Liquid chromatography tandem mass chromatography （LC-MS/MS） is an important hyphenated technique for quantitative analysis of drugs in biological fluids. Because of high sensitivity and selectivity, LC-MS/MS has bee...Liquid chromatography tandem mass chromatography （LC-MS/MS） is an important hyphenated technique for quantitative analysis of drugs in biological fluids. Because of high sensitivity and selectivity, LC-MS/MS has been used for pharmacokinetic studies, metabolites identification in the plasma and urine. This manuscript gives comprehensive analytical review, focusing on chromatographic separation approaches （column packing materials, column length and mobile phase） as well as different acquisition modes （SIM, MRM） for quantitative analysis of glucocorticoids and stimulants. This review is not meant to be exhaustive but rather to provide a general overview for detection and confirmation of target drugs using LC-MS/MS and thus useful in the doping analysis, toxicological studies as well as in pharmaceutical analysis.展开更多
Salinity is a major impediment to crop production. This study was undertaken to compare the effect of seaweed extract, humic acid, and potassium sulfate nanoparticles in alleviating salt stress in Alfalfa (Medicago sa...Salinity is a major impediment to crop production. This study was undertaken to compare the effect of seaweed extract, humic acid, and potassium sulfate nanoparticles in alleviating salt stress in Alfalfa (Medicago sativa L.). Seeds of ten alfalfa genotypes were germinated in a growth chamber at five salt concentrations (0%, 0.5%, 1.0%, 1.5%, and 2.00%). Salt concentrations above 1% reduced seed germination by more than 70% in most genotypes. One salt tolerant genotype (Mesa-Sirsa) and one salt sensitive (Bulldog 505) were selected and planted in greenhouse pots containing 2 kg of sand and subjected to two salt levels (10 and 15 dS· m-1). Four treatments consisting of 1) control (Hoagland solution, no-salt), 2) seaweed extract at 4 Kg·ha-1, 3) humic acid at 28 L· ha-1, and 4) potassium sulfate at 300 Kg· ha-1. Plant biomass was reduced under both salt concentrations in both genotypes, with a greater magnitude in the salt sensitive genotype. Application of seaweed extract resulted in higher relative water content and proline under both salt concentrations (10 and 15 dS·m-1) in the salt sensitive genotype, and lower electrolyte leakage in both salt tolerant and salt sensitive genotypes, under both salt concentrations. Seaweed extract also resulted in higher catalase and SOD activities in both genotypes under 10 dS·m-1. Catalase and SOD activities were associated with significantly (p < 0.01) reduced electrolyte leakage and increased shoot dry weight. Overall, seaweed extract seemed to have a positive effect in alleviating salt stress in alfalfa.展开更多
Monocytes (MC), lymphocytes (LC) and Kupffer cells (KC) were isolated respectively from blood and surgical liver samples of patients suffering from he-patocellular carcinoma (HCC). 13 patients were given BCG, mixed ba...Monocytes (MC), lymphocytes (LC) and Kupffer cells (KC) were isolated respectively from blood and surgical liver samples of patients suffering from he-patocellular carcinoma (HCC). 13 patients were given BCG, mixed bacterium vaccine (MBV) and human white blood cell interferon (IFN), the other 3 patients were not treated with any biological immune stimulants (BIS) and served as controls. The cytosta-tic and cytotoxic effects of MC and KC on human hepatoma SMMC-7721 (TC) were assayed in vitro and the numbers of T total (Tt), T helper (Th) and T suppressor (Ts) cells were counted using CD monoclonal antibody immunofluorescence. The results were as follows: (1) On the 7th day after the first administration of BIS, the cytostatic and cytotoxic effects of MC on TC showed obvious increase over pre-administration. The activity of BIS was 1 ?5 times as high as that in the controls. (2) After 3 administrations, the cytostatic effect of MC on TC increased to the normal level (84%), while the controls remained as before (45%). (3) On the 7th day after first administration, cytostatic and cytotoxic effects of KC on TC were 0.5 and 1 times higher respectively than those of the controls. (4) The numbers of Tt and Th of patients given BIS increased continuously; on the contrary Ts decreased in number. These results indicate that combined use of BCG, MBV and IFN can actively enhance the immune anti-hepatoma function of patients suffering from HCC.展开更多
BACKGROUND Children with attention-deficit/hyperactivity disorder(ADHD)often exhibit behaviour challenges and deficits in executive functions(EF).Psychostimulant medications[e.g.,methylphenidate(MPH)]are commonly pres...BACKGROUND Children with attention-deficit/hyperactivity disorder(ADHD)often exhibit behaviour challenges and deficits in executive functions(EF).Psychostimulant medications[e.g.,methylphenidate(MPH)]are commonly prescribed for children with ADHD and are considered effective in 70%of the cases.Furthermore,only a handful of studies have investigated the long-term impact of MPH medication on EF and behaviour.AIM To evaluate behaviour and EF challenges in children with ADHD who were involved in an MPH treatment trial across three-time points.METHODS Thirty-seven children with ADHD completed a stimulant medication trial to study the short-and long-term impact of medication.Children with ADHD completed three neuropsychological assessments[Continuous Performance Test(CPT)-II,Digit Span Backwards and Spatial Span Backwards].Parents of children with ADHD completed behaviour rating scales[Behaviour Rating Inventory of Executive Functioning(BRIEF)and Behaviour Assessment System for Children-Second Edition(BASC-2)].Participants were evaluated at:(1)Baseline(no medication);and(2)Best-dose(BD;following four-week MPH treatment).Additionally,18 participants returned for a long-term naturalistic follow up(FU;up to two years following BD).RESULTS Repeated measure analyses of variance found significant effects of time on two subscales of BRIEF and four subscales of BASC-2.Neuropsychological assessments showed some improvement,but not on all tasks following the medication trial.These improvements did not sustain at FU,with increases in EF and behaviour challenges,and a decline in performance on the CPT-II task being observed.CONCLUSION Parents of children with ADHD reported improvements in EF and behaviours during the MPH trial but were not sustained at FU.Combining screening tools and neuropsychological assessments may be useful for monitoring medication responses.展开更多
The Enhanced Geothermal System(EGS) is an artificial geothermal system that aims to economically extract heat from hot dry rock(HDR) through the creation of an artificial geothermal reservoir. Chemical stimulation is ...The Enhanced Geothermal System(EGS) is an artificial geothermal system that aims to economically extract heat from hot dry rock(HDR) through the creation of an artificial geothermal reservoir. Chemical stimulation is thought to be an effective method to create fracture networks and open existing fractures in hot dry rocks by injecting chemical agents into the reservoir to dissolve the minerals. Granite is a common type of hot dry rock. In this paper, a series of chemical stimulation experiments were implemented using acid and alkaline agents under high temperature and pressure conditions that mimic the environment of formation. Granite rock samples used in the experiments are collected from the potential EGS reservoir in the Matouying area, Hebei, China. Laboratory experimental results show that the corrosion ratio per unit area of rock is 3.2% in static acid chemical experiments and 0.51% in static alkaline chemical experiments. The permeability of the core is increased by 1.62 times in dynamic acid chemical experiments and 2.45 times in dynamic alkaline chemical experiments. A scanning electron microscope analysis of the core illustrates that secondary minerals, such as chlorite, spherical silica, and montmorillonite, were formed, due to acid-rock interaction with plagioclase being precipitated by alkaline-rock interactions. Masking agents in alkaline chemical agents can slightly reduce the degree of plagioclase formation. A chemical simulation model was built using TOUGHREACT, the mineral dissolution and associated ion concentration variation being reproduced by this reactive transport model.展开更多
