OBJECTIVE To investigate the intervention effects of tissue-bone homeostasis manipulation(TBHM)on peripatellar biomechanical parameters and knee joint function in knee osteoarthritis(KOA)patients.METHODS Sixty patient...OBJECTIVE To investigate the intervention effects of tissue-bone homeostasis manipulation(TBHM)on peripatellar biomechanical parameters and knee joint function in knee osteoarthritis(KOA)patients.METHODS Sixty patients with KOA(Kellgren-Lawrence gradeⅡ-Ⅲ)were recruited from the Acupuncture-Moxibustion Rehabilitation Department,Anhui University of Chinese Medicine between October 2024 and May 2025.Participants were randomized into a TBHM group(n=30)or a transcutaneous electrical neuromuscular stimulation(TENS)group(n=30).Using two-way repeated measures ANOVA,biomechanical indicators,including rectus femoris tension,vastus medialis tension,vastus lateralis tension,patellar ligament tension,lateral patellar displacement(LPD),medial patellar displacement(MPD),normalized patellar mobility(LPD/patellar width[PW],MPD/PW),knee flexion range of motion,and functional indicators,including KOOS subscales,time up and go test(TUGT),were compared between groups at baseline and after 6 weeks of intervention.RESULTS After intervention,all biomechanical and knee joint function indicators in the TBHM group were significantly improved(P<0.05,P<0.01),while only the vastus medialis tension,TUGT and KOOS Pain,ADL and QoL scores in the control group were significantly improved(P<0.01).The improvement amplitudes of biomechanical indicators in the TBHM group,including rectus femoris tension,vastus lateralis tension,patellar ligament tension,MPD/PW,LPD/PW and knee flexion range of motion were better than those in the control group(P<0.05,P<0.01).In the functional evaluation,the interaction effects of the TBHM group in all dimensions of the KOOS score and TUGT were statistically significant(P<0.05,P<0.01).Post-hoc simple effect analysis confirmed that there were significant differences in the above indicators between the two groups after intervention(P<0.05),and all indicators showed a significant main effect of time(P<0.01),suggesting that the intervention measures had continuous and cumulative curative effects.CONCLUSION TBHM effectively improves joint function and quality of life in KOA patients by restoring dynamic equilibrium in soft tissue tension and patellar mobility,ultimately achieving the therapeutic goal of concurrent tissue-bone management.展开更多
Objective Heart failure(HF)is divided into two types:Heart failure with reduced ejection fraction(HFrEF)and heart failure with preserved ejection fraction(HFpEF).The latter always results in diastolic dysfunction,char...Objective Heart failure(HF)is divided into two types:Heart failure with reduced ejection fraction(HFrEF)and heart failure with preserved ejection fraction(HFpEF).The latter always results in diastolic dysfunction,characterized by changes in mechanical properties.The objective of this study is to build a finite element(FE)model of HFpEF and analyze diastolic and systolic function in rats.Methods Ten Dahl salt-sensitive rats were fed either a low-salt(LS)(n=5)or highsalt(HS)(n=5)diet beginning at 7 weeks of age and scanned by ultrasonic machine at 14 weeks of age.A non-linear FE model of the left ventricle(LV)was built from cardiac echo images at end-diastole and passive material properties of the LV were prescribed using Fung’s transversely isotropic constitutive law.Fiber angles of the endocardium and epicardium were prescribed as 53°°and-52°,respectively,with respect to the circumferential direction and varied linearly through the LV wall.The method developed by Krishnamurthywas used to determine the unloaded geometry to estimate the Fung passive material parameters.LV end-diastolic pressure(EDP)was determined from the measured pressure waves and applied to the endocardium at the unloaded geometry to simulate passive filling.Active material properties of the LV were prescribed using Guccione’s time-varying elastance model and maximum isometric tension was scaled to match the measured peak systolic pressure.The finite element model was then coupled to the Windkessel model,whose parameters were adjusted to the measured hemodynamics.Results Measured LVEDPs of LS and HS rats were 4.9±3.4 mmHg and 13.2±5.4 mmHg(P-0.030 8),respectively.End-diastolic Cauchy stress along the fiber direction for LS rats was significantly lower than for HS rats(0.91±0.60 kPa vs 3.00±0.63 kPa,P=0.001 4)and there was a similar trend in end-diastolic Green Strain along the fiber direction(0.058±0.003 vs 0.072±0.010,P=0.012 8,Figure 1b),as well.There was no distinctive difference between end-systolic Cauchy stress along the fiber direction for LS rats and HS rats(17.2±4.3 kPa vs 17.2±5.5 kPa,P=0.991 9)but end-systolic Green Strain along the fiber direction for LS rats was significantly higher than for HS rats(-0. 108±0.017 vs-0.065±0.024,negative sign represents direction).Conclusions For rats with HFpEF,it is the elevated LVEDP that induces the increase in end-diastolic stress and strain,thereby leading to diastolic dysfunction.Because of the preserved ejection fraction,HFpEF has less effect on systolic function.展开更多
The bone is a naturally occurring composite system comprising collagen matrix and hydroxyapatites capable of generating sufficient strength and toughness to support mechanical loads and resist fracture,respectively.Th...The bone is a naturally occurring composite system comprising collagen matrix and hydroxyapatites capable of generating sufficient strength and toughness to support mechanical loads and resist fracture,respectively.The material strength depends largely on the elastic properties,whereas the toughness depends on not only the elastic,but also the plastic properties.Thus,both elastic and plastic properties must be considered in the analysis of bone biomechanics and the design of osteogenic materials.The bone is capable of optimizing its elastic and plastic properties by integrating stiff hydroxyapatites and ductile collagen fibrils into a hierarchically ordered architecture,an effective mechanism to support the bone strength and toughness.Such a mechanism can be used as a model for designing osteogenic materials.展开更多
Objective The binding of cell adhesive peptides(such as RGD)to integrins initiates the recruitment of cytoplasmic adaptor proteins(e.g.,vinculin)and the formation of focal adhesion(FA)complexes required for cell adhes...Objective The binding of cell adhesive peptides(such as RGD)to integrins initiates the recruitment of cytoplasmic adaptor proteins(e.g.,vinculin)and the formation of focal adhesion(FA)complexes required for cell adhesion.The ability to manipulate this ligand-mediated cell adhesion process is crucial for regulating cell migration,cell differentiation,injury healing,and immune response.Some recent studies reported the importance of the tether length/mobility of the cell adhesive ligands in regulating the traction force development of cells.In the native cellular microenvironment,such a dynamic change in the nanoscale tether length of bioactive ligands is often mediated by conformational changes of the structural proteins due to protein folding or degradation.However,no prior studies have demonstrated the modulation of the ligand tether mobility by controlling the intramolecular folding of polymeric linkers.Unfoldable synthetic macromolecules with easy synthetic routes and controllable structures,such as supramolecular host-guest single chain nanogels(SCNGs),are ideal candidates for mimicking the changes in the tether mobility of bioactive ligands via biorthogonal triggers.Methods S,S’-bis(a’a’-dimethyl-a’’-propargyl acetate)trithiocarbonate was first used to mediate the RAFT polymerization of N,N-dimethyl acrylamide,vinyl-adamantane and vinyl-β-cyclodextrin to yield the ADA@CD-SCNGs.The preparation