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High-frequency repetitive transcranial magnetic stimulation promotes neural stem cell proliferation after ischemic stroke

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Neural Regeneration Research 2024年第8期19卷 1772-1780页

作者： Jing Luo Yuan Feng Zhongqiu Hong Mingyu Yin Haiqing Zheng liying zhang Xiquan Hu Department of Rehabilitation Medicine The Third Affiliated HospitalSun Yat-sen UniversityGuangzhouGuangdong ProvinceChina Department of Hepatobiliary Surgery The Third Affiliated HospitalSun Yat-sen UniversityGuangzhouGuangdong ProvinceChina

Prolife ration of neural stem cells is crucial for promoting neuronal regeneration and repairing cerebral infarction damage.Transcranial magnetic stimulation(TMS)has recently emerged as a tool for inducing endogenous neural stem cell regeneration,but its underlying mechanisms remain unclea r In this study,we found that repetitive TMS effectively promotes the proliferation of oxygen-glucose deprived neural stem cells.Additionally,repetitive TMS reduced the volume of cerebral infa rction in a rat model of ischemic stro ke caused by middle cerebral artery occlusion,im p roved rat cognitive function,and promoted the proliferation of neural stem cells in the ischemic penumbra.RNA-sequencing found that repetitive TMS activated the Wnt signaling pathway in the ischemic penumbra of rats with cerebral ischemia.Furthermore,PCR analysis revealed that repetitive TMS promoted AKT phosphorylation,leading to an increase in mRNA levels of cell cycle-related proteins such as Cdk2 and Cdk4.This effect was also associated with activation of the glycogen synthase kinase 3β/β-catenin signaling pathway,which ultimately promotes the prolife ration of neural stem cells.Subsequently,we validated the effect of repetitive TMS on AKT phosphorylation.We found that repetitive TMS promoted Ca2+influx into neural stem cells by activating the P2 calcium channel/calmodulin pathway,thereby promoting AKT phosphorylation and activating the glycogen synthase kinase 3β/β-catenin pathway.These findings indicate that repetitive TMS can promote the proliferation of endogenous neural stem cells through a Ca2+influx-dependent phosphorylated AKT/glycogen synthase kinase 3β/β-catenin signaling pathway.This study has produced pioneering res ults on the intrinsic mechanism of repetitive TMS to promote neural function recove ry after ischemic stro ke.These results provide a stro ng scientific foundation for the clinical application of repetitive TMS.Moreover,repetitive TMS treatment may not only be an efficient and potential approach to support neurogenesis for

关键词： AKT/β-catenin signaling brain stimulation Ca2+influx cell proliferation ischemic stroke middle cerebral artery occlusion neural stem cells neurological rehabilitation repetitive transcranial magnetic stimulation

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A simple and efficient CRISPR/Cas9 system permits ultra-multiplex genome editing in plants

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The Crop Journal 2024年第2期12卷 569-582页

作者： Suting Wu Htin Kyaw Zhijun Tong Yirong Yang Zhiwei Wang liying zhang Lihua Deng Zhiguo zhang Bingguang Xiao William Paul Quick Tiegang Lu Guoying Xiao Guannan Qin Xue'an Cui Biotechnology Research Institute Chinese Academy of Agricultural SciencesBeijing 100081China Key Laboratory of Genetics Breeding and Multiple Utilization of CropsMinistry of EducationCollege of AgricultureFujian Agriculture and Forestry UniversityFuzhou 350002FujianChina Key Laboratory of Biological Breeding for Fujian and Taiwan Crops Ministry of Agriculture and Rural AffairsCollege of AgricultureFujian Agriculture and Forestry UniversityFuzhou 350002FujianChina Key Laboratory of Agro-ecological Processes in Subtropical Region Institute of Subtropical AgricultureChinese Academy of SciencesChangsha 410125HunanChina School of Biosciences The University of SheffieldFirth CourtWestern BankSheffield S102TNUK Key Laboratory of Tobacco Biotechnological Breeding National Tobacco Genetic Engineering Research CenterYunnan Academy of Tobacco Agricultural SciencesKunming 650021YunnanChina

