The ultimate goal of foreign language teaching is to enable the students to use the foreign language in work of life when necessary.Thus we should teach language in the way that is used in the real world.But the basic...The ultimate goal of foreign language teaching is to enable the students to use the foreign language in work of life when necessary.Thus we should teach language in the way that is used in the real world.But the basic precondition is that learner must be interested in foreign language.In my opinion,during the English learning process,"interest is the best teacher".But many students don’t like to learn English,the reason is that they are not interested in English.Therefore,a successful language teacher must know how to raise students’interest in learning English,make them enjoy learning English.In addition,the language teaching method is very important,it must renew continuously,teachers should use the vivid and diverse teaching method to organize students to participate in extensive language practice activities,so as to improve students’study enthusiasm.展开更多
Vagus nerve stimulation(VNS)and stroke:Stroke is the second leading cause of death and the third leading cause of disability worldwide(Baig et al.,2023).There have been significant paradigm shifts in the management of...Vagus nerve stimulation(VNS)and stroke:Stroke is the second leading cause of death and the third leading cause of disability worldwide(Baig et al.,2023).There have been significant paradigm shifts in the management of acute ischemic stroke through mechanical thrombectomy.In chronic ischemic stroke,invasive VNS paired with rehabilitation is associated with a significant increase in upper limb motor recovery and is FDA-approved(Baig et al.,2023).There are no treatments of similar efficacy in acute intracerebral hemorrhage(ICH)where several promising trials,e.g.,TICH-2,STOP-AUST,and TRAIGE did not show improvements in functional outcomes(Puy et al.,2023).展开更多
The cyclic GMP-AMP synthase(cGAS)-stimulator of interferon genes(STING)signaling pathway has emerged as a key mediator of neuroinflammation.While current studies primarily attribute its effects to neurons and glial ce...The cyclic GMP-AMP synthase(cGAS)-stimulator of interferon genes(STING)signaling pathway has emerged as a key mediator of neuroinflammation.While current studies primarily attribute its effects to neurons and glial cells,emerging research suggests that cGAS-STING signaling may play a critical role in cerebral vasculature,particularly in brain endothelial cells.Therefore,studying the role 7of inflammation caused by the cGAS-STING pathway in brain endothelial cells could provide a more comprehensive understanding of neuroinflammatory disease and new avenues for therapeutic interventions.Here,we review the multifaceted role of global cGAS-STING signaling in various neurological and neuroinflammatory diseases and the potential contribution of cGAS-STING in brain endothelial cells.展开更多
Spinal cord injuries have profound detrimental effects on individuals, regardless of whether they are caused by trauma or non-traumatic events. The compromised regeneration of the spinal cord is primarily attributed t...Spinal cord injuries have profound detrimental effects on individuals, regardless of whether they are caused by trauma or non-traumatic events. The compromised regeneration of the spinal cord is primarily attributed to damaged neurons, inhibitory molecules, dysfunctional immune response, and glial scarring. Unfortunately, currently, there are no effective treatments available that can fully repair the spinal cord and improve functional outcomes. Nevertheless, numerous pre-clinical approaches have been studied for spinal cord injury recovery, including using biomaterials, cells, drugs, or technological-based strategies. Combinatorial treatments, which target various aspects of spinal cord injury pathophysiology, have been extensively tested in the last decade. These approaches aim to synergistically enhance repair processes by addressing various obstacles faced during spinal cord regeneration. Thus, this review intends to provide scientists and clinicians with an overview of pre-clinical combinatorial approaches that have been developed toward the solution of spinal cord regeneration as well as update the current knowledge about spinal cord injury pathophysiology with an emphasis on the current clinical management.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