of the unfoldable host-guest SCNGs was evidenced by the by gel permeation chromatography,proton nuclear magnetic resonance spectroscopy,atomic force microscopy and dynamic light scattering.Then the RGD peptide was conjugated to the alkynyl group on one end of the SCNGs before immobilizing the material on the substrate,which was confirmed by scanning electron microscopy(SEM).The regulation of cell behaviours by unfolding of the SCNG-RGD was confirmed by immunofluorescence staining of vinculin and Yes-associated protein(YAP).Results The preparation of ADA@CD-SCNGs was confirmed by GPC which showed a unimodal molecular weight distribution.DLS and AFM data also proved that the SCNGs had an average diameter of 12±3nm.SEM images showed that SCNGs were conjugated as a linker of RGD peptide to thiolated glass substrate at an average density of 162±11 particles/μm2.These particles disappeared after adding free competitive ADA guest molecules,indicating the triggered unfolding of the tether SCNGs.In addition,the unfolding of supramolecular ADA@CD-SCNGs was also evidenced by a decrease in the GPC elution time and a slight increase in the apparent molecular weight.These results show that the immobilized ADA@CD-SCNGs can be unfolded to tune the tether length and mobility of the conjugated RGD ligands.Then we investigated the regulation of the cell behaviors on the substrate by triggering the unfolding of SCNG linkers.A critical level of traction force is required to effectively initiate and maintain integrin-mediated formation of FA complexes and subsequent mechano-transduction signaling.An increased tether length in cell-adhesive ligands can lead to a diminished cell traction force as if cells are adhering to soft substrates.Here,the unfolding of the ADA@CD-SCNG-RGD triggered by the addition of free ADA led to disassembly of the mature focal adhesions in the cells as evidenced by the reduced vinculin and F-actin in staining.Subsequently,nuclear YAP also decreased significantly because of the impaired mechano-sensing and diminished cell cytoskeleton tension.In addition,the extensively spread cells gradually became round after the medium was supplemented with free competitive ADA to unfold the SCNG linker.These finding demonstrates that the substrates with the unfolded ADA@CD-SCNG-RGD only supported weak cell adhesions.In contrast,on the substrate conjugated with the nonunfoldable MBA-SCNG-RGD linker,the addition of free ADA resulted in no change in the spread cell morphology and protein expressions.These results indicate that the unfoldable host-guest ADA@CD-SCNG can be used to manipulate the nanoscale presentation of ligands to regulate cell behaviors.Conclusions We demonstrate the application of SCNGs as the supramolecular linker to tune the nanoscale ligand tether length.These findings demonstrate that the strategy of manipulating the tether mobility of bioactive ligands by using supramolecular SCNGs as linkers provides a highly tunable,biomimetic,and bio-orthogonal approach to study the dynamic events of cell adhesion.展开更多
Rehabilitation engineering aims in the upmost degree to restore the lost functions for those persons with physical disability. Biomechanical modeling has been widely used for different purposes in rehabilitation engin...Rehabilitation engineering aims in the upmost degree to restore the lost functions for those persons with physical disability. Biomechanical modeling has been widely used for different purposes in rehabilitation engineering to understand the bio-展开更多
Introduction Atherosclerosis is a potentially life-threatening disease of large arteries that is strongly associated with systemic risk factors such as hypercholesterolemia,hypertension,smoking,and diabetes. However,a...Introduction Atherosclerosis is a potentially life-threatening disease of large arteries that is strongly associated with systemic risk factors such as hypercholesterolemia,hypertension,smoking,and diabetes. However,atherosclerosis develops as a展开更多
Mechanobiology has been a highly recognized field in studying the importance of physical forces in physiologies at the molecular,cellular,tissue,organ and body-levels.Beside the intensive work focusing on the fine loc...Mechanobiology has been a highly recognized field in studying the importance of physical forces in physiologies at the molecular,cellular,tissue,organ and body-levels.Beside the intensive work focusing on the fine local biomechanical forces,the long-range force which can propagate through a relatively distant scale(in hundreds of micrometers and beyond)has been an intriguing topic with increasing attentions in recent years.The collective functions at cell population level often rely on cell-cell communications with or without direct contacts.Recent progresses including our own work indicate that the long-range biomechanical force propagating across scales far beyond single cell size may reserve the capability to trigger coordinative biological responses within cell population.Whether and how cells communicate mechanically in a distant manner remains largely to be explored.In respiratory system,the mechanical property of airway smooth muscle(ASM)is associated with asthma attack with prolonged contraction during airway hyper-responsiveness.In this work,we found that ASM cells rapidly self-assembled into a well-constructed network on 3D matrigel containing type I collagen(COL I),which required the collective functions and coordination of thousands of cells completed within 12-16 hours.Cells were assembled with aligned actin stress fibers and elongated nuclei.The assembling process relied on the long-range mechanical forces across the matrix to direct cell-cell distant interactions.We further found that single ASM cells could rapidly initiate multiple buds precisely pointing to neighboring cells in distance,which relied on cell traction force and force strain on the matrix.Beads tracking assay demonstrated the long-range transmission of cellular traction force to distant locations,and modeling of maximum strain distribution on matrix by finite element method predicted the consistency with cell directional protrusions and movements in experiments.Cells could sense each other in distance to move directionally on both non-fibrous matrigel and in much more efficient way when containing COL I.Cells recruited COL I from the hydrogel to build nearly identical COL I fibrous network to mechanically stabilize the cell network.Our results revealed that ASM cells can sense the traction strain transmitted through matrix to initiate distant communications and rapidly coordinate the network assembly at the population level through active cell-matrix interactions.As an interesting phenomenon,cells sound able to’make phone call’via the role of long-range mechanical force.In summary,this work demonstrated that long-range biomechanical force facilitates the collective functions of ASM cell population for network assembly.The cells reacted to traction strain on the matrix for distant communications,which resulted in directional budding and movement.Fibrous COL I had important roles in facilitating the efficiency of force transmission to induce the assembly and stabilizing the cell network.This work has helped advance the understanding of the feature andfunction of long-range biomechanical force at the cell population level.The observed high mechano-sensitivity of ASM cells might suggest a re-enforced feedback of enhanced contraction by excessive ASM under asthmatic condition.展开更多