The development and maturation of the CRISPR/Cas genome editing system provides a valuable tool for plant functional genomics and genetic improvement.Currently available genome-editing tools have a limited number of targets,restricting their application in genetic research.In this study,we developed a novel CRISPR/Cas9 plant ultra-multiplex genome editing system consisting of two template vectors,eight donor vectors,four destination vectors,and one primer-design software package.By combining the advantages of Golden Gate cloning to assemble multiple repetitive fragments and Gateway recombination to assemble large fragments and by changing the structure of the amplicons used to assemble sg RNA expression cassettes,the plant ultra-multiplex genome editing system can assemble a single binary vector targeting more than 40 genomic loci.A rice knockout vector containing 49 sg RNA expression cassettes was assembled and a high co-editing efficiency was observed.This plant ultra-multiplex genome editing system advances synthetic biology and plant genetic engineering.

关键词： CRISPR/Cas9 Multiplex genome editing Assembly system Plant

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Gene expression profiles in early leaf of rice(Oryza sativa)and foxtail millet(Setaria italica)

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The Crop Journal 2024年第3期12卷 776-787页

作者： Jing Sun Chen Deng Xiuru Dai Haoshu Li liying zhang Jingke Wang Hang Zhao Yirong Yang NghiVan Phung Zhiguo zhang Pinghua Li Xuehui Sun Tiegang Lu Biotechnology Research Institute Chinese Academy of Agricultural SciencesBeijing 100081China College of Agronomy Shandong Agricultural UniversityTai’an 271018ShandongChina Qingdao Institute of Bioenergy and Bioprocess Technology Chinese Academy of SciencesQingdao 266101ShandongChina

Plant anatomy is patterned early during leaf development which suggests studying the spatial–temporal transcriptomes of primordia will help identify critical regulative and functional genes.We successfully isolated the leaf primordia tissues from the C3grass rice and the C4grass foxtail millet by laser capture microdissection(LCM)and studied the gene expression throughout leaf developmental stages.Our data analysis uncovered the conserved expression patterns of certain gene clusters both in rice and foxtail millet during leaf development.We revealed genes and transcription factors involved in vein formation,stomatal development,and suberin accumulation.We identified 79 candidate genes associated with functional regulation of C4anatomy formation.Screening phenotype of the candidate genes revealed that knock-out of a putative polar auxin transport related gene NAL1 resulted significantly reduced veinal space in rice leaf.Our present work provides a foundation for future analyses of genes with novel functions in grasses and their role in leaf development,in particular the role in leaves with a contrasting C3vs.C4biosynthetic pathway.

关键词： Rice Foxtail millet Leaf development RNA-seq LCM

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Artificial intelligence-assisted repair of peripheral nerve injury: a new research hotspot and associated challenges

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Neural Regeneration Research 2024年第3期19卷 663-670页

作者： Yang Guo liying Sun Wenyao Zhong Nan zhang Zongxuan Zhao Wen Tian Department of Hand Surgery Beijing Jishuitan HospitalBeijingChina

Artificial intelligence can be indirectly applied to the repair of peripheral nerve injury.Specifically,it can be used to analyze and process data regarding peripheral nerve injury and repair,while study findings on peripheral nerve injury and repair can provide valuable data to enrich artificial intelligence algorithms.To investigate advances in the use of artificial intelligence in the diagnosis,rehabilitation,and scientific examination of peripheral nerve injury,we used CiteSpace and VOSviewer software to analyze the relevant literature included in the Web of Science from 1994–2023.We identified the following research hotspots in peripheral nerve injury and repair:(1)diagnosis,classification,and prognostic assessment of peripheral nerve injury using neuroimaging and artificial intelligence techniques,such as corneal confocal microscopy and coherent anti-Stokes Raman spectroscopy;(2)motion control and rehabilitation following peripheral nerve injury using artificial neural networks and machine learning algorithms,such as wearable devices and assisted wheelchair systems;(3)improving the accuracy and effectiveness of peripheral nerve electrical stimulation therapy using artificial intelligence techniques combined with deep learning,such as implantable peripheral nerve interfaces;(4)the application of artificial intelligence technology to brain-machine interfaces for disabled patients and those with reduced mobility,enabling them to control devices such as networked hand prostheses;(5)artificial intelligence robots that can replace doctors in certain procedures during surgery or rehabilitation,thereby reducing surgical risk and complications,and facilitating postoperative recovery.Although artificial intelligence has shown many benefits and potential applications in peripheral nerve injury and repair,there are some limitations to this technology,such as the consequences of missing or imbalanced data,low data accuracy and reproducibility,and ethical issues(e.g.,privacy,data security,research transparency).Future re