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:Clinical education plays a key role in preparing students for patient care.Laparoscopy is one of the most important minimally invasive surgeries(MISs)wherein surgical technologists are responsible for camera...Objective:Clinical education plays a key role in preparing students for patient care.Laparoscopy is one of the most important minimally invasive surgeries(MISs)wherein surgical technologists are responsible for camera navigation and assistant surgeons are responsible for peg transfer.Therefore,it is necessary to improve the attitude of the operating room students toward these skills during their study period.The present study was conducted to determine the effect of simulating training in the fundamentals of laparoscopic surgery(FLS)on the attitude of the operating room students.Methods:This interventional study was conducted on 28 operating room students of Iran University of Medical Sciences in 2019.The census sampling method was used.The data-collection tool included the“Intrinsic motivation inventory(IMI)questionnaire.”The educational intervention was carried out in theoretical(booklet design)and practical(simulation)sections.Data analysis was carried out using descriptive and inferential analyses including the paired t-test,Mann–Whitney U test,and independent t-test.The collected data were analyzed using R and SPSS software.P-value<0.05 was considered as the significant level.Results:The mean±SD of the participants'age was 22.93±2.14 years,and the majority of them were women(67.9%).There was a significant difference in the mean scores of students'attitudes toward the FLS before and after the educational intervention(P<0.001)in all dimensions(interest,perceived competence,perceived choice,and tension).There was also a significant correlation between gender and interest dimension(P=0.005).Conclusions:The results of the present study showed that simulating the training FLS curriculum positively affects students'attitudes.Therefore,the researchers suggest that for creating a positive attitude,increasing students'interest in laparoscopic surgery,and ensuring a more effective presence in the operating room,this training should be considered in the operating room curriculum.展开更多
Alzheimer’s disease is a prominent chronic neurodegenerative condition characterized by a gradual decline in memory leading to dementia.Growing evidence suggests that Alzheimer’s disease is associated with accumulat...Alzheimer’s disease is a prominent chronic neurodegenerative condition characterized by a gradual decline in memory leading to dementia.Growing evidence suggests that Alzheimer’s disease is associated with accumulating various amyloid-βoligomers in the brain,influenced by complex genetic and environmental factors.The memory and cognitive deficits observed during the prodromal and mild cognitive impairment phases of Alzheimer’s disease are believed to primarily result from synaptic dysfunction.Throughout life,environmental factors can lead to enduring changes in gene expression and the emergence of brain disorders.These changes,known as epigenetic modifications,also play a crucial role in regulating the formation of synapses and their adaptability in response to neuronal activity.In this context,we highlight recent advances in understanding the roles played by key components of the epigenetic machinery,specifically DNA methylation,histone modification,and microRNAs,in the development of Alzheimer’s disease,synaptic function,and activity-dependent synaptic plasticity.Moreover,we explore various strategies,including enriched environments,exposure to non-invasive brain stimulation,and the use of pharmacological agents,aimed at improving synaptic function and enhancing long-term potentiation,a process integral to epigenetic mechanisms.Lastly,we deliberate on the development of effective epigenetic agents and safe therapeutic approaches for managing Alzheimer’s disease.We suggest that addressing Alzheimer’s disease may require distinct tailored epigenetic drugs targeting different disease stages or pathways rather than relying on a single drug.展开更多
Alzheimer’s disease is a common neurodegenerative disorder defined by decreased reasoning abilities,memory loss,and cognitive deterioration.The presence of the blood-brain barrier presents a major obstacle to the dev...Alzheimer’s disease is a common neurodegenerative disorder defined by decreased reasoning abilities,memory loss,and cognitive deterioration.The presence of the blood-brain barrier presents a major obstacle to the development of effective drug therapies for Alzheimer’s disease.The use of ultrasound as a novel physical modulation approach has garnered widespread attention in recent years.As a safe and feasible therapeutic and drug-delivery method,ultrasound has shown promise in improving cognitive deficits.This article provides a summary of the application of ultrasound technology for treating Alzheimer’s disease over the past 5 years,including standalone ultrasound treatment,ultrasound combined with microbubbles or drug therapy,and magnetic resonance imaging-guided focused ultrasound therapy.Emphasis is placed on the benefits of introducing these treatment methods and their potential mechanisms.We found that several ultrasound methods can open the blood-brain barrier and effectively alleviate amyloid-βplaque deposition.We believe that ultrasound is an effective therapy for Alzheimer’s disease,and this review provides a theoretical basis for future ultrasound treatment methods.展开更多