Objective Mitral valve(MV)plays an importance role in regulating blood flow from left atrium to left ventricle and preventing backflow to left atrium.Mitral Valve consist of four important parts;anterior leaflet,poste...Objective Mitral valve(MV)plays an importance role in regulating blood flow from left atrium to left ventricle and preventing backflow to left atrium.Mitral Valve consist of four important parts;anterior leaflet,posterior leaflet,chordae tendineae,and papillary muscles,which all work in harmony.The material properties alteration on the leaflet causes MV malfunction,and leading to valve diseases such as regurgitation and stenosis.The alteration may be caused by several factors such as calcification,genetic disorders,and infection,which usually have an influence to the mechanical properties,and thus affecting the mechanical behavior of MV.In consequence,some of the patients need MV replacement or repair to restore the normal function of MV.The important point for succeeding such a medical treatment depends on the technique,design,and material used in the treatment shall help rebuild the normal mechanical environment and behavior of MV.Therefore,the mechanical and materials characteristics of MV become a magnetism to explore.In this study,we present an integrated experimental and mathematical constitutive study base in collagen distribution aiming at the mechanical property differences in various region on MV.Methods and materials Both the size and composition of porcine valves are similar to human’s,so the porcine heart valve is often being used in experimental research.Mitral valve was isolated from fresh eight porcine hearts(250-500 gr),and perfused in PBS solution to maintain moist.Anterior and posterior leaflets were separated and dissected into 4 part(two 8~*8 mm rough zone and two clear zone samples)and 2 part(8~*8 mm belly and edge of the clear zone)respectively.Tracking markers(glass bean)were stickled on specimen with superglue(cyanoacrylate adhesive).Then,the specimen was mounted onto biaxial tester machine(CeIIScale,Biotester),and the tests are run by force control.During mechanical test,the specimen is immersed into PBS solution in physiological temperature(37℃).Every test procedure contains 8 preconditioning cycles and 8 loading cycles.The mechanical behavior was determined from the relationship between first Piola-Kirchoff stress and stretch.Constitutive model was reconstructed and material parameters were fitted from biaxial tensile result.Histological analyses were performed in the specimen before and after test.First,a piece of the specimen was cut and immersed in fixation solution(4%paraformaldehyde),then it was dehydrated in graded alcohol solution,and next embedding in paraffin wax block.Paraffin block was then cut and stained with VVG and Picro-sirius red.The collagen fibril orientation was observed from those histological results.Results The experimental results of the clear zone of MV’s first Piola-Kirchhoff stress and stretch curve are similar to those of the recent study from others,while result of the rough zone shows a different trend.This can be explained by differences in collagen distribution between clear zone and rough zone of MV.Our result thus allows for a refinement of computational models for more accurately predicting MV condition,where tissue heterogeneity plays an important role in the MV function.展开更多
Objective Fumonisin B1(FB1)is an important mycotoxin in nature worldwide.The biomechanical properties of cells are closely related to their structure and function,and the cytoskeleton is the structural and functional ...Objective Fumonisin B1(FB1)is an important mycotoxin in nature worldwide.The biomechanical properties of cells are closely related to their structure and function,and the cytoskeleton is the structural and functional basis of cells motility,and therefore,from a biomechanical point of view,the purpose of this study is to investigate the effects of FB1 on the biomechanical properties,migration capacity and cytoskeletal structure of human umbilical vein endothelial cells(HUVECs),which may lay an experimental foundation for further exploration of the toxicity mechanism of fumonisin.Methods HUVECs were cultured and treated with different concentrations of FB1.Then,CCK-8 kit was used to detect the effect of FB1 on the survival rate.The osmotic fragility of the cells was measured after treatment with different osmotic pressures for30 min.The cell membrane fluidity was measured by fluorescence polarization method.The cell electrophoretic mobility was measured by cell electrophoretic apparatus.The migration capacity of the cells was observed by scratch repair assay.The changes of reactive oxygen species and cytoskeletal structure were observed by confocal laser scanning microscopy.Finally,the mRNA and protein relative expression levels of cytoskeletal binding proteins were detected by real-time PCR,Western blotting and confocal laser scanning.Results The results of CCK-8 showed that FB1 could significantly inhibit the proliferation of HUVECs in a dose-and time-dependent manner.After treatment of HUVECs with FB1,the hypotonic resistance of the cell,cell surface charge,cell membrane fluidity and migration capacity were all weakened,while reactive oxygen species were significantly increased and the cytoskeletal structure was significantly reorganized.Furthermore,RTPCR results showed that the mRNA relative expression levels of cytoskeletal binding proteins,exception of actin,were down-regulated after treated with FB1.Besides,Western blotting and statistical analysis based on fluorescence intensity of laser confocal microscopy confirmed theses changes in protein level.Conclusions FB1 can significantly affect the biomechanical properties and motility of HUVECs,which may be directly correlated to the remodel of F-actin cytoskeleton,as well as the relative expression changes of cytoskeletal binding proteins.It is significant for further exploring the toxicity mechanism of fumonisin.展开更多
To explore the response law of non-lethal large-size kinetic energy projectiles to blunt attack on skin tissue,and to evaluate the skin injury characteristics of the attacked personnel and the use safety of kinetic en...To explore the response law of non-lethal large-size kinetic energy projectiles to blunt attack on skin tissue,and to evaluate the skin injury characteristics of the attacked personnel and the use safety of kinetic energy projectiles.Based on the LS-DYNA simulation software,a three-layer skin simulation model and a Flash-Ball rubber bullet model are established,and the force-time and deformation-time biomechanical corridors of the Flash-Ball rubber bullet impacting human skin tissue are obtained.The corridor curve and the energy transfer and diffusion are analyzed and compared.The safety evaluation of the damage caused by the rubber bullet shooting a human body at different distances is carried out using the empirical formula of the penetration limit.Finally,the safe shooting distance is obtained.The results show that the model used in the simulation has a good correlation with the experimental data,its biomechanical corridor characteristics are different from those of conventional vehicle impact and smallsize projectile response characteristics.The energy transfer and action time of medium and low-speed impact may cause greater damage.The fat layer is the largest energy absorption unit.The minimum safe shooting distance to ensure skin tissue from penetrating damage is 15.8 m,and the limit specific kinetic energy of skin damage is 7.88 J/cm^(2).This study can be extended to the study of biomechanical response law and safety evaluation under the impact of the same type of large kinetic energy projectile,which provides an important theoretical reference for the police to use large kinetic energy projectiles to conduct safe shooting in peacekeeping operations.展开更多