关键词： artificial intelligence artificial prosthesis medical-industrial integration brain-machine interface deep learning machine learning networked hand prosthesis neural interface neural network neural regeneration peripheral nerve

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Formation and transformation of metastable LPSO building blocks clusters in Mg-Gd-Y-Zn-Zr alloys by spinodal decomposition and heterogeneous nucleation

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Journal of Magnesium and Alloys 2024年第2期12卷 673-686页

作者： Xin Zhao Zhong Yang Jiachen zhang Minxian Liang liying Wang School of Materials Science and Chemical Engineering Xi’an Technological UniversityXi’an 710021China Xi’an Tianli Metal Composite Material Co.Ltd. Xi’an 710299China

To study the formation and transformation mechanism of long-period stacked ordered(LPSO)structures,a systematic atomic scale analysis was conducted for the structural evolution of long-period stacked ordered(LPSO)structures in the Mg-Gd-Y-Zn-Zr alloy annealed at 300℃~500℃.Various types of metastable LPSO building block clusters were found to exist in alloy structures at different temperatures,which precipitate during the solidification and homogenization process.The stability of Zn/Y clusters is explained by the first principles of density functional theory.The LPSO structure is distinguished by the arrangement of its different Zn/Y enriched LPSO structural units,which comprises local fcc stacking sequences upon a tightly packed plane.The presence of solute atoms causes local lattice distortion,thereby enabling the rearrangement of Mg atoms in the different configurations in the local lattice,and local HCP-FCC transitions occur between Mg and Zn atoms occupying the nearest neighbor positions.This finding indicates that LPSO structures can generate necessary Schockley partial dislocations on specific slip surfaces,providing direct evidence of the transition from 18R to 14H.Growth of the LPSO,devoid of any defects and non-coherent interfaces,was observed separately from other precipitated phases.As a result,the precipitation sequence of LPSO in the solidification stage was as follows:Zn/Ycluster+Mg layers→various metastable LPSO building block clusters→18R/24R LPSO;whereas the precipitation sequence of LPSO during homogenization treatment was observed to be as follows:18R LPSO→various metastable LPSO building block clusters→14H LPSO.Of these,14H LPSO was found to be the most thermodynamically stable structure.

关键词： LPSO Spinodal decomposition Homogenization treatment Clusters Phase transformation

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Molecular toxicity and defense mechanisms induced by silver nanoparticles in Drosophila melanogaster

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Journal of Environmental Sciences 2023年第3期125卷 616-629页

作者： Zhidi Wang liying zhang Xing Wang College of Resources and Environmental Sciences China Agricultural UniversityBeijing 100193China Beijing Key Laboratory of Biodiversity and Organic Farming Beijing 100193China

The widely use of silver nanoparticles(AgNPs) as antimicrobial agents gives rise to potential environmental risks. AgNPs exposure have been reported to cause toxicity in animals.Nevertheless, the known mechanisms of AgNPs toxicity are still limited. In this study, we systematically investigated the toxicity of AgNPs exposure using Drosophila melanogaster.We show here that AgNPs significantly decreased Drosophila fecundity, the third-instar larvae weight and rates of pupation and eclosion in a dose-dependent manner. AgNPs reduced fat body cell viability in MTT(3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide)assays. AgNPs caused DNA damage in hemocytes and S2 cells. Interestingly, the mRNA levels of the entire metallothionein gene family were increased under AgNPs exposure as determined by RNA-seq analysis and validated by qRT-PCR, indicating that Drosophila responded to the metal toxicity of AgNPs by producing metallothioneins for detoxification. These findings provide a better understanding of the mechanisms of AgNPs toxicity and may provide clues to effect on other organisms, including humans.

关键词： Drosophila melanogaster Silver nanoparticles(AgNPs) Reactive oxygen species(ROS) DNA damage RNA-seq Metallothionein

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Dysregulated N6-methyladenosine modification in peripheral immune cells contributes to the pathogenesis of amyotrophic lateral sclerosis

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Frontiers of Medicine 2024年第2期18卷 285-302页

作者： Di He Xunzhe Yang Liyang Liu Dongchao Shen Qing Liu Mingsheng Liu Xue zhang liying Cui Department of Neurology Peking Union Medical College Hospital(PUMCH)Chinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing100730China Medical Doctor Program Chinese Academy of Medical Science and Peking Union Medical CollegeBeijing100730China McKusick-zhang Center for Genetic Medicine State Key Laboratory of Medical Molecular BiologyInstitute of Basic Medical Sciences Chinese Academy of Medical SciencesSchool of Basic MedicinePeking Union Medical CollegeBeijing100730China Neuroscience Center Chinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing100730China

Amyotrophic lateral sclerosis(ALS)is a progressive neurogenerative disorder with uncertain origins.Emerging evidence implicates N6-methyladenosine(m6A)modification in ALS pathogenesis.Methylated RNA immunoprecipitation sequencing(MeRIP-seq)and liquid chromatography–mass spectrometry were utilized for m6A profiling in peripheral immune cells and serum proteome analysis,respectively,in patients with ALS(n=16)and controls(n=6).The single-cell transcriptomic dataset(GSE174332)of primary motor cortex was further analyzed to illuminate the biological implications of differentially methylated genes and cell communication changes.Analysis of peripheral immune cells revealed extensive RNA hypermethylation,highlighting candidate genes with differential m6A modification and expression,including C-X3-C motif chemokine receptor 1(CX3CR1).In RAW264.7 macrophages,disrupted CX3CR1 signaling affected chemotaxis,potentially influencing immune cell migration in ALS.Serum proteome analysis demonstrated the role of dysregulated immune cell migration in ALS.Cell type-specific expression variations of these genes in the central nervous system(CNS),particularly microglia,were observed.Intercellular communication between neurons and glial cells was selectively altered in ALS CNS.This integrated approach underscores m6A dysregulation in immune cells as a potential ALS contributor.

关键词： amyotrophic lateral sclerosis N^(6)-methyladenosine epi-transcriptome proteome single cell RNA sequencing analysis CX3CR1

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Comparative study on the hydrogen storage performance of as-milled MgRENi rapid quenched alloy catalyzed by metal sulfides

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Journal of Magnesium and Alloys 2024年第5期12卷 2010-2023页

作者： Xiaoping Dong Zhaoqing zhang liying Yang Shenghai Xin Dandan Su Zhiyuan Li Department of Mechanical Design and Manufacture and Automation Hebei University Baoding New Energy Vehicle Power Engineering Technology Research Center Hebei University Hebei Technology Innovation Center for Lightweight of New Energy Vehicle Power System(Preparation) Hebei University

The composites of Mg20Pr1Sm3Y1Ni10as-quenched alloy and 3 wt.% M（M = CoS, CoS2, MoS2） catalyst were prepared by high-speed vibration ball mill. The effects of metal sulfides on the hydrogenation and dehydrogenation dynamics of alloys were compared. The results show that the as-milled composites contain a large number of amorphous embedded by a small amount of nanocrystals, and there are many point defects. After ball milling, the crystal grain size in the composites containing CoS is relatively larger, followed by CoS2and MoS2again. After hydrogenation, the amorphous phase is crystallized to form Mg2NiH4, YH3, Pr8H18.96, Sm3H7, Mg, Co or Mo phases, however,Mg2Ni, YH2, PrH2and Ni3Y phases appeared after dehydrogenation. The maximum hydrogenation capacity of the composites containing CoS, CoS2and MoS2are 3.939, 4.265 and 4.507 wt.%, respectively. The hydrogenation saturation ratio of composite containing MoS2is higher than that of the composites containing CoS and CoS2. The dehydrogenation activation energy of the composites containing CoS, CoS2and MoS2is 107.76, 68.43 and 63.28 kJ.mol-1.H2. On the improvement of hydrogen storage performance of Mg20Pr1Sm3Y1Ni10alloy, the catalytic effect of MoS2sulfide is better than that of CoS2sulfide, and which is better than CoS sulfide.

