Astrocytes are indispensable for central nervous system development and homeostasis.In response to injury and disease,astrocytes are integral to the immunological-and the,albeit limited,repair response.In this review,...Astrocytes are indispensable for central nervous system development and homeostasis.In response to injury and disease,astrocytes are integral to the immunological-and the,albeit limited,repair response.In this review,we will examine some of the functions reactive astrocytes play in the context of multiple sclerosis and related animal models.We will consider the heterogeneity or plasticity of astrocytes and the mechanisms by which they promote or mitigate demyelination.Finally,we will discuss a set of biomedical strategies that can stimulate astrocytes in their promyelinating response.展开更多
ZrB_(2)-based ceramics typically necessitate high temperature and pressure for sintering,whereas ZrB_(2)-SiC ceramics can be fabricated at 1500℃using the process of reactive melt infiltration with Si.In comparison to...ZrB_(2)-based ceramics typically necessitate high temperature and pressure for sintering,whereas ZrB_(2)-SiC ceramics can be fabricated at 1500℃using the process of reactive melt infiltration with Si.In comparison to the conventional preparation method,reactive synthesis allows for the more facile production of ultra-high temperature ceramics with fine particle size and homogeneous composition.In this work,ZrSi_(2),B4C,and C were used as raw materials to prepare ZrB_(2)-SiC via combination of tape casting and reactive melt infiltration herein referred to as ZBC ceramics.Control sample of ZrB_(2)-SiC was also prepared using ZrB_(2) and SiC as raw materials through an identical process designated as ZS ceramics.Microscopic analysis of both ceramic groups revealed smaller and more uniformly distributed particles of the ZrB_(2) phase in ZBC ceramics compared to the larger particles in ZS ceramics.Both sets of ceramics underwent cyclic oxidation testing in the air at 1600℃for a cumulative duration of 5 cycles,each cycle lasting 2 h.Analysis of the oxidation behavior showed that both ZBC ceramics and ZS ceramics developed a glassy SiO_(2)-ZrO_(2) oxide layer on their surfaces during the oxidation.This layer severed as a barrier against oxygen.In ZBC ceramics,ZrO_(2) is finely distributed in SiO_(2),whereas in ZS ceramics,larger ZrO_(2) particles coexist with glassy SiO_(2).The surface oxide layer of ZBC ceramics maintains a dense structure because the well-dispersed ZrO_(2) increases the viscosity of glassy SiO_(2),preventing its crystallization during the cooling.Conversely,some SiO_(2) in the oxide layer of ZS ceramics may crystallize and form a eutectic with ZrO_(2),leading to the formation of ZrSiO_(4).This leads to cracking of the oxide layer due to differences in thermal expansion coefficients,weakening its barrier effect.An analysis of the oxidation resistance shows that ZBC ceramics exhibit less increase in oxide layer thickness and mass compared to ZS ceramics,suggesting superior oxidation resistance of ZBC ceramics.展开更多
Wounds pose a risk to the skin,our body's primary defence against infections.The rise of antibiotic resistance has prompted the development of novel therapies.RO-101^(■)is an antimicrobial gel that delivers thera...Wounds pose a risk to the skin,our body's primary defence against infections.The rise of antibiotic resistance has prompted the development of novel therapies.RO-101^(■)is an antimicrobial gel that delivers therapeutic levels of hydrogen peroxide(H_(2)O_(2)),a reactive oxygen species,directly to the wound bed.In this study,electrospinning was used to incorporate RO-101^(■)into a polyvinyl alcohol(PVA)sub-micron fibrous mesh that can act as a delivery agent,achieve a sustained release profile,and provide a barrier against infection.Adequate incorporation of this gel into sub-micron fibres was confirmed via nuclear magnetic resonance spectroscopy.Furthermore,scanning electron microscopy exhibited smooth and uniform meshes with diameters in the 200-500 nm range.PVA/RO-101 electrospun meshes generated H_(2)O_(2) in concentrations exceeding 1 m M/(g·m L)(1 m M=1 mmol/L)after 24 h,and the role of sterilisation on H_(2)O_(2) release was evaluated.PVA/RO-101meshes exhibited antimicrobial activity against both Gram-positive Staphylococcus aureus(S.aureus)and Gram-negative Pseudomonas aeruginosa(P.aeruginosa)bacteria,achieving viable count reductions of up to 1 log unit CFU/mm^(2)(CFU:colony-forming units).Moreover,these meshes were capable of disrupting biofilm formation,even against multidrug-resistant organisms such as methicillin-resistant S.aureus(MRSA).Furthermore,increasing the RO-101^(■)concentration resulted in higher H_(2)O_(2) production and an enhanced antimicrobial effect,while fibroblast cell viability and proliferation tests showed a concentration-dependent response with high cytocompatibility at low RO-101^(■)concentrations.This study therefore demonstrates the potential of highly absorbent PVA/RO-101 meshes as potential antimicrobial wound dressings.展开更多
