Stiffness-tunable biomaterials provide a good extracellular matrix environment for axon growth and regeneration

Neuronal growth, extension, branching, and formation of neural networks are markedly influenced by the extracellular matrix—a complex network composed of proteins and carbohydrates secreted by cells. In addition to providing physical support for cells, the extracellular matrix also conveys critical mechanical stiffness cues. During the development of the nervous system, extracellular matrix stiffness plays a central role in guiding neuronal growth, particularly in the context of axonal extension, which is crucial for the formation of neural networks. In neural tissue engineering, manipulation of biomaterial stiffness is a promising strategy to provide a permissive environment for the repair and regeneration of injured nervous tissue. Recent research has fine-tuned synthetic biomaterials to fabricate scaffolds that closely replicate the stiffness profiles observed in the nervous system. In this review, we highlight the molecular mechanisms by which extracellular matrix stiffness regulates axonal growth and regeneration. We highlight the progress made in the development of stiffness-tunable biomaterials to emulate in vivo extracellular matrix environments, with an emphasis on their application in neural repair and regeneration, along with a discussion of the current limitations and future prospects. The exploration and optimization of the stiffness-tunable biomaterials has the potential to markedly advance the development of neural tissue engineering.

Telencephalic stab wound injury induces regenerative angiogenesis and neurogenesis in zebrafish:unveiling the role of vascular endothelial growth factor signaling and microglia

After brain damage,regenerative angiogenesis and neurogenesis have been shown to occur simultaneously in mammals,suggesting a close link between these processes.However,the mechanisms by which these processes interact are not well understood.In this work,we aimed to study the correlation between angiogenesis and neurogenesis after a telencephalic stab wound injury.To this end,we used zebrafish as a relevant model of neuroplasticity and brain repair mechanisms.First,using the Tg(fli1:EGFP×mpeg1.1:mCherry)zebrafish line,which enables visualization of blood vessels and microglia respectively,we analyzed regenerative angiogenesis from 1 to 21 days post-lesion.In parallel,we monitored brain cell proliferation in neurogenic niches localized in the ventricular zone by using immunohistochemistry.We found that after brain damage,the blood vessel area and width as well as expression of the fli1 transgene and vascular endothelial growth factor(vegfaa and vegfbb)were increased.At the same time,neural stem cell proliferation was also increased,peaking between 3 and 5 days post-lesion in a manner similar to angiogenesis,along with the recruitment of microglia.Then,through pharmacological manipulation by injecting an anti-angiogenic drug(Tivozanib)or Vegf at the lesion site,we demonstrated that blocking or activating Vegf signaling modulated both angiogenic and neurogenic processes,as well as microglial recruitment.Finally,we showed that inhibition of microglia by clodronate-containing liposome injection or dexamethasone treatment impairs regenerative neurogenesis,as previously described,as well as injury-induced angiogenesis.In conclusion,we have described regenerative angiogenesis in zebrafish for the first time and have highlighted the role of inflammation in this process.In addition,we have shown that both angiogenesis and neurogenesis are involved in brain repair and that microglia and inflammation-dependent mechanisms activated by Vegf signaling are important contributors to these processes.This study paves the way for a better understanding of the effect of Vegf on microglia and for studies aimed at promoting angiogenesis to improve brain plasticity after brain injury.

Transforming growth factor-beta 1 enhances discharge activity of cortical neurons

Transforming growth factor-beta 1(TGF-β1)has been extensively studied for its pleiotropic effects on central nervous system diseases.The neuroprotective or neurotoxic effects of TGF-β1 in specific brain areas may depend on the pathological process and cell types involved.Voltage-gated sodium channels(VGSCs)are essential ion channels for the generation of action potentials in neurons,and are involved in various neuroexcitation-related diseases.However,the effects of TGF-β1 on the functional properties of VGSCs and firing properties in cortical neurons remain unclear.In this study,we investigated the effects of TGF-β1 on VGSC function and firing properties in primary cortical neurons from mice.We found that TGF-β1 increased VGSC current density in a dose-and time-dependent manner,which was attributable to the upregulation of Nav1.3 expression.Increased VGSC current density and Nav1.3 expression were significantly abolished by preincubation with inhibitors of mitogen-activated protein kinase kinase(PD98059),p38 mitogen-activated protein kinase(SB203580),and Jun NH2-terminal kinase 1/2 inhibitor(SP600125).Interestingly,TGF-β1 significantly increased the firing threshold of action potentials but did not change their firing rate in cortical neurons.These findings suggest that TGF-β1 can increase Nav1.3 expression through activation of the ERK1/2-JNK-MAPK pathway,which leads to a decrease in the firing threshold of action potentials in cortical neurons under pathological conditions.Thus,this contributes to the occurrence and progression of neuroexcitatory-related diseases of the central nervous system.

