Streptococcus suis serotype 2(S.suis 2)is a zoonotic pathogen that clinically causes severe swine and human infections(such as meningitis,endocarditis,and septicemia).In order to cause widespread diseases in different...Streptococcus suis serotype 2(S.suis 2)is a zoonotic pathogen that clinically causes severe swine and human infections(such as meningitis,endocarditis,and septicemia).In order to cause widespread diseases in different organs,S.suis 2 must colonize the host,break the blood barrier,and cause exaggerated inflammation.In the last few years,most studies have focused on a single virulence factor and its influences on the host.Membrane vesicles(MVs)can be actively secreted into the extracellular environment contributing to bacteria-host interactions.Gram-negative bacteria-derived outer membrane vesicles(OMVs)were recently shown to activate host Caspase-11-mediated non-canonical inflammasome pathway via deliverance of OMV-bound lipopolysaccharide(LPS),causing host cell pyroptosis.However,little is known about the effect of the MVs from S.suis 2(Gram-positive bacteria without LPS)on cell pyroptosis.Thus,we investigated the molecular mechanism by which S.suis 2 MVs participate in endothelial cell pyroptosis.In this study,we used proteomics,electron scanning microscopy,fluorescence microscope,Western blotting,and bioassays,to investigate the MVs secreted by S.suis 2.First,we demonstrated that S.suis 2 secreted MVs with an average diameter of 72.04 nm,and 200 proteins in MVs were identified.Then,we showed that MVs were transported to cells via mainly dynamin-dependent endocytosis.The S.suis 2 MVs activated NLRP3/Caspase-1/GSDMD canonical inflammasome signaling pathway,resulting in cell pyroptosis,but it did not activate the Caspase-4/-5 pathway.More importantly,endothelial cells produce large amounts of reactive oxygen species(ROS)and lost their mitochondrial membrane potential under induction by S.suis 2 MVs.The results in this study suggest for the first time that MVs from S.suis 2 were internalized by endothelial cells via mainly dynamin-dependent endocytosis and might promote NLRP3/Caspase-1/GSDMD pathway by mitochondrial damage,which produced mtDNA and ROS under induction,leading to the pyroptosis of endothelial cells.展开更多
Osteochondral defects (OCD) are common but difficult to heal due to the low intrinsic repair capacity of cartilage and its complex hierarchical structure. In osteoarthritis (OA), OCD become more challenging to repair ...Osteochondral defects (OCD) are common but difficult to heal due to the low intrinsic repair capacity of cartilage and its complex hierarchical structure. In osteoarthritis (OA), OCD become more challenging to repair as both cartilage and subchondral bone regeneration are further impaired due to the arthritic environment. Numerous biomaterials have been developed and tested in osteochondral defects while ignoring the inflammatory environment. To target this challenging underlying pathophysiology, we designed and fabricated a biphasic porous and degradable scaffold incorporating anti-inflammatory and anabolic molecules by low-temperature rapid prototyping technology, and its effects on promoting osteochondral regeneration were evaluated using our well-established OA-OCD rabbit model. The biphasic porous scaffolds consisted of poly lactic-co-glycolic acid (PLGA) with kartogenin (KGN) for cartilage repair and PLGA and β-calcium phosphate (PLGA/β-TCP) with cinnamaldehyde (CIN) for subchondral bone repair. KGN is a molecule for promoting chondrogenesis and CIN is a phytomolecule for enhancing osteogenesis and alleviating inflammation. The biphasic scaffolds PLGA/KGN-PLGA/β-TCP/CIN (PK/PTC) with bio-mimic structure provided stable mechanical properties and exhibited excellent biocompatibility to support cell adhesion, proliferation, migration, and distribution. Furthermore, KGN and CIN within biphasic scaffolds could be released in a controlled and sustained mode, and the biphasic scaffold degraded slowly in vitro . Evaluating the repair of 16-weeks post-implantation into critically sized OA-OCD rabbit models revealed that the biphasic scaffold could promote subchondral bone and cartilage regeneration, as well as reverse subchondral osteosclerosis caused by inflammation in vivo . These findings support the utilization of the PK/PTC scaffold for osteochondral regeneration and provide a promising potential strategy for clinical application for the treatment of patients with OA-OCD.展开更多
The development of precise and sensitive electrophysiological recording platforms holds the utmost importance for research in the fields of cardiology and neuroscience.In recent years,active micro/nano-bioelectronic d...The development of precise and sensitive electrophysiological recording platforms holds the utmost importance for research in the fields of cardiology and neuroscience.In recent years,active micro/nano-bioelectronic devices have undergone significant advancements,thereby facilitating the study of electrophysiology.The distinctive configuration and exceptional functionality of these active micro-nano-collaborative bioelectronic devices offer the potential for the recording of high-fidelity action potential signals on a large scale.In this paper,we review three-dimensional active nano-transistors and planar active micro-transistors in terms of their applications in electroexcitable cells,focusing on the evaluation of the effects of active micro/nano-bioelectronic devices on electrophysiological signals.Looking forward to the possibilities,challenges,and wide prospects of active micro-nano-devices,we expect to advance their progress to satisfy the demands of theoretical investigations and medical implementations within the domains of cardiology and neuroscience research.展开更多