The current single-atom catalysts(SACs)for medicine still suffer from the limited active site density.Here,we develop a synthetic method capable of increasing both the metal loading and mass-specific activity of SACs ...The current single-atom catalysts(SACs)for medicine still suffer from the limited active site density.Here,we develop a synthetic method capable of increasing both the metal loading and mass-specific activity of SACs by exchanging zinc with iron.The constructed iron SACs(h^(3)-FNC)with a high metal loading of 6.27 wt%and an optimized adjacent Fe distance of~4 A exhibit excellent oxidase-like catalytic performance without significant activity decay after being stored for six months and promising antibacterial effects.Attractively,a“density effect”has been found at a high-enough metal doping amount,at which individual active sites become close enough to interact with each other and alter the electronic structure,resulting in significantly boosted intrinsic activity of single-atomic iron sites in h^(3)-FNCs by 2.3 times compared to low-and medium-loading SACs.Consequently,the overall catalytic activity of h^(3)-FNC is highly improved,with mass activity and metal mass-specific activity that are,respectively,66 and 315 times higher than those of commercial Pt/C.In addition,h^(3)-FNCs demonstrate efficiently enhanced capability in catalyzing oxygen reduction into superoxide anion(O_(2)·^(−))and glutathione(GSH)depletion.Both in vitro and in vivo assays demonstrate the superior antibacterial efficacy of h^(3)-FNCs in promoting wound healing.This work presents an intriguing activity-enhancement effect in catalysts and exhibits impressive therapeutic efficacy in combating bacterial infections.展开更多
This study proposed three types of Al—Hf reactive materials with particle size ratios(a),which were almost completely dense(porosity of<5.40%)owing to their preparation using hot-pressing technology.Microstructure...This study proposed three types of Al—Hf reactive materials with particle size ratios(a),which were almost completely dense(porosity of<5.40%)owing to their preparation using hot-pressing technology.Microstructure characteristics and phase composition were analyzed,and the influence of particle size ratios on dynamic mechanical behavior and damage mechanism were investigated.The prepared sample with a=0.1 exhibited continuous wrapping of the Hf phase by the Al phase.Hf—Hf contact(continuous Hf phase)within the sample gradually increased with increasing a,and a small amount of fine Hf appeared for the sample with a=1.The reactive materials exhibited clear strain-rate sensitivity,with flow stressσ0.05and failure strainεfincreasing approximately linearly with increasing strain rate.ε.It is found that the plastic deformation of the material increased with increasing strain rate.As a increased from 0.1 to 1,the flow stress gradually increased.Impact failure of the material was dominated by ductile fracture with a large Al phase plastic deformation band for lower a,while brittle fracture with crushed Hf particles occurred at higher a.Finally,a constitutive model based on BP neural network was proposed to describe the stress-strain relationships of the materials,with an average relative error of 2.22%.展开更多
Astrocytes are the most abundant type of glial cell in the central nervous system.Upon injury and inflammation,astrocytes become reactive and undergo morphological and functional changes.Depending on their phenotypic ...Astrocytes are the most abundant type of glial cell in the central nervous system.Upon injury and inflammation,astrocytes become reactive and undergo morphological and functional changes.Depending on their phenotypic classification as A1 or A2,reactive astrocytes contribute to both neurotoxic and neuroprotective responses,respectively.However,this binary classification does not fully capture the diversity of astrocyte responses observed across different diseases and injuries.Transcriptomic analysis has revealed that reactive astrocytes have a complex landscape of gene expression profiles,which emphasizes the heterogeneous nature of their reactivity.Astrocytes actively participate in regulating central nervous system inflammation by interacting with microglia and other cell types,releasing cytokines,and influencing the immune response.The phosphoinositide 3-kinase(PI3K)/protein kinase B(AKT)signaling pathway is a central player in astrocyte reactivity and impacts various aspects of astrocyte behavior,as evidenced by in silico,in vitro,and in vivo results.In astrocytes,inflammatory cues trigger a cascade of molecular events,where nuclear factor-κB serves as a central mediator of the pro-inflammatory responses.Here,we review