Cerenkov Luminescence Tomography(CLT)is a novel and potential imaging modality which can display the three-dimensional distribution of radioactive probes.However,due to severe ill-posed inverse problem,obtaining accur...Cerenkov Luminescence Tomography(CLT)is a novel and potential imaging modality which can display the three-dimensional distribution of radioactive probes.However,due to severe ill-posed inverse problem,obtaining accurate reconstruction results is still a challenge for traditional model-based methods.The recently emerged deep learning-based methods can directly learn the mapping relation between the surface photon intensity and the distribution of the radioactive source,which effectively improves the performance of CLT reconstruction.However,the previously proposed deep learning-based methods cannot work well when the order of input is disarranged.In this paper,a novel 3D graph convolution-based residual network,GCR-Net,is proposed,which can obtain a robust and accurate reconstruction result from the photon intensity of the surface.Additionally,it is proved that the network is insensitive to the order of input.The performance of this method was evaluated with numerical simulations and in vivo experiments.The results demonstrated that compared with the existing methods,the proposed method can achieve efficient and accurate reconstruction in localization and shape recovery by utilizing threedimensional information.展开更多
Osteoarthritis(OA)is a highly incident total joint degenerative disease with cartilage degeneration as the primary pathogenesis.The cartilage matrix is mainly composed of collagen,a matrix protein with a hallmark trip...Osteoarthritis(OA)is a highly incident total joint degenerative disease with cartilage degeneration as the primary pathogenesis.The cartilage matrix is mainly composed of collagen,a matrix protein with a hallmark triplehelix structure,which unfolds with collagen degradation on the cartilage surface.A collagen hybridizing peptide(CHP)is a synthetic peptide that binds the denatured collagen triple helix,conferring a potential diseasetargeting possibility for early-stage OA.Here,we constructed an albumin nanoparticle(An)conjugated with CHP,loaded with a chondrogenesis-promoting small molecule drug,kartogenin(KGN).The CHP-KGN-An particle exhibited sustained release of KGN in vitro and prolonged in vivo retention selectively within the degenerated cartilage in the knee joints of model mice with early-stage OA.Compared to treatment with KGN alone,CHP-KGN-An robustly attenuated cartilage degradation,synovitis,osteophyte formation,and subchondral bone sclerosis in OA model mice and exhibited a more prominent effect on physical activity improvement and pain alleviation.Our study showcases that targeting the degenerated cartilage by collagen hybridization can remarkably promote the efficacy of small molecule drugs and may provide a novel delivery strategy for earlystage OA therapeutics.展开更多
Background:Reactive oxygen species(ROS)is considered as ubiquitous and highly active chemicals that influence tendon integrity and orchestrate tendon repair.With significant recent advances in nanomaterials,cerium oxi...Background:Reactive oxygen species(ROS)is considered as ubiquitous and highly active chemicals that influence tendon integrity and orchestrate tendon repair.With significant recent advances in nanomaterials,cerium oxide nanoparticles(CeO_(2)NPs)exhibit superoxide dismutase-and catalase-like activities.Herein,we introduced a therapeutic approach of CeO_(2)NPs for Achilles tendinopathy(AT)healing.Methods:CeO_(2)NPs were synthesized to examine their effect as ROS scavengers on AT healing in vitro and in vivo.The mRNA levels of inflammatory factors were evaluated in AT after CeO_(2)NPs treatment in vitro.The mechanisms underlying CeO_(2)NPs-mediated stimulation of NRF2 translocation and ERK signaling were verified through immunofluorescence and Western blot analysis.The efficacy of CeO_(2)NPs was tested in an AT rat model in comparison with the control.Results:CeO_(2)NPs not only significantly scavenged multiple ROS and suppressed ROS-induced inflammatory reactions but also protected cell proliferation under oxidative stress induced by tert-butyl hydroperoxide(TBHP).Moreover,CeO_(2)NPs could promote NRF_(2)nuclear translocation for anti-oxidation and anti-inflammation through the ERK signaling pathway.In a rat model of collagenase-induced tendon injuries,CeO_(2)NPs showed significant therapeutic efficacy by ameliorating tendon damage.Conclusion:The present study provides valuable insights into the molecular mechanism of CeO_(2)NPs to ameliorate ROS in tenocytes via the ERK/NRF_(2)signaling pathway,which underscores the potential of CeO_(2)NPs for application in the treatment of enthesopathy healing.展开更多
基金National Key Research and Development Program of China (2019YFC1521102)National Natural Science Foundation of China (61701403,61806164,62101439,61906154)+4 种基金China Postdoctoral Science Foundation (2018M643719)Natural Science Foundation of Shaanxi Province (2020JQ-601)Young Talent Support Program of the Shaanxi Association for Science and Technology (20190107)Key Research and Development Program of Shaanxi Province (2019GY-215,2021ZDLSF06-04)Major research and development project of Qinghai (2020-SF-143).
