Small extracellular vesicles derived from cerebral endothelial cells with elevated microRNA 27a promote ischemic stroke recovery

Axonal remodeling is a critical aspect of ischemic brain repair processes and contributes to spontaneous functional recovery.Our previous in vitro study demonstrated that exosomes/small extracellular vesicles(sEVs)isolated from cerebral endothelial cells(CEC-sEVs)of ischemic brain promote axonal growth of embryonic cortical neurons and that microRNA 27a(miR-27a)is an elevated miRNA in ischemic CEC-sEVs.In the present study,we investigated whether normal CEC-sEVs engineered to enrich their levels of miR-27a(27a-sEVs)further enhance axonal growth and improve neurological outcomes after ischemic stroke when compared with treatment with non-engineered CEC-sEVs.27a-sEVs were isolated from the conditioned medium of healthy mouse CECs transfected with a lentiviral miR-27a expression vector.Small EVs isolated from CECs transfected with a scramble vector(Scra-sEVs)were used as a control.Adult male mice were subjected to permanent middle cerebral artery occlusion and then were randomly treated with 27a-sEVs or Scra-sEVs.An array of behavior assays was used to measure neurological function.Compared with treatment of ischemic stroke with Scra-sEVs,treatment with 27a-sEVs significantly augmented axons and spines in the peri-infarct zone and in the corticospinal tract of the spinal grey matter of the denervated side,and significantly improved neurological outcomes.In vitro studies demonstrated that CEC-sEVs carrying reduced miR-27a abolished 27a-sEV-augmented axonal growth.Ultrastructural analysis revealed that 27a-sEVs systemically administered preferentially localized to the pre-synaptic active zone,while quantitative reverse transcription-polymerase chain reaction and Western Blot analysis showed elevated miR-27a,and reduced axonal inhibitory proteins Semaphorin 6A and Ras Homolog Family Member A in the peri-infarct zone.Blockage of the Clathrin-dependent endocytosis pathway substantially reduced neuronal internalization of 27a-sEVs.Our data provide evidence that 27a-sEVs have a therapeutic effect on stroke recovery by promoting axonal remodeling and improving neurological outcomes.Our findings also suggest that suppression of axonal inhibitory proteins such as Semaphorin 6A may contribute to the beneficial effect of 27a-sEVs on axonal remodeling.

Axonal remodeling of the corticospinal tract during neurological recovery after stroke

Stroke remains the leading cause of long-term disability.Hemiparesis is one of the most common post-stroke motor deficits and is largely attributed to loss or disruption of the motor signals from the affected motor cortex.As the only direct descending motor pathway,the corticospinal tract(CST)is the primary pathway to innervate spinal motor neurons,and thus,forms the neuroanatomical basis to control the peripheral muscles for voluntary movements.Here,we review evidence from both experimental animals and stroke patients,regarding CST axonal damage,functional contribution of CST axonal integrity and remodeling to neurological recovery,and therapeutic approaches aimed to enhance CST axonal remodeling after stroke.The new insights gleaned from preclinical and clinical studies may encourage the development of more rational therapeutics with a strategy targeted to promote axonal rewiring for corticospinal innervation,which will significantly impact the current clinical needs of subacute and chronic stroke treatment.

Reactive astrocytes promote axonal remodeling and neurological recovery after stroke

Stroke is a leading cause of death and disability in adults worldwide. For decades, the primary approach and goal of therapy for stroke has focused on neuroprotection, namely treating the injured tissue, with interventions designed to reduce the volume of cerebral infarction. Enormous effort in the laboratory has been devoted to the development of neuroprotective agents in an attempt to salvage ischemic neurons in the brain from irreversible injury; however, all these efforts have failed to demonstrate efficacy in clinical trials of stroke. In order to treat stroke, we have to re-con- ceptualize and redefine our therapeutic targets. Acute neu- roprotective treatments for stroke fight a temporal battle of salvaging cerebral tissue before the onset of death, as well as a physiological impediment of delivery of therapy to tissue which has inadequate blood flow.

