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
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
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
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
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
Nut shells have good impact and fracture resistance,but many kinds of nut shells have suture structures with low bonding strength.Therefore,the mechanism of impact and fracture resistance of nut shells as a whole is i...Nut shells have good impact and fracture resistance,but many kinds of nut shells have suture structures with low bonding strength.Therefore,the mechanism of impact and fracture resistance of nut shells as a whole is important to study,particularly given that sutures maintain low bonding strength.In this study,we investigated the effect of the geometrical characteristics of sutures(morphology,thickness,and number)on the overall fracture resistance of walnuts,based on mechanical tests of C-ring samples,microstructure analysis after cracking,quantitative analysis of suture geometric model,and numerical simulations.We found that the cracking of walnuts was mainly caused by tensile stress,and the bonding strength was approximately 2.48±0.64 MPa.We discovered that the thickness of the suture was 1.55±0.32 times thicker than the shell,which improved the fracture resistance ability by more than 28.4%.The undulating and inclined morphology of the walnut suture also increased the fracture force.Additionally,an appropriate suture number reduced the cracking of walnuts.In conclusion,our study sheds light on the physiological function of walnut sutures from a biomechanical perspective and provides useful references for designing fracture resistance measures in thin shell structures.展开更多
Irisin,a myokine mainly secreted from contracted skeleton muscle,plays a profound role in bone formation and remodeling.Although irisin has been revealed to elevate bone mass in vivo,details whether there is a dosedep...Irisin,a myokine mainly secreted from contracted skeleton muscle,plays a profound role in bone formation and remodeling.Although irisin has been revealed to elevate bone mass in vivo,details whether there is a dosedependent relationship between irisin and bone formation remain unclear.In this study,we explored the dosedependent effects of irisin on osteoblast proliferation and differentiation.Our results first demonstrated a remarkable increase in cell proliferation rate and viability in response to elevated concentrations of r-irisin,which was further enhanced over time.Notably,this increase was subject to complex dose-response relationships as the proliferation-enhancing effects of r-irisin may have a saturation point between 10 ng/ml and 100 ng/ml.Furthermore,we determined that 1,10,and 100 ng/ml r-irisin were able to upregulate the expression of osteogenic transcription factors(Runx2,Osx,and Atf4),as well as osteogenic markers(Alp,Col1a1 and Spp1),albeit without significant difference among these 3 concentrations.Interestingly,nutrient-depleted osteoblasts and those with standard culture showed distinct responses to higher doses of irisin regarding osteogenic differentiation.Further investigation is required to uncover the molecular mechanisms underlying the observed tandem effects of irisin on osteogenesis.展开更多
The development of small-diameter vascular grafts that can meet the long-term patency required for implementation in clinical practice presents a key challenge to the research field.Although techniques such as the bra...The development of small-diameter vascular grafts that can meet the long-term patency required for implementation in clinical practice presents a key challenge to the research field.Although techniques such as the braiding of scaffolds can offer a tunable platform for fabricating vascular grafts,the effects of braided silk fiber skeletons on the porosity,remodeling,and patency in vivo have not been thoroughly investigated.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
