Considering that the assumption of time consistency does not adequately reveal the mechanisms of exit decisions of venture capital(VC),this study proposes two kinds of time-inconsistent preferences(i.e.,time-flow inco...Considering that the assumption of time consistency does not adequately reveal the mechanisms of exit decisions of venture capital(VC),this study proposes two kinds of time-inconsistent preferences(i.e.,time-flow inconsistency and time-point incon-sistency)to advance research in this field.Time-flow inconsistency is in line with the previous time inconsistency literature,while time-point inconsistency is rooted in the VC fund’s finite lifespan.Based on the assumption about the strategies guiding future behaviors,we consider four types of venture capitalists:time-consistent,time-point-inconsistent,naïve,and sophisticated venture capitalists,of which the latter three are time-inconsistent.We derive and compare the exit thresholds of these four types of venture capitalists.The main results include:(1)time-inconsistent preferences acceler-ate the exits of venture capitalists;(2)the closer the VC funds expiry dates are,t`he more likely time-inconsistent venture capitalists are to accelerate their exits;and(3)future selves caused by time-flow inconsistency weaken the effect of time-point inconsist-ency.Our study provides a behavioral explanation for the empirical fact of young VCs’grandstanding.展开更多
The purpose of this study was to analyze the clinical experience of Zan Qiang,a famous doctor of Traditional Chinese Medicine in Shaanxi province,in the treatment of perimenopausal osteoporosis.Zan believed that the m...The purpose of this study was to analyze the clinical experience of Zan Qiang,a famous doctor of Traditional Chinese Medicine in Shaanxi province,in the treatment of perimenopausal osteoporosis.Zan believed that the main etiology and pathogenesis of perimenopausal osteoporosis were "deficiency of kidney essence,decreased marrow and bone",deficiency of liver and kidney"and"stasis caused by deficiency".Although it is a chronic physiological disease,and the pathological process is irreversible,the treatment groups of"tonifying kidney and filling essence","tonifying liver and tonifying kidney"and "tonifying deficiency and promoting blood circulation" can significantly improve the symptoms of patients,slow down the progress of the disease and improve the quality of life of patients.展开更多
Displays play an extremely important role in modern information society,which creates a never-ending demand for the new and better products and technologies.The latest requirements for novel display technologies focus...Displays play an extremely important role in modern information society,which creates a never-ending demand for the new and better products and technologies.The latest requirements for novel display technologies focus on high resolution and high color gamut.Among emerging technologies that include organic light-emitting diode(OL ED),micro light-emiting diode(micro-LED),quantum dot light-emitting diode(QLED),laser display,holographic display and others,QLED is promising owing to its intrinsic high color gamut and the possibility to achieve high resolution with photolithography approach.However,previously demonstrated photolthography techniques suffer from reduced device performance and color Impurities in subpixels from the process.In this study,we demonstrated a sacrificial layer assisted patterming(SLAP)approach,which can be applied in conjunction with photolithography to fabricate high-resolution,full-colo quantum dot(QD)patterns.In this approach,the negative photoresist(PR)and sacrificial layer(SL)were uilized to determine the pixels for QD deposition,while at the same time the SL helps protect the QD layer and keep it intact(named PR-SL approach).To prove this method's viability for QLED display manufacture,a 500-ppi,full-color passive matrix(PM)-QLED prototype was fabricated via this process.Results show that there were no color impurities in the subpixels,and the PM-QL ED has a high color gamut of 114%National Television Standards Committee(NTSC).To the best of our knowledge,this is the first ull-olor QLED prototype with such a high resolution.We anticipate that this innovative patteming technique will open a new horizon for future display technologies and may lead to a disruptive and innovative change in display industry.展开更多
