Osteoarthritis(OA)is one of the most common degenerative and age-related diseases in joints,which affects 654 million people worldwide.Current therapies could not fundamentally reverse the pathologic process of OA due...Osteoarthritis(OA)is one of the most common degenerative and age-related diseases in joints,which affects 654 million people worldwide.Current therapies could not fundamentally reverse the pathologic process of OA due to the complex pathogenesis.Although OA mechanisms have been investigated on a large scale over the past decade,the OA pathology correlated with aging-associated changes is still largely unrevealed.Therefore,in-depth analysis of the aging microenvironment and aging-related molecular mechanisms in OA may offer additional strategies for clinical prevention and treatment.In this review,we discuss the potential pathogenesis of OA in light of aging-associated changes and summarize three main components of the aging microenvironment of the OA joint:immune homeostatic imbalance,cellular senescence,and stem cell exhaustion,which could be induced by aging and further exacerbate OA progression.Additionally,it is emphasized that immune homeostatic imbalance appears before established OA,which occurs in the early stage and is the therapeutic window of opportunity for better clinical outcomes.Importantly,we evaluate recent therapeutic targets and promising interventions against these components,as well as the challenges and prospects for precise and individualized therapies of OA patients,which we believe would guide the construction of novel combined strategies targeting aging-related factors against OA for better treatments in the future.展开更多
Osteoarthritis(OA)is a common degenerative disease worldwide and new therapeutics that target inflammation and the crosstalk between immunocytes and chondrocytes are being developed to prevent and treat OA.These attem...Osteoarthritis(OA)is a common degenerative disease worldwide and new therapeutics that target inflammation and the crosstalk between immunocytes and chondrocytes are being developed to prevent and treat OA.These attempts involve repolarizing pro-inflammatory M1 macrophages into the anti-inflammatory M2 phenotype in synovium.In this study,we found that phosphoglycerate mutase 5(PGAM5)significantly increased in macrophages in OA synovium compared to controls based on histology of human samples and single-cell RNA sequencing results of mice models.To address the role of PGAM5 in macrophages in OA,we found conditional knockout of PGAM5 in macrophages greatly alleviated OA symptoms and promoted anabolic metabolism of chondrocytes in vitro and in vivo.Mechanistically,we found that PGAM5 enhanced M1 polarization via AKT-mTOR/p38/ERK pathways,whereas inhibited M2 polarization via STAT6-PPARγpathway in murine bone marrow-derived macrophages.Furthermore,we found that PGAM5 directly dephosphorylated Dishevelled Segment Polarity Protein 2(DVL2)which resulted in the inhibition ofβ-catenin and repolarization of M2 macrophages into M1 macrophages.Conditional knockout of both PGAM5 andβ-catenin in macrophages significantly exacerbated osteoarthritis compared to PGAM5-deficient mice.Motivated by these findings,we successfully designed mannose modified fluoropolymers combined with siPGAM5 to inhibit PGAM5 specifically in synovial macrophages via intra-articular injection,which possessed desired targeting abilities of synovial macrophages and greatly attenuated murine osteoarthritis.Collectively,these findings defined a key role for PGAM5 in orchestrating macrophage polarization and provides insights into novel macrophage-targeted strategy for treating OA.展开更多
To solve the divergence problem and overcome the difficulty in guaranteeing filtering accuracy during estimation of the process noise covariance or the measurement noise covariance with traditional new information-bas...To solve the divergence problem and overcome the difficulty in guaranteeing filtering accuracy during estimation of the process noise covariance or the measurement noise covariance with traditional new information-based nonlinear filtering methods,we design a new method for estimating noise statistical characteristics of nonlinear systems based on the credibility Kalman Filter(KF)theory considering noise correlation.This method first extends credibility to the Unscented Kalman Filter(UKF)and Extended Kalman Filter(EKF)based on the credibility theory.Further,an optimization model for nonlinear credibility under noise related conditions is established considering noise correlation.A combination of filtering smoothing and credibility iteration formula is used to improve the real-time performance of the nonlinear adaptive credibility KF algorithm,further expanding its application scenarios,and the derivation process of the formula theory is provided.Finally,the performance of the nonlinear credibility filtering algorithm is simulated and analyzed from multiple perspectives,and a comparative analysis conducted on specific experimental data.The simulation and experimental results show that the proposed credibility EKF and credibility UKF algorithms can estimate the noise covariance more accurately and effectively with lower average estimation time than traditional methods,indicating that the proposed algorithm has stable estimation performance and good real-time performance.展开更多