The globus pallidus plays a pivotal role in the basal ganglia circuit. Parkinson's disease is characterized by degeneration of dopamine-producing cells in the substantia nigra, which leads to dopamine deficiency i...The globus pallidus plays a pivotal role in the basal ganglia circuit. Parkinson's disease is characterized by degeneration of dopamine-producing cells in the substantia nigra, which leads to dopamine deficiency in the brain that subsequently manifests as various motor and non-motor symptoms. This review aims to summarize the involvement of the globus pallidus in both motor and non-motor manifestations of Parkinson's disease. The firing activities of parvalbumin neurons in the medial globus pallidus, including both the firing rate and pattern, exhibit strong correlations with the bradykinesia and rigidity associated with Parkinson's disease. Increased beta oscillations, which are highly correlated with bradykinesia and rigidity, are regulated by the lateral globus pallidus. Furthermore,bradykinesia and rigidity are strongly linked to the loss of dopaminergic projections within the cortical-basal ganglia-thalamocortical loop. Resting tremors are attributed to the transmission of pathological signals from the basal ganglia through the motor cortex to the cerebellum-ventral intermediate nucleus circuit. The cortico–striato–pallidal loop is responsible for mediating pallidi-associated sleep disorders. Medication and deep brain stimulation are the primary therapeutic strategies addressing the globus pallidus in Parkinson's disease. Medication is the primary treatment for motor symptoms in the early stages of Parkinson's disease, while deep brain stimulation has been clinically proven to be effective in alleviating symptoms in patients with advanced Parkinson's disease,particularly for the movement disorders caused by levodopa. Deep brain stimulation targeting the globus pallidus internus can improve motor function in patients with tremordominant and non-tremor-dominant Parkinson's disease, while deep brain stimulation targeting the globus pallidus externus can alter the temporal pattern of neural activity throughout the basal ganglia–thalamus network. Therefore, the composition of the globus pallidus neurons, the neurotransmitters that act on them, their electrical activity,and the neural circuits they form can guide the search for new multi-target drugs to treat Parkinson's disease in clinical practice. Examining the potential intra-nuclear and neural circuit mechanisms of deep brain stimulation associated with the globus pallidus can facilitate the management of both motor and non-motor symptoms while minimizing the side effects caused by deep brain stimulation.展开更多
Motivation to language learning is a complex set of variables including effort, desire to achieve goals, as well as attitudes toward the learning of the language. Individuals' motivation to second-language learnin...Motivation to language learning is a complex set of variables including effort, desire to achieve goals, as well as attitudes toward the learning of the language. Individuals' motivation to second-language learning also includes their motivation orientations, interest in the second language, attitudes toward the second-language group, attitudes toward the second-language learning situations and second-language anxiety. Based on the basic theories and approaches, teaching activities are part of motivation in English classes. The teacher of language should have a good influence on students and develop students' keen interest in study in order to strengthen their intrinsic motivation, and set up some new goals for students to pursue and give the feedback to reinforce their inner drive and confidence. Thus, students will become major conductors, make full use of their potentials and enhance their study results.展开更多
With the increasing use of nuclear energy, there is a need for a wider range of efficient dosimeters for radiation detection and assessment. There has been a tremendous growth in the development of radiation detectors...With the increasing use of nuclear energy, there is a need for a wider range of efficient dosimeters for radiation detection and assessment. There has been a tremendous growth in the development of radiation detectors and devices in the past few decades. In recent years, the development of new materials for radiation dosimetry has progressed significantly. Alkaline earth sulfides (AES) have been known for a long time as excellent and versatile phosphor materials. In the present investigation, a number of phosphor samples such as mono-, binary and ternary sulfides of alkaline earths (II^a-VI^b) have been prepared and their TL properties have been studied with respect to exposure (x-ray) response and fading. In this paper, some results on SrS:Eu, Sm and CaS:Eu, Sm phosphors are presented. A type of novel OSL dosimeter is described. The dosimeter takes advantage of the characteristics of charge trapping materials SrS:Eu, Sm and CaS:Eu, Sm that exhibit optically stimulated luminescence (OSL). The measuring range of the dosimeter is from 0.01 to 1000 Gy. The OSL dosimeters provide capability for remote monitoring radiation locations which are difficult to access and hazardous. This equipment is relatively simple, small in size and has low power consumption. The device is suitable for space radiation dose exploration. In addition, it also can be used in IC and other radiation occasions and has good prospects.展开更多