哺乳仔猪的非疾病死亡原因分析与对策

哺乳仔猪的高死亡率是生猪产业发展的主要挑战,极大程度上影响经济效益、动物福利,同时造成资源浪费,哺乳仔猪的死亡是许多综合因素作用的结果。文章中就引发哺乳仔猪死亡的非疾病原因进行分析总结,并针对相应问题提出应对性策略。

^(57)Fe Mössbauer spectrometry: A powerful technique to analyze the magnetic and phase characteristics in RE–Fe–B permanent magnets

This review summarizes the recent advances on the application of ^(57)Fe Mössbauer spectrometry to study the magnetic and phase characteristics of Nd–Fe–B-based permanent magnets. First of all, the hyperfine structures of the Ce_(2)Fe_(14)B,(Ce,Nd)_(2)Fe_(14)B and MM_(2)Fe_(14)B phases are well-defined by using the model based on the Wigner-Seitz analysis of the crystal structure. The results show that the isomer shift δ and the quadrupole splitting öEQ of those 2:14:1 phases show minor changes with the Nd content, while the hyperfine field Bhfincreases monotonically with increasing Nd content and its value is influenced by the element segregation and phase separation in the 2:14:1 phase. Then, the hyperfine structures of the low fraction secondary phases are determined by the ^(57)Fe Mössbauer spectrometry due to its high sensitivity. On this basis,the content, magnetic behavior, and magnetization of the REFe_(2) phase, the amorphous grain boundary(GB) phase, and the amorphous worm-like phase, as well as their effects on the magnetic properties, are systematically studied.

Superior comprehensive properties of LaFe_(11.8)Si_(1.2)/Ce_(60)Co_(40) magnetocaloric composites

LaFe_(11.8)Si_(1.2)/10 wt%Ce_(60)Co_(40) composites were prepared by spark plasma sintering and subsequent diffusion annealing.A novel core-shell structure is observed with the LaFe11.8Si1.2 particles as the core and the(La,Ce)_(2)(Fe,Co,Si)_(17)(2:17)phase as the shell.As diffusion annealing time(t_(a))increases,this core-shell structure is replaced by the formation of the(La,Ce)_(1)(Fe,Co,Si)_(13) phase.Annealing at 1323 K for 12 h results in samples with(-ΔSM)^(max) of 9.30 J/(kg·K)(Δμ0H=2 T),good mechanical properties((σbc)^(max)=402 MPa,ε=4.21%)and thermal conductivity of 8.7 W/(m·K).Thus,bulk composites with excellent comprehensive properties for magnetic refrigeration are obtained in this work.

Hierarchical design of FeCo-based microchains for enhanced microwave absorption in C band

Microwave absorbing materials(MAMs)has been intensively investigated in order to meet the requirement of electromagnetic radiation control,especially in S and C band.In this work,FeCo-based magnetic MAMs are hydrothermally synthesized via a magnetic-field-induced process.The composition and morphology of the MAMs are capable of being adjusted simultaneously by the atomic ratio of Fe2+to Co2+in the precursor.The hierarchical magnetic microchain,which has a core–shell structure of twodimensional FexCo1−xOOH nanosheets anchored vertically on the surface of a one-dimensional(1D)Co microchain,shows significantly enhanced microwave absorption in C band,resulting in a reflection loss(RL)of lower than−20 dB at frequencies ranging from 4.4 to 8.0 GHz under a suitable matching thickness.The magnetic coupling of Co microcrystals and the double-loss mechanisms out of the core-shell structure are considered to promote the microwave attenuation capability.The hierarchical design of 1D magnetic MAMs provides a feasible strategy to solve the electromagnetic pollution in C band.

