Conditioned medium from human dental pulp stem cells treats spinal cord injury by inhibiting microglial pyroptosis

Human dental pulp stem cell transplantation has been shown to be an effective therapeutic strategy for spinal cord injury.However,whether the human dental pulp stem cell secretome can contribute to functional recovery after spinal cord injury remains unclear.In the present study,we established a rat model of spinal cord injury based on impact injury from a dropped weight and then intraperitoneally injected the rats with conditioned medium from human dental pulp stem cells.We found that the conditioned medium effectively promoted the recovery of sensory and motor functions in rats with spinal cord injury,decreased expression of the microglial pyroptosis markers NLRP3,GSDMD,caspase-1,and interleukin-1β,promoted axonal and myelin regeneration,and inhibited the formation of glial scars.In addition,in a lipopolysaccharide-induced BV2 microglia model,conditioned medium from human dental pulp stem cells protected cells from pyroptosis by inhibiting the NLRP3/caspase-1/interleukin-1βpathway.These results indicate that conditioned medium from human dental pulp stem cells can reduce microglial pyroptosis by inhibiting the NLRP3/caspase-1/interleukin-1βpathway,thereby promoting the recovery of neurological function after spinal cord injury.Therefore,conditioned medium from human dental pulp stem cells may become an alternative therapy for spinal cord injury.

Influence of variable viscosity and double diffusion on the convective stability of a nanofluid flow in an inclined porous channel

The influence of variable viscosity and double diffusion on the convective stability of a nanofluid flow in an inclined porous channel is investigated.The DarcyBrinkman model is used to characterize the fluid flow dynamics in porous materials.The analytical solutions are obtained for the unidirectional and completely developed flow.Based on a normal mode analysis,the generalized eigenvalue problem under a perturbed state is solved.The eigenvalue problem is then solved by the spectral method.Finally,the critical Rayleigh number with the corresponding wavenumber is evaluated at the assigned values of the other flow-governing parameters.The results show that increasing the Darcy number,the Lewis number,the Dufour parameter,or the Soret parameter increases the stability of the system,whereas increasing the inclination angle of the channel destabilizes the flow.Besides,the flow is the most unstable when the channel is vertically oriented.

Therapeutic advances in neural regeneration for Huntington’s disease

Huntington’s disease is a neurodegenerative disease caused by the expansion mutation of a cytosine-adenine-guanine triplet in the exon 1 of the HTT gene which is responsible for the production of the huntingtin (Htt) protein. In physiological conditions, Htt is involved in many cellular processes such as cell signaling, transcriptional regulation, energy metabolism regulation, DNA maintenance, axonal trafficking, and antiapoptotic activity. When the genetic alteration is present, the production of a mutant version of Htt (mHtt) occurs, which is characterized by a plethora of pathogenic activities that, finally, lead to cell death. Among all the cells in which mHtt exerts its dangerous activity, the GABAergic Medium Spiny Neurons seem to be the most affected by the mHtt-induced excitotoxicity both in the cortex and in the striatum. However, as the neurodegeneration proceeds ahead the neuronal loss grows also in other brain areas such as the cerebellum, hypothalamus, thalamus, subthalamic nucleus, globus pallidus, and substantia nigra, determining the variety of symptoms that characterize Huntington’s disease. From a clinical point of view, Huntington’s disease is characterized by a wide spectrum of symptoms spanning from motor impairment to cognitive disorders and dementia. Huntington’s disease shows a prevalence of around 3.92 cases every 100,000 worldwide and an incidence of 0.48 new cases every 100,000/year. To date, there is no available cure for Huntington’s disease. Several treatments have been developed so far, aiming to reduce the severity of one or more symptoms to slow down the inexorable decline caused by the disease. In this context, the search for reliable strategies to target the different aspects of Huntington’s disease become of the utmost interest. In recent years, a variety of studies demonstrated the detrimental role of neuronal loss in Huntington’s disease condition highlighting how the replacement of lost cells would be a reasonable strategy to overcome the neurodegeneration. In this view, numerous have been the attempts in several preclinical models of Huntington’s disease to evaluate the feasibility of invasive and non-invasive approaches. Thus, the aim of this review is to offer an overview of the most appealing approaches spanning from stem cell-based cell therapy to extracellular vesicles such as exosomes in light of promoting neurogenesis, discussing the results obtained so far, their limits and the future perspectives regarding the neural regeneration in the context of Huntington’s disease.

Prediction of subsurface settlement induced by shield tunnelling in sandy cobble stratum

This study focuses on the analytical prediction of subsurface settlement induced by shield tunnelling in sandy cobble stratum considering the volumetric deformation modes of the soil above the tunnel crown.A series of numerical analyses is performed to examine the effects of cover depth ratio(C/D),tunnel volume loss rate(h t)and volumetric block proportion(VBP)on the characteristics of subsurface settle-ment trough and soil volume loss.Considering the ground loss variation with depth,three modes are deduced from the volumetric deformation responses of the soil above the tunnel crown.Then,analytical solutions to predict subsurface settlement for each mode are presented using stochastic medium theory.The influences of C/D,h t and VBP on the key parameters(i.e.B and N)in the analytical expressions are discussed to determine the fitting formulae of B and N.Finally,the proposed analytical solutions are validated by the comparisons with the results of model test and numerical simulation.Results show that the fitting formulae provide a convenient and reliable way to evaluate the key parameters.Besides,the analytical solutions are reasonable and available in predicting the subsurface settlement induced by shield tunnelling in sandy cobble stratum.

Preparation of FeCoNi medium entropy alloy from Fe^(3+)-Co^(2+)-Ni^(2+)solution system

In recent years,medium entropy alloys have become a research hotspot due to their excellent physical and chemical performances.By controlling reasonable elemental composition and processing parameters,the medium entropy alloys can exhibit similar properties to high entropy alloys and have lower costs.In this paper,a FeCoNi medium entropy alloy precursor was prepared via sol-gel and coprecipitation methods,respectively,and FeCoNi medium entropy alloys were prepared by carbothermal and hydrogen reduction.The phases and magnetic properties of FeCoNi medium entropy alloy were investigated.Results showed that FeCoNi medium entropy alloy was produced by carbothermal and hydrogen reduction at 1500℃.Some carbon was detected in the FeCoNi medium entropy alloy prepared by carbothermal reduction.The alloy prepared by hydrogen reduction was uniform and showed a relatively high purity.Moreover,the hydrogen reduction product exhibited better saturation magnetization and lower coercivity.

揭示氨对正己酸生产影响的机制——影响途径、关键酶和微生物

n-Caproate,which is produced via chain elongation(CE)using waste biomass,can supply various fossilderived products,thus advancing the realization of carbon neutrality.Ammonia released from the degradation of nitrogen-rich waste biomass can act as a nutrient or an inhibitor in anaerobic bioprocesses,including CE,with the distinction being primarily dependent on its concentration.Currently,the optimal concentration of ammonia and the threshold of toxicity for open-culture n-caproate production using ethanol as an electron donor,along with the underlying mechanisms,remain unclear.This study revealed that the optimal concentration of ammonia for n-caproate production was 2.0 g∙L^(-1),whereas concentrations exceeding this threshold markedly suppressed the CE performance.Exploration of the mechanism revealed the involvement of two forms of ammonia(i.e.,ammonium ions and free ammonia)in this inhibitory behavior.High ammonia levels(5.0 g∙L^(-1))induced excessive ethanol oxidation and suppressed the reverse β-oxidation(RBO)process,directly leading to the enhanced activities of enzymes(phosphotransacetylase and acetate kinase)responsible for acetate formation and diminished activities of butyryl-coenzyme A(CoA):acetyl-CoA transferase,caproyl-CoA:butyryl-CoA transferase,and caproyl-CoA:acetyl-CoA transferase that are involved in the syntheses of n-butyrate and n-caproate.Furthermore,the composition of the microbial community shifted from Paraclostridium dominance(at 0.1 g∙L^(-1)ammonia)to a co-dominance of Fermentimonas,Clostridium sensu stricto 12,and Clostridium sensu stricto 15 at 2.0 g∙L^(-1)ammonia.However,these CE-functional bacteria were mostly absent in the presence of excessive ammonia(5.0 g∙L^(-1)ammonia).Metagenomic analysis revealed the upregulation of functions such as RBO,fatty acid synthesis,K^(+)efflux,adenosine triphosphatase(ATPase)metabolism,and metal cation export in the presence of 2.0 g∙L^(-1)ammonia,collectively contributing to enhanced n-caproate production.Conversely,the aforementioned functions(excluding metal cation export)and K^(+)influx were suppressed by excessive ammonia,undermining both ammonia detoxification and n-caproate biosynthesis.The comprehensive elucidation of ammonia-driven mechanisms influencing n-caproate production,as provided in this study,is expected to inspire researchers to devise effective strategies to alleviate ammonia-induced inhibition.

Review on the plastic instability of medium -Mn steels for identifying the formation mechanisms of Lüders and Portevin -Le Chatelier bands

Plastic instability,including both the discontinuous yielding and stress serrations,has been frequently observed during the tensile deformation of medium-Mn steels(MMnS)and has been intensively studied in recent years.Unfortunately,research results are controversial,and no consensus has been achieved regarding the topic.Here,we first summarize all the possible factors that affect the yielding and flow stress serrations in MMnS,including the morphology and stability of austenite,the feature of the phase interface,and the deformation parameters.Then,we propose a universal mechanism to explain the conflicting experimental results.We conclude that the discontinuous yielding can be attributed to the lack of mobile dislocation before deformation and the rapid dislocation multiplication at the beginning of plastic deformation.Meanwhile,the results show that the stress serrations are formed due to the pinning and depinning between dislocations and interstitial atoms in austenite.Strain-induced martensitic transformation,influenced by the mechanical stability of austenite grain and deformation parameters,should not be the intrinsic cause of plastic instability.However,it can intensify or weaken the discontinuous yielding and the stress serrations by affecting the mobility and density of dislocations,as well as the interaction between the interstitial atoms and dislocations in austenite grains.

Micromechanism and mathematical model of stress sensitivity in tight reservoirs of binary granular medium

Research on reservoir rock stress sensitivity has traditionally focused on unary granular structures,neglecting the binary nature of real reservoirs,especially tight reservoirs.Understanding the stresssensitive behavior and mathematical characterization of binary granular media remains a challenging task.In this study,we conducted online-NMR experiments to investigate the permeability and porosity evolution as well as stress-sensitive control mechanisms in tight sandy conglomerate samples.The results revealed stress sensitivity coefficients between 0.042 and 0.098 and permeability damage rates ranging from 65.6%to 90.9%,with an average pore compression coefficient of 0.0168—0.0208 MPa 1.Pore-scale compression occurred in three stages:filling,compression,and compaction,with matrix pores playing a dominant role in pore compression.The stress sensitivity of binary granular media was found to be influenced by the support structure and particle properties.High stress sensitivity was associated with small fine particle size,high fines content,high uniformity coefficient of particle size,high plastic deformation,and low Young's modulus.Matrix-supported samples exhibited a high irreversible permeability damage rate(average=74.2%)and stress sensitivity coefficients(average=0.089),with pore spaces more slit-like.In contrast,grain-supported samples showed low stress sensitivity coefficients(average=0.021)at high stress stages.Based on the experiments,we developed a mathematical model for stress sensitivity in binary granular media,considering binary granular properties and nested interactions using Hertz contact deformation and Poiseuille theory.By describing the change in activity content of fines under stress,we characterized the non-stationary state of compressive deformation in the binary granular structure and classified the reservoir into three categories.The model was applied for production prediction using actual data from the Mahu reservoir in China,showing that the energy retention rates of support-dominated,fill-dominated,and matrix-controlled reservoirs should be higher than 70.1%,88%,and 90.2%,respectively.

Fiber Bundle Topology Optimization for Surface Flows

This paper presents a topology optimization approach for the surface flows on variable design domains.Via this approach,the matching between the pattern of a surface flow and the 2-manifold used to define the pattern can be optimized,where the 2-manifold is implicitly defined on another fixed 2-manifold named as the base manifold.The fiber bundle topology optimization approach is developed based on the description of the topological structure of the surface flow by using the differential geometry concept of the fiber bundle.The material distribution method is used to achieve the evolution of the pattern of the surface flow.The evolution of the implicit 2-manifold is realized via a homeomorphous map.The design variable of the pattern of the surface flow and that of the implicit 2-manifold are regularized by two sequentially implemented surface-PDE filters.The two surface-PDE filters are coupled,because they are defined on the implicit 2-manifold and base manifold,respectively.The surface Navier-Stokes equations,defined on the implicit 2-manifold,are used to describe the surface flow.The fiber bundle topology optimization problem is analyzed using the continuous adjoint method implemented on the first-order Sobolev space.Several numerical examples have been provided to demonstrate this approach,where the combination of the viscous dissipation and pressure drop is used as the design objective.

Imaging through scattering layers using a near-infrared low-spatial-coherence fiber random laser

Optical memory effect-based speckle-correlated technology has been developed for reconstructing hidden objectsfrom disordered speckle patterns,achieving imaging through scattering layers.However,the lighting efficiency and fieldof view of existing speckle-correlated imaging systems are limited.Here,a near-infrared low spatial coherence fiberrandom laser illumination method is proposed to address the above limitations.Through the utilization of random Rayleighscattering within dispersion-shifted fibers to provide feedback,coupled with stimulated Raman scattering for amplification,a near-infrared fiber random laser exhibiting a high spectral density and extremely low spatial coherence is generated.Based on the designed fiber random laser,speckle-correlated imaging through scattering layers is achieved,with highlighting efficiency and a large imaging field of view.This work improves the performance of speckle-correlated imagingand enriches the research on imaging through scattering medium.

Cosmic Ray-driven Bioenergetics for Life in Molecular Clouds

According to models such as panspermia or the Nebula-Relay hypothesis,the ancestors of life on Earth once lived in molecular clouds.Then what are the energy source and bioenergetics for such lifeforms?A new bioenergetic mechanism powered by cosmic ray ionization of hydrogen molecules is proposed and its relation with the origin of chemiosmosis is also discussed in this paper.Based on this mechanism,the Last Universal Common Ancestor may be a type of lifeform that utilizes hydrogen molecules as donors of electron transport chains.

Dynamic thermo-mechanical responses of road-soft ground system under vehicle load and daily temperature variation

A complete road-soft ground model is established in this paper to study the dynamic responses caused by vehicle loads and/or daily temperature variation.A dynamic thermo-elastic model is applied to capturing the behavior of the rigid pavement,the base course,and the subgrade,while the soft ground is characterized using a dynamic thermo-poroelastic model.Solutions to the road-soft ground system are derived in the Laplace-Hankel transform domain.The time domain solutions are obtained using an integration approach.The temperature,thermal stress,pore water pressure,and displacement responses caused by the vehicle load and the daily temperature variation are presented.Results show that obvious temperature change mainly exists within 0.3 m of the road when subjected to the daily temperature variation,whereas the stress responses can still be found in deeper places because of the thermal swelling/shrinkage deformation within the upper road structures.Moreover,it is important to consider the coupling effects of the vehicle load and the daily temperature variation when calculating the dynamic responses inside the road-soft ground system.

Deep bed filtration model for cake filtration and erosion

Many phenomena in nature and technology are associated with the filtration of suspensions and colloids in porous media. Two main types of particle deposition,namely, cake filtration at the inlet and deep bed filtration throughout the entire porous medium, are studied by different models. A unified approach for the transport and deposition of particles based on the deep bed filtration model is proposed. A variable suspension flow rate, proportional to the number of free pores at the inlet of the porous medium, is considered. To model cake filtration, this flow rate is introduced into the mass balance equation of deep bed filtration. For the cake filtration without deposit erosion,the suspension flow rate decreases to zero, and the suspension does not penetrate deep into the porous medium. In the case of the cake filtration with erosion, the suspension flow rate is nonzero, and the deposit is distributed throughout the entire porous medium. An exact solution is obtained for a constant filtration function. The method of characteristics is used to construct the asymptotics of the concentration front of suspended and retained particles for a filtration function in a general form. Explicit formulae are obtained for a linear filtration function. The properties of these solutions are studied in detail.

Nonlinear phenomena in vibrations of embedded carbon nanotubes conveying viscous fluid

Various nonlinear phenomena such as bifurcations and chaos in the responses of carbon nanotubes(CNTs)are recognized as being major contributors to the inaccuracy and instability of nanoscale mechanical systems.Therefore,the main purpose of this paper is to predict the nonlinear dynamic behavior of a CNT conveying viscousfluid and supported on a nonlinear elastic foundation.The proposed model is based on nonlocal Euler–Bernoulli beam theory.The Galerkin method and perturbation analysis are used to discretize the partial differential equation of motion and obtain the frequency-response equation,respectively.A detailed parametric study is reported into how the nonlocal parameter,foundation coefficients,fluid viscosity,and amplitude and frequency of the external force influence the nonlinear dynamics of the system.Subharmonic,quasi-periodic,and chaotic behaviors and hardening nonlinearity are revealed by means of the vibration time histories,frequency-response curves,bifurcation diagrams,phase portraits,power spectra,and Poincarémaps.Also,the results show that it is possible to eliminate irregular motion in the whole range of external force amplitude by selecting appropriate parameters.

Mathematical framework of nonlinear elastic waves propagating in pre-stressed media

Acoustic nonlinearity holds potential as a method for assessing material stress.Analogous to the acoustoelastic effect,where the velocity of elastic waves is influenced by third-order elastic constants,the propagation of nonlinear acoustic waves in pre-stressed materials would be influenced by higher-order elastic constants.Despite this,there has been a notable absence of research exploring this phenomenon.Consequently,this paper aims to establish a theoretical framework for governing the propagation of nonlinear acoustic waves in pre-stressed materials.It delves into the impact of pre-stress on higher-order material parameters,and specifically examines the propagation of one-dimensional acoustic waves within the contexts of the uniaxial stress and the biaxial stress.This paper establishes a theoretical foundation for exploring the application of nonlinear ultrasonic techniques to measure pre-stress in materials.

THE INTERIOR TRANSMISSION EIGENVALUE PROBLEM FOR AN ANISOTROPIC MEDIUM BY A PARTIALLY COATED BOUNDARY

We consider the interior transmission eigenvalue problem corresponding to the scattering for an anisotropic medium of the scalar Helmholtz equation in the case where the boundary?Ωis split into two disjoint parts and possesses different transmission conditions.Using the variational method,we obtain the well posedness of the interior transmission problem,which plays an important role in the proof of the discreteness of eigenvalues.Then we achieve the existence of an infinite discrete set of transmission eigenvalues provided that n≡1,where a fourth order differential operator is applied.In the case of n■1,we show the discreteness of the transmission eigenvalues under restrictive assumptions by the analytic Fredholm theory and the T-coercive method.

Theoretical study on the effective thermal conductivity of silica aerogels based on a cross-aligned and cubic pore model

Aerogel nanoporous materials possess high porosity, high specific surface area, and extremely low density due to their unique nanoscale network structure. Moreover, their effective thermal conductivity is very low, making them a new type of lightweight and highly efficient nanoscale super-insulating material. However, prediction of their effective thermal conductivity is challenging due to their uneven pore size distribution. To investigate the internal heat transfer mechanism of aerogel nanoporous materials, this study constructed a cross-aligned and cubic pore model(CACPM) based on the actual pore arrangement of SiO_(2) aerogel. Based on the established CACPM, the effective thermal conductivity expression for the aerogel was derived by simultaneously considering gas-phase heat conduction, solid-phase heat conduction, and radiative heat transfer. The derived expression was then compared with available experimental data and the Wei structure model. The results indicate that, according to the model established in this study for the derived thermal conductivity formula of silica aerogel, for powdery silica aerogel under the conditions of T = 298 K, a_(2)= 0.85, D_(1)= 90 μm, ρ = 128 kg/m^(3), within the pressure range of 0–10^(5)Pa, the average deviation between the calculated values and experimental values is 10.51%. In the pressure range of 10^(3)–10^(4)Pa, the deviation between calculated values and experimental values is within 4%. Under these conditions, the model has certain reference value in engineering verification. This study also makes a certain contribution to the research of aerogel thermal conductivity heat transfer models and calculation formulae.

miRNA-21-5p is an important contributor to the promotion of injured peripheral nerve regeneration using hypoxia-pretreated bone marrow-derived neural crest cells

Our previous study found that rat bone marrow–derived neural crest cells(acting as Schwann cell progenitors)have the potential to promote long-distance nerve repair.Cell-based therapy can enhance peripheral nerve repair and regeneration through paracrine bioactive factors and intercellular communication.Nevertheless,the complex contributions of various types of soluble cytokines and extracellular vesicle cargos to the secretome remain unclear.To investigate the role of the secretome and extracellular vesicles in repairing damaged peripheral nerves,we collected conditioned culture medium from hypoxia-pretreated neural crest cells,and found that it significantly promoted the repair of sensory neurons damaged by oxygen-glucose deprivation.The mRNA expression of trophic factors was highly expressed in hypoxia-pretreated neural crest cells.We performed RNA sequencing and bioinformatics analysis and found that miR-21-5p was enriched in hypoxia-pretreated extracellular vesicles of neural crest cells.Subsequently,to further clarify the role of hypoxia-pretreated neural crest cell extracellular vesicles rich in miR-21-5p in axonal growth and regeneration of sensory neurons,we used a microfluidic axonal dissociation model of sensory neurons in vitro,and found that hypoxia-pretreated neural crest cell extracellular vesicles promoted axonal growth and regeneration of sensory neurons,which was greatly dependent on loaded miR-21-5p.Finally,we constructed a miR-21-5p-loaded neural conduit to repair the sciatic nerve defect in rats and found that the motor and sensory functions of injured rat hind limb,as well as muscle tissue morphology of the hind limbs,were obviously restored.These findings suggest that hypoxia-pretreated neural crest extracellular vesicles are natural nanoparticles rich in miRNA-21-5p.miRNA-21-5p is one of the main contributors to promoting nerve regeneration by the neural crest cell secretome.This helps to explain the mechanism of action of the secretome and extracellular vesicles of neural crest cells in repairing damaged peripheral nerves,and also promotes the application of miR-21-5p in tissue engineering regeneration medicine.

A Dual-Cluster-Head Based Medium Access Control for Large-Scale UAV Ad-Hoc Networks

Unmanned Aerial Vehicle(UAV)ad hoc network has achieved significant growth for its flexibility,extensibility,and high deployability in recent years.The application of clustering scheme for UAV ad hoc network is imperative to enhance the performance of throughput and energy efficiency.In conventional clustering scheme,a single cluster head(CH)is always assigned in each cluster.However,this method has some weaknesses such as overload and premature death of CH when the number of UAVs increased.In order to solve this problem,we propose a dual-cluster-head based medium access control(DCHMAC)scheme for large-scale UAV networks.In DCHMAC,two CHs are elected to manage resource allocation and data forwarding cooperatively.Specifically,two CHs work on different channels.One of CH is used for intra-cluster communication and the other one is for inter-cluster communication.A Markov chain model is developed to analyse the throughput of the network.Simulation result shows that compared with FM-MAC(flying ad hoc networks multi-channel MAC,FM-MAC),DCHMAC improves the throughput by approximately 20%~50%and prolongs the network lifetime by approximately 40%.

Modeling of Leachate Propagation in a Municipal Solid Waste Landfill Foundation

The study deals with the numerical modeling of leachate distribution in the porous medium located under a municipal solid waste disposal landfill(MSWLF).The considered three-layer system is based on geological data obtained from field measurements.For simplicity,the problem is investigated by assuming a two-component approach.Nevertheless,the heat produced by landfills due to biological and chemical processes and the thermal diffusion mechanism contributing to pollution transport are taken into account.The numerical modeling of the propagation of leachate in the considered layered porous medium is implemented for parameters corresponding to natural soil and for the case where disruption of the porous medium structure is due to cracks formation or erosion.The latter is accompanied by an increase in rock permeability.In this case,the emergence of multi-vortex flow in the layer of high permeability is observed to substantially influence the bottom layers and cause intensification of the leachate propagation.These effects should be taken into account when estimating the parameters and properties of materials required for the construction of solid waste disposal facilities.