The 'Old Red Sand' is a type of semicemented medium-fine sandy sediment that is red(10R_4/8) or brown red(2.5YR_4/8) in colour and is found in late Quaternary deposits. The sediments have distinctive character...The 'Old Red Sand' is a type of semicemented medium-fine sandy sediment that is red(10R_4/8) or brown red(2.5YR_4/8) in colour and is found in late Quaternary deposits. The sediments have distinctive characteristics and are a critical archive for understanding climatic changes in the coastal areas of East Asia. The ages of the late Quaternary aeolian sand dunes from Haitan Island in the coastal area of South China are still in debate. In this study, three sets of marine terraces were identified in the northern region of Haitan Island. Aeolian dune sands are well preserved on the top of these terraces. Quartz Optically Stimulated Luminescence dating and the distribution of the formation ages demonstrated that the palaeo-dunes are deposits from the middle-late period of the Late Pleistocene(Q_3^(2-3)). The period may be divided into three stages, 100-90 ka, 70-60 ka, and 40-20 ka, in which the palaeo-dunes of the first two stages are more widespread and were formed separately during a low-sea level period of the Marine Isotope Stages 5 b and 4. Several depositional palaeo-flood event records were preserved during the last stage due to the increasing gradient of mountain gullies formed during the Last Glacial Maximum.展开更多
Emotional factors and motivations should be taken into considerations,and combine grammar,rules with practical skills in communications,the stimulation of children's English learning at the initial stage must take...Emotional factors and motivations should be taken into considerations,and combine grammar,rules with practical skills in communications,the stimulation of children's English learning at the initial stage must take effect and lead to good results.展开更多
The resonances of parametric vibration with forced vibration isanalyzed, the bifurca- tion equation of the system is obtained andthe singularity analysis is made. Some of the laws and phe- nomenaare revealed. The tran...The resonances of parametric vibration with forced vibration isanalyzed, the bifurca- tion equation of the system is obtained andthe singularity analysis is made. Some of the laws and phe- nomenaare revealed. The transition variety and bifurcation diagram of thephysical parameteric plane are given. the results can be used inengineering.展开更多
This paper studies power dependent photoluminescence spectra, the stimulated emission occurring at ultraviolet (UV) band instead of the green emission band of ZnO nanowires, which are prepared with a chemical reduct...This paper studies power dependent photoluminescence spectra, the stimulated emission occurring at ultraviolet (UV) band instead of the green emission band of ZnO nanowires, which are prepared with a chemical reduction method. The dynamics of the UV emission and green emission is given to demonstrate the reason of stimulated emission occurring at UV band but not the green emission band under high excitation, which indicates that the slow decay rate of trap state makes it easy to be fully filled and saturated, while the fast decay rate of near-band-edge exciton state makes the UV emission dominate the radiative recombination under high excitation. The UV emission, as well as the corresponding stimulated emission, occurs in competition with the green deep-trap emission. In addition, when pump fluence further increases, the multiple lasing modes appear. The dependence of these lasing modes on the pump fluence is first discussed. This diagram should be helpful to understand and design the optical nanodevices of ZnO nanowires.展开更多
文摘The ultimate goal of foreign language teaching is to enable the students to use the foreign language in work of life when necessary.Thus we should teach language in the way that is used in the real world.But the basic precondition is that learner must be interested in foreign language.In my opinion,during the English learning process,"interest is the best teacher".But many students don’t like to learn English,the reason is that they are not interested in English.Therefore,a successful language teacher must know how to raise students’interest in learning English,make them enjoy learning English.In addition,the language teaching method is very important,it must renew continuously,teachers should use the vivid and diverse teaching method to organize students to participate in extensive language practice activities,so as to improve students’study enthusiasm.
