Classic paired associative stimulation can improve synaptic plasticity,as demonstrated by animal expe riments and human clinical trials in spinal cord injury patients.Paired associative magnetic stimulation(dual-targe...Classic paired associative stimulation can improve synaptic plasticity,as demonstrated by animal expe riments and human clinical trials in spinal cord injury patients.Paired associative magnetic stimulation(dual-target peripheral and central magnetic stimulation)has been shown to promote neurologic recove ry after stroke.However,it remains unclear whether paired associative magnetic stimulation can promote recovery of lower limb motor dysfunction after spinal cord injury.We hypothesize that the curre nt caused by central and peripheral magnetic stimulation will conve rge at the synapse,which will promote synapse function and improve the motor function of the relevant muscles.Therefore,this study aimed to examine the effects of paired associative magnetic stimulation on neural circuit activation by measuring changes in motor evoked and somatosensory evoked potentials,motor and sensory function of the lower limbs,functional health and activities of daily living,and depression in patients with spinal co rd injury.We will recruit 110 thora cic spinal trauma patients treated in the Department of Spinal Cord Injury,China Rehabilitation Hospital and randomly assign them to expe rimental and control groups in a 1:1 ratio.The trial group(n=55)will be treated with paired associative magnetic stimulation and conventional rehabilitation treatment.The control group(n=55)will be treated with sham stimulation and co nventional rehabilitation treatment.Outcomes will be measured at four time points:baseline and 4,12,and 24 wee ks after the start of inte rvention(active or sham paired associative magnetic stimulation).The primary outcome measure of this trial is change in lower limb American Spinal Injury Association Impairment Scale motor function score from baseline to last follow-up.Secondary outcome measures include changes in lower limb American Spinal Injury Association sensory function sco re,motor evoked potentials,sensory evoked potentials,modified Ashwo rth scale score,Maslach Burnout Invento ry score,and Hamilton Depression Scale score over time.Motor evoked potential latency reflects corticospinal tract transmission time,while amplitude reflects recruitment ability;both measures can help elucidate the mechanism underlying the effect of paired associative magnetic stimulation on synaptic efficiency.Adve rse events will be recorded.Findings from this trial will help to indicate whether paired associative magnetic stimulation(1)promotes recove ry of lower limb sensory and motor function,reduces spasticity,and improves quality of life;(2)promotes neurologic recovery by increasing excitability of spinal cord motor neurons and stimulating synaptic plasticity;and(3)improves rehabilitation outcome in patients with spinal cord injury.Recruitment for this trial began in April 2021 and is currently ongoing.It was approved by the Ethics Committee of Yangzhi Affiliated Rehabilitation Hospital of Tongji University,China(approval No.YZ2020-018)on May 18,2020.The study protocol was registered in the Chinese Clinical Trial Registry(registration number:ChiCTR2100044794)on March 27,2021(protocol version 1.0).This trial will be completed in April 2022.展开更多
Diversified synthetic strategies are extremely important for the structural diversity of uranium-containing polyoxometalates(U-POMs)and their functional expansion.Herein,two sandwich-type U-POMs were reported,which ar...Diversified synthetic strategies are extremely important for the structural diversity of uranium-containing polyoxometalates(U-POMs)and their functional expansion.Herein,two sandwich-type U-POMs were reported,which are Na_(5.6)K_(6.4)[(UO_(2))(H_(2)O)(TeW_(9)O_(33))]_(2)·21H_(2)O(UTeW_(9))and Na_(8.9)K_(2.7)H_(1.19)[K_(0.79)(UO_(2))_(2.21)(PW_(9)O_(34))_(2)]·12H_(2)O(UPW_9)using in-situ strategy and lacunary precursor strategy,respectively.UTeW_9 shows a typical Keggin-typeopen or half-sandwich configuration.展开更多
Site-selective modification of peptide/protein is a vital approach to disclose post-translational modifications(PTMs) and plays a crucial role in chemical biology, as well as drug development. Compared with synthetic ...Site-selective modification of peptide/protein is a vital approach to disclose post-translational modifications(PTMs) and plays a crucial role in chemical biology, as well as drug development. Compared with synthetic and chemical biology methods, chemical modification of native peptide/protein provides a more versatile approach to achieve late-stage diversification for functional studies. Lysine featured high nucleophilicity, frequency, and solvent accessibility, making its site-selective modification important but elusive. Herein, we reported a visible-light-driven and Cys-directed Lys site-selective stapling approach for peptide/protein. By cleavable Cys anchoring, site-selective Lys single-site modification was achieved, and this method could be applied to multi-functionalization.展开更多
