A zero-crossing dynamic speckle method is proposed to determine the velocities of nanoparticles in nanofluids.A Gaussian laser beam is used to illuminate nanofluids in a pipe,and the dynamic speckles are detected by a...A zero-crossing dynamic speckle method is proposed to determine the velocities of nanoparticles in nanofluids.A Gaussian laser beam is used to illuminate nanofluids in a pipe,and the dynamic speckles are detected by a spatially integrating detector with an aperture.The integrated speckle intensity signal is processed by a computer and the zero-crossing rate is counted.The velocity of the nanoparticles can be determined from its relationship to zero-crossing rate.The results show that the nanoparticles exhibit features of flowing nanofluids,and when the average velocity of the nanofluids is 53.4mm/s,the average velocity of the nanoparticles is 51.8 ± 5.1 mm/s.展开更多
Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease accompanied by persistent multiarticular synovitis and cartilage degradation. The present clinical treatments are limited to disease-modifying ant...Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease accompanied by persistent multiarticular synovitis and cartilage degradation. The present clinical treatments are limited to disease-modifying anti-rheumatic drugs (DMARDs) and aims to relieve pain and control the inflammation of RA. Despite considerable advances in the research of RA, the employment of current clinical procedure is enormous, hindered by systemic side effect, frequent administration, tolerance from long-lasting administration, and high costs. Emerging immunoengineering-based strategies, such as multiple immune-active nanotechnologies via mechanism-based immunology approaches, have been developed to improve specific targeting and to reduce adverse reactions for RA treatments. Here, we review recent studies in immunoengineering for the treatment of RA. The prospect of future immunoengineering treatment for RA has also been discussed.展开更多
Osteoporosis is an osteolytic disorder commonly associated with excessive osteoclast formation.Transcriptional coactivator with PDZ-binding motif(TAZ)is a key downstream effector of the Hippo signaling pathway;it was ...Osteoporosis is an osteolytic disorder commonly associated with excessive osteoclast formation.Transcriptional coactivator with PDZ-binding motif(TAZ)is a key downstream effector of the Hippo signaling pathway;it was suggested to be involved in the regulation of bone homeostasis.However,the exact role of TAZ in osteoclasts has not yet been established.In this study,we demonstrated that global knockout and osteoclast-specific knockout of TAZ led to a low-bone mass phenotype due to elevated osteoclast formation,which was further evidenced by in vitro osteoclast formation assays.Moreover,the overexpression of TAZ inhibited RANKL-induced osteoclast formation,whereas silencing of TAZ reduced it.Mechanistically,TAZ bound to TGF-activated kinase 1(TAK1)and reciprocally inhibited NF-κB signaling,suppressing osteoclast differentiation.Collectively,our findings highlight an essential role of TAZ in the regulation of osteoclastogenesis in osteoporosis and its underlying mechanism.展开更多
Lumbar degenerative disc diseases cause low back pain(LBP). The maintenance of the height and stability of the intervertebral disc(IVD) space is an effective treatment for LBP. The following study evaluated the effect...Lumbar degenerative disc diseases cause low back pain(LBP). The maintenance of the height and stability of the intervertebral disc(IVD) space is an effective treatment for LBP. The following study evaluated the effects of fibroblast injection on intervertebral disc degeneration(IDD) in a preclinical setting. Compared with the IDD group, the fibroblast treatment group demonstrated effective maintenance of IVD height, reduced endplate degeneration, and improved nuclear magnetic resonance signals and overall histological structure. In doing so, fibrotic IVDs maintained the stability and biomechanics of the vertebra. This finding is in agreement with clinical findings that human nucleus pulposus(NP) fibrosis is essential for the maintenance of IVD height and mechanical properties in patients following percutaneous endoscopic lumbar discectomy(PELD). Mechanistically, we demonstrated that injected fibroblasts not only proliferated but also induced NP cells to adopt a fibrotic phenotype via the secretion of TGF-β.Finally, to better mimic human conditions, the efficacy of autologous fibroblast injection in the treatment of IDD was further examined in a nonhuman primate cynomolgus monkey model due to their capacity for upright posture. We showed that the injection of fibroblasts could maintain the IVD height and rescue IVD signals in cynomolgus monkeys. Taken together, the results of our study reveal that autologous fibroblast injection can enhance the natural process of fibrosis during acute and subacute stages of stress-induced IDD. Fibrotic IVDs can maintain the stability, biological activity, and mechanical properties of the intervertebral space, thus providing a new direction for the treatment of intervertebral space-derived lumbar degenerative diseases.展开更多
Breast cancer bone metastasis poses significant challenge for therapeutic strategies.Inside the metastatic environment,osteoclasts and tumor cells interact synergistically to promote cancer progression.In this study,t...Breast cancer bone metastasis poses significant challenge for therapeutic strategies.Inside the metastatic environment,osteoclasts and tumor cells interact synergistically to promote cancer progression.In this study,the proprotein convertase furin is targeted due to its critical roles in both tumor cell invasion and osteoclast function.Importantly,the furin inhibitor is specifically delivered by bone targeting superparamagnetic iron oxide(SPIO)nanoparticles.Our in vitro and in vivo data demonstrate that this system can effectively inhibit both osteoclastic bone resorption and breast cancer invastion,leading to alleviated osteolysis.Therefore,the bone targeting&furin inhibition nanoparticle system is a promising therapeutic and diagnostic strategy for breast cancer bone metastasis.展开更多