Effects of grain boundary diffusion process on magnetic properties enhancement and microstructure evolution of hot-deformed Nd-Fe-B magnets

Grain boundary diffusion(GBD)process is an important approach for producing Nd-Fe-B magnets with high coercivity and high thermal stability.The GBD for hot-deformed Nd-Fe-B magnets with nanocrystalline micro structure is more complicated compared to sintered magnets.Here,we investigated the effects of different GBD methods,i.e.,intergranular addition(in-situ GBD 1#),in-situ GBD from magnet surface during hot pressing and hot deformation(in-situ GBD 2#),and conventional GBD,on the magnetic properties and microstructure of hot deformed magnets.After the treatment by these three GBD approaches using 2 wt%Pr_(40)Tb_(30)Cu_(30)diffusion source,the coercivity of the hot-deformed magnet increases from 1281 to 1567,1412 and 2022 kA/m,respectively.The coercivity enhancement is attributed to the formation of local(Nd,Tb)2Fe14B phase with stro ng magnetic anisotropy.Reduced grain orientation is found in both in-situ GBD 1#and conventional GBD treated samples mainly due to the local stress state variation and the rotation of platelet grains.Interestingly,the in-situ GBD 2#processed sample has a high orientation at diffusion surface,which may be caused by the modified surface state of the magnet by the diffusion source.Compared with the in-situ GBD processes,the conventional GBD exhibits a higher utilization efficiency of Tb.Since the in-situ GBD is effective to treat thick hot-deformed magnets,further effort should be aimed at enhancing its diffusion efficiency.

Simultaneous enhancement of coercivity and electric resistivity of Nd-Fe-B magnets by Pr-Tb-Al-Cu synergistic grain boundary diffusion toward high-temperature motor rotors

To high-power permanent magnetic motors,it is critical for Nd-Fe-B magnets to maintain the desirable coercivity at high-temperature operating conditions.To address this,two approaches have been proven effective:(1)enhancing the room temperature coercivity;(2)reducing the eddy current loss.However,these two items are difficult to be simultaneously achieved.Here,the grain boundary diffusion(GBD)of the Pr-Tb-Al-Cu-based source is applied to enhance the coercivity and electric resistivity at room temperature from 1101 kA m-1 and 2.13×10–6Ωm to 1917 kA m-1 and 2.60×10–6Ωm,and those at 120°C from 384 kA m-1 and 4.31×10–6Ωm to 783 kA m-1 and 4.86×10–6Ωm,respectively.Such optimization is ascribed to the improved formation depth of Tb-rich 2:14:1 shells with large magnetocrystalline anisotropy and the increased intergranular Pr-based oxides with high electric resistivity,induced by the coordination effects of Tb and Pr,as proven by the atomic-scale observations and the first principles calculations.It thus results in the simultaneously improved output power and energy efficiency of the motor because of the combination of magnetic thermal stability enhancement and eddy current loss reduction,as theoretically confirmed by electromagnetic simulation.

Phase precipitation and magnetic properties of melt-spun ternary Gd_(2)Fe_(14)B alloy and advantages of gadolinium substitution in Y_(2)Fe_(14)B alloy

To take the advantage of gadolinium(Gd) in developing and manufacturing RE-permanent magnets,the magnetic properties and phase precipitation behavior of Gd_(2)Fe_(14)B alloys prepared by melt spinning were investigated in this work.The results show that optimally direct quenched nanocrystalline Gd_(2)Fe_(14)B alloy exhibits the magnetic properties with remanence J_(r) of 0.51 T,coercivity H_(c) of 187 kA/m,and maximum energy product(BH)_(max) of 33.1 kJ/m^(3).It also shows excellent thermal stability with a small negative temperature coefficient of J_(r)(α=-0.066%/K) and a positive temperature coefficient of H_(c)(β=0.171 %/K).The phase precipitations of as spun Gd_(2)Fe_(14)B alloy during melt spinning and over-quenched amorphous Gd_(2)Fe_(14)B alloy during heat treatment were clarified.The magnetic properties of the crystallized alloys annealed at 800℃ are close to those of the optimized directly quenched as-spun alloys,indicating good performance stability under various processes.In addition,the role of Gd substitution in(Y_(1-x)Gd_(x))_(2)Fe_(14)B alloys was systematically studied.Gd substitution can significantly enhance the thermal stability and decrease the irreve rsible remanence loss of Y_(2)Fe_(14)B alloy.With increasing Gd conte nt,Gd-doped Y_(2)Fe_(14)B alloys show continuous enhancement of H_(c) at elevated temperatures.The highest β value of 0.22%/K was obtained in(Y_(0.2)Gd_(0.8))_(2)Fe_(14)B alloy at 300—400 K.Gd substitution is not only effective in improving the exchange coupling effect and corrosion resistance of Y_(2)Fe_(14)B alloy but also superior to Nd in terms of improving the oxidation resistance.The present work has certain instructions for designing and developing new low cost RE permanent magnets with improved thermal and environment stability.

