Parkinson’s disease is a neurodegenerative disorder,and fe rroptosis plays a significant role in the pathological mechanism underlying Parkinson’s disease.Rapamycin,an autophagy inducer,has been shown to have neurop...Parkinson’s disease is a neurodegenerative disorder,and fe rroptosis plays a significant role in the pathological mechanism underlying Parkinson’s disease.Rapamycin,an autophagy inducer,has been shown to have neuroprotective effects in Parkinson’s disease.However,the link between rapamycin and ferroptosis in Parkinson’s disease is not entirely clear.In this study,rapamycin was administe red to a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced Parkinson’s disease mouse model and a 1-methyl-4-phenylpyridinium-induced Parkinson’s disease PC12 cell model.The results showed that rapamycin improved the behavioral symptoms of Parkinson’s disease model mice,reduced the loss of dopamine neurons in the substantia nigra pars compacta,and reduced the expression of ferroptosis-related indicators(glutathione peroxidase 4,recombinant solute carrier family 7,member 11,glutathione,malondialdehyde,and reactive oxygen species).In the Parkinson’s disease cell model,rapamycin improved cell viability and reduced ferro ptosis.The neuroprotective effect of rapamycin was attenuated by a ferroptosis inducer(methyl(1S,3R)-2-(2-chloroacetyl)-1-(4-methoxycarbonylphenyl)-1,3,4,9-tetrahyyridoindole-3-carboxylate)and an autophagy inhibitor(3-methyladenine).Inhibiting ferro ptosis by activating autophagy may be an important mechanism by which rapamycin exerts its neuroprotective effects.Therefo re,the regulation of ferroptosis and autophagy may provide a therapeutic target for drug treatments in Parkinson’s disease.展开更多
Lidar and visual data are affected heavily in adverse weather conditions due to sensing mechanisms,which bring potential safety hazards for vehicle navigation.Radar sensing is desirable to build a more robust navigati...Lidar and visual data are affected heavily in adverse weather conditions due to sensing mechanisms,which bring potential safety hazards for vehicle navigation.Radar sensing is desirable to build a more robust navigation system.In this paper,a cross-modality radar localisation on prior lidar maps is presented.Specifically,the proposed workflow consists of two parts:first,bird's-eye-view radar images are transferred to fake lidar images by training a generative adversarial network offline.Then with online radar scans,a Monte Carlo localisation framework is built to track the robot pose on lidar maps.The whole online localisation system only needs a rotating radar sensor and a pre-built global lidar map.In the experimental section,the authors conduct an ablation study on image settings and test the proposed system on Oxford Radar Robot Car Dataset.The promising results show that the proposed localisation system could track the robot pose successfully,thus demonstrating the feasibility of radar style transfer for metric robot localisation on lidar maps.展开更多
Ultrahigh-temperature ceramics were added to C/C composites to meet their application requirement in a high-temperature oxidizing environment. C/C-ZrB2-SiC composites were fabricated by high-solid-loading slurry impre...Ultrahigh-temperature ceramics were added to C/C composites to meet their application requirement in a high-temperature oxidizing environment. C/C-ZrB2-SiC composites were fabricated by high-solid-loading slurry impregnation with polymer infiltration and pyrolysis. The dispersion and rheological behavior of ZrB2 slurry and the microstructural, mechanical, and ablation properties of the C/C-ZrB2-SiC composites were investigated. Results indicated that a well-dispersed and low-viscosity ZrB2 slurry was obtained using 0.40 wt.% polyethyleneimine as a dispersant at pH 5. Ceramics were uniformly distributed in the short-cut fiber layer and needle-punched area. The flexural strength of the C/C-ZrB2-SiC composites was 309.30 MPa. The composites exhibited satisfactory ablation resistance under the oxyacetylene flame of 2500℃, and the mass and linear ablation rates were 0.40 mg/s and 0.91 μm/s, respectively. A continuous and compact Zr O2 layer, which could effectively reduce the diffusion rate of oxygen and protect the composites from being ablated, was formed.展开更多
Salmonella Choleraesuis,S.Enteritidis and S.Typhimurium are the main pathogens that contaminate animal products and cause human Salmonella food poisoning.To establish the loop-mediated isothermal amplification(LAMP)me...Salmonella Choleraesuis,S.Enteritidis and S.Typhimurium are the main pathogens that contaminate animal products and cause human Salmonella food poisoning.To establish the loop-mediated isothermal amplification(LAMP)method for the rapid detection of Salmonella and 3 common Salmonella serotypes,inner and outer primer sets targeting Salmonella invE gene and 3 serotype-specific genes fliC,lygD and STM4495 were designed.The LAMP reaction conditions were optimized.The specificity of LAMP primers was identified by testing 10 different bacterial strains including S.Choleraesuis,S.Enteritidis and S.Typhimurium.Take S.Choleraesuis as example,the detection limit of LAMP assay was 1.33×10^1 CFU/mL for bacteria culture and 2.0×10^1 CFU/mL for simulated pork sample.The results show that LAMP is a rapid,sensitive and specific method for Salmonella detection and can be used for the rapid detection of Salmonella in food.展开更多
