In the event of a significant natural disaster or a local conflict,the demand for a regional satellite navigation becomes imperative.The navigation can provide accurate position information and navigation augmentation...In the event of a significant natural disaster or a local conflict,the demand for a regional satellite navigation becomes imperative.The navigation can provide accurate position information and navigation augmentation services for regional emergency operations.To satisfy the requirements,a formation configuration of low-Earth orbit(LEO)regional navigation satellites is proposed innovatively.The strategy offly-around formation consisting of four satellites for LEO regional navigation is determined and a comprehensive configuration design method for the formation is presented,encompassing the determination of configuration parameters,the establishment of dynamic equations and the presentation of performance indicators,including duration of ground coverage,positioning accuracy Geometric Dilution Precision(GDOP)and fuel consumption.The effects of formation radius and orbit altitude on the performance indicators are analyzed,respectively.Based on the above investigations,a method to enhance regional navigation performances by using genetic algorithm(GA)guided by penalty function is introduced.The rationality and feasibility of the formation configuration are verified through simulation studies.展开更多
Considering the surgical risk stratification for patients with severe calcific aortic stenosis(AS),transcatheter aortic valve replacement(TAVR)is a reliable alternative to surgical aortic valve replacement(SAVR)(Fan e...Considering the surgical risk stratification for patients with severe calcific aortic stenosis(AS),transcatheter aortic valve replacement(TAVR)is a reliable alternative to surgical aortic valve replacement(SAVR)(Fan et al.,2020,2021;Lee et al.,2021).Despite the favorable clinical benefits of TAVR,stroke remains a dreaded perioperative complication(Auffret et al.,2016;Kapadia et al.,2016;Kleiman et al.,2016;Huded et al.,2019).Ischemic overt stroke,identified in 1.4%to 4.3%of patients in TAVR clinical practice,has been associated with prolonged disability and increased mortality(Auffret et al.,2016;Kapadia et al.,2016;Levi et al.,2022).The prevalence of hyperintensity cerebral ischemic lesions detected by diffusion-weighted magnetic resonance imaging(DW-MRI)was reported to be about 80%,which is associated with impaired neurocognitive function and vascular dementia(Vermeer et al.,2003;Barber et al.,2008;Kahlert et al.,2010).展开更多
Immunity-and-matrix-regulatory cells(IMRCs)derived from human embryonic stem cells have unique abilities in modulating immunity and regulating the extracellular matrix,which could be mass-produced with stable biologic...Immunity-and-matrix-regulatory cells(IMRCs)derived from human embryonic stem cells have unique abilities in modulating immunity and regulating the extracellular matrix,which could be mass-produced with stable biological properties.Despite resemblance to mesenchymal stem cells(MSCs)in terms of self-renew and tri-lineage differentiation,the ability of IMRCs to repair the meniscus and the underlying mechanism remains undetermined.Here,we showed that IMRCs demonstrated stronger immunomodulatory and pro-regenerative potential than umbilical cord MSCs when stimulated by synovial fluid from patients with meniscus injury.Following injection into the knees of rabbits with meniscal injury,IMRCs enhanced endogenous fibrocartilage regeneration.In the dose-escalating phase I clinical trial(NCT03839238)with eighteen patients recruited,we found that intra-articular IMRCs injection in patients was safe over 12 months post-grafting.Furthermore,the effective results of magnetic resonance imaging(MRI)of meniscus repair and knee functional scores suggested that 5×107 cells are optimal for meniscus injury treatment.In summary,we present the first report of a phase I clinical trial using IMRCs to treat meniscus injury.Our results demonstrated that intra-articular injection of IMRCs is a safe and effective therapy by providing a permissive niche for cartilage regeneration.展开更多
Angiogenesis occurs during the process of tumor growth,invasion and metastasis,and is essential for the survival of solid tumors.As an integrin significantly ove rexpressed in human tumor vascular endothelial cells,α...Angiogenesis occurs during the process of tumor growth,invasion and metastasis,and is essential for the survival of solid tumors.As an integrin significantly ove rexpressed in human tumor vascular endothelial cells,αvβ3 is a suitable targeting site for anti-angiogenesis of tumor.We designed and prepared a selfassembling peptide(SAP)with the ability to targeting αvβ3 and self-assembly.SAP formed nanoparticles in solution and transformed into nanofibrous network once specifically binding to integrin αvβ3 on the surface of human umbilical vein endothelial cells(HUVECs).The SAP network stably anchored on HUVECs over 24h,which consequently resulted in high-efficient inhibition of vascularization.In vitro anti-angiogenesis experiment displayed that the inhibition rate of tube-formation reached 94.9%.In vivo anti-angiogenesis array based on chick chorioallantoic membrane(CAM)model exhibited that the SAP had an inhibition rate up to 63.1%.These results indicated the outstanding anti-angiogenic ability of SAP,potentially for tumor therapy.展开更多
