Activation and reconstruction of the spinal cord circuitry is important for improving motor function following spinal cord injury.We conducted a case series study to investigate motor function improvement in 14 patien...Activation and reconstruction of the spinal cord circuitry is important for improving motor function following spinal cord injury.We conducted a case series study to investigate motor function improvement in 14 patients with chronic spinal cord injury treated with 4 weeks of unilateral(right only)cortical intermittent theta burst stimulation combined with bilateral magnetic stimulation of L3-L4 nerve roots,five times a week.Bilateral resting motor evoked potential amplitude was increased,central motor conduction time on the side receiving cortical stimulation was significantly decreased,and lower extremity motor score,Berg balance score,spinal cord independence measure-III score,and 10 m-walking speed were all increased after treatment.Right resting motor evoked potential amplitude was positively correlated with lower extremity motor score after 4 weeks of treatment.These findings suggest that cortical intermittent theta burst stimulation combined with precise root stimulation can improve nerve conduction of the corticospinal tract and lower limb motor function recovery in patients with chronic spinal cord injury.展开更多
Intermittent fasting can benefit breast cancer patients undergoing chemotherapy or immunotherapy.However,it is still uncertain how to select immunotherapy drugs to combine with intermittent fasting.Herein we observed ...Intermittent fasting can benefit breast cancer patients undergoing chemotherapy or immunotherapy.However,it is still uncertain how to select immunotherapy drugs to combine with intermittent fasting.Herein we observed that two cycles of fasting treatment significantly inhibited breast tumor growth and lung tissue metastasis,as well as prolonged overall survival in mice bearing 4T1 and 4T07 breast cancer.During this process,both the immunosuppressive monocytic-(M-)and granulocytic-(G-)myeloid-derived suppressor cell(MDSC)decreased,accompanied by an increase in interleukin(IL)7R^(+)and granzyme B^(+)T cells in the tumor microenvironment.Interestingly,we observed that Ly6G^(low)G-MDSC sharply decreased after fasting treatment,and the cell surface markers and protein mass spectrometry data showed potential therapeutic targets.Mechanistic investigation revealed that glucose metabolism restriction suppressed the splenic granulocytemonocyte progenitor and the generation of colony-stimulating factors and IL-6,which both contributed to the accumulation of G-MDSC.On the other hand,glucose metabolism restriction can directly induce the apoptosis of Ly6G^(low)G-MDSC,but not Ly6G^(high)subsets.In summary,these results suggest that glucose metabolism restriction induced by fasting treatment attenuates the immune-suppressive milieu and enhances the activation of CD3^(+)T cells,providing potential solutions for enhancing immune-based cancer interventions.展开更多
Intermittent theta burst stimulation(iTBS),a time-saving and cost-effective repetitive transcranial magnetic stimulation regime,has been shown to improve cognition in patients with Alzheimer’s disease(AD).However,the...Intermittent theta burst stimulation(iTBS),a time-saving and cost-effective repetitive transcranial magnetic stimulation regime,has been shown to improve cognition in patients with Alzheimer’s disease(AD).However,the specific mechanism underlying iTBS-induced cognitive enhancement remains unknown.Previous studies suggested that mitochondrial functions are modulated by magnetic stimulation.Here,we showed that iTBS upregulates the expression of iron-sulfur cluster assembly 1(ISCA1,an essential regulatory factor for mitochondrial respiration)in the brain of APP/PS1 mice.In vivo and in vitro studies revealed that iTBS modulates mitochondrial iron-sulfur cluster assembly to facilitate mitochondrial respiration and function,which is required for ISCA1.Moreover,iTBS rescues cognitive decline and attenuates AD-type pathologies in APP/PS1 mice.The present study uncovers a novel mechanism by which iTBS modulates mitochondrial respiration and function via ISCA1-mediated iron-sulfur cluster assembly to alleviate cognitive impairments and pathologies in AD.We provide the mechanistic target of iTBS that warrants its therapeutic potential for AD patients.展开更多
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
Objective:To investigate the clinical efficacy of intermittent theta burst stimulation(iTBS)and high frequency repetitive transcranial magnetic stimulation(rTMS)on post‑stroke executive impairment(PSEI).Methods:Ninety...Objective:To investigate the clinical efficacy of intermittent theta burst stimulation(iTBS)and high frequency repetitive transcranial magnetic stimulation(rTMS)on post‑stroke executive impairment(PSEI).Methods:Ninety patients with PSEI who were hospitalized in the rehabilitation department of Xuzhou Central Hospital and Xuzhou Rehabilitation Hospital from April 2021 to June 2022 were selected and divided into iTBS group,high‑frequency group and control group.All three groups of patients received routine rehabilitation training,given rTMS treatment with iTBS,10 Hz and shame stimulation for 4 weeks.Before and after treatment,all the patients were evaluated with the Montreal cognitive assessment(MoCA),the frontal assessment battery(FAB),troop color‑word test(SCWT),shape trails test(STT),digit span test(DST)and event related potential P300.Results:After treatment,MoCA,FAB,SCWT,STT,DST scores,P300 latency and amplitude were significantly better in the three groups than before treatment(P<0.05).MoCA,FAB,SCWT,STT‑B,DST scores,P300 latency and amplitude in the iTBS group and high‑frequency group were better than in the control group,with significant differences(P<0.05).The difference between iTBS group and high‑frequency group was not statistically significant(P>0.05).Conclusion:iTBS can improve PSEI,and the efficacy is comparable to 10Hz rTMS.iTBS takes less time with better efficiency,and it is worth popularizing and applying in clinic.展开更多