The rapid endothelialization of tissue-engineered blood vessels(TEBVs) can effectively prevent thrombosis and inhibit intimal hyperplasia. The traditional Chinese medicine ingredient icariin is highly promising for th...The rapid endothelialization of tissue-engineered blood vessels(TEBVs) can effectively prevent thrombosis and inhibit intimal hyperplasia. The traditional Chinese medicine ingredient icariin is highly promising for the treatment of cardiovascular diseases.β-cyclodextrin sulfate is a type of hollow molecule that has good biocompatibility and anticoagulation properties and exhibits a sustained release of icariin. We studied whether icariin-loaded β-cyclodextrin sulfate can promote the endothelialization of TEBVs. The experimental results showed that icariin could significantly promote the proliferation and migration of endothelial progenitor cells; at the same time, icariin could promote the migration of rat vascular endothelial cells(RAVECs). Subsequently,we used an electrostatic force to modify the surface of the TEBVs with icariin-loaded β-cyclodextrin sulfate, and these vessels were implanted into the rat common carotid artery. After 3 months, micro-CT results showed that the TEBVs modified using icariin-loaded β-cyclodextrin sulfate had a greater patency rate. Scanning electron microscopy(SEM) and CD31 immunofluorescence results showed a better degree of endothelialization. Taken together, icariin-loaded β-cyclodextrin sulfate can achieve anticoagulation and rapid endothelialization of TEBVs to ensure their long-term patency.展开更多
Tissue-engineered vascular grafts(TEVGs)have enormous potential for vascular replacement therapy.However,thrombosis and intimal hyperplasia are important problems associated with TEVGs especially small diameter TEVGs(...Tissue-engineered vascular grafts(TEVGs)have enormous potential for vascular replacement therapy.However,thrombosis and intimal hyperplasia are important problems associated with TEVGs especially small diameter TEVGs(<6 mm)after transplantation.Endothelialization of TEVGs is a key point to prevent thrombosis.Here,we discuss different types of endothelialization and different seed cells of tissue-engineered vascular grafts.Meanwhile,endothelial heterogeneity is also discussed.Based on it,we provide a new perspective for selecting suitable types of endothelialization and suitable seed cells to improve the long-term patency rate of tissue-engineered vascular grafts with different diameters and lengths.展开更多
Under the internal dissipative condition, the Cauchy problem for inhomogeneous quasilinear hyperbolic systems with small initial data admits a unique global C1 solution, which exponentially decays to zero as t → +∞,...Under the internal dissipative condition, the Cauchy problem for inhomogeneous quasilinear hyperbolic systems with small initial data admits a unique global C1 solution, which exponentially decays to zero as t → +∞, while if the coefficient matrixΘ of boundary conditions satisfies the boundary dissipative condition, the mixed initialboundary value problem with small initial data for quasilinear hyperbolic systems with nonlinear terms of at least second order admits a unique global C1 solution, which also exponentially decays to zero as t → +∞. In this paper, under more general conditions, the authors investigate the combined effect of the internal dissipative condition and the boundary dissipative condition, and prove the global existence and exponential decay of the C1 solution to the mixed initial-boundary value problem for quasilinear hyperbolic systems with small initial data. This stability result is applied to a kind of models, and an example is given to show the possible exponential instability if the corresponding conditions are not satisfied.展开更多
High resolution and wide color gamut are two key requirements for novel display technologies. Owing to the distinguishing advantages over conventional displays, such as intrinsic wide color gamut and the possibility t...High resolution and wide color gamut are two key requirements for novel display technologies. Owing to the distinguishing advantages over conventional displays, such as intrinsic wide color gamut and the possibility to achieve high resolution, quantum dot light-emitting diodes (QLED) have drawn considerable attention in recent years. On the other hand, indium phosphide quantum dots (InP QDs) have shown a great potential as a replacement for cadmium selenide (CdSe) QDs in display applications due to the inherent toxicity of cadmium-based QDs. In this study, we investigate a top-emission InP-based green QLED with optimized angular distribution. By adjusting the electrical and optical architecture, the device exhibits improved properties with a maximum current efficiency of 30.1 cd/A and a narrowed full width at half maxima (FWHM)of 31 nm, which are the best results ever reported to our knowledge.展开更多