Activation of adult endogenous neurogenesis by a hyaluronic acid collagen gel containing basic fibroblast growth factor promotes remodeling and functional recovery of the injured cerebral cortex

The presence of endogenous neural stem/progenitor cells in the adult mammalian brain suggests that the central nervous system can be repaired and regenerated after injury.However,whether it is possible to stimulate neurogenesis and reconstruct cortical layers II to VI in non-neurogenic regions,such as the cortex,remains unknown.In this study,we implanted a hyaluronic acid collagen gel loaded with basic fibroblast growth factor into the motor cortex immediately following traumatic injury.Our findings reveal that this gel effectively stimulated the proliferation and migration of endogenous neural stem/progenitor cells,as well as their differentiation into mature and functionally integrated neurons.Importantly,these new neurons reconstructed the architecture of cortical layers II to VI,integrated into the existing neural circuitry,and ultimately led to improved brain function.These findings offer novel insight into potential clinical treatments for traumatic cerebral cortex injuries.

Growth interface of CdMnTe crystal by traveling heater method

The growth interfaces of CdMnTe（CMT） crystals grown by traveling heater method（THM） were studied. Two types of polycrystalline CMT feed ingots synthesized in a traditional rocking furnace and vertical Bridgman（VB） furnace were adopted in THM growth, and the effects of the polycrystalline feed on the growth interface were revealed. The morphology of the growth interface of CMT crystal（CMT2） grown from the feed by vertical Bridgman was smoother with lower curvature compared with that of CMT crystal（CMT1） from the feed by rocking furnace. The radial Mn composition and Te inclusion distribution of the CMT wafers were analyzed and correlated to the growth interface. The Mn segregation along the radial direction and Te inclusion density of CMT2 were lower than those of CMT1. The VB method synthesized polycrystalline feed could improve the growth interface morphology, which is beneficial for decreasing the Te inclusions and Mn segregation in CMT wafers.

Growth kinetics of interfacial intermetallic compounds formed in SnPbInBiSb high entropy alloy soldered joints on Cu substrates

The growth behavior of the complex intermetallic compounds(IMCs)formed at the interface of Cu/SnPbInBiSb high entropy alloy solder joints was explored.The growth inhibition mechanism of the IMCs at the Cu/SnPbInBiSb solid−liquid reaction interface was revealed.The results showed that the growth rate of the complex IMCs obviously decreased at the Cu/SnPbInBiSb solid−liquid reaction interface.The maximum average thickness of IMCs only reached up to 1.66μm after reflowing at 200℃for 10 min.The mechanism for the slow growth of the complex IMCs was analyzed into three aspects.Firstly,the high entropy of the liquid SnPbInBiSb alloy reduced the growth rate of the complex IMCs.Secondly,the distorted lattice of complex IMCs restrained the diffusion of Cu atoms.Lastly,the higher activation energy(40.9 kJ/mol)of Cu/SnPbInBiSb solid−liquid interfacial reaction essentially impeded the growth of the complex IMCs.

Platelet-rich plasma increases transforming growth factor-beta1 expression at graft-host interface following autologous osteochondral transplantation in a rabbit model

