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Chondroitinase ABC combined with Schwann cell transplantation enhances restoration of neural connection and functional recovery following acute and chronic spinal cord injury

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Neural Regeneration research 2025年第5期20卷 1467-1482页

作者： Wenrui Qu Xiangbing Wu Wei Wu Ying Wang Yan Sun Lingxiao Deng Melissa Walker Chen Chen Heqiao Dai Qi Han Ying Ding Yongzhi Xia George Smith Rui Li Nai-Kui Liu Xiao-Ming Xu Spinal Cord and Brain Injury research group Stark Neurosciences Research InstituteDepartment of Neurological SurgeryIndiana University School of MedicineIndianapolisINUSA Department of Hand Surgery the Second Hospital of Jilin UniversityChangchunJilin ProvinceChina Shriners Hospitals Pediatric research Center Temple University School of MedicinePhiladelphiaPAUSA Department of Anatomy&cell Biology Indiana University School of MedicineIndianapolisINUSA

Schwann cell transplantation is considered one of the most promising cell-based therapy to repair injured spinal cord due to its unique growth-promoting and myelin-forming properties.A the Food and Drug Administration-approved Phase I clinical trial has been conducted to evaluate the safety of transplanted human autologous Schwann cells to treat patients with spinal cord injury.A major challenge for Schwann cell transplantation is that grafted Schwann cells are confined within the lesion cavity,and they do not migrate into the host environment due to the inhibitory barrier formed by injury-induced glial scar,thus limiting axonal reentry into the host spinal *** we introduce a combinatorial strategy by suppressing the inhibitory extracellular environment with injection of lentivirus-mediated transfection of chondroitinase ABC gene at the rostral and caudal borders of the lesion site and simultaneously leveraging the repair capacity of transplanted Schwann cells in adult rats following a mid-thoracic contusive spinal cord *** report that when the glial scar was degraded by chondroitinase ABC at the rostral and caudal lesion borders,Schwann cells migrated for considerable distances in both rostral and caudal *** Schwann cell migration led to enhanced axonal regrowth,including the serotonergic and dopaminergic axons originating from supraspinal regions,and promoted recovery of locomotor and urinary bladder ***,the Schwann cell survival and axonal regrowth persisted up to 6 months after the injury,even when treatment was delayed for 3 months to mimic chronic spinal cord *** findings collectively show promising evidence for a combinatorial strategy with chondroitinase ABC and Schwann cells in promoting remodeling and recovery of function following spinal cord injury.

关键词： axonal regrowth bladder function chondroitinase ABC functional recovery glial scar lentivirus migration Schwann cell spinal cord injury transplantation

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Efficacy and safety of Yiqi Peiyuan granules for improving the short-term prognosis of patients with acute kidney injury:A multicenter,double-blind,placebo-controlled,randomized trial

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Journal of Integrative medicine 2024年第3期22卷 279-285页

作者： Jia-jia Wu Tian-yi Zhang Ying-hui Qi Min-yan Zhu Yan Fang Chao-jun Qi Li-ou Cao Ji-fang Lu Bo-han Lu Lu-min Tang Jian-xiao Shen Shan Mou Department of Nephrology Molecular Cell Lab for Kidney DiseaseShanghai Peritoneal Dialysis Research CenterUremia Diagnosis and Treatment CenterRenji Hospital Affiliated to Shanghai Jiaotong University School of MedicineShanghai 200127China Department of Nephrology Shanghai Pudong New Area Punan HospitalShanghai 200125China Department of Nephrology Ningbo Hangzhou Bay HospitalNingbo 315336Zhejiang ProvinceChina