The wettability of rocks affects the balance between capillary and viscous forces during multiphase flow through porous media,which in turn determines the fluid displacement process governing the recovery of oil from ...The wettability of rocks affects the balance between capillary and viscous forces during multiphase flow through porous media,which in turn determines the fluid displacement process governing the recovery of oil from subsurface formations.In this work,the mechanism of wettability reversal of aged synthetic sandstones by metal oxide nanoparticles(SiO_(2) and Al_(2)O_(3))was investigated with particular focus on the impact of surface roughness,zeta potential,and temperature.The synthetic surfaces were prepared from powders of Berea sandstone with known grain size ranges and their average roughness and roughness ratio were obtained from the 3D surface reconstruction of their microscope images.Each surface was subsequently aged in Permian crude oil to alter its wettability.For surfaces with larger grain sizes and lower surface roughness ratios,the lower capillary pressure allowed stronger oil/surface interactions,leading to enhanced oil-wetness.The wettability alteration effects of nanoparticles were then examined through real-time top view imaging and dynamic front view contact angle experiments.The negatively charged SiO_(2) nanoparticles rapidly reversed the sandstone wettability,indicating their potential applicability as wettability alteration agents.By contrast,the positively charged Al_(2)O_(3) counterpart caused no wettability reversal.The mechanism of wettability alteration was further studied by microscale interaction analyses and nanoscale transmission electron microscopy.Because nanoparticles were only a few nanometers large,the microscale roughness had a negligible effect on the wettability reversal.Instead,the combined effect of van der Waals dispersion forces and surface-charge-induced electrostatic forces were recognized as the two key factors affecting the wettability of sandstone particles.Such interactions may be curbed at elevated temperatures due to a decrease in the zeta potential and colloidal stability of the particles.展开更多
To address the issue of low denoising accuracy of unmanned aerial vehicle(UAV)sensor data in a nonlinear non-Gaussian system,an adaptive central error entropy(CEE)—strong tracking cubature Kalman filter(STCKF)algorit...To address the issue of low denoising accuracy of unmanned aerial vehicle(UAV)sensor data in a nonlinear non-Gaussian system,an adaptive central error entropy(CEE)—strong tracking cubature Kalman filter(STCKF)algorithm based on fuzzy broad learning system(fuzzy-BLS)is proposed in this paper.Although entropy algorithms are known to be effective for denoising in non-Gaussian systems,their application in nonlinear systems is still limited.To address this issue,this study combines the central error entropy criterion with the STCKF algorithm.This approach is boosted by the denoising capabilities of the STCKF algorithm for nonlinear systems,thereby compensating for the shortcomings of the CEE criterion for nonlinear systems and leveraging the advantages of CEE in non-Gaussian systems.Thus,the new algorithm has enhanced robustness and accuracy for nonlinear non-Gaussian systems.To further optimize this algorithm,a parameter update method based on fuzzyBLS is adopted to address the problem of excessive reliance on experience and lack of dependency in the selection of parameters,such as weight and kernel width,in the fusion of the CEE criterion.This method can dynamically adjust the optimal parameter template obtained from offline training online to minimize the root mean square error of the denoising results and provide adaptive denoising capability.Simulation and actual data denoising experiments confirmed that the proposed data denoising method accurately addresses the denoising problem of UAV sensor data in nonlinear non-Gaussian systems.展开更多