In this study, mechanical properties of bionic porous structures with diagonal-symmetrical and midline-symmetrical unit cells were studied when the porosities were same. Three typical unit cells (Diamond (DO), Rhombic...In this study, mechanical properties of bionic porous structures with diagonal-symmetrical and midline-symmetrical unit cells were studied when the porosities were same. Three typical unit cells (Diamond (DO), Rhombic Dodecahedron (RD), and Octet Truss (OT)) were selected, in which DO has diagonal-symmetrical shape, while RD and OT share midline-symmetrical structure. Based on the same porosity, corresponding models were designed, and Ti6Al4V samples were manufactured by electron beam melting. Then, using Mechanical Properties Testing (MPT) and Finite Element Analysis (FEA) methodologies, mechanical properties and transmissions of different porous structures were evaluated. Besides, composition and details before and after printing were analyzed with Energy Dispersive Spectrometer (EDS), X-ray diffraction (XRD) and Scanning Electron Microscope (SEM). MPT results showed that midline-symmetrical shape would have superior compressive performance than diagonal-symmetrical shape, but opposite trend for the torsion performance, which were in line with FEA prediction. Furthermore, effective modulus of DO, RD and OT were 2.59 GPa, 4.89 GPa, and 1.77 GPa, approximating the mechanical properties of human bones. Additionally, manufacturing defects and discrepancies between FEA and MPT were found. This study would provide great helps for unit cell selection and initial mechanical properties matching for optimum bone implants.展开更多
A co-location pattern is a set of spatial features whose instances frequently appear in a spatial neighborhood. This paper efficiently mines the top-k probabilistic prevalent co-locations over spatially uncertain data...A co-location pattern is a set of spatial features whose instances frequently appear in a spatial neighborhood. This paper efficiently mines the top-k probabilistic prevalent co-locations over spatially uncertain data sets and makes the following contributions: 1) the concept of the top-k prob- abilistic prevalent co-locations based on a possible world model is defined; 2) a framework for discovering the top- k probabilistic prevalent co-locations is set up; 3) a matrix method is proposed to improve the computation of the preva- lence probability of a top-k candidate, and two pruning rules of the matrix block are given to accelerate the search for ex- act solutions; 4) a polynomial matrix is developed to further speed up the top-k candidate refinement process; 5) an ap- proximate algorithm with compensation factor is introduced so that relatively large quantity of data can be processed quickly. The efficiency of our proposed algorithms as well as the accuracy of the approximation algorithms is evaluated with an extensive set of experiments using both synthetic and real uncertain data sets.展开更多
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 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This work was supported by the National Natural Science Foundation of China[U2241273,12172034,U20A20390,11827803,11822201]Beijing Municipal Natural Science Foundation[7212205]+1 种基金the 111 project[B13003]the Fundamental Research Funds for the Central Universities.
文摘Nut shells have good impact and fracture resistance,but many kinds of nut shells have suture structures with low bonding strength.Therefore,the mechanism of impact and fracture resistance of nut shells as a whole is important to study,particularly given that sutures maintain low bonding strength.In this study,we investigated the effect of the geometrical characteristics of sutures(morphology,thickness,and number)on the overall fracture resistance of walnuts,based on mechanical tests of C-ring samples,microstructure analysis after cracking,quantitative analysis of suture geometric model,and numerical simulations.We found that the cracking of walnuts was mainly caused by tensile stress,and the bonding strength was approximately 2.48±0.64 MPa.We discovered that the thickness of the suture was 1.55±0.32 times thicker than the shell,which improved the fracture resistance ability by more than 28.4%.The undulating and inclined morphology of the walnut suture also increased the fracture force.Additionally,an appropriate suture number reduced the cracking of walnuts.In conclusion,our study sheds light on the physiological function of walnut sutures from a biomechanical perspective and provides useful references for designing fracture resistance measures in thin shell structures.
基金The study was supported by National Natural Science Foundation of China(No.12172034,U2241273,11827803,U20A20390)Beijing Municipal Natural Science Foundation(7212205)+1 种基金the 111 project(B13003)the Fundamental Research Funds for the Central Universities.
文摘Irisin,a myokine mainly secreted from contracted skeleton muscle,plays a profound role in bone formation and remodeling.Although irisin has been revealed to elevate bone mass in vivo,details whether there is a dosedependent relationship between irisin and bone formation remain unclear.In this study,we explored the dosedependent effects of irisin on osteoblast proliferation and differentiation.Our results first demonstrated a remarkable increase in cell proliferation rate and viability in response to elevated concentrations of r-irisin,which was further enhanced over time.Notably,this increase was subject to complex dose-response relationships as the proliferation-enhancing effects of r-irisin may have a saturation point between 10 ng/ml and 100 ng/ml.Furthermore,we determined that 1,10,and 100 ng/ml r-irisin were able to upregulate the expression of osteogenic transcription factors(Runx2,Osx,and Atf4),as well as osteogenic markers(Alp,Col1a1 and Spp1),albeit without significant difference among these 3 concentrations.Interestingly,nutrient-depleted osteoblasts and those with standard culture showed distinct responses to higher doses of irisin regarding osteogenic differentiation.Further investigation is required to uncover the molecular mechanisms underlying the observed tandem effects of irisin on osteogenesis.
基金The authors graciously acknowledge professor Deling Kong's lab for their assistance with the animal experiments.This project was supported by the National Natural Science Foundation of China(T2288101,32000968,32071359,11827803,and U20A20390)Beijing Natural Science Foundation(M22026)Fundamental Research Funds for the Central Universities,and 111 Project(B13003).
文摘The development of small-diameter vascular grafts that can meet the long-term patency required for implementation in clinical practice presents a key challenge to the research field.Although techniques such as the braiding of scaffolds can offer a tunable platform for fabricating vascular grafts,the effects of braided silk fiber skeletons on the porosity,remodeling,and patency in vivo have not been thoroughly investigated.
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.
基金China National Key Research and Development Plan Project (Nos. 2016YFB1101101 and 2016YFB1101102)Beij ing Outstanding Young Backbone Personnel Training Project (No. 2017000026825G280)+2 种基金Sichuan Science and Technology Program (No. 18ZDYF1362)Fundamental Research Funds for Central Public Welfare Research Institutes (No. 118009001000160001)National Natural Science Foundation of China (Nos. 11421202 and 11572029).
文摘In this study, mechanical properties of bionic porous structures with diagonal-symmetrical and midline-symmetrical unit cells were studied when the porosities were same. Three typical unit cells (Diamond (DO), Rhombic Dodecahedron (RD), and Octet Truss (OT)) were selected, in which DO has diagonal-symmetrical shape, while RD and OT share midline-symmetrical structure. Based on the same porosity, corresponding models were designed, and Ti6Al4V samples were manufactured by electron beam melting. Then, using Mechanical Properties Testing (MPT) and Finite Element Analysis (FEA) methodologies, mechanical properties and transmissions of different porous structures were evaluated. Besides, composition and details before and after printing were analyzed with Energy Dispersive Spectrometer (EDS), X-ray diffraction (XRD) and Scanning Electron Microscope (SEM). MPT results showed that midline-symmetrical shape would have superior compressive performance than diagonal-symmetrical shape, but opposite trend for the torsion performance, which were in line with FEA prediction. Furthermore, effective modulus of DO, RD and OT were 2.59 GPa, 4.89 GPa, and 1.77 GPa, approximating the mechanical properties of human bones. Additionally, manufacturing defects and discrepancies between FEA and MPT were found. This study would provide great helps for unit cell selection and initial mechanical properties matching for optimum bone implants.
文摘A co-location pattern is a set of spatial features whose instances frequently appear in a spatial neighborhood. This paper efficiently mines the top-k probabilistic prevalent co-locations over spatially uncertain data sets and makes the following contributions: 1) the concept of the top-k prob- abilistic prevalent co-locations based on a possible world model is defined; 2) a framework for discovering the top- k probabilistic prevalent co-locations is set up; 3) a matrix method is proposed to improve the computation of the preva- lence probability of a top-k candidate, and two pruning rules of the matrix block are given to accelerate the search for ex- act solutions; 4) a polynomial matrix is developed to further speed up the top-k candidate refinement process; 5) an ap- proximate algorithm with compensation factor is introduced so that relatively large quantity of data can be processed quickly. The efficiency of our proposed algorithms as well as the accuracy of the approximation algorithms is evaluated with an extensive set of experiments using both synthetic and real uncertain data sets.