An imbalance in adenosine-mediated signaling,particularly the increased A_(2A)R-mediated signaling,plays a role in the pathogenesis of Parkinson's disease.Existing therapeutic approaches fail to alter disease prog...An imbalance in adenosine-mediated signaling,particularly the increased A_(2A)R-mediated signaling,plays a role in the pathogenesis of Parkinson's disease.Existing therapeutic approaches fail to alter disease progression,demonstrating the need for novel approaches in PD.Repetitive transcranial magnetic stimulation is a non-invasive approach that has been shown to improve motor and non-motor symptoms of Parkinson's disease.However,the underlying mechanisms of the beneficial effects of repetitive transcranial magnetic stimulation remain unknown.The purpose of this study is to investigate the extent to which the beneficial effects of prolonged intermittent theta burst stimulation in the 6-hydroxydopamine model of experimental parkinsonism are based on modulation of adenosine-mediated signaling.Animals with unilateral 6-hydroxydopamine lesions underwent intermittent theta burst stimulation for 3 weeks and were tested for motor skills using the Rotarod test.Immunoblot,quantitative reverse transcription polymerase chain reaction,immunohistochemistry,and biochemical analysis of components of adenosine-mediated signaling were performed on the synaptosomal fraction of the lesioned caudate putamen.Prolonged intermittent theta burst stimulation improved motor symptoms in 6-hydroxydopamine-lesioned animals.A 6-hydroxydopamine lesion resulted in progressive loss of dopaminergic neurons in the caudate putamen.Treatment with intermittent theta burst stimulation began 7 days after the lesion,coinciding with the onset of motor symptoms.After treatment with prolonged intermittent theta burst stimulation,complete motor recovery was observed.This improvement was accompanied by downregulation of the e N/CD73-A_(2A)R pathway and a return to physiological levels of A_(1)R-adenosine deaminase 1 after 3 weeks of intermittent theta burst stimulation.Our results demonstrated that 6-hydroxydopamine-induced degeneration reduced the expression of A_(1)R and elevated the expression of A_(2A)R.Intermittent theta burst stimulation reversed these effects by restoring the abundances of A_(1)R and A_(2A)R to control levels.The shift in ARs expression likely restored the balance between dopamine-adenosine signaling,ultimately leading to the recovery of motor control.展开更多
优化氮肥施用和秸秆还田技术为途径的农业管理措施被认为是提升农业可持续性的有效手段,然而当前关于氮肥和秸秆还田对小麦产量和N_(2)O排放影响的研究仍十分有限。为此,本研究基于2000—2022年发表的关于长江中下游流域氮肥和秸秆投入...优化氮肥施用和秸秆还田技术为途径的农业管理措施被认为是提升农业可持续性的有效手段,然而当前关于氮肥和秸秆还田对小麦产量和N_(2)O排放影响的研究仍十分有限。为此,本研究基于2000—2022年发表的关于长江中下游流域氮肥和秸秆投入下小麦产量和N_(2)O排放变化的文献,运用随机森林建模,定量分析氮肥和秸秆还田对小麦产量和N_(2)O排放的影响,并结合情景设置进行了特定地点的小麦产量和N_(2)O排放模拟,同时评估了碳排放强度(CEE)和净生态系统经济效益(NEEB)。结果表明,建立的区域尺度小麦产量与N_(2)O排放对氮秸互作响应的随机森林模型,验证结果R^(2)分别为0.66和0.65,RMSE分别为0.70和1.11。结果表明施氮量和土壤有机质是影响小麦产量和N_(2)O排放的重要因素。综合来看,达到最大产量所需的氮肥量为208~212 kg hm^(-2),达到最小CEE所需的氮肥量为113~130 kg hm^(-2),达到最高的NEEB所需的氮肥量为202~205 kg hm^(-2),其中在6.75 t hm^(-2)的秸秆投入下施用202 kg hm^(-2)的氮肥可以获得最高的生态收益1.37万元。优化氮肥和秸秆投入具备减少作物碳排放强度并获得最大净生态环境效益的潜力。展开更多