The information stored in working memory can be transformed into the system of long-term memory due to the long-term potential （LTP） mechanism. The 8- burst stimulation （TBS） can be used as an LTP induction protoc...The information stored in working memory can be transformed into the system of long-term memory due to the long-term potential （LTP） mechanism. The 8- burst stimulation （TBS） can be used as an LTP induction protocol in some experiments, but it has not been used in the models related to memory. In this work, an improved Camperi-Wang （C-W） model with the Ca2＋ subsystem-induced bistability is adopted, and the TBS is simulated to be the initial stimuli of this model. With the evolution of the effects of the stimuli properties such as the cycle, the amplitude, and the duty ration on the memory mechanism of this model, the TBS can be adopted to activate working memory models and produce long-term memory. The study helps to propose the relationship between working memory and long-term memory, which lays a theoretical basis for the study of the neural mechanism of long-term memory.展开更多
Intermittent characteristics of turbulence induced by coherent structures （blobs） was clearly observed in the ion saturation current signal, density fluctuation, particle flux and heat flux in HT-7. It is obvious th...Intermittent characteristics of turbulence induced by coherent structures （blobs） was clearly observed in the ion saturation current signal, density fluctuation, particle flux and heat flux in HT-7. It is obvious that ion saturation current signal has deviated from Gaussian distribution and the skewness （S） and flatness （K） of signal increase radially outwards in the scrape-off layer （SOL）. Using conditional analysis （CA）, asymmetric character of the intermittent bursts are demonstrated. Owing to the radial propagation of the coherent structures, the particle density profile in SOL is non-exponential and flat outwards from the last close flux surface （LCFS）. It is found around LCFS that the large burst fluctuations （above 2.5 rms） are responsible for about 50% of the total particle transport. Burst events move radially outwards with Ee ~ B velocity, and the blob size can be calculated as 5r ~ V^rc. Our experiment shows that the blob size, life time and drift velocity experienced a pronounced decorrelation in the shear layer. The electrostatic Reynolds stress components become very strong and show a radially steep gradient in the proximity of the shear layer. These experimental findings may imply that the coherent structures are titled by the developed shear flow in the E × B shear layer.展开更多
Stimulated Brillouin scattering is studied by numerically solving the Vlasov Maxwell system. A cascade of stim- ulated Brillouin scattering can occur when a linearly polarized laser pulse propagates in a plasma. It is...Stimulated Brillouin scattering is studied by numerically solving the Vlasov Maxwell system. A cascade of stim- ulated Brillouin scattering can occur when a linearly polarized laser pulse propagates in a plasma. It is found that a stimulated Brillouin scattering cascade can reduce the scattering and increase the transmission of light, as well as intro- duce a bursting behaviour in the evolution of the laser-plasma interaction. The bursting time in the reflectivity is found to be less than half the ion acoustic period. The ion temperature can affect the stimulated Brillouin scattering cascade, which can repeat several times at low ion temperatures and can be completely eliminated at high ion temperatures. For stimulated Brillouin scattering saturation, higher-harmonic generation and wave wave interaction of the excited ion acoustic waves can restrict the amplitude of the latter. In addition, stimulated Brillouin scattering cascade can restrict. the amplitude of the scattered light.展开更多
The scavenging effect of berbamine（Ber） on active oxygen radicals was studied, using a spin-trapping technique and a chemiluminescence（CL） method in phorbol myristate acetate（PMA） stimulated polymorphonuclear le...The scavenging effect of berbamine（Ber） on active oxygen radicals was studied, using a spin-trapping technique and a chemiluminescence（CL） method in phorbol myristate acetate（PMA） stimulated polymorphonuclear leukocytes（PMN） and in four cell-free superoxide（O<sub>2</sub>） or hydroxyl radical（OH） generating systems. Ber（0.1 to 0.3 mM） effectively reduced active oxygen radicals in PMN stimulated with PMA, but had no obvious effect on oxygen consumption during the respiratory burst of PMN, measured with spin probe oxymetry. Ber（0.3 mM） prominently inhibited the CL response of展开更多
基金supported by National Key R&D Program of China,No.2020YFC2004202the National Natural Science Foundation of China,Nos.81974358 and 81772453(all to DSX).
