformative pathway for valorizing waste plastics into value-added chemicals,yet persistent challenges in catalytic activity and product selectivity demand systematic resolution.This review decodes cutting-edge advances in thermal depolymerization by converging two critical dimensions:atomic-scale active site engineering-where rational design of coordination features and interfacial architectures regulates C-C cleavage energetics and intermediate adsorption-and macromolecular-scale manipulation of polymer transient states-leveraging nanoconfinement effects,chain folding dynamics,and thermal fragmentation to accelerate conversion kinetics.We further highlight breakthroughs in operando char-acterization techniques that resolve time-evolving reaction coordinates across catalytic systems.By establishing multiscale structure-activity relationships linking catalyst configurations to polymer dynamics,this analysis derives design paradigms for next-generation upcycling systems.These principles enable economically viable,industrially scalable plastic valorization while charting a strategic trajectory toward carbon-circular economies.
基金supported by Key Tackling Project of the Education Department of Liaoning Province,No.2024C011the Medical-Industrial Joint Innovation Funding Project of the First Hospital of Dalian Medical University and Dalian Institute of Chemical Physics,No.DMU-1&DICP UN202311(both to ZL).
摘要Chronic pain following a spinal cord injury refers to pain that persists or recurs after the injury.This pain can manifest as burning,stinging,or sensations similar to electric shocks.Recent studies have shown that spinal cord stimulation is an effective way to treat chronic pain after spinal cord injury.The purpose of this review is to introduce the technique of spinal cord stimulation,the clinical manifestations of spinal cord injury,and the role of spinal cord stimulation in the treatment of spinal cord injury.The mechanism and clinical application of spinal cord stimulation in the treatment of pain after spinal cord injury are discussed.The mechanism of spinal cord stimulation primarily involves three aspects:neuromodulation,neurochemical regulation,and anti-inflammatory effects,along with nerve repair.In terms of neuromodulation,spinal cord stimulation is based on the gate control theory of pain.It activates large-diameter amyloid-β nerve fibers to promote the release of inhibitory neurotransmitters by gamma-aminobutyric acidergic inhibitory interneurons in the spinal cord,thereby blocking the transmission of pain signals from small-diameter C fibers.Neurochemical studies indicate that spinal cord stimulation can regulate the balance of neurotransmitters within the spinal cord,increasing the release of inhibitory neurotransmitters such as gamma-aminobutyric acid,serotonin,and acetylcholine while reducing the levels of excitatory neurotransmitters.Additionally,spinal cord stimulation exhibits significant anti-inflammatory and neuroprotective effects,downregulating pro-inflammatory factor levels,upregulating anti-inflammatory factor expression,alleviating neuroinflammatory responses,and repairing damaged neural circuits by promoting the secretion of neurotrophic factors and axonal regeneration.Spinal cord stimulation have demonstrated remarkable efficacy in the clinical treatment of pain after spinal cord injury,but there are still limitations such as small sample size and high heterogeneity in clinical studies,as well as insufficient long-term efficacy data.Future research should conduct multi-center large-sample randomized controlled trials,and establish long-term follow-up mechanisms to improve evidence-based medical evidence.
基金supported in part by NIH/NIA grant R03AG070766-03(to SL)。
摘要Alzheimer's disease is typified by amyloid-beta oligomer-mediated synaptic disruption,neuroinflammation,and mitochondrial loss of function,culminating in cognitive decline.Recent evidence points toward the β2-adrenergic receptor as a target through its regulation of synaptic plasticity,neuroinflammation,and epigenetic control.Activation of β2-adrenergic receptor potentiates long-term potentiation,reverses amyloid-beta-mediated synaptic loss,and stimulates neuroprotective gene expression through cyclic adenosine monophosphateprotein kinase A-cyclic AMP response element-binding protein.Moreover,β2-adrenergic receptor suppression of histone deacetylase 2/3 promotes transcriptional reprogramming,supporting synaptic function.Beyond synaptic maintenance,activation of β2-adrenergic receptor prevents neuroinflammation by polarizing microglia toward an anti-inflammatory phenotype and augmenting amyloid-beta degradation.Additionally,mitochondrial metabolism is regulated by β2-adrenergic receptor,diminishing oxidative stress and allowing for bioenergetic resilience.Enriched environments mediate their neuroprotective effects through,in part,activation of β2-adrenergic receptor,supporting its role in promoting synaptic resilience.Pharmacological activation of β2-adrenergic receptor with specific agonists such as formoterol and clenbuterol has shown promise in preclinical models of Alzheimer's disease by restoring cognitive function and synaptic integrity.In this review,the molecular mechanisms of β2-adrenergic receptor-mediated neuroprotection are examined,with specific emphasis on its regulation of synaptic plasticity,neuroinflammation,mitochondrial function,and epigenetic control.Due to its multi-faceted action for maintenance of neuronal health,activation of β2-adrenergic receptor is an appealing therapy for Alzheimer's disease.Future research needs to target optimizing brain-penetrant β2-adrenergic receptor agonists and determining their longterm effects on Alzheimer's disease pathology.
基金funded by the Alexander von Humboldt Stiftungsupported by DFG (SCH W534/6-1 to SWS)
摘要The dentate gyrus of the hippocampus is a plastic structure that displays modifications at different levels in response to positive stimuli as well as to negative conditions such as brain damage.The latter involves global alterations,making understanding plastic responses triggered by local damage difficult.One key feature of the dentate gyrus is that it contains a well-defined neurogenic niche,the subgranular zone,and beyond neurogenesis,newly born granule cells may maintain a“young”phenotype throughout life,adding to the plastic nature of the structure.Here,we present a novel experimental model of local brain damage in organotypic entorhino-hippocampal cultures that results in the activation of adjacent newly born granule cells.A small piece of filter paper was placed on the surface of the granule cell layer of the dentate gyrus,which evoked a foreign body reaction of astrocytes,along with the activation of local young neurons expressing doublecortin.Forty-eight hours after foreign body placement,the number of doublecortin-immunoreactive cells increased in the subgranular zone in the direct vicinity of the foreign body,whereas overall increased doublecortin immunoreactivity was observed in the granule cell layer and molecular layer of the dentate gyrus.Foreign body placement in the pyramidal layer of the CA1 region evoked a comparable local astroglial reaction but did not lead to an increase in doublecortin-immunoreactive in either the CA1 region or the adjacent dentate gyrus.Seven days after foreign body placement in the dentate gyrus,the increase in doublecortin-immunoreactivity was no longer observed,indicating the transient activation of young cells.However,7 days after foreign body placement,the number of doublecortin-immunoreactive granule cells coimmunoreactive for calbindin was lower than that under the control conditions.As calbindin is a marker for mature granule cells,this result suggests that activated young cells remain at a more immature stage following foreign body placement.Live imaging of retrovirally green fluorescent protein-labeled newly born granule cells revealed the orientation and growth of their dendrites toward the foreign body placement.This novel experimental model of foreign body placement in organotypic entorhino-hippocampal cultures could serve as a valuable tool for studying both glial reactivity and neuronal plasticity,specifically of newly born neurons under controlled in vitro conditions.