Human glycerol channel aquaporin 7(AQP7)conducts glycerol release from adipocyte and enters the cells in pancreatic islets,muscles,and kidney tubules,and thus regulates glycerol metabolism in those tissues.Compared wi...Human glycerol channel aquaporin 7(AQP7)conducts glycerol release from adipocyte and enters the cells in pancreatic islets,muscles,and kidney tubules,and thus regulates glycerol metabolism in those tissues.Compared with other human aquaglyceroporins,AQP7 shows a less conserved‘‘NPA”motif in the center cavity and a pair of aromatic residues at Ar/R selectivity filter.To understand the structural basis for the glycerol conductance,we crystallized the human AQP7 and determined the structure at 3.7Å.A substrate binding pocket was found near the Ar/R filter where a glycerol molecule is bound and stabilized by R229.Glycerol uptake assay on human AQP7 as well as AQP3 and AQP10 demonstrated strong glycerol transportation activities at the physiological condition.The human AQP7 structure,in combination with the molecular dynamics simulation thereon,reveals a fully closed conformation with its permeation pathway strictly confined by the Ar/R filter at the exoplasmic side and the gate at the cytoplasmic side,and the binding of glycerol at the Ar/R filter plays a critical role in controlling the glycerol flux by driving the dislocation of the residues at narrowest parts of glycerol pathway in AQP7.展开更多
基金Supported by the Natural Science Foundation of Jiangsu Province under Grant No BK2008409the National Natural Science Foundation of China under Grant No 11174151.
文摘A zero-crossing dynamic speckle method is proposed to determine the velocities of nanoparticles in nanofluids.A Gaussian laser beam is used to illuminate nanofluids in a pipe,and the dynamic speckles are detected by a spatially integrating detector with an aperture.The integrated speckle intensity signal is processed by a computer and the zero-crossing rate is counted.The velocity of the nanoparticles can be determined from its relationship to zero-crossing rate.The results show that the nanoparticles exhibit features of flowing nanofluids,and when the average velocity of the nanofluids is 53.4mm/s,the average velocity of the nanoparticles is 51.8 ± 5.1 mm/s.
基金the National Science Foundation of China(82130073 and 61973206)Shanghai Leading Talents Program in 2020(110)+5 种基金Science and Technology Commission of Shanghai Municipality(23ZR1437600,23S31905900)Biomaterials and Regenerative Medicine Institute Cooperative Research Project,Shanghai Jiaotong University School of Medicine(2022LHA01)Science and Technology Commission of Shanghai Municipality(23S31905900)Shanghai Pujiang Program(21PJ1409200)China Postdoctoral Science Foundation(2022M722122)Shanghai Frontiers Science Center of Degen-eration and Regeneration in Skeletal System,and the Project of Biobank(YBKB202118)from Shanghai Ninth People's Hospital,Shanghai Jiao Tong University School of Medicine.
文摘Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease accompanied by persistent multiarticular synovitis and cartilage degradation. The present clinical treatments are limited to disease-modifying anti-rheumatic drugs (DMARDs) and aims to relieve pain and control the inflammation of RA. Despite considerable advances in the research of RA, the employment of current clinical procedure is enormous, hindered by systemic side effect, frequent administration, tolerance from long-lasting administration, and high costs. Emerging immunoengineering-based strategies, such as multiple immune-active nanotechnologies via mechanism-based immunology approaches, have been developed to improve specific targeting and to reduce adverse reactions for RA treatments. Here, we review recent studies in immunoengineering for the treatment of RA. The prospect of future immunoengineering treatment for RA has also been discussed.
基金funded by the National Natural Science Foundation of China(Grant No.82002329,82072467,81871801 and 81772373)the Natural Science Foundation of Zhejiang Province(Grant No.LQ19H060001)Shanghai Municipal Education Commission-Gaofeng Clinical Medicine Grant Support,and SHIPM-pi fund Nos.JY201804 and JC201801 from the Shanghai Institute of Precision Medicine,Ninth People’s Hospital of Shanghai,Jiao Tong University School of Medicine.
文摘Osteoporosis is an osteolytic disorder commonly associated with excessive osteoclast formation.Transcriptional coactivator with PDZ-binding motif(TAZ)is a key downstream effector of the Hippo signaling pathway;it was suggested to be involved in the regulation of bone homeostasis.However,the exact role of TAZ in osteoclasts has not yet been established.In this study,we demonstrated that global knockout and osteoclast-specific knockout of TAZ led to a low-bone mass phenotype due to elevated osteoclast formation,which was further evidenced by in vitro osteoclast formation assays.Moreover,the overexpression of TAZ inhibited RANKL-induced osteoclast formation,whereas silencing of TAZ reduced it.Mechanistically,TAZ bound to TGF-activated kinase 1(TAK1)and reciprocally inhibited NF-κB signaling,suppressing osteoclast differentiation.Collectively,our findings highlight an essential role of TAZ in the regulation of osteoclastogenesis in osteoporosis and its underlying mechanism.