This paper presents a flexible radio-frequency microelectromechanical system(RF MEMS)switch integrated on cyclo-olefin polymer(COP)substrate using a modified surface MEMS processing technology,which could be used in t...This paper presents a flexible radio-frequency microelectromechanical system(RF MEMS)switch integrated on cyclo-olefin polymer(COP)substrate using a modified surface MEMS processing technology,which could be used in the 17-19 GHz frequency band of satellite communication.Through systematic simulation analysis,it is found that flexible RF MEMS switch can achieve certain bending radius by miniaturizing the electronic dimension,without degrading the RF performance.It is demonstrated that the RF characteristics of flexible RF MEMS switch with special anchor structural design,fabricated by modified surface MEMS processing,are not sensitive to bending deformation under the curvature of 0 mm^(-1),0.05 mm^(-1),0.10 mm^(-1).Furthermore,the range of bending curvature which will affect the RF characteristics is given through systematic simulation.The flexible RF MEMS switch with high process compatibility and stable RF performance is believed to be promising candidates for future microwave communications and other consumer electronics.展开更多
Cell therapy has been a promising strategy for cardiac repair after myocardial infarction(MI),but a poor ischemic environment and low cell delivery efficiency remain significant challenges.The spleen serves as a hemat...Cell therapy has been a promising strategy for cardiac repair after myocardial infarction(MI),but a poor ischemic environment and low cell delivery efficiency remain significant challenges.The spleen serves as a hematopoietic stem cell niche and secretes cardioprotective factors after MI,but it is unclear whether it could be used for human pluripotent stem cell(hiPSC)cultivation and provide a proper microenvironment for cell grafts against the ischemic environment.Herein,we developed a splenic extracellular matrix derived thermoresponsive hydrogel(SpGel).Proteomics analysis indicated that SpGel is enriched with proteins known to modulate the Wnt signaling pathway,cell-substrate adhesion,cardiac muscle contraction and oxidation-reduction processes.In vitro studies demonstrated that hiPSCs could be efficiently induced into endothelial cells(iECs)and cardiomyocytes(iCMs)with enhanced function on SpGel.The cytoprotective effect of SpGel on iECs/iCMs against oxidative stress damage was also proven.Furthermore,in vivo studies revealed that iEC/iCM-laden SpGel improved cardiac function and inhibited cardiac fibrosis of infarcted hearts by improving cell survival,revascularization and remuscularization.In conclusion,we successfully established a novel platform for the efficient generation and delivery of autologous cell grafts,which could be a promising clinical therapeutic strategy for cardiac repair and regeneration after MI.展开更多
Rapid integration into the host tissue is critical for long-term patency after small diameter tissue engineering vascular grafts(sdTEVGs)transplantation.Neural recognition may be required for host integration and func...Rapid integration into the host tissue is critical for long-term patency after small diameter tissue engineering vascular grafts(sdTEVGs)transplantation.Neural recognition may be required for host integration and functionalization of the graft.However,immune rejection and inflammation hinder nerve regeneration of sdTEVGs.Here,a CRISPR/dCas9-nanocarrier was used for targeted programming of regulatory T cells(Treg cells)in situ to promote nerve regeneration of sdTEVGs by preventing excessive inflammation.Treg cells and(C-C chemokine receptor)CCR2+macrophage recruitment occurred after transplantation.The nanodelivery system upregulated ten eleven translocation(TET2)in Treg cells in vitro.Reprogrammed Treg cells upregulated anti-inflammatory cytokines and decreased the proportion of CCR2+macrophages.IL-6 concentrations decreased to the levels required for nerve regeneration.Implantation of CRISPR/dCas9 nanodelivery system-modified sdTEVGs in rats resulted in Treg cell editing,control of excessive inflammation,and promoted nerve regeneration.After 3 months,nerve regeneration was similar to that observed in normal blood vessels;good immune homeostasis,consistency of hemodynamics,and matrix regeneration were observed.Neural recognition promotes further integration of the graft into the host,with unobstructed blood vessels without intimal hyperplasia.Our findings provide new insights into vascular implant functionalization by the host.展开更多