Introduction Neurons are situated in a microenvironment composed of various biochemical and biophysical cues,where stretching is thought to have a major impact on neurons.For instance,during a moderate traumatic brain...Introduction Neurons are situated in a microenvironment composed of various biochemical and biophysical cues,where stretching is thought to have a major impact on neurons.For instance,during a moderate traumatic brain impact,the injury region in axons exhibits significant longitudinal strain;and in a rat model of spinal cord injury,the most severe axonal injury is located in the largest strain region.Stretching may result in microstructural changes in neural tissue and further leading to abnormal electrophysiological function.Hence,it is of great importance to understand the coupled mechanoelectricalbehaviors of neurons under stretching.In spite of significant experimental efforts,the underlying mechanism remains elusive,more works are needed to provide a detailed description of the process that leads to the observed phenomena.Mathematical modeling is a powerful tool that offers a quantitative description of the underlying mechanism of an observed biological phenomenon,including mechanical and electrophysiological behaviors of neurons.Thus,we developed a mechanoelectrical coupling model of neurons under stretching in this study.Mathematical model The mathematical model consists of three submodels,i.e.,the mechanical submodel,the mechanoelectrical coupling submodel and the electrophysiological submodel.The mechanical submodel deals with the relationship between stretching and the deformation of axons,which has specially considered the plastic deformation of axons.The electrophysiological submodel characterizes the feature of neuronal action potential(AP),which is based on the classical H-H model and the cable theory.The mechanoelectrical coupling submodel links the mechanical and electrophysiological submodels through strain-induced equivalent circuit parameter alteration and ion channel injury.Besides,we have discussed a more general deformation condition,where an expanded model coupling the axonal deformation and electrophysiology alteration was explored.As the most essential parameters in an electrophysiological assessment,the amplitude of the AP,the neuronal firing frequency and the electrophysiological signal conduction velocity,which could be affected by stretching,were used as outputs of the model.Results&discussion To understand the mechanoelectrical coupling of neurons under stretching,we developed a mechanoelectrical coupling model.To verify the model,we simulated a slow stretching on an axon following the experimental study in the literature,we observed that as the strain increases,the peak AP declines faster,which is consistent with the experimental data.Moreover,the reduced AP cannot be restored to the original peak,implying that the damage is irreversible.The simulation results also predict that strain induces a more frequent neuronal firing and a faster conduction.In a realistic situation,in addition to stretching,the loading condition is very complicated,which may induce complex axonal deformation(e.g., necking and swelling along the axons).We also simulated such necking deformation impairment and observed that the AP amplitude decreases at the necking region and recovers after that,indicating a blockage of the AP;and the conduction velocity decreases with the increase in deformation degree.Conclusions In this study,we developed a mechanoelectrical coupling model of neurons under stretching with consideration of axonal plastic deformation.With the model,we found that the effect of mechanical loading on electrophysiology mainly manifests as decreased membrane AP amplitude,a more frequent neuronal firing and a faster electrophysiological signal conduction.The model predicts not only stretch-induced injury but also a more gene ral necking deformation case,which may someday be revealed in future by experiments,providing a reference for the prediction and regulation of neuronal function under mechanical loadings.展开更多
Dendritic cells(DCs)are the most important antigen-presenting cells due to their professional and extremely efficient antigen-presenting function.In view of their exceptional ability to present antigen and to interact...Dendritic cells(DCs)are the most important antigen-presenting cells due to their professional and extremely efficient antigen-presenting function.In view of their exceptional ability to present antigen and to interact with T cells,DC play distinct roles in linking innate and adaptive immune responses and thus become logical targets for cancer immunotherapy.Evidences show that tumor-derived cytokines could impair DCs’biomechanics properties,which lead to inefficacy of DCs-based immune therapies.Our previous studies found that IL-10,as one of the widespread suppressive cytokines from tumor microenvironment(TME),could deteriorate DCs’motility and biomechanics properties while the underlying mechanism is unknown.In this study,CD14+monocytes were induced to differentiate into mature dendritic cells after isolation in vitro using recombinant cytokines IL-4,GM-CSF,LPS,and IFN-γ.And we also have compared the proteomic changes of mDCs treated by IL-10 and control group via two-dimensional electrophoresis combine with MALDI-TOF/TOF MS.Then we analyzed the function of differentially expressed proteins through bioinformatics methods include GO analysis that clarified the biological functions of differential proteins and KEGG analysis which enriched signal pathways of differential proteins to explore the molecular mechanism of IL-10 which has inhibitory effect on mDCs.The results showed that IL-10 significantly affected the morphology of mDCs,especially reducing the number and length of filopodia.Different expressed proteins were analyzed by two-dimensional electrophoresis combined with bioinformatics analysis to enrich for glycolytic signaling pathway,HIF-1 signaling pathway and cytoskeletal binding protein expression changes.The results of two-dimensional electrophoresis were verified by Western blot,and the results showed that the data were reliable.In addition,the intracellular ROS levels were significantly higher in mDCs treated with IL-10,validating the previously enriched HIF-1 signaling pathway.In summary,it indicated that IL-10 may interfered with the oxidative metabolic process,glycolytic metabolism,and expression of cytoskeleton-related proteins in mDCs,and disturbances in these physiological processes resulted in reduced biomechanics properties and motility of mDCs and subsequently impaired their immune functions,making DC-based tumor vaccines less effective than which we desired.Our study reveals alterations in the physiological metabolism of mDCs under IL-10 treatment from the proteome,which lays the foundation for further exploration of the altered state of mDCs in the tumor microenvironment.展开更多
Heterotopic ossification(HO)is a consequence of traumatic bone and tissue damage,which occurs in 65%of military casualties with blast-associated amputations.However,the mechanisms behind blast-induced HO remain unclea...Heterotopic ossification(HO)is a consequence of traumatic bone and tissue damage,which occurs in 65%of military casualties with blast-associated amputations.However,the mechanisms behind blast-induced HO remain unclear.Animal models are used to study blast-induced HO,but developing such models is challenging,particularly in how to use a pure blast wave(primary blast)to induce limb fracture that then requires an amputation.Several studies,including our recent study,have developed platforms to induce limb fractures in rats with blast loading or a mixture of blast and impact loading.However,these models are limited by the survivability of the animal and repeatability of the model.In this study,we developed an improved platform,aiming to improve the animal's survivability and injury repeatability as well as focusing on primary blast only.The platform exposed only one limb of the rat to a blast wave while providing proper protection to the rest of the rat's body.We obtained very consistent fracture outcome in the tibia(location and pattern)in cadaveric rats with a large range of size and weight.Importantly,the rats did not obviously move during the test,where movement is a potential cause of uncontrolled injury.We further conducted parametric studies by varying the features of the design of the platform.These factors,such as how the limb is fixed and how the cavity through which the limb is placed is sealed,significantly affect the resulting injury.This platform and test setups enable well-controlled limb fracture induced directly by pure blast wave,which is the fundamental step towards a complete in vivo animal model for blast-induced HO induced by primary blast alone,excluding secondary and tertiary blast injury.In addition,the platform design and the findings presented here,particularly regarding the proper protection of the animal,have implications for future studies investigating localized blast injuries,such as blast induced brain and lung injuries.展开更多
