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Drosophila models used to simulate human ATP1A1 gene mutations that cause Charcot-Marie-Tooth type 2 disease and refractory seizures

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Neural Regeneration research 2025年第1期20卷 265-276页

作者： Yao Yuan Lingqi Yu Xudong Zhuang Dongjing Wen Jin He Jingmei Hong Jiayu Xie Shengan Ling Xiaoyue Du Wenfeng Chen Xinrui Wang institute of Life Sciences College of Biological Science and EngineeringFuzhou UniversityFuzhouFujian ProvinceChina NHC Key Laboratory of Technical evaluation of Fertility Regulation for Non-human Primate(Fujian Maternity and Child Health Hospital) FuzhouFujian ProvinceChina Medical research Center Fujian Maternity and Child Health HospitalCollege of Clinical Medicine for Obstetrics&Gynecology and PediatricsFujian Medical UniversityFuzhouFujian ProvinceChina Department of Neurology and institute of Neurology of The First Affiliated Hospital Institute of Neuroscienceand Fujian Key Laboratory of Molecular NeurologyFujian Medical UniversityFuzhouFujian ProvinceChina

Certain amino acids changes in the human Na^(+)/K^(+)-ATPase pump,ATPase Na^(+)/K^(+)transporting subunit alpha 1(ATP1A1),cause Charcot-Marie-Tooth disease type 2(CMT2)disease and refractory *** develop in vivo models to study the role of Na^(+)/K^(+)-ATPase in these diseases,we modified the Drosophila gene homolog,Atpα,to mimic the human ATP1A1 gene mutations that cause *** located within the helical linker region of human ATP1A1(I592T,A597T,P600T,and D601F)were simultaneously introduced into endogenous Drosophila Atpαby CRISPR/Cas9-mediated genome editing,generating the Atpα^(TTTF)*** addition,the same strategy was used to generate the corresponding single point mutations in flies(Atpα^(I571T),Atpα^(A576T),Atpα^(P579T),and Atpα^(D580F)).Moreover,a deletion mutation(Atpα^(mut))that causes premature termination of translation was generated as a positive *** these alleles,we found two that could be maintained as homozygotes(Atpα^(I571T)and Atpα^(P579T)).Three alleles(Atpα^(A576T),Atpα^(P579)and Atpα^(D580F))can form heterozygotes with the Atpαmut *** found that the Atpαallele carrying these CMT2-associated mutations showed differential phenotypes in *** heterozygous for Atpα^(TTTF)mutations have motor performance defects,a reduced lifespan,seizures,and an abnormal neuronal *** Drosophila models will provide a new platform for studying the function and regulation of the sodium-potassium pump.

关键词： ATP1A1 Atpα bang-sensitive paralysis Charcot-Marie-Tooth disease type 2 CRISPR/Cas9 homology-directed repair Na^(+)/K^(+)-ATPase point mutation seizures sodium pump

Passive activity enhances residual control ability in patients with complete spinal cord injury

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Neural Regeneration research 2025年第8期20卷 2337-2347页

作者： Yanqing Xiao Mingming Gao Zejia He Jia Zheng Hongming Bai Jia-Sheng Rao Guiyun Song Wei Song Xiaoguang Li Beijing Key Laboratory for Biomaterials and Neural Regeneration Beijing Advanced Innovation Center for Biomedical EngineeringSchool of Biological Science and Medical EngineeringBeihang UniversityBeijingChina Department of Rehabilitation evaluation China Rehabilitation Research CenterBeijingChina Cardiac Center Beijing Children’s HospitalCapital Medical UniversityBeijingChina The State Key Laboratory of Virtual Reality Technology and Systems Beihang UniversityBeijingChina Department of Rehabilitation Engineering China Rehabilitation Science InstituteBeijingChina

Patients with complete spinal cord injury retain the potential for volitional muscle activity in muscles located below the spinal injury ***,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 *** this study,we further explored the effect of passive activity on surface electromyographic signals during volitional control tasks among individuals with complete spinal cord *** patients with chronic complete thoracic spinal cord injury were *** electromyography data from eight major leg muscles were acquired and compared before and after the passive activity *** results indicated that the passive activity led to an increased number of activated volitional muscles and an increased frequency of *** 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 *** 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.