Primary cilium is an antenna-like and non-motile structure protruding from the apical surface of most mammalian cells including endothelial cells lining the inner side of all the blood vessels in our body.Although it ...Primary cilium is an antenna-like and non-motile structure protruding from the apical surface of most mammalian cells including endothelial cells lining the inner side of all the blood vessels in our body.Although it has been over a century since primary cilia were discovered,the investigation about their mechano-sensing and other roles in maintaining normal functions of cardiovascular system has just started in recent years.This focused review aims to give an update about the current literature for the role of endothelial primary cilia in blood flow mechanosensing and shear stress-shielding.To do this,we first summarized the characteristic features of endothelial primary cilia in terms of structure,dimension,molecular composition,and mechanical properties(e.g.,bending rigidity),which are the dominant factors for their functions in mechano-sensing and transduction,as well as vascular protection from the blood flow-induced wall shear stress.We also described the experimental techniques and mathematical models for determining the dimension and mechanical properties of the primary cilium.Then we reviewed the molecular mechanisms underlying mechano-sensing and transduction by endothelial primary cilia and the mathematical model prediction for their roles in redistribution and reduction of wall shear stresses.Finally,we briefly discussed the common cardiovascular diseases,e.g.,atherosclerosis,hypertension,and aneurysm,due to defects and malfunction of endothelial primary cilia and suggested potential targets for therapeutic treatments.展开更多
Introduction Primary cilium is a non-motile microstructure,protruding from cell surface of most mammalian cells.It was previously thought to be vestigial.However,recent studies indicate that it may serve as one of the...Introduction Primary cilium is a non-motile microstructure,protruding from cell surface of most mammalian cells.It was previously thought to be vestigial.However,recent studies indicate that it may serve as one of the most vital mechanosensors for many types of cells such as epithelial and endothelial cells and osteocytes.Protruding from the apical membrane,the primary cilium can directly sense subtle variation of mechanical forces exerted on the cell and then transduce the mechanical cues into biochemical signals into the cell,although the mechanism remain elusive.Vascular endothelial cells(ECs)lining the inner wall of our blood vessels are continuously exposed to the blood flow.In order to maintain proper functions for the cardiovascular system,ECs should have a variety of mechano-sensors and transducers to sense the blood flow change and adjust the vessel size and transport across the vessel wall accordingly.Among more than a dozen recognized EC mechano-sensors,the primary cilium has drawn more and more attention recently.Primary cilium on endothelial cells is essential for the homeostasis of vessels.It is reported to be prevalent in areas of disturbed flow where atherosclerosis and intracranial aneurysm usually occur.Deficiencies of primary cilia may promote atherosclerosis,endothelial-to-mesenchymal transition(EndoMT)and loss of direction orientation,to name a few.Therefore understanding why the primary cilia are necessary to maintain the homeostasis of blood vessels and how will help us develop better treatment strategies for the common cardiovascular diseases.Dimension and structure of primary cilium Primary cilium is reported to be shorter than 8 in length and about 0.2 in diameter.The length of primary cilium varies in different cell types and under different conditions.The major structural components of the primary cilium include basal body,ciliary axoneme(consisting of nine doublet microtubules),ciliary membrane,transition zone,basal feet,and striated rootlets.Each part of the primary cilium is essential and has specific function.Current methods investigating the EC primary cilium as a mechano-sensor:Immunostaining and imaging techniques have been used to investigate the molecular mechanisms by which EC primary cilium serves as a mechano-sensor and transducer.It has been found that various proteins locate on the primary cilium,working together to maintain the function of primary cilium.Some proteins function as ion-channels,mediating Ca2+entry into the primary cilium.Some are involved in the cascade signal pathway.Others are related to the assembly and maintenance of primary cilium.Briefly,the flow induces the deflection of the EC primary cilium,which triggers calcium increase via opening of the PC2 cation channel that is responsible for calcium ion influx.This PC2 cation channel is localized to the primary cilium and is assumed to be stretch-activated.The resulting change in the intracellular calcium concentration then regulates numerous molecular activities inside the cell that contribute to vessel homeostasis.In addition to triggering calcium release,another mechanism has also been found in blood-pressure maintenance in the vasculature,where the vessel diameter is regulated by endothelial primary cilia through adjusting nitric oxide production.So far,little is known about the