the heterogeneity of reactive astrocytes and the molecular mechanisms underlying their activation.We highlight the involvement of various signaling pathways that regulate astrocyte reactivity,including the PI3K/AKT/mammalian target of rapamycin(mTOR),αvβ3 integrin/PI3K/AKT/connexin 43,and Notch/PI3K/AKT pathways.While targeting the inactivation of the PI3K/AKT cellular signaling pathway to control reactive astrocytes and prevent central nervous system damage,evidence suggests that activating this pathway could also yield beneficial outcomes.This dual function of the PI3K/AKT pathway underscores its complexity in astrocyte reactivity and brain function modulation.The review emphasizes the importance of employing astrocyte-exclusive models to understand their functions accurately and these models are essential for clarifying astrocyte behavior.The findings should then be validated using in vivo models to ensure real-life relevance.The review also highlights the significance of PI3K/AKT pathway modulation in preventing central nervous system damage,although further studies are required to fully comprehend its role due to varying factors such as different cell types,astrocyte responses to inflammation,and disease contexts.Specific strategies are clearly necessary to address these variables effectively.展开更多
Memristive crossbar arrays(MCAs)offer parallel data storage and processing for energy-efficient neuromorphic computing.However,most wafer-scale MCAs that are compatible with complementary metal-oxide-semiconductor(CMO...Memristive crossbar arrays(MCAs)offer parallel data storage and processing for energy-efficient neuromorphic computing.However,most wafer-scale MCAs that are compatible with complementary metal-oxide-semiconductor(CMOS)technology still suffer from substantially larger energy consumption than biological synapses,due to the slow kinetics of forming conductive paths inside the memristive units.Here we report wafer-scale Ag_(2)S-based MCAs realized using CMOS-compatible processes at temperatures below 160℃.Ag_(2)S electrolytes supply highly mobile Ag+ions,and provide the Ag/Ag_(2)S interface with low silver nucleation barrier to form silver filaments at low energy costs.By further enhancing Ag+migration in Ag_(2)S electrolytes via microstructure modulation,the integrated memristors exhibit a record low threshold of approximately−0.1 V,and demonstrate ultra-low switching-energies reaching femtojoule values as observed in biological synapses.The low-temperature process also enables MCA integration on polyimide substrates for applications in flexible electronics.Moreover,the intrinsic nonidealities of the memristive units for deep learning can be compensated by employing an advanced training algorithm.An impressive accuracy of 92.6%in image recognition simulations is demonstrated with the MCAs after the compensation.The demonstrated MCAs provide a promising device option for neuromorphic computing with ultra-high energy-efficiency.展开更多
Introduction: Intramuscular depot betamethasone treatment had resulted in a significant improvement among fibromyalgia patients with elevated C-reactive protein (C-RP) levels. Here, we wanted to evaluate the same regi...Introduction: Intramuscular depot betamethasone treatment had resulted in a significant improvement among fibromyalgia patients with elevated C-reactive protein (C-RP) levels. Here, we wanted to evaluate the same regimen of treatment among fibromyalgia patients with normal C-RP levels. These patients represent the overwhelming majority of fibromyalgia patients. Patients and Methods: Consecutive patients with fibromyalgia attending the outpatient rheumatology clinic, with normal C-RP level and negative serology, who had failed different medical treatment, were asked to participate in our study. All patients have qualified the American College of Rheumatology (ACR) criteria from 2010. After consent, patients had an intra-muscular injection of 14 mg depot betamethasone at the gluteal area. Just prior to the injection, 1 week and 1 month later, patients were interviewed by phone and asked to answer the Fibromyalgia Revised Questionnaire (FIQR). Wilcoxon’s signed ranked test was used to compare the results 1 week and 1 month following the injection, compared to the base line scores. Results: Seventeen (17) patients completed the study. Favorable effects were seen regarding 13 out of 19 parameters one week following the injection, including functional parameters, mood and anxiety, tenderness to touch and intolerance to noise and light. No significant favorable effect was seen 1 month following the injection except for one parameter: ability of walking for twenty minutes. Conclusions: IM depot betamethasone injection had very limited and transient favorable effects on fibromyalgia patients with normal C-RP levels. Such a treatment is not a recommended modality of routine treatment, among fibromyalgia patients with normal C-RP levels.展开更多