Thrombotic disease is a major problem that endangers human health. At present, MRI and CT are commonly used clinically to diagnose thrombosis, and thrombolytic drugs are used for treatment), but the diagnosis time is ...Thrombotic disease is a major problem that endangers human health. At present, MRI and CT are commonly used clinically to diagnose thrombosis, and thrombolytic drugs are used for treatment), but the diagnosis time is lagging, the utilization of drugs is low, and the resulting systemic toxicity problems such as side effects lead to poor treatment effects. Nanotechnology combining photoacoustic dynamics and chemical dynamics has shown great application value in tumor targeting, diagnosis, detection and treatment. It has also become a new direction in the diagnosis and treatment of thrombotic diseases, and has created new applications in the field of nanomaterials. This review summarizes the new progress of this combination in the diagnosis and treatment of thrombotic diseases according to the differences in the construction of the nanotherapy system, at the same time, we put forward some new problems and prospects for the integration of thrombosis diagnosis and treatment.展开更多
Small-diameter tissue-engineered vascular grafts(sdTEVGs)with hyperglycemia resistance have not been constructed.The intimal hyperplasia caused by hyperglycemia remains problem to hinder the patency of sdTEVGs.Here,in...Small-diameter tissue-engineered vascular grafts(sdTEVGs)with hyperglycemia resistance have not been constructed.The intimal hyperplasia caused by hyperglycemia remains problem to hinder the patency of sdTEVGs.Here,inspired by bionic regulation of nerve on vascular,we found the released neural exosomes could inhibit the abnormal phenotype transformation of vascular smooth muscle cells(VSMCs).The transformation was a prime culprit causing the intimal hyperplasia of sdTEVGs.To address this concern,sdTEVGs were modified with an on-demand programmable dual-responsive system of ultrathin hydrogels.An external primary Reactive Oxygen Species(ROS)-responsive Netrin-1 system was initially triggered by local inflammation to induce nerve remolding of the sdTEVGs overcoming the difficulty of nerve regeneration under hyperglycemia.Then,the internal secondary ATP-responsive DENND1A(guanine nucleotide exchange factor)system was turned on by the neurotransmitter ATP from the immigrated nerve fibers to stimulate effective release of neural exosomes.The results showed nerve fibers grow into the sdTEVGs in diabetic rats 30 days after transplantation.At day 90,the abnormal VSMCs phenotype was not detected in the sdTEVGs,which maintained long-time patency without intima hyperplasia.Our study provides new insights to construct vascular grafts resisting hyperglycemia damage.展开更多
基金supported by the Major Program of the National Social Science Foundation of China under Grant No.17ZDA083the National Natural Science Foundation of China under Grant No.71932002the Natural Science Foundation of Beijing Municipality under Grant No.9192001.
文摘Considering that the assumption of time consistency does not adequately reveal the mechanisms of exit decisions of venture capital(VC),this study proposes two kinds of time-inconsistent preferences(i.e.,time-flow inconsistency and time-point incon-sistency)to advance research in this field.Time-flow inconsistency is in line with the previous time inconsistency literature,while time-point inconsistency is rooted in the VC fund’s finite lifespan.Based on the assumption about the strategies guiding future behaviors,we consider four types of venture capitalists:time-consistent,time-point-inconsistent,naïve,and sophisticated venture capitalists,of which the latter three are time-inconsistent.We derive and compare the exit thresholds of these four types of venture capitalists.The main results include:(1)time-inconsistent preferences acceler-ate the exits of venture capitalists;(2)the closer the VC funds expiry dates are,t`he more likely time-inconsistent venture capitalists are to accelerate their exits;and(3)future selves caused by time-flow inconsistency weaken the effect of time-point inconsist-ency.Our study provides a behavioral explanation for the empirical fact of young VCs’grandstanding.
文摘The purpose of this study was to analyze the clinical experience of Zan Qiang,a famous doctor of Traditional Chinese Medicine in Shaanxi province,in the treatment of perimenopausal osteoporosis.Zan believed that the main etiology and pathogenesis of perimenopausal osteoporosis were "deficiency of kidney essence,decreased marrow and bone",deficiency of liver and kidney"and"stasis caused by deficiency".Although it is a chronic physiological disease,and the pathological process is irreversible,the treatment groups of"tonifying kidney and filling essence","tonifying liver and tonifying kidney"and "tonifying deficiency and promoting blood circulation" can significantly improve the symptoms of patients,slow down the progress of the disease and improve the quality of life of patients.
基金This work was supported by the National Key R&D Program of China(No.2016YFB0401700).