Background Enterobacterial translocation is a leading contributor to fatal infection among patients with acute ischaemic stroke(AIS).Accumulative evidence suggests that mesenchymal stem cell(MSC)effectively ameliorate...Background Enterobacterial translocation is a leading contributor to fatal infection among patients with acute ischaemic stroke(AIS).Accumulative evidence suggests that mesenchymal stem cell(MSC)effectively ameliorates stroke outcomes.Whether MSC could inhibit post-stroke enterobacterial translocation remains elusive.Methods Patients with AIS and healthy individuals were enrolled in the study.Mice subjected to transient middle cerebral artery occlusion were treated with bone marrow-derived MSC(BM-MSC)right after reperfusion.Enterobacterial translocation was evaluated with Stroke Dysbiosis Index and circulating endotoxin.Thickness of mucus was assessed with Alcian blue staining.Hepatic glucocorticoid(GC)metabolism was analysed with expression of HSD11B2,HSD11B1 and SRD5A1.Results We report that the gut mucus layer was attenuated after the stroke leading to pronounced enterobacterial translocation.The attenuation of the gut mucus was attributed to diminished mucin production by goblet cells in response to the elevated systemic GC after cerebral ischaemia.Transferred-BM MSC restored the mucus thickness,thus preserving gut microbiota homeostasis and preventing enterobacterial invasion.Mechanistically,the transferred-BM MSC stationed in the liver and enhanced peroxisome proliferator-activated receptorγsignalling in hepatocytes.Consequently,expression of HSD11B2 and SRD5A1 was increased while HSD11B1 expression was downregulated which promoted GC catabolism and subsequently restored mucin production.Conclusions Our findings reveal that MSC transfer improves post-stroke gut barrier integrity and inhibits enterobacterial translocation by enhancing the hepatic GC metabolism thus representing a protective modulator of the liver-gut brain axis in AIS.展开更多
This paper describes an autonomous intelligent unmanned system test platform designed.The platform integrates multiple sensors to support experiments related to unmanned aerial vehicle(UAV)identification,tracking,and ...This paper describes an autonomous intelligent unmanned system test platform designed.The platform integrates multiple sensors to support experiments related to unmanned aerial vehicle(UAV)identification,tracking,and landing on water-based surfaces.Our current configuration includes an Inertial Measurement Unit(IMU),an ultra-wideband radar,and a dual-camera carousel system with infrared and visible cameras.We have also developed a comprehensive frontend interface for this multi-sensor fusion system.The platform's integrated hardware and software components bridge the gap between simulation and real-world testing.To validate the platform's performance,we conducted several autonomous landing experiments on a water-based deck to demonstrate the feasibility of autonomous landing of fixed-wing UAVs.展开更多
Tendon-bone healing is essential for an effective rotator cuff tendon repair surgery,however,this remains a significant challenge due to the lack of biomaterials with high strength and bioactivity.Inspired by the high...Tendon-bone healing is essential for an effective rotator cuff tendon repair surgery,however,this remains a significant challenge due to the lack of biomaterials with high strength and bioactivity.Inspired by the high-performance exoskeleton of natural organisms,we set out to apply natural fish scale(FS)modified by calcium silicate nanoparticles(CS NPs)as a new biomaterial(CS-FS)to overcome the challenge.Benefit from its“Bouligand”microstructure,such FS-based scaffold maintained excellent tensile strength(125.05 MPa)and toughness(14.16 MJ/m^(3)),which are 1.93 and 2.72 times that of natural tendon respectively,allowing it to well meet the requirements for rotator cuff tendon repair.Additionally,CS-FS showed diverse bioactivities by stimulating the differentiation and phenotypic maintenance of multiple types of cells participated into the composition of tendon-bone junction,(e.g.bone marrow mesenchymal stem cells(BMSCs),chondrocyte,and tendon stem/progenitor cells(TSPCs)).In both rat and rabbit rotator cuff tear(RCT)models,CS-FS played a key role in the tendon-bone interface regeneration and biomechanical function,which may be achieved by activating BMP-2/Smad/Runx2 pathway in BMSCs.Therefore,natural fish scale-based biomaterials are the promising candidate for clinical tendon repair due to their outstanding strength and bioactivity.展开更多
基金supported by grants from National Natural Science Foundation of China(32370892)Science and Technology Commission of Shanghai Municipality(23141901200)+3 种基金Shanghai Natural Science Foundation(24ZR1450100)Health Commission of Shanghai Municipality(2022JC029)Biomaterials and Regenerative Medicine Institute Cooperative Research Project,Shanghai Jiaotong University School of Medicine(2022LHA11)Talent-Introduction Program of Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine(2022YJRC05).