Aortic stenosis(AS)is a progressive heart valve disease occurring predominantly in older patients.According to a survey in a western country,the prevalence of AS is nearly 6.4%in patients over 75 years old(Carabello a...Aortic stenosis(AS)is a progressive heart valve disease occurring predominantly in older patients.According to a survey in a western country,the prevalence of AS is nearly 6.4%in patients over 75 years old(Carabello and Paulus,2009).Transcatheter aortic valve replacement(TAVR)is an alternative method for AS patients.Previous studies have described how up to 66%of TAVR patients have concomitant baseline kidney dysfunction(Ferro et al.,2015;Gargiulo et al.,2015).The majority of patients can benefit from the TAVR procedure with the recovery of kidney function.展开更多
Vascular endothelial growth factor(VEGF)-vascular endothelial growth factor receptor(VEGFR)pathways are essential in tumor angiogenesis,growth and metastasis.Studies on anti-angiogenic therapy have been mostly focused...Vascular endothelial growth factor(VEGF)-vascular endothelial growth factor receptor(VEGFR)pathways are essential in tumor angiogenesis,growth and metastasis.Studies on anti-angiogenic therapy have been mostly focused on the blockage of VEGF-VEGFR pathways.We report an extracellularly transformable peptide-based nanomaterial to develop artificial extracellular matrix(ECM)-like networks for high-efficient blockage of natural VEGF-VEGFR interactions.The transformable peptide-based nanomaterial transforms from nanoparticles into nanofibers upon binding to VEGFR in solution.In addition,the transformable peptide-based nanomate rial forms ECM-like fibrous netwo rks on VEGFR overexpressed cells,inhibiting the VEGF-VEGFR interactions and the subsequent angiogenesis.The tube formation is reduced by nearly 85.1% after treatment.This strategy shows excellent potential for anti-angiogenesis,and inhibition of tumor invasion and metastasis.展开更多
About 90%cancer-related mortality results from the cancer metastasis,which generally undergoes after epithelial-mesenchymal transition(EMT)process.N-Cadherin,overexpressed on cancer cell surface during EMT,can enhance...About 90%cancer-related mortality results from the cancer metastasis,which generally undergoes after epithelial-mesenchymal transition(EMT)process.N-Cadherin,overexpressed on cancer cell surface during EMT,can enhance the migration of cancer cells.He rein,we design and synthesize a transformable peptide BP-KLVFF-SWTLYTPSGQSK(BFS)that can block N-cadherin for inhibiting cancer migration and metastasis.The peptide BFS consists of three modules including(1)the hydrophobic bis-pyrene(BP)unit for forming and locating nanoparticles,(2)the KLVFF peptide sequence for forming and stabilizing fibrous structures and(3)the targeting peptide sequence SWTLYTPSGQSK that can specifically bind to Ncadherin.The peptide BFS can form nanoparticles in PBS,which can transform to nanofibers when targeting and binding to N-cadherin.The nanofibers inhibit the migration of N-cadherin overexpressed MDA-MB-436 cancer cells.The peptide BFS shows 83.6%inhibiting rate in cells wound healing assay.In addition,the inhibition rate is 67.9%when the BFS applied in transwell migration assay.These results indicate that the BFS has excellent ability to inhibit migration of cancer cells.This self-assembly strategy could be potentially utilized to regulate the key protein during EMT for inhibiting the tumor metastasis.展开更多
Transcatheter aortic valve replacement(TAVR)has emerged as a viable treatment option for patients with severe aortic stenosis regardless of its surgical risk stratification(Otto et al.,2021).Aortic angulation is usual...Transcatheter aortic valve replacement(TAVR)has emerged as a viable treatment option for patients with severe aortic stenosis regardless of its surgical risk stratification(Otto et al.,2021).Aortic angulation is usually measured as the angle between the horizon-tai and the aortic annulus planes based on preprocedural multidetector computed tomography(MDCT)(Al-Lamee et al.,2011).Extremely horizontal aorta,defined as an aortic angulation greater than 70°.展开更多
基金supported by the National Natural Science Foundation of China under Grant Nos.52305117 and 52075446.
