Background:Radiation ulcers are a common and severe injury after uncontrolled exposure to ionizing radiation.The most important feature of radiation ulcers is progressive ulceration,which results in the expansion of r...Background:Radiation ulcers are a common and severe injury after uncontrolled exposure to ionizing radiation.The most important feature of radiation ulcers is progressive ulceration,which results in the expansion of radiation injury to the nonirradiated area and refractory wounds.Current theories cannot explain the progression of radiation ulcers.Cellular senescence refers to as irre-versible growth arrest that occurs after exposure to stress,which contributes to tissue dysfunction by inducing paracrine senescence,stem cell dysfunction and chronic inflammation.However,it is not yet clear how cellular senescence facilitates the continuous progression of radiation ulcers.Here,we aim to investigate the role of cellular senescence in promoting progressive radiation ulcers and indicate a potential therapeutic strategy for radiation ulcers.Methods:Radiation ulcer animal models were established by local exposure to 40 Gy X-ray radiation and continuously evaluated for>260 days.The roles of cellular senescence in the progression of radiation ulcers were assessed using pathological analysis,molecular detection and RNA sequencing.Then,the therapeutic effects of conditioned medium from human umbilical cord mesenchymal stem cells(uMSC-CM)were investigated in radiation ulcer models.Results:Radiation ulcer animal models with features of clinical patients were established to investigate the primary mechanisms responsible for the progression of radiation ulcers.We have characterized cellular senescence as being closely associated with the progression of radiation ulcers and found that exogenous transplantation of senescent cells significantly aggravated them.Mechanistic studies and RNA sequencing suggested that radiation-induced senescent cell secretions were responsible for facilitating paracrine senescence and promoting the progression of radiation ulcers.Finally,we found that uMSC-CM was effective in mitigating the progression of radiation ulcers by inhibiting cellular senescence.Conclusions:Our findings not only characterize 展开更多
The solidification of Sn-Ni peritectic alloys in which both the primary Ni_(3)Sn_(2)and peritectic Ni_(3)Sn_(4)phases were intermetallic compound phases(IMCs)with narrow solubility ranges was investigated through conf...The solidification of Sn-Ni peritectic alloys in which both the primary Ni_(3)Sn_(2)and peritectic Ni_(3)Sn_(4)phases were intermetallic compound phases(IMCs)with narrow solubility ranges was investigated through confocal laser scanning microscope.Analysis on the interface migration at different cooling rates shows that the rate of peritectic reaction is much smaller than previous reports,and the growth of peritectic phase is mainly attributed to direct precipitation from the melt in Sn-Ni alloy after peritectic reaction.In addition,different from other peritectic alloys where the solidified phases are solid solution phases,the"step"growth of both Ni_(3)Sn_(2)and Ni_(3)Sn_(4)phases was observed.The dependences of the step thickness on both the cooling rate and solidification time were measured,which shows that the step thicknesses of both phases gradually decrease as solidification proceeds.This was confirmed to be attributed to the difference between the actual and equilibrium melt concentrations during solidification.In addition,the increase of the normal growth velocity of Ni_(3)Sn_(4)phase with increasing cooling rate was also proved through both the experimental observation and quantitative prediction.展开更多
基金supported by the Key Program of the National Natural Science Foundation of China(82030056)the Intramural Research Project Grants(2021-JCJQ-ZD-077-11,AWS17J007 and 2018-JCJQ-ZQ-001)Postdoctoral Innovative Talent Support Program in Chongqing(CQBX2021010).
文摘Background:Radiation ulcers are a common and severe injury after uncontrolled exposure to ionizing radiation.The most important feature of radiation ulcers is progressive ulceration,which results in the expansion of radiation injury to the nonirradiated area and refractory wounds.Current theories cannot explain the progression of radiation ulcers.Cellular senescence refers to as irre-versible growth arrest that occurs after exposure to stress,which contributes to tissue dysfunction by inducing paracrine senescence,stem cell dysfunction and chronic inflammation.However,it is not yet clear how cellular senescence facilitates the continuous progression of radiation ulcers.Here,we aim to investigate the role of cellular senescence in promoting progressive radiation ulcers and indicate a potential therapeutic strategy for radiation ulcers.Methods:Radiation ulcer animal models were established by local exposure to 40 Gy X-ray radiation and continuously evaluated for>260 days.The roles of cellular senescence in the progression of radiation ulcers were assessed using pathological analysis,molecular detection and RNA sequencing.Then,the therapeutic effects of conditioned medium from human umbilical cord mesenchymal stem cells(uMSC-CM)were investigated in radiation ulcer models.Results:Radiation ulcer animal models with features of clinical patients were established to investigate the primary mechanisms responsible for the progression of radiation ulcers.We have characterized cellular senescence as being closely associated with the progression of radiation ulcers and found that exogenous transplantation of senescent cells significantly aggravated them.Mechanistic studies and RNA sequencing suggested that radiation-induced senescent cell secretions were responsible for facilitating paracrine senescence and promoting the progression of radiation ulcers.Finally,we found that uMSC-CM was effective in mitigating the progression of radiation ulcers by inhibiting cellular senescence.Conclusions:Our findings not only characterize
基金financially supported by the National Natural Science Foundation of China(No.51871118)the Fundamental Research Funds for the Central Universities(No.lzujbky-2019-sp03)the fund of Science and Technology Project of Lanzhou(No.2019-1-30)。
文摘The solidification of Sn-Ni peritectic alloys in which both the primary Ni_(3)Sn_(2)and peritectic Ni_(3)Sn_(4)phases were intermetallic compound phases(IMCs)with narrow solubility ranges was investigated through confocal laser scanning microscope.Analysis on the interface migration at different cooling rates shows that the rate of peritectic reaction is much smaller than previous reports,and the growth of peritectic phase is mainly attributed to direct precipitation from the melt in Sn-Ni alloy after peritectic reaction.In addition,different from other peritectic alloys where the solidified phases are solid solution phases,the"step"growth of both Ni_(3)Sn_(2)and Ni_(3)Sn_(4)phases was observed.The dependences of the step thickness on both the cooling rate and solidification time were measured,which shows that the step thicknesses of both phases gradually decrease as solidification proceeds.This was confirmed to be attributed to the difference between the actual and equilibrium melt concentrations during solidification.In addition,the increase of the normal growth velocity of Ni_(3)Sn_(4)phase with increasing cooling rate was also proved through both the experimental observation and quantitative prediction.