AIM: To explore the effect of platelet-rich plasma on protein expression patterns of transforming growth factor-beta1(TGF-β1) in cartilage following autologous osteochondral transplantation(AOT) in a rabbit knee cartilage defect model.METHODS: Twelve New Zealand white rabbits received bilateral AOT. In each rabbit, one knee was randomized to receive an autologous platelet rich plasma(PRP) injection and the contralateral knee received saline injection. Rabbits were euthanized at 3, 6 and 12 wk post-operatively. Articular cartilage sections were stained with TGF-β1 antibody. Histological regions of interest(ROI)(left, right and center of the autologous grafts interfaces) were evaluated using Meta Morph. Percentage of chondrocytes positive for TGF-β1 was then assessed.RESULTS: Percentage of chondrocytes positive for TGF-β1 was higher in PRP treated knees for selected ROIs(left; P = 0.03, center; P = 0.05) compared to control and was also higher in the PRP group at each post-operative time point(P = 6.6 × 10^(-4), 3.1 × 10^(-4) and 7.3 × 10^(-3) for 3, 6 and 12 wk, respectively). TGF-β1 expression was higher in chondrocytes of PRP-treated knees(36% ± 29% vs 15% ± 18%)(P = 1.8 × 10^(-6)) overall for each post-operative time point and ROI. CONCLUSION: Articular cartilage of rabbits treated with AOT and PRP exhibit increased TGF-β1 expression compared to those treated with AOT and saline. Our findings suggest that adjunctive PRP may increase TGF-β1 expression, which may play a role in the chondrogenic effect of PRP in vivo.

Investigation on hydrate growth at the oil–water interface:In the presence of asphaltene

Natural gas hydrates can readily form in deep-water oil production processes and pose a great threat to the oil industry.Moreover,the coexistence of hydrate and asphaltene can result in more severe challenges to subsea flow assurance.In order to study the effects of asphaltene on hydrate growth at the oil-water interface,a series of micro-experiments were conducted in a self-made reactor,where hydrates nucleated and grew on the surface of a water droplet immersed in asphaltene-containing oil.Based on the micro-observations,the shape and growth rate of the hydrate shell formed at the oil-water interface were mainly investigated and the effects of asphaltene on hydrate growth were analyzed.According to the experimental results,the shape of the water droplet and the interfacial area changed significantly after the formation of the hydrate shell when the asphaltene concentration was higher than a certain value.A mechanism related to the reduction of the interfacial tension caused by the absorption of asphaltenes on the interface was proposed for illustration.Moreover,the growth rate of the hydrate shell decreased significantly with the increasing asphaltene concentration under experimental conditions.The conclusions of this paper could provide preliminary insight how asphaltene affect hydrate growth at the oil-water interface.

INTERFACE MORPHOLOGIES AND MICROSTRUCTURES DURING DENDRITE-TO-CELL TRANSITION AT HIGH GROWTH RATE

The interface morphologies and microstruetures of the directionally solidified Ni-5wt-% Cu alloy during dendrite-to-cell transition at high growth rates have been investigated with a newly developed apparatus for unidirectional solidification with the temperature gradient at the solid/liquid interface higher than 1000 K/cm.The results show that in the vicinity of dendrite-to-cell transition point,the well developed sidebranches become shrivelled with the increase of growth rate and disappear at the dendrite-to-cell transition,and the primary spacing decreases simultaneously.Moreover,the length of mushy zone decreases greatly dur- ing the dendrite-to-cell transition.Cells obtained at high growth rates have very similar morphologies to those at low growth rates,but with much smaller cell spacings and unsmoothed cell walls which may be attributed to the different stability conditions of the cell walls at low and high growth rates respectively.

Growth and aggregation micromorphology of natural gas hydrate particles near gas-liquid interface under stirring condition

To investigate the morphological evolution of the whole growth and aggregation processes of hydrate crystals near the gas–liquid interface,we used a high-pressure visual reactor with high-speed camera to capture the micromorphology of hydrate particles in a natural gas+pure water system with pressure from 2.6 to 3.6 MPa and sub-cooling from 4.7 to 6.23C.The results showed that under low sub-cooling conditions,the amount and size of particles increased first and then decreased in the range of 0–330 lm,and the small particles always dominated.These particles can be roughly classified into two categories:planar flake particles and polyhedral solid particles.Then,the concept of maximum growth dominant particle size was proposed to distinguish the morphological boundary of growth and aggregation.In addition,the micro model was established to better reflect the effects of particle formation process and evolution mechanism near the gas–liquid interface under stirring condition.The results of this study can provide a guidance for flow assurance in multiphase pipeline.

ELASTIC-PLASTIC CRACK GROWTH ON PLANE STRAIN BIMATERIAL INTERFACE

Finite element computations are carried out to simulate plane strain crack growth on a bimaterial interface under the assumption of small scale yielding.The modified Guron constitutive equation and the element vanish technique introduced by Tvergaard et al.are used to model the final formation of an open crack.It is found from the calculation that the critical fracture toughness for crack growth is much low- er in bimaterials than that in homogeneous material.The critical fracture toughness is strongly dependent on material properties of the bimaterial pair and the mixed mode of remote loads.The interface crack grows in the more compliant(lower hardening)material or in the weaker(lower yield strength)material.In Mode-Ⅰ loading,the crack grows zigzag along the interface.