文摘Osteoarthritis(OA)is one of the most common degenerative and age-related diseases in joints,which affects 654 million people worldwide.Current therapies could not fundamentally reverse the pathologic process of OA due to the complex pathogenesis.Although OA mechanisms have been investigated on a large scale over the past decade,the OA pathology correlated with aging-associated changes is still largely unrevealed.Therefore,in-depth analysis of the aging microenvironment and aging-related molecular mechanisms in OA may offer additional strategies for clinical prevention and treatment.In this review,we discuss the potential pathogenesis of OA in light of aging-associated changes and summarize three main components of the aging microenvironment of the OA joint:immune homeostatic imbalance,cellular senescence,and stem cell exhaustion,which could be induced by aging and further exacerbate OA progression.Additionally,it is emphasized that immune homeostatic imbalance appears before established OA,which occurs in the early stage and is the therapeutic window of opportunity for better clinical outcomes.Importantly,we evaluate recent therapeutic targets and promising interventions against these components,as well as the challenges and prospects for precise and individualized therapies of OA patients,which we believe would guide the construction of novel combined strategies targeting aging-related factors against OA for better treatments in the future.
基金This work was supported by grants from National Natural Science Foundation of China(81830078,82071868,32370892)Science and Technology Commission of Shanghai Municipality(23141901200)+2 种基金Health Commission of Shanghai Municipality(2022JC029)Biomaterials and Regenerative Medicine Institute Cooperative Research Project,Shanghai Jiaotong University School of Medicine(2022LHA11)Shanghai Key Laboratory of Orthopedic Implant(No.KFKT202206).
文摘Osteoarthritis(OA)is a common degenerative disease worldwide and new therapeutics that target inflammation and the crosstalk between immunocytes and chondrocytes are being developed to prevent and treat OA.These attempts involve repolarizing pro-inflammatory M1 macrophages into the anti-inflammatory M2 phenotype in synovium.In this study,we found that phosphoglycerate mutase 5(PGAM5)significantly increased in macrophages in OA synovium compared to controls based on histology of human samples and single-cell RNA sequencing results of mice models.To address the role of PGAM5 in macrophages in OA,we found conditional knockout of PGAM5 in macrophages greatly alleviated OA symptoms and promoted anabolic metabolism of chondrocytes in vitro and in vivo.Mechanistically,we found that PGAM5 enhanced M1 polarization via AKT-mTOR/p38/ERK pathways,whereas inhibited M2 polarization via STAT6-PPARγpathway in murine bone marrow-derived macrophages.Furthermore,we found that PGAM5 directly dephosphorylated Dishevelled Segment Polarity Protein 2(DVL2)which resulted in the inhibition ofβ-catenin and repolarization of M2 macrophages into M1 macrophages.Conditional knockout of both PGAM5 andβ-catenin in macrophages significantly exacerbated osteoarthritis compared to PGAM5-deficient mice.Motivated by these findings,we successfully designed mannose modified fluoropolymers combined with siPGAM5 to inhibit PGAM5 specifically in synovial macrophages via intra-articular injection,which possessed desired targeting abilities of synovial macrophages and greatly attenuated murine osteoarthritis.Collectively,these findings defined a key role for PGAM5 in orchestrating macrophage polarization and provides insights into novel macrophage-targeted strategy for treating OA.
基金supported by the National Natural Science Foundation of China(No.62033010)the Qing Lan Project of Jiangsu Province,China(No.R2023Q07)the Aeronautical Science Foundation of China(No.2019460T5001).
文摘To solve the divergence problem and overcome the difficulty in guaranteeing filtering accuracy during estimation of the process noise covariance or the measurement noise covariance with traditional new information-based nonlinear filtering methods,we design a new method for estimating noise statistical characteristics of nonlinear systems based on the credibility Kalman Filter(KF)theory considering noise correlation.This method first extends credibility to the Unscented Kalman Filter(UKF)and Extended Kalman Filter(EKF)based on the credibility theory.Further,an optimization model for nonlinear credibility under noise related conditions is established considering noise correlation.A combination of filtering smoothing and credibility iteration formula is used to improve the real-time performance of the nonlinear adaptive credibility KF algorithm,further expanding its application scenarios,and the derivation process of the formula theory is provided.Finally,the performance of the nonlinear credibility filtering algorithm is simulated and analyzed from multiple perspectives,and a comparative analysis conducted on specific experimental data.The simulation and experimental results show that the proposed credibility EKF and credibility UKF algorithms can estimate the noise covariance more accurately and effectively with lower average estimation time than traditional methods,indicating that the proposed algorithm has stable estimation performance and good real-time performance.