Reactive brazing of TiAl-based intermetallics and Ni-based alloy with Ti foil as interlayer was investigated. The interfacial microstructure and shear strength of the joints were studied. According to the experimental...Reactive brazing of TiAl-based intermetallics and Ni-based alloy with Ti foil as interlayer was investigated. The interfacial microstructure and shear strength of the joints were studied. According to the experimental observations, the molten interlayer reacts vigorously with base metals, forming several continuous reaction layers. The typical interfacial microstructure of the joint can be expressed as GH99/（Ni,Cr）ss（γ）/TiNi（β2）＋TiNi2Al（τ4）＋Ti2Ni（δ）/δ＋Ti3Al（α2）＋Al3NiTi2（τ3）/α2＋τ3/TiAl. The maximum shear strength is 258 MPa for the specimen brazed at 1000°C for 10 min. Higher brazing temperature or longer brazing time causes coarsening of the phases in the brazing seam and formation of brittle intermetallic layer, which greatly depresses the shear strength of the joints.展开更多
TiN-matrix composite coating was prepared on 45# steel by reactive high-velocity oxy-fuel （HVOF） spraying. Its microstructure, phase composition, micro-hardness, corrosion resistance in 3.5% NaC1 solution and wear r...TiN-matrix composite coating was prepared on 45# steel by reactive high-velocity oxy-fuel （HVOF） spraying. Its microstructure, phase composition, micro-hardness, corrosion resistance in 3.5% NaC1 solution and wear resistance were analyzed. The results suggest that the TiN-matrix composite coating is well bonded with the substrate. The micro-hardness measured decreases with the increase of applied test loads. And the micro-hardness of the coating under heavy loads is relatively high. The TiN-matrix composite coating exhibits an excellent corrosion resistance in 3.5% NaC1 solution. The corrosion potential of coating is positive and the passivation zone is broad, which indicates that the TiN-matrix composite coating is stable in the electrolyte and provides excellent protection to the substrate. The wear coefficient of the coating under all loads maintains at 0.49-0.50. The wear mechanism of the coating is revealed to be three-body abrasive wear. Yet the failure forms of TiN-matrix composite coating under different loads have an obvious difference. The failure form of coating under light loads is particle spallation due to the stress concentration while that of coating under heavy loads is crackin~ between inter-lamellae.展开更多
Age related defect of the osteogenic differentiation of mesenchymal stem cells（MSCs） plays a key role in osteoporosis. Mechanical loading is one of the most important physical stimuli for osteoblast differentiation....Age related defect of the osteogenic differentiation of mesenchymal stem cells（MSCs） plays a key role in osteoporosis. Mechanical loading is one of the most important physical stimuli for osteoblast differentiation.Here, we compared the osteogenic potential of MSCs from young and adult rats under three rounds of 2 h of cyclic stretch of 2.5% elongation at 1 Hz on 3 consecutive days. Cyclic stretch induced a significant osteogenic differentiation of MSCs from young rats, while a compromised osteogenesis in MSCs from the adult rats.Accordingly, there were much more reactive oxygen species（ROS） production in adult MSCs under cyclic stretch compared to young MSCs. Moreover, ROS scavenger N-acetylcysteine rescued the osteogenic differentiation of adult MSCs under cyclic stretch. Gene expression analysis revealed that superoxide dismutase 1（SOD1） was significantly downregulated in those MSCs from adult rats. In summary, our data suggest that reduced SOD1 may result in excessive ROS production in adult MSCs under cyclic stretch, and thus manipulation of the MSCs from the adult donors with antioxidant would improve their osteogenic ability.展开更多
基金supported by the Heart and Stroke Foundation and Ontario Institute of Regenerative Medicine (New Ideas Grant)Canada First Research Excellence Fund(Medicine by Design)+2 种基金the National Sciences and Engineering Research Councilthe Jurgen Manchot Foundationthe Christiane and Claudia Hempel Foundation for Clinical Stem Cell Research and the James and Elisabeth Cloppenburg,Peek and Cloppenburg Düsseldorf Stiftung (to PK)
文摘Astrocytes are indispensable for central nervous system development and homeostasis.In response to injury and disease,astrocytes are integral to the immunological-and the,albeit limited,repair response.In this review,we will examine some of the functions reactive astrocytes play in the context of multiple sclerosis and related animal models.We will consider the heterogeneity or plasticity of astrocytes and the mechanisms by which they promote or mitigate demyelination.Finally,we will discuss a set of biomedical strategies that can stimulate astrocytes in their promyelinating response.