文摘Displays play an extremely important role in modern information society,which creates a never-ending demand for the new and better products and technologies.The latest requirements for novel display technologies focus on high resolution and high color gamut.Among emerging technologies that include organic light-emitting diode(OL ED),micro light-emiting diode(micro-LED),quantum dot light-emitting diode(QLED),laser display,holographic display and others,QLED is promising owing to its intrinsic high color gamut and the possibility to achieve high resolution with photolithography approach.However,previously demonstrated photolthography techniques suffer from reduced device performance and color Impurities in subpixels from the process.In this study,we demonstrated a sacrificial layer assisted patterming(SLAP)approach,which can be applied in conjunction with photolithography to fabricate high-resolution,full-colo quantum dot(QD)patterns.In this approach,the negative photoresist(PR)and sacrificial layer(SL)were uilized to determine the pixels for QD deposition,while at the same time the SL helps protect the QD layer and keep it intact(named PR-SL approach).To prove this method's viability for QLED display manufacture,a 500-ppi,full-color passive matrix(PM)-QLED prototype was fabricated via this process.Results show that there were no color impurities in the subpixels,and the PM-QL ED has a high color gamut of 114%National Television Standards Committee(NTSC).To the best of our knowledge,this is the first ull-olor QLED prototype with such a high resolution.We anticipate that this innovative patteming technique will open a new horizon for future display technologies and may lead to a disruptive and innovative change in display industry.
基金supported by the National Science Fund for Distinguished Young Scholars (31625011)the National Key Research and Development Program (2016YFC1101100)+1 种基金the National Key Research and Development Plan Young Scientists Program (2017YFA0106000)the Young Elite Scientists Sponsorship Program by Cast (YESS20160180)
文摘The rapid endothelialization of tissue-engineered blood vessels(TEBVs) can effectively prevent thrombosis and inhibit intimal hyperplasia. The traditional Chinese medicine ingredient icariin is highly promising for the treatment of cardiovascular diseases.β-cyclodextrin sulfate is a type of hollow molecule that has good biocompatibility and anticoagulation properties and exhibits a sustained release of icariin. We studied whether icariin-loaded β-cyclodextrin sulfate can promote the endothelialization of TEBVs. The experimental results showed that icariin could significantly promote the proliferation and migration of endothelial progenitor cells; at the same time, icariin could promote the migration of rat vascular endothelial cells(RAVECs). Subsequently,we used an electrostatic force to modify the surface of the TEBVs with icariin-loaded β-cyclodextrin sulfate, and these vessels were implanted into the rat common carotid artery. After 3 months, micro-CT results showed that the TEBVs modified using icariin-loaded β-cyclodextrin sulfate had a greater patency rate. Scanning electron microscopy(SEM) and CD31 immunofluorescence results showed a better degree of endothelialization. Taken together, icariin-loaded β-cyclodextrin sulfate can achieve anticoagulation and rapid endothelialization of TEBVs to ensure their long-term patency.
基金supported by The National Science Fund for Outstanding Young Scholars(No:31822021)The Key Research and Development Plan Young Scientists Program(No:2017YFA0106000)+1 种基金The National Key Research and Development Plan(No:2016YFC1101100)National Science Foundation of China(No:31771057).
文摘Tissue-engineered vascular grafts(TEVGs)have enormous potential for vascular replacement therapy.However,thrombosis and intimal hyperplasia are important problems associated with TEVGs especially small diameter TEVGs(<6 mm)after transplantation.Endothelialization of TEVGs is a key point to prevent thrombosis.Here,we discuss different types of endothelialization and different seed cells of tissue-engineered vascular grafts.Meanwhile,endothelial heterogeneity is also discussed.Based on it,we provide a new perspective for selecting suitable types of endothelialization and suitable seed cells to improve the long-term patency rate of tissue-engineered vascular grafts with different diameters and lengths.
基金supported by the National Natural Science Foundation of China(Nos.11326159,11401421)the China Postdoctoral Science Foundation(No.2014M560287)the Shanxi Scholarship Council of China(No.2013-045)
文摘Under the internal dissipative condition, the Cauchy problem for inhomogeneous quasilinear hyperbolic systems with small initial data admits a unique global C1 solution, which exponentially decays to zero as t → +∞, while if the coefficient matrixΘ of boundary conditions satisfies the boundary dissipative condition, the mixed initialboundary value problem with small initial data for quasilinear hyperbolic systems with nonlinear terms of at least second order admits a unique global C1 solution, which also exponentially decays to zero as t → +∞. In this paper, under more general conditions, the authors investigate the combined effect of the internal dissipative condition and the boundary dissipative condition, and prove the global existence and exponential decay of the C1 solution to the mixed initial-boundary value problem for quasilinear hyperbolic systems with small initial data. This stability result is applied to a kind of models, and an example is given to show the possible exponential instability if the corresponding conditions are not satisfied.