Modern conflicts demand substantial physical and psychological exertion,often resulting in fatigue and diminished combat or operational readiness.Several exoskeletons have been developed recently to address these chal...Modern conflicts demand substantial physical and psychological exertion,often resulting in fatigue and diminished combat or operational readiness.Several exoskeletons have been developed recently to address these challenges,presenting various limitations that affect their operational or everyday usability.This article evaluates the performance of a dual-purpose passive ankle exoskeleton developed for the reduction of metabolic costs during walking,seeking to identify a force element that could be applied to the target population.Based on the 6-min walk test,twenty-nine subjects participated in the study using three different force elements.The results indicate that it is possible to reduce metabolic expenditure while using the developed exoskeleton.Additionally,the comfort and range of motion results verify the exoskeleton's suitability for use in uneven terrain and during extended periods.Nevertheless,the choice of the force element should be tailored to each user,and the control system should be adjustable to optimise the exoskeleton's performance.展开更多
文摘OBJECTIVE To investigate the intervention effects of tissue-bone homeostasis manipulation(TBHM)on peripatellar biomechanical parameters and knee joint function in knee osteoarthritis(KOA)patients.METHODS Sixty patients with KOA(Kellgren-Lawrence gradeⅡ-Ⅲ)were recruited from the Acupuncture-Moxibustion Rehabilitation Department,Anhui University of Chinese Medicine between October 2024 and May 2025.Participants were randomized into a TBHM group(n=30)or a transcutaneous electrical neuromuscular stimulation(TENS)group(n=30).Using two-way repeated measures ANOVA,biomechanical indicators,including rectus femoris tension,vastus medialis tension,vastus lateralis tension,patellar ligament tension,lateral patellar displacement(LPD),medial patellar displacement(MPD),normalized patellar mobility(LPD/patellar width[PW],MPD/PW),knee flexion range of motion,and functional indicators,including KOOS subscales,time up and go test(TUGT),were compared between groups at baseline and after 6 weeks of intervention.RESULTS After intervention,all biomechanical and knee joint function indicators in the TBHM group were significantly improved(P<0.05,P<0.01),while only the vastus medialis tension,TUGT and KOOS Pain,ADL and QoL scores in the control group were significantly improved(P<0.01).The improvement amplitudes of biomechanical indicators in the TBHM group,including rectus femoris tension,vastus lateralis tension,patellar ligament tension,MPD/PW,LPD/PW and knee flexion range of motion were better than those in the control group(P<0.05,P<0.01).In the functional evaluation,the interaction effects of the TBHM group in all dimensions of the KOOS score and TUGT were statistically significant(P<0.05,P<0.01).Post-hoc simple effect analysis confirmed that there were significant differences in the above indicators between the two groups after intervention(P<0.05),and all indicators showed a significant main effect of time(P<0.01),suggesting that the intervention measures had continuous and cumulative curative effects.CONCLUSION TBHM effectively improves joint function and quality of life in KOA patients by restoring dynamic equilibrium in soft tissue tension and patellar mobility,ultimately achieving the therapeutic goal of concurrent tissue-bone management.
基金supported by the National Natural Science Foundation of China ( 11732001)
文摘Objective Heart failure(HF)is divided into two types:Heart failure with reduced ejection fraction(HFrEF)and heart failure with preserved ejection fraction(HFpEF).The latter always results in diastolic dysfunction,characterized by changes in mechanical properties.The objective of this study is to build a finite element(FE)model of HFpEF and analyze diastolic and systolic function in rats.Methods Ten Dahl salt-sensitive rats were fed either a low-salt(LS)(n=5)or highsalt(HS)(n=5)diet beginning at 7 weeks of age and scanned by ultrasonic machine at 14 weeks of age.A non-linear FE model of the left ventricle(LV)was built from cardiac echo images at end-diastole and passive material properties of the LV were prescribed using Fung’s transversely isotropic constitutive law.Fiber angles of the endocardium and epicardium were prescribed as 53°°and-52°,respectively,with respect to the circumferential direction and varied linearly through the LV wall.The method developed by Krishnamurthywas used to determine the unloaded geometry to estimate the Fung passive material parameters.LV end-diastolic pressure(EDP)was determined from the measured pressure waves and applied to the endocardium at the unloaded geometry to simulate passive filling.Active material properties of the LV were prescribed using Guccione’s time-varying elastance model and maximum isometric tension was scaled to match the measured peak systolic pressure.The finite element model was then coupled to the Windkessel model,whose parameters were adjusted to the measured hemodynamics.Results Measured LVEDPs of LS and HS rats were 4.9±3.4 mmHg and 13.2±5.4 mmHg(P-0.030 8),respectively.End-diastolic Cauchy stress along the fiber direction for LS rats was significantly lower than for HS rats(0.91±0.60 kPa vs 3.00±0.63 kPa,P=0.001 4)and there was a similar trend in end-diastolic Green Strain along the fiber direction(0.058±0.003 vs 0.072±0.010,P=0.012 8,Figure 1b),as well.There was no distinctive difference between end-systolic Cauchy stress along the fiber direction for LS rats and HS rats(17.2±4.3 kPa vs 17.2±5.5 kPa,P=0.991 9)but end-systolic Green Strain along the fiber direction for LS rats was significantly higher than for HS rats(-0. 108±0.017 vs-0.065±0.024,negative sign represents direction).Conclusions For rats with HFpEF,it is the elevated LVEDP that induces the increase in end-diastolic stress and strain,thereby leading to diastolic dysfunction.Because of the preserved ejection fraction,HFpEF has less effect on systolic function.
文摘The bone is a naturally occurring composite system comprising collagen matrix and hydroxyapatites capable of generating sufficient strength and toughness to support mechanical loads and resist fracture,respectively.The material strength depends largely on the elastic properties,whereas the toughness depends on not only the elastic,but also the plastic properties.Thus,both elastic and plastic properties must be considered in the analysis of bone biomechanics and the design of osteogenic materials.The bone is capable of optimizing its elastic and plastic properties by integrating stiff hydroxyapatites and ductile collagen fibrils into a hierarchically ordered architecture,an effective mechanism to support the bone strength and toughness.Such a mechanism can be used as a model for designing osteogenic materials.