基金supported by the National Natural Science Foundation of China (81871790) & (81572167)the Shanghai Hospital Development Center Foundation (SHDC12016110)
文摘Lumbar degenerative disc diseases cause low back pain(LBP). The maintenance of the height and stability of the intervertebral disc(IVD) space is an effective treatment for LBP. The following study evaluated the effects of fibroblast injection on intervertebral disc degeneration(IDD) in a preclinical setting. Compared with the IDD group, the fibroblast treatment group demonstrated effective maintenance of IVD height, reduced endplate degeneration, and improved nuclear magnetic resonance signals and overall histological structure. In doing so, fibrotic IVDs maintained the stability and biomechanics of the vertebra. This finding is in agreement with clinical findings that human nucleus pulposus(NP) fibrosis is essential for the maintenance of IVD height and mechanical properties in patients following percutaneous endoscopic lumbar discectomy(PELD). Mechanistically, we demonstrated that injected fibroblasts not only proliferated but also induced NP cells to adopt a fibrotic phenotype via the secretion of TGF-β.Finally, to better mimic human conditions, the efficacy of autologous fibroblast injection in the treatment of IDD was further examined in a nonhuman primate cynomolgus monkey model due to their capacity for upright posture. We showed that the injection of fibroblasts could maintain the IVD height and rescue IVD signals in cynomolgus monkeys. Taken together, the results of our study reveal that autologous fibroblast injection can enhance the natural process of fibrosis during acute and subacute stages of stress-induced IDD. Fibrotic IVDs can maintain the stability, biological activity, and mechanical properties of the intervertebral space, thus providing a new direction for the treatment of intervertebral space-derived lumbar degenerative diseases.
基金supported by grants from Natural Science Foundation of China(No.81772373,No.81572167)by Shanghai Municipal Education Commission-Gaofeng Clinical Medicine Grant Support,the SHIPM-pi fund No.JY201804&No.JC201801 from Shanghai Institute of Precision Medicine,Ninth People's Hospital Shanghai Jiao Tong University,Shanghai Jiao Tong University School of Medicine,and by the Foundation of National Facility for Translational Medicine(Shanghai)(No.TMSK-2020-119).
文摘Breast cancer bone metastasis poses significant challenge for therapeutic strategies.Inside the metastatic environment,osteoclasts and tumor cells interact synergistically to promote cancer progression.In this study,the proprotein convertase furin is targeted due to its critical roles in both tumor cell invasion and osteoclast function.Importantly,the furin inhibitor is specifically delivered by bone targeting superparamagnetic iron oxide(SPIO)nanoparticles.Our in vitro and in vivo data demonstrate that this system can effectively inhibit both osteoclastic bone resorption and breast cancer invastion,leading to alleviated osteolysis.Therefore,the bone targeting&furin inhibition nanoparticle system is a promising therapeutic and diagnostic strategy for breast cancer bone metastasis.
基金the National Key Research and Development Program of China(2018YFC1004704 and 2017YFC1001303)the National Natural Science Foundation of China(U1632132,31670849,and 91853206)+3 种基金the Shanghai Science and Technology Committee(20S11902000)the SHIPM-pi fund(JY201804)the SHIPM-sigma fund(2018JC002)from Shanghai Institute of Precision Medicine,Ninth People’s Hospital Shanghai Jiao Tong University School of Medicinethe Innovative Research Team of Highlevel Local Universities in Shanghai(SSMU-ZLCX20180600)。
文摘Human glycerol channel aquaporin 7(AQP7)conducts glycerol release from adipocyte and enters the cells in pancreatic islets,muscles,and kidney tubules,and thus regulates glycerol metabolism in those tissues.Compared with other human aquaglyceroporins,AQP7 shows a less conserved‘‘NPA”motif in the center cavity and a pair of aromatic residues at Ar/R selectivity filter.To understand the structural basis for the glycerol conductance,we crystallized the human AQP7 and determined the structure at 3.7Å.A substrate binding pocket was found near the Ar/R filter where a glycerol molecule is bound and stabilized by R229.Glycerol uptake assay on human AQP7 as well as AQP3 and AQP10 demonstrated strong glycerol transportation activities at the physiological condition.The human AQP7 structure,in combination with the molecular dynamics simulation thereon,reveals a fully closed conformation with its permeation pathway strictly confined by the Ar/R filter at the exoplasmic side and the gate at the cytoplasmic side,and the binding of glycerol at the Ar/R filter plays a critical role in controlling the glycerol flux by driving the dislocation of the residues at narrowest parts of glycerol pathway in AQP7.