文摘In the event of a significant natural disaster or a local conflict,the demand for a regional satellite navigation becomes imperative.The navigation can provide accurate position information and navigation augmentation services for regional emergency operations.To satisfy the requirements,a formation configuration of low-Earth orbit(LEO)regional navigation satellites is proposed innovatively.The strategy offly-around formation consisting of four satellites for LEO regional navigation is determined and a comprehensive configuration design method for the formation is presented,encompassing the determination of configuration parameters,the establishment of dynamic equations and the presentation of performance indicators,including duration of ground coverage,positioning accuracy Geometric Dilution Precision(GDOP)and fuel consumption.The effects of formation radius and orbit altitude on the performance indicators are analyzed,respectively.Based on the above investigations,a method to enhance regional navigation performances by using genetic algorithm(GA)guided by penalty function is introduced.The rationality and feasibility of the formation configuration are verified through simulation studies.
基金supported by the Zhejiang Province Science and Technology Department Key R&D Program(No.2021C03097),China.
文摘Considering the surgical risk stratification for patients with severe calcific aortic stenosis(AS),transcatheter aortic valve replacement(TAVR)is a reliable alternative to surgical aortic valve replacement(SAVR)(Fan et al.,2020,2021;Lee et al.,2021).Despite the favorable clinical benefits of TAVR,stroke remains a dreaded perioperative complication(Auffret et al.,2016;Kapadia et al.,2016;Kleiman et al.,2016;Huded et al.,2019).Ischemic overt stroke,identified in 1.4%to 4.3%of patients in TAVR clinical practice,has been associated with prolonged disability and increased mortality(Auffret et al.,2016;Kapadia et al.,2016;Levi et al.,2022).The prevalence of hyperintensity cerebral ischemic lesions detected by diffusion-weighted magnetic resonance imaging(DW-MRI)was reported to be about 80%,which is associated with impaired neurocognitive function and vascular dementia(Vermeer et al.,2003;Barber et al.,2008;Kahlert et al.,2010).
基金supported by the Natural Key Research and Development Program(No:2021YFA1101604)the key Research and Development program of Hubei province(2022BCA028)the international cooperation project of China Manned Space Program,and program for Tongji Hospital Academic Frontier Youth Team(2019A20)。
文摘Immunity-and-matrix-regulatory cells(IMRCs)derived from human embryonic stem cells have unique abilities in modulating immunity and regulating the extracellular matrix,which could be mass-produced with stable biological properties.Despite resemblance to mesenchymal stem cells(MSCs)in terms of self-renew and tri-lineage differentiation,the ability of IMRCs to repair the meniscus and the underlying mechanism remains undetermined.Here,we showed that IMRCs demonstrated stronger immunomodulatory and pro-regenerative potential than umbilical cord MSCs when stimulated by synovial fluid from patients with meniscus injury.Following injection into the knees of rabbits with meniscal injury,IMRCs enhanced endogenous fibrocartilage regeneration.In the dose-escalating phase I clinical trial(NCT03839238)with eighteen patients recruited,we found that intra-articular IMRCs injection in patients was safe over 12 months post-grafting.Furthermore,the effective results of magnetic resonance imaging(MRI)of meniscus repair and knee functional scores suggested that 5×107 cells are optimal for meniscus injury treatment.In summary,we present the first report of a phase I clinical trial using IMRCs to treat meniscus injury.Our results demonstrated that intra-articular injection of IMRCs is a safe and effective therapy by providing a permissive niche for cartilage regeneration.
基金the National Natural Science Foundation of China(Nos.51890891,51725302,21807020,51573031 and 51573032)Science Fund for Creative Research Groups of the National Natural Science Foundation of China(No.11621505)+1 种基金CAS Interdisciplinary Innovation Team,Jilin Province Key Laboratory of Organic Functional Molecular Design and Synthesis(No.130028911)Key Laboratory of Biomedical Effects of Nanomaterials and Nanosafety,CAS(No.NSKF201807)。
文摘Angiogenesis occurs during the process of tumor growth,invasion and metastasis,and is essential for the survival of solid tumors.As an integrin significantly ove rexpressed in human tumor vascular endothelial cells,αvβ3 is a suitable targeting site for anti-angiogenesis of tumor.We designed and prepared a selfassembling peptide(SAP)with the ability to targeting αvβ3 and self-assembly.SAP formed nanoparticles in solution and transformed into nanofibrous network once specifically binding to integrin αvβ3 on the surface of human umbilical vein endothelial cells(HUVECs).The SAP network stably anchored on HUVECs over 24h,which consequently resulted in high-efficient inhibition of vascularization.In vitro anti-angiogenesis experiment displayed that the inhibition rate of tube-formation reached 94.9%.In vivo anti-angiogenesis array based on chick chorioallantoic membrane(CAM)model exhibited that the SAP had an inhibition rate up to 63.1%.These results indicated the outstanding anti-angiogenic ability of SAP,potentially for tumor therapy.