An efficient asymmetric and enantio-swithchable organocatalytic[3+3]annulation reaction using MBH-2-naphthoates of nitroalkenes and 4-hydroxyquinolin-2(1H)-ones has been developed.Densely substituted tetrahydropyrano[...An efficient asymmetric and enantio-swithchable organocatalytic[3+3]annulation reaction using MBH-2-naphthoates of nitroalkenes and 4-hydroxyquinolin-2(1H)-ones has been developed.Densely substituted tetrahydropyrano[3,2-c]qui noli nones scaffolds with two adjacent stereogenic centers are obtained with high yield(up to 95%yield)and good stereoselectivities(up to>20:1 dr and 96%ee)in an enantio-switchable manner.Furthermore,gram scale synthesis was achieved and the nitro group could easily transform into an amino group without any appreciable loss in the diastereo-and enantioselectivity.展开更多
On-resin peptide modification renders an easy-to-operate method that combines solid-phase peptide synthesis efficiency and avoids tedious purification procedures. Herein, we report the transition-metal-free and redox-...On-resin peptide modification renders an easy-to-operate method that combines solid-phase peptide synthesis efficiency and avoids tedious purification procedures. Herein, we report the transition-metal-free and redox-neutral approach for solid-phase Met diversification with substrate diversity, which could be applied to synthesize cyclic peptides of different sizes.展开更多
基金the National Key Research and Development Program of China,No.2020YFC2004202(to DSX)the National Natural Science Foundation of China(General Program),Nos.81772453,81974358(to DSX)Scientific Research Project of Yangzhi Rehabilitation Hospital Affliated to Tongji University,No.KYPY202006(to TTS)。
文摘Classic paired associative stimulation can improve synaptic plasticity,as demonstrated by animal expe riments and human clinical trials in spinal cord injury patients.Paired associative magnetic stimulation(dual-target peripheral and central magnetic stimulation)has been shown to promote neurologic recove ry after stroke.However,it remains unclear whether paired associative magnetic stimulation can promote recovery of lower limb motor dysfunction after spinal cord injury.We hypothesize that the curre nt caused by central and peripheral magnetic stimulation will conve rge at the synapse,which will promote synapse function and improve the motor function of the relevant muscles.Therefore,this study aimed to examine the effects of paired associative magnetic stimulation on neural circuit activation by measuring changes in motor evoked and somatosensory evoked potentials,motor and sensory function of the lower limbs,functional health and activities of daily living,and depression in patients with spinal co rd injury.We will recruit 110 thora cic spinal trauma patients treated in the Department of Spinal Cord Injury,China Rehabilitation Hospital and randomly assign them to expe rimental and control groups in a 1:1 ratio.The trial group(n=55)will be treated with paired associative magnetic stimulation and conventional rehabilitation treatment.The control group(n=55)will be treated with sham stimulation and co nventional rehabilitation treatment.Outcomes will be measured at four time points:baseline and 4,12,and 24 wee ks after the start of inte rvention(active or sham paired associative magnetic stimulation).The primary outcome measure of this trial is change in lower limb American Spinal Injury Association Impairment Scale motor function score from baseline to last follow-up.Secondary outcome measures include changes in lower limb American Spinal Injury Association sensory function sco re,motor evoked potentials,sensory evoked potentials,modified Ashwo rth scale score,Maslach Burnout Invento ry score,and Hamilton Depression Scale score over time.Motor evoked potential latency reflects corticospinal tract transmission time,while amplitude reflects recruitment ability;both measures can help elucidate the mechanism underlying the effect of paired associative magnetic stimulation on synaptic efficiency.Adve rse events will be recorded.Findings from this trial will help to indicate whether paired associative magnetic stimulation(1)promotes recove ry of lower limb sensory and motor function,reduces spasticity,and improves quality of life;(2)promotes neurologic recovery by increasing excitability of spinal cord motor neurons and stimulating synaptic plasticity;and(3)improves rehabilitation outcome in patients with spinal cord injury.Recruitment for this trial began in April 2021 and is currently ongoing.It was approved by the Ethics Committee of Yangzhi Affiliated Rehabilitation Hospital of Tongji University,China(approval No.YZ2020-018)on May 18,2020.The study protocol was registered in the Chinese Clinical Trial Registry(registration number:ChiCTR2100044794)on March 27,2021(protocol version 1.0).This trial will be completed in April 2022.
