3D printing techniques offer an effective method in fabricating complex radially multi-material structures.However,it is challenging for complex and delicate radially multi-material model geometries without supporting...3D printing techniques offer an effective method in fabricating complex radially multi-material structures.However,it is challenging for complex and delicate radially multi-material model geometries without supporting structures,such as tissue vessels and tubular graft,among others.In this work,we tackle these challenges by developing a polar digital light processing technique which uses a rod as the printing platform.The 3D model fabrication is accomplished through line projection.The rotation and translation of the rod are synchronized to project and illuminate the photosensitive material volume.By controlling the distance between the rod and the printing window,we achieved the printing of tubular structures with a minimum wall thickness as thin as 50 micrometers.By controlling the width of fine slits at the printing window,we achieved the printing of structures with a minimum feature size of 10 micrometers.Our process accomplished the fabrication of thin-walled tubular graft structure with a thickness of only 100 micrometers and lengths of several centimeters within a timeframe of just 100 s.Additionally,it enables the printing of axial multi-material structures,thereby achieving adjustable mechanical strength.This method is conducive to rapid customization of tubular grafts and the manufacturing of tubular components in fields such as dentistry,aerospace,and more.展开更多
Pseudorabies(PR)is an acute infectious disease of pigs caused by the PR virus(PRV)and results in great economic losses to the pig industry worldwide.PRV glycoprotein E(gE)-based enzyme-linked immunosorbent assay(ELISA...Pseudorabies(PR)is an acute infectious disease of pigs caused by the PR virus(PRV)and results in great economic losses to the pig industry worldwide.PRV glycoprotein E(gE)-based enzyme-linked immunosorbent assay(ELISA)has been used to distinguish gE-deleted vaccine-immunized pigs from wild-type virus-infected pigs to eradicate PR in some countries.Nanobody has the advantages of small size and easy genetic engineering and has been a promising diagnostic reagent.However,there were few reports about developing nanobody-based ELISA for detecting anti-PRV-gE antibodies.In the present study,the recombinant PRV-gE was expressed with a bacterial system and used to immunize the Bactrian camel.Then,two nanobodies against PRV-gE were screened from the immunized camel by phage display technique.Subsequently,two nanobody-HRP fusion proteins were expressed with HEK293T cells.The PRV-gE-Nb36-HRP fusion protein was selected as the probe for developing the blocking ELISA(bELISA)to detect anti-PRV-gE antibodies.Through optimizing the conditions of bELISA,the amount of coated antigen was 200 ng per well,and dilutions of the fusion protein and tested pig sera were separately 1:320 and 1:5.The cut-off value of bELISA was 24.20%,and the sensitivity and specificity were 96.43 and 92.63%,respectively.By detecting 233 clinical pig sera with the developed bELISA and a commercial kit,the results showed that the coincidence rate of two assays was 93.99%.Additionallly,epitope mapping showed that PRV-gE-Nb36 recognized a conserved conformational epitope in different reference PRV strains.Simple,great stability and low-cost nanobody-based bELISA for detecting anti-PRV-gE antibodies were developed.The bELISA could be used for monitoring and eradicating PR.展开更多
In offshore engineering design, it is considerably significant to have an adequately accurate estimation of marine environmental parameters, in particular, the extreme wind speed of tropical cyclone （TC） with differ...In offshore engineering design, it is considerably significant to have an adequately accurate estimation of marine environmental parameters, in particular, the extreme wind speed of tropical cyclone （TC） with different return periods to guarantee the safety in projected operating life period. Based on the 71-year （1945-2015） TC data in the Northwest Pacific （NWP） by the Joint Typhoon Warning Center （JTWC） of US, a notable growth of the TC intensity is observed in the context of climate change. The fact implies that the traditional stationary model might be incapable of predicting parameters in the extreme events. Therefore, a non-stationary model is proposed in this study to estimate extreme wind speed in the South China Sea （SCS） and NWP. We find that the extreme wind speeds of different return periods exhibit an evident enhancement trend, for instance, the extreme wind speeds with different return periods by non- stationary model are 4.1%-4.4% higher than stationary ones in SCS. Also, the spatial distribution of extreme wind speed in NWP has been examined with the same methodology by dividing the west sea areas of the NWP 0°-45°N, 105°E-130°E into 45 subareas of 5° × 5°, where oil and gas resources are abundant. Similarly, remarkable spacial in-homogeneity in the extreme wind speed is seen in this area： the extreme wind speed with 50-year return period in the subarea （15°N-20°N, 115°E-120°E） of Zhongsha and Dongsha Islands is 73.8 m/s, while that in the subarea of Yellow Sea （30°N-35°N, 120°E-125°E） is only 47.1 m/s. As a result, the present study demonstrates that non-stationary and in-homogeneous effects should be taken into consideration in the estimation of extreme wind speed.展开更多
Primary cilium is an antenna-like and non-motile structure protruding from the apical surface of most mammalian cells including endothelial cells lining the inner side of all the blood vessels in our body.Although it ...Primary cilium is an antenna-like and non-motile structure protruding from the apical surface of most mammalian cells including endothelial cells lining the inner side of all the blood vessels in our body.Although it has been over a century since primary cilia were discovered,the investigation about their mechano-sensing and other roles in maintaining normal functions of cardiovascular system has just started in recent years.This focused review aims to give an update about the current literature for the role of endothelial primary cilia in blood flow mechanosensing and shear stress-shielding.To do this,we first summarized the characteristic features of endothelial primary cilia in terms of structure,dimension,molecular composition,and mechanical properties(e.g.,bending rigidity),which are the dominant factors for their functions in mechano-sensing and transduction,as well as vascular protection from the blood flow-induced wall shear stress.We also described the experimental techniques and mathematical models for determining the dimension and mechanical properties of the primary cilium.Then we reviewed the molecular mechanisms underlying mechano-sensing and transduction by endothelial primary cilia and the mathematical model prediction for their roles in redistribution and reduction of wall shear stresses.Finally,we briefly discussed the common cardiovascular diseases,e.g.,atherosclerosis,hypertension,and aneurysm,due to defects and malfunction of endothelial primary cilia and suggested potential targets for therapeutic treatments.展开更多