基金the financial support from Baker Hughes Company and the U.S.National Science Foundation(NSF CAREER Award 1351296).
文摘The wettability of rocks affects the balance between capillary and viscous forces during multiphase flow through porous media,which in turn determines the fluid displacement process governing the recovery of oil from subsurface formations.In this work,the mechanism of wettability reversal of aged synthetic sandstones by metal oxide nanoparticles(SiO_(2) and Al_(2)O_(3))was investigated with particular focus on the impact of surface roughness,zeta potential,and temperature.The synthetic surfaces were prepared from powders of Berea sandstone with known grain size ranges and their average roughness and roughness ratio were obtained from the 3D surface reconstruction of their microscope images.Each surface was subsequently aged in Permian crude oil to alter its wettability.For surfaces with larger grain sizes and lower surface roughness ratios,the lower capillary pressure allowed stronger oil/surface interactions,leading to enhanced oil-wetness.The wettability alteration effects of nanoparticles were then examined through real-time top view imaging and dynamic front view contact angle experiments.The negatively charged SiO_(2) nanoparticles rapidly reversed the sandstone wettability,indicating their potential applicability as wettability alteration agents.By contrast,the positively charged Al_(2)O_(3) counterpart caused no wettability reversal.The mechanism of wettability alteration was further studied by microscale interaction analyses and nanoscale transmission electron microscopy.Because nanoparticles were only a few nanometers large,the microscale roughness had a negligible effect on the wettability reversal.Instead,the combined effect of van der Waals dispersion forces and surface-charge-induced electrostatic forces were recognized as the two key factors affecting the wettability of sandstone particles.Such interactions may be curbed at elevated temperatures due to a decrease in the zeta potential and colloidal stability of the particles.
基金partially supported by the National Natural Science Foundation of China(Grant Nos.62033010,U23B2061)the Qing Lan Project of Jiangsu Province of China(Grant No.R2023Q07)the Joint Fund of Zhejiang Provincial Natural Science Foundation of China(Grant No.ZJMD25D050002)。
文摘To address the issue of low denoising accuracy of unmanned aerial vehicle(UAV)sensor data in a nonlinear non-Gaussian system,an adaptive central error entropy(CEE)—strong tracking cubature Kalman filter(STCKF)algorithm based on fuzzy broad learning system(fuzzy-BLS)is proposed in this paper.Although entropy algorithms are known to be effective for denoising in non-Gaussian systems,their application in nonlinear systems is still limited.To address this issue,this study combines the central error entropy criterion with the STCKF algorithm.This approach is boosted by the denoising capabilities of the STCKF algorithm for nonlinear systems,thereby compensating for the shortcomings of the CEE criterion for nonlinear systems and leveraging the advantages of CEE in non-Gaussian systems.Thus,the new algorithm has enhanced robustness and accuracy for nonlinear non-Gaussian systems.To further optimize this algorithm,a parameter update method based on fuzzyBLS is adopted to address the problem of excessive reliance on experience and lack of dependency in the selection of parameters,such as weight and kernel width,in the fusion of the CEE criterion.This method can dynamically adjust the optimal parameter template obtained from offline training online to minimize the root mean square error of the denoising results and provide adaptive denoising capability.Simulation and actual data denoising experiments confirmed that the proposed data denoising method accurately addresses the denoising problem of UAV sensor data in nonlinear non-Gaussian systems.
基金supported by Guangzhou Key Research Program on Brain Science(202206060001 to ZL)Guangdong Basic and Applied Basic Research Foundation(2020A1515010056 to BZ)+3 种基金National Natural Science Foundation of China(82171307 to ZL)National Natural Science Foundation of China(82271348 to WC)Fundamental Research Funds for the Central Universities(23ykbj006 to WC)Science and Technology Program of Guangzhou(2023B01J1002 to ZL).