基金This work was supported by the National Key R&D Program of China under Grant No.2016YFB0401700.
文摘High resolution and wide color gamut are two key requirements for novel display technologies. Owing to the distinguishing advantages over conventional displays, such as intrinsic wide color gamut and the possibility to achieve high resolution, quantum dot light-emitting diodes (QLED) have drawn considerable attention in recent years. On the other hand, indium phosphide quantum dots (InP QDs) have shown a great potential as a replacement for cadmium selenide (CdSe) QDs in display applications due to the inherent toxicity of cadmium-based QDs. In this study, we investigate a top-emission InP-based green QLED with optimized angular distribution. By adjusting the electrical and optical architecture, the device exhibits improved properties with a maximum current efficiency of 30.1 cd/A and a narrowed full width at half maxima (FWHM)of 31 nm, which are the best results ever reported to our knowledge.
基金supported by BOE Technology Group Co.,Ltd.Y.L.acknowledges support from the National Natural Science Foundation of China under grant numbers 61825102 and U21A20460.
文摘This paper presents a flexible radio-frequency microelectromechanical system(RF MEMS)switch integrated on cyclo-olefin polymer(COP)substrate using a modified surface MEMS processing technology,which could be used in the 17-19 GHz frequency band of satellite communication.Through systematic simulation analysis,it is found that flexible RF MEMS switch can achieve certain bending radius by miniaturizing the electronic dimension,without degrading the RF performance.It is demonstrated that the RF characteristics of flexible RF MEMS switch with special anchor structural design,fabricated by modified surface MEMS processing,are not sensitive to bending deformation under the curvature of 0 mm^(-1),0.05 mm^(-1),0.10 mm^(-1).Furthermore,the range of bending curvature which will affect the RF characteristics is given through systematic simulation.The flexible RF MEMS switch with high process compatibility and stable RF performance is believed to be promising candidates for future microwave communications and other consumer electronics.
基金This work was supported by the Key projects of the National Natural Science Foundation of China(No.81830055)National Science Fund for Distinguished Young Scholars(No.31625011)+1 种基金the National Key Research and Development Program(No.2016YFC1101100)the National Science Fund for Outstanding Young Scholars(No.31822021).
文摘Cell therapy has been a promising strategy for cardiac repair after myocardial infarction(MI),but a poor ischemic environment and low cell delivery efficiency remain significant challenges.The spleen serves as a hematopoietic stem cell niche and secretes cardioprotective factors after MI,but it is unclear whether it could be used for human pluripotent stem cell(hiPSC)cultivation and provide a proper microenvironment for cell grafts against the ischemic environment.Herein,we developed a splenic extracellular matrix derived thermoresponsive hydrogel(SpGel).Proteomics analysis indicated that SpGel is enriched with proteins known to modulate the Wnt signaling pathway,cell-substrate adhesion,cardiac muscle contraction and oxidation-reduction processes.In vitro studies demonstrated that hiPSCs could be efficiently induced into endothelial cells(iECs)and cardiomyocytes(iCMs)with enhanced function on SpGel.The cytoprotective effect of SpGel on iECs/iCMs against oxidative stress damage was also proven.Furthermore,in vivo studies revealed that iEC/iCM-laden SpGel improved cardiac function and inhibited cardiac fibrosis of infarcted hearts by improving cell survival,revascularization and remuscularization.In conclusion,we successfully established a novel platform for the efficient generation and delivery of autologous cell grafts,which could be a promising clinical therapeutic strategy for cardiac repair and regeneration after MI.
基金This study was funded by the National Key Research and Development Plan Young Scientists Program Grant(2021YFA1102100)the National Science Fund for Excellent Young Scholars(2021-JCJQ-ZQ-003)+1 种基金the National Science Foundation of China Grant(31771057)the Science Fund for Distinguished Young Scholars of Chongqing Municipality(cstc2020jcyj-jqX0023).