Cardiovascular diseases(CVDs)are the first cause of death globally,posing a significant threat to human health.Cardiac electrophysiology is pivotal for the understanding and management of CVDs,particularly for address...Cardiovascular diseases(CVDs)are the first cause of death globally,posing a significant threat to human health.Cardiac electrophysiology is pivotal for the understanding and management of CVDs,particularly for addressing arrhythmias.A significant proliferation of micro-nano bioelectric devices and systems has occurred in the field of cardiomyocyte electrophysiology.These bioelectronic platforms feature distinctive electrode geometries that improve the fidelity of native electrophysiological signals.Despite the prevalence of planar microelectrode arrays(MEAs)for simultaneous multichannel recording of cellular electrophysiological signals,extracellular recordings often yield suboptimal signal quality.In contrast,three-dimensional(3D)MEAs and advanced penetration strategies allow highfidelity intracellular signal detection.3D nanodevices are categorized into the active and the passive.Active devices rely on external power sources to work,while passive devices operate without external power.Passive devices possess simplicity,biocompatibility,stability,and lower power consumption compared to active ones,making them ideal for sensors and implantable applications.This review comprehensively discusses the fabrication,geometric configuration,and penetration strategies of passive 3D micro/nanodevices,emphasizing their application in drug screening and disease modeling.Moreover,we summarize existing challenges and future opportunities to develop passive micro/nanobioelectronic devices from cardiac electrophysiological research to cardiovascular clinical practice.展开更多
基金supported by the National Natural Science Foundation of China(U22A20520)the Innovation Team Project of Modern Agricultural Industrial Technology System of Guangdong Province,China(2023KJ119)the Natural Science Foundation Program of Guangdong Province,China(2023A1515012206)。
文摘Streptococcus suis serotype 2(S.suis 2)is a zoonotic pathogen that clinically causes severe swine and human infections(such as meningitis,endocarditis,and septicemia).In order to cause widespread diseases in different organs,S.suis 2 must colonize the host,break the blood barrier,and cause exaggerated inflammation.In the last few years,most studies have focused on a single virulence factor and its influences on the host.Membrane vesicles(MVs)can be actively secreted into the extracellular environment contributing to bacteria-host interactions.Gram-negative bacteria-derived outer membrane vesicles(OMVs)were recently shown to activate host Caspase-11-mediated non-canonical inflammasome pathway via deliverance of OMV-bound lipopolysaccharide(LPS),causing host cell pyroptosis.However,little is known about the effect of the MVs from S.suis 2(Gram-positive bacteria without LPS)on cell pyroptosis.Thus,we investigated the molecular mechanism by which S.suis 2 MVs participate in endothelial cell pyroptosis.In this study,we used proteomics,electron scanning microscopy,fluorescence microscope,Western blotting,and bioassays,to investigate the MVs secreted by S.suis 2.First,we demonstrated that S.suis 2 secreted MVs with an average diameter of 72.04 nm,and 200 proteins in MVs were identified.Then,we showed that MVs were transported to cells via mainly dynamin-dependent endocytosis.The S.suis 2 MVs activated NLRP3/Caspase-1/GSDMD canonical inflammasome signaling pathway,resulting in cell pyroptosis,but it did not activate the Caspase-4/-5 pathway.More importantly,endothelial cells produce large amounts of reactive oxygen species(ROS)and lost their mitochondrial membrane potential under induction by S.suis 2 MVs.The results in this study suggest for the first time that MVs from S.suis 2 were internalized by endothelial cells via mainly dynamin-dependent endocytosis and might promote NLRP3/Caspase-1/GSDMD pathway by mitochondrial damage,which produced mtDNA and ROS under induction,leading to the pyroptosis of endothelial cells.
基金supported by the collaborative project from the National Key R&D Program of China and Innovation and Tech-nology Fund Mainland-Hong Kong Joint Funding Scheme(Nos.2021YFE0202300 and MHP/011/20)the Sino-Swiss collaborative project from the Ministry of Science and Technology and the Swiss National Science Foundation under the SSSTC program(Grant Nos.2015DFG32200 and 156362)+2 种基金Shenzhen Collaborative Innovation Plan-International Cooperation Project(Grant No.GJHZ20190821160803823)Development and Reform Commission of Shenzhen Municipality(2019)(No.561)Shenzhen Double Chain Project for Innovation and Development Industry supported by Bureau of Industry and Information Technology of Shenzhen(No.201908141541).