文摘Background Enterobacterial translocation is a leading contributor to fatal infection among patients with acute ischaemic stroke(AIS).Accumulative evidence suggests that mesenchymal stem cell(MSC)effectively ameliorates stroke outcomes.Whether MSC could inhibit post-stroke enterobacterial translocation remains elusive.Methods Patients with AIS and healthy individuals were enrolled in the study.Mice subjected to transient middle cerebral artery occlusion were treated with bone marrow-derived MSC(BM-MSC)right after reperfusion.Enterobacterial translocation was evaluated with Stroke Dysbiosis Index and circulating endotoxin.Thickness of mucus was assessed with Alcian blue staining.Hepatic glucocorticoid(GC)metabolism was analysed with expression of HSD11B2,HSD11B1 and SRD5A1.Results We report that the gut mucus layer was attenuated after the stroke leading to pronounced enterobacterial translocation.The attenuation of the gut mucus was attributed to diminished mucin production by goblet cells in response to the elevated systemic GC after cerebral ischaemia.Transferred-BM MSC restored the mucus thickness,thus preserving gut microbiota homeostasis and preventing enterobacterial invasion.Mechanistically,the transferred-BM MSC stationed in the liver and enhanced peroxisome proliferator-activated receptorγsignalling in hepatocytes.Consequently,expression of HSD11B2 and SRD5A1 was increased while HSD11B1 expression was downregulated which promoted GC catabolism and subsequently restored mucin production.Conclusions Our findings reveal that MSC transfer improves post-stroke gut barrier integrity and inhibits enterobacterial translocation by enhancing the hepatic GC metabolism thus representing a protective modulator of the liver-gut brain axis in AIS.
基金supported in part by Qing Lan Project of Jiangsu Province(Grant.R2023Q07)in part by National Natural Science Foundation of China(No.62033010,U23B2061)
文摘This paper describes an autonomous intelligent unmanned system test platform designed.The platform integrates multiple sensors to support experiments related to unmanned aerial vehicle(UAV)identification,tracking,and landing on water-based surfaces.Our current configuration includes an Inertial Measurement Unit(IMU),an ultra-wideband radar,and a dual-camera carousel system with infrared and visible cameras.We have also developed a comprehensive frontend interface for this multi-sensor fusion system.The platform's integrated hardware and software components bridge the gap between simulation and real-world testing.To validate the platform's performance,we conducted several autonomous landing experiments on a water-based deck to demonstrate the feasibility of autonomous landing of fixed-wing UAVs.
基金supported by the National Basic Research Program of China(grant No.2021YFA0715700)the Natural Science Foundation of China(32130062)+1 种基金Innovation Cross Team of Chinese Academy of Sciences(JCTD-2018-13)Science and Technology Commission of Shanghai Municipality(20442420300,21DZ1205600).
文摘Tendon-bone healing is essential for an effective rotator cuff tendon repair surgery,however,this remains a significant challenge due to the lack of biomaterials with high strength and bioactivity.Inspired by the high-performance exoskeleton of natural organisms,we set out to apply natural fish scale(FS)modified by calcium silicate nanoparticles(CS NPs)as a new biomaterial(CS-FS)to overcome the challenge.Benefit from its“Bouligand”microstructure,such FS-based scaffold maintained excellent tensile strength(125.05 MPa)and toughness(14.16 MJ/m^(3)),which are 1.93 and 2.72 times that of natural tendon respectively,allowing it to well meet the requirements for rotator cuff tendon repair.Additionally,CS-FS showed diverse bioactivities by stimulating the differentiation and phenotypic maintenance of multiple types of cells participated into the composition of tendon-bone junction,(e.g.bone marrow mesenchymal stem cells(BMSCs),chondrocyte,and tendon stem/progenitor cells(TSPCs)).In both rat and rabbit rotator cuff tear(RCT)models,CS-FS played a key role in the tendon-bone interface regeneration and biomechanical function,which may be achieved by activating BMP-2/Smad/Runx2 pathway in BMSCs.Therefore,natural fish scale-based biomaterials are the promising candidate for clinical tendon repair due to their outstanding strength and bioactivity.