The rubber tree Hevea brasiliensis(Willd.Ex Adr.De Juss.)Müell Arg.]is an important source of latex for the production natural rubber.Natural rubber is an important biopolymer used in various industries,but aspec...The rubber tree Hevea brasiliensis(Willd.Ex Adr.De Juss.)Müell Arg.]is an important source of latex for the production natural rubber.Natural rubber is an important biopolymer used in various industries,but aspects related to hormonal regulation in biosynthesis are still unknown,which would allow optimizing its production.We review the molecular and physiological mechanisms of increases latex regeneration and flow by the stimulation of rubber trees with exogenous applications of ethylene and jasmonate.We found that the increase in latex regeneration by ethylene is due to the increase in gene level expression and enzymatic activity of key photosynthesis and glycolysis enzymes for the generation of precursors in the first phase of rubber biosynthesis.Latex flow is supported by up-regulated genes in sucrose metabolism such as invertases,induction of sucrose transporters(SUT),and aquaporins(PIP)to maintain flow and turgor pressure in laticifers.Meanwhile,the increase in latex yield mediated by jasmonate may be due to the induction of laticifer differentiation in the long term and in the short term be mediated by the induction of small rubber particles(SRPP)as non-enzymatic cofactors in the production of latex.This information contributes to the knowledge of latex biosynthesis,which allows for a greater support for the exogenous application of jasmonates and ethylene to regulate its production.展开更多
The utilization of hybrid vigor is an important breakthrough in the history of rice breeding.To select the best hybrid combinations,breeders manually perform extensive testing of hybridizations between restorer and st...The utilization of hybrid vigor is an important breakthrough in the history of rice breeding.To select the best hybrid combinations,breeders manually perform extensive testing of hybridizations between restorer and sterile lines,which is a laborious and time-consuming process.Here,we report that a modified flowering stimulant containing methyl jasmonate(MeJA),6-benzylamine adenine and kinetin effectively promotes the flowering and seed set of male-sterile rice lines.Different concentrations of the ingredients were tested to identify an optimal formulation.Seed quality evaluation indicated that hybrid seeds from plants sprayed with the flowering stimulant had a higher germination rate than seeds from plants prepared by glume-cutting.In summary,the modified flowering stimulant described in this study may help reduce the labor requirement associated with hybrid rice breeding and improve yield and efficiency.展开更多
After spinal cord injury,impairment of the sensorimotor circuit can lead to dysfunction in the motor,sensory,proprioceptive,and autonomic nervous systems.Functional recovery is often hindered by constraints on the tim...After spinal cord injury,impairment of the sensorimotor circuit can lead to dysfunction in the motor,sensory,proprioceptive,and autonomic nervous systems.Functional recovery is often hindered by constraints on the timing of interventions,combined with the limitations of current methods.To address these challenges,various techniques have been developed to aid in the repair and reconstruction of neural circuits at different stages of injury.Notably,neuromodulation has garnered considerable attention for its potential to enhance nerve regeneration,provide neuroprotection,restore neurons,and regulate the neural reorganization of circuits within the cerebral cortex and corticospinal tract.To improve the effectiveness of these interventions,the implementation of multitarget early interventional neuromodulation strategies,such as electrical and magnetic stimulation,is recommended to enhance functional recovery across different phases of nerve injury.This review concisely outlines the challenges encountered following spinal cord injury,synthesizes existing neurostimulation techniques while emphasizing neuroprotection,repair,and regeneration of impaired connections,and advocates for multi-targeted,task-oriented,and timely interventions.展开更多
Spinal cord injury represents a severe form of central nervous system trauma for which effective treatments remain limited.Microglia is the resident immune cells of the central nervous system,play a critical role in s...Spinal cord injury represents a severe form of central nervous system trauma for which effective treatments remain limited.Microglia is the resident immune cells of the central nervous system,play a critical role in spinal cord injury.Previous studies have shown that microglia can promote neuronal survival by phagocytosing dead cells and debris and by releasing neuroprotective and anti-inflammatory factors.However,excessive activation of microglia can lead to persistent inflammation and contribute to the formation of glial scars,which hinder axonal regeneration.Despite this,the precise role and mechanisms of microglia during the acute phase of spinal cord injury remain controversial and poorly understood.To elucidate the role of microglia in spinal cord injury,we employed the colony-stimulating factor 1 receptor inhibitor PLX5622 to deplete microglia.We observed that sustained depletion of microglia resulted in an expansion of the lesion area,downregulation of brain-derived neurotrophic factor,and impaired functional recovery after spinal cord injury.Next,we generated a transgenic mouse line with conditional overexpression of brain-derived neurotrophic factor specifically in microglia.We found that brain-derived neurotrophic factor overexpression in microglia increased angiogenesis and blood flow following spinal cord injury and facilitated the recovery of hindlimb motor function.Additionally,brain-derived neurotrophic factor overexpression in microglia reduced inflammation and neuronal apoptosis during the acute phase of spinal cord injury.Furthermore,through using specific transgenic mouse lines,TMEM119,and the colony-stimulating factor 1 receptor inhibitor PLX73086,we demonstrated that the neuroprotective effects were predominantly due to brain-derived neurotrophic factor overexpression in microglia rather than macrophages.In conclusion,our findings suggest the critical role of microglia in the formation of protective glial scars.Depleting microglia is detrimental to recovery of spinal cord injury,whereas targeting brain-derived neurotrophic factor overexpression in microglia represents a promising and novel therapeutic strategy to enhance motor function recovery in patients with spinal cord injury.展开更多
Spontaneous recovery frequently proves maladaptive or insufficient because the plasticity of the injured adult mammalian central nervous system is limited.This limited plasticity serves as a primary barrier to functio...Spontaneous recovery frequently proves maladaptive or insufficient because the plasticity of the injured adult mammalian central nervous system is limited.This limited plasticity serves as a primary barrier to functional recovery after brain injury.Neuromodulation technologies represent one of the fastest-growing fields in medicine.These techniques utilize electricity,magnetism,sound,and light to restore or optimize brain functions by promoting reorganization or long-term changes that support functional recovery in patients with brain injury.Therefore,this review aims to provide a comprehensive overview of the effects and underlying mechanisms of neuromodulation technologies in supporting motor function recovery after brain injury.Many of these technologies are widely used in clinical practice and show significant improvements in motor function across various types of brain injury.However,studies report negative findings,potentially due to variations in stimulation protocols,differences in observation periods,and the severity of functional impairments among participants across different clinical trials.Additionally,we observed that different neuromodulation techniques share remarkably similar mechanisms,including promoting neuroplasticity,enhancing neurotrophic factor release,improving cerebral blood flow,suppressing neuroinflammation,and providing neuroprotection.Finally,considering the advantages and disadvantages of various neuromodulation techniques,we propose that future development should focus on closed-loop neural circuit stimulation,personalized treatment,interdisciplinary collaboration,and precision stimulation.展开更多
Noninvasive brain stimulation techniques offer promising therapeutic and regenerative prospects in neurological diseases by modulating brain activity and improving cognitive and motor functions.Given the paucity of kn...Noninvasive brain stimulation techniques offer promising therapeutic and regenerative prospects in neurological diseases by modulating brain activity and improving cognitive and motor functions.Given the paucity of knowledge about the underlying modes of action and optimal treatment modalities,a thorough translational investigation of noninvasive brain stimulation in preclinical animal models is urgently needed.Thus,we reviewed the current literature on the mechanistic underpinnings of noninvasive brain stimulation in models of central nervous system impairment,with a particular emphasis on traumatic brain injury and stroke.Due to the lack of translational models in most noninvasive brain stimulation techniques proposed,we found this review to the most relevant techniques used in humans,i.e.,transcranial magnetic stimulation and transcranial direct current stimulation.We searched the literature in Pub Med,encompassing the MEDLINE and PMC databases,for studies published between January 1,2020 and September 30,2024.Thirty-five studies were eligible.Transcranial magnetic stimulation and transcranial direct current stimulation demonstrated distinct strengths in augmenting rehabilitation post-stroke and traumatic brain injury,with emerging mechanistic evidence.Overall,we identified neuronal,inflammatory,microvascular,and apoptotic pathways highlighted in the literature.This review also highlights a lack of translational surrogate parameters to bridge the gap between preclinical findings and their clinical translation.展开更多