Numerical simulation of TBCs residual stresses by the growth of TGO on typical interface morphology

The effect of TGO （ thermally grown oxide ） growth based on typical interface morphology on residual stresses distribution in thermal barrier coatings was analyzed by ABAQUS software. TGO oxidation kinetics, the relationship between TGO thickness and thermal cycles number, and typical morphology including sinusoid , cone and groove were considered in the calculation process. 13 FEM （finite element method） models with different TGO thickness based on uniform interface morphology were established for analysis. The calculation results show that TCC （ top ceramic coating ） /TGO and TGO/BC （bond coating） interface residual stresses are affected significantly by inter）hce morphology and TGO thickness, both of which increase significantly with TGO growth ; the stress level in TCC/TGO interface is greater than that of TGO/BC interface ; each morphology peak exhibits tensile stress while each valley exhibits compressive stress in TCC/TGO interface; stress concentrates in such locations as each morphology center with sharp angle and the stress reaches the maximal value at the tip of each angle.

Numerical Study on Effect of Non-uniform CMAS Penetration on TGO Growth and Interface Stress Behavior of APS TBCs

The penetration of CaO-MgO-Al_(2)O_(3)-SiO_(2)(CMAS)is one of the most significant factors that induce the failure of air-plasma-sprayed thermal barrier coatings(APS TBCs).The direct penetration of CMAS changes the thermal/mechanical properties of the top coat(TC)layer,which affects the thermal mismatch stress behavior and the growth of thermally grown oxide(TGO)at the TC/bond coat(BC)interface,thereby resulting in a more complicated interface stress state.In the present study,a two-dimensional global model of APS TBCs with half of the TC layer penetrated by CMAS is established to investigate the effect of non-uniform CMAS penetration on the interface stress behavior.Subsequently,a local model extracted from the global model is established to investigate the effects of interface morphologies and CMAS penetration depth.The results show that non-uniform CMAS penetration causes non-uniform TGO growth in APS TBCs,which consequently causes the stress behavior to vary along the interface.Furthermore,the CMAS pen-etration depth imposes a significant effect on the TC/TGO interface stress behavior,whereas the interface roughness exerts a prominent effect on the stress level at the BC/TGO interface under CMAS penetration.This study reveals the mechanism associated with the effect of non-uniform CMAS penetration on the interface stress behavior in APS TBCSs.

Influence of Thermal Conductivity on Interface Shape during Growth of Sapphire Crystal Using a Heat-Exchanger-Method

The internal radiative contributed on heat transfer will enhance the heat transport inside the crystalline phase during growth the transparent sapphire crystal using a heat-exchanger-method (HEM). The artificially enhanced thermal conductivity of the solid to include the internal radiation effect was used in the present study. Numerical simulations using FIDAP were performed to investigate the effects of the thermal conductivity on the shape of the melt-crystal interface, the temperature distribution, and the velocity distribution. Heat transfer (including radiation) from the furnace to the crucible and heat extraction from the heat exchanger can be modeled by the convection boundary conditions. In the present study, we focus on the influence of the conductivity on the shape of the melt-crystal interface. Therefore, the effect of the others growth parameters during the HEM crystal growth was neglected. For the homogenous conductivity (km=kS=k), the maximum convexity decreases as k increases and the rate of maximum convexity increases for a higher conductivity is less abrupt than for a lower conductivity. For the no homogenous conductivity (km≠kS), the higher solid's kS generates lower maximum convexity and the variation in maximum convexity was less abrupt for the different melt's km. The maximum convexity decreases slightly as the enhance conductivity of the sapphire crystal increases. The effects of the anisotropic conductivity of the sapphire crystal were also addressed. The maximum convexity of the melt-crystal interface decreases when the radial conductivity (ksr) of the crystal increases. The maximum convexity increases as the axial conductivity (ksz) of the crucible increases.