Background:Yiqi Peiyuan(YQPY)prescription,a composite prescription of traditional Chinese medicine,has been used to prevent or delay the continued deterioration of renal function after acute kidney injury(AKI)in some institutions and has shown considerable ***:This is the first randomized controlled trial to assess efficacy and safety of YQPY for improving short-term prognosis in adult patients with ***,setting,participants and interventions:This is a prospective,double-blind,multicenter,randomized,and placebo-controlled clinical trial.A total of 144 enrolled participants were randomly allocated to two groups according to a randomization ***,caregivers and investigators assessing the outcomes were blinded to group *** in the YQPY group received 36 g YQPY granules twice a day for 28 *** in the placebo group received a placebo in the same dose as the YQPY *** outcome measures:The primary outcome was the change in the estimated glomerular filtration rate(eGFR)between baseline and after 4 and 24 weeks of *** secondary outcomes were the change of serum creatinine(Scr)level between baseline and after treatment,and the incidence of endpoint events,defined as eGFR increasing by more than 25%above baseline,eGFR>75 mL/min per1.73 m2or the composite endpoint,which was defined as the sum of patients meeting either of the above ***:Data from a total of 114 patients(59 in the YQPY group and 55 in the control group)were *** mean changes in eGFR and Scr in weeks 4 and 24 had no difference between the two *** further subgroup analysis(22 in the YQPY group and 31 in the control group),the mean change in eGFR after treatment for 4 weeks was 27.39 mL/min per 1.73 m2in the YQPY group and 5.78 mL/min per1.73 m2in the placebo group,and the mean difference between groups was 21.61 mL/min per 1.73 m2(Pgroup and 5(16.1%)in the placebo g

关键词： Chinese herbal medicine Randomized controlled trial Acute kidney injury Renal function

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Black radish root extract alleviates sodium valproate-induced liver damage via inhibiting mitochondrial membrane potential collapse and oxidative stress in mice

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Asian Pacific Journal of Tropical Biomedicine 2024年第7期14卷 298-306页

作者： Mohammad Hadi Zarei Sami Akbulut Maryam Zafari Elham Saghaei Zahra Lorigooini Hossein AminiKhoei Somaye Khosravi Elham Bijad Medical Plants research Center Basic Health Sciences InstituteShahrekord University of Medical SciencesShahrekordIran Department of Liver Transplant Institute and Biostatistics Inonu University Faculty of Medicine44280MalatyaTurkey student research Committee Shahrekord University of Medical SciencesShahrekordIran Physiology and Pharmacology Department School of MedicineShahrekord University of Medical SciencesShahrekordIran Department of Anatomical Sciences School of MedicineShahrekord University of Medical SciencesShahrekordIran

Objective:To explore the effect of black radish(Raphanus sativus *** niger)root extract on liver enzymes,oxidative stress,and histopathological alterations in mice with sodium valproate-induced ***:Thirty-two mice were divided into four groups:the control group received drinking water by gavage,the second group was administered with 100 mg/kg of sodium valproate,the third group received 300 mg/kg of black radish root extract,and the fourth group was given both sodium valproate(100 mg/kg)and black radish root extract(300 mg/kg).After 28 days,the mice were euthanized,and serum levels of aspartate aminotransferase(AST),alanine aminotransferase(ALT),and alkaline phosphatase(ALP),along with liver malondialdehyde(MDA),reactive oxygen species(ROS),mitochondrial parameters,tumor necrosis factor-alpha(TNF-α)gene expression,and histopathological changes were ***:Sodium valproate caused hepatic damage in mice,characterized by elevated serum levels of liver enzymes,increased MDA and ROS levels and TNF-αgene expression,as well as histopathological *** black radish root extract significantly alleviated sodium valproate-caused hepatic injury by decreasing the serum levels of ALT and AST,MDA,ROS,TNF-αgene expression,as well as mitochondrial impairment,but did not have a significant effect on sodium valproate-induced histopathological ***:The black radish root extract demonstrates protective effects against sodium valproate-induced liver injury,possibly through mitigating oxidative stress,mitochondrial impairment,and inflammatory mediator expression.