Grain boundary construction and properties enhancement for hot deformed(Ce,La,Y)-Fe-B magnet by a two-step diffusion process

The rare earth-iron-boron magnets based on high abundance rare earths(REs)show potential for costeffective permanent magnets but their hard magnetic properties have to be greatly improved.The grain boundary diffusion process(GBDP)is known as an effective way to improve the coercivity of Nd-Fe-B magnets,however,the conventional diffusion method faces a challenge for Ce-based magnets since there is no enough continuous GB layer as the diffusion channel.Here,a two-step(Nd-Cu doping followed by Nd-Cu diffusion)GBDP was introduced for hot deformed(Ce,La,Y)-Fe-B magnet,and the excellent magnetic properties ofμ0Hc=0.63 T,μ0Mr=0.68 T,and(BH)max=72.4 kJ/m^(3)were achieved.The Nd-Cu doping helps the formation of RE-rich GB layer,and then it acts as the diffusion channel for increasing the ef-ficiency of the subsequent Nd-Cu diffusion and results in the increased volume fraction of continuously distributed GB phase,whose paramagnetism was verified by 57Fe Mössbauer spectrometry.Those paramagnetic GB phases help to form the discontinuous domain walls,as observed by Lorentz transmission electron microscopy,and break the magnetic exchange coupling of RE2Fe14B grains.It thus contributes to the coercivity enhancement of the hot deformed magnet with two-step diffusion,which is further proved by micromagnetic simulation.This study proposes a potential technique to prepare anisotropic hot deformed(Ce,La,Y)-Fe-B magnet with high cost-performance.

Recovering REEs from NdFeB wastes with high purity and efficiency by leaching and selective precipitation process with modified agents

A leaching and selective precipitation approach is proposed in this work to recover rare earth elements(REEs) from NdFeB magnet wastes collected from industry. Hydrochloric acid and oxalic acid were employed as the leaching and precipitation agents, respectively. Hexamethylenetetramine(HMTA) or tartaric acid was used as the chelating agent during leaching. Both leaching and precipitation processes were optimized individually. For leaching process, the effects of two different chelating agents, the concentrations of leaching agent, chelating agent, and temperature on the extraction and recovery yields were investigated. The optimized process based on the factorial experiment was determined to be the hydrochloric acid concentration of 6 mol/L, the tartaric acid concentration of 50 g/L, and the temperature of 313 K, by which the extraction yields of Fe and REEs up to 67.99% and 99.27%, respectively, are obtained. For the precipitation process, the optimized oxalic acid dosage and pH value were also determined. The produced RE oxide products have the purity and recovery yield up to 95.83% and 90.18%,respectively. These results indicate that the present method with low acid consumption and high product purity has advantages over many other approaches for REE recovery.