Although previous studies have demonstrated that transcranial focused ultrasound stimulation protects the ischemic brain,clear criteria for the stimulation time window and intensity are lacking.Electrical impedance to...Although previous studies have demonstrated that transcranial focused ultrasound stimulation protects the ischemic brain,clear criteria for the stimulation time window and intensity are lacking.Electrical impedance tomography enables real-time monitoring of changes in cerebral blood perfusion within the ischemic brain,but investigating the feasibility of using this method to assess post-stroke rehabilitation in vivo remains critical.In this study,ischemic stroke was induced in rats through middle cerebral artery occlusion surgery.Transcranial focused ultrasound stimulation was used to treat the rat model of ischemia,and electrical impedance tomography was used to measure impedance during both the acute stage of ischemia and the rehabilitation stage following the stimulation.Electrical impedance tomography results indicated that cerebral impedance increased after the onset of ischemia and decreased following transcranial focused ultrasound stimulation.Furthermore,the stimulation promoted motor function recovery,reduced cerebral infarction volume in the rat model of ischemic stroke,and induced the expression of brain-derived neurotrophic factor in the ischemic brain.Our results also revealed a significant correlation between the impedance of the ischemic brain post-intervention and improvements in behavioral scores and infarct volume.This study shows that daily administration of transcranial focused ultrasound stimulation for 20 minutes to the ischemic hemisphere 24 hours after cerebral ischemia enhanced motor recovery in a rat model of ischemia.Additionally,our findings indicate that electrical impedance tomography can serve as a valuable tool for quantitatively evaluating rehabilitation after ischemic stroke in vivo.These findings suggest the feasibility of using impedance data collected via electrical impedance tomography to clinically assess the effects of rehabilitatory interventions for patients with ischemic stroke.展开更多
Neuromodulation techniques effectively intervene in cognitive function,holding considerable scientific and practical value in fields such as aerospace,medicine,life sciences,and brain research.These techniques utilize...Neuromodulation techniques effectively intervene in cognitive function,holding considerable scientific and practical value in fields such as aerospace,medicine,life sciences,and brain research.These techniques utilize electrical stimulation to directly or indirectly target specific brain regions,modulating neural activity and influencing broader brain networks,thereby regulating cognitive function.Regulating cognitive function involves an understanding of aspects such as perception,learning and memory,attention,spatial cognition,and physical function.To enhance the application of cognitive regulation in the general population,this paper reviews recent publications from the Web of Science to assess the advancements and challenges of invasive and non-invasive stimulation methods in modulating cognitive functions.This review covers various neuromodulation techniques for cognitive intervention,including deep brain stimulation,vagus nerve stimulation,and invasive methods using microelectrode arrays.The non-invasive techniques discussed include transcranial magnetic stimulation,transcranial direct current stimulation,transcranial alternating current stimulation,transcutaneous electrical acupoint stimulation,and time interference stimulation for activating deep targets.Invasive stimulation methods,which are ideal for studying the pathogenesis of neurological diseases,tend to cause greater trauma and have been less researched in the context of cognitive function regulation.Non-invasive methods,particularly newer transcranial stimulation techniques,are gentler and more appropriate for regulating cognitive functions in the general population.These include transcutaneous acupoint electrical stimulation using acupoints and time interference methods for activating deep targets.This paper also discusses current technical challenges and potential future breakthroughs in neuromodulation technology.It is recommended that neuromodulation techniques be combined with neural detection methods to better assess their effects and improve the accuracy of non-invasive neuromodulation.Additionally,researching closed-loop feedback neuromodulation methods is identified as a promising direction for future development.展开更多
Brain lesions,such as those caused by stroke or traumatic brain injury(TBI),frequently result in persistent motor and cognitive impairments that significantly affect the individual patient's quality of life.Despit...Brain lesions,such as those caused by stroke or traumatic brain injury(TBI),frequently result in persistent motor and cognitive impairments that significantly affect the individual patient's quality of life.Despite differences in the mechanisms of injury,both conditions share a high prevalence of motor and cognitive impairments.These deficits show only limited natural recovery.展开更多
Alzheimer's disease is the most common type of cognitive disorder,and there is an urgent need to develop more effective,targeted and safer therapies for patients with this condition.Deep brain stimulation is an in...Alzheimer's disease is the most common type of cognitive disorder,and there is an urgent need to develop more effective,targeted and safer therapies for patients with this condition.Deep brain stimulation is an invasive surgical treatment that modulates abnormal neural activity by implanting electrodes into specific brain areas followed by electrical stimulation.As an emerging therapeutic approach,deep brain stimulation shows significant promise as a potential new therapy for Alzheimer's disease.Here,we review the potential mechanisms and therapeutic effects of deep brain stimulation in the treatment of Alzheimer's disease based on existing clinical and basic research.In clinical studies,the most commonly targeted sites include the fornix,the nucleus basalis of Meynert,and the ventral capsule/ventral striatum.Basic research has found that the most frequently targeted areas include the fornix,nucleus basalis of Meynert,hippocampus,entorhinal cortex,and rostral intralaminar thalamic nucleus.All of these individual targets exhibit therapeutic potential for patients with Alzheimer's disease and associated mechanisms of action have been investigated.Deep brain stimulation may exert therapeutic effects on Alzheimer's disease through various mechanisms,including reducing the deposition of amyloid-β,activation of the cholinergic system,increasing the levels of neurotrophic factors,enhancing synaptic activity and plasticity,promoting neurogenesis,and improving glucose metabolism.Currently,clinical trials investigating deep brain stimulation for Alzheimer's disease remain insufficient.In the future,it is essential to focus on translating preclinical mechanisms into clinical trials.Furthermore,consecutive follow-up studies are needed to evaluate the long-term safety and efficacy of deep brain stimulation for Alzheimer's disease,including cognitive function,neuropsychiatric symptoms,quality of life and changes in Alzheimer's disease biomarkers.Researchers must also prioritize the initiation of multi-center clinical trials of deep brain stimulation with large sample sizes and target earlier therapeutic windows,such as the prodromal and even the preclinical stages of Alzheimer's disease.Adopting these approaches will permit the efficient exploration of more effective and safer deep brain stimulation therapies for patients with Alzheimer's disease.展开更多