文摘Objective The binding of cell adhesive peptides(such as RGD)to integrins initiates the recruitment of cytoplasmic adaptor proteins(e.g.,vinculin)and the formation of focal adhesion(FA)complexes required for cell adhesion.The ability to manipulate this ligand-mediated cell adhesion process is crucial for regulating cell migration,cell differentiation,injury healing,and immune response.Some recent studies reported the importance of the tether length/mobility of the cell adhesive ligands in regulating the traction force development of cells.In the native cellular microenvironment,such a dynamic change in the nanoscale tether length of bioactive ligands is often mediated by conformational changes of the structural proteins due to protein folding or degradation.However,no prior studies have demonstrated the modulation of the ligand tether mobility by controlling the intramolecular folding of polymeric linkers.Unfoldable synthetic macromolecules with easy synthetic routes and controllable structures,such as supramolecular host-guest single chain nanogels(SCNGs),are ideal candidates for mimicking the changes in the tether mobility of bioactive ligands via biorthogonal triggers.Methods S,S’-bis(a’a’-dimethyl-a’’-propargyl acetate)trithiocarbonate was first used to mediate the RAFT polymerization of N,N-dimethyl acrylamide,vinyl-adamantane and vinyl-β-cyclodextrin to yield the ADA@CD-SCNGs.The preparation of the unfoldable host-guest SCNGs was evidenced by the by gel permeation chromatography,proton nuclear magnetic resonance spectroscopy,atomic force microscopy and dynamic light scattering.Then the RGD peptide was conjugated to the alkynyl group on one end of the SCNGs before immobilizing the material on the substrate,which was confirmed by scanning electron microscopy(SEM).The regulation of cell behaviours by unfolding of the SCNG-RGD was confirmed by immunofluorescence staining of vinculin and Yes-associated protein(YAP).Results The preparation of ADA@CD-SCNGs was confirmed by GPC which showed a unimodal molecular weight distribution.DLS and AFM data also proved that the SCNGs had an average diameter of 12±3nm.SEM images showed that SCNGs were conjugated as a linker of RGD peptide to thiolated glass substrate at an average density of 162±11 particles/μm2.These particles disappeared after adding free competitive ADA guest molecules,indicating the triggered unfolding of the tether SCNGs.In addition,the unfolding of supramolecular ADA@CD-SCNGs was also evidenced by a decrease in the GPC elution time and a slight increase in the apparent molecular weight.These results show that the immobilized ADA@CD-SCNGs can be unfolded to tune the tether length and mobility of the conjugated RGD ligands.Then we investigated the regulation of the cell behaviors on the substrate by triggering the unfolding of SCNG linkers.A critical level of traction force is required to effectively initiate and maintain integrin-mediated formation of FA complexes and subsequent mechano-transduction signaling.An increased tether length in cell-adhesive ligands can lead to a diminished cell traction force as if cells are adhering to soft substrates.Here,the unfolding of the ADA@CD-SCNG-RGD triggered by the addition of free ADA led to disassembly of the mature focal adhesions in the cells as evidenced by the reduced vinculin and F-actin in staining.Subsequently,nuclear YAP also decreased significantly because of the impaired mechano-sensing and diminished cell cytoskeleton tension.In addition,the extensively spread cells gradually became round after the medium was supplemented with free competitive ADA to unfold the SCNG linker.These finding demonstrates that the substrates with the unfolded ADA@CD-SCNG-RGD only supported weak cell adhesions.In contrast,on the substrate conjugated with the nonunfoldable MBA-SCNG-RGD linker,the addition of free ADA resulted in no change in the spread cell morphology and protein expressions.These results indicate that the unfoldable host-guest ADA@CD-SCNG can be used to manipulate the nanoscale presentation of ligands to regulate cell behaviors.Conclusions We demonstrate the application of SCNGs as the supramolecular linker to tune the nanoscale ligand tether length.These findings demonstrate that the strategy of manipulating the tether mobility of bioactive ligands by using supramolecular SCNGs as linkers provides a highly tunable,biomimetic,and bio-orthogonal approach to study the dynamic events of cell adhesion.
基金Research Grant Council of Hong Kong (GRF Project nos PolyU5331 /07E,PolyU5352 /08E)a grant from Ministry of Sciences and Technology,China (No 2006BAI22B00)
文摘Rehabilitation engineering aims in the upmost degree to restore the lost functions for those persons with physical disability. Biomechanical modeling has been widely used for different purposes in rehabilitation engineering to understand the bio-
基金support from National Heart Lung and Blood Institute Grants P50-HL56985 and R01-HL61794
文摘Introduction Atherosclerosis is a potentially life-threatening disease of large arteries that is strongly associated with systemic risk factors such as hypercholesterolemia,hypertension,smoking,and diabetes. However,atherosclerosis develops as a
基金supported financially by Natural Science Foundation of China ( 11532003,11872129, 31670950)Natural Science Foundation of Jiangsu Province ( BK20181416)CZSTB Grant ( CZ20180017) from Changzhou City,Jiangsu Province
文摘Mechanobiology has been a highly recognized field in studying the importance of physical forces in physiologies at the molecular,cellular,tissue,organ and body-levels.Beside the intensive work focusing on the fine local biomechanical forces,the long-range force which can propagate through a relatively distant scale(in hundreds of micrometers and beyond)has been an intriguing topic with increasing attentions in recent years.The collective functions at cell population level often rely on cell-cell communications with or without direct contacts.Recent progresses including our own work indicate that the long-range biomechanical force propagating across scales far beyond single cell size may reserve the capability to trigger coordinative biological responses within cell population.Whether and how cells communicate mechanically in a distant manner remains largely to be explored.In respiratory system,the mechanical property of airway smooth muscle(ASM)is associated with asthma attack with prolonged contraction during airway hyper-responsiveness.In this work,we found that ASM cells rapidly self-assembled into a well-constructed network on 3D matrigel containing type I collagen(COL I),which required the collective functions and coordination of thousands of cells completed within 12-16 hours.Cells were assembled with aligned actin stress fibers and elongated nuclei.The assembling process relied on the long-range mechanical forces across the matrix to direct cell-cell distant interactions.We further found that single ASM cells could rapidly initiate multiple buds precisely pointing to neighboring cells in distance,which relied on cell traction force and force strain on the matrix.Beads tracking assay demonstrated the long-range transmission of cellular traction force to distant locations,and modeling of maximum strain distribution on matrix by finite element method predicted the consistency with cell directional protrusions and movements in experiments.Cells could sense each other in distance to move directionally on both non-fibrous matrigel and in much more efficient way when containing COL I.Cells recruited COL I from the hydrogel to build nearly identical COL I fibrous network to mechanically stabilize the cell network.Our results revealed that ASM cells can sense the traction strain transmitted through matrix to initiate distant communications and rapidly coordinate the network assembly at the population level through active cell-matrix interactions.As an interesting phenomenon,cells sound able to’make phone call’via the role of long-range mechanical force.In summary,this work demonstrated that long-range biomechanical force facilitates the collective functions of ASM cell population for network assembly.The cells reacted to traction strain on the matrix for distant communications,which resulted in directional budding and movement.Fibrous COL I had important roles in facilitating the efficiency of force transmission to induce the assembly and stabilizing the cell network.This work has helped advance the understanding of the feature andfunction of long-range biomechanical force at the cell population level.The observed high mechano-sensitivity of ASM cells might suggest a re-enforced feedback of enhanced contraction by excessive ASM under asthmatic condition.