文摘Rapid integration into the host tissue is critical for long-term patency after small diameter tissue engineering vascular grafts(sdTEVGs)transplantation.Neural recognition may be required for host integration and functionalization of the graft.However,immune rejection and inflammation hinder nerve regeneration of sdTEVGs.Here,a CRISPR/dCas9-nanocarrier was used for targeted programming of regulatory T cells(Treg cells)in situ to promote nerve regeneration of sdTEVGs by preventing excessive inflammation.Treg cells and(C-C chemokine receptor)CCR2+macrophage recruitment occurred after transplantation.The nanodelivery system upregulated ten eleven translocation(TET2)in Treg cells in vitro.Reprogrammed Treg cells upregulated anti-inflammatory cytokines and decreased the proportion of CCR2+macrophages.IL-6 concentrations decreased to the levels required for nerve regeneration.Implantation of CRISPR/dCas9 nanodelivery system-modified sdTEVGs in rats resulted in Treg cell editing,control of excessive inflammation,and promoted nerve regeneration.After 3 months,nerve regeneration was similar to that observed in normal blood vessels;good immune homeostasis,consistency of hemodynamics,and matrix regeneration were observed.Neural recognition promotes further integration of the graft into the host,with unobstructed blood vessels without intimal hyperplasia.Our findings provide new insights into vascular implant functionalization by the host.
基金supported by the National Key Research and Development Plan Young Scientists Program (No. 2017YFA0106000)the National Science Fund for Outstanding Young Scholars (No. 31822021)+1 种基金the National Natural Science Foundation of China (No. 31771057)the National Key Research and Development Plan (No. 2016YFC1101100)。
文摘Thrombotic disease is a major problem that endangers human health. At present, MRI and CT are commonly used clinically to diagnose thrombosis, and thrombolytic drugs are used for treatment), but the diagnosis time is lagging, the utilization of drugs is low, and the resulting systemic toxicity problems such as side effects lead to poor treatment effects. Nanotechnology combining photoacoustic dynamics and chemical dynamics has shown great application value in tumor targeting, diagnosis, detection and treatment. It has also become a new direction in the diagnosis and treatment of thrombotic diseases, and has created new applications in the field of nanomaterials. This review summarizes the new progress of this combination in the diagnosis and treatment of thrombotic diseases according to the differences in the construction of the nanotherapy system, at the same time, we put forward some new problems and prospects for the integration of thrombosis diagnosis and treatment.
基金We would like to thank Xing Shen and Yaqing Tang in the Innovative Drug Research Center of Chongqing University and Jing Zhou in the Department of Physiology,Basic Medical College,Peking University,for their support with the work.Thank Zhang San from Shiyanjia Lab(www.shiyanjia.com)for the modulus analysis.This work was supported by the National Key Research and Development Plan Young Scientists Program(No:2017YFA0106000)The National Science Fund for Outstanding Young Scholars(No.31822021)+1 种基金the National Science Foundation of China(No:31771057)and The National Key Research and Development Plan(No:2016YFC1101100).
文摘Small-diameter tissue-engineered vascular grafts(sdTEVGs)with hyperglycemia resistance have not been constructed.The intimal hyperplasia caused by hyperglycemia remains problem to hinder the patency of sdTEVGs.Here,inspired by bionic regulation of nerve on vascular,we found the released neural exosomes could inhibit the abnormal phenotype transformation of vascular smooth muscle cells(VSMCs).The transformation was a prime culprit causing the intimal hyperplasia of sdTEVGs.To address this concern,sdTEVGs were modified with an on-demand programmable dual-responsive system of ultrathin hydrogels.An external primary Reactive Oxygen Species(ROS)-responsive Netrin-1 system was initially triggered by local inflammation to induce nerve remolding of the sdTEVGs overcoming the difficulty of nerve regeneration under hyperglycemia.Then,the internal secondary ATP-responsive DENND1A(guanine nucleotide exchange factor)system was turned on by the neurotransmitter ATP from the immigrated nerve fibers to stimulate effective release of neural exosomes.The results showed nerve fibers grow into the sdTEVGs in diabetic rats 30 days after transplantation.At day 90,the abnormal VSMCs phenotype was not detected in the sdTEVGs,which maintained long-time patency without intima hyperplasia.Our study provides new insights to construct vascular grafts resisting hyperglycemia damage.