The major aim of stroke therapy is to stimulate brain repair and improve behavioral recovery after cerebral ischemia.One option is to stimulate endogenous neurogenesis in the subventricular zone and direct the newly f...The major aim of stroke therapy is to stimulate brain repair and improve behavioral recovery after cerebral ischemia.One option is to stimulate endogenous neurogenesis in the subventricular zone and direct the newly formed neurons to the damaged area.However,only a small percentage of these neurons survive,and many do not reach the damaged area,possibly because the corpus callosum impedes the migration of subventricular zone-derived stem cells into the lesioned cortex.A second major obstacle to stem cell therapy is the strong inflammatory reaction induced by cerebral ischemia,whereby the associated phagocytic activity of brain macrophages removes both therapeutic cells and/or cell-based drug carriers.To address these issues,neurogenesis was electrically stimulated in the subventricular zone,followed by isolation of proliferating cells,including newly formed neurons,which were subsequently mixed with a nutritional hydrogel.This mixture was then transferred to the stroke cavity of day 14 post-stroke mice.We found that the performance of the treated animals improved in behavioral tests,including novel object,open field,hole board,grooming,and“time-to-feel”adhesive tape tests.Furthermore,immunostaining revealed that the stem cell marker nestin,the neuroepithelial marker Mash1,and the immature neuronal marker doublecortin-positive cells survived in the transplanted area for 2 weeks,possibly due to reduced phagocytic activity and supportive angiogenesis.These results clearly indicate that the transplantation of committed subventricular zone stem cells combined with a protective nutritional gel directly into the infarct cavity after the peak of stroke-induced neuroinflammation represents a feasible approach to improve neurorestoration after cerebral ischemia.展开更多
经颅磁刺激(transcranial magnetic stimulation, TMS)是一种神经调制方法,临床中凭借医生经验手动确定TMS线圈摆放位姿,导致线圈摆放位置和姿态不准确且重复定位精度差。针对上述问题,提出一种TMS线圈机器人辅助定位系统,使用RGB相机...经颅磁刺激(transcranial magnetic stimulation, TMS)是一种神经调制方法,临床中凭借医生经验手动确定TMS线圈摆放位姿,导致线圈摆放位置和姿态不准确且重复定位精度差。针对上述问题,提出一种TMS线圈机器人辅助定位系统,使用RGB相机替代导航系统中双目红外相机,采用一种基于神经网络的无标志物TMS线圈机器人辅助定位方法。搭建神经网络实现相机空间线圈姿态到操作臂空间关节角度的映射,并通过仿真数据训练验证了该神经网络架构适用于TMS线圈位姿摆放问题。随后,通过实验验证了该方法的可行性,同时表明训练的神经网络针对TMS线圈定位任务具有良好的泛化能力。最后,在笛卡儿空间的位姿验证结果显示TMS线圈三维位置平均误差为2.16 mm,总体姿态误差为0.055 rad,使用RGB相机的TMS线圈机器人辅助定位系统在精度上达到了与其他使用双目红外相机的科研或商用系统相同的水平,满足TMS临床治疗要求,具备临床应用的可行性。展开更多
Patients with complete spinal cord injury retain the potential for volitional muscle activity in muscles located below the spinal injury level.However,because of prolonged inactivity,initial attempts to activate these...Patients with complete spinal cord injury retain the potential for volitional muscle activity in muscles located below the spinal injury level.However,because of prolonged inactivity,initial attempts to activate these muscles may not effectively engage any of the remaining neurons in the descending pathway.A previous study unexpectedly found that a brief clinical round of passive activity significantly increased volitional muscle activation,as measured by surface electromyography.In this study,we further explored the effect of passive activity on surface electromyographic signals during volitional control tasks among individuals with complete spinal cord injury.Eleven patients with chronic complete thoracic spinal cord injury were recruited.Surface electromyography data from eight major leg muscles were acquired and compared before and after the passive activity protocol.The results indicated that the passive activity led to an increased number of activated volitional muscles and an increased frequency of activation.Although the cumulative root mean square of surface electromyography amplitude for volitional control of movement showed a slight increase after passive activity,the difference was not statistically significant.These findings suggest that brief passive activity may enhance the ability to initiate volitional muscle activity during surface electromyography tasks and underscore the potential of passive activity for improving residual motor control among patients with motor complete spinal cord injury.展开更多
A reduction in adult neurogenesis is associated with behavioral abnormalities in patients with Alzheimer's disease.Consequently,enhancing adult neurogenesis represents a promising therapeutic approach for mitigati...A reduction in adult neurogenesis is associated with behavioral abnormalities in patients with Alzheimer's disease.Consequently,enhancing adult neurogenesis represents a promising therapeutic approach for mitigating disease symptoms and progression.Nonetheless,nonpharmacological interventions aimed at inducing adult neurogenesis are currently limited.Although individual non-pharmacological interventions,such as aerobic exercise,acousto-optic stimulation,and olfactory stimulation,have shown limited capacity to improve neurogenesis and cognitive function in patients with Alzheimer's disease,the therapeutic effect of a strategy that combines these interventions has not been fully explored.In this study,we observed an age-dependent decrease in adult neurogenesis and a concurrent increase in amyloid-beta accumulation in the hippocampus of amyloid precursor protein/presenilin 1 mice aged 2-8 months.Amyloid deposition became evident at 4 months,while neurogenesis declined by 6 months,further deteriorating as the disease progressed.However,following a 4-week multifactor stimulation protocol,which encompassed treadmill running(46 min/d,10 m/min,6 days per week),40 Hz acousto-optic stimulation(1 hour/day,6 days/week),and olfactory stimulation(1 hour/day,6 days/week),we found a significant increase in the number of newborn cells(5'-bromo-2'-deoxyuridine-positive cells),immature neurons(doublecortin-positive cells),newborn immature neurons(5'-bromo-2'-deoxyuridine-positive/doublecortin-positive cells),and newborn astrocytes(5'-bromo-2'-deoxyuridine-positive/glial fibrillary acidic protein-positive cells).Additionally,the amyloid-beta load in the hippocampus decreased.These findings suggest that multifactor stimulation can enhance adult hippocampal neurogenesis and mitigate amyloid-beta neuropathology in amyloid precursor protein/presenilin 1 mice.Furthermore,cognitive abilities were improved,and depressive symptoms were alleviated in amyloid precursor protein/presenilin 1 mice following multifactor stimulation,as evidenced by Morris water maze,novel object recognition,forced swimming test,and tail suspension test results.Notably,the efficacy of multifactor stimulation in consolidating immature neurons persisted for at least 2weeks after treatment cessation.At the molecular level,multifactor stimulation upregulated the expression of neuron-related proteins(NeuN,doublecortin,postsynaptic density protein-95,and synaptophysin),anti-apoptosis-related proteins(Bcl-2 and PARP),and an autophagyassociated protein(LC3B),while decreasing the expression of apoptosis-related proteins(BAX and caspase-9),in the hippocampus of amyloid precursor protein/presenilin 1 mice.These observations might be attributable to both the brain-derived neurotrophic factor-mediated signaling pathway and antioxidant pathways.Furthermore,serum metabolomics analysis indicated that multifactor stimulation regulated differentially expressed metabolites associated with cell apoptosis,oxidative damage,and cognition.Collectively,these findings suggest that multifactor stimulation is a novel non-invasive approach for the prevention and treatment of Alzheimer's disease.展开更多
Attempts have been made to modulate motor sequence learning(MSL)through repetitive transcranial magnetic stimulation,targeting different sites within the sensorimotor network.However,the target with the optimum modula...Attempts have been made to modulate motor sequence learning(MSL)through repetitive transcranial magnetic stimulation,targeting different sites within the sensorimotor network.However,the target with the optimum modulatory effect on neural plasticity associated with MSL remains unclarified.This study was therefore designed to compare the role of the left primary motor cortex and the left supplementary motor area proper(SMAp)in modulating MSL across different complexity levels and for both hands,as well as the associated neuroplasticity by applying intermittent theta burst stimulation together with the electroencephalogram and concurrent transcranial magnetic stimulation.Our data demonstrated the role of SMAp stimulation in modulating neural communication to support MSL,which is achieved by facilitating regional activation and orchestrating neural coupling across distributed brain regions,particularly in interhemispheric connections.These findings may have important clinical implications,particularly for motor rehabilitation in populations such as post-stroke patients.展开更多
文摘Liquid chromatography tandem mass chromatography （LC-MS/MS） is an important hyphenated technique for quantitative analysis of drugs in biological fluids. Because of high sensitivity and selectivity, LC-MS/MS has been used for pharmacokinetic studies, metabolites identification in the plasma and urine. This manuscript gives comprehensive analytical review, focusing on chromatographic separation approaches （column packing materials, column length and mobile phase） as well as different acquisition modes （SIM, MRM） for quantitative analysis of glucocorticoids and stimulants. This review is not meant to be exhaustive but rather to provide a general overview for detection and confirmation of target drugs using LC-MS/MS and thus useful in the doping analysis, toxicological studies as well as in pharmaceutical analysis.
文摘Salinity is a major impediment to crop production. This study was undertaken to compare the effect of seaweed extract, humic acid, and potassium sulfate nanoparticles in alleviating salt stress in Alfalfa (Medicago sativa L.). Seeds of ten alfalfa genotypes were germinated in a growth chamber at five salt concentrations (0%, 0.5%, 1.0%, 1.5%, and 2.00%). Salt concentrations above 1% reduced seed germination by more than 70% in most genotypes. One salt tolerant genotype (Mesa-Sirsa) and one salt sensitive (Bulldog 505) were selected and planted in greenhouse pots containing 2 kg of sand and subjected to two salt levels (10 and 15 dS· m-1). Four treatments consisting of 1) control (Hoagland solution, no-salt), 2) seaweed extract at 4 Kg·ha-1, 3) humic acid at 28 L· ha-1, and 4) potassium sulfate at 300 Kg· ha-1. Plant biomass was reduced under both salt concentrations in both genotypes, with a greater magnitude in the salt sensitive genotype. Application of seaweed extract resulted in higher relative water content and proline under both salt concentrations (10 and 15 dS·m-1) in the salt sensitive genotype, and lower electrolyte leakage in both salt tolerant and salt sensitive genotypes, under both salt concentrations. Seaweed extract also resulted in higher catalase and SOD activities in both genotypes under 10 dS·m-1. Catalase and SOD activities were associated with significantly (p < 0.01) reduced electrolyte leakage and increased shoot dry weight. Overall, seaweed extract seemed to have a positive effect in alleviating salt stress in alfalfa.
文摘Monocytes (MC), lymphocytes (LC) and Kupffer cells (KC) were isolated respectively from blood and surgical liver samples of patients suffering from he-patocellular carcinoma (HCC). 13 patients were given BCG, mixed bacterium vaccine (MBV) and human white blood cell interferon (IFN), the other 3 patients were not treated with any biological immune stimulants (BIS) and served as controls. The cytosta-tic and cytotoxic effects of MC and KC on human hepatoma SMMC-7721 (TC) were assayed in vitro and the numbers of T total (Tt), T helper (Th) and T suppressor (Ts) cells were counted using CD monoclonal antibody immunofluorescence. The results were as follows: (1) On the 7th day after the first administration of BIS, the cytostatic and cytotoxic effects of MC on TC showed obvious increase over pre-administration. The activity of BIS was 1 ?5 times as high as that in the controls. (2) After 3 administrations, the cytostatic effect of MC on TC increased to the normal level (84%), while the controls remained as before (45%). (3) On the 7th day after first administration, cytostatic and cytotoxic effects of KC on TC were 0.5 and 1 times higher respectively than those of the controls. (4) The numbers of Tt and Th of patients given BIS increased continuously; on the contrary Ts decreased in number. These results indicate that combined use of BCG, MBV and IFN can actively enhance the immune anti-hepatoma function of patients suffering from HCC.
基金Supported by the Alberta Children's Hospital Foundation,Werklund School of Education,University of Calgary.
文摘BACKGROUND Children with attention-deficit/hyperactivity disorder(ADHD)often exhibit behaviour challenges and deficits in executive functions(EF).Psychostimulant medications[e.g.,methylphenidate(MPH)]are commonly prescribed for children with ADHD and are considered effective in 70%of the cases.Furthermore,only a handful of studies have investigated the long-term impact of MPH medication on EF and behaviour.AIM To evaluate behaviour and EF challenges in children with ADHD who were involved in an MPH treatment trial across three-time points.METHODS Thirty-seven children with ADHD completed a stimulant medication trial to study the short-and long-term impact of medication.Children with ADHD completed three neuropsychological assessments[Continuous Performance Test(CPT)-II,Digit Span Backwards and Spatial Span Backwards].Parents of children with ADHD completed behaviour rating scales[Behaviour Rating Inventory of Executive Functioning(BRIEF)and Behaviour Assessment System for Children-Second Edition(BASC-2)].Participants were evaluated at:(1)Baseline(no medication);and(2)Best-dose(BD;following four-week MPH treatment).Additionally,18 participants returned for a long-term naturalistic follow up(FU;up to two years following BD).RESULTS Repeated measure analyses of variance found significant effects of time on two subscales of BRIEF and four subscales of BASC-2.Neuropsychological assessments showed some improvement,but not on all tasks following the medication trial.These improvements did not sustain at FU,with increases in EF and behaviour challenges,and a decline in performance on the CPT-II task being observed.CONCLUSION Parents of children with ADHD reported improvements in EF and behaviours during the MPH trial but were not sustained at FU.Combining screening tools and neuropsychological assessments may be useful for monitoring medication responses.
基金jointly supported by the National Key R&D Program of China(No.2018YFB1501802)the National Natural Science Foundation of China(No.41902309)funded by the Engineering Research Center of Geothermal Resources Development Technology and Equipment,Ministry of Education,Jilin University。
文摘The Enhanced Geothermal System(EGS) is an artificial geothermal system that aims to economically extract heat from hot dry rock(HDR) through the creation of an artificial geothermal reservoir. Chemical stimulation is thought to be an effective method to create fracture networks and open existing fractures in hot dry rocks by injecting chemical agents into the reservoir to dissolve the minerals. Granite is a common type of hot dry rock. In this paper, a series of chemical stimulation experiments were implemented using acid and alkaline agents under high temperature and pressure conditions that mimic the environment of formation. Granite rock samples used in the experiments are collected from the potential EGS reservoir in the Matouying area, Hebei, China. Laboratory experimental results show that the corrosion ratio per unit area of rock is 3.2% in static acid chemical experiments and 0.51% in static alkaline chemical experiments. The permeability of the core is increased by 1.62 times in dynamic acid chemical experiments and 2.45 times in dynamic alkaline chemical experiments. A scanning electron microscope analysis of the core illustrates that secondary minerals, such as chlorite, spherical silica, and montmorillonite, were formed, due to acid-rock interaction with plagioclase being precipitated by alkaline-rock interactions. Masking agents in alkaline chemical agents can slightly reduce the degree of plagioclase formation. A chemical simulation model was built using TOUGHREACT, the mineral dissolution and associated ion concentration variation being reproduced by this reactive transport model.