基金funded by National Nature Foundation of China ( 11532004,1140204,11832008)
文摘Objective Mitral valve(MV)plays an importance role in regulating blood flow from left atrium to left ventricle and preventing backflow to left atrium.Mitral Valve consist of four important parts;anterior leaflet,posterior leaflet,chordae tendineae,and papillary muscles,which all work in harmony.The material properties alteration on the leaflet causes MV malfunction,and leading to valve diseases such as regurgitation and stenosis.The alteration may be caused by several factors such as calcification,genetic disorders,and infection,which usually have an influence to the mechanical properties,and thus affecting the mechanical behavior of MV.In consequence,some of the patients need MV replacement or repair to restore the normal function of MV.The important point for succeeding such a medical treatment depends on the technique,design,and material used in the treatment shall help rebuild the normal mechanical environment and behavior of MV.Therefore,the mechanical and materials characteristics of MV become a magnetism to explore.In this study,we present an integrated experimental and mathematical constitutive study base in collagen distribution aiming at the mechanical property differences in various region on MV.Methods and materials Both the size and composition of porcine valves are similar to human’s,so the porcine heart valve is often being used in experimental research.Mitral valve was isolated from fresh eight porcine hearts(250-500 gr),and perfused in PBS solution to maintain moist.Anterior and posterior leaflets were separated and dissected into 4 part(two 8~*8 mm rough zone and two clear zone samples)and 2 part(8~*8 mm belly and edge of the clear zone)respectively.Tracking markers(glass bean)were stickled on specimen with superglue(cyanoacrylate adhesive).Then,the specimen was mounted onto biaxial tester machine(CeIIScale,Biotester),and the tests are run by force control.During mechanical test,the specimen is immersed into PBS solution in physiological temperature(37℃).Every test procedure contains 8 preconditioning cycles and 8 loading cycles.The mechanical behavior was determined from the relationship between first Piola-Kirchoff stress and stretch.Constitutive model was reconstructed and material parameters were fitted from biaxial tensile result.Histological analyses were performed in the specimen before and after test.First,a piece of the specimen was cut and immersed in fixation solution(4%paraformaldehyde),then it was dehydrated in graded alcohol solution,and next embedding in paraffin wax block.Paraffin block was then cut and stained with VVG and Picro-sirius red.The collagen fibril orientation was observed from those histological results.Results The experimental results of the clear zone of MV’s first Piola-Kirchhoff stress and stretch curve are similar to those of the recent study from others,while result of the rough zone shows a different trend.This can be explained by differences in collagen distribution between clear zone and rough zone of MV.Our result thus allows for a refinement of computational models for more accurately predicting MV condition,where tissue heterogeneity plays an important role in the MV function.
基金funded by the National Natural Science Foundation of China ( 31660258, 31771014,31860262,11762006)the Science and Technology Foundation of Guizhou Province ( 2019-2787,2018-1412, 2016-5676,2017-5718)+2 种基金the Science and Technology Innovative Talent Team of Guizhou Province ( 2015-4021)the 2011 Collaborative Innovation Program of Guizhou Province ( 2015-04 )the Cell and Gene Engineering Innovative Research Groups of Guizhou Province ( KY-2016-031)
文摘Objective Fumonisin B1(FB1)is an important mycotoxin in nature worldwide.The biomechanical properties of cells are closely related to their structure and function,and the cytoskeleton is the structural and functional basis of cells motility,and therefore,from a biomechanical point of view,the purpose of this study is to investigate the effects of FB1 on the biomechanical properties,migration capacity and cytoskeletal structure of human umbilical vein endothelial cells(HUVECs),which may lay an experimental foundation for further exploration of the toxicity mechanism of fumonisin.Methods HUVECs were cultured and treated with different concentrations of FB1.Then,CCK-8 kit was used to detect the effect of FB1 on the survival rate.The osmotic fragility of the cells was measured after treatment with different osmotic pressures for30 min.The cell membrane fluidity was measured by fluorescence polarization method.The cell electrophoretic mobility was measured by cell electrophoretic apparatus.The migration capacity of the cells was observed by scratch repair assay.The changes of reactive oxygen species and cytoskeletal structure were observed by confocal laser scanning microscopy.Finally,the mRNA and protein relative expression levels of cytoskeletal binding proteins were detected by real-time PCR,Western blotting and confocal laser scanning.Results The results of CCK-8 showed that FB1 could significantly inhibit the proliferation of HUVECs in a dose-and time-dependent manner.After treatment of HUVECs with FB1,the hypotonic resistance of the cell,cell surface charge,cell membrane fluidity and migration capacity were all weakened,while reactive oxygen species were significantly increased and the cytoskeletal structure was significantly reorganized.Furthermore,RTPCR results showed that the mRNA relative expression levels of cytoskeletal binding proteins,exception of actin,were down-regulated after treated with FB1.Besides,Western blotting and statistical analysis based on fluorescence intensity of laser confocal microscopy confirmed theses changes in protein level.Conclusions FB1 can significantly affect the biomechanical properties and motility of HUVECs,which may be directly correlated to the remodel of F-actin cytoskeleton,as well as the relative expression changes of cytoskeletal binding proteins.It is significant for further exploring the toxicity mechanism of fumonisin.
文摘To explore the response law of non-lethal large-size kinetic energy projectiles to blunt attack on skin tissue,and to evaluate the skin injury characteristics of the attacked personnel and the use safety of kinetic energy projectiles.Based on the LS-DYNA simulation software,a three-layer skin simulation model and a Flash-Ball rubber bullet model are established,and the force-time and deformation-time biomechanical corridors of the Flash-Ball rubber bullet impacting human skin tissue are obtained.The corridor curve and the energy transfer and diffusion are analyzed and compared.The safety evaluation of the damage caused by the rubber bullet shooting a human body at different distances is carried out using the empirical formula of the penetration limit.Finally,the safe shooting distance is obtained.The results show that the model used in the simulation has a good correlation with the experimental data,its biomechanical corridor characteristics are different from those of conventional vehicle impact and smallsize projectile response characteristics.The energy transfer and action time of medium and low-speed impact may cause greater damage.The fat layer is the largest energy absorption unit.The minimum safe shooting distance to ensure skin tissue from penetrating damage is 15.8 m,and the limit specific kinetic energy of skin damage is 7.88 J/cm^(2).This study can be extended to the study of biomechanical response law and safety evaluation under the impact of the same type of large kinetic energy projectile,which provides an important theoretical reference for the police to use large kinetic energy projectiles to conduct safe shooting in peacekeeping operations.
基金financially supported by the National Natural Science Foundation of China ( 11522219, 11532009)the Projects of International ( Regional) Cooperation and Exchanges of NSFC ( 11761161004)+3 种基金the Natural Science Basic Research Plan in Shaanxi Province of China ( 2017JM1026,2017JM8097)the National Project Cultivating Foundation of Xi’an Medical University ( 2017GJFY23)Young Talent Support Plan of Shaanxi Provincethe China Postdoctoral Science Foundation ( 2018M631141,2018M631173)
文摘Introduction Neurons are situated in a microenvironment composed of various biochemical and biophysical cues,where stretching is thought to have a major impact on neurons.For instance,during a moderate traumatic brain impact,the injury region in axons exhibits significant longitudinal strain;and in a rat model of spinal cord injury,the most severe axonal injury is located in the largest strain region.Stretching may result in microstructural changes in neural tissue and further leading to abnormal electrophysiological function.Hence,it is of great importance to understand the coupled mechanoelectricalbehaviors of neurons under stretching.In spite of significant experimental efforts,the underlying mechanism remains elusive,more works are needed to provide a detailed description of the process that leads to the observed phenomena.Mathematical modeling is a powerful tool that offers a quantitative description of the underlying mechanism of an observed biological phenomenon,including mechanical and electrophysiological behaviors of neurons.Thus,we developed a mechanoelectrical coupling model of neurons under stretching in this study.Mathematical model The mathematical model consists of three submodels,i.e.,the mechanical submodel,the mechanoelectrical coupling submodel and the electrophysiological submodel.The mechanical submodel deals with the relationship between stretching and the deformation of axons,which has specially considered the plastic deformation of axons.The electrophysiological submodel characterizes the feature of neuronal action potential(AP),which is based on the classical H-H model and the cable theory.The mechanoelectrical coupling submodel links the mechanical and electrophysiological submodels through strain-induced equivalent circuit parameter alteration and ion channel injury.Besides,we have discussed a more general deformation condition,where an expanded model coupling the axonal deformation and electrophysiology alteration was explored.As the most essential parameters in an electrophysiological assessment,the amplitude of the AP,the neuronal firing frequency and the electrophysiological signal conduction velocity,which could be affected by stretching,were used as outputs of the model.Results&discussion To understand the mechanoelectrical coupling of neurons under stretching,we developed a mechanoelectrical coupling model.To verify the model,we simulated a slow stretching on an axon following the experimental study in the literature,we observed that as the strain increases,the peak AP declines faster,which is consistent with the experimental data.Moreover,the reduced AP cannot be restored to the original peak,implying that the damage is irreversible.The simulation results also predict that strain induces a more frequent neuronal firing and a faster conduction.In a realistic situation,in addition to stretching,the loading condition is very complicated,which may induce complex axonal deformation(e.g., necking and swelling along the axons).We also simulated such necking deformation impairment and observed that the AP amplitude decreases at the necking region and recovers after that,indicating a blockage of the AP;and the conduction velocity decreases with the increase in deformation degree.Conclusions In this study,we developed a mechanoelectrical coupling model of neurons under stretching with consideration of axonal plastic deformation.With the model,we found that the effect of mechanical loading on electrophysiology mainly manifests as decreased membrane AP amplitude,a more frequent neuronal firing and a faster electrophysiological signal conduction.The model predicts not only stretch-induced injury but also a more gene ral necking deformation case,which may someday be revealed in future by experiments,providing a reference for the prediction and regulation of neuronal function under mechanical loadings.