关键词： Black radish Raphanus sativus Sodium valproate Hepatotoxicity Oxidative stress Anti-inflammation

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Rethinking neurodegenerative diseases:neurometabolic concept linking lipid oxidation to diseases in the central nervous system

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Neural Regeneration research 2024年第7期19卷 1437-1445页

作者： Steinunn Sara Helgudóttir Anne Skøttrup Mørkholt Jacek Lichota Preben Bruun-Nyzell Mads Christian Andersen Nanna Marie Juhl Kristensen Amanda Krøger Johansen Mikela Reinholdt Zinn Hulda Maria Jensdóttir John Dirk Vestergaard Nieland 2N Pharma ApS NOVI Science ParkAalborgDenmark molecular Pharmacology group Department of Health Science and TechnologyAalborg UniversityAalborgDenmark

Currently,there is a lack of effective medicines capable of halting or reve rsing the progression of neurodegenerative disorde rs,including amyotrophic lateral sclerosis,Parkinson s disease,multiple sclerosis,or Alzheimer s *** the unmet medical need,it is necessary to reevaluate the existing para digms of how to to rget these *** considering neurodegenerative diseases from a systemic neurometabolic perspective,it becomes possible to explain the shared pathological *** innovative approach presented in this paper draws upon exte nsive research conducted by the authors and researchers *** this review,we highlight the importance of metabolic mitochondrial dysfunction in the context of neurodegenerative *** provide an overview of the risk factors associated with developing neurodegenerative disorders,including genetic,epigenetic,and environmental fa ***,we examine pathological mechanisms implicated in these diseases such as oxidative stress,accumulation of misfolded proteins,inflammation,demyelination,death of neurons,insulin resistance,dysbiosis,and neurotransmitter ***,we outline a proposal for the restoration of mitochondrial metabolism,a crucial aspect that may hold the key to facilitating curative therapeutic interventions for neurodegenerative disorders in forthcoming advancements.

关键词： brain disease carnitine palmitoyl transferase 1 epigenetics metabolism gut microbiome mitochondrial dysfunction neurodegeneration oxidative stress

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G protein-mediated signal transduction: a molecular choreography of G protein activation after GTP binding

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Signal Transduction and Targeted Therapy 2024年第8期9卷 3155-3157页

作者： Evi Kostenis Lars Jurgenliemke Judith Alenfelder Department of molecular- Cellular-and PharmacobiologyInstitute of Pharmaceutical BiologyUniversity of BonnBonnGermany Graduate Training group RTG2873 University of BonnBonnGermany

A recent report from the Skiniotis group,'published in Nature,provides fascinating insight into the molecular choreography underlying a quintessential cellular signaling mechanism:G protein-mediated signal *** time-resolved cryo-EM,the authors pieced together many sequential structural snapshots to visualize how a trimeric aβy G protein-after being convinced by its activated G protein-coupled receptor(GPCR)to release GDP-picks up GTP,to set in motion finely tuned conformational transitions that lead to the conversion into the active state and,finally,subunit dissociation as well as disengagement from the receptor.

关键词： Skin activation finally

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Allogeneic mesenchymal stem cells may be a viable treatment modality in cerebral palsy

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World Journal of Clinical Cases 2024年第9期12卷 1585-1596页

作者： Osman Boyalı Serdar Kabatas ErdinçCivelek Omer Ozdemir Yeliz Bahar-Ozdemir Necati Kaplan Eyüp Can Savrunlu Erdal Karaöz Department of Neurosurgery University of Health Sciences TurkeyGaziosmanpaşa Training and Research HospitalIstanbul 34360Turkey Center for Stem cell&Gene Therapy research and Practice University of Health Sciences TurkeyIstanbul 34360Turkey Department of Physical medicine and Rehabilitation Health Sciences University Sultan Abdulhamid Han Training and Research HospitalIstanbul 34668Turkey Department of Neurosurgery Istanbul Rumeli UniversityÇorlu Reyap HospitalTekirdağ59860Turkey Department of Neurosurgery Nevşehir State HospitalNevşehir 50300Turkey Center for Regenerative medicine and Stem cell research&Manufacturing(LivMedcell) Liv HospitalIstanbul 34340Turkey Department of Histology and Embryology Istinye UniversityFaculty of Medicineİstanbul 34010Turkey Center for Stem cell and Tissue Engineering research and Practice Istinye UniversityIstanbul 34340Turkey