文摘The rubber tree Hevea brasiliensis(Willd.Ex Adr.De Juss.)Müell Arg.]is an important source of latex for the production natural rubber.Natural rubber is an important biopolymer used in various industries,but aspects related to hormonal regulation in biosynthesis are still unknown,which would allow optimizing its production.We review the molecular and physiological mechanisms of increases latex regeneration and flow by the stimulation of rubber trees with exogenous applications of ethylene and jasmonate.We found that the increase in latex regeneration by ethylene is due to the increase in gene level expression and enzymatic activity of key photosynthesis and glycolysis enzymes for the generation of precursors in the first phase of rubber biosynthesis.Latex flow is supported by up-regulated genes in sucrose metabolism such as invertases,induction of sucrose transporters(SUT),and aquaporins(PIP)to maintain flow and turgor pressure in laticifers.Meanwhile,the increase in latex yield mediated by jasmonate may be due to the induction of laticifer differentiation in the long term and in the short term be mediated by the induction of small rubber particles(SRPP)as non-enzymatic cofactors in the production of latex.This information contributes to the knowledge of latex biosynthesis,which allows for a greater support for the exogenous application of jasmonates and ethylene to regulate its production.
基金This work was supported by the National Natural Science Foundation of China(Grant No.31571634,31701406)and the Foundation of the Sichuan Provincial Department of Education(Grant No.17ZB0347).
文摘The utilization of hybrid vigor is an important breakthrough in the history of rice breeding.To select the best hybrid combinations,breeders manually perform extensive testing of hybridizations between restorer and sterile lines,which is a laborious and time-consuming process.Here,we report that a modified flowering stimulant containing methyl jasmonate(MeJA),6-benzylamine adenine and kinetin effectively promotes the flowering and seed set of male-sterile rice lines.Different concentrations of the ingredients were tested to identify an optimal formulation.Seed quality evaluation indicated that hybrid seeds from plants sprayed with the flowering stimulant had a higher germination rate than seeds from plants prepared by glume-cutting.In summary,the modified flowering stimulant described in this study may help reduce the labor requirement associated with hybrid rice breeding and improve yield and efficiency.
基金supported by the National Key Research and Development Program of China,No.2023YFC3603705(to DX)the National Natural Science Foundation of China,No.82302866(to YZ).
文摘After spinal cord injury,impairment of the sensorimotor circuit can lead to dysfunction in the motor,sensory,proprioceptive,and autonomic nervous systems.Functional recovery is often hindered by constraints on the timing of interventions,combined with the limitations of current methods.To address these challenges,various techniques have been developed to aid in the repair and reconstruction of neural circuits at different stages of injury.Notably,neuromodulation has garnered considerable attention for its potential to enhance nerve regeneration,provide neuroprotection,restore neurons,and regulate the neural reorganization of circuits within the cerebral cortex and corticospinal tract.To improve the effectiveness of these interventions,the implementation of multitarget early interventional neuromodulation strategies,such as electrical and magnetic stimulation,is recommended to enhance functional recovery across different phases of nerve injury.This review concisely outlines the challenges encountered following spinal cord injury,synthesizes existing neurostimulation techniques while emphasizing neuroprotection,repair,and regeneration of impaired connections,and advocates for multi-targeted,task-oriented,and timely interventions.
基金supported by the National Natural Science Foundation of China,Nos.82072165 and 82272256(both to XM)the Key Project of Xiangyang Central Hospital,No.2023YZ03(to RM)。
文摘Spinal cord injury represents a severe form of central nervous system trauma for which effective treatments remain limited.Microglia is the resident immune cells of the central nervous system,play a critical role in spinal cord injury.Previous studies have shown that microglia can promote neuronal survival by phagocytosing dead cells and debris and by releasing neuroprotective and anti-inflammatory factors.However,excessive activation of microglia can lead to persistent inflammation and contribute to the formation of glial scars,which hinder axonal regeneration.Despite this,the precise role and mechanisms of microglia during the acute phase of spinal cord injury remain controversial and poorly understood.To elucidate the role of microglia in spinal cord injury,we employed the colony-stimulating factor 1 receptor inhibitor PLX5622 to deplete microglia.We observed that sustained depletion of microglia resulted in an expansion of the lesion area,downregulation of brain-derived neurotrophic factor,and impaired functional recovery after spinal cord injury.Next,we generated a transgenic mouse line with conditional overexpression of brain-derived neurotrophic factor specifically in microglia.We found that brain-derived neurotrophic factor overexpression in microglia increased angiogenesis and blood flow following spinal cord injury and facilitated the recovery of hindlimb motor function.Additionally,brain-derived neurotrophic factor overexpression in microglia reduced inflammation and neuronal apoptosis during the acute phase of spinal cord injury.Furthermore,through using specific transgenic mouse lines,TMEM119,and the colony-stimulating factor 1 receptor inhibitor PLX73086,we demonstrated that the neuroprotective effects were predominantly due to brain-derived neurotrophic factor overexpression in microglia rather than macrophages.In conclusion,our findings suggest the critical role of microglia in the formation of protective glial scars.Depleting microglia is detrimental to recovery of spinal cord injury,whereas targeting brain-derived neurotrophic factor overexpression in microglia represents a promising and novel therapeutic strategy to enhance motor function recovery in patients with spinal cord injury.
基金supported by the National Natural Science Foundation of China,No.82371399(to YY)the Natural Science Foundation of Jiangsu Province,No.BK20221206(to YY)+1 种基金the Young Elite Scientists Sponsorship Program of Jiangsu Province,No.TJ-2022-028(to YY)the Scientific Research Program of Wuxi Health Commission,No.Z202302(to LY)。
文摘Spontaneous recovery frequently proves maladaptive or insufficient because the plasticity of the injured adult mammalian central nervous system is limited.This limited plasticity serves as a primary barrier to functional recovery after brain injury.Neuromodulation technologies represent one of the fastest-growing fields in medicine.These techniques utilize electricity,magnetism,sound,and light to restore or optimize brain functions by promoting reorganization or long-term changes that support functional recovery in patients with brain injury.Therefore,this review aims to provide a comprehensive overview of the effects and underlying mechanisms of neuromodulation technologies in supporting motor function recovery after brain injury.Many of these technologies are widely used in clinical practice and show significant improvements in motor function across various types of brain injury.However,studies report negative findings,potentially due to variations in stimulation protocols,differences in observation periods,and the severity of functional impairments among participants across different clinical trials.Additionally,we observed that different neuromodulation techniques share remarkably similar mechanisms,including promoting neuroplasticity,enhancing neurotrophic factor release,improving cerebral blood flow,suppressing neuroinflammation,and providing neuroprotection.Finally,considering the advantages and disadvantages of various neuromodulation techniques,we propose that future development should focus on closed-loop neural circuit stimulation,personalized treatment,interdisciplinary collaboration,and precision stimulation.
基金funded by the Deutsche Forschungsgemeinschaft(DFG,German Research Foundation):project ID 431549029-SFB 1451the Marga-und-Walter-Boll-Stiftung(#210-10-15)(to MAR)a stipend from the'Gerok Program'(Faculty of Medicine,University of Cologne,Germany)。
文摘Noninvasive brain stimulation techniques offer promising therapeutic and regenerative prospects in neurological diseases by modulating brain activity and improving cognitive and motor functions.Given the paucity of knowledge about the underlying modes of action and optimal treatment modalities,a thorough translational investigation of noninvasive brain stimulation in preclinical animal models is urgently needed.Thus,we reviewed the current literature on the mechanistic underpinnings of noninvasive brain stimulation in models of central nervous system impairment,with a particular emphasis on traumatic brain injury and stroke.Due to the lack of translational models in most noninvasive brain stimulation techniques proposed,we found this review to the most relevant techniques used in humans,i.e.,transcranial magnetic stimulation and transcranial direct current stimulation.We searched the literature in Pub Med,encompassing the MEDLINE and PMC databases,for studies published between January 1,2020 and September 30,2024.Thirty-five studies were eligible.Transcranial magnetic stimulation and transcranial direct current stimulation demonstrated distinct strengths in augmenting rehabilitation post-stroke and traumatic brain injury,with emerging mechanistic evidence.Overall,we identified neuronal,inflammatory,microvascular,and apoptotic pathways highlighted in the literature.This review also highlights a lack of translational surrogate parameters to bridge the gap between preclinical findings and their clinical translation.