基金supported by a grant from Ministry of Science,Technological Development and Innovation,Serbia,No.451-03-68/2022-14/200178(to NN)University of Defence,No.MFVMA/02/22-24(to MN)。
文摘An imbalance in adenosine-mediated signaling,particularly the increased A_(2A)R-mediated signaling,plays a role in the pathogenesis of Parkinson's disease.Existing therapeutic approaches fail to alter disease progression,demonstrating the need for novel approaches in PD.Repetitive transcranial magnetic stimulation is a non-invasive approach that has been shown to improve motor and non-motor symptoms of Parkinson's disease.However,the underlying mechanisms of the beneficial effects of repetitive transcranial magnetic stimulation remain unknown.The purpose of this study is to investigate the extent to which the beneficial effects of prolonged intermittent theta burst stimulation in the 6-hydroxydopamine model of experimental parkinsonism are based on modulation of adenosine-mediated signaling.Animals with unilateral 6-hydroxydopamine lesions underwent intermittent theta burst stimulation for 3 weeks and were tested for motor skills using the Rotarod test.Immunoblot,quantitative reverse transcription polymerase chain reaction,immunohistochemistry,and biochemical analysis of components of adenosine-mediated signaling were performed on the synaptosomal fraction of the lesioned caudate putamen.Prolonged intermittent theta burst stimulation improved motor symptoms in 6-hydroxydopamine-lesioned animals.A 6-hydroxydopamine lesion resulted in progressive loss of dopaminergic neurons in the caudate putamen.Treatment with intermittent theta burst stimulation began 7 days after the lesion,coinciding with the onset of motor symptoms.After treatment with prolonged intermittent theta burst stimulation,complete motor recovery was observed.This improvement was accompanied by downregulation of the e N/CD73-A_(2A)R pathway and a return to physiological levels of A_(1)R-adenosine deaminase 1 after 3 weeks of intermittent theta burst stimulation.Our results demonstrated that 6-hydroxydopamine-induced degeneration reduced the expression of A_(1)R and elevated the expression of A_(2A)R.Intermittent theta burst stimulation reversed these effects by restoring the abundances of A_(1)R and A_(2A)R to control levels.The shift in ARs expression likely restored the balance between dopamine-adenosine signaling,ultimately leading to the recovery of motor control.
文摘优化氮肥施用和秸秆还田技术为途径的农业管理措施被认为是提升农业可持续性的有效手段,然而当前关于氮肥和秸秆还田对小麦产量和N_(2)O排放影响的研究仍十分有限。为此,本研究基于2000—2022年发表的关于长江中下游流域氮肥和秸秆投入下小麦产量和N_(2)O排放变化的文献,运用随机森林建模,定量分析氮肥和秸秆还田对小麦产量和N_(2)O排放的影响,并结合情景设置进行了特定地点的小麦产量和N_(2)O排放模拟,同时评估了碳排放强度(CEE)和净生态系统经济效益(NEEB)。结果表明,建立的区域尺度小麦产量与N_(2)O排放对氮秸互作响应的随机森林模型,验证结果R^(2)分别为0.66和0.65,RMSE分别为0.70和1.11。结果表明施氮量和土壤有机质是影响小麦产量和N_(2)O排放的重要因素。综合来看,达到最大产量所需的氮肥量为208~212 kg hm^(-2),达到最小CEE所需的氮肥量为113~130 kg hm^(-2),达到最高的NEEB所需的氮肥量为202~205 kg hm^(-2),其中在6.75 t hm^(-2)的秸秆投入下施用202 kg hm^(-2)的氮肥可以获得最高的生态收益1.37万元。优化氮肥和秸秆投入具备减少作物碳排放强度并获得最大净生态环境效益的潜力。