文摘Activation and reconstruction of the spinal cord circuitry is important for improving motor function following spinal cord injury.We conducted a case series study to investigate motor function improvement in 14 patients with chronic spinal cord injury treated with 4 weeks of unilateral(right only)cortical intermittent theta burst stimulation combined with bilateral magnetic stimulation of L3-L4 nerve roots,five times a week.Bilateral resting motor evoked potential amplitude was increased,central motor conduction time on the side receiving cortical stimulation was significantly decreased,and lower extremity motor score,Berg balance score,spinal cord independence measure-III score,and 10 m-walking speed were all increased after treatment.Right resting motor evoked potential amplitude was positively correlated with lower extremity motor score after 4 weeks of treatment.These findings suggest that cortical intermittent theta burst stimulation combined with precise root stimulation can improve nerve conduction of the corticospinal tract and lower limb motor function recovery in patients with chronic spinal cord injury.
基金supported by the Postdoctoral Research Funds of Hebei Medical University(30705010016-3759)Natural Science Foundation of China(32272328)+4 种基金Natural Science Foundation of Hebei Province(B2022321001)National Key Research Project of Hebei Province(20375502D)Postdoctoral Research Project of Hebei Province(B2022003031)Science and Technology Research Program of Hebei Provincial Colleges(QN2023229)Hebei Provincial Key Laboratory of Nutrition and Health(2023YDYY-KF05)。
文摘Intermittent fasting can benefit breast cancer patients undergoing chemotherapy or immunotherapy.However,it is still uncertain how to select immunotherapy drugs to combine with intermittent fasting.Herein we observed that two cycles of fasting treatment significantly inhibited breast tumor growth and lung tissue metastasis,as well as prolonged overall survival in mice bearing 4T1 and 4T07 breast cancer.During this process,both the immunosuppressive monocytic-(M-)and granulocytic-(G-)myeloid-derived suppressor cell(MDSC)decreased,accompanied by an increase in interleukin(IL)7R^(+)and granzyme B^(+)T cells in the tumor microenvironment.Interestingly,we observed that Ly6G^(low)G-MDSC sharply decreased after fasting treatment,and the cell surface markers and protein mass spectrometry data showed potential therapeutic targets.Mechanistic investigation revealed that glucose metabolism restriction suppressed the splenic granulocytemonocyte progenitor and the generation of colony-stimulating factors and IL-6,which both contributed to the accumulation of G-MDSC.On the other hand,glucose metabolism restriction can directly induce the apoptosis of Ly6G^(low)G-MDSC,but not Ly6G^(high)subsets.In summary,these results suggest that glucose metabolism restriction induced by fasting treatment attenuates the immune-suppressive milieu and enhances the activation of CD3^(+)T cells,providing potential solutions for enhancing immune-based cancer interventions.
基金supported by the National Natural Science Foundation of China(81901142)funds for key support objects of Third Military Medical University.
文摘Intermittent theta burst stimulation(iTBS),a time-saving and cost-effective repetitive transcranial magnetic stimulation regime,has been shown to improve cognition in patients with Alzheimer’s disease(AD).However,the specific mechanism underlying iTBS-induced cognitive enhancement remains unknown.Previous studies suggested that mitochondrial functions are modulated by magnetic stimulation.Here,we showed that iTBS upregulates the expression of iron-sulfur cluster assembly 1(ISCA1,an essential regulatory factor for mitochondrial respiration)in the brain of APP/PS1 mice.In vivo and in vitro studies revealed that iTBS modulates mitochondrial iron-sulfur cluster assembly to facilitate mitochondrial respiration and function,which is required for ISCA1.Moreover,iTBS rescues cognitive decline and attenuates AD-type pathologies in APP/PS1 mice.The present study uncovers a novel mechanism by which iTBS modulates mitochondrial respiration and function via ISCA1-mediated iron-sulfur cluster assembly to alleviate cognitive impairments and pathologies in AD.We provide the mechanistic target of iTBS that warrants its therapeutic potential for AD patients.
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.