基金financially supported by the National Natural Science Foundation of China(No.22001034)Jiangxi Provincial Natural Science Foundation(No.20212BAB213001)。
文摘Diversified synthetic strategies are extremely important for the structural diversity of uranium-containing polyoxometalates(U-POMs)and their functional expansion.Herein,two sandwich-type U-POMs were reported,which are Na_(5.6)K_(6.4)[(UO_(2))(H_(2)O)(TeW_(9)O_(33))]_(2)·21H_(2)O(UTeW_(9))and Na_(8.9)K_(2.7)H_(1.19)[K_(0.79)(UO_(2))_(2.21)(PW_(9)O_(34))_(2)]·12H_(2)O(UPW_9)using in-situ strategy and lacunary precursor strategy,respectively.UTeW_9 shows a typical Keggin-typeopen or half-sandwich configuration.
基金supported by Guangdong Natural Science Funds for Distinguished Young Scholar (2018B030306017)the National Natural Science Foundation of China (22077144)+1 种基金Guangdong Provincial Key Laboratory of Chiral Molecule and Drug Discovery (2019B030301005)Key Research and Development Program of Guangdong Province (2020B1111110003)。
文摘Site-selective modification of peptide/protein is a vital approach to disclose post-translational modifications(PTMs) and plays a crucial role in chemical biology, as well as drug development. Compared with synthetic and chemical biology methods, chemical modification of native peptide/protein provides a more versatile approach to achieve late-stage diversification for functional studies. Lysine featured high nucleophilicity, frequency, and solvent accessibility, making its site-selective modification important but elusive. Herein, we reported a visible-light-driven and Cys-directed Lys site-selective stapling approach for peptide/protein. By cleavable Cys anchoring, site-selective Lys single-site modification was achieved, and this method could be applied to multi-functionalization.
基金financial support from the National Natural Science Foundation of China(No.81602972)Guangdong Natural Science Funds for Distinguished Young Scholar(No.2018B030306017)Guangdong Province Universities and Colleges Pearl River Scholar Funded Scheme(2018)。
文摘An efficient asymmetric and enantio-swithchable organocatalytic[3+3]annulation reaction using MBH-2-naphthoates of nitroalkenes and 4-hydroxyquinolin-2(1H)-ones has been developed.Densely substituted tetrahydropyrano[3,2-c]qui noli nones scaffolds with two adjacent stereogenic centers are obtained with high yield(up to 95%yield)and good stereoselectivities(up to>20:1 dr and 96%ee)in an enantio-switchable manner.Furthermore,gram scale synthesis was achieved and the nitro group could easily transform into an amino group without any appreciable loss in the diastereo-and enantioselectivity.
基金financial supported by the National Natural Science Foundation of China (No. 22077144)Guangdong Natural Science Funds for Distinguished Young Scholar (No.2018B030306017)+1 种基金Guangdong Provincial Key Laboratory of Chiral Molecule and Drug Discovery (No. 2019B030301005)Key Research and Development Program of Guangdong Province (No.2020B1111110003)。
文摘On-resin peptide modification renders an easy-to-operate method that combines solid-phase peptide synthesis efficiency and avoids tedious purification procedures. Herein, we report the transition-metal-free and redox-neutral approach for solid-phase Met diversification with substrate diversity, which could be applied to synthesize cyclic peptides of different sizes.