Growth rate of CO_(2) hydrate film on water-oil and water-gaseous CO_(2) interface

It is known that injection of carbon dioxide into the petroleum reservoir(CO_(2) flooding) is one of the effective methods for enhanced oil recovery. CO_(2) flooding may be complicated by formation of CO_(2) hydrate plugs. It makes topical investigation of CO_(2) hydrate formation in the system gaseous CO_(2)-oil-water. In this work, the growth rates of carbon dioxide hydrate films at the water-oil as well as the water-gas interface are studied in the pressure range of 2.30-3.04 MPa and at temperatures between -5.4 and 5.0℃. It is found that the growth rate for the water-oil interface is 3.5 times lower than that for the water-gas interface with carbon dioxide. It is hypothesised that the observed decrease in the growth rate is related to the mechanical resistance of the oil components adsorbed on the interface to the growth of the hydrate film. The growth rate of the film has been shown to depend on the experimental procedure,most likely due to the different initial concentrations of carbon dioxide in the aqueous solutions.

Growth behavior and microstructure of intermetallics at interface of AuSn20 solder and metalized-Ni layer

The AuSn20/Ni joints were prepared by the reflow soldering technology and then annealed at solid-state temperature to form diffusion couples.The interfacial reactions and the growth kinetics of the intermetallic compounds(IMC)at the AuSn20/Ni soldering interface were investigated by scanning electron microscopy(SEM)and electron probe microanalysis(EPMA).The results show that,the(Ni,Au)3Sn2phases are formed at the AuSn20/Ni interface after soldering at583K.The thickness l of the IMC layer monotonically increases with increasing annealing time t according to the relationship l=k(t/t0)n,where the exponent n is0.527,0.476and0.471for393,433and473K annealing,respectively.This indicates that the volume diffusion contributes to the growth of the IMC layer at the AuSn20/Ni interface at solid-sate temperature.The pre-exponential factor K0=1.23×10?7m2/s and the activation enthalpy QK=81.8kJ/mol are obtained from the results of the parabolic coefficient K by a least-squares method.

Kinetics of Spherical Interface in Crystal Growth

The growth kinetics of spherical NiAl and CuZr crystals are studied by using molecular dynamics simulations. The growth rates of crystals are found to increase with the grain radius. The simulations show that the interface thickness and the Jackson α-faetor increase as the growth proceeds, indicating that the interface becomes increasingly rough during growth. Due to the increasing interface roughening, the fraction of repeatable growth sites at interface f is proposed to actually increase in growth. An attachment rate, which is defined as the fraction of atoms that join the crystal interface without leaving, is used to approximate f, displaying a linear increase. With this approximation, we predict the growth rates as a function of the crystal radius, and the results qualitatively agree with those from the direct simulations.

A Statistical Rate Theory of Interface Concentration during Solution ZeoliteCrystal Growth

A theoretical model is developed using statistical rate theory to determine the rate of molecular transport across the interface of a growing spherical zeolite crystal. The model is expressed in terms of the interface concentration. Two model constants appear in the expression for the equilibrium exchange rate. In order to validate the model, zeolite crystallization is investigated for a system for which experimental data exist. The model constants were first established using the measured growth rates at a specific temperature. Then the model was used to predict the growth rate at other temperatures.

基于FP-growth算法的交通事故数据关联规则挖掘研究

为了探寻多种事故影响因素共同作用下诱发交通事故的某种规律以及各因素间的关系,本文采用FP-growth算法对收集到的交通事故数据进行分析研究,挖掘其中的潜在价值信息,找出事故发生的原因,根据分析结果给相关部门提出建议,帮助城市交通管理者制定更有效的管理措施,以达到降低交通事故发生频率的目的。

基于FP-growth的老年行人交通事故损伤致因研究

为研究老年行人交通事故相关因素及其对损伤程度的影响,以中国交通事故深度调查数据库中2013—2023年710起机动车-老年行人事故为分析对象,利用FP-growth算法挖掘出4类影响因素28个类型变量共5594项关联规则。研究结果表明:行人年龄、碰撞速度、事故时间段及事故地点是影响老年行人事故死亡率的显著因素。特别是,行人年龄和碰撞速度对死亡率有显著影响,随着碰撞速度的增加,死亡率显著上升;60岁及以上老年行人年龄每增加1岁,其死亡率提升0.037倍。此外,事故发生在夜间、郊区或村庄的死亡率更高。研究结果可为提高老年行人交通安全,制定相关安全措施提供一定参考。