基金supported by the Fundamental Research Funds for the Central Universities,Nos.G2021KY05107,G2021KY05101the National Natural Science Foundation of China,Nos.32071316,32211530049+1 种基金the Natural Science Foundation of Shaanxi Province,No.2022-JM482the Education and Teaching Reform Funds for the Central Universities,No.23GZ230102(all to LL and HH).
文摘Although previous studies have demonstrated that transcranial focused ultrasound stimulation protects the ischemic brain,clear criteria for the stimulation time window and intensity are lacking.Electrical impedance tomography enables real-time monitoring of changes in cerebral blood perfusion within the ischemic brain,but investigating the feasibility of using this method to assess post-stroke rehabilitation in vivo remains critical.In this study,ischemic stroke was induced in rats through middle cerebral artery occlusion surgery.Transcranial focused ultrasound stimulation was used to treat the rat model of ischemia,and electrical impedance tomography was used to measure impedance during both the acute stage of ischemia and the rehabilitation stage following the stimulation.Electrical impedance tomography results indicated that cerebral impedance increased after the onset of ischemia and decreased following transcranial focused ultrasound stimulation.Furthermore,the stimulation promoted motor function recovery,reduced cerebral infarction volume in the rat model of ischemic stroke,and induced the expression of brain-derived neurotrophic factor in the ischemic brain.Our results also revealed a significant correlation between the impedance of the ischemic brain post-intervention and improvements in behavioral scores and infarct volume.This study shows that daily administration of transcranial focused ultrasound stimulation for 20 minutes to the ischemic hemisphere 24 hours after cerebral ischemia enhanced motor recovery in a rat model of ischemia.Additionally,our findings indicate that electrical impedance tomography can serve as a valuable tool for quantitatively evaluating rehabilitation after ischemic stroke in vivo.These findings suggest the feasibility of using impedance data collected via electrical impedance tomography to clinically assess the effects of rehabilitatory interventions for patients with ischemic stroke.
基金supported by STI 2030-Major Projects,No.2021ZD0201603(to JL)the Joint Foundation Program of the Chinese Academy of Sciences,No.8091A170201(to JL)+1 种基金the National Natural Science Foundation of China,Nos.T2293730(to XC),T2293731(to XC),T2293734(to XC),62471291(to YW),62121003(to XC),61960206012(to XC),62333020(to XC),and 62171434(to XC)the National Key Research and Development Program of China,Nos.2022YFC2402501(to XC),2022YFB3205602(to XC).
文摘Neuromodulation techniques effectively intervene in cognitive function,holding considerable scientific and practical value in fields such as aerospace,medicine,life sciences,and brain research.These techniques utilize electrical stimulation to directly or indirectly target specific brain regions,modulating neural activity and influencing broader brain networks,thereby regulating cognitive function.Regulating cognitive function involves an understanding of aspects such as perception,learning and memory,attention,spatial cognition,and physical function.To enhance the application of cognitive regulation in the general population,this paper reviews recent publications from the Web of Science to assess the advancements and challenges of invasive and non-invasive stimulation methods in modulating cognitive functions.This review covers various neuromodulation techniques for cognitive intervention,including deep brain stimulation,vagus nerve stimulation,and invasive methods using microelectrode arrays.The non-invasive techniques discussed include transcranial magnetic stimulation,transcranial direct current stimulation,transcranial alternating current stimulation,transcutaneous electrical acupoint stimulation,and time interference stimulation for activating deep targets.Invasive stimulation methods,which are ideal for studying the pathogenesis of neurological diseases,tend to cause greater trauma and have been less researched in the context of cognitive function regulation.Non-invasive methods,particularly newer transcranial stimulation techniques,are gentler and more appropriate for regulating cognitive functions in the general population.These include transcutaneous acupoint electrical stimulation using acupoints and time interference methods for activating deep targets.This paper also discusses current technical challenges and potential future breakthroughs in neuromodulation technology.It is recommended that neuromodulation techniques be combined with neural detection methods to better assess their effects and improve the accuracy of non-invasive neuromodulation.Additionally,researching closed-loop feedback neuromodulation methods is identified as a promising direction for future development.
基金supported by the Defitech Foundation(Morges,CH)to FCHthe Bertarelli Foundation-Catalyst program(Gstaad,CH)to FCH+2 种基金the Wyss Center for Bio and Neuroengineering the Lighthouse Partnership for AI-guided Neuromodulation to FCHthe Fonds de recherche du Quebec-Sante(FRQS#342969)to CEPthe Neuro X Postdoctoral Fellowship Program to CEP。
文摘Brain lesions,such as those caused by stroke or traumatic brain injury(TBI),frequently result in persistent motor and cognitive impairments that significantly affect the individual patient's quality of life.Despite differences in the mechanisms of injury,both conditions share a high prevalence of motor and cognitive impairments.These deficits show only limited natural recovery.
基金supported by the Capital Fund for Health Improvement and Research,No.2022-2-2048(to WZ)the National Natural Science Foundation of China,No.81970992(to WZ)+3 种基金Capital Clinical Characteristic Application Research,No.Z121107001012161(to WZ)the Natural Science Foundation of Beijing,No.7082032(to WZ)the Key Technology R&D Program of Beijing Municipal Education Commission,No.KZ201610025030(to WZ)Project of Scientific and Technological Development of Traditional Chinese Medicine in Beijing,No.JJ2018-48(to WZ)。
文摘Alzheimer's disease is the most common type of cognitive disorder,and there is an urgent need to develop more effective,targeted and safer therapies for patients with this condition.Deep brain stimulation is an invasive surgical treatment that modulates abnormal neural activity by implanting electrodes into specific brain areas followed by electrical stimulation.As an emerging therapeutic approach,deep brain stimulation shows significant promise as a potential new therapy for Alzheimer's disease.Here,we review the potential mechanisms and therapeutic effects of deep brain stimulation in the treatment of Alzheimer's disease based on existing clinical and basic research.In clinical studies,the most commonly targeted sites include the fornix,the nucleus basalis of Meynert,and the ventral capsule/ventral striatum.Basic research has found that the most frequently targeted areas include the fornix,nucleus basalis of Meynert,hippocampus,entorhinal cortex,and rostral intralaminar thalamic nucleus.All of these individual targets exhibit therapeutic potential for patients with Alzheimer's disease and associated mechanisms of action have been investigated.Deep brain stimulation may exert therapeutic effects on Alzheimer's disease through various mechanisms,including reducing the deposition of amyloid-β,activation of the cholinergic system,increasing the levels of neurotrophic factors,enhancing synaptic activity and plasticity,promoting neurogenesis,and improving glucose metabolism.Currently,clinical trials investigating deep brain stimulation for Alzheimer's disease remain insufficient.In the future,it is essential to focus on translating preclinical mechanisms into clinical trials.Furthermore,consecutive follow-up studies are needed to evaluate the long-term safety and efficacy of deep brain stimulation for Alzheimer's disease,including cognitive function,neuropsychiatric symptoms,quality of life and changes in Alzheimer's disease biomarkers.Researchers must also prioritize the initiation of multi-center clinical trials of deep brain stimulation with large sample sizes and target earlier therapeutic windows,such as the prodromal and even the preclinical stages of Alzheimer's disease.Adopting these approaches will permit the efficient exploration of more effective and safer deep brain stimulation therapies for patients with Alzheimer's disease.