关键词： Mg 20 Pr 1 Sm 3 Y 1 Ni 10 as-quenched alloy CoS CoS 2 and MoS 2 sulfide Milling Activation energy Hydrogen storage dynamics

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Development and performance evaluation of a culture-independent nanopore amplicon-based sequencing method for accurate typing and antimicrobial resistance profiling in Neisseria gonorrhoeae

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Science China(Life Sciences) 2024年第2期67卷 421-423页

作者： Chi zhang Lulu zhang Feng Wang Yaling Zeng liying Sun Di Wang Yamei Li Liqin Wang Junping Peng NHC Key Laboratory of Systems Biology of Pathogens Institute of Pathogen BiologyChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100176China Key Laboratory of Respiratory Disease Pathogenomics Chinese Academy of Medical SciencesBeijing 100730China Shenzhen Center for Chronic Disease Control Shenzhen 518020China

Dear Editor,Bacterial antimicrobial resistance(AMR)poses a serious threat to global human health(Antimicrobial Resistance Collaborators,2022).Comprehensive profiling of AMR and accurate molecular typing are important for tracking and controlling the emergence and dissemination of antibiotic-resistant bacteria(Yahara et al.,2021).We previously developed a multiplex amplicon sequencing-based method for directly sequencing AMR-related loci in N.gonorrhoeae from clinical samples(zhang et al.,2021).

关键词： gonorrhoeae resistance

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Ethanol extract of Cyathulae Radix inhibits osteoclast differentiation and bone loss

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Chinese Journal of Natural Medicines 2024年第3期22卷 212-223页

作者： SHI liying REN Liuyi LI Jinping LIU Xin LU Jingjing JIA Lujuan XIE Baoping TANG Siyuan LIU Wei zhang Jie Department of Pharmachemistry Xiangya School of Pharmaceutical SciencesCentral South UniversityChangsha 410013China Hunan Key laboratory of Diagnostic and Therapeutic Drug Research for Chronic Diseases Central South UniversityChangsha 410013China Key Laboratory of Prevention and Treatment of Cardiovascular and Cerebrovascular Diseases Ministry of EducationGannan Medical UniversityGanzhou 341000China Xiangya Nursing School Central South UniversityChangsha 410013China The Third Xiangya Hospital Central South UniversityChangsha 410013China

Cyathulae Radix,a traditional Chinese medicine and a common vegetable,boasts a history spanning millennia.It enhances bone density,boosts metabolism,and effectively alleviates osteoporosis-induced pain.Despite its historical use,the molecular mechanisms behind Cyathulae Radix’s impact on osteoporosis remain unexplored.In this study,we investigated the effects and mechanisms of Cyathulae Radix ethanol extract(CEE)in inhibiting osteoporosis and osteoclastogenesis.Eight-week-old female mice underwent ovariectomy and were treated with CEE for eight weeks.Micro-computed tomography(micro-CT)assessed histomorphometric parameters,bone tissue staining observed distal femur histomorphology,and three-point bending tests evaluated tibia mechanical properties.Enzyme-linked immunosorbent assay(ELISA)measured serum estradiol(E2),receptor activator for nuclear factor B ligand(RANKL),and osteoprotegerin(OPG)levels.Osteoclastogenesis-related markers were analyzed via Western blotting(WB)and quantitative real-time polymerase chain reaction(qRT-PCR).Additionally,CEE effects on RANKL-induced osteoclast formation and bone resorption were investigated in vitro using tartrate-resistant acid phosphatase(TRAP)staining,qRT-PCR,and WB assay.Compared with the ovariectomy(OVX)group,CEE treatment enhanced trabecular bone density,maximal load-bearing capacity,and various histomorphometric parameters.Serum E2 and OPG levels significantly increased,while Receptor activator of nuclear factor-κB(RANK)decreased in the CEE group.CEE downregulated matrix metallopeptidase 9(MMP-9),Cathepsin K(CTSK),and TRAP gene and protein expression.In bone marrow macrophages(BMMs),CEE reduced mature osteoclasts,bone resorption pit areas,and MMP-9,CTSK,and TRAP expression during osteoclast differentiation.Compared with DMSO treatment,CEE markedly inhibited RANK,TNF receptor associated factor 6(TRAF6),Proto-oncogene c-Fos(c-Fos),Nuclear factor of activated T-cells cytoplasmic 1(NFATc1)expressions,and Extracellular regulated protein kinases(ERK),c-Jun N-terminal kinase

关键词： Osteoporosis Osteoclast BMMs Cyathulae Radix RANKL ER/RANK/NFATc1 signaling pathway

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