基金supported by on Association of British Neurologists Fellowship(Stroke Association/Berkeley Foundation)supported by the NIHR Sheffield Biomedical Research Centre。
文摘Vagus nerve stimulation(VNS)and stroke:Stroke is the second leading cause of death and the third leading cause of disability worldwide(Baig et al.,2023).There have been significant paradigm shifts in the management of acute ischemic stroke through mechanical thrombectomy.In chronic ischemic stroke,invasive VNS paired with rehabilitation is associated with a significant increase in upper limb motor recovery and is FDA-approved(Baig et al.,2023).There are no treatments of similar efficacy in acute intracerebral hemorrhage(ICH)where several promising trials,e.g.,TICH-2,STOP-AUST,and TRAIGE did not show improvements in functional outcomes(Puy et al.,2023).
基金partially supported by a grant(RF1AG059694)from the U.S.National Institutes of Healthby Polytrauma System of Care,VAPAHCS(to JL)。
文摘The cyclic GMP-AMP synthase(cGAS)-stimulator of interferon genes(STING)signaling pathway has emerged as a key mediator of neuroinflammation.While current studies primarily attribute its effects to neurons and glial cells,emerging research suggests that cGAS-STING signaling may play a critical role in cerebral vasculature,particularly in brain endothelial cells.Therefore,studying the role 7of inflammation caused by the cGAS-STING pathway in brain endothelial cells could provide a more comprehensive understanding of neuroinflammatory disease and new avenues for therapeutic interventions.Here,we review the multifaceted role of global cGAS-STING signaling in various neurological and neuroinflammatory diseases and the potential contribution of cGAS-STING in brain endothelial cells.
基金funded by National funds,through the Foundation for Science and Technology (FCT)-project UIDB/50026/2020 (DOI 10.54499/UIDB/50026/2020),UIDP/50026/2020 (DOI 10.54499/UIDP/50026/2020) and LA/P/0050/2020 (DOI 10.54499/LA/P/0050/2020)(to NAS)Financial support was also provided by Prémios Santa Casa Neurociências–Prize Melo e Castro for Spinal Cord Injury Research (MC-18-2021)Wings for Life Spinal Cord Research Foundation (WFL-PT-14/23)(to NAS)。
文摘Spinal cord injuries have profound detrimental effects on individuals, regardless of whether they are caused by trauma or non-traumatic events. The compromised regeneration of the spinal cord is primarily attributed to damaged neurons, inhibitory molecules, dysfunctional immune response, and glial scarring. Unfortunately, currently, there are no effective treatments available that can fully repair the spinal cord and improve functional outcomes. Nevertheless, numerous pre-clinical approaches have been studied for spinal cord injury recovery, including using biomaterials, cells, drugs, or technological-based strategies. Combinatorial treatments, which target various aspects of spinal cord injury pathophysiology, have been extensively tested in the last decade. These approaches aim to synergistically enhance repair processes by addressing various obstacles faced during spinal cord regeneration. Thus, this review intends to provide scientists and clinicians with an overview of pre-clinical combinatorial approaches that have been developed toward the solution of spinal cord regeneration as well as update the current knowledge about spinal cord injury pathophysiology with an emphasis on the current clinical management.