基金supported by the National Key R&D Program of China(Nos.2019YFA0110400 and 2016YFC13010204)the National Natural Science Foundation of China(Nos.81870292,81570233,81770252)+1 种基金the Key Social Development Program of Major Science and Technology Projects in Zhejiang Province(No.2015C03028)the Fundamental Research Funds for the Central Universities(No.2019XZZX005-4-03),China。
文摘Aortic stenosis(AS)is a progressive heart valve disease occurring predominantly in older patients.According to a survey in a western country,the prevalence of AS is nearly 6.4%in patients over 75 years old(Carabello and Paulus,2009).Transcatheter aortic valve replacement(TAVR)is an alternative method for AS patients.Previous studies have described how up to 66%of TAVR patients have concomitant baseline kidney dysfunction(Ferro et al.,2015;Gargiulo et al.,2015).The majority of patients can benefit from the TAVR procedure with the recovery of kidney function.
基金the National Natural Science Foundation of China(Nos.51890891,51725302,21807020,51573031 and 51573032)National Key R&D Program of China(No.2018YFE0205400)Science Fund for Creative Research Groups of the National Natural Science Foundation of China(No.11621505)。
文摘Vascular endothelial growth factor(VEGF)-vascular endothelial growth factor receptor(VEGFR)pathways are essential in tumor angiogenesis,growth and metastasis.Studies on anti-angiogenic therapy have been mostly focused on the blockage of VEGF-VEGFR pathways.We report an extracellularly transformable peptide-based nanomaterial to develop artificial extracellular matrix(ECM)-like networks for high-efficient blockage of natural VEGF-VEGFR interactions.The transformable peptide-based nanomaterial transforms from nanoparticles into nanofibers upon binding to VEGFR in solution.In addition,the transformable peptide-based nanomate rial forms ECM-like fibrous netwo rks on VEGFR overexpressed cells,inhibiting the VEGF-VEGFR interactions and the subsequent angiogenesis.The tube formation is reduced by nearly 85.1% after treatment.This strategy shows excellent potential for anti-angiogenesis,and inhibition of tumor invasion and metastasis.
基金the National Natural Science Foundation of China(Nos.51890891,51725302,21807020,51573031 and 51573032)National Key R&D Program of China(No.2018YFE0205400)+1 种基金Science Fund for Creative Research Groups of the National Natural Science Foundation of China(No.11621505)CAS Interdisciplinary Innovation Team。
文摘About 90%cancer-related mortality results from the cancer metastasis,which generally undergoes after epithelial-mesenchymal transition(EMT)process.N-Cadherin,overexpressed on cancer cell surface during EMT,can enhance the migration of cancer cells.He rein,we design and synthesize a transformable peptide BP-KLVFF-SWTLYTPSGQSK(BFS)that can block N-cadherin for inhibiting cancer migration and metastasis.The peptide BFS consists of three modules including(1)the hydrophobic bis-pyrene(BP)unit for forming and locating nanoparticles,(2)the KLVFF peptide sequence for forming and stabilizing fibrous structures and(3)the targeting peptide sequence SWTLYTPSGQSK that can specifically bind to Ncadherin.The peptide BFS can form nanoparticles in PBS,which can transform to nanofibers when targeting and binding to N-cadherin.The nanofibers inhibit the migration of N-cadherin overexpressed MDA-MB-436 cancer cells.The peptide BFS shows 83.6%inhibiting rate in cells wound healing assay.In addition,the inhibition rate is 67.9%when the BFS applied in transwell migration assay.These results indicate that the BFS has excellent ability to inhibit migration of cancer cells.This self-assembly strategy could be potentially utilized to regulate the key protein during EMT for inhibiting the tumor metastasis.
基金This work was supported by the Zhejiang Province Science and Technology Department Key R&D Program(Nos.2021C03097 and 2018C03084),China.
文摘Transcatheter aortic valve replacement(TAVR)has emerged as a viable treatment option for patients with severe aortic stenosis regardless of its surgical risk stratification(Otto et al.,2021).Aortic angulation is usually measured as the angle between the horizon-tai and the aortic annulus planes based on preprocedural multidetector computed tomography(MDCT)(Al-Lamee et al.,2011).Extremely horizontal aorta,defined as an aortic angulation greater than 70°.