Ultrafine particles represent a growing concern in the public health community but their precise role in many illnesses is still unknown. This lack of knowledge is related to the experimental difficulty in linking the...Ultrafine particles represent a growing concern in the public health community but their precise role in many illnesses is still unknown. This lack of knowledge is related to the experimental difficulty in linking their biological effects to their multiple properties, which are important determinants of toxicity. Our aim is to propose an interdisciplinary approach to study fine(FP) and ultrafine(UFP) particles, generated in a controlled manner using a mini CAST(Combustion Aerosol Standard) soot generator used with two different operating conditions(CAST1 and CAST3). The chemical characterization was performed by an untargeted analysis using ultra-high resolution mass spectrometry. In conjunction with this approach, subsequent analysis by gas chromatography–mass spectrometry(GC–MS) was performed to identify polycyclic aromatic hydrocarbons(PAH). CAST1 enabled the generation of FP with a predominance of small PAH molecules, and CAST3 enabled the generation of UFP, which presented higher numbers of carbon atoms corresponding to larger PAH molecules. Healthy normal human bronchial epithelial(NHBE) cells differentiated at the air-liquid interface(ALI) were directly exposed to these freshly emitted FP and UFP. Expression of MUC5AC, FOXJ1, OCLN and ZOI as well as microscopic observation confirmed the ciliated pseudostratified epithelial phenotype. Study of the mass deposition efficiency revealed a difference between the two operating conditions, probably due to the morphological differences between the two categories of particles. We demonstrated that only NHBE cells exposed to CAST3 particles induced upregulation in the gene expression of IL-8 and NQO1. This approach offers new perspectives to study FP and UFP with stable and controlled properties.展开更多
In this paper, the effect of fluid in a tunnel of Corti （TC） on organ of Corti （OC） is studied. A three-dimensional OC model including basilar membrane （BM）, tectorial membrane （TM）, inner and outer hair cells...In this paper, the effect of fluid in a tunnel of Corti （TC） on organ of Corti （OC） is studied. A three-dimensional OC model including basilar membrane （BM）, tectorial membrane （TM）, inner and outer hair cells （OHCs）, and reticular lamina （RL） is established by COMSOL. An initial pressure is applied to the fluid in the TC. The frequency response of the structure is analyzed, and the displacement of the BM is achieved. The results are in good agreement with the experimental data, confirming validity of the finite element model. Based on the model, the effect of fluid in the TC on the OC is studied. The results show that, when the pressure gradient is absent in the fluid, with the increase of the initial fluid pressure, the displacement of the BM increases. However, when the initial fluid pressure increases to a certain value, the increase rate of the displacement of the BM becomes very slow. The movement of the fluid amplifies the BM movement. Furthermore, the movement of the fluid can strengthen the movement of the OHCs and the shear movement of the stereocilia, especially in the vicinity of the characteristic frequency at which the amplification effect reaches a peak. Nevertheless, a pressure gradient in the fluid affects the BM movement.展开更多
基金supported by ANSES (French Agency for Food,Environmental and Occupational Health and SafetyPUFBIO project,Grant number EST-2017-190)+5 种基金co-supported by the Regional Council of Normandy and the European Union in the framework of the ERDF-ESF (CellSTEM project)a PhD fellowship funded by ADEME(Agency for Ecological Transition)financed by the Labex SynOrg(ANR-11-LABX-0029)the European Regional Development Fund (ERDF HN0001343)Financial support from the National Fourier transform ion cyclotron resonance network (FR 3624 CNRS)the European Union’s Horizon 2020 Research Infrastructures program (grant agreement 731077).
文摘Ultrafine particles represent a growing concern in the public health community but their precise role in many illnesses is still unknown. This lack of knowledge is related to the experimental difficulty in linking their biological effects to their multiple properties, which are important determinants of toxicity. Our aim is to propose an interdisciplinary approach to study fine(FP) and ultrafine(UFP) particles, generated in a controlled manner using a mini CAST(Combustion Aerosol Standard) soot generator used with two different operating conditions(CAST1 and CAST3). The chemical characterization was performed by an untargeted analysis using ultra-high resolution mass spectrometry. In conjunction with this approach, subsequent analysis by gas chromatography–mass spectrometry(GC–MS) was performed to identify polycyclic aromatic hydrocarbons(PAH). CAST1 enabled the generation of FP with a predominance of small PAH molecules, and CAST3 enabled the generation of UFP, which presented higher numbers of carbon atoms corresponding to larger PAH molecules. Healthy normal human bronchial epithelial(NHBE) cells differentiated at the air-liquid interface(ALI) were directly exposed to these freshly emitted FP and UFP. Expression of MUC5AC, FOXJ1, OCLN and ZOI as well as microscopic observation confirmed the ciliated pseudostratified epithelial phenotype. Study of the mass deposition efficiency revealed a difference between the two operating conditions, probably due to the morphological differences between the two categories of particles. We demonstrated that only NHBE cells exposed to CAST3 particles induced upregulation in the gene expression of IL-8 and NQO1. This approach offers new perspectives to study FP and UFP with stable and controlled properties.
基金Project supported by the National Natural Science Foundation of China(Nos.11272200 and 11572186)
文摘In this paper, the effect of fluid in a tunnel of Corti （TC） on organ of Corti （OC） is studied. A three-dimensional OC model including basilar membrane （BM）, tectorial membrane （TM）, inner and outer hair cells （OHCs）, and reticular lamina （RL） is established by COMSOL. An initial pressure is applied to the fluid in the TC. The frequency response of the structure is analyzed, and the displacement of the BM is achieved. The results are in good agreement with the experimental data, confirming validity of the finite element model. Based on the model, the effect of fluid in the TC on the OC is studied. The results show that, when the pressure gradient is absent in the fluid, with the increase of the initial fluid pressure, the displacement of the BM increases. However, when the initial fluid pressure increases to a certain value, the increase rate of the displacement of the BM becomes very slow. The movement of the fluid amplifies the BM movement. Furthermore, the movement of the fluid can strengthen the movement of the OHCs and the shear movement of the stereocilia, especially in the vicinity of the characteristic frequency at which the amplification effect reaches a peak. Nevertheless, a pressure gradient in the fluid affects the BM movement.