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 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supported by the Iran University of Medical Science。
文摘Objective:Clinical education plays a key role in preparing students for patient care.Laparoscopy is one of the most important minimally invasive surgeries(MISs)wherein surgical technologists are responsible for camera navigation and assistant surgeons are responsible for peg transfer.Therefore,it is necessary to improve the attitude of the operating room students toward these skills during their study period.The present study was conducted to determine the effect of simulating training in the fundamentals of laparoscopic surgery(FLS)on the attitude of the operating room students.Methods:This interventional study was conducted on 28 operating room students of Iran University of Medical Sciences in 2019.The census sampling method was used.The data-collection tool included the“Intrinsic motivation inventory(IMI)questionnaire.”The educational intervention was carried out in theoretical(booklet design)and practical(simulation)sections.Data analysis was carried out using descriptive and inferential analyses including the paired t-test,Mann–Whitney U test,and independent t-test.The collected data were analyzed using R and SPSS software.P-value<0.05 was considered as the significant level.Results:The mean±SD of the participants'age was 22.93±2.14 years,and the majority of them were women(67.9%).There was a significant difference in the mean scores of students'attitudes toward the FLS before and after the educational intervention(P<0.001)in all dimensions(interest,perceived competence,perceived choice,and tension).There was also a significant correlation between gender and interest dimension(P=0.005).Conclusions:The results of the present study showed that simulating the training FLS curriculum positively affects students'attitudes.Therefore,the researchers suggest that for creating a positive attitude,increasing students'interest in laparoscopic surgery,and ensuring a more effective presence in the operating room,this training should be considered in the operating room curriculum.
基金supported by a grant from the Massachusetts Alzheimer’s Disease Research Center(5P50 AG 005134)(to SL).
文摘Alzheimer’s disease is a prominent chronic neurodegenerative condition characterized by a gradual decline in memory leading to dementia.Growing evidence suggests that Alzheimer’s disease is associated with accumulating various amyloid-βoligomers in the brain,influenced by complex genetic and environmental factors.The memory and cognitive deficits observed during the prodromal and mild cognitive impairment phases of Alzheimer’s disease are believed to primarily result from synaptic dysfunction.Throughout life,environmental factors can lead to enduring changes in gene expression and the emergence of brain disorders.These changes,known as epigenetic modifications,also play a crucial role in regulating the formation of synapses and their adaptability in response to neuronal activity.In this context,we highlight recent advances in understanding the roles played by key components of the epigenetic machinery,specifically DNA methylation,histone modification,and microRNAs,in the development of Alzheimer’s disease,synaptic function,and activity-dependent synaptic plasticity.Moreover,we explore various strategies,including enriched environments,exposure to non-invasive brain stimulation,and the use of pharmacological agents,aimed at improving synaptic function and enhancing long-term potentiation,a process integral to epigenetic mechanisms.Lastly,we deliberate on the development of effective epigenetic agents and safe therapeutic approaches for managing Alzheimer’s disease.We suggest that addressing Alzheimer’s disease may require distinct tailored epigenetic drugs targeting different disease stages or pathways rather than relying on a single drug.
基金supported by the National Natural Science Foundation of China,Nos.82371886(to JY),81925020(to DM),82202797(to LW),and 82271218(to CZ).
文摘Alzheimer’s disease is a common neurodegenerative disorder defined by decreased reasoning abilities,memory loss,and cognitive deterioration.The presence of the blood-brain barrier presents a major obstacle to the development of effective drug therapies for Alzheimer’s disease.The use of ultrasound as a novel physical modulation approach has garnered widespread attention in recent years.As a safe and feasible therapeutic and drug-delivery method,ultrasound has shown promise in improving cognitive deficits.This article provides a summary of the application of ultrasound technology for treating Alzheimer’s disease over the past 5 years,including standalone ultrasound treatment,ultrasound combined with microbubbles or drug therapy,and magnetic resonance imaging-guided focused ultrasound therapy.Emphasis is placed on the benefits of introducing these treatment methods and their potential mechanisms.We found that several ultrasound methods can open the blood-brain barrier and effectively alleviate amyloid-βplaque deposition.We believe that ultrasound is an effective therapy for Alzheimer’s disease,and this review provides a theoretical basis for future ultrasound treatment methods.
