A micro-nano structure CaF_(2)chemical conversion layer was prepared on fluoride-treated AZ31 alloy,then the composite fluoride conversion film(CaF_(2)/MgF_(2))was modified by stearic acid(SA)and fabricated a superhyd...A micro-nano structure CaF_(2)chemical conversion layer was prepared on fluoride-treated AZ31 alloy,then the composite fluoride conversion film(CaF_(2)/MgF_(2))was modified by stearic acid(SA)and fabricated a superhydrophobic surface.The fluoride-treated magnesium,fluoride conversion film and superhydrophobic coating were characterized by SEM,EDS,XRD and FTIR.The properties of coatings1 adhesion and corrosion resistance were evaluated via tape test and electrochemical measurement.The cytocompatibility of the MgF_(2),CaF_(2)and superhydrophobic CaF_(2)/SA surface was investigated with bone marrow-derived mesenchymal stem cells(BMSCs)by direct culture for 24 h.The results showed that the superhydrophobic fluoride conversion coating composed of inner MgF_(2)layer and the outer CaF_(2)/SA composite layer had an average water contact angle of 152°.SA infiltrated into the micro-nano structure CaF_(2)layer and formed a strong adhesion with CaF_(2)layer.Furthermore,the super-hydrophobic coating showed higher barrier properties and corrosion resistance compared with the fluoride conversion film and fluoride-treated AZ31 alloy.The BMSC adhesion test results demonstrated MgF_(2)CaF_(2)and CaF_(2)/SA coatings were all nontoxic to BMSC.At the condition of in direct contact with cells,MgF_(2)showed higher cell density and enhanced the BMSCs proliferation,while CaF_(2)and CaF_(2)/SA coating showed no statistically difference in cell density compared with glass reference but the CaF_(2)and CaF_(2)/SA coating were not conducive to BMSCs adhesion.展开更多
Polycaprolactone/hydroxyapatite(PCL/HA)composite coating was fabricated by a combination of hydrothermal and dipping methods to delay the degradation of Mg alloy AZ31 as bioresorbable materials.The PCL/HA coating was ...Polycaprolactone/hydroxyapatite(PCL/HA)composite coating was fabricated by a combination of hydrothermal and dipping methods to delay the degradation of Mg alloy AZ31 as bioresorbable materials.The PCL/HA coating was composed of nano rod-shape HA crystals and PCL filled in the space of HA crystals.Compared with the single HA coating,the binding strength between the PCL/HA composite coating and Mg alloy was obviously improved and the PCL/HA coating still adhered to the surface of AZ31 substrate even after 38 days of immersion.The electrochemical corrosion rate of HA coated sample was reduced by ten times after being filled by PCL.The electrochemical impedance spectroscopy(EIS)and immersion test results showed that the PCL/HA composite coating could provide a more effective barrier for Mg substrate than the HA coating alone.The cytocompatibility and the antibacterial property of HA coating and PCL/HA coating were evaluated by culturing with bone marrow-derived mesenchymal stem cells(BMSCs)and methicillin-resistant staphylococcus aureus(MRSA)for 24 h under direct culture conditions,respectively.The PCL/HA composite coating showed better BMSC cell compatibility,more suitable for BMSC adhesion than HA coating alone and showed a potential application prospect as a biological materials.However,from the perspective of clinical applications,the antibacterial property of PCL/HA composite coating needs to be further improved.展开更多
Endothelial cell dysfunction occurs in a variety of acute and chronic pulmonary diseases including pulmonary hypertension,viral and bacterial pneumonia,bronchopulmonary dysplasia,and congenital lung diseases such as a...Endothelial cell dysfunction occurs in a variety of acute and chronic pulmonary diseases including pulmonary hypertension,viral and bacterial pneumonia,bronchopulmonary dysplasia,and congenital lung diseases such as alveolar capillary dysplasia with misalignment of pulmonary veins(ACDMPV).To correct endothelial dysfunction,there is a critical need for the development of nanoparticle systems that can deliver drugs and nucleic acids to endothelial cells with high efficiency and precision.While several nanoparticle delivery systems targeting endothelial cells have been recently developed,none of them are specific to lung endothelial cells without targeting other organs in the body.In the present study,we successfully solved this problem by developing non-toxic poly(β-amino)ester(PBAE)nanoparticles with specific structure design and