DNA–RNA hybrid(DRH)plays important roles in many biological processes.Here,we use a thermodynamic theory to analyze the free energy and unpeeling properties of the overstretching transition for the DRH molecule and c...DNA–RNA hybrid(DRH)plays important roles in many biological processes.Here,we use a thermodynamic theory to analyze the free energy and unpeeling properties of the overstretching transition for the DRH molecule and compare the results with double-helix DNA.We report that the RNA strand of DRH is easier to get unpeeled than the DNA strand while the difficulty in unpeeling the double helix DNA lies in between.We also investigate the sequence effect,such as GC content and purine content,on the properties of unpeeling the DRH.Further,to study the temperature effect,the forcetemperature phase diagram of DRH and DNA are calculated and compared.Finally,using a kinetic model,we calculate the force–extension curves in the DRH stretching and relaxation process under different pulling rates and temperatures.Our results show that both pulling rate and temperature have important influences on the stretching and relaxation kinetics of unpeeling the DRH.Putting all these results together,our work provides a comprehensive view of both the thermodynamics and kinetics in DRH overstretching.展开更多
At the bend and bifurcation of arteries prone to atherosclerosis,pulsatile blood retention may cause overstretch on the tube wall.It has been reported that more than half of the foam cells found in atherosclerotic pla...At the bend and bifurcation of arteries prone to atherosclerosis,pulsatile blood retention may cause overstretch on the tube wall.It has been reported that more than half of the foam cells found in atherosclerotic plaques are derived from vascular smooth muscle cells(VSMCs),but the mechanism is not adequately understood.In this work,we used a microfluidic device to apply a cyclic stretch(15%and 0.05 Hz)on the VSMC for 24 h.The stretch caused a significant increase in the intracellular lipid accumulation,accompanying with the increased NOX1 and CD36 protein expression.On the other hand,inhibition of NOX1 activity,elimination of reactive oxygen species(ROS),or knockdown of NOX1 expression could significantly inhibit intracellular lipid accumulation.In addition,the NOX1 upregulation caused by 15%stretch was related to the JAK/STAT signaling pathway.Our results reveal a novel mechanism of VSMC foam cell formation caused by the upregulation of NOX1.展开更多
基金Project supported by the National Natural Science Foundation of China(Grant No.11674403)the Young Scientists Fund of the National Natural Science Foundation of China(Grant No.31700809)+1 种基金the Fundamental Research Funds for the Central Universities(Grant No.18lgzd16)the Open Fund of the State Key Laboratory of Optoelectronic Materials and Technologies,Sun Yat-sen University
文摘DNA–RNA hybrid(DRH)plays important roles in many biological processes.Here,we use a thermodynamic theory to analyze the free energy and unpeeling properties of the overstretching transition for the DRH molecule and compare the results with double-helix DNA.We report that the RNA strand of DRH is easier to get unpeeled than the DNA strand while the difficulty in unpeeling the double helix DNA lies in between.We also investigate the sequence effect,such as GC content and purine content,on the properties of unpeeling the DRH.Further,to study the temperature effect,the forcetemperature phase diagram of DRH and DNA are calculated and compared.Finally,using a kinetic model,we calculate the force–extension curves in the DRH stretching and relaxation process under different pulling rates and temperatures.Our results show that both pulling rate and temperature have important influences on the stretching and relaxation kinetics of unpeeling the DRH.Putting all these results together,our work provides a comprehensive view of both the thermodynamics and kinetics in DRH overstretching.
基金supported by the National Natural Science Foundation of China(31571481,31771585,and 32070799).
文摘At the bend and bifurcation of arteries prone to atherosclerosis,pulsatile blood retention may cause overstretch on the tube wall.It has been reported that more than half of the foam cells found in atherosclerotic plaques are derived from vascular smooth muscle cells(VSMCs),but the mechanism is not adequately understood.In this work,we used a microfluidic device to apply a cyclic stretch(15%and 0.05 Hz)on the VSMC for 24 h.The stretch caused a significant increase in the intracellular lipid accumulation,accompanying with the increased NOX1 and CD36 protein expression.On the other hand,inhibition of NOX1 activity,elimination of reactive oxygen species(ROS),or knockdown of NOX1 expression could significantly inhibit intracellular lipid accumulation.In addition,the NOX1 upregulation caused by 15%stretch was related to the JAK/STAT signaling pathway.Our results reveal a novel mechanism of VSMC foam cell formation caused by the upregulation of NOX1.