基金supported by the National Natural Science Foundation of China,No.31771143 (to QZ)Shanghai Municipal Science and Technology Major Project,ZJ Lab+1 种基金Shanghai Center for Brain Science and Brain-Inspired Technology,No.2018SHZDZX01 (to LC)Shanghai Zhou Liangfu Medical Development Foundation “Brain Science and Brain Diseases Youth Innovation Program”(to ZQ)。
文摘The globus pallidus plays a pivotal role in the basal ganglia circuit. Parkinson's disease is characterized by degeneration of dopamine-producing cells in the substantia nigra, which leads to dopamine deficiency in the brain that subsequently manifests as various motor and non-motor symptoms. This review aims to summarize the involvement of the globus pallidus in both motor and non-motor manifestations of Parkinson's disease. The firing activities of parvalbumin neurons in the medial globus pallidus, including both the firing rate and pattern, exhibit strong correlations with the bradykinesia and rigidity associated with Parkinson's disease. Increased beta oscillations, which are highly correlated with bradykinesia and rigidity, are regulated by the lateral globus pallidus. Furthermore,bradykinesia and rigidity are strongly linked to the loss of dopaminergic projections within the cortical-basal ganglia-thalamocortical loop. Resting tremors are attributed to the transmission of pathological signals from the basal ganglia through the motor cortex to the cerebellum-ventral intermediate nucleus circuit. The cortico–striato–pallidal loop is responsible for mediating pallidi-associated sleep disorders. Medication and deep brain stimulation are the primary therapeutic strategies addressing the globus pallidus in Parkinson's disease. Medication is the primary treatment for motor symptoms in the early stages of Parkinson's disease, while deep brain stimulation has been clinically proven to be effective in alleviating symptoms in patients with advanced Parkinson's disease,particularly for the movement disorders caused by levodopa. Deep brain stimulation targeting the globus pallidus internus can improve motor function in patients with tremordominant and non-tremor-dominant Parkinson's disease, while deep brain stimulation targeting the globus pallidus externus can alter the temporal pattern of neural activity throughout the basal ganglia–thalamus network. Therefore, the composition of the globus pallidus neurons, the neurotransmitters that act on them, their electrical activity,and the neural circuits they form can guide the search for new multi-target drugs to treat Parkinson's disease in clinical practice. Examining the potential intra-nuclear and neural circuit mechanisms of deep brain stimulation associated with the globus pallidus can facilitate the management of both motor and non-motor symptoms while minimizing the side effects caused by deep brain stimulation.
文摘Motivation to language learning is a complex set of variables including effort, desire to achieve goals, as well as attitudes toward the learning of the language. Individuals' motivation to second-language learning also includes their motivation orientations, interest in the second language, attitudes toward the second-language group, attitudes toward the second-language learning situations and second-language anxiety. Based on the basic theories and approaches, teaching activities are part of motivation in English classes. The teacher of language should have a good influence on students and develop students' keen interest in study in order to strengthen their intrinsic motivation, and set up some new goals for students to pursue and give the feedback to reinforce their inner drive and confidence. Thus, students will become major conductors, make full use of their potentials and enhance their study results.