mechanical mechanism behind this deflection-triggered o-pening of signaling pathways.For example,what is the flow induced bending behavior and force distribution? What is the threshold value of stretch/defection for activating a corresponding signaling pathway? These all remain to be answered.In combination of image data and experiments,several computational models have been established to answer these questions.However,the current models are not able to include the complex structure of primary cilium and the model predictions are limited.Future studies With the development of super high resolution optical microscopy,more detailed images for the structural(molecular)components of EC primary cilia will be revealed,especially when the ECs are alive and the forces are known.Combining these experimental observations with more sophisticated mathematical models will elucidate the mechano-sensing mechanism of EC primary cilia,as the force and stress distribution on cilium along with other mechanical properties are still beyond the capability of experimental approaches due to the scales of the quantities involved.By using numerical approaches,much more detailed dynamic information can be obtained.展开更多
This paper demonstrates the design and fabrication of three-dimensional(3 D) hexagonally ordered microbowl arrays(MBAs) decorated with Cu In S2 nanosheets for enhanced photoelectrochemical(PEC) performance. The 3 D MB...This paper demonstrates the design and fabrication of three-dimensional(3 D) hexagonally ordered microbowl arrays(MBAs) decorated with Cu In S2 nanosheets for enhanced photoelectrochemical(PEC) performance. The 3 D MBAs are fabricated by a micro-fabrication technique. The ultrathin CuInS2 nanosheets are grown on the 3 D electrodes by solvothermal transformation of Cu film. The photocurrent density of 3 D photocathode(CuInS2@MBAs) is about two times higher than that of the planar counterpart(CuInS2@Planar). The improved PEC performance can be ascribed to the elevated light trapping ability and the increased surface area for loading photocatalysts. In addition, CdS quantum dots as cocatalysts are modified onto the Cu In S2 nanosheets to further enhance the PEC activity because the formed p-n heterojunction can accelerate the separation of photogenerated carriers. As a result, the 3 D photocathode of CuInS2/CdS@MBAs shows an optimal incident photon to current efficiency of 10% at the wavelength of400 nm. It is believed that this work can be generalized to design other hierarchical 3 D photoelectrodes for improved solar water splitting.展开更多
文摘Parkinson’s disease is a neurodegenerative disorder,and fe rroptosis plays a significant role in the pathological mechanism underlying Parkinson’s disease.Rapamycin,an autophagy inducer,has been shown to have neuroprotective effects in Parkinson’s disease.However,the link between rapamycin and ferroptosis in Parkinson’s disease is not entirely clear.In this study,rapamycin was administe red to a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced Parkinson’s disease mouse model and a 1-methyl-4-phenylpyridinium-induced Parkinson’s disease PC12 cell model.The results showed that rapamycin improved the behavioral symptoms of Parkinson’s disease model mice,reduced the loss of dopamine neurons in the substantia nigra pars compacta,and reduced the expression of ferroptosis-related indicators(glutathione peroxidase 4,recombinant solute carrier family 7,member 11,glutathione,malondialdehyde,and reactive oxygen species).In the Parkinson’s disease cell model,rapamycin improved cell viability and reduced ferro ptosis.The neuroprotective effect of rapamycin was attenuated by a ferroptosis inducer(methyl(1S,3R)-2-(2-chloroacetyl)-1-(4-methoxycarbonylphenyl)-1,3,4,9-tetrahyyridoindole-3-carboxylate)and an autophagy inhibitor(3-methyladenine).Inhibiting ferro ptosis by activating autophagy may be an important mechanism by which rapamycin exerts its neuroprotective effects.Therefo re,the regulation of ferroptosis and autophagy may provide a therapeutic target for drug treatments in Parkinson’s disease.
基金National Key R&D Program of China,Grant/Award Number:2020YFB1313300National Nature Science Foundation of China under Grant,Grant/Award Number:61903332Hong Kong Center for Construction Robotics(InnoHK center supported by Hong Kong ITC)。
文摘Lidar and visual data are affected heavily in adverse weather conditions due to sensing mechanisms,which bring potential safety hazards for vehicle navigation.Radar sensing is desirable to build a more robust navigation system.In this paper,a cross-modality radar localisation on prior lidar maps is presented.Specifically,the proposed workflow consists of two parts:first,bird's-eye-view radar images are transferred to fake lidar images by training a generative adversarial network offline.Then with online radar scans,a Monte Carlo localisation framework is built to track the robot pose on lidar maps.The whole online localisation system only needs a rotating radar sensor and a pre-built global lidar map.In the experimental section,the authors conduct an ablation study on image settings and test the proposed system on Oxford Radar Robot Car Dataset.The promising results show that the proposed localisation system could track the robot pose successfully,thus demonstrating the feasibility of radar style transfer for metric robot localisation on lidar maps.