关键词： complete spinal cord injury cycle training epidural electrical stimulation motor training passive activity physiological state spinal cord circuit surface electromyography volitional control task

Enhancement of motor functional recovery in thoracic spinal cord injury: voluntary wheel running versus forced treadmill exercise

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Neural Regeneration research 2025年第3期20卷 836-844页

作者： Do-Hun Lee Dan Cao Younghye Moon Chen Chen Nai-Kui Liu Xiao-Ming Xu Wei Wu Spinal Cord and Brain Injury research Group Stark Neurosciences Research InstituteIndiana University School of MedicineIndianapolisINUSA Department of Neurological Surgery Indiana University School of MedicineIndianapolisINUSA Department of Neuroscience Baylor College of MedicineHoustonTXUSA

Spinal cord injury necessitates effective rehabilitation strategies, with exercise therapies showing promise in promoting recovery. This study investigated the impact of rehabilitation exercise on functional recovery and morphological changes following thoracic contusive spinal cord injury. After a 7-day recovery period after spinal cord injury, mice were assigned to either a trained group(10 weeks of voluntary running wheel or forced treadmill exercise) or an untrained group. Bi-weekly assessments revealed that the exercise-trained group, particularly the voluntary wheel exercise subgroup, displayed significantly improved locomotor recovery, more plasticity of dopaminergic and serotonin modulation compared with the untrained group. Additionally, exercise interventions led to gait pattern restoration and enhanced transcranial magnetic motor-evoked potentials. Despite consistent injury areas across groups, exercise training promoted terminal innervation of descending axons. In summary, voluntary wheel exercise shows promise for enhancing outcomes after thoracic contusive spinal cord injury, emphasizing the role of exercise modality in promoting recovery and morphological changes in spinal cord injuries. Our findings will influence future strategies for rehabilitation exercises, restoring functional movement after spinal cord injury.

关键词： behavioral assessment motor function neural plasticity running wheel exercise spinal cord injury treadmill exercise voluntary exercise

Mutation Testing for Integer Overflow in Ethereum Smart Contracts

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Tsinghua Science and Technology 2022年第1期27卷 27-40页

作者： Jinlei Sun Song Huang Changyou Zheng Tingyong Wang Cheng Zong Zhanwei Hui Command&Control Engineering College Army Engineering University of PLANanjing 210000China institute of evaluation and assessment research Academy of Military ScienceBeijing 100091China

Integer overflow is a common vulnerability in Ethereum Smart Contracts(ESCs)and often causes huge economic *** contracts cannot be changed once it is deployed on the blockchain and thus demand further *** testing is a fault-based testing method that can effectively improve the sufficiency of a test for smart ***,existing methods cannot efficiently perform mutation testing specifically for integer overflow in ***,by analyzing integer overflow in ESCs,we propose five special mutation operators to address such vulnerability in terms of detecting sufficiency in ESC *** empirical study on 40 open-source ESCs is conducted to evaluate the effectiveness of the proposed mutation *** show that(1)our proposed mutation operators can reproduce all 179 integer overflow vulnerabilities in 40 smart contracts,and the generated mutants have high compilation pass rate and integer overflow vulnerability generation rate;moreover,(2)the generated mutants can find the shortcomings of existing testing methods for integer overflow vulnerability,thereby providing effective support to improve the sufficiency of the test.

关键词： blockchain Ethereum Smart Contracts(ESCs) integer overflow mutation testing

Temporal dynamics of neonatal hypoxic-ischemic encephalopathy injuries on magnetic resonance imaging

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Neural Regeneration research 2025年第11期20卷 3144-3150页

作者： Holly Flyger Samantha J.Holdsworth Alistair J.Gunn Laura Bennet Hamid Abbasi Mātai Medical research institute Tairāwhiti GisborneNew Zealand Department of Anatomy&Medical Imaging Faculty of Medical and Health SciencesThe University of AucklandAucklandNew Zealand Center for Brain research The University of AucklandAucklandNew Zealand Auckland Bioengineering institute The University of AucklandAucklandNew Zealand