基金Research project of Jiangsu Provincial Health Commission(No.K2019012)Xuzhou Science and Technology Bureau planned project(No.KC19156)。
文摘Objective:To investigate the clinical efficacy of intermittent theta burst stimulation(iTBS)and high frequency repetitive transcranial magnetic stimulation(rTMS)on post‑stroke executive impairment(PSEI).Methods:Ninety patients with PSEI who were hospitalized in the rehabilitation department of Xuzhou Central Hospital and Xuzhou Rehabilitation Hospital from April 2021 to June 2022 were selected and divided into iTBS group,high‑frequency group and control group.All three groups of patients received routine rehabilitation training,given rTMS treatment with iTBS,10 Hz and shame stimulation for 4 weeks.Before and after treatment,all the patients were evaluated with the Montreal cognitive assessment(MoCA),the frontal assessment battery(FAB),troop color‑word test(SCWT),shape trails test(STT),digit span test(DST)and event related potential P300.Results:After treatment,MoCA,FAB,SCWT,STT,DST scores,P300 latency and amplitude were significantly better in the three groups than before treatment(P<0.05).MoCA,FAB,SCWT,STT‑B,DST scores,P300 latency and amplitude in the iTBS group and high‑frequency group were better than in the control group,with significant differences(P<0.05).The difference between iTBS group and high‑frequency group was not statistically significant(P>0.05).Conclusion:iTBS can improve PSEI,and the efficacy is comparable to 10Hz rTMS.iTBS takes less time with better efficiency,and it is worth popularizing and applying in clinic.
基金supported by the National Natural Science Foundation of China(Nos.11232005 and11472104)the Ministry of Education Doctoral Foundation of China(No.20120074110020)
文摘The information stored in working memory can be transformed into the system of long-term memory due to the long-term potential （LTP） mechanism. The 8- burst stimulation （TBS） can be used as an LTP induction protocol in some experiments, but it has not been used in the models related to memory. In this work, an improved Camperi-Wang （C-W） model with the Ca2＋ subsystem-induced bistability is adopted, and the TBS is simulated to be the initial stimuli of this model. With the evolution of the effects of the stimuli properties such as the cycle, the amplitude, and the duty ration on the memory mechanism of this model, the TBS can be adopted to activate working memory models and produce long-term memory. The study helps to propose the relationship between working memory and long-term memory, which lays a theoretical basis for the study of the neural mechanism of long-term memory.
基金supported by National Natural Science Foundation of China (Nos.10605028, 10675127, 10675126 and 10675124)
文摘Intermittent characteristics of turbulence induced by coherent structures （blobs） was clearly observed in the ion saturation current signal, density fluctuation, particle flux and heat flux in HT-7. It is obvious that ion saturation current signal has deviated from Gaussian distribution and the skewness （S） and flatness （K） of signal increase radially outwards in the scrape-off layer （SOL）. Using conditional analysis （CA）, asymmetric character of the intermittent bursts are demonstrated. Owing to the radial propagation of the coherent structures, the particle density profile in SOL is non-exponential and flat outwards from the last close flux surface （LCFS）. It is found around LCFS that the large burst fluctuations （above 2.5 rms） are responsible for about 50% of the total particle transport. Burst events move radially outwards with Ee ~ B velocity, and the blob size can be calculated as 5r ~ V^rc. Our experiment shows that the blob size, life time and drift velocity experienced a pronounced decorrelation in the shear layer. The electrostatic Reynolds stress components become very strong and show a radially steep gradient in the proximity of the shear layer. These experimental findings may imply that the coherent structures are titled by the developed shear flow in the E × B shear layer.
基金Project supported by the Science and Technology Funds of China Academy of Engineering Physics(Grant Nos.2010B0102018 and 2010A0102004)the National Basic Research Program of China(Grant No.2010CB832904)the National Natural Science Foundation of China(Grant Nos.10975023,10835003 and 10935003)
文摘Stimulated Brillouin scattering is studied by numerically solving the Vlasov Maxwell system. A cascade of stim- ulated Brillouin scattering can occur when a linearly polarized laser pulse propagates in a plasma. It is found that a stimulated Brillouin scattering cascade can reduce the scattering and increase the transmission of light, as well as intro- duce a bursting behaviour in the evolution of the laser-plasma interaction. The bursting time in the reflectivity is found to be less than half the ion acoustic period. The ion temperature can affect the stimulated Brillouin scattering cascade, which can repeat several times at low ion temperatures and can be completely eliminated at high ion temperatures. For stimulated Brillouin scattering saturation, higher-harmonic generation and wave wave interaction of the excited ion acoustic waves can restrict the amplitude of the latter. In addition, stimulated Brillouin scattering cascade can restrict. the amplitude of the scattered light.
文摘The scavenging effect of berbamine（Ber） on active oxygen radicals was studied, using a spin-trapping technique and a chemiluminescence（CL） method in phorbol myristate acetate（PMA） stimulated polymorphonuclear leukocytes（PMN） and in four cell-free superoxide（O<sub>2</sub>） or hydroxyl radical（OH） generating systems. Ber（0.1 to 0.3 mM） effectively reduced active oxygen radicals in PMN stimulated with PMA, but had no obvious effect on oxygen consumption during the respiratory burst of PMN, measured with spin probe oxymetry. Ber（0.3 mM） prominently inhibited the CL response of