Development of non-rare earth grain boundary modification techniques for Nd-Fe-B permanent magnets

The magnetic performance of Nd-Fe-B magnets depends on their grain boundary structure.Intergranular addition and grain boundary diffusion(GBD)process are effective approaches for enhancing coercivity with low material cost.This review summarizes the development of grain boundary modification techniques with emphasis on our recent work using cost-effective non-rare earth(non-RE)sources for GBD.Up to now,heavy rare earth(HRE)based compounds,metals and light rare earth(LRE)based alloys have been successfully employed as the diffusion sources for coercivity enhancement.Inspired from the previous investigations on the intergranular addition of non-RE compounds and alloys for Nd-Fe-B magnets,in 2015,we firstly proposed a novel GBD process based on diffusion source of Mg O.After that,various non-RE diffusion sources have been developed.The fundamentals of non-RE additives and non-RE diffusion sources for hard magnetic properties enhancement of Nd-Fe-B magnets are summarized here based on both the experimental and computational results.In particular,the properties-microstructure relationships of non-RE GBD modified magnets are discussed.The non-RE alloys or compounds modify the composition and structure of the grain boundary by diffusing into the intergranular regions,resulting in enhanced coercivity and corrosion resistance.Recently,we used Al-Cr coatings for both coercivity enhancement and surface protection,which shortens the production process and makes non-RE diffusion sources more competitive.The opportunity and future directions for non-RE GBD are also discussed in this review.

Development of cost-effective nanocrystalline multi-component(Ce,La,Y)-Fe-B permanent magnetic alloys containing no critical rare earth elements of Dy,Tb,Pr and Nd

Here we first report the fully abundant rare earth(RE)-based nanocrystalline multi-component(Ce,La,Y)-Fe-B alloys containing no critical RE elements of Nd,Pr,Dy,and Tb by melt-spinning technique.The roles of La and Y substitutions for Ce have been fully understood.La plays a positive role on both thermal stability and room-temperature(RT)magnetic properties.The enhanced coercivity H_(cj)by partial substitution of La is attributed to the increases of anisotropy field H_A and the formation of continuously distributed grain boundaries resulting from the suppre s sion of CeFe_(2)phase.Although Y substitution is not benefit for H_(cj),both remanent polarization J_r and thermal stability have been effectively improved since Y_(2)Fe_(14)B shows relatively high saturation magnetization M_s and a positive temperature coefficient of HA over a certain temperature range.In addition,RE element segregation has been confirmed,La prefers to enter into the grain boundaries than Ce and Y prefers to remain in the 2:14:1 phase.Based on these understanding,a series of melt-spun(Ce,La,Y)-Fe-B alloys have been designed.A relatively good combination of magnetic properties with maximum energy product(BH)_(max)=7.4 MGOe,H_(Cj)=400 kA/m,and J_r=0.63 T has been obtained in[(Ce_(0.8)La_(0.2))_(0.7)Y_(0.3)]_(17)Fe_(78)B_6 alloy,together with high Curie temperature(T_c=488 K)and low temperature coefficients of remanence(α=-0.255%/K)and coercivity(β=-0.246%/K).

Effective rare earth extraction from Nd-Fe-B waste by liquid cuprum extraction method

Recovery of rare earth(RE)elements from Nd-Fe-B waste is one of the ways to solve the problem of socalled RE-crisis,An alternative approach of extracting RE elements from Nd-Fe-B waste by molten Cu extraction based on liquid-solid diffusion and reaction is reported in this paper.The extraction process,product microstructure and extraction efficiency were systematically studied.The results show that the extraction rate of RE at 1200℃is about 20%higher than that at 1100℃.The enhanced extraction efficiency at 1200℃results from the fact that the liquid Fe and Fe2 B are not co-soluble with Cu,Reducing the mass ratio of Cu to waste and the size of the waste scraps is also beneficial to enhancing the separation of RE and Fe elements.In addition,the extraction time should be well controlled,for example,less than 2 h at 1100℃,in order to avoid the increased Fe content in the extracted product.Based on optimized process,the RE elements ca n be almost fully extracted from the waste.This work thus provides an effective method to recover the RE elements.