BACKGROUND Cerebral palsy(CP)describes a group of disorders affecting movement,balance,and *** in motor functions constitute the main body of CP *** symptoms surface in early childhood and patients are affected for the rest of their ***,treatment involves various pharmacotherapies for different types of CP,including antiepileptics for epilepsy and Botox A for focal ***,none of these methods can provide full symptom *** has prompted researchers to look for new treatment modalities,one of which is mesenchymal stem cell therapy(MSCT).Despite being a promising tool and offering a wide array of possibilities,mesenchymal stem cells(MSCs)still need to be investigated for their efficacy and *** To analyze the efficacy and safety of MSCT in CP *** Our sample consists of four CP patients who cannot stand or walk without external *** of these cases received allogeneic MSCT six times as 1×106/kg intrathecally,intravenously,and intramuscularly using umbilical cord-derived MSCs(UC-MSC).We monitored and assessed the patients pre-and post-treatment using the Wee Functional Independence Measure(WeeFIM),Gross Motor Function Classification System(GMFCS),and Manual Ability Classification Scale(MACS)*** utilized the Modified Ashworth Scale(MAS)to measure *** We found significant improvements in MAS scores after the intervention on both *** months:Rightχ^(2)=4000,P=0.046,leftχ^(2)=4000,P=0.046;four months:Rightχ^(2)=4000,P=0.046,leftχ^(2)=4000,P=0.046;12 months:Rightχ^(2)=4000,P=0.046,leftχ^(2)=4000,P=***,there was no significant difference in motor functions based on WeeFIM results(P>0.05).GMFCS and MACS scores differed significantly at 12 months after the intervention(P=0.046,P=0.046).Finally,there was no significant change in cognitive functions(P>0.05).CONCLUSION In light of our findings,we believe that UC-MSC therapy has a positive effect on spasticity

关键词： Cerebral palsy Mesenchymal stem cell Transplantation Wharton’s jelly Muscle spasticity

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Unveiling DNA methylation in Alzheimer’s disease:a review of array-based human brain studies

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Neural Regeneration research 2024年第11期19卷 2365-2376页

作者： Victoria Cunha Alves Eva Carro Joana Figueiro-Silva Neurodegenerative Diseases group Hospital Universitario 12 de Octubre Research Institute(imas12)MadridSpain Network Center for Biomedical research Neurodegenerative Diseases(CIBERNED)MadridSpain PhD Program in Neuroscience Autonoma de Madrid UniversityMadridSpain Neurotraumatology and Subarachnoid Hemorrhage group Hospital Universitario 12 de Octubre Research Institute(imas12)MadridSpain Neurobiology of Alzheimer’s Disease Unit Functional Unit for Research Into Chronic DiseasesInstituto de Salud Carlos IIIMadridSpain Institute of Medical Genetics University of ZurichZurichSwitzerland Department of molecular Life Science University of ZurichZurichSwitzerland

The intricacies of Alzheimer’s disease pathogenesis are being increasingly illuminated by the exploration of epigenetic mechanisms,particularly DNA *** review comprehensively surveys recent human-centered studies that investigate whole genome DNA methylation in Alzheimer’s disease *** examination of various brain regions reveals distinctive DNA methylation patterns that associate with the Braak stage and Alzheimer’s disease *** entorhinal cortex emerges as a focal point due to its early histological alterations and subsequent impact on downstream regions like the ***,ANK1 hypermethylation,a protein implicated in neurofibrillary tangle formation,was recurrently identified in the entorhinal ***,the middle temporal gyrus and prefrontal cortex were shown to exhibit significant hypermethylation of genes like HOXA3,RHBDF2,and MCF2L,potentially influencing neuroinflammatory *** complex role of BIN1 in late-onset Alzheimer’s disease is underscored by its association with altered methylation *** the disparities across studies,these findings highlight the intricate interplay between epigenetic modifications and Alzheimer’s disease *** research efforts should address methodological variations,incorporate diverse cohorts,and consider environmental factors to unravel the nuanced epigenetic landscape underlying Alzheimer’s disease progression.

关键词： Alzheimer’s disease ANK1 BIN1 DNA methylation epigenome-wide association studies HOXA3 MCF2L RHBDF2

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Artemisia vulgaris Induces Tumor-Selective Ