In contrast to private interest litigation,public interest litigation provides a more potent solution to personal information infringements marked by extensive scope,unspecified victims,and limited individual loss.How...In contrast to private interest litigation,public interest litigation provides a more potent solution to personal information infringements marked by extensive scope,unspecified victims,and limited individual loss.However,com⁃pensatory damages remain a contentious issue,both in theory and in practice,within the legal framework of personal in⁃formation public interest litigation.Through an empirical study conducted within China's judicial practice,this paper reveals that the pending issue concerning the nature and function of compensatory damages has caused highly contra⁃dictory verdicts regarding their calculation and allocation,as well as their relationship with other forms of pecuniary li⁃abilities.Only by acknowledging the role of compensatory damages imposed in personal information public interest liti⁃gation as"Skimming off Excess Profits",and affirming their function as deterrence rather than compensation can they truly achieve the broader objective of safeguarding personal information security and promoting public welfare,as well as avoid disrupting the harmony of the existing legal landscape.展开更多
The possibility of determining the integrity of a real structure subjected to non-invasive and non-destructive monitoring,such as that carried out by a series of accelerometers placed on the structure,is certainly a g...The possibility of determining the integrity of a real structure subjected to non-invasive and non-destructive monitoring,such as that carried out by a series of accelerometers placed on the structure,is certainly a goal of extreme and current interest.In the present work,the results obtained from the processing of experimental data of a real structure are shown.The analyzed structure is a lattice structure approximately 9 m high,monitored with 18 uniaxial accelerometers positioned in pairs on 9 different levels.The data used refer to continuous monitoring that lasted for a total of 1 year,during which minor damage was caused to the structure by alternatively removing some bracings and repositioning them in the structure.Two methodologies detecting damage based on decomposition techniques of the acquired data were used and tested,as well as a methodology combining the two techniques.The results obtained are extremely interesting,as all the minor damage caused to the structure was identified by the processing methods used,based solely on the monitored data and without any knowledge of the real structure being analyzed.The results use 15 acquisitions in environmental conditions lasting 10 min each,a reasonable amount of time to get immediate feedback on possible damage to the structure.展开更多
The question of the impact of war on ecosystems still remains secondary in the internal and external policy of states, society and the agenda of international organizations. From the point of view of losses in monetar...The question of the impact of war on ecosystems still remains secondary in the internal and external policy of states, society and the agenda of international organizations. From the point of view of losses in monetary terms, the values of ecosystem damages obtained in the work, which are a consequence of the impact of hostilities on the environment, correspond to the annual budgets of the largest countries in the world or exceed them. The presented calculations significantly exceed the known normative methods, the use of which in the conditions of war is limited in space and time. Objective difficulties associated with the uncertainty of many processes of the development of ecological systems and their reaction to the multifactorial impact of war are also significant limitations. Therefore, as part of the study, a method of assessing the impact of war on the environment is proposed, which is based on the patterns of energy flows in ecosystems from the moment it is binding by producers. This made it possible to take into account in the calculations the principle of functional integrity of the ecological system, according to which the destruction or damage of the components of a functionally whole environment will necessarily cause negative phenomena in the development of ecological systems. The results are presented in the form of real values of ecological losses in energy and monetary equivalents, as consequences of the loss of ecosystem services. As the results of the research show, the minimum amount of damage to ecosystems from Russian tanks is 43,500 USD per day. Environmental damage from Russian fighter jets has been estimated at $1.5 billion per week since the start of the war. Noise from military operations causes losses of at least 2.3 billion US dollars per year. The obtained results create prerequisites for improving the system of ensuring environmental safety at the local, state, and international levels and transferring the obtained solutions into safety-shaping practice.展开更多
Hybrid composite materials combine different fibers in preform and take advantages of different mechanical behaviors for improving ballistic impact damage tolerances.Here we report ballistic impact damages of plain-wo...Hybrid composite materials combine different fibers in preform and take advantages of different mechanical behaviors for improving ballistic impact damage tolerances.Here we report ballistic impact damages of plain-woven laminates with different hybrids and stacking sequences.Three kinds of hybrid laminates,i.e.,carbon/Kevlar,carbon/ultra-high molecular weight polyethylene(UHMWPE),and UHMWPE/Kevlar,had been prepared and tested in ballistic penetration with fragment simulating projectiles(FSP).The residual velocities of the projectiles and impact damage morphologies of the laminates have been obtained to show impact energy absorptions for the different hybrid schemes.A microstructural model of the hybrid laminates had also been established to show impact damage mechanisms with finite element analysis(FEA).We found that the UHMWPE/Kevlar hybrid laminates with Kevlar layers as the front face have the highest energy absorption capacity,followed by the carbon/Kevlar hybrid laminates with carbon layers as the front face.The main damage modes are fiber breakages,matrix crack and interlayer delamination.The ballistic damage evolutions from the FEA results show that the major damage is shear failure for front layers,while tension failure for the back layers.We expect that the ballistic impact performance could be improved from the different hybrid schemes.展开更多
Alzheimer’s disease is the most prevalent neurodegenerative disease affecting older adults.Primary features of Alzheimer’s disease include extra cellular aggregation of amyloid-βplaques and the accumulation of neur...Alzheimer’s disease is the most prevalent neurodegenerative disease affecting older adults.Primary features of Alzheimer’s disease include extra cellular aggregation of amyloid-βplaques and the accumulation of neurofibrillary tangles,fo rmed by tau protein,in the cells.While there are amyloid-β-ta rgeting therapies for the treatment of Alzheimer’s disease,these therapies are costly and exhibit potential negative side effects.Mounting evidence suggests significant involvement of tau protein in Alzheimer’s disease-related neurodegeneration.As an important microtubule-associated protein,tau plays an important role in maintaining the stability of neuronal microtubules and promoting axonal growth.In fact,clinical studies have shown that abnormal phosphorylation of tau protein occurs before accumulation of amyloid-βin the brain.Various therapeutic strategies targeting tau protein have begun to emerge,and are considered possible methods to prevent and treat Alzheimer’s disease.Specifically,abnormalities in post-translational modifications of the tau protein,including aberrant phosphorylation,ubiquitination,small ubiquitin-like modifier(SUMO)ylation,acetylation,and truncation,contribute to its microtubule dissociation,misfolding,and subcellular missorting.This causes mitochondrial damage,synaptic impairments,gliosis,and neuroinflammation,eventually leading to neurodegeneration and cognitive deficits.This review summarizes the recent findings on the underlying mechanisms of tau protein in the onset and progression of Alzheimer’s disease and discusses tau-targeted treatment of Alzheimer’s disease.展开更多
Traumatic brain injury(TBI)is an acquired injury of the brain caused by the impact of external forces on the brain(Maas et al.,2008).It is a major cause of death and disability among people of all ages(Maas et al.,200...Traumatic brain injury(TBI)is an acquired injury of the brain caused by the impact of external forces on the brain(Maas et al.,2008).It is a major cause of death and disability among people of all ages(Maas et al.,2008).The primary mechanical injury to the brain initiates a cascade of secondary biochemical events that lead to acute and chronic neurodegeneration and activation of inflammatory pathways(Maas et al.,2008).Both brain-resident microglia and blood-derived myeloid cells-macrophages and monocytes that infiltrate the brain due to injury-induced blood-brain barrier damage,contribute to the inflammatory responses after TBI(Morganti et al.,2015).展开更多
Dynamic load on anchoring structures(AS)within deep roadways can result in cumulative damage and failure.This study develops an experimental device designed to test AS under triaxial loads.The device enables the inves...Dynamic load on anchoring structures(AS)within deep roadways can result in cumulative damage and failure.This study develops an experimental device designed to test AS under triaxial loads.The device enables the investigation of the mechanical response,failure mode,instability assessment criteria,and anchorage effect of AS subjected to combined cyclic dynamic-static triaxial stress paths.The results show that the peak bearing strength is positively correlated with the anchoring matrix strength,anchorage length,and edgewise compressive strength.The bearing capacity decreases significantly when the anchorage direction is severely inclined.The free face failure modes are typically transverse cracking,concave fracturing,V-shaped slipping and detachment,and spallation detachment.Besides,when the anchoring matrix strength and the anchorage length decrease while the edgewise compressive strength,loading rate,and anchorage inclination angle increase,the failure intensity rises.Instability is determined by a negative tangent modulus of the displacement-strength curve or the continued deformation increase against the general downward trend.Under cyclic loads,the driving force that breaks the rock mass along the normal vector and the rigidity of the AS are the two factors that determine roadway stability.Finally,a control measure for surrounding rock stability is proposed to reduce the internal driving force via a pressure relief method and improve the rigidity of the AS by full-length anchorage and grouting modification.展开更多
Deep and ultra-deep reservoirs have gradually become the primary focus of hydrocarbon exploration as a result of a series of significant discoveries in deep hydrocarbon exploration worldwide.These reservoirs present u...Deep and ultra-deep reservoirs have gradually become the primary focus of hydrocarbon exploration as a result of a series of significant discoveries in deep hydrocarbon exploration worldwide.These reservoirs present unique challenges due to their deep burial depth(4500-8882 m),low matrix permeability,complex crustal stress conditions,high temperature and pressure(HTHP,150-200℃,105-155 MPa),coupled with high salinity of formation water.Consequently,the costs associated with their exploitation and development are exceptionally high.In deep and ultra-deep reservoirs,hydraulic fracturing is commonly used to achieve high and stable production.During hydraulic fracturing,a substantial volume of fluid is injected into the reservoir.However,statistical analysis reveals that the flowback rate is typically less than 30%,leaving the majority of the fluid trapped within the reservoir.Therefore,hydraulic fracturing in deep reservoirs not only enhances the reservoir permeability by creating artificial fractures but also damages reservoirs due to the fracturing fluids involved.The challenging“three-high”environment of a deep reservoir,characterized by high temperature,high pressure,and high salinity,exacerbates conventional forms of damage,including water sensitivity,retention of fracturing fluids,rock creep,and proppant breakage.In addition,specific damage mechanisms come into play,such as fracturing fluid decomposition at elevated temperatures and proppant diagenetic reactions at HTHP conditions.Presently,the foremost concern in deep oil and gas development lies in effectively assessing the damage inflicted on these reservoirs by hydraulic fracturing,comprehending the underlying mechanisms,and selecting appropriate solutions.It's noteworthy that the majority of existing studies on reservoir damage primarily focus on conventional reservoirs,with limited attention given to deep reservoirs and a lack of systematic summaries.In light of this,our approach entails initially summarizing the current knowledge pertaining to the types of fracturing fluids employed in deep and ultra-deep reservoirs.Subsequently,we delve into a systematic examination of the damage processes and mechanisms caused by fracturing fluids within the context of hydraulic fracturing in deep reservoirs,taking into account the unique reservoir characteristics of high temperature,high pressure,and high in-situ stress.In addition,we provide an overview of research progress related to high-temperature deep reservoir fracturing fluid and the damage of aqueous fracturing fluids to rock matrix,both artificial and natural fractures,and sand-packed fractures.We conclude by offering a summary of current research advancements and future directions,which hold significant potential for facilitating the efficient development of deep oil and gas reservoirs while effectively mitigating reservoir damage.展开更多
Studies have shown that C1q/tumor necrosis factor-related protein-6 (CTRP6) can alleviate renal ischemia/reperfusion injury in mice. However, its role in the brain remains poorly understood. To investigate the role of...Studies have shown that C1q/tumor necrosis factor-related protein-6 (CTRP6) can alleviate renal ischemia/reperfusion injury in mice. However, its role in the brain remains poorly understood. To investigate the role of CTRP6 in cerebral ischemia/reperfusion injury associated with diabetes mellitus, a diabetes mellitus mouse model of cerebral ischemia/reperfusion injury was established by occlusion of the middle cerebral artery. To overexpress CTRP6 in the brain, an adeno-associated virus carrying CTRP6 was injected into the lateral ventricle. The result was that oxygen injury and inflammation in brain tissue were clearly attenuated, and the number of neurons was greatly reduced. In vitro experiments showed that CTRP6 knockout exacerbated oxidative damage, inflammatory reaction, and apoptosis in cerebral cortical neurons in high glucose hypoxia-simulated diabetic cerebral ischemia/reperfusion injury. CTRP6 overexpression enhanced the sirtuin-1 signaling pathway in diabetic brains after ischemia/reperfusion injury. To investigate the mechanism underlying these effects, we examined mice with depletion of brain tissue-specific sirtuin-1. CTRP6-like protection was achieved by activating the sirtuin-1 signaling pathway. Taken together, these results indicate that CTRP6 likely attenuates cerebral ischemia/reperfusion injury through activation of the sirtuin-1 signaling pathway.展开更多
Stability analysis of underground constructions requires a model study of rock masses’ long-term performance. Creep tests under different stress conditions was conducted on intact granite and granite samples fracture...Stability analysis of underground constructions requires a model study of rock masses’ long-term performance. Creep tests under different stress conditions was conducted on intact granite and granite samples fractured at 30° and 45° angles. The experimental results indicate that the steady creep strain rates of intact and fractured rock present an exponential increase trend with the increase of stress level. A nonlinear creep model is developed based on the experimental results, in which the initial damage caused by fracture together with the damage caused by constant load have been taken into consideration. The fitting analysis results indicated that the model proposed is more accurate at identifying the full creep regions in fractured granite, especially the accelerated stage of creep deformation. The least-square fit error of the proposed creep model is significantly lower than that of Nishihara model by almost an order of magnitude. An analysis of the effects of elastic modulus, viscosity coefficient, and damage factors on fractured rock strain rate and creep strain is conducted. If no consideration is given to the effects of the damage, the proposed nonlinear creep model can degenerate into to the classical Nishihara model.展开更多
After spinal cord injury,there is an extensive infiltration of immune cells,which exacerbates the injury and leads to further neural degeneration.Therefore,a major aim of current research involves targeting the immune...After spinal cord injury,there is an extensive infiltration of immune cells,which exacerbates the injury and leads to further neural degeneration.Therefore,a major aim of current research involves targeting the immune response as a treatment for spinal cord injury.Although much research has been performed analyzing the complex inflammatory process following spinal cord injury,there remain major discrepancies within previous literature regarding the timeline of local cytokine regulation.The objectives of this study were to establish an overview of the timeline of cytokine regulation for 2 weeks after spinal cord injury,identify sexual dimorphisms in terms of cytokine levels,and determine local cytokines that significantly change based on the severity of spinal cord injury.Rats were inflicted with either a mild contusion,moderate contusion,severe contusion,or complete transection,7 mm of spinal cord centered on the injury was harvested at varying times post-injury,and tissue homogenates were analyzed with a Cytokine/Chemokine 27-Plex assay.Results demonstrated pro-inflammatory cytokines including tumor necrosis factorα,interleukin-1β,and interleukin-6 were all upregulated after spinal cord injury,but returned to uninjured levels within approximately 24 hours post-injury,while chemokines including monocyte chemoattractant protein-1 remained upregulated for days post-injury.In contrast,several anti-inflammatory cytokines and growth factors including interleukin-10 and vascular endothelial growth factor were downregulated by 7 days post-injury.After spinal cord injury,tissue inhibitor of metalloproteinase-1,which specifically affects astrocytes involved in glial scar development,increased more than all other cytokines tested,reaching 26.9-fold higher than uninjured rats.After a mild injury,11 cytokines demonstrated sexual dimorphisms;however,after a severe contusion only leptin levels were different between female and male rats.In conclusion,pro-inflammatory cytokines initiate the inflammatory process and return to baseline within hours post-injury,chemokines continue to recruit immune cells for days post-injury,while anti-inflammatory cytokines are downregulated by a week post-injury,and sexual dimorphisms observed after mild injury subsided with more severe injuries.Results from this work define critical chemokines that influence immune cell infiltration and important cytokines involved in glial scar development after spinal cord injury,which are essential for researchers developing treatments targeting secondary damage after spinal cord injury.展开更多
Stroke is a significant leading cause of death and disability in the United States(Tsao et al.,2022).Approximately 87% of strokes fall into the ischemic category,mainly caused by arterial blockage(Jayaraj et al.,2019)...Stroke is a significant leading cause of death and disability in the United States(Tsao et al.,2022).Approximately 87% of strokes fall into the ischemic category,mainly caused by arterial blockage(Jayaraj et al.,2019).Although the only FDA-approved effective medication is tissue plasminogen activator(tPA),it should be administrated within 4.5 hours of ischemic stroke.Furthermore,tPA has been an integral part of managing acute ischemic stro ke.展开更多
A series of ballistic experiments were performed to investigate the damage behavior of high velocity reactive material projectiles(RMPs) impacting liquid-filled tanks,and the corresponding hydrodynamic ram(HRAM) was s...A series of ballistic experiments were performed to investigate the damage behavior of high velocity reactive material projectiles(RMPs) impacting liquid-filled tanks,and the corresponding hydrodynamic ram(HRAM) was studied in detail.PTFE/Al/W RMPs with steel-like and aluminum-like densities were prepared by a pressing/sintering process.The projectiles impacted a liquid-filled steel tank with front aluminum panel at approximately 1250 m/s.The corresponding cavity evolution characteristics and HRAM pressure were recorded by high-speed camera and pressure acquisition system,and further compared to those of steel and aluminum projectiles.Significantly different from the conical cavity formed by the inert metal projectile,the cavity formed by the RMP appeared as an ellipsoid with a conical front.The RMPs were demonstrated to enhance the radial growth velocity of cavity,the global HRAM pressure amplitude and the front panel damage,indicating the enhanced HRAM and structural damage behavior.Furthermore,combining the impact-induced fragmentation and deflagration characteristics,the cavity evolution of RMPs under the combined effect of kinetic energy impact and chemical energy release was analyzed.The mechanism of enhanced HRAM pressure induced by the RMPs was further revealed based on the theoretical model of the initial impact wave and the impulse analysis.Finally,the linear correlation between the deformation-thickness ratio and the non-dimensional impulse for the front panel was obtained and analyzed.It was determined that the enhanced near-field impulse induced by the RMPs was the dominant reason for the enhanced structural damage behavior.展开更多
In the context of repositories for nuclear waste,understanding the behavior of gas migration through clayey rocks with inherent anisotropy is crucial for assessing the safety of geological disposal facilities.The prim...In the context of repositories for nuclear waste,understanding the behavior of gas migration through clayey rocks with inherent anisotropy is crucial for assessing the safety of geological disposal facilities.The primary mechanism for gas breakthrough is the opening of micro-fractures due to high gas pressure.This occurs at gas pressures lower than the combined strength of the rock and its minimum principal stress under external loading conditions.To investigate the mechanism of microscale mode-I ruptures,it is essential to incorporate a multiscale approach that includes subcritical microcracks in the modeling framework.In this contribution,we derive the model from microstructures that contain periodically distributed microcracks within a porous material.The damage evolution law is coupled with the macroscopic poroelastic system by employing the asymptotic homogenization method and considering the inherent hydro-mechanical(HM)anisotropy at the microscale.The resulting permeability change induced by fracture opening is implicitly integrated into the gas flow equation.Verification examples are presented to validate the developed model step by step.An analysis of local macroscopic response is undertaken to underscore the influence of factors such as strain rate,initial damage,and applied stress,on the gas migration process.Numerical examples of direct tension tests are used to demonstrate the model’s efficacy in describing localized failure characteristics.Finally,the simulation results for preferential gas flow reveal the robustness of the two-scale model in explicitly depicting gas-induced fracturing in anisotropic clayey rocks.The model successfully captures the common behaviors observed in laboratory experiments,such as a sudden drop in gas injection pressure,rapid build-up of downstream gas pressure,and steady-state gas flow following gas breakthrough.展开更多
BACKGROUND Diabetic kidney disease(DKD)is a major complication of diabetes mellitus.Renal tubular epithelial cell(TEC)damage,which is strongly associated with the inflammatory response and mesenchymal trans-differenti...BACKGROUND Diabetic kidney disease(DKD)is a major complication of diabetes mellitus.Renal tubular epithelial cell(TEC)damage,which is strongly associated with the inflammatory response and mesenchymal trans-differentiation,plays a significant role in DKD;However,the precise molecular mechanism is unknown.The recently identified microRNA-630(miR-630)has been hypothesized to be closely associated with cell migration,apoptosis,and autophagy.However,the association between miR-630 and DKD and the underlying mechanism remain unknown.AIM To investigate how miR-630 affects TEC injury and the inflammatory response in DKD rats.METHODS Streptozotocin was administered to six-week-old male rats to create a hypergly cemic diabetic model.In the second week of modeling,the rats were divided into control,DKD,negative control of lentivirus,and miR-630 overexpression groups.After 8 wk,urine and blood samples were collected for the kidney injury assays,and renal tissues were removed for further molecular assays.The target gene for miR-630 was predicted using bioinformatics,and the association between miR-630 and toll-like receptor 4(TLR4)was confirmed using in vitro investigations and double luciferase reporter gene assays.Overexpression of miR-630 in DKD rats led to changes in body weight,renal weight index,basic blood parameters and histopathological changes.RESULTS The expression level of miR-630 was reduced in the kidney tissue of rats with DKD(P<0.05).The miR-630 and TLR4 expressions in rat renal TECs(NRK-52E)were measured using quantitative reverse transcription polymerase chain reaction.The mRNA expression level of miR-630 was significantly lower in the high-glucose(HG)and HG+mimic negative control(NC)groups than in the normal glucose(NG)group(P<0.05).In contrast,the mRNA expression level of TLR4 was significantly higher in these groups(P<0.05).However,miR-630 mRNA expression increased and TLR4 mRNA expression significantly decreased in the HG+miR-630 mimic group than in the HG+mimic NC group(P<0.05).Furthermore,the levels of tumor necrosis factor-alpha(TNF-α),interleukin-1β(IL-1β),and IL-6 were significantly higher in the HG and HG+mimic NC groups than in NG group(P<0.05).However,the levels of these cytokines were significantly lower in the HG+miR-630 mimic group than in the HG+mimic NC group(P<0.05).Notably,changes in protein expression were observed.The HG and HG+mimic NC groups showed a significant decrease in E-cadherin protein expression,whereas TLR4,α-smooth muscle actin(SMA),and collagen IV protein expression increased(P<0.05).Conversely,the HG+miR-630 mimic group exhibited a significant increase in E-cadherin protein expression and a notable decrease in TLR4,α-SMA,and collagen IV protein expression than in the HG+mimic NC group(P<0.05).The miR-630 targets TLR4 gene expression.In vivo experiments demonstrated that DKD rats treated with miR-630 agomir exhibited significantly higher miR-630 mRNA expression than DKD rats injected with agomir NC.Additionally,rats treated with miR-630 agomir showed significant reductions in urinary albumin,blood glucose,TLR4,and proinflammatory markers(TNF-α,IL-1β,and IL-6)expression levels(P<0.05).Moreover,these rats exhibited fewer kidney lesions and reduced infiltration of inflammatory cells.CONCLUSION MiR-630 may inhibit the inflammatory reaction of DKD by targeting TLR4,and has a protective effect on DKD.展开更多
We have proposed a methodology to assess the robustness of underground tunnels against potential failure.This involves developing vulnerability functions for various qualities of rock mass and static loading intensiti...We have proposed a methodology to assess the robustness of underground tunnels against potential failure.This involves developing vulnerability functions for various qualities of rock mass and static loading intensities.To account for these variations,we utilized a Monte Carlo Simulation(MCS)technique coupled with the finite difference code FLAC^(3D),to conduct two thousand seven hundred numerical simulations of a horseshoe tunnel located within a rock mass with different geological strength index system(GSIs)and subjected to different states of static loading.To quantify the severity of damage within the rock mass,we selected one stress-based(brittle shear ratio(BSR))and one strain-based failure criterion(plastic damage index(PDI)).Based on these criteria,we then developed fragility curves.Additionally,we used mathematical approximation techniques to produce vulnerability functions that relate the probabilities of various damage states to loading intensities for different quality classes of blocky rock mass.The results indicated that the fragility curves we obtained could accurately depict the evolution of the inner and outer shell damage around the tunnel.Therefore,we have provided engineers with a tool that can predict levels of damages associated with different failure mechanisms based on variations in rock mass quality and in situ stress state.Our method is a numerically developed,multi-variate approach that can aid engineers in making informed decisions about the robustness of underground tunnels.展开更多
Thermal damage and thermal fracture of rocks are two important indicators in geothermal mining projects.This paper investigates the effects of heating and water-cooling on granite specimens at various temperatures.The...Thermal damage and thermal fracture of rocks are two important indicators in geothermal mining projects.This paper investigates the effects of heating and water-cooling on granite specimens at various temperatures.The laboratory uniaxial compression experiments were also conducted.Then,a coupled thermo-mechanical ordinary state-based peridynamic(OSB-PD)model and corresponding numerical scheme were developed to simulate the damage of rocks after the heating and cooling processes,and the change of crack evolution process was predicted.The results demonstrate that elevated heating temperatures exacerbate the thermal damage to the specimens,resulting in a decrease in peak strength and an increase in ductility of granite.The escalating occurrence of thermal-induced cracks significantly affects the crack evolution process during the loading phase.The numerical results accurately reproduce the damage and fracture characteristics of the granite under different final heating temperatures(FHTs),which are consistent with the test results in terms of strength,crack evolution process,and failure mode.展开更多
Rock-encased-backfill(RB)structures are common in underground mining,for example in the cut-andfill and stoping methods.To understand the effects of cyclic excavation and blasting activities on the damage of these RB ...Rock-encased-backfill(RB)structures are common in underground mining,for example in the cut-andfill and stoping methods.To understand the effects of cyclic excavation and blasting activities on the damage of these RB structures,a series of triaxial stepwise-increasing-amplitude cyclic loading experiments was conducted with cylindrical RB specimens(rock on outside,backfill on inside)with different volume fractions of rock(VF=0.48,0.61,0.73,and 0.84),confining pressures(0,6,9,and 12 MPa),and cyclic loading rates(200,300,400,and 500 N/s).The damage evolution and meso-crack formation during the cyclic tests were analyzed with results from stress-strain hysteresis loops,acoustic emission events,and post-failure X-ray 3D fracture morphology.The results showed significant differences between cyclic and monotonic loadings of RB specimens,particularly with regard to the generation of shear microcracks,the development of stress memory and strain hardening,and the contact forces and associated friction that develops along the rock-backfill interface.One important finding is that as a function of the number of cycles,the elastic strain increases linearly and the dissipated energy increases exponentially.Also,compared with monotonic loading,the cyclic strain hardening characteristics are more sensitive to rising confining pressures during the initial compaction stage.Another finding is that compared with monotonic loading,more shear microcracks are generated during every reloading stage,but these microcracks tend to be dispersed and lessen the likelihood of large shear fracture formation.The transition from elastic to plastic behavior varies depending on the parameters of each test(confinement,volume fraction,and cyclic rate),and an interesting finding was that the transformation to plastic behavior is significantly lower under the conditions of 0.73 rock volume fraction,400 N/s cyclic loading rate,and 9 MPa confinement.All the findings have important practical implications on the ability of backfill to support underground excavations.展开更多
The Steel Catenary Riser(SCR)is a vital component for transporting oil and gas from the seabed to the floating platform.The harsh environmental conditions and complex platform motion make the SCR’s girth-weld prone t...The Steel Catenary Riser(SCR)is a vital component for transporting oil and gas from the seabed to the floating platform.The harsh environmental conditions and complex platform motion make the SCR’s girth-weld prone to fatigue failure.The structural stress fatigue theory and Master S-N curve method provide accurate predictions for the fatigue damage on the welded joints,which demonstrate significant potential and compatibility in multi-axial and random fatigue evaluation.Here,we propose a new frequency fatigue model subjected to welded joints of SCR under multiaxial stress,which fully integrates the mesh-insensitive structural stress and frequency domain random process and transforms the conventional welding fatigue technique of SCR into a spectrum analysis technique utilizing structural stress.Besides,a full-scale FE model of SCR with welds is established to obtain the modal structural stress of the girth weld and the frequency response function(FRF)of modal coordinate,and a biaxial fatigue evaluation about the girth weld of the SCR can be achieved by taking the effects of multi-load correlation and pipe-soil interaction into account.The research results indicate that the frequency-domain fatigue results are aligned with the time-domain results,meeting the fatigue evaluation requirements of the SCR.展开更多
Numerous studies have shown that cell replacement therapy can replenish lost cells and rebuild neural circuitry in animal models of Parkinson’s disease.Transplantation of midbrain dopaminergic progenitor cells is a p...Numerous studies have shown that cell replacement therapy can replenish lost cells and rebuild neural circuitry in animal models of Parkinson’s disease.Transplantation of midbrain dopaminergic progenitor cells is a promising treatment for Parkinson’s disease.However,transplanted cells can be injured by mechanical damage during handling and by changes in the transplantation niche.Here,we developed a one-step biomanufacturing platform that uses small-aperture gelatin microcarriers to produce beads carrying midbrain dopaminergic progenitor cells.These beads allow midbrain dopaminergic progenitor cell differentiation and cryopreservation without digestion,effectively maintaining axonal integrity in vitro.Importantly,midbrain dopaminergic progenitor cell bead grafts showed increased survival and only mild immunoreactivity in vivo compared with suspended midbrain dopaminergic progenitor cell grafts.Overall,our findings show that these midbrain dopaminergic progenitor cell beads enhance the effectiveness of neuronal cell transplantation.展开更多
文摘In contrast to private interest litigation,public interest litigation provides a more potent solution to personal information infringements marked by extensive scope,unspecified victims,and limited individual loss.However,com⁃pensatory damages remain a contentious issue,both in theory and in practice,within the legal framework of personal in⁃formation public interest litigation.Through an empirical study conducted within China's judicial practice,this paper reveals that the pending issue concerning the nature and function of compensatory damages has caused highly contra⁃dictory verdicts regarding their calculation and allocation,as well as their relationship with other forms of pecuniary li⁃abilities.Only by acknowledging the role of compensatory damages imposed in personal information public interest liti⁃gation as"Skimming off Excess Profits",and affirming their function as deterrence rather than compensation can they truly achieve the broader objective of safeguarding personal information security and promoting public welfare,as well as avoid disrupting the harmony of the existing legal landscape.
基金The author N.I.Giannoccaro received funds from the Department of Innovation Engineering,University of Salento,for acquiring the tool Structural Health Monitoring.
文摘The possibility of determining the integrity of a real structure subjected to non-invasive and non-destructive monitoring,such as that carried out by a series of accelerometers placed on the structure,is certainly a goal of extreme and current interest.In the present work,the results obtained from the processing of experimental data of a real structure are shown.The analyzed structure is a lattice structure approximately 9 m high,monitored with 18 uniaxial accelerometers positioned in pairs on 9 different levels.The data used refer to continuous monitoring that lasted for a total of 1 year,during which minor damage was caused to the structure by alternatively removing some bracings and repositioning them in the structure.Two methodologies detecting damage based on decomposition techniques of the acquired data were used and tested,as well as a methodology combining the two techniques.The results obtained are extremely interesting,as all the minor damage caused to the structure was identified by the processing methods used,based solely on the monitored data and without any knowledge of the real structure being analyzed.The results use 15 acquisitions in environmental conditions lasting 10 min each,a reasonable amount of time to get immediate feedback on possible damage to the structure.
文摘The question of the impact of war on ecosystems still remains secondary in the internal and external policy of states, society and the agenda of international organizations. From the point of view of losses in monetary terms, the values of ecosystem damages obtained in the work, which are a consequence of the impact of hostilities on the environment, correspond to the annual budgets of the largest countries in the world or exceed them. The presented calculations significantly exceed the known normative methods, the use of which in the conditions of war is limited in space and time. Objective difficulties associated with the uncertainty of many processes of the development of ecological systems and their reaction to the multifactorial impact of war are also significant limitations. Therefore, as part of the study, a method of assessing the impact of war on the environment is proposed, which is based on the patterns of energy flows in ecosystems from the moment it is binding by producers. This made it possible to take into account in the calculations the principle of functional integrity of the ecological system, according to which the destruction or damage of the components of a functionally whole environment will necessarily cause negative phenomena in the development of ecological systems. The results are presented in the form of real values of ecological losses in energy and monetary equivalents, as consequences of the loss of ecosystem services. As the results of the research show, the minimum amount of damage to ecosystems from Russian tanks is 43,500 USD per day. Environmental damage from Russian fighter jets has been estimated at $1.5 billion per week since the start of the war. Noise from military operations causes losses of at least 2.3 billion US dollars per year. The obtained results create prerequisites for improving the system of ensuring environmental safety at the local, state, and international levels and transferring the obtained solutions into safety-shaping practice.
文摘Hybrid composite materials combine different fibers in preform and take advantages of different mechanical behaviors for improving ballistic impact damage tolerances.Here we report ballistic impact damages of plain-woven laminates with different hybrids and stacking sequences.Three kinds of hybrid laminates,i.e.,carbon/Kevlar,carbon/ultra-high molecular weight polyethylene(UHMWPE),and UHMWPE/Kevlar,had been prepared and tested in ballistic penetration with fragment simulating projectiles(FSP).The residual velocities of the projectiles and impact damage morphologies of the laminates have been obtained to show impact energy absorptions for the different hybrid schemes.A microstructural model of the hybrid laminates had also been established to show impact damage mechanisms with finite element analysis(FEA).We found that the UHMWPE/Kevlar hybrid laminates with Kevlar layers as the front face have the highest energy absorption capacity,followed by the carbon/Kevlar hybrid laminates with carbon layers as the front face.The main damage modes are fiber breakages,matrix crack and interlayer delamination.The ballistic damage evolutions from the FEA results show that the major damage is shear failure for front layers,while tension failure for the back layers.We expect that the ballistic impact performance could be improved from the different hybrid schemes.
基金supported by the National Natural Science Foundation of China,No.82101493(to JY)。
文摘Alzheimer’s disease is the most prevalent neurodegenerative disease affecting older adults.Primary features of Alzheimer’s disease include extra cellular aggregation of amyloid-βplaques and the accumulation of neurofibrillary tangles,fo rmed by tau protein,in the cells.While there are amyloid-β-ta rgeting therapies for the treatment of Alzheimer’s disease,these therapies are costly and exhibit potential negative side effects.Mounting evidence suggests significant involvement of tau protein in Alzheimer’s disease-related neurodegeneration.As an important microtubule-associated protein,tau plays an important role in maintaining the stability of neuronal microtubules and promoting axonal growth.In fact,clinical studies have shown that abnormal phosphorylation of tau protein occurs before accumulation of amyloid-βin the brain.Various therapeutic strategies targeting tau protein have begun to emerge,and are considered possible methods to prevent and treat Alzheimer’s disease.Specifically,abnormalities in post-translational modifications of the tau protein,including aberrant phosphorylation,ubiquitination,small ubiquitin-like modifier(SUMO)ylation,acetylation,and truncation,contribute to its microtubule dissociation,misfolding,and subcellular missorting.This causes mitochondrial damage,synaptic impairments,gliosis,and neuroinflammation,eventually leading to neurodegeneration and cognitive deficits.This review summarizes the recent findings on the underlying mechanisms of tau protein in the onset and progression of Alzheimer’s disease and discusses tau-targeted treatment of Alzheimer’s disease.
基金supported by NIH funding(R01NS091218 and R01NS115876)to MML.
文摘Traumatic brain injury(TBI)is an acquired injury of the brain caused by the impact of external forces on the brain(Maas et al.,2008).It is a major cause of death and disability among people of all ages(Maas et al.,2008).The primary mechanical injury to the brain initiates a cascade of secondary biochemical events that lead to acute and chronic neurodegeneration and activation of inflammatory pathways(Maas et al.,2008).Both brain-resident microglia and blood-derived myeloid cells-macrophages and monocytes that infiltrate the brain due to injury-induced blood-brain barrier damage,contribute to the inflammatory responses after TBI(Morganti et al.,2015).
基金This paper is financially supported by the National Natural Science Foundation of China(Grant Nos.52074263 and 52034007)the Postgraduate Research and Practice Innovation Program of Jiangsu Province(Grant No.KYCX21_2332).
文摘Dynamic load on anchoring structures(AS)within deep roadways can result in cumulative damage and failure.This study develops an experimental device designed to test AS under triaxial loads.The device enables the investigation of the mechanical response,failure mode,instability assessment criteria,and anchorage effect of AS subjected to combined cyclic dynamic-static triaxial stress paths.The results show that the peak bearing strength is positively correlated with the anchoring matrix strength,anchorage length,and edgewise compressive strength.The bearing capacity decreases significantly when the anchorage direction is severely inclined.The free face failure modes are typically transverse cracking,concave fracturing,V-shaped slipping and detachment,and spallation detachment.Besides,when the anchoring matrix strength and the anchorage length decrease while the edgewise compressive strength,loading rate,and anchorage inclination angle increase,the failure intensity rises.Instability is determined by a negative tangent modulus of the displacement-strength curve or the continued deformation increase against the general downward trend.Under cyclic loads,the driving force that breaks the rock mass along the normal vector and the rigidity of the AS are the two factors that determine roadway stability.Finally,a control measure for surrounding rock stability is proposed to reduce the internal driving force via a pressure relief method and improve the rigidity of the AS by full-length anchorage and grouting modification.
基金Dao-Bing Wang was supported by the Beijing Natural Science Foundation Project(No.3222030)the National Natural Science Foundation of China(No.52274002)+1 种基金the PetroChina Science and Technology Innovation Foundation Project(No.2021DQ02-0201)Fu-Jian Zhou was supported by the National Natural Science Foundation of China(No.52174045).
文摘Deep and ultra-deep reservoirs have gradually become the primary focus of hydrocarbon exploration as a result of a series of significant discoveries in deep hydrocarbon exploration worldwide.These reservoirs present unique challenges due to their deep burial depth(4500-8882 m),low matrix permeability,complex crustal stress conditions,high temperature and pressure(HTHP,150-200℃,105-155 MPa),coupled with high salinity of formation water.Consequently,the costs associated with their exploitation and development are exceptionally high.In deep and ultra-deep reservoirs,hydraulic fracturing is commonly used to achieve high and stable production.During hydraulic fracturing,a substantial volume of fluid is injected into the reservoir.However,statistical analysis reveals that the flowback rate is typically less than 30%,leaving the majority of the fluid trapped within the reservoir.Therefore,hydraulic fracturing in deep reservoirs not only enhances the reservoir permeability by creating artificial fractures but also damages reservoirs due to the fracturing fluids involved.The challenging“three-high”environment of a deep reservoir,characterized by high temperature,high pressure,and high salinity,exacerbates conventional forms of damage,including water sensitivity,retention of fracturing fluids,rock creep,and proppant breakage.In addition,specific damage mechanisms come into play,such as fracturing fluid decomposition at elevated temperatures and proppant diagenetic reactions at HTHP conditions.Presently,the foremost concern in deep oil and gas development lies in effectively assessing the damage inflicted on these reservoirs by hydraulic fracturing,comprehending the underlying mechanisms,and selecting appropriate solutions.It's noteworthy that the majority of existing studies on reservoir damage primarily focus on conventional reservoirs,with limited attention given to deep reservoirs and a lack of systematic summaries.In light of this,our approach entails initially summarizing the current knowledge pertaining to the types of fracturing fluids employed in deep and ultra-deep reservoirs.Subsequently,we delve into a systematic examination of the damage processes and mechanisms caused by fracturing fluids within the context of hydraulic fracturing in deep reservoirs,taking into account the unique reservoir characteristics of high temperature,high pressure,and high in-situ stress.In addition,we provide an overview of research progress related to high-temperature deep reservoir fracturing fluid and the damage of aqueous fracturing fluids to rock matrix,both artificial and natural fractures,and sand-packed fractures.We conclude by offering a summary of current research advancements and future directions,which hold significant potential for facilitating the efficient development of deep oil and gas reservoirs while effectively mitigating reservoir damage.
基金supported by the National Natural Science Foundation of China,Nos.82102295(to WG),82071339(to LG),82001119(to JH),and 81901994(to BZ).
文摘Studies have shown that C1q/tumor necrosis factor-related protein-6 (CTRP6) can alleviate renal ischemia/reperfusion injury in mice. However, its role in the brain remains poorly understood. To investigate the role of CTRP6 in cerebral ischemia/reperfusion injury associated with diabetes mellitus, a diabetes mellitus mouse model of cerebral ischemia/reperfusion injury was established by occlusion of the middle cerebral artery. To overexpress CTRP6 in the brain, an adeno-associated virus carrying CTRP6 was injected into the lateral ventricle. The result was that oxygen injury and inflammation in brain tissue were clearly attenuated, and the number of neurons was greatly reduced. In vitro experiments showed that CTRP6 knockout exacerbated oxidative damage, inflammatory reaction, and apoptosis in cerebral cortical neurons in high glucose hypoxia-simulated diabetic cerebral ischemia/reperfusion injury. CTRP6 overexpression enhanced the sirtuin-1 signaling pathway in diabetic brains after ischemia/reperfusion injury. To investigate the mechanism underlying these effects, we examined mice with depletion of brain tissue-specific sirtuin-1. CTRP6-like protection was achieved by activating the sirtuin-1 signaling pathway. Taken together, these results indicate that CTRP6 likely attenuates cerebral ischemia/reperfusion injury through activation of the sirtuin-1 signaling pathway.
基金supported by the National Natural Science Foundation of China(No.42307258)the technological research projects in Sichuan Province(No.2022YFSY0007)the China Atomic Energy Authority(CAEA)through the Geological Disposal Program.
文摘Stability analysis of underground constructions requires a model study of rock masses’ long-term performance. Creep tests under different stress conditions was conducted on intact granite and granite samples fractured at 30° and 45° angles. The experimental results indicate that the steady creep strain rates of intact and fractured rock present an exponential increase trend with the increase of stress level. A nonlinear creep model is developed based on the experimental results, in which the initial damage caused by fracture together with the damage caused by constant load have been taken into consideration. The fitting analysis results indicated that the model proposed is more accurate at identifying the full creep regions in fractured granite, especially the accelerated stage of creep deformation. The least-square fit error of the proposed creep model is significantly lower than that of Nishihara model by almost an order of magnitude. An analysis of the effects of elastic modulus, viscosity coefficient, and damage factors on fractured rock strain rate and creep strain is conducted. If no consideration is given to the effects of the damage, the proposed nonlinear creep model can degenerate into to the classical Nishihara model.
基金supported by the National Institutes of HealthNo.R56 NS117935(to ASH and WLM)+1 种基金funded by Institutional Clinical and Translational Science AwardNo.UL1 TR002373。
文摘After spinal cord injury,there is an extensive infiltration of immune cells,which exacerbates the injury and leads to further neural degeneration.Therefore,a major aim of current research involves targeting the immune response as a treatment for spinal cord injury.Although much research has been performed analyzing the complex inflammatory process following spinal cord injury,there remain major discrepancies within previous literature regarding the timeline of local cytokine regulation.The objectives of this study were to establish an overview of the timeline of cytokine regulation for 2 weeks after spinal cord injury,identify sexual dimorphisms in terms of cytokine levels,and determine local cytokines that significantly change based on the severity of spinal cord injury.Rats were inflicted with either a mild contusion,moderate contusion,severe contusion,or complete transection,7 mm of spinal cord centered on the injury was harvested at varying times post-injury,and tissue homogenates were analyzed with a Cytokine/Chemokine 27-Plex assay.Results demonstrated pro-inflammatory cytokines including tumor necrosis factorα,interleukin-1β,and interleukin-6 were all upregulated after spinal cord injury,but returned to uninjured levels within approximately 24 hours post-injury,while chemokines including monocyte chemoattractant protein-1 remained upregulated for days post-injury.In contrast,several anti-inflammatory cytokines and growth factors including interleukin-10 and vascular endothelial growth factor were downregulated by 7 days post-injury.After spinal cord injury,tissue inhibitor of metalloproteinase-1,which specifically affects astrocytes involved in glial scar development,increased more than all other cytokines tested,reaching 26.9-fold higher than uninjured rats.After a mild injury,11 cytokines demonstrated sexual dimorphisms;however,after a severe contusion only leptin levels were different between female and male rats.In conclusion,pro-inflammatory cytokines initiate the inflammatory process and return to baseline within hours post-injury,chemokines continue to recruit immune cells for days post-injury,while anti-inflammatory cytokines are downregulated by a week post-injury,and sexual dimorphisms observed after mild injury subsided with more severe injuries.Results from this work define critical chemokines that influence immune cell infiltration and important cytokines involved in glial scar development after spinal cord injury,which are essential for researchers developing treatments targeting secondary damage after spinal cord injury.
基金supported by the UTHSC Bridge funding award (E073005058 Bridge Support-2022)the National Institute of Health (R01-NS09 7800 and R56 NS127924-01) to TI。
文摘Stroke is a significant leading cause of death and disability in the United States(Tsao et al.,2022).Approximately 87% of strokes fall into the ischemic category,mainly caused by arterial blockage(Jayaraj et al.,2019).Although the only FDA-approved effective medication is tissue plasminogen activator(tPA),it should be administrated within 4.5 hours of ischemic stroke.Furthermore,tPA has been an integral part of managing acute ischemic stro ke.
基金supported by the Youth Foundation of State Key Laboratory of Explosion Science and Technology (Grant No.QNKT22-12)the State Key Program of National Natural Science Foundation of China (Grant No.12132003)。
文摘A series of ballistic experiments were performed to investigate the damage behavior of high velocity reactive material projectiles(RMPs) impacting liquid-filled tanks,and the corresponding hydrodynamic ram(HRAM) was studied in detail.PTFE/Al/W RMPs with steel-like and aluminum-like densities were prepared by a pressing/sintering process.The projectiles impacted a liquid-filled steel tank with front aluminum panel at approximately 1250 m/s.The corresponding cavity evolution characteristics and HRAM pressure were recorded by high-speed camera and pressure acquisition system,and further compared to those of steel and aluminum projectiles.Significantly different from the conical cavity formed by the inert metal projectile,the cavity formed by the RMP appeared as an ellipsoid with a conical front.The RMPs were demonstrated to enhance the radial growth velocity of cavity,the global HRAM pressure amplitude and the front panel damage,indicating the enhanced HRAM and structural damage behavior.Furthermore,combining the impact-induced fragmentation and deflagration characteristics,the cavity evolution of RMPs under the combined effect of kinetic energy impact and chemical energy release was analyzed.The mechanism of enhanced HRAM pressure induced by the RMPs was further revealed based on the theoretical model of the initial impact wave and the impulse analysis.Finally,the linear correlation between the deformation-thickness ratio and the non-dimensional impulse for the front panel was obtained and analyzed.It was determined that the enhanced near-field impulse induced by the RMPs was the dominant reason for the enhanced structural damage behavior.
基金financially supported by the National Natural Science Foundation of China(Grant Nos.12302503 and U20A20266)Scientific and Technological Research Projects in Sichuan Province,China(Grant No.2023ZYD0154).
文摘In the context of repositories for nuclear waste,understanding the behavior of gas migration through clayey rocks with inherent anisotropy is crucial for assessing the safety of geological disposal facilities.The primary mechanism for gas breakthrough is the opening of micro-fractures due to high gas pressure.This occurs at gas pressures lower than the combined strength of the rock and its minimum principal stress under external loading conditions.To investigate the mechanism of microscale mode-I ruptures,it is essential to incorporate a multiscale approach that includes subcritical microcracks in the modeling framework.In this contribution,we derive the model from microstructures that contain periodically distributed microcracks within a porous material.The damage evolution law is coupled with the macroscopic poroelastic system by employing the asymptotic homogenization method and considering the inherent hydro-mechanical(HM)anisotropy at the microscale.The resulting permeability change induced by fracture opening is implicitly integrated into the gas flow equation.Verification examples are presented to validate the developed model step by step.An analysis of local macroscopic response is undertaken to underscore the influence of factors such as strain rate,initial damage,and applied stress,on the gas migration process.Numerical examples of direct tension tests are used to demonstrate the model’s efficacy in describing localized failure characteristics.Finally,the simulation results for preferential gas flow reveal the robustness of the two-scale model in explicitly depicting gas-induced fracturing in anisotropic clayey rocks.The model successfully captures the common behaviors observed in laboratory experiments,such as a sudden drop in gas injection pressure,rapid build-up of downstream gas pressure,and steady-state gas flow following gas breakthrough.
基金Supported by the Huadong Medicine Joint Funds of the Zhejiang Provincial Natural Science Foundation of China,No.LHDMZ22H050001the Construction of Key Projects by Zhejiang Provincial Ministry,No.WKJ-ZJ-2302+3 种基金the Zhejiang Province Chinese Medicine Modernization Program,No.2020ZX001the Key Project of Scientific Research Foundation of Chinese Medicine,No.2022ZZ002the“Pioneer”and“LeadingGoose”R&D Program of Zhejiang,No.2022C03118 and 2023C03075the Key Project of Basic Scientific Research Operating Funds of Hangzhou Medical College,No.KYZD202002.
文摘BACKGROUND Diabetic kidney disease(DKD)is a major complication of diabetes mellitus.Renal tubular epithelial cell(TEC)damage,which is strongly associated with the inflammatory response and mesenchymal trans-differentiation,plays a significant role in DKD;However,the precise molecular mechanism is unknown.The recently identified microRNA-630(miR-630)has been hypothesized to be closely associated with cell migration,apoptosis,and autophagy.However,the association between miR-630 and DKD and the underlying mechanism remain unknown.AIM To investigate how miR-630 affects TEC injury and the inflammatory response in DKD rats.METHODS Streptozotocin was administered to six-week-old male rats to create a hypergly cemic diabetic model.In the second week of modeling,the rats were divided into control,DKD,negative control of lentivirus,and miR-630 overexpression groups.After 8 wk,urine and blood samples were collected for the kidney injury assays,and renal tissues were removed for further molecular assays.The target gene for miR-630 was predicted using bioinformatics,and the association between miR-630 and toll-like receptor 4(TLR4)was confirmed using in vitro investigations and double luciferase reporter gene assays.Overexpression of miR-630 in DKD rats led to changes in body weight,renal weight index,basic blood parameters and histopathological changes.RESULTS The expression level of miR-630 was reduced in the kidney tissue of rats with DKD(P<0.05).The miR-630 and TLR4 expressions in rat renal TECs(NRK-52E)were measured using quantitative reverse transcription polymerase chain reaction.The mRNA expression level of miR-630 was significantly lower in the high-glucose(HG)and HG+mimic negative control(NC)groups than in the normal glucose(NG)group(P<0.05).In contrast,the mRNA expression level of TLR4 was significantly higher in these groups(P<0.05).However,miR-630 mRNA expression increased and TLR4 mRNA expression significantly decreased in the HG+miR-630 mimic group than in the HG+mimic NC group(P<0.05).Furthermore,the levels of tumor necrosis factor-alpha(TNF-α),interleukin-1β(IL-1β),and IL-6 were significantly higher in the HG and HG+mimic NC groups than in NG group(P<0.05).However,the levels of these cytokines were significantly lower in the HG+miR-630 mimic group than in the HG+mimic NC group(P<0.05).Notably,changes in protein expression were observed.The HG and HG+mimic NC groups showed a significant decrease in E-cadherin protein expression,whereas TLR4,α-smooth muscle actin(SMA),and collagen IV protein expression increased(P<0.05).Conversely,the HG+miR-630 mimic group exhibited a significant increase in E-cadherin protein expression and a notable decrease in TLR4,α-SMA,and collagen IV protein expression than in the HG+mimic NC group(P<0.05).The miR-630 targets TLR4 gene expression.In vivo experiments demonstrated that DKD rats treated with miR-630 agomir exhibited significantly higher miR-630 mRNA expression than DKD rats injected with agomir NC.Additionally,rats treated with miR-630 agomir showed significant reductions in urinary albumin,blood glucose,TLR4,and proinflammatory markers(TNF-α,IL-1β,and IL-6)expression levels(P<0.05).Moreover,these rats exhibited fewer kidney lesions and reduced infiltration of inflammatory cells.CONCLUSION MiR-630 may inhibit the inflammatory reaction of DKD by targeting TLR4,and has a protective effect on DKD.
基金funding received by a grant from the Natural Sciences and Engineering Research Council of Canada(NSERC)(Grant No.CRDPJ 469057e14).
文摘We have proposed a methodology to assess the robustness of underground tunnels against potential failure.This involves developing vulnerability functions for various qualities of rock mass and static loading intensities.To account for these variations,we utilized a Monte Carlo Simulation(MCS)technique coupled with the finite difference code FLAC^(3D),to conduct two thousand seven hundred numerical simulations of a horseshoe tunnel located within a rock mass with different geological strength index system(GSIs)and subjected to different states of static loading.To quantify the severity of damage within the rock mass,we selected one stress-based(brittle shear ratio(BSR))and one strain-based failure criterion(plastic damage index(PDI)).Based on these criteria,we then developed fragility curves.Additionally,we used mathematical approximation techniques to produce vulnerability functions that relate the probabilities of various damage states to loading intensities for different quality classes of blocky rock mass.The results indicated that the fragility curves we obtained could accurately depict the evolution of the inner and outer shell damage around the tunnel.Therefore,we have provided engineers with a tool that can predict levels of damages associated with different failure mechanisms based on variations in rock mass quality and in situ stress state.Our method is a numerically developed,multi-variate approach that can aid engineers in making informed decisions about the robustness of underground tunnels.
基金funded by the Postgraduate Research&Practice Innovation Program of Jiangsu Province(Grant No.KYCX22_0613)the National Natural Science Foundation of China(Grant Nos.41831278 and 51878249).
文摘Thermal damage and thermal fracture of rocks are two important indicators in geothermal mining projects.This paper investigates the effects of heating and water-cooling on granite specimens at various temperatures.The laboratory uniaxial compression experiments were also conducted.Then,a coupled thermo-mechanical ordinary state-based peridynamic(OSB-PD)model and corresponding numerical scheme were developed to simulate the damage of rocks after the heating and cooling processes,and the change of crack evolution process was predicted.The results demonstrate that elevated heating temperatures exacerbate the thermal damage to the specimens,resulting in a decrease in peak strength and an increase in ductility of granite.The escalating occurrence of thermal-induced cracks significantly affects the crack evolution process during the loading phase.The numerical results accurately reproduce the damage and fracture characteristics of the granite under different final heating temperatures(FHTs),which are consistent with the test results in terms of strength,crack evolution process,and failure mode.
基金We acknowledge the funding support from the National Natural Science Foundation of China Youth Fund(Grant No.52004019)the National Natural Science Foundation of China(Grant No.41825018)China Postdoctoral Science Foundation(Grant No.2023M733481).
文摘Rock-encased-backfill(RB)structures are common in underground mining,for example in the cut-andfill and stoping methods.To understand the effects of cyclic excavation and blasting activities on the damage of these RB structures,a series of triaxial stepwise-increasing-amplitude cyclic loading experiments was conducted with cylindrical RB specimens(rock on outside,backfill on inside)with different volume fractions of rock(VF=0.48,0.61,0.73,and 0.84),confining pressures(0,6,9,and 12 MPa),and cyclic loading rates(200,300,400,and 500 N/s).The damage evolution and meso-crack formation during the cyclic tests were analyzed with results from stress-strain hysteresis loops,acoustic emission events,and post-failure X-ray 3D fracture morphology.The results showed significant differences between cyclic and monotonic loadings of RB specimens,particularly with regard to the generation of shear microcracks,the development of stress memory and strain hardening,and the contact forces and associated friction that develops along the rock-backfill interface.One important finding is that as a function of the number of cycles,the elastic strain increases linearly and the dissipated energy increases exponentially.Also,compared with monotonic loading,the cyclic strain hardening characteristics are more sensitive to rising confining pressures during the initial compaction stage.Another finding is that compared with monotonic loading,more shear microcracks are generated during every reloading stage,but these microcracks tend to be dispersed and lessen the likelihood of large shear fracture formation.The transition from elastic to plastic behavior varies depending on the parameters of each test(confinement,volume fraction,and cyclic rate),and an interesting finding was that the transformation to plastic behavior is significantly lower under the conditions of 0.73 rock volume fraction,400 N/s cyclic loading rate,and 9 MPa confinement.All the findings have important practical implications on the ability of backfill to support underground excavations.
基金financially supported by the Director Fund of National Energy Deepwater Oil and Gas Engineering Technology Research and Development Center(Grant No.KJQZ-2024-2103)。
文摘The Steel Catenary Riser(SCR)is a vital component for transporting oil and gas from the seabed to the floating platform.The harsh environmental conditions and complex platform motion make the SCR’s girth-weld prone to fatigue failure.The structural stress fatigue theory and Master S-N curve method provide accurate predictions for the fatigue damage on the welded joints,which demonstrate significant potential and compatibility in multi-axial and random fatigue evaluation.Here,we propose a new frequency fatigue model subjected to welded joints of SCR under multiaxial stress,which fully integrates the mesh-insensitive structural stress and frequency domain random process and transforms the conventional welding fatigue technique of SCR into a spectrum analysis technique utilizing structural stress.Besides,a full-scale FE model of SCR with welds is established to obtain the modal structural stress of the girth weld and the frequency response function(FRF)of modal coordinate,and a biaxial fatigue evaluation about the girth weld of the SCR can be achieved by taking the effects of multi-load correlation and pipe-soil interaction into account.The research results indicate that the frequency-domain fatigue results are aligned with the time-domain results,meeting the fatigue evaluation requirements of the SCR.
基金supported by the National Key Research and Development Program of China,Nos.2017YFE0122900(to BH),2019YFA0110800(to WL),2019YFA0903802(to YW),2021YFA1101604(to LW),2018YFA0108502(to LF),and 2020YFA0804003(to JW)the National Natural Science Foundation of China,Nos.31621004(to WL,BH)and 31970821(to YW)+1 种基金CAS Project for Young Scientists in Basic Research,No.YSBR-041(to YW)Joint Funds of the National Natural Science Foundation of China,No.U21A20396(to BH)。
文摘Numerous studies have shown that cell replacement therapy can replenish lost cells and rebuild neural circuitry in animal models of Parkinson’s disease.Transplantation of midbrain dopaminergic progenitor cells is a promising treatment for Parkinson’s disease.However,transplanted cells can be injured by mechanical damage during handling and by changes in the transplantation niche.Here,we developed a one-step biomanufacturing platform that uses small-aperture gelatin microcarriers to produce beads carrying midbrain dopaminergic progenitor cells.These beads allow midbrain dopaminergic progenitor cell differentiation and cryopreservation without digestion,effectively maintaining axonal integrity in vitro.Importantly,midbrain dopaminergic progenitor cell bead grafts showed increased survival and only mild immunoreactivity in vivo compared with suspended midbrain dopaminergic progenitor cell grafts.Overall,our findings show that these midbrain dopaminergic progenitor cell beads enhance the effectiveness of neuronal cell transplantation.