The combined application of stem cells and three-dimensional bioprinting scaffolds for the repair of spinal cord injury

Spinal cord injury is considered one of the most difficult injuries to repair and has one of the worst prognoses for injuries to the nervous system.Following surgery,the poor regenerative capacity of nerve cells and the generation of new scars can make it very difficult for the impaired nervous system to restore its neural functionality.Traditional treatments can only alleviate secondary injuries but cannot fundamentally repair the spinal cord.Consequently,there is a critical need to develop new treatments to promote functional repair after spinal cord injury.Over recent years,there have been seve ral developments in the use of stem cell therapy for the treatment of spinal cord injury.Alongside significant developments in the field of tissue engineering,three-dimensional bioprinting technology has become a hot research topic due to its ability to accurately print complex structures.This led to the loading of three-dimensional bioprinting scaffolds which provided precise cell localization.These three-dimensional bioprinting scaffolds co uld repair damaged neural circuits and had the potential to repair the damaged spinal cord.In this review,we discuss the mechanisms underlying simple stem cell therapy,the application of different types of stem cells for the treatment of spinal cord injury,and the different manufa cturing methods for three-dimensional bioprinting scaffolds.In particular,we focus on the development of three-dimensional bioprinting scaffolds for the treatment of spinal cord injury.

Role of transforming growth factor-βin peripheral nerve regeneration

Injuries caused by trauma and neurodegenerative diseases can damage the peripheral nervous system and cause functional deficits.Unlike in the central nervous system,damaged axons in peripheral nerves can be induced to regenerate in response to intrinsic cues after reprogramming or in a growth-promoting microenvironment created by Schwann cells.However,axon regeneration and repair do not automatically result in the restoration of function,which is the ultimate therapeutic goal but also a major clinical challenge.Transforming growth factor(TGF)is a multifunctional cytokine that regulates various biological processes including tissue repair,embryo development,and cell growth and differentiation.There is accumulating evidence that TGF-βfamily proteins participate in peripheral nerve repair through various factors and signaling pathways by regulating the growth and transformation of Schwann cells;recruiting specific immune cells;controlling the permeability of the blood-nerve barrier,thereby stimulating axon growth;and inhibiting remyelination of regenerated axons.TGF-βhas been applied to the treatment of peripheral nerve injury in animal models.In this context,we review the functions of TGF-βin peripheral nerve regeneration and potential clinical applications.

Analysis of the interaction between bolt-reinforced rock and surface support in tunnels based on convergence-confinement method

To investigate the interaction of the bolt-reinforced rock and the surface support,an analytical model of the convergence-confinement type is proposed,considering the sequential installation of the fully grouted rockbolts and the surface support.The rock mass is assumed to be elastic-brittle-plastic material,obeying the linear Mohr-Coulomb criterion or the non-linear Hoek-Brown criterion.According to the strain states of the tunnel wall at bolt and surface support installation and the relative magnitude between the bolt length and the plastic depth during the whole process,six cases are categorized upon solving the problem.Each case is divided into three stages due to the different effects of the active rockbolts and the passive surface support.The fictitious pressure is introduced to quantify the threedimensional(3D)effect of the tunnel face,and thus,the actual physical location along the tunnel axis of the analytical section can be considered.By using the bolt-rock strain compatibility and the rocksurface support displacement compatibility conditions,the solutions of longitudinal tunnel displacement and the reaction pressure of surface support along the tunnel axis are obtained.The proposed analytical solutions are validated by a series of 3D numerical simulations.Extensive parametric studies are conducted to examine the effect of the typical parameters of rockbolts and surface support on the tunnel displacement and the reaction pressure of the surface support under different rock conditions.The results show that the rockbolts are more effective in controlling the tunnel displacement than the surface support,which should be installed as soon as possible with a suitable length.For tunnels excavated in weak rocks or with restricted displacement control requirements,the surface support should also be installed or closed timely with a certain stiffness.The proposed method provides a convenient alternative approach for the optimization of rockbolts and surface support at the preliminary stage of tunnel design.

Ionization Engineering of Hydrogels Enables Highly Efficient Salt‑Impeded Solar Evaporation and Night‑Time Electricity Harvesting

Interfacial solar evaporation holds immense potential for brine desalination with low carbon footprints and high energy utilization.Hydrogels,as a tunable material platform from the molecular level to the macroscopic scale,have been considered the most promising candidate for solar evaporation.However,the simultaneous achievement of high evaporation efficiency and satisfactory tolerance to salt ions in brine remains a challenging scientific bottleneck,restricting the widespread application.Herein,we report ionization engineering,which endows polymer chains of hydrogels with electronegativity for impeding salt ions and activating water molecules,fundamentally overcoming the hydrogel salt-impeded challenge and dramatically expediting water evaporating in brine.The sodium dodecyl benzene sulfonate-modified carbon black is chosen as the solar absorbers.The hydrogel reaches a ground-breaking evaporation rate of 2.9 kg m−2 h−1 in 20 wt%brine with 95.6%efficiency under one sun irradiation,surpassing most of the reported literature.More notably,such a hydrogel-based evaporator enables extracting clean water from oversaturated salt solutions and maintains durability under different high-strength deformation or a 15-day continuous operation.Meantime,on the basis of the cation selectivity induced by the electronegativity,we first propose an all-day system that evaporates during the day and generates salinity-gradient electricity using waste-evaporated brine at night,anticipating pioneer a new opportunity for all-day resource-generating systems in fields of freshwater and electricity.

Transplantation of fibrin-thrombin encapsulated human induced neural stem cells promotes functional recovery of spinal cord injury rats through modulation of the microenvironment

Recent studies have mostly focused on engraftment of cells at the lesioned spinal cord,with the expectation that differentiated neurons facilitate recovery.Only a few studies have attempted to use transplanted cells and/or biomaterials as major modulators of the spinal cord injury microenvironment.Here,we aimed to investigate the role of microenvironment modulation by cell graft on functional recovery after spinal cord injury.Induced neural stem cells reprogrammed from human peripheral blood mononuclear cells,and/or thrombin plus fibrinogen,were transplanted into the lesion site of an immunosuppressed rat spinal cord injury model.Basso,Beattie and Bresnahan score,electrophysiological function,and immunofluorescence/histological analyses showed that transplantation facilitates motor and electrophysiological function,reduces lesion volume,and promotes axonal neurofilament expression at the lesion core.Examination of the graft and niche components revealed that although the graft only survived for a relatively short period(up to 15 days),it still had a crucial impact on the microenvironment.Altogether,induced neural stem cells and human fibrin reduced the number of infiltrated immune cells,biased microglia towards a regenerative M2 phenotype,and changed the cytokine expression profile at the lesion site.Graft-induced changes of the microenvironment during the acute and subacute stages might have disrupted the inflammatory cascade chain reactions,which may have exerted a long-term impact on the functional recovery of spinal cord injury rats.

Neutrophil peptide 1 accelerates the clearance of degenerative axons during Wallerian degeneration by activating macrophages after peripheral nerve crush injury

Macrophages play an important role in peripheral nerve regeneration,but the specific mechanism of regeneration is still unclear.Our preliminary findings indicated that neutrophil peptide 1 is an innate immune peptide closely involved in peripheral nerve regeneration.However,the mechanism by which neutrophil peptide 1 enhances nerve regeneration remains unclear.This study was designed to investigate the relationship between neutrophil peptide 1 and macrophages in vivo and in vitro in peripheral nerve crush injury.The functions of RAW 264.7 cells we re elucidated by Cell Counting Kit-8 assay,flow cytometry,migration assays,phagocytosis assays,immunohistochemistry and enzyme-linked immunosorbent assay.Axonal debris phagocytosis was observed using the CUBIC(Clear,Unobstructed Brain/Body Imaging Cocktails and Computational analysis)optical clearing technique during Wallerian degeneration.Macrophage inflammatory factor expression in different polarization states was detected using a protein chip.The results showed that neutrophil peptide 1 promoted the prolife ration,migration and phagocytosis of macrophages,and CD206 expression on the surfa ce of macrophages,indicating M2 polarization.The axonal debris clearance rate during Wallerian degeneration was enhanced after neutrophil peptide 1 intervention.Neutrophil peptide 1 also downregulated inflammatory factors interleukin-1α,-6,-12,and tumor necrosis factor-αin invo and in vitro.Thus,the results suggest that neutrophil peptide 1 activates macrophages and accelerates Wallerian degeneration,which may be one mechanism by which neutrophil peptide 1 enhances peripheral nerve regeneration.

Tau truncation in the pathogenesis of Alzheimer's disease:a narrative review

Alzheimer's disease is characterized by two major neuropathological hallmarks—the extracellularβ-amyloid plaques and intracellular neurofibrillary tangles consisting of aggregated and hyperphosphorylated Tau protein.Recent studies suggest that dysregulation of the microtubuleassociated protein Tau,especially specific proteolysis,could be a driving force for Alzheimer's disease neurodegeneration.Tau physiologically promotes the assembly and stabilization of microtubules,whereas specific truncated fragments are sufficient to induce abnormal hyperphosphorylation and aggregate into toxic oligomers,resulting in them gaining prion-like characteristics.In addition,Tau truncations cause extensive impairments to neural and glial cell functions and animal cognition and behavior in a fragment-dependent manner.This review summarizes over 60 proteolytic cleavage sites and their corresponding truncated fragments,investigates the role of specific truncations in physiological and pathological states of Alzheimer's disease,and summarizes the latest applications of strategies targeting Tau fragments in the diagnosis and treatment of Alzheimer's disease.

High-efficiency sodium storage of Co_(0.85)Se/WSe_(2) encapsulated in N-doped carbon polyhedron via vacancy and heterojunction engineering

With the advantage of fast charge transfer,heterojunction engineering is identified as a viable method to reinforce the anodes'sodium storage performance.Also,vacancies can effectively strengthen the Na+adsorption ability and provide extra active sites for Na+adsorption.However,their synchronous engineering is rarely reported.Herein,a hybrid of Co_(0.85)Se/WSe_(2) heterostructure with Se vacancies and N-doped carbon polyhedron(CoWSe/NCP)has been fabricated for the first time via a hydrothermal and subsequent selenization strategy.Spherical aberration-corrected transmission electron microscopy confirms the phase interface of the Co_(0.85)Se/WSe_(2) heterostructure and the existence of Se vacancies.Density functional theory simulations reveal the accelerated charge transfer and enhanced Na+adsorption ability,which are contributed by the Co_(0.85)Se/WSe_(2) heterostructure and Se vacancies,respectively.As expected,the CoWSe/NCP anode in sodium-ion battery achieves outstanding rate capability(339.6 mAh g^(−1) at 20 A g^(−1)),outperforming almost all Co/W-based selenides.

Intermittent disturbance mechanical behavior and fractional deterioration mechanical model of rock under complex true triaxial stress paths

Mechanical excavation,blasting,adjacent rockburst and fracture slip that occur during mining excavation impose dynamic loads on the rock mass,leading to further fracture of damaged surrounding rock in three-dimensional high-stress and even causing disasters.Therefore,a novel complex true triaxial static-dynamic combined loading method reflecting underground excavation damage and then frequent intermittent disturbance failure is proposed.True triaxial static compression and intermittent disturbance tests are carried out on monzogabbro.The effects of intermediate principal stress and amplitude on the strength characteristics,deformation characteristics,failure characteristics,and precursors of monzogabbro are analyzed,intermediate principal stress and amplitude increase monzogabbro strength and tensile fracture mechanism.Rapid increases in microseismic parameters during rock loading can be precursors for intermittent rock disturbance.Based on the experimental result,the new damage fractional elements and method with considering crack initiation stress and crack unstable stress as initiation and acceleration condition of intermittent disturbance irreversible deformation are proposed.A novel three-dimensional disturbance fractional deterioration model considering the intermediate principal stress effect and intermittent disturbance damage effect is established,and the model predicted results align well with the experimental results.The sensitivity of stress states and model parameters is further explored,and the intermittent disturbance behaviors at different f are predicted.This study provides valuable theoretical bases for the stability analysis of deep mining engineering under dynamic loads.

Probabilistic analysis of tunnel face seismic stability in layered rock masses using Polynomial Chaos Kriging metamodel

Face stability is an essential issue in tunnel design and construction.Layered rock masses are typical and ubiquitous;uncertainties in rock properties always exist.In view of this,a comprehensive method,which combines the Upper bound Limit analysis of Tunnel face stability,the Polynomial Chaos Kriging,the Monte-Carlo Simulation and Analysis of Covariance method(ULT-PCK-MA),is proposed to investigate the seismic stability of tunnel faces.A two-dimensional analytical model of ULT is developed to evaluate the virtual support force based on the upper bound limit analysis.An efficient probabilistic analysis method PCK-MA based on the adaptive Polynomial Chaos Kriging metamodel is then implemented to investigate the parameter uncertainty effects.Ten input parameters,including geological strength indices,uniaxial compressive strengths and constants for three rock formations,and the horizontal seismic coefficients,are treated as random variables.The effects of these parameter uncertainties on the failure probability and sensitivity indices are discussed.In addition,the effects of weak layer position,the middle layer thickness and quality,the tunnel diameter,the parameters correlation,and the seismic loadings are investigated,respectively.The results show that the layer distributions significantly influence the tunnel face probabilistic stability,particularly when the weak rock is present in the bottom layer.The efficiency of the proposed ULT-PCK-MA is validated,which is expected to facilitate the engineering design and construction.

Treadmill exercise improves hippocampal neural plasticity and relieves cognitive deficits in a mouse model of epilepsy

Epilepsy frequently leads to cognitive dysfunction and approaches to treatment remain limited.Although regular exercise effectively improves learning and memory functions across multiple neurological diseases,its application in patients with epilepsy remains controversial.Here,we adopted a 14-day treadmill-exercise paradigm in a pilocarpine injection-induced mouse model of epilepsy.Cognitive assays confirmed the improvement of object and spatial memory after endurance training,and electrophysiological studies revealed the maintenance of hippocampal plasticity as a result of physical exercise.Investigations of the mechanisms underlying this effect revealed that exercise protected parvalbumin interneurons,probably via the suppression of neuroinflammation and improved integrity of blood-brain barrier.In summary,this work identified a previously unknown mechanism through which exercise improves cognitive rehabilitation in epilepsy.

Forebrain excitatory neuron-specific loss of Brpf1 attenuates excitatory synaptic transmission and impairs spatial and fear memory

Bromodomain and plant homeodomain(PHD)finger containing protein 1(Brpf1)is an activator and scaffold protein of a multiunit complex that includes other components involving lysine acetyltransferase(KAT)6A/6B/7.Brpf1,KAT6A,and KAT6B mutations were identified as the causal genes of neurodevelopmental disorders leading to intellectual disability.Our previous work revealed strong and specific expression of Brpf1 in both the postnatal and adult forebrain,especially the hippocampus,which has essential roles in learning and memory.Here,we hypothesized that Brpf1 plays critical roles in the function of forebrain excitatory neurons,and that its deficiency leads to learning and memory deficits.To test this,we knocked out Brpf1 in forebrain excitatory neurons using CaMKIIa-Cre.We found that Brpf1 deficiency reduced the frequency of miniature excitatory postsynaptic currents and downregulated the expression of genes Pcdhgb1,Slc16a7,Robo3,and Rho,which are related to neural development,synapse function,and memory,thereby damaging spatial and fear memory in mice.These findings help explain the mechanisms of intellectual impairment in patients with BRPF1 mutation.

Intelligent Small Sample Defect Detection of Concrete Surface Using Novel Deep Learning Integrating Improved YOLOv5

Dear Editor,This letter presents an intelligent small sample defect detection of concrete surface using novel deep learning integrating the improved YOLOv5 based on the Wasserstein GAN(WGAN)enhancement algorithm.The proposed method is capable of producing top-notch data sets to address the issues of insufficient samples and substandard quality.

Identification and evaluation of shale oil micromigration and its petroleum geological significance

Taking the Lower Permian Fengcheng Formation shale in Mahu Sag of Junggar Basin,NW China,as an example,core observation,test analysis,geological analysis and numerical simulation were applied to identify the shale oil micro-migration phenomenon.The hydrocarbon micro-migration in shale oil was quantitatively evaluated and verified by a self-created hydrocarbon expulsion potential method,and the petroleum geological significance of shale oil micro-migration evaluation was determined.Results show that significant micro-migration can be recognized between the organic-rich lamina and organic-poor lamina.The organic-rich lamina has strong hydrocarbon generation ability.The heavy components of hydrocarbon preferentially retained by kerogen swelling or adsorption,while the light components of hydrocarbon were migrated and accumulated to the interbedded felsic or carbonate organic-poor laminae as free oil.About 69% of the Fengcheng Formation shale samples in Well MY1 exhibit hydrocarbon charging phenomenon,while 31% of those exhibit hydrocarbon expulsion phenomenon.The reliability of the micro-migration evaluation results was verified by combining the group components based on the geochromatography effect,two-dimension nuclear magnetic resonance analysis,and the geochemical behavior of inorganic manganese elements in the process of hydrocarbon migration.Micro-migration is a bridge connecting the hydrocarbon accumulation elements in shale formations,which reflects the whole process of shale oil generation,expulsion and accumulation,and controls the content and composition of shale oil.The identification and evaluation of shale oil micro-migration will provide new perspectives for dynamically differential enrichment mechanism of shale oil and establishing a“multi-peak model in oil generation”of shale.

Influence of layer thickness on formation quality,microstructure,mechanical properties,and corrosion resistance of WE43 magnesium alloy fabricated by laser powder bed fusion

Laser powder bed fusion(L-PBF)of Mg alloys has provided tremendous opportunities for customized production of aeronautical and medical parts.Layer thickness(LT)is of great significance to the L-PBF process but has not been studied for Mg alloys.In this study,WE43 Mg alloy bulk cubes,porous scaffolds,and thin walls with layer thicknesses of 10,20,30,and 40μm were fabricated.The required laser energy input increased with increasing layer thickness and was different for the bulk cubes and porous scaffolds.Porosity tended to occur at the connection joints in porous scaffolds for LT40 and could be eliminated by reducing the laser energy input.For thin wall parts,a large overhang angle or a small wall thickness resulted in porosity when a large layer thicknesses was used,and the porosity disappeared by reducing the layer thickness or laser energy input.A deeper keyhole penetration was found in all occasions with porosity,explaining the influence of layer thickness,geometrical structure,and laser energy input on the porosity.All the samples achieved a high fusion quality with a relative density of over 99.5%using the optimized laser energy input.The increased layer thickness resulted to more precipitation phases,finer grain sizes and decreased grain texture.With the similar high fusion quality,the tensile strength and elongation of bulk samples were significantly improved from 257 MPa and 1.41%with the 10μm layer to 287 MPa and 15.12%with the 40μm layer,in accordance with the microstructural change.The effect of layer thickness on the compressive properties of porous scaffolds was limited.However,the corrosion rate of bulk samples accelerated with increasing the layer thickness,mainly attributed to the increased number of precipitation phases.

Effect of Interface Form on Creep Failure and Life of Dissimilar Metal Welds Involving Nickel-Based Weld Metal and Ferritic Base Metal

For dissimilar metal welds(DMWs)involving nickel-based weld metal(WM)and ferritic heat resistant steel base metal(BM)in power plants,there must be an interface between WM and BM,and this interface suffers mechanical and microstructure mismatches and is often the rupture location of premature failure.In this study,a new form of WM/BM interface form,namely double Y-type interface was designed for the DMWs.Creep behaviors and life of DMWs containing double Y-type interface and conventional I-type interface were compared by finite element analysis and creep tests,and creep failure mechanisms were investigated by stress-strain analysis and microstructure characterization.By applying double Y-type interface instead of conventional I-type interface,failure location of DMW could be shifted from the WM/ferritic heat-affected zone(HAZ)interface into the ferritic HAZ or even the ferritic BM,and the failure mode change improved the creep life of DMW.The interface premature failure of I-type interface DMW was related to the coupling effect of microstructure degradation,stress and strain concentrations,and oxide notch on the WM/HAZ interface.The creep failure of double Y-type interface DMW was the result of Type IV fracture due to the creep voids and micro-cracks on fine-grain boundaries in HAZ,which was a result of the matrix softening of HAZ and lack of precipitate pinning at fine-grain boundaries.The double Y-type interface form separated the stress and strain concentrations in DMW from the WM/HAZ interface,preventing the trigger effect of oxide notch on interface failure and inhibiting the interfacial microstructure cracking.It is a novel scheme to prolong creep life and enhance reliability of DMW,by means of optimizing the interface form,decoupling the damage factors from WM/HAZ interface,and then changing the failure mechanism and shifting the failure location.

3D DEM simulation of hard rock fracture in deep tunnel excavation induced by changes in principal stress magnitude and orientation

To achieve the loading of the stress path of hard rock,the spherical discrete element model(DEM)and the new flexible membrane technology were utilized to realize the transient loading of three principal stresses with arbitrary magnitudes and orientations.Furthermore,based on the deep tunnel of China Jinping Underground Laboratory II(CJPL-II),the deformation and fracture evolution characteristics of deep hard rock induced by excavation stress path were analyzed,and the mechanisms of transient loading-unloading and stress rotation-induced fractures were revealed from a mesoscopic perspective.The results indicated that the stressestrain curve exhibits different trends and degrees of sudden changes when subjected to transient changes in principal stress,accompanied by sudden changes in strain rate.Stress rotation induces spatially directional deformation,resulting in fractures of different degrees and orientations,and increasing the degree of deformation anisotropy.The correlation between the degree of induced fracture and the unloading magnitude of minimum principal stress,as well as its initial level is significant and positive.The process of mechanical response during transient unloading exhibits clear nonlinearity and directivity.After transient unloading,both the minimum principal stress and minimum principal strain rate decrease sharply and then tend to stabilize.This occurs from the edge to the interior and from the direction of the minimum principal stress to the direction of the maximum principal stress on theε1-ε3 plane.Transient unloading will induce a tensile stress wave.The ability to induce fractures due to changes in principal stress magnitude,orientation and rotation paths gradually increases.The analysis indicates a positive correlation between the abrupt change amplitude of strain rate and the maximum unloading magnitude,which is determined by the magnitude and rotation of principal stress.A high tensile strain rate is more likely to induce fractures under low minimum principal stress.

Activation of endogenous neurogenesis and angiogenesis by basic fibroblast growth factor-chitosan gel in an adult rat model of ischemic stroke

Attempts have been made to use cell transplantation and biomaterials to promote cell proliferation,differentiation,migration,and survival,as well as angiogenesis,in the context of brain injury.However,whether bioactive materials can repair the damage caused by ischemic stroke by activating endogenous neurogenesis and angiogenesis is still unknown.In this study,we applied chitosan gel loaded with basic fibroblast growth factor to the stroke cavity 7 days after ischemic stroke in rats.The gel slowly released basic fibroblast growth factor,which improved the local microenvironment,activated endogenous neural stem/progenitor cells,and recruited these cells to migrate toward the penumbra and stroke cavity and subsequently differentiate into neurons,while enhancing angiogenesis in the penumbra and stroke cavity and ultimately leading to partial functional recovery.This study revealed the mechanism by which bioactive materials repair ischemic strokes,thus providing a new strategy for the clinical application of bioactive materials in the treatment of ischemic stroke.

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.

Effect of fracture fluid flowback on shale microfractures using CT scanning

The field data of shale fracturing demonstrate that the flowback performance of fracturing fluid is different from that of conventional reservoirs,where the flowback rate of shale fracturing fluid is lower than that of conventional reservoirs.At the early stage of flowback,there is no single-phase flow of the liquid phase in shale,but rather a gas-water two-phase flow,such that the single-phase flow model for tight oil and gas reservoirs is not applicable.In this study,pores and microfractures are extracted based on the experimental results of computed tomography(CT)scanning,and a spatial model of microfractures is established.Then,the influence of rough microfracture surfaces on the flow is corrected using the modified cubic law,which was modified by introducing the average deviation of the microfracture height as a roughness factor to consider the influence of microfracture surface roughness.The flow in the fracture network is simulated using the modified cubic law and the lattice Boltzmann method(LBM).The results obtained demonstrate that most of the fracturing fluid is retained in the shale microfractures,which explains the low fracturing fluid flowback rate in shale hydraulic fracturing.