Introduction Primary cilium is a non-motile microstructure,protruding from cell surface of most mammalian cells.It was previously thought to be vestigial.However,recent studies indicate that it may serve as one of the...Introduction Primary cilium is a non-motile microstructure,protruding from cell surface of most mammalian cells.It was previously thought to be vestigial.However,recent studies indicate that it may serve as one of the most vital mechanosensors for many types of cells such as epithelial and endothelial cells and osteocytes.Protruding from the apical membrane,the primary cilium can directly sense subtle variation of mechanical forces exerted on the cell and then transduce the mechanical cues into biochemical signals into the cell,although the mechanism remain elusive.Vascular endothelial cells(ECs)lining the inner wall of our blood vessels are continuously exposed to the blood flow.In order to maintain proper functions for the cardiovascular system,ECs should have a variety of mechano-sensors and transducers to sense the blood flow change and adjust the vessel size and transport across the vessel wall accordingly.Among more than a dozen recognized EC mechano-sensors,the primary cilium has drawn more and more attention recently.Primary cilium on endothelial cells is essential for the homeostasis of vessels.It is reported to be prevalent in areas of disturbed flow where atherosclerosis and intracranial aneurysm usually occur.Deficiencies of primary cilia may promote atherosclerosis,endothelial-to-mesenchymal transition(EndoMT)and loss of direction orientation,to name a few.Therefore understanding why the primary cilia are necessary to maintain the homeostasis of blood vessels and how will help us develop better treatment strategies for the common cardiovascular diseases.Dimension and structure of primary cilium Primary cilium is reported to be shorter than 8 in length and about 0.2 in diameter.The length of primary cilium varies in different cell types and under different conditions.The major structural components of the primary cilium include basal body,ciliary axoneme(consisting of nine doublet microtubules),ciliary membrane,transition zone,basal feet,and striated rootlets.Each part of the primary cilium is essential and has specific function.Current methods investigating the EC primary cilium as a mechano-sensor:Immunostaining and imaging techniques have been used to investigate the molecular mechanisms by which EC primary cilium serves as a mechano-sensor and transducer.It has been found that various proteins locate on the primary cilium,working together to maintain the function of primary cilium.Some proteins function as ion-channels,mediating Ca2+entry into the primary cilium.Some are involved in the cascade signal pathway.Others are related to the assembly and maintenance of primary cilium.Briefly,the flow induces the deflection of the EC primary cilium,which triggers calcium increase via opening of the PC2 cation channel that is responsible for calcium ion influx.This PC2 cation channel is localized to the primary cilium and is assumed to be stretch-activated.The resulting change in the intracellular calcium concentration then regulates numerous molecular activities inside the cell that contribute to vessel homeostasis.In addition to triggering calcium release,another mechanism has also been found in blood-pressure maintenance in the vasculature,where the vessel diameter is regulated by endothelial primary cilia through adjusting nitric oxide production.So far,little is known about the mechanical mechanism behind this deflection-triggered o-pening of signaling pathways.For example,what is the flow induced bending behavior and force distribution? What is the threshold value of stretch/defection for activating a corresponding signaling pathway? These all remain to be answered.In combination of image data and experiments,several computational models have been established to answer these questions.However,the current models are not able to include the complex structure of primary cilium and the model predictions are limited.Future studies With the development of super high resolution optical microscopy,more detailed images for the structural(molecular)components of EC primary cilia will be revealed,especially when the ECs are alive and the forces are known.Combining these experimental observations with more sophisticated mathematical models will elucidate the mechano-sensing mechanism of EC primary cilia,as the force and stress distribution on cilium along with other mechanical properties are still beyond the capability of experimental approaches due to the scales of the quantities involved.By using numerical approaches,much more detailed dynamic information can be obtained.展开更多
Background:Port-wine stain(PWS)has been classified not as the hyperplasia of cells,but rather,as an expansion of malformed vessels.However,previous studies have reported upregulated expression of proangiogenic factors...Background:Port-wine stain(PWS)has been classified not as the hyperplasia of cells,but rather,as an expansion of malformed vessels.However,previous studies have reported upregulated expression of proangiogenic factors in PWS.Several studies have indicated that the pathology exhibits proliferation of numerous endothelial cells in hypertrophic/nodular PWS.This study aimed to determine the expression of vascular epithelial growth factor(VEGF),matrix metalloproteinase-9(MMP-9),angiopoietin-2(ANG-2),and basic fibroblast growth factor(bFGF)in hypertrophic PWS.Methods:Immunohistochemistry was used to analyze skin samples from 33 patients with hypertrophic PWS.Expression levels of VEGF,MMP-9,ANG-2,and bFGF in hypertrophic PWS were determined by multiplying the intensity by the percentage of