基金National Key R&D Program of China(2022YFB3707700)Shanghai Science and Technology Innovation Action Plan(21511104800)+3 种基金National Natural Science Foundation of China(52172111)National Science and Technology Major Project(2017-IV-0005-0042)Key Research Program of the Chinese Academy of Sciences(ZDRW-CN-2021-2-2)Science Center for Gas Turbine Project(P2022-B-IV-001-001)。
文摘ZrB_(2)-based ceramics typically necessitate high temperature and pressure for sintering,whereas ZrB_(2)-SiC ceramics can be fabricated at 1500℃using the process of reactive melt infiltration with Si.In comparison to the conventional preparation method,reactive synthesis allows for the more facile production of ultra-high temperature ceramics with fine particle size and homogeneous composition.In this work,ZrSi_(2),B4C,and C were used as raw materials to prepare ZrB_(2)-SiC via combination of tape casting and reactive melt infiltration herein referred to as ZBC ceramics.Control sample of ZrB_(2)-SiC was also prepared using ZrB_(2) and SiC as raw materials through an identical process designated as ZS ceramics.Microscopic analysis of both ceramic groups revealed smaller and more uniformly distributed particles of the ZrB_(2) phase in ZBC ceramics compared to the larger particles in ZS ceramics.Both sets of ceramics underwent cyclic oxidation testing in the air at 1600℃for a cumulative duration of 5 cycles,each cycle lasting 2 h.Analysis of the oxidation behavior showed that both ZBC ceramics and ZS ceramics developed a glassy SiO_(2)-ZrO_(2) oxide layer on their surfaces during the oxidation.This layer severed as a barrier against oxygen.In ZBC ceramics,ZrO_(2) is finely distributed in SiO_(2),whereas in ZS ceramics,larger ZrO_(2) particles coexist with glassy SiO_(2).The surface oxide layer of ZBC ceramics maintains a dense structure because the well-dispersed ZrO_(2) increases the viscosity of glassy SiO_(2),preventing its crystallization during the cooling.Conversely,some SiO_(2) in the oxide layer of ZS ceramics may crystallize and form a eutectic with ZrO_(2),leading to the formation of ZrSiO_(4).This leads to cracking of the oxide layer due to differences in thermal expansion coefficients,weakening its barrier effect.An analysis of the oxidation resistance shows that ZBC ceramics exhibit less increase in oxide layer thickness and mass compared to ZS ceramics,suggesting superior oxidation resistance of ZBC ceramics.
基金supported by Matoke Holdings,the United Kingdom(UK)Engineering and Physical Sciences Research Council(EPSRC)Doctoral Prize Fellowship(No.EP/R513131/1)the Henry Royce Institute for Advanced Materials,funded through EPSRC grants(Nos.EP/R00661X/1,EP/S019367/1,EP/P025021/1,and EP/P025498/1)+1 种基金Ruth Edge and Kevin Warren(Dalton Nuclear Institute,The University of Manchester)for facilitating gamma sterilisation for our samplesfinancial support from Matoke Holdings。
文摘Wounds pose a risk to the skin,our body's primary defence against infections.The rise of antibiotic resistance has prompted the development of novel therapies.RO-101^(■)is an antimicrobial gel that delivers therapeutic levels of hydrogen peroxide(H_(2)O_(2)),a reactive oxygen species,directly to the wound bed.In this study,electrospinning was used to incorporate RO-101^(■)into a polyvinyl alcohol(PVA)sub-micron fibrous mesh that can act as a delivery agent,achieve a sustained release profile,and provide a barrier against infection.Adequate incorporation of this gel into sub-micron fibres was confirmed via nuclear magnetic resonance spectroscopy.Furthermore,scanning electron microscopy exhibited smooth and uniform meshes with diameters in the 200-500 nm range.PVA/RO-101 electrospun meshes generated H_(2)O_(2) in concentrations exceeding 1 m M/(g·m L)(1 m M=1 mmol/L)after 24 h,and the role of sterilisation on H_(2)O_(2) release was evaluated.PVA/RO-101meshes exhibited antimicrobial activity against both Gram-positive Staphylococcus aureus(S.aureus)and Gram-negative Pseudomonas aeruginosa(P.aeruginosa)bacteria,achieving viable count reductions of up to 1 log unit CFU/mm^(2)(CFU:colony-forming units).Moreover,these meshes were capable of disrupting biofilm formation,even against multidrug-resistant organisms such as methicillin-resistant S.aureus(MRSA).Furthermore,increasing the RO-101^(■)concentration resulted in higher H_(2)O_(2) production and an enhanced antimicrobial effect,while fibroblast cell viability and proliferation tests showed a concentration-dependent response with high cytocompatibility at low RO-101^(■)concentrations.This study therefore demonstrates the potential of highly absorbent PVA/RO-101 meshes as potential antimicrobial wound dressings.