fluorinated modification for high efficiency and specific delivery of nucleic acids to the pulmonary endothelial cells.After intravenous administration,the PBAE nanoparticles were capable of delivering non-integrating DNA plasmids to lung microvascular endothelial cells but not to other lung cell types.IVIS whole body imaging and flow cytometry demonstrated that DNA plasmid were functional in the lung endothelial cells but not in endothelial cells of other organs.Fluorination of PBAE was required for lung endothelial cell-specific targeting.Hematologic analysis and liver and kidney metabolic panels demonstrated the lack of toxicity in experimental mice.Thus,fluorinated PBAE nanoparticles can be an ideal vehicle for gene therapy targeting lung microvascular endothelium in pulmonary vascular disorders.展开更多
Lysosomes are essential organelles for cells that act as the“recycling center”for decomposing biomolecules and clearing out damaged organelles.The status of lysosomes is tightly regulated by cells to maintain normal...Lysosomes are essential organelles for cells that act as the“recycling center”for decomposing biomolecules and clearing out damaged organelles.The status of lysosomes is tightly regulated by cells to maintain normal homeostasis.To monitor subcellular lysosomal status,super-resolution imaging has emerged as a promising technology that surpasses conventional imaging limitations,offering extraordinary visualization capability.However,existing fluorescent probes for super-resolution imaging still suffer from significant drawbacks,such as complex synthesis,poor intracellular stability,and the lack of near-infrared(NIR)imaging capability.Besides,to quantitatively analyze fluorescence images,traditional human-driven image interpretation is time-consuming and prone to information loss and human error.To tackle these challenges,we first developed a quinoliniumbased fluorescent probe,PA-2,for NIR super-resolution imaging of lysosomes with low cytotoxicity and stable fluorescence.Harnessing PA-2’s strong resistance to photobleaching,the lysosomal dynamic statuses,encompassing autophagy,mitochondrialysosome contacts,and mitophagy,were successfully visualized.Building on this,we next demonstrate a novel approach leveraging a large multimodal model(LMM),an advanced artificial intelligence(AI)tool,for automated analysis of super-resolution images.The LMM accurately interprets images of PA-2 and predicts lysosomal status under various drug treatments with remarkable speed,precision,and explainability,significantly outperforming human experts in image analysis.To sum up,this work highlights the strong potential of combining advanced fluorescent probe design with AI-assisted image interpretation to drive revolutionary innovation in bioimaging and beyond.展开更多
基金supported by the National Natural Science Foundation of China[Grant No.51201192]Natural Science Foundation of Chongqing[Grant No.cstc2018jcyj A2285]。
文摘A micro-nano structure CaF_(2)chemical conversion layer was prepared on fluoride-treated AZ31 alloy,then the composite fluoride conversion film(CaF_(2)/MgF_(2))was modified by stearic acid(SA)and fabricated a superhydrophobic surface.The fluoride-treated magnesium,fluoride conversion film and superhydrophobic coating were characterized by SEM,EDS,XRD and FTIR.The properties of coatings1 adhesion and corrosion resistance were evaluated via tape test and electrochemical measurement.The cytocompatibility of the MgF_(2),CaF_(2)and superhydrophobic CaF_(2)/SA surface was investigated with bone marrow-derived mesenchymal stem cells(BMSCs)by direct culture for 24 h.The results showed that the superhydrophobic fluoride conversion coating composed of inner MgF_(2)layer and the outer CaF_(2)/SA composite layer had an average water contact angle of 152°.SA infiltrated into the micro-nano structure CaF_(2)layer and formed a strong adhesion with CaF_(2)layer.Furthermore,the super-hydrophobic coating showed higher barrier properties and corrosion resistance compared with the fluoride conversion film and fluoride-treated AZ31 alloy.The BMSC adhesion test results demonstrated MgF_(2)CaF_(2)and CaF_(2)/SA coatings were all nontoxic to BMSC.At the condition of in direct contact with cells,MgF_(2)showed higher cell density and enhanced the BMSCs proliferation,while CaF_(2)and CaF_(2)/SA coating showed no statistically difference in cell density compared with glass reference but the CaF_(2)and CaF_(2)/SA coating were not conducive to BMSCs adhesion.