Moderate to severe perinatal hypoxic-ischemic encephalopathy occurs in~1 to 3/1000 live births in high-income countries and is associated with a significant risk of death or neurodevelopmental *** assessment is important to help identify highrisk infants,to help families,and to support appropriate interventions.A wide range of monitoring tools is available to assess changes over time,including urine and blood biomarkers,neurological examination,and *** present,magnetic resonance imaging is unique as although it is expensive and not suited to monitoring the early evolution of hypoxic-ischemic encephalopathy by a week of life it can provide direct insight into the anatomical changes in the brain after hypoxic-ischemic encephalopathy and so offers strong prognostic information on the long-term outcome after hypoxic-ischemic *** review investigated the temporal dynamics of neonatal hypoxic-ischemic encephalopathy injuries,with a particular emphasis on exploring the correlation between the prognostic implications of magnetic resonance imaging scans in the first week of life and their relationship to long-term outcome prediction,particularly for infants treated with therapeutic hypothermia.A comprehensive literature search,from 2016 to 2024,identified 20 pertinent *** review highlights that while the optimal timing of magnetic resonance imaging scans is not clear,overall,it suggests that magnetic resonance imaging within the first week of life provides strong prognostic *** challenges limit the timing consistency,particularly the need for intensive care and clinical ***,although most reports examined the prognostic value of scans taken between 4 and 10 days after birth,there is evidence from small numbers of cases that,at times,brain injury may continue to evolve for weeks after *** suggests that in the future it will be important to explore a wider range of times after hypo

关键词： magnetic resonance imaging neonatal hypoxic-ischemic encephalopathy neurodevelopmental outcomes prognostic biomarkers in neuroimaging scan timing therapeutic hypothermia

T-2 toxin induces developmental toxicity and apoptosis in zebrafish embryos

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Journal of Environmental Sciences 2014年第4期26卷 917-925页

作者： Guogang Yuan Yimei Wang Xiaoyan Yuan Tingfen Zhang Jun Zhao Liuyu Huang Shuangqing Peng evaluation and research Center for Toxicology Institute of Disease Control and Prevention Academy of Military Medical Sciences

T-2 toxin is one of the most important trichothecene mycotoxins occurring in various agriculture products. The developmental toxicity of T-2 toxin and the exact mechanism of action at early life stages are not understood precisely. Zebrafish embryos were exposed to different concentrations of the toxin at 4-6 hours post fertilization （hpf） stage of development, and were observed for different developmental toxic effects at 24, 48, 72, and 144 hpf. Exposure to 0.20 Ixmol/L or higher concentrations of T-2 toxin significantly increased the mortality and malformation rate such as tail deformities, cardiovascular defects and behavioral changes in early developmental stages of zebrafish. T-2 toxin exposure resulted in significant increases in reactive oxygen species （ROS） production and cell apoptosis, mainly in the tall areas, as revealed by Acridine Orange staining at 24 hpf. In addition, T-2 toxin-induced severe tail deformities could be attenuated by co-exposure to reduced glutathione （GSH）. T-2 toxin and GSH co-exposure induced a significant decrease of ROS production in the embryos. The overall results demonstrate that T-2 toxin is able to produce oxidative stress and induce apoptosis, which are involved in the developmental toxicity of T-2 toxin in zebrafish embryos.

关键词： T-2 toxin developmental toxicity apoptosis zebrafish embryo oxidative stress

Microstructure Characterization of the Fusion Zone of an Alloy 600-82 Weld Joint

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Journal of Materials Science & Technology 2015年第10期31卷 1011-1017页

作者： Cheng Ma Jinna Mei Qunjia Peng Ping Deng En-Hou Han Wei Ke Key Laboratory of Nuclear Materials and Safety assessment Institute of Metal ResearchChinese Academy of Sciences Suzhou Nuclear Power research institute

Characterization of the microstructure of the fusion zone of an Alloy 600-82 weld joint was conducted, with focus on the weld residual strain distribution and the comparison of the microstructure of heat affected zone （HAZ） with that of cold worked alloy. Peak of the residual strain was observed to approach to the fusion boundary in HAZ while the strain increased from the top of the weld to the root. Strain distribution in the HAZ was found to be concentrated adjacent to grain boundaries （GBs）, with a peak of approximately three times of that in grain. Further, triple junctions of the GB appear to cause a higher strain concentration than single GBs. The microstructure of HAZ consists of partially tangled dislocations, which is different from slip bands of high density dislocations in cold worked alloy. This may cause a relatively higher intergranular cracking resistance of HAZ due to the difficulty in transferring tangled dislocations to GB in HAZ under deformation.