基金Project(GFZX0101040101-2012C20X) supported by the National Basic Research Program of ChinaProject(2017JJ2320) supported by the Natural Science Foundation of Hunan Province,China
文摘Ultrahigh-temperature ceramics were added to C/C composites to meet their application requirement in a high-temperature oxidizing environment. C/C-ZrB2-SiC composites were fabricated by high-solid-loading slurry impregnation with polymer infiltration and pyrolysis. The dispersion and rheological behavior of ZrB2 slurry and the microstructural, mechanical, and ablation properties of the C/C-ZrB2-SiC composites were investigated. Results indicated that a well-dispersed and low-viscosity ZrB2 slurry was obtained using 0.40 wt.% polyethyleneimine as a dispersant at pH 5. Ceramics were uniformly distributed in the short-cut fiber layer and needle-punched area. The flexural strength of the C/C-ZrB2-SiC composites was 309.30 MPa. The composites exhibited satisfactory ablation resistance under the oxyacetylene flame of 2500℃, and the mass and linear ablation rates were 0.40 mg/s and 0.91 μm/s, respectively. A continuous and compact Zr O2 layer, which could effectively reduce the diffusion rate of oxygen and protect the composites from being ablated, was formed.
基金Wuhan Science and Technology Planning Project(201070934341)Wuhan Agricultural Technology Innovation Project(201120637175)Wuhan Polytechnic University Major Incubation Planning(2011z01).
文摘Salmonella Choleraesuis,S.Enteritidis and S.Typhimurium are the main pathogens that contaminate animal products and cause human Salmonella food poisoning.To establish the loop-mediated isothermal amplification(LAMP)method for the rapid detection of Salmonella and 3 common Salmonella serotypes,inner and outer primer sets targeting Salmonella invE gene and 3 serotype-specific genes fliC,lygD and STM4495 were designed.The LAMP reaction conditions were optimized.The specificity of LAMP primers was identified by testing 10 different bacterial strains including S.Choleraesuis,S.Enteritidis and S.Typhimurium.Take S.Choleraesuis as example,the detection limit of LAMP assay was 1.33×10^1 CFU/mL for bacteria culture and 2.0×10^1 CFU/mL for simulated pork sample.The results show that LAMP is a rapid,sensitive and specific method for Salmonella detection and can be used for the rapid detection of Salmonella in food.
基金Grants(11421202,11572029)from National Natural Science Foundation of ChinaNIH 1UG3UH3TR002151.
文摘Primary cilium is an antenna-like and non-motile structure protruding from the apical surface of most mammalian cells including endothelial cells lining the inner side of all the blood vessels in our body.Although it has been over a century since primary cilia were discovered,the investigation about their mechano-sensing and other roles in maintaining normal functions of cardiovascular system has just started in recent years.This focused review aims to give an update about the current literature for the role of endothelial primary cilia in blood flow mechanosensing and shear stress-shielding.To do this,we first summarized the characteristic features of endothelial primary cilia in terms of structure,dimension,molecular composition,and mechanical properties(e.g.,bending rigidity),which are the dominant factors for their functions in mechano-sensing and transduction,as well as vascular protection from the blood flow-induced wall shear stress.We also described the experimental techniques and mathematical models for determining the dimension and mechanical properties of the primary cilium.Then we reviewed the molecular mechanisms underlying mechano-sensing and transduction by endothelial primary cilia and the mathematical model prediction for their roles in redistribution and reduction of wall shear stresses.Finally,we briefly discussed the common cardiovascular diseases,e.g.,atherosclerosis,hypertension,and aneurysm,due to defects and malfunction of endothelial primary cilia and suggested potential targets for therapeutic treatments.