Influence of gadolinium and dysprosium substitution on magnetic properties and magnetocaloric effect of Fe78-xRExSi4Nb5B12Cu1 amorphous alloys

Amorphous Fe78-xRExSi4 Nb5 B12Cu1(RE=Gd,Dy) ribbons with different RE contents were prepared by melt spinning to investigate the effect of heavy rare earth(Gd,Dy) substitution on the hyperfine structure,magnetic properties and magnetocaloric effect.The Curie temperature of RE substituted alloys,hyperfine field and magnetic moments of Fe atoms initially increase up to 1 at% RE content and then decrease monotonously for increasing RE content up to 10 at%.The dependence of magnetic entropy change(-△SM) and refrigeration capacity(RC) of the alloys on RE contents displays the same tendency.The RCAREA values of the alloys substituted with 1 at% Gd and Dy are similar to those of recently reported Fe-based metallic glasses with enhanced RC values compared with those of Gd5 Ge1.9Si2 Fe0.1.Enhanced-△SM and RC values,negligible coercive force and hysteresis commonly make these Fe78-xREx-Si4 Nb5 B12Cu1 amorphous alloys as low-cost candidates for high-temperature magnetic refrigeration.

Microstructure improvement related coercivity enhancement for sintered NdFeB magnets after optimized additional heat treatment

The micro structure, especially the Nd-rich phase and the grain boundary, in sintered NdFeB magnets plays an important role in magnetic reversal and coercivity mechanism. To better understand the effects of the microstructure on the coercivity, we investigated the microstructure and properties improvements of a commercial sintered NdFeB magnet after optimized additional heat treatment. The coercivity is enhanced from 1399 to 1560 kA/m. This enhancement has been explained in terms of the evolution of the grain boundary structure, and the formation of continuous thin layers of Nd-rich phase is important for high coercivity. The micromagnetic simulation together with the numerical analysis based on the nucleation model suggest that the reversed magnetic domains nucleate mainly at the interface of multijunctions of Nd_2 Fe_（14）B grains with high stray fields during the demagnetization process. Both improved anisotropy fields at grain boundaries and reduced stray fields at multi-junction Nd-rich phases contribute to the coercivity enhancement. This work has importance in understanding the crucial micro structure parameters and enhancing the obtainable properties for sintered NdFeB magnets.

Micromagnetic investigation by a simplified approach on the demagnetization field of permanent magnets with nonmagnetic phase inside

A simplified analysis method based on micromagnetic simulation is proposed to investigate effects of nonmagnetic particles on the demagnetizing field of a permanent magnet By applying the additivity law of the demagnetizing field,the complicated demagnetizing field of the real magnet could be analyzed by only focusing on the stray field of the reserved magnet For a magnet with nonmagnetic particles inside,the particle size has no significant effect on the maximum value of the demagnetization field,but the area of the affected region by the particle is proportional to the particle size.A large particle produces a large affected area overlapped with those influenced by other particles,which leads to the large demagnetization field.With increasing the length of the particle along the magnetization direction,the demagnetization field on the pole surface increases.The pole surface with a convex shape will increase the demagnetization field.The demagnetizing field near the nonmagnetic particle will be further increased by the large macroscopic demagnetizing field near the pole surface.This work suggests some practical approaches to optimize the microstructure of permanent magnets.

Nucleation barrier height in undercooled metallic melts

The phase-field model of a liquid-to-solid transition was constructed where the model parameters were linked quantitatively to the interfacial properties, and the variation of nucleation barrier height in undercooled metallic melts with respect to undercooling was studied respectively based on two kinds of forms of local free energy density. The calculation results show that, with the increase of undercooling, the critical nucleus does not show bulk properties, and the nucleation barrier height decreases gradually and deviates more and more from that predicted by the classical nucleation theory in both cases. The physical spinodal occurs for a specific form of the local free energy density, where the nucleation barrier height vanishes when the undercooling reaches a critical value and the reduced nucleation barrier height can be expressed by a function of the ratio of undercooling to critical undercooling.