基金supported by European Union Funding Programme,PNRR,No. 760058(to DMH)the UEFISCDI Project,No. PN-III-P4-IDPCE-2020-059(to APW)
文摘The major aim of stroke therapy is to stimulate brain repair and improve behavioral recovery after cerebral ischemia.One option is to stimulate endogenous neurogenesis in the subventricular zone and direct the newly formed neurons to the damaged area.However,only a small percentage of these neurons survive,and many do not reach the damaged area,possibly because the corpus callosum impedes the migration of subventricular zone-derived stem cells into the lesioned cortex.A second major obstacle to stem cell therapy is the strong inflammatory reaction induced by cerebral ischemia,whereby the associated phagocytic activity of brain macrophages removes both therapeutic cells and/or cell-based drug carriers.To address these issues,neurogenesis was electrically stimulated in the subventricular zone,followed by isolation of proliferating cells,including newly formed neurons,which were subsequently mixed with a nutritional hydrogel.This mixture was then transferred to the stroke cavity of day 14 post-stroke mice.We found that the performance of the treated animals improved in behavioral tests,including novel object,open field,hole board,grooming,and“time-to-feel”adhesive tape tests.Furthermore,immunostaining revealed that the stem cell marker nestin,the neuroepithelial marker Mash1,and the immature neuronal marker doublecortin-positive cells survived in the transplanted area for 2 weeks,possibly due to reduced phagocytic activity and supportive angiogenesis.These results clearly indicate that the transplantation of committed subventricular zone stem cells combined with a protective nutritional gel directly into the infarct cavity after the peak of stroke-induced neuroinflammation represents a feasible approach to improve neurorestoration after cerebral ischemia.
基金supported by the Fundamental Research Funds for Central Public Welfare Research Institute,No.2020CZ-5(to WS and GS)the National Natural Science Foundation of China,No.31970970(to JSR)Fundamental Research Funds for the Central Universities,No.YWF-23-YG-QB-010(to JSR)。
文摘Patients with complete spinal cord injury retain the potential for volitional muscle activity in muscles located below the spinal injury level.However,because of prolonged inactivity,initial attempts to activate these muscles may not effectively engage any of the remaining neurons in the descending pathway.A previous study unexpectedly found that a brief clinical round of passive activity significantly increased volitional muscle activation,as measured by surface electromyography.In this study,we further explored the effect of passive activity on surface electromyographic signals during volitional control tasks among individuals with complete spinal cord injury.Eleven patients with chronic complete thoracic spinal cord injury were recruited.Surface electromyography data from eight major leg muscles were acquired and compared before and after the passive activity protocol.The results indicated that the passive activity led to an increased number of activated volitional muscles and an increased frequency of activation.Although the cumulative root mean square of surface electromyography amplitude for volitional control of movement showed a slight increase after passive activity,the difference was not statistically significant.These findings suggest that brief passive activity may enhance the ability to initiate volitional muscle activity during surface electromyography tasks and underscore the potential of passive activity for improving residual motor control among patients with motor complete spinal cord injury.
基金supported by the National Natural Science Foundation of China,No.82001155(to LL)the Natural Science Foundation of Zhejiang Province,No.LY23H090004(to LL)+5 种基金the Natural Science Foundation of Ningbo,No.2023J068(to LL)the Fundamental Research Funds for the Provincial Universities of Zhejiang Province,No.SJLY2023008(to LL)the College Students'Scientific and Technological Innovation Project(Xin Miao Talent Plan)of Zhejiang Province,No.2022R405A045(to CC)the Student ResearchInnovation Program(SRIP)of Ningbo University,Nos.20235RIP1919(to CZ),2023SRIP1938(to YZ)the K.C.Wong Magna Fund in Ningbo University。
文摘A reduction in adult neurogenesis is associated with behavioral abnormalities in patients with Alzheimer's disease.Consequently,enhancing adult neurogenesis represents a promising therapeutic approach for mitigating disease symptoms and progression.Nonetheless,nonpharmacological interventions aimed at inducing adult neurogenesis are currently limited.Although individual non-pharmacological interventions,such as aerobic exercise,acousto-optic stimulation,and olfactory stimulation,have shown limited capacity to improve neurogenesis and cognitive function in patients with Alzheimer's disease,the therapeutic effect of a strategy that combines these interventions has not been fully explored.In this study,we observed an age-dependent decrease in adult neurogenesis and a concurrent increase in amyloid-beta accumulation in the hippocampus of amyloid precursor protein/presenilin 1 mice aged 2-8 months.Amyloid deposition became evident at 4 months,while neurogenesis declined by 6 months,further deteriorating as the disease progressed.However,following a 4-week multifactor stimulation protocol,which encompassed treadmill running(46 min/d,10 m/min,6 days per week),40 Hz acousto-optic stimulation(1 hour/day,6 days/week),and olfactory stimulation(1 hour/day,6 days/week),we found a significant increase in the number of newborn cells(5'-bromo-2'-deoxyuridine-positive cells),immature neurons(doublecortin-positive cells),newborn immature neurons(5'-bromo-2'-deoxyuridine-positive/doublecortin-positive cells),and newborn astrocytes(5'-bromo-2'-deoxyuridine-positive/glial fibrillary acidic protein-positive cells).Additionally,the amyloid-beta load in the hippocampus decreased.These findings suggest that multifactor stimulation can enhance adult hippocampal neurogenesis and mitigate amyloid-beta neuropathology in amyloid precursor protein/presenilin 1 mice.Furthermore,cognitive abilities were improved,and depressive symptoms were alleviated in amyloid precursor protein/presenilin 1 mice following multifactor stimulation,as evidenced by Morris water maze,novel object recognition,forced swimming test,and tail suspension test results.Notably,the efficacy of multifactor stimulation in consolidating immature neurons persisted for at least 2weeks after treatment cessation.At the molecular level,multifactor stimulation upregulated the expression of neuron-related proteins(NeuN,doublecortin,postsynaptic density protein-95,and synaptophysin),anti-apoptosis-related proteins(Bcl-2 and PARP),and an autophagyassociated protein(LC3B),while decreasing the expression of apoptosis-related proteins(BAX and caspase-9),in the hippocampus of amyloid precursor protein/presenilin 1 mice.These observations might be attributable to both the brain-derived neurotrophic factor-mediated signaling pathway and antioxidant pathways.Furthermore,serum metabolomics analysis indicated that multifactor stimulation regulated differentially expressed metabolites associated with cell apoptosis,oxidative damage,and cognition.Collectively,these findings suggest that multifactor stimulation is a novel non-invasive approach for the prevention and treatment of Alzheimer's disease.
基金supported by grants from the Zhejiang Provincial Natural Science Foundation(LGJ22H180001)Zhejiang Medical and Health Science and Technology Project(2021KY249)the National Key R&D Program of China(2017YFC1310000).
文摘Attempts have been made to modulate motor sequence learning(MSL)through repetitive transcranial magnetic stimulation,targeting different sites within the sensorimotor network.However,the target with the optimum modulatory effect on neural plasticity associated with MSL remains unclarified.This study was therefore designed to compare the role of the left primary motor cortex and the left supplementary motor area proper(SMAp)in modulating MSL across different complexity levels and for both hands,as well as the associated neuroplasticity by applying intermittent theta burst stimulation together with the electroencephalogram and concurrent transcranial magnetic stimulation.Our data demonstrated the role of SMAp stimulation in modulating neural communication to support MSL,which is achieved by facilitating regional activation and orchestrating neural coupling across distributed brain regions,particularly in interhemispheric connections.These findings may have important clinical implications,particularly for motor rehabilitation in populations such as post-stroke patients.