基金supported by the National Natural Science Foundation of China[Grant No.51201192]Natural Science Foundation of Chongqing[Grant No.cstc2018jcyj A2285cstc2018jcyjA 2285]。
文摘Polycaprolactone/hydroxyapatite(PCL/HA)composite coating was fabricated by a combination of hydrothermal and dipping methods to delay the degradation of Mg alloy AZ31 as bioresorbable materials.The PCL/HA coating was composed of nano rod-shape HA crystals and PCL filled in the space of HA crystals.Compared with the single HA coating,the binding strength between the PCL/HA composite coating and Mg alloy was obviously improved and the PCL/HA coating still adhered to the surface of AZ31 substrate even after 38 days of immersion.The electrochemical corrosion rate of HA coated sample was reduced by ten times after being filled by PCL.The electrochemical impedance spectroscopy(EIS)and immersion test results showed that the PCL/HA composite coating could provide a more effective barrier for Mg substrate than the HA coating alone.The cytocompatibility and the antibacterial property of HA coating and PCL/HA coating were evaluated by culturing with bone marrow-derived mesenchymal stem cells(BMSCs)and methicillin-resistant staphylococcus aureus(MRSA)for 24 h under direct culture conditions,respectively.The PCL/HA composite coating showed better BMSC cell compatibility,more suitable for BMSC adhesion than HA coating alone and showed a potential application prospect as a biological materials.However,from the perspective of clinical applications,the antibacterial property of PCL/HA composite coating needs to be further improved.
文摘Endothelial cell dysfunction occurs in a variety of acute and chronic pulmonary diseases including pulmonary hypertension,viral and bacterial pneumonia,bronchopulmonary dysplasia,and congenital lung diseases such as alveolar capillary dysplasia with misalignment of pulmonary veins(ACDMPV).To correct endothelial dysfunction,there is a critical need for the development of nanoparticle systems that can deliver drugs and nucleic acids to endothelial cells with high efficiency and precision.While several nanoparticle delivery systems targeting endothelial cells have been recently developed,none of them are specific to lung endothelial cells without targeting other organs in the body.In the present study,we successfully solved this problem by developing non-toxic poly(β-amino)ester(PBAE)nanoparticles with specific structure design and fluorinated modification for high efficiency and specific delivery of nucleic acids to the pulmonary endothelial cells.After intravenous administration,the PBAE nanoparticles were capable of delivering non-integrating DNA plasmids to lung microvascular endothelial cells but not to other lung cell types.IVIS whole body imaging and flow cytometry demonstrated that DNA plasmid were functional in the lung endothelial cells but not in endothelial cells of other organs.Fluorination of PBAE was required for lung endothelial cell-specific targeting.Hematologic analysis and liver and kidney metabolic panels demonstrated the lack of toxicity in experimental mice.Thus,fluorinated PBAE nanoparticles can be an ideal vehicle for gene therapy targeting lung microvascular endothelium in pulmonary vascular disorders.
基金support of the US National Science Foundation(CHE-2453603)supported by the National Institutes of Health(NIH R35GM128837).
文摘Lysosomes are essential organelles for cells that act as the“recycling center”for decomposing biomolecules and clearing out damaged organelles.The status of lysosomes is tightly regulated by cells to maintain normal homeostasis.To monitor subcellular lysosomal status,super-resolution imaging has emerged as a promising technology that surpasses conventional imaging limitations,offering extraordinary visualization capability.However,existing fluorescent probes for super-resolution imaging still suffer from significant drawbacks,such as complex synthesis,poor intracellular stability,and the lack of near-infrared(NIR)imaging capability.Besides,to quantitatively analyze fluorescence images,traditional human-driven image interpretation is time-consuming and prone to information loss and human error.To tackle these challenges,we first developed a quinoliniumbased fluorescent probe,PA-2,for NIR super-resolution imaging of lysosomes with low cytotoxicity and stable fluorescence.Harnessing PA-2’s strong resistance to photobleaching,the lysosomal dynamic statuses,encompassing autophagy,mitochondrialysosome contacts,and mitophagy,were successfully visualized.Building on this,we next demonstrate a novel approach leveraging a large multimodal model(LMM),an advanced artificial intelligence(AI)tool,for automated analysis of super-resolution images.The LMM accurately interprets images of PA-2 and predicts lysosomal status under various drug treatments with remarkable speed,precision,and explainability,significantly outperforming human experts in image analysis.To sum up,this work highlights the strong potential of combining advanced fluorescent probe design with AI-assisted image interpretation to drive revolutionary innovation in bioimaging and beyond.