关键词： Microstructure Fusion zone Weld joint Strain concentration Alloy 600

Subchronic Oral Toxicity evaluation of Lanthanum： A 90-day, Repeated Dose Study in Rats

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Biomedical and Environmental Sciences 2018年第5期31卷 363-375页

作者： FANG Hai Qin YU Zhou ZHI Yuan FANG Jin LIChen Xi WANG Yi Mei PENG Shuang Qing JIA Xu Dongl Key Laboratory of Food Safety Risk assessment of Ministry of Health China National Center for Food Safety Risk AssessmentBeijing 100021China evaluation and research Centre for Toxicology Institute of Disease Control and PreventionAcademy of Military Medical SciencesBeijing 100071China

Objective The present study was undertaken to evaluate the subchronic toxicity of lanthanum and to determine the no observed adverse effect level（NOAEL）,which is a critical factor in the establishment of an acceptable dietary intake（ADI）.Methods In accordance with the Organization for Economic Co-operation and Development（OECD） testing guidelines,lanthanum nitrate was administered once daily by gavage to Sprague-Dawley（SD） rats at dose levels of 0,1.5,6.0,24.0,and 144.0 mg/kg body weight（BW） per day for 90 days,followed by a recovery period of 4 weeks in the 144.0 mg/kg BW per day and normal control *** parameters were mortality,clinical symptoms,body and organ weights,serum chemistry,and food consumption,as well as ophthalmic,urinary,hematologic,and histopathologic *** benchmark dose（BMD） approach was applied to estimate a point of departure for the hazard risk assessment of *** Significant decreases were found in the 144.0 mg/kg BW group in the growth index,including body weight,organ weights,and food *** study suggests that the NOAEL of lanthanum nitrate is 24.0 mg/kg BW per ***,the 95% lower confidence value of the benchmark dose（BMDL） was estimated as 9.4 mg/kg BW per day in females and 19.3 mg/kg BW per day in *** The present subchronic oral exposure toxicity study may provide scientific data for the risk assessment of lanthanum and other rare earth elements（REEs）.

关键词： Lanthanum Subchronic toxicity 90-day repeated oral dose test No observed adverse effectLevel Acceptable dietary intake Benchmark dose

Pitting corrosion of a Rare Earth Mg alloy GW93

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Journal of Materials Science & Technology 2017年第9期33卷 954-960页

作者： Yingwei Song Dayong Shan En-Hou Han Key Laboratory of Nuclear Materials and Safety assessment Institute of Metal ResearchChinese Academy of Sciences

Pitting corrosion of magnesium(Mg) alloys is greatly associated with their microstructure, especially second phases. The second phases in traditional Mg alloys such as AZ91 are electrochemically nobler than Mg matrix, while the second phases in Rare earth(RE) Mg alloy GW93 are more active than Mg matrix. As a result, the pitting corrosion mechanism of Mg alloy GW93 is different from the traditional ones. This paper aims to clarify the pitting corrosion mechanism of Mg alloy GW93 through the studies of Volta potential by Scanning Kelvin Probe Force Microscopy(SKPFM), corrosion morphology by Scanning Electron Microscope(SEM), and corrosion resistance by electrochemical tests. Results reveal that the pitting corrosion of GW93 includes three stages, first, dissolution of the second phases, followed by corrosion of Mg matrix adjacent to the dissolved second phases, and finally, propagation of corrosion pits along the depth direction of the dissolved second phases. Anodic second phases and enrichment of Clin the thick corrosion product films dominate the propagation of pitting corrosion.

关键词： Mg alloys Pitting corrosion Second phases Oxide films