基金supported by grants ( 11421202,11572029) from National Natural Science Foundation of China
文摘Introduction Primary cilium is a non-motile microstructure,protruding from cell surface of most mammalian cells.It was previously thought to be vestigial.However,recent studies indicate that it may serve as one of the most vital mechanosensors for many types of cells such as epithelial and endothelial cells and osteocytes.Protruding from the apical membrane,the primary cilium can directly sense subtle variation of mechanical forces exerted on the cell and then transduce the mechanical cues into biochemical signals into the cell,although the mechanism remain elusive.Vascular endothelial cells(ECs)lining the inner wall of our blood vessels are continuously exposed to the blood flow.In order to maintain proper functions for the cardiovascular system,ECs should have a variety of mechano-sensors and transducers to sense the blood flow change and adjust the vessel size and transport across the vessel wall accordingly.Among more than a dozen recognized EC mechano-sensors,the primary cilium has drawn more and more attention recently.Primary cilium on endothelial cells is essential for the homeostasis of vessels.It is reported to be prevalent in areas of disturbed flow where atherosclerosis and intracranial aneurysm usually occur.Deficiencies of primary cilia may promote atherosclerosis,endothelial-to-mesenchymal transition(EndoMT)and loss of direction orientation,to name a few.Therefore understanding why the primary cilia are necessary to maintain the homeostasis of blood vessels and how will help us develop better treatment strategies for the common cardiovascular diseases.Dimension and structure of primary cilium Primary cilium is reported to be shorter than 8 in length and about 0.2 in diameter.The length of primary cilium varies in different cell types and under different conditions.The major structural components of the primary cilium include basal body,ciliary axoneme(consisting of nine doublet microtubules),ciliary membrane,transition zone,basal feet,and striated rootlets.Each part of the primary cilium is essential and has specific function.Current methods investigating the EC primary cilium as a mechano-sensor:Immunostaining and imaging techniques have been used to investigate the molecular mechanisms by which EC primary cilium serves as a mechano-sensor and transducer.It has been found that various proteins locate on the primary cilium,working together to maintain the function of primary cilium.Some proteins function as ion-channels,mediating Ca2+entry into the primary cilium.Some are involved in the cascade signal pathway.Others are related to the assembly and maintenance of primary cilium.Briefly,the flow induces the deflection of the EC primary cilium,which triggers calcium increase via opening of the PC2 cation channel that is responsible for calcium ion influx.This PC2 cation channel is localized to the primary cilium and is assumed to be stretch-activated.The resulting change in the intracellular calcium concentration then regulates numerous molecular activities inside the cell that contribute to vessel homeostasis.In addition to triggering calcium release,another mechanism has also been found in blood-pressure maintenance in the vasculature,where the vessel diameter is regulated by endothelial primary cilia through adjusting nitric oxide production.So far,little is known about the mechanical mechanism behind this deflection-triggered o-pening of signaling pathways.For example,what is the flow induced bending behavior and force distribution? What is the threshold value of stretch/defection for activating a corresponding signaling pathway? These all remain to be answered.In combination of image data and experiments,several computational models have been established to answer these questions.However,the current models are not able to include the complex structure of primary cilium and the model predictions are limited.Future studies With the development of super high resolution optical microscopy,more detailed images for the structural(molecular)components of EC primary cilia will be revealed,especially when the ECs are alive and the forces are known.Combining these experimental observations with more sophisticated mathematical models will elucidate the mechano-sensing mechanism of EC primary cilia,as the force and stress distribution on cilium along with other mechanical properties are still beyond the capability of experimental approaches due to the scales of the quantities involved.By using numerical approaches,much more detailed dynamic information can be obtained.
基金sponsored by the National Key Research and Development Program of China (2016YFA0200800)National Natural Science Foundation of China (61804156)Shanghai Sailing Program (18YF1427800)。
文摘This paper demonstrates the design and fabrication of three-dimensional(3 D) hexagonally ordered microbowl arrays(MBAs) decorated with Cu In S2 nanosheets for enhanced photoelectrochemical(PEC) performance. The 3 D MBAs are fabricated by a micro-fabrication technique. The ultrathin CuInS2 nanosheets are grown on the 3 D electrodes by solvothermal transformation of Cu film. The photocurrent density of 3 D photocathode(CuInS2@MBAs) is about two times higher than that of the planar counterpart(CuInS2@Planar). The improved PEC performance can be ascribed to the elevated light trapping ability and the increased surface area for loading photocatalysts. In addition, CdS quantum dots as cocatalysts are modified onto the Cu In S2 nanosheets to further enhance the PEC activity because the formed p-n heterojunction can accelerate the separation of photogenerated carriers. As a result, the 3 D photocathode of CuInS2/CdS@MBAs shows an optimal incident photon to current efficiency of 10% at the wavelength of400 nm. It is believed that this work can be generalized to design other hierarchical 3 D photoelectrodes for improved solar water splitting.