文摘Osteochondral defects (OCD) are common but difficult to heal due to the low intrinsic repair capacity of cartilage and its complex hierarchical structure. In osteoarthritis (OA), OCD become more challenging to repair as both cartilage and subchondral bone regeneration are further impaired due to the arthritic environment. Numerous biomaterials have been developed and tested in osteochondral defects while ignoring the inflammatory environment. To target this challenging underlying pathophysiology, we designed and fabricated a biphasic porous and degradable scaffold incorporating anti-inflammatory and anabolic molecules by low-temperature rapid prototyping technology, and its effects on promoting osteochondral regeneration were evaluated using our well-established OA-OCD rabbit model. The biphasic porous scaffolds consisted of poly lactic-co-glycolic acid (PLGA) with kartogenin (KGN) for cartilage repair and PLGA and β-calcium phosphate (PLGA/β-TCP) with cinnamaldehyde (CIN) for subchondral bone repair. KGN is a molecule for promoting chondrogenesis and CIN is a phytomolecule for enhancing osteogenesis and alleviating inflammation. The biphasic scaffolds PLGA/KGN-PLGA/β-TCP/CIN (PK/PTC) with bio-mimic structure provided stable mechanical properties and exhibited excellent biocompatibility to support cell adhesion, proliferation, migration, and distribution. Furthermore, KGN and CIN within biphasic scaffolds could be released in a controlled and sustained mode, and the biphasic scaffold degraded slowly in vitro . Evaluating the repair of 16-weeks post-implantation into critically sized OA-OCD rabbit models revealed that the biphasic scaffold could promote subchondral bone and cartilage regeneration, as well as reverse subchondral osteosclerosis caused by inflammation in vivo . These findings support the utilization of the PK/PTC scaffold for osteochondral regeneration and provide a promising potential strategy for clinical application for the treatment of patients with OA-OCD.
基金The work is supported in part by the National Natural Science Foundation of China(Grant Nos.62171483,82061148011)Zhejiang Provincial Natural Science Foundation of China(Grant No.LZ23F010004)+1 种基金Hangzhou Agricultural and Social Development Research Key Project(Grant No.20231203A08)Doctoral Initiation Program of the Tenth Affiliated Hospital,Southern Medical University(Grant No.K202308).
文摘The development of precise and sensitive electrophysiological recording platforms holds the utmost importance for research in the fields of cardiology and neuroscience.In recent years,active micro/nano-bioelectronic devices have undergone significant advancements,thereby facilitating the study of electrophysiology.The distinctive configuration and exceptional functionality of these active micro-nano-collaborative bioelectronic devices offer the potential for the recording of high-fidelity action potential signals on a large scale.In this paper,we review three-dimensional active nano-transistors and planar active micro-transistors in terms of their applications in electroexcitable cells,focusing on the evaluation of the effects of active micro/nano-bioelectronic devices on electrophysiological signals.Looking forward to the possibilities,challenges,and wide prospects of active micro-nano-devices,we expect to advance their progress to satisfy the demands of theoretical investigations and medical implementations within the domains of cardiology and neuroscience research.
文摘Cardiovascular diseases(CVDs)are the first cause of death globally,posing a significant threat to human health.Cardiac electrophysiology is pivotal for the understanding and management of CVDs,particularly for addressing arrhythmias.A significant proliferation of micro-nano bioelectric devices and systems has occurred in the field of cardiomyocyte electrophysiology.These bioelectronic platforms feature distinctive electrode geometries that improve the fidelity of native electrophysiological signals.Despite the prevalence of planar microelectrode arrays(MEAs)for simultaneous multichannel recording of cellular electrophysiological signals,extracellular recordings often yield suboptimal signal quality.In contrast,three-dimensional(3D)MEAs and advanced penetration strategies allow highfidelity intracellular signal detection.3D nanodevices are categorized into the active and the passive.Active devices rely on external power sources to work,while passive devices operate without external power.Passive devices possess simplicity,biocompatibility,stability,and lower power consumption compared to active ones,making them ideal for sensors and implantable applications.This review comprehensively discusses the fabrication,geometric configuration,and penetration strategies of passive 3D micro/nanodevices,emphasizing their application in drug screening and disease modeling.Moreover,we summarize existing challenges and future opportunities to develop passive micro/nanobioelectronic devices from cardiac electrophysiological research to cardiovascular clinical practice.