基金Project supported by the National Natural Science Foundation of China (Grant No 10475112)the Western Light Foundation of 2005 years
文摘With the increasing use of nuclear energy, there is a need for a wider range of efficient dosimeters for radiation detection and assessment. There has been a tremendous growth in the development of radiation detectors and devices in the past few decades. In recent years, the development of new materials for radiation dosimetry has progressed significantly. Alkaline earth sulfides (AES) have been known for a long time as excellent and versatile phosphor materials. In the present investigation, a number of phosphor samples such as mono-, binary and ternary sulfides of alkaline earths (II^a-VI^b) have been prepared and their TL properties have been studied with respect to exposure (x-ray) response and fading. In this paper, some results on SrS:Eu, Sm and CaS:Eu, Sm phosphors are presented. A type of novel OSL dosimeter is described. The dosimeter takes advantage of the characteristics of charge trapping materials SrS:Eu, Sm and CaS:Eu, Sm that exhibit optically stimulated luminescence (OSL). The measuring range of the dosimeter is from 0.01 to 1000 Gy. The OSL dosimeters provide capability for remote monitoring radiation locations which are difficult to access and hazardous. This equipment is relatively simple, small in size and has low power consumption. The device is suitable for space radiation dose exploration. In addition, it also can be used in IC and other radiation occasions and has good prospects.
基金funded by the National Natural Science Foundation of China (Grants Nos. 41301012, 41771020 and U1405231)Natural Science Foundation of Fujian (Grant No. 2018R1034-5)Innovation Research Team Fund of Fujian Normal University (Grant No. IRTL1705)
文摘The 'Old Red Sand' is a type of semicemented medium-fine sandy sediment that is red(10R_4/8) or brown red(2.5YR_4/8) in colour and is found in late Quaternary deposits. The sediments have distinctive characteristics and are a critical archive for understanding climatic changes in the coastal areas of East Asia. The ages of the late Quaternary aeolian sand dunes from Haitan Island in the coastal area of South China are still in debate. In this study, three sets of marine terraces were identified in the northern region of Haitan Island. Aeolian dune sands are well preserved on the top of these terraces. Quartz Optically Stimulated Luminescence dating and the distribution of the formation ages demonstrated that the palaeo-dunes are deposits from the middle-late period of the Late Pleistocene(Q_3^(2-3)). The period may be divided into three stages, 100-90 ka, 70-60 ka, and 40-20 ka, in which the palaeo-dunes of the first two stages are more widespread and were formed separately during a low-sea level period of the Marine Isotope Stages 5 b and 4. Several depositional palaeo-flood event records were preserved during the last stage due to the increasing gradient of mountain gullies formed during the Last Glacial Maximum.
文摘Emotional factors and motivations should be taken into considerations,and combine grammar,rules with practical skills in communications,the stimulation of children's English learning at the initial stage must take effect and lead to good results.
基金National Natural Science FoundationDoctoral Programme Foundation of Institution of Higher Education of China
文摘The resonances of parametric vibration with forced vibration isanalyzed, the bifurca- tion equation of the system is obtained andthe singularity analysis is made. Some of the laws and phe- nomenaare revealed. The transition variety and bifurcation diagram of thephysical parameteric plane are given. the results can be used inengineering.
基金Project supported by the National Natural Science Foundation of China (Grant No 20173073), National 973 Project (Grant No 2002CB713802), Nano- and Bio-device Key Project of CAS, 985 Project of Hunan University.
文摘This paper studies power dependent photoluminescence spectra, the stimulated emission occurring at ultraviolet (UV) band instead of the green emission band of ZnO nanowires, which are prepared with a chemical reduction method. The dynamics of the UV emission and green emission is given to demonstrate the reason of stimulated emission occurring at UV band but not the green emission band under high excitation, which indicates that the slow decay rate of trap state makes it easy to be fully filled and saturated, while the fast decay rate of near-band-edge exciton state makes the UV emission dominate the radiative recombination under high excitation. The UV emission, as well as the corresponding stimulated emission, occurs in competition with the green deep-trap emission. In addition, when pump fluence further increases, the multiple lasing modes appear. The dependence of these lasing modes on the pump fluence is first discussed. This diagram should be helpful to understand and design the optical nanodevices of ZnO nanowires.