immunoreactive cells.Immunoreactivity scores were classified as follows:negative(0),low(1),moderate(2,3,and 4),or high(6).Results:Based on pathological characteristics,hypertrophic PWS was divided into vascular malformation and pyogenic granuloma(PG)types.VEGF,MMP-9,ANG-2,and bFGF were significantly activated in the blood vessels of PG-type PWS samples compared with their counterparts in blood vessels of vascular malformation-type PWS samples and controls.PG-type hypertrophic PWS,which exhibited proliferation of endothelial cells,showed the strongest activation.Conclusion:The exuberant proliferation of endothelial cells in PG-type hypertrophic PWS may be associated with the regulation of proangiogenic factors during development.These proangiogenic factors that function in the angiogenesis and proliferation of endothelial cells may play an important role in the pathogenesis and progression of PWS.Furthermore,these factors may be dynamic and behave differently in various types of hypertrophic PWS.展开更多
High-purity(HP)magnesium(Mg)has emerged as a promising biomaterial for supporting functional bone tissue.Our previous study found that mechanical stresses and the surrounding fibrotic tissue(subcuta-neous)both play cr...High-purity(HP)magnesium(Mg)has emerged as a promising biomaterial for supporting functional bone tissue.Our previous study found that mechanical stresses and the surrounding fibrotic tissue(subcuta-neous)both play crucial roles in the degradation of HP Mg.However,due to challenges in the degradation and regeneration process in vivo,it remains unclear how stress affects HP Mg degradation in bone en-vironments,limiting its further application.In this study,novel loading devices were designed and the effects of tensile and compressive stresses on HP Mg degradation in vivo and in vitro bone environments were quantitatively analyzed.In addition,bone osteointegration around HP Mg was explored preliminar-ily.Tensile stress increases the degradation rate of HP Mg in vivo and in vitro.HP Mg degradation in vivo is more sensitive to stress factors than in vitro,but the sensitivity decreases with corrosion time.The volume loss rate of HP Mg is multilinear with the applied stress and degradation time.The volume of bone tissue surrounding HP Mg is larger in the no-stress group compared to the stressed groups,which is more pronounced with increasing implantation time.These results provide valuable insights for optimiz-ing the design of HP Mg-based implants considering load conditions.This will help to achieve a balance between the degradation rate of the implant and the regeneration rate of the surrounding bone.展开更多
Osteoblasts are mechanosensitive cells.Tensile stress with different conditions,including loading time,frequency,magnitude,etc.would cause varied responses in osteoblasts.However,it was not clarified that the effect o...Osteoblasts are mechanosensitive cells.Tensile stress with different conditions,including loading time,frequency,magnitude,etc.would cause varied responses in osteoblasts.However,it was not clarified that the effect of the loading types on the osteoblasts.In this study,we focused on the effect of varied tensile stress types on osteoblasts,including isotropic stretch,biaxial stretch,and uniaxial stretch with the negative ratio of transverse strain to axial strain(NR)-1,0,and 0.2 respectively.Cell proliferation was determined to be most efficient when stimulated by 6%strain at a frequency of 1 Hz and a negative value of 0 for 1 h/day.The varied strain resulted in a thickening of the F-actin cytoskeleton and a thinning of the nucleus.Nuclear flattening caused Yes-associated protein(YAP)to be transported to the nucleus.It was suggested that the influence of loading types on the mechanobiology responses must be noticed.The mechanism of cell mechanical sensitivity under varied loading types was explored,which would provide good sugges-tions for designing microstructures to control deformation patterns in bone tissue engineering.展开更多
In this paper,two types of fractional nonlinear equations in Caputo sense,time-fractional Newell–Whitehead equation(FNWE)and time-fractional generalized Hirota–Satsuma coupled KdV system(HS-cKdVS),are investigated b...In this paper,two types of fractional nonlinear equations in Caputo sense,time-fractional Newell–Whitehead equation(FNWE)and time-fractional generalized Hirota–Satsuma coupled KdV system(HS-cKdVS),are investigated by means of the q-homotopy analysis method(q-HAM).The approximate solutions of the proposed equations are constructed in the form of a convergent series and are compared with the corresponding exact solutions.Due to the presence of the auxiliary parameter h in this method,just a few terms of the series solution are required in order to obtain better approximation.For the sake of visualization,the numerical results obtained in this paper are graphically displayed with the help of Maple.展开更多
Background:Mg alloys have attractive properties,including biocompatibility,biodegradability,and ideal mechanical properties.Moreover,Mg alloys are regarded as one of the promising candidates for manufacturing ureteral...Background:Mg alloys have attractive properties,including biocompatibility,biodegradability,and ideal mechanical properties.Moreover,Mg alloys are regarded as one of the promising candidates for manufacturing ureteral stents.This study proposed a multi-objective optimization method based on the Kriging surrogate model,NSGA-III,and finite element analysis to improve the degradation performance of Mg alloy ureteral stents.Methods:The finite element model for the degradation of Mg alloy ureteral stents has been established to compare the degradation performance of the stents under different parameters.Latin hypercube sampling was adopted to generate train sample points in the design space.Meanwhile,the Kriging surrogate model was constructed between strut parameters and stent degradation behavior.The NSGA-III was utilized to determine the optimal solution in the global design space.Results:The optimized stent achieved 5.52degradation uniformity(M),10degradation time(DT),and 4work time(FT).The errors between the Kriging surrogate model and the finite element calculation results were less than 6%.Conclusion:The optimized stent achieved better degradation performance.The degradation behavior of stents was dependent on the design parameters.The multi-objective optimization method based on the Kriging surrogate model and finite element analysis was effective in stent design optimization problems.展开更多
Accurately characterizing the liver's mechanical properties is of paramount importance for disease diagnosis,treatment,surgical prosthetic modeling,and impact injury dummies.However,due to its inherent biological ...Accurately characterizing the liver's mechanical properties is of paramount importance for disease diagnosis,treatment,surgical prosthetic modeling,and impact injury dummies.However,due to its inherent biological soft tissue nature,the characterization of mechanical behavior varies across testing methods and sample types.In this study,we employed transmission electron microscope and Micro CT to observe the morphology of the marginal and center of rat livers and conducted macroscopic mechanical tests to characterize their elasticity and viscoelasticity.The results revealed that the central region displayed higher metabolic levels,elongated mitochondria,and an abundance of rough endoplasmic reticulum at the microscale.At the mesoscale,larger diameter portal veins were mainly distributed in the central region,while smaller diameter arteries were predominantly located at the periphery.At the macroscale,under a strain rate of 0.0167 s^(-1),no significant differences were observed in the elastic properties between the two regions.However,as the strain rate increased up to 0.167 s^(-1),the central region displayed higher porosity,resulting in reduced liquid loss,increased hardness,and higher viscosity compared to the periphery.Consequently,the liver demonstrated overall heterogeneity,with isotropic models suitable for the peripheral region,while more intricate models may be required to capture the complexity of the central region with its intricate vasculature.展开更多
Poly(glycerol-dodecanoate)(PGD)has aroused increasing attention in biomedical engineering for its degradability,shape memory and rubber-like mechanical properties,giving it potential to fabricate intelligent implants ...Poly(glycerol-dodecanoate)(PGD)has aroused increasing attention in biomedical engineering for its degradability,shape memory and rubber-like mechanical properties,giving it potential to fabricate intelligent implants for soft tissues.Adjustable degradation is important for biodegradable implants and is affected by various factors.The mechanical load has been shown to play an important role in regulating polymer degradation in vivo.An in-depth investigation of PGD degradation under mechanical load is essential for adjusting its degradation behavior after implantation,further guiding to regulate degradation behavior of soft tissue implants made by PGD.In vitro degradation of PGD under different compressive and tensile load has proceeded in this study and describes the relationships by empirical equations.Based on the equations,a continuum damage model is designed to simulate surface erosion degradation of PGD under stress through finite element analysis,which provides a protocol for PGD implants with different geometric structures at varied mechanical conditions and provides solutions for predicting in vivo degradation processes,stress distribution during degradation and optimization of the loaded drug release.展开更多
The mechanical properties of biological soft tissues are inextricably linked to the field of health care,and their mechanical properties can be important indicators for diagnosing and detecting diseases;they can also ...The mechanical properties of biological soft tissues are inextricably linked to the field of health care,and their mechanical properties can be important indicators for diagnosing and detecting diseases;they can also be used to analyze the causes of organ diseases from a pathological point of view and thus guide the deployment of medical solutions.As an effective method to characterize the mechanical properties of materials,mechanical loading experiments have been successfully applied to the mechanical properties of materials,including tension,compression,pure shear,and so on.Under quasi-static loading,when the material is a biological soft tissue material between a solid and an ideal fluid,its viscoelastic properties strongly respond to the force stimulus,and the stress-strain-time in the elastic phase will have obvious disturbance characteristics.Therefore,the existing statistical methods are often difficult to quantitatively describe the mechanical properties of materials.Therefore,this study proposes an Interval Capture Point based on the principle of integration.The experimental data based on this method can characterize its nonlinear mechanical properties well,especially when the loading speed is extremely low and the soft materials show strong disturbance characteristics.The proposed method can still accurately characterize the hyperelastic and viscoelastic properties of the mechanical properties of biological soft tissues under quasi-static loading.展开更多
基金supported financially by the Fundamental Research Funds for the Central Universities (YWF-22-K-101,YWF-23-L-805 and YWF-23-YG-QB-006)the support from the National Natural Science Foundation of China (12372106)Fundamental Research Funds for the Central Universities
文摘3D printing techniques offer an effective method in fabricating complex radially multi-material structures.However,it is challenging for complex and delicate radially multi-material model geometries without supporting structures,such as tissue vessels and tubular graft,among others.In this work,we tackle these challenges by developing a polar digital light processing technique which uses a rod as the printing platform.The 3D model fabrication is accomplished through line projection.The rotation and translation of the rod are synchronized to project and illuminate the photosensitive material volume.By controlling the distance between the rod and the printing window,we achieved the printing of tubular structures with a minimum wall thickness as thin as 50 micrometers.By controlling the width of fine slits at the printing window,we achieved the printing of structures with a minimum feature size of 10 micrometers.Our process accomplished the fabrication of thin-walled tubular graft structure with a thickness of only 100 micrometers and lengths of several centimeters within a timeframe of just 100 s.Additionally,it enables the printing of axial multi-material structures,thereby achieving adjustable mechanical strength.This method is conducive to rapid customization of tubular grafts and the manufacturing of tubular components in fields such as dentistry,aerospace,and more.
基金supported by the National Natural Science Foundation of China(32273041)the Key R&D Program of Shaanxi Province,China(2022NY-104)the Natural Science Foundation of Shaanxi Province,China(2022JC-12)。
文摘Pseudorabies(PR)is an acute infectious disease of pigs caused by the PR virus(PRV)and results in great economic losses to the pig industry worldwide.PRV glycoprotein E(gE)-based enzyme-linked immunosorbent assay(ELISA)has been used to distinguish gE-deleted vaccine-immunized pigs from wild-type virus-infected pigs to eradicate PR in some countries.Nanobody has the advantages of small size and easy genetic engineering and has been a promising diagnostic reagent.However,there were few reports about developing nanobody-based ELISA for detecting anti-PRV-gE antibodies.In the present study,the recombinant PRV-gE was expressed with a bacterial system and used to immunize the Bactrian camel.Then,two nanobodies against PRV-gE were screened from the immunized camel by phage display technique.Subsequently,two nanobody-HRP fusion proteins were expressed with HEK293T cells.The PRV-gE-Nb36-HRP fusion protein was selected as the probe for developing the blocking ELISA(bELISA)to detect anti-PRV-gE antibodies.Through optimizing the conditions of bELISA,the amount of coated antigen was 200 ng per well,and dilutions of the fusion protein and tested pig sera were separately 1:320 and 1:5.The cut-off value of bELISA was 24.20%,and the sensitivity and specificity were 96.43 and 92.63%,respectively.By detecting 233 clinical pig sera with the developed bELISA and a commercial kit,the results showed that the coincidence rate of two assays was 93.99%.Additionallly,epitope mapping showed that PRV-gE-Nb36 recognized a conserved conformational epitope in different reference PRV strains.Simple,great stability and low-cost nanobody-based bELISA for detecting anti-PRV-gE antibodies were developed.The bELISA could be used for monitoring and eradicating PR.
基金financially supported by the Ministry of Science and Technology(863 program)(2006AA09A103-4)the National Natural Science Foundation of China(11232012)the Chinese Academy of Sciences(CAS)knowledge innovation program(KJCXYW-L02)
文摘In offshore engineering design, it is considerably significant to have an adequately accurate estimation of marine environmental parameters, in particular, the extreme wind speed of tropical cyclone （TC） with different return periods to guarantee the safety in projected operating life period. Based on the 71-year （1945-2015） TC data in the Northwest Pacific （NWP） by the Joint Typhoon Warning Center （JTWC） of US, a notable growth of the TC intensity is observed in the context of climate change. The fact implies that the traditional stationary model might be incapable of predicting parameters in the extreme events. Therefore, a non-stationary model is proposed in this study to estimate extreme wind speed in the South China Sea （SCS） and NWP. We find that the extreme wind speeds of different return periods exhibit an evident enhancement trend, for instance, the extreme wind speeds with different return periods by non- stationary model are 4.1%-4.4% higher than stationary ones in SCS. Also, the spatial distribution of extreme wind speed in NWP has been examined with the same methodology by dividing the west sea areas of the NWP 0°-45°N, 105°E-130°E into 45 subareas of 5° × 5°, where oil and gas resources are abundant. Similarly, remarkable spacial in-homogeneity in the extreme wind speed is seen in this area： the extreme wind speed with 50-year return period in the subarea （15°N-20°N, 115°E-120°E） of Zhongsha and Dongsha Islands is 73.8 m/s, while that in the subarea of Yellow Sea （30°N-35°N, 120°E-125°E） is only 47.1 m/s. As a result, the present study demonstrates that non-stationary and in-homogeneous effects should be taken into consideration in the estimation of extreme wind speed.
基金Grants(11421202,11572029)from National Natural Science Foundation of ChinaNIH 1UG3UH3TR002151.
文摘Primary cilium is an antenna-like and non-motile structure protruding from the apical surface of most mammalian cells including endothelial cells lining the inner side of all the blood vessels in our body.Although it has been over a century since primary cilia were discovered,the investigation about their mechano-sensing and other roles in maintaining normal functions of cardiovascular system has just started in recent years.This focused review aims to give an update about the current literature for the role of endothelial primary cilia in blood flow mechanosensing and shear stress-shielding.To do this,we first summarized the characteristic features of endothelial primary cilia in terms of structure,dimension,molecular composition,and mechanical properties(e.g.,bending rigidity),which are the dominant factors for their functions in mechano-sensing and transduction,as well as vascular protection from the blood flow-induced wall shear stress.We also described the experimental techniques and mathematical models for determining the dimension and mechanical properties of the primary cilium.Then we reviewed the molecular mechanisms underlying mechano-sensing and transduction by endothelial primary cilia and the mathematical model prediction for their roles in redistribution and reduction of wall shear stresses.Finally,we briefly discussed the common cardiovascular diseases,e.g.,atherosclerosis,hypertension,and aneurysm,due to defects and malfunction of endothelial primary cilia and suggested potential targets for therapeutic treatments.
基金supported by grants ( 11421202,11572029) from National Natural Science Foundation of China
文摘Introduction Primary cilium is a non-motile microstructure,protruding from cell surface of most mammalian cells.It was previously thought to be vestigial.However,recent studies indicate that it may serve as one of the most vital mechanosensors for many types of cells such as epithelial and endothelial cells and osteocytes.Protruding from the apical membrane,the primary cilium can directly sense subtle variation of mechanical forces exerted on the cell and then transduce the mechanical cues into biochemical signals into the cell,although the mechanism remain elusive.Vascular endothelial cells(ECs)lining the inner wall of our blood vessels are continuously exposed to the blood flow.In order to maintain proper functions for the cardiovascular system,ECs should have a variety of mechano-sensors and transducers to sense the blood flow change and adjust the vessel size and transport across the vessel wall accordingly.Among more than a dozen recognized EC mechano-sensors,the primary cilium has drawn more and more attention recently.Primary cilium on endothelial cells is essential for the homeostasis of vessels.It is reported to be prevalent in areas of disturbed flow where atherosclerosis and intracranial aneurysm usually occur.Deficiencies of primary cilia may promote atherosclerosis,endothelial-to-mesenchymal transition(EndoMT)and loss of direction orientation,to name a few.Therefore understanding why the primary cilia are necessary to maintain the homeostasis of blood vessels and how will help us develop better treatment strategies for the common cardiovascular diseases.Dimension and structure of primary cilium Primary cilium is reported to be shorter than 8 in length and about 0.2 in diameter.The length of primary cilium varies in different cell types and under different conditions.The major structural components of the primary cilium include basal body,ciliary axoneme(consisting of nine doublet microtubules),ciliary membrane,transition zone,basal feet,and striated rootlets.Each part of the primary cilium is essential and has specific function.Current methods investigating the EC primary cilium as a mechano-sensor:Immunostaining and imaging techniques have been used to investigate the molecular mechanisms by which EC primary cilium serves as a mechano-sensor and transducer.It has been found that various proteins locate on the primary cilium,working together to maintain the function of primary cilium.Some proteins function as ion-channels,mediating Ca2+entry into the primary cilium.Some are involved in the cascade signal pathway.Others are related to the assembly and maintenance of primary cilium.Briefly,the flow induces the deflection of the EC primary cilium,which triggers calcium increase via opening of the PC2 cation channel that is responsible for calcium ion influx.This PC2 cation channel is localized to the primary cilium and is assumed to be stretch-activated.The resulting change in the intracellular calcium concentration then regulates numerous molecular activities inside the cell that contribute to vessel homeostasis.In addition to triggering calcium release,another mechanism has also been found in blood-pressure maintenance in the vasculature,where the vessel diameter is regulated by endothelial primary cilia through adjusting nitric oxide production.So far,little is known about the mechanical mechanism behind this deflection-triggered o-pening of signaling pathways.For example,what is the flow induced bending behavior and force distribution? What is the threshold value of stretch/defection for activating a corresponding signaling pathway? These all remain to be answered.In combination of image data and experiments,several computational models have been established to answer these questions.However,the current models are not able to include the complex structure of primary cilium and the model predictions are limited.Future studies With the development of super high resolution optical microscopy,more detailed images for the structural(molecular)components of EC primary cilia will be revealed,especially when the ECs are alive and the forces are known.Combining these experimental observations with more sophisticated mathematical models will elucidate the mechano-sensing mechanism of EC primary cilia,as the force and stress distribution on cilium along with other mechanical properties are still beyond the capability of experimental approaches due to the scales of the quantities involved.By using numerical approaches,much more detailed dynamic information can be obtained.
基金the National Natural Science Foundation of China(grant no.81602777).
文摘Background:Port-wine stain(PWS)has been classified not as the hyperplasia of cells,but rather,as an expansion of malformed vessels.However,previous studies have reported upregulated expression of proangiogenic factors in PWS.Several studies have indicated that the pathology exhibits proliferation of numerous endothelial cells in hypertrophic/nodular PWS.This study aimed to determine the expression of vascular epithelial growth factor(VEGF),matrix metalloproteinase-9(MMP-9),angiopoietin-2(ANG-2),and basic fibroblast growth factor(bFGF)in hypertrophic PWS.Methods:Immunohistochemistry was used to analyze skin samples from 33 patients with hypertrophic PWS.Expression levels of VEGF,MMP-9,ANG-2,and bFGF in hypertrophic PWS were determined by multiplying the intensity by the percentage of immunoreactive cells.Immunoreactivity scores were classified as follows:negative(0),low(1),moderate(2,3,and 4),or high(6).Results:Based on pathological characteristics,hypertrophic PWS was divided into vascular malformation and pyogenic granuloma(PG)types.VEGF,MMP-9,ANG-2,and bFGF were significantly activated in the blood vessels of PG-type PWS samples compared with their counterparts in blood vessels of vascular malformation-type PWS samples and controls.PG-type hypertrophic PWS,which exhibited proliferation of endothelial cells,showed the strongest activation.Conclusion:The exuberant proliferation of endothelial cells in PG-type hypertrophic PWS may be associated with the regulation of proangiogenic factors during development.These proangiogenic factors that function in the angiogenesis and proliferation of endothelial cells may play an important role in the pathogenesis and progression of PWS.Furthermore,these factors may be dynamic and behave differently in various types of hypertrophic PWS.
基金supported by the National Natural Science Foundation of China(Nos.T2288101,12172034,U20A20390,11827803,12202036)the Beijing Municipal Natural Science Foundation(No.7212205)+1 种基金the 111 Project(No.B13003)the Fundamental Research Funds for the Central Universities.
文摘High-purity(HP)magnesium(Mg)has emerged as a promising biomaterial for supporting functional bone tissue.Our previous study found that mechanical stresses and the surrounding fibrotic tissue(subcuta-neous)both play crucial roles in the degradation of HP Mg.However,due to challenges in the degradation and regeneration process in vivo,it remains unclear how stress affects HP Mg degradation in bone en-vironments,limiting its further application.In this study,novel loading devices were designed and the effects of tensile and compressive stresses on HP Mg degradation in vivo and in vitro bone environments were quantitatively analyzed.In addition,bone osteointegration around HP Mg was explored preliminar-ily.Tensile stress increases the degradation rate of HP Mg in vivo and in vitro.HP Mg degradation in vivo is more sensitive to stress factors than in vitro,but the sensitivity decreases with corrosion time.The volume loss rate of HP Mg is multilinear with the applied stress and degradation time.The volume of bone tissue surrounding HP Mg is larger in the no-stress group compared to the stressed groups,which is more pronounced with increasing implantation time.These results provide valuable insights for optimiz-ing the design of HP Mg-based implants considering load conditions.This will help to achieve a balance between the degradation rate of the implant and the regeneration rate of the surrounding bone.
基金supported by the Beijing Municipal Natural Science Foundation [7212205]National Key Research and Development Program of China [2023YFC2410404]+2 种基金National Natural Science Foundation of China [12172034,U20A20390,11827803]Fundamental Research Funds for the Central Universities111 project [B13003].
文摘Osteoblasts are mechanosensitive cells.Tensile stress with different conditions,including loading time,frequency,magnitude,etc.would cause varied responses in osteoblasts.However,it was not clarified that the effect of the loading types on the osteoblasts.In this study,we focused on the effect of varied tensile stress types on osteoblasts,including isotropic stretch,biaxial stretch,and uniaxial stretch with the negative ratio of transverse strain to axial strain(NR)-1,0,and 0.2 respectively.Cell proliferation was determined to be most efficient when stimulated by 6%strain at a frequency of 1 Hz and a negative value of 0 for 1 h/day.The varied strain resulted in a thickening of the F-actin cytoskeleton and a thinning of the nucleus.Nuclear flattening caused Yes-associated protein(YAP)to be transported to the nucleus.It was suggested that the influence of loading types on the mechanobiology responses must be noticed.The mechanism of cell mechanical sensitivity under varied loading types was explored,which would provide good sugges-tions for designing microstructures to control deformation patterns in bone tissue engineering.
基金supported by the National Natural Science Foundation of China(Grant No.12271433)。
文摘In this paper,two types of fractional nonlinear equations in Caputo sense,time-fractional Newell–Whitehead equation(FNWE)and time-fractional generalized Hirota–Satsuma coupled KdV system(HS-cKdVS),are investigated by means of the q-homotopy analysis method(q-HAM).The approximate solutions of the proposed equations are constructed in the form of a convergent series and are compared with the corresponding exact solutions.Due to the presence of the auxiliary parameter h in this method,just a few terms of the series solution are required in order to obtain better approximation.For the sake of visualization,the numerical results obtained in this paper are graphically displayed with the help of Maple.
基金supported by the National Natural Science Foundation of China(12172034,U20A20390,and 11827803)Beijing Municipal Natural Science Foundation(7212205)+1 种基金the 111 project(B13003)the Fundamental Research Funds for the Central Universities.
文摘Background:Mg alloys have attractive properties,including biocompatibility,biodegradability,and ideal mechanical properties.Moreover,Mg alloys are regarded as one of the promising candidates for manufacturing ureteral stents.This study proposed a multi-objective optimization method based on the Kriging surrogate model,NSGA-III,and finite element analysis to improve the degradation performance of Mg alloy ureteral stents.Methods:The finite element model for the degradation of Mg alloy ureteral stents has been established to compare the degradation performance of the stents under different parameters.Latin hypercube sampling was adopted to generate train sample points in the design space.Meanwhile,the Kriging surrogate model was constructed between strut parameters and stent degradation behavior.The NSGA-III was utilized to determine the optimal solution in the global design space.Results:The optimized stent achieved 5.52degradation uniformity(M),10degradation time(DT),and 4work time(FT).The errors between the Kriging surrogate model and the finite element calculation results were less than 6%.Conclusion:The optimized stent achieved better degradation performance.The degradation behavior of stents was dependent on the design parameters.The multi-objective optimization method based on the Kriging surrogate model and finite element analysis was effective in stent design optimization problems.
基金supported by the National Natural Science Foundation of China(Grant Nos.U2241273,12172034,U20A20390,and 11827803)the Beijing Municipal Natural Science Foundation(Grant No.7212205)+1 种基金the 111 project(Grant No.B13003)the Fundamental Research Funds for the Central Universities.
文摘Accurately characterizing the liver's mechanical properties is of paramount importance for disease diagnosis,treatment,surgical prosthetic modeling,and impact injury dummies.However,due to its inherent biological soft tissue nature,the characterization of mechanical behavior varies across testing methods and sample types.In this study,we employed transmission electron microscope and Micro CT to observe the morphology of the marginal and center of rat livers and conducted macroscopic mechanical tests to characterize their elasticity and viscoelasticity.The results revealed that the central region displayed higher metabolic levels,elongated mitochondria,and an abundance of rough endoplasmic reticulum at the microscale.At the mesoscale,larger diameter portal veins were mainly distributed in the central region,while smaller diameter arteries were predominantly located at the periphery.At the macroscale,under a strain rate of 0.0167 s^(-1),no significant differences were observed in the elastic properties between the two regions.However,as the strain rate increased up to 0.167 s^(-1),the central region displayed higher porosity,resulting in reduced liquid loss,increased hardness,and higher viscosity compared to the periphery.Consequently,the liver demonstrated overall heterogeneity,with isotropic models suitable for the peripheral region,while more intricate models may be required to capture the complexity of the central region with its intricate vasculature.
基金supported by the National Natural Science Foundation of China(T2288101,12172034,U20A20390,11827803)Beijing Municipal Natural Science Foundation(7212205)the 111 project(B13003)and the Fundamental Research Funds for the Central Universities。
文摘Poly(glycerol-dodecanoate)(PGD)has aroused increasing attention in biomedical engineering for its degradability,shape memory and rubber-like mechanical properties,giving it potential to fabricate intelligent implants for soft tissues.Adjustable degradation is important for biodegradable implants and is affected by various factors.The mechanical load has been shown to play an important role in regulating polymer degradation in vivo.An in-depth investigation of PGD degradation under mechanical load is essential for adjusting its degradation behavior after implantation,further guiding to regulate degradation behavior of soft tissue implants made by PGD.In vitro degradation of PGD under different compressive and tensile load has proceeded in this study and describes the relationships by empirical equations.Based on the equations,a continuum damage model is designed to simulate surface erosion degradation of PGD under stress through finite element analysis,which provides a protocol for PGD implants with different geometric structures at varied mechanical conditions and provides solutions for predicting in vivo degradation processes,stress distribution during degradation and optimization of the loaded drug release.
基金supported by the National Natural Science Foundation of China[U2241273,12172034,U20A20390,11827803]Beijing Municipal Natural Science Foundation[7212205]the 111 project[B13003]]and the Fundamental Research Funds for the Central Universities.
文摘The mechanical properties of biological soft tissues are inextricably linked to the field of health care,and their mechanical properties can be important indicators for diagnosing and detecting diseases;they can also be used to analyze the causes of organ diseases from a pathological point of view and thus guide the deployment of medical solutions.As an effective method to characterize the mechanical properties of materials,mechanical loading experiments have been successfully applied to the mechanical properties of materials,including tension,compression,pure shear,and so on.Under quasi-static loading,when the material is a biological soft tissue material between a solid and an ideal fluid,its viscoelastic properties strongly respond to the force stimulus,and the stress-strain-time in the elastic phase will have obvious disturbance characteristics.Therefore,the existing statistical methods are often difficult to quantitatively describe the mechanical properties of materials.Therefore,this study proposes an Interval Capture Point based on the principle of integration.The experimental data based on this method can characterize its nonlinear mechanical properties well,especially when the loading speed is extremely low and the soft materials show strong disturbance characteristics.The proposed method can still accurately characterize the hyperelastic and viscoelastic properties of the mechanical properties of biological soft tissues under quasi-static loading.