文摘Cerenkov Luminescence Tomography(CLT)is a novel and potential imaging modality which can display the three-dimensional distribution of radioactive probes.However,due to severe ill-posed inverse problem,obtaining accurate reconstruction results is still a challenge for traditional model-based methods.The recently emerged deep learning-based methods can directly learn the mapping relation between the surface photon intensity and the distribution of the radioactive source,which effectively improves the performance of CLT reconstruction.However,the previously proposed deep learning-based methods cannot work well when the order of input is disarranged.In this paper,a novel 3D graph convolution-based residual network,GCR-Net,is proposed,which can obtain a robust and accurate reconstruction result from the photon intensity of the surface.Additionally,it is proved that the network is insensitive to the order of input.The performance of this method was evaluated with numerical simulations and in vivo experiments.The results demonstrated that compared with the existing methods,the proposed method can achieve efficient and accurate reconstruction in localization and shape recovery by utilizing threedimensional information.
基金supported by the National Natural Science Foundation of China(82325035,82172481,32271409,82071977,and 92059104)the Six Talent Peaks Project of Jiangsu Province(WSW-079)+1 种基金the 2018 High-Level Health Team of Zhuhai,the Innovation Project of National Orthopedics and Sports Medicine Rehabilitation Clinical Medical Research Center(2021-NCRC-CXJJ-ZH-16)the Guangdong-Hong Kong-Macao University Joint Laboratory of Interventional Medicine Foundation of Guangdong Province(2023LSYS001).Fig.1a was created by Biorender.com.
文摘Osteoarthritis(OA)is a highly incident total joint degenerative disease with cartilage degeneration as the primary pathogenesis.The cartilage matrix is mainly composed of collagen,a matrix protein with a hallmark triplehelix structure,which unfolds with collagen degradation on the cartilage surface.A collagen hybridizing peptide(CHP)is a synthetic peptide that binds the denatured collagen triple helix,conferring a potential diseasetargeting possibility for early-stage OA.Here,we constructed an albumin nanoparticle(An)conjugated with CHP,loaded with a chondrogenesis-promoting small molecule drug,kartogenin(KGN).The CHP-KGN-An particle exhibited sustained release of KGN in vitro and prolonged in vivo retention selectively within the degenerated cartilage in the knee joints of model mice with early-stage OA.Compared to treatment with KGN alone,CHP-KGN-An robustly attenuated cartilage degradation,synovitis,osteophyte formation,and subchondral bone sclerosis in OA model mice and exhibited a more prominent effect on physical activity improvement and pain alleviation.Our study showcases that targeting the degenerated cartilage by collagen hybridization can remarkably promote the efficacy of small molecule drugs and may provide a novel delivery strategy for earlystage OA therapeutics.
基金the National Natural Science Foundation of China(Nos.81941009,81991514,32271409,and 82202778)Nanjing Distinguished Youth Fund(No.JQX20001)+3 种基金Jiangsu Provincial Key R&D Program(No.BE2022836)China Postdoctoral Science Foundation(No.2020M671456)National Basic Research Program of China(No.2021YFA1201404)Jiangsu Provincial Key Medical Center Foundation,Jiangsu Provincial Medical Outstanding Talent Foundation,Jiangsu Provincial Medical Youth Talent Foundation and Jiangsu Provincial Key Medical Talent Foundation,and the Fundamental Research Funds for the Central Universities(Nos.14380493 and 14380494).
文摘Background:Reactive oxygen species(ROS)is considered as ubiquitous and highly active chemicals that influence tendon integrity and orchestrate tendon repair.With significant recent advances in nanomaterials,cerium oxide nanoparticles(CeO_(2)NPs)exhibit superoxide dismutase-and catalase-like activities.Herein,we introduced a therapeutic approach of CeO_(2)NPs for Achilles tendinopathy(AT)healing.Methods:CeO_(2)NPs were synthesized to examine their effect as ROS scavengers on AT healing in vitro and in vivo.The mRNA levels of inflammatory factors were evaluated in AT after CeO_(2)NPs treatment in vitro.The mechanisms underlying CeO_(2)NPs-mediated stimulation of NRF2 translocation and ERK signaling were verified through immunofluorescence and Western blot analysis.The efficacy of CeO_(2)NPs was tested in an AT rat model in comparison with the control.Results:CeO_(2)NPs not only significantly scavenged multiple ROS and suppressed ROS-induced inflammatory reactions but also protected cell proliferation under oxidative stress induced by tert-butyl hydroperoxide(TBHP).Moreover,CeO_(2)NPs could promote NRF_(2)nuclear translocation for anti-oxidation and anti-inflammation through the ERK signaling pathway.In a rat model of collagenase-induced tendon injuries,CeO_(2)NPs showed significant therapeutic efficacy by ameliorating tendon damage.Conclusion:The present study provides valuable insights into the molecular mechanism of CeO_(2)NPs to ameliorate ROS in tenocytes via the ERK/NRF_(2)signaling pathway,which underscores the potential of CeO_(2)NPs for application in the treatment of enthesopathy healing.