基金funded by the National Natural Science Foundation of China ( 31660258,31771014, 31860262,11762006)the Science and Technology Foundation of Guizhou Province ( 2019-2787,2018-1412,2016-5676, 2017-5718)+2 种基金the Science and Technology Innovative Talent Team of Guizhou Province ( 2015-4021)the 2011 Collaborative Innovation Program of Guizhou Province ( 2015-04)the Cell and Gene Engineering Innovative Research Groups of Guizhou Province ( KY-2016-031)
文摘Dendritic cells(DCs)are the most important antigen-presenting cells due to their professional and extremely efficient antigen-presenting function.In view of their exceptional ability to present antigen and to interact with T cells,DC play distinct roles in linking innate and adaptive immune responses and thus become logical targets for cancer immunotherapy.Evidences show that tumor-derived cytokines could impair DCs’biomechanics properties,which lead to inefficacy of DCs-based immune therapies.Our previous studies found that IL-10,as one of the widespread suppressive cytokines from tumor microenvironment(TME),could deteriorate DCs’motility and biomechanics properties while the underlying mechanism is unknown.In this study,CD14+monocytes were induced to differentiate into mature dendritic cells after isolation in vitro using recombinant cytokines IL-4,GM-CSF,LPS,and IFN-γ.And we also have compared the proteomic changes of mDCs treated by IL-10 and control group via two-dimensional electrophoresis combine with MALDI-TOF/TOF MS.Then we analyzed the function of differentially expressed proteins through bioinformatics methods include GO analysis that clarified the biological functions of differential proteins and KEGG analysis which enriched signal pathways of differential proteins to explore the molecular mechanism of IL-10 which has inhibitory effect on mDCs.The results showed that IL-10 significantly affected the morphology of mDCs,especially reducing the number and length of filopodia.Different expressed proteins were analyzed by two-dimensional electrophoresis combined with bioinformatics analysis to enrich for glycolytic signaling pathway,HIF-1 signaling pathway and cytoskeletal binding protein expression changes.The results of two-dimensional electrophoresis were verified by Western blot,and the results showed that the data were reliable.In addition,the intracellular ROS levels were significantly higher in mDCs treated with IL-10,validating the previously enriched HIF-1 signaling pathway.In summary,it indicated that IL-10 may interfered with the oxidative metabolic process,glycolytic metabolism,and expression of cytoskeleton-related proteins in mDCs,and disturbances in these physiological processes resulted in reduced biomechanics properties and motility of mDCs and subsequently impaired their immune functions,making DC-based tumor vaccines less effective than which we desired.Our study reveals alterations in the physiological metabolism of mDCs under IL-10 treatment from the proteome,which lays the foundation for further exploration of the altered state of mDCs in the tumor microenvironment.
基金the auspices of the Royal British Legion Centre for Blast Injury Studies at Imperial College Londonthe financial support of the Royal British Legion。
文摘Heterotopic ossification(HO)is a consequence of traumatic bone and tissue damage,which occurs in 65%of military casualties with blast-associated amputations.However,the mechanisms behind blast-induced HO remain unclear.Animal models are used to study blast-induced HO,but developing such models is challenging,particularly in how to use a pure blast wave(primary blast)to induce limb fracture that then requires an amputation.Several studies,including our recent study,have developed platforms to induce limb fractures in rats with blast loading or a mixture of blast and impact loading.However,these models are limited by the survivability of the animal and repeatability of the model.In this study,we developed an improved platform,aiming to improve the animal's survivability and injury repeatability as well as focusing on primary blast only.The platform exposed only one limb of the rat to a blast wave while providing proper protection to the rest of the rat's body.We obtained very consistent fracture outcome in the tibia(location and pattern)in cadaveric rats with a large range of size and weight.Importantly,the rats did not obviously move during the test,where movement is a potential cause of uncontrolled injury.We further conducted parametric studies by varying the features of the design of the platform.These factors,such as how the limb is fixed and how the cavity through which the limb is placed is sealed,significantly affect the resulting injury.This platform and test setups enable well-controlled limb fracture induced directly by pure blast wave,which is the fundamental step towards a complete in vivo animal model for blast-induced HO induced by primary blast alone,excluding secondary and tertiary blast injury.In addition,the platform design and the findings presented here,particularly regarding the proper protection of the animal,have implications for future studies investigating localized blast injuries,such as blast induced brain and lung injuries.
基金the Portuguese Army,through CINAMIL,within project ELITE2-Enhancement LITe ExoskeletonFoundation for Science and Technology (FCT),through IDMEC,under LAETA,project UIDB/50022/2020 for supporting this research。
文摘Modern conflicts demand substantial physical and psychological exertion,often resulting in fatigue and diminished combat or operational readiness.Several exoskeletons have been developed recently to address these challenges,presenting various limitations that affect their operational or everyday usability.This article evaluates the performance of a dual-purpose passive ankle exoskeleton developed for the reduction of metabolic costs during walking,seeking to identify a force element that could be applied to the target population.Based on the 6-min walk test,twenty-nine subjects participated in the study using three different force elements.The results indicate that it is possible to reduce metabolic expenditure while using the developed exoskeleton.Additionally,the comfort and range of motion results verify the exoskeleton's suitability for use in uneven terrain and during extended periods.Nevertheless,the choice of the force element should be tailored to each user,and the control system should be adjustable to optimise the exoskeleton's performance.