基金supported by the National Key Research and Development Program of China(Grant No.2022YFB3804500)the National Natural Science Foundation of China(Grant No.52202352,22335006)+4 种基金the Shanghai Municipal Health Commission(Grant No.20224Y0010)the CAMS Innovation Fund for Medical Sciences(Grant No.2021-I2M-5-012)the Basic Research Program of Shanghai Municipal Government(Grant No.21JC1406000)the Fundamental Research Funds for the Central Universities(Grant No.22120230237,2023-3-YB-11,22120220618)the Basic Research Program of Shanghai Municipal Government(23DX1900200).
文摘The current single-atom catalysts(SACs)for medicine still suffer from the limited active site density.Here,we develop a synthetic method capable of increasing both the metal loading and mass-specific activity of SACs by exchanging zinc with iron.The constructed iron SACs(h^(3)-FNC)with a high metal loading of 6.27 wt%and an optimized adjacent Fe distance of~4 A exhibit excellent oxidase-like catalytic performance without significant activity decay after being stored for six months and promising antibacterial effects.Attractively,a“density effect”has been found at a high-enough metal doping amount,at which individual active sites become close enough to interact with each other and alter the electronic structure,resulting in significantly boosted intrinsic activity of single-atomic iron sites in h^(3)-FNCs by 2.3 times compared to low-and medium-loading SACs.Consequently,the overall catalytic activity of h^(3)-FNC is highly improved,with mass activity and metal mass-specific activity that are,respectively,66 and 315 times higher than those of commercial Pt/C.In addition,h^(3)-FNCs demonstrate efficiently enhanced capability in catalyzing oxygen reduction into superoxide anion(O_(2)·^(−))and glutathione(GSH)depletion.Both in vitro and in vivo assays demonstrate the superior antibacterial efficacy of h^(3)-FNCs in promoting wound healing.This work presents an intriguing activity-enhancement effect in catalysts and exhibits impressive therapeutic efficacy in combating bacterial infections.
基金funded by the National Natural Science Foundation of China(Grant No.12302437)China Postdoctoral Science Foundation(Grant No.2021M701710)。
文摘This study proposed three types of Al—Hf reactive materials with particle size ratios(a),which were almost completely dense(porosity of<5.40%)owing to their preparation using hot-pressing technology.Microstructure characteristics and phase composition were analyzed,and the influence of particle size ratios on dynamic mechanical behavior and damage mechanism were investigated.The prepared sample with a=0.1 exhibited continuous wrapping of the Hf phase by the Al phase.Hf—Hf contact(continuous Hf phase)within the sample gradually increased with increasing a,and a small amount of fine Hf appeared for the sample with a=1.The reactive materials exhibited clear strain-rate sensitivity,with flow stressσ0.05and failure strainεfincreasing approximately linearly with increasing strain rate.ε.It is found that the plastic deformation of the material increased with increasing strain rate.As a increased from 0.1 to 1,the flow stress gradually increased.Impact failure of the material was dominated by ductile fracture with a large Al phase plastic deformation band for lower a,while brittle fracture with crushed Hf particles occurred at higher a.Finally,a constitutive model based on BP neural network was proposed to describe the stress-strain relationships of the materials,with an average relative error of 2.22%.
基金supported by Fondo Nacional de Desarrollo Científico y Tecnológico(FONDECYT)#1200836,#1210644,and#1240888,and Agencia Nacional de Investigación y Desarrollo(ANID)-FONDAP#15130011(to LL)FONDECYT#3230227(to MFG).
文摘Astrocytes are the most abundant type of glial cell in the central nervous system.Upon injury and inflammation,astrocytes become reactive and undergo morphological and functional changes.Depending on their phenotypic classification as A1 or A2,reactive astrocytes contribute to both neurotoxic and neuroprotective responses,respectively.However,this binary classification does not fully capture the diversity of astrocyte responses observed across different diseases and injuries.Transcriptomic analysis has revealed that reactive astrocytes have a complex landscape of gene expression profiles,which emphasizes the heterogeneous nature of their reactivity.Astrocytes actively participate in regulating central nervous system inflammation by interacting with microglia and other cell types,releasing cytokines,and influencing the immune response.The phosphoinositide 3-kinase(PI3K)/protein kinase B(AKT)signaling pathway is a central player in astrocyte reactivity and impacts various aspects of astrocyte behavior,as evidenced by in silico,in vitro,and in vivo results.In astrocytes,inflammatory cues trigger a cascade of molecular events,where nuclear factor-κB serves as a central mediator of the pro-inflammatory responses.Here,we review the heterogeneity of reactive astrocytes and the molecular mechanisms underlying their activation.We highlight the involvement of various signaling pathways that regulate astrocyte reactivity,including the PI3K/AKT/mammalian target of rapamycin(mTOR),αvβ3 integrin/PI3K/AKT/connexin 43,and Notch/PI3K/AKT pathways.While targeting the inactivation of the PI3K/AKT cellular signaling pathway to control reactive astrocytes and prevent central nervous system damage,evidence suggests that activating this pathway could also yield beneficial outcomes.This dual function of the PI3K/AKT pathway underscores its complexity in astrocyte reactivity and brain function modulation.The review emphasizes the importance of employing astrocyte-exclusive models to understand their functions accurately and these models are essential for clarifying astrocyte behavior.The findings should then be validated using in vivo models to ensure real-life relevance.The review also highlights the significance of PI3K/AKT pathway modulation in preventing central nervous system damage,although further studies are required to fully comprehend its role due to varying factors such as different cell types,astrocyte responses to inflammation,and disease contexts.Specific strategies are clearly necessary to address these variables effectively.
基金supported by the Swedish Strategic Research Foundation(SSF FFL15-0174 to Zhen Zhang)the Swedish Research Council(VR 2018-06030 and 2019-04690 to Zhen Zhang)+1 种基金the Wallenberg Academy Fellow Extension Program(KAW 2020-0190 to Zhen Zhang)the Olle Engkvist Foundation(Postdoc grant 214-0322 to Zhen Zhang).
文摘Memristive crossbar arrays(MCAs)offer parallel data storage and processing for energy-efficient neuromorphic computing.However,most wafer-scale MCAs that are compatible with complementary metal-oxide-semiconductor(CMOS)technology still suffer from substantially larger energy consumption than biological synapses,due to the slow kinetics of forming conductive paths inside the memristive units.Here we report wafer-scale Ag_(2)S-based MCAs realized using CMOS-compatible processes at temperatures below 160℃.Ag_(2)S electrolytes supply highly mobile Ag+ions,and provide the Ag/Ag_(2)S interface with low silver nucleation barrier to form silver filaments at low energy costs.By further enhancing Ag+migration in Ag_(2)S electrolytes via microstructure modulation,the integrated memristors exhibit a record low threshold of approximately−0.1 V,and demonstrate ultra-low switching-energies reaching femtojoule values as observed in biological synapses.The low-temperature process also enables MCA integration on polyimide substrates for applications in flexible electronics.Moreover,the intrinsic nonidealities of the memristive units for deep learning can be compensated by employing an advanced training algorithm.An impressive accuracy of 92.6%in image recognition simulations is demonstrated with the MCAs after the compensation.The demonstrated MCAs provide a promising device option for neuromorphic computing with ultra-high energy-efficiency.
文摘Introduction: Intramuscular depot betamethasone treatment had resulted in a significant improvement among fibromyalgia patients with elevated C-reactive protein (C-RP) levels. Here, we wanted to evaluate the same regimen of treatment among fibromyalgia patients with normal C-RP levels. These patients represent the overwhelming majority of fibromyalgia patients. Patients and Methods: Consecutive patients with fibromyalgia attending the outpatient rheumatology clinic, with normal C-RP level and negative serology, who had failed different medical treatment, were asked to participate in our study. All patients have qualified the American College of Rheumatology (ACR) criteria from 2010. After consent, patients had an intra-muscular injection of 14 mg depot betamethasone at the gluteal area. Just prior to the injection, 1 week and 1 month later, patients were interviewed by phone and asked to answer the Fibromyalgia Revised Questionnaire (FIQR). Wilcoxon’s signed ranked test was used to compare the results 1 week and 1 month following the injection, compared to the base line scores. Results: Seventeen (17) patients completed the study. Favorable effects were seen regarding 13 out of 19 parameters one week following the injection, including functional parameters, mood and anxiety, tenderness to touch and intolerance to noise and light. No significant favorable effect was seen 1 month following the injection except for one parameter: ability of walking for twenty minutes. Conclusions: IM depot betamethasone injection had very limited and transient favorable effects on fibromyalgia patients with normal C-RP levels. Such a treatment is not a recommended modality of routine treatment, among fibromyalgia patients with normal C-RP levels.
基金Projects (50975062, 51105107, 51021002) supported by the National Natural Science Foundation of ChinaProjects (QC2011C044) supported by the Natural Science Foundation of Heilongjiang Province,China+1 种基金Project (20112302130005) supported by the Specialized Research Fund for the Doctoral Program of Higher Education,ChinaProject (CUGA4130902510) supported by the China Postdoctoral Science Foundation Funded
文摘Reactive brazing of TiAl-based intermetallics and Ni-based alloy with Ti foil as interlayer was investigated. The interfacial microstructure and shear strength of the joints were studied. According to the experimental observations, the molten interlayer reacts vigorously with base metals, forming several continuous reaction layers. The typical interfacial microstructure of the joint can be expressed as GH99/（Ni,Cr）ss（γ）/TiNi（β2）＋TiNi2Al（τ4）＋Ti2Ni（δ）/δ＋Ti3Al（α2）＋Al3NiTi2（τ3）/α2＋τ3/TiAl. The maximum shear strength is 258 MPa for the specimen brazed at 1000°C for 10 min. Higher brazing temperature or longer brazing time causes coarsening of the phases in the brazing seam and formation of brittle intermetallic layer, which greatly depresses the shear strength of the joints.
基金Project(KFJJ10-15M) supported by the Open Fund of State Key Laboratory of Explosion Science and Technology,Beijing Institute of Technology,ChinaProject(E2013208101) supported by the Nature Science Fund of Hebei Province,China+1 种基金Project(Z2012100) supported by Colleges and Universities Science and Technology Research Fund of Hebei Province,ChinaProject supported by the Outstanding Youth Fund of Hebei University of Science and Technology,China
文摘TiN-matrix composite coating was prepared on 45# steel by reactive high-velocity oxy-fuel （HVOF） spraying. Its microstructure, phase composition, micro-hardness, corrosion resistance in 3.5% NaC1 solution and wear resistance were analyzed. The results suggest that the TiN-matrix composite coating is well bonded with the substrate. The micro-hardness measured decreases with the increase of applied test loads. And the micro-hardness of the coating under heavy loads is relatively high. The TiN-matrix composite coating exhibits an excellent corrosion resistance in 3.5% NaC1 solution. The corrosion potential of coating is positive and the passivation zone is broad, which indicates that the TiN-matrix composite coating is stable in the electrolyte and provides excellent protection to the substrate. The wear coefficient of the coating under all loads maintains at 0.49-0.50. The wear mechanism of the coating is revealed to be three-body abrasive wear. Yet the failure forms of TiN-matrix composite coating under different loads have an obvious difference. The failure form of coating under light loads is particle spallation due to the stress concentration while that of coating under heavy loads is crackin~ between inter-lamellae.
基金financially supported by National Natural Science Foundation of China (81100240)‘985’ project of Sun Yat-Sen University grant+2 种基金Sun Yat-Sen university young teachers training project (13YKPY42)Natural Science Foundation of Guangdong Province,China(S2012010009495)Science and Technology Planning Project of Guangdong Province,China(2012B031800185)
文摘Age related defect of the osteogenic differentiation of mesenchymal stem cells（MSCs） plays a key role in osteoporosis. Mechanical loading is one of the most important physical stimuli for osteoblast differentiation.Here, we compared the osteogenic potential of MSCs from young and adult rats under three rounds of 2 h of cyclic stretch of 2.5% elongation at 1 Hz on 3 consecutive days. Cyclic stretch induced a significant osteogenic differentiation of MSCs from young rats, while a compromised osteogenesis in MSCs from the adult rats.Accordingly, there were much more reactive oxygen species（ROS） production in adult MSCs under cyclic stretch compared to young MSCs. Moreover, ROS scavenger N-acetylcysteine rescued the osteogenic differentiation of adult MSCs under cyclic stretch. Gene expression analysis revealed that superoxide dismutase 1（SOD1） was significantly downregulated in those MSCs from adult rats. In summary, our data suggest that reduced SOD1 may result in excessive ROS production in adult MSCs under cyclic stretch, and thus manipulation of the MSCs from the adult donors with antioxidant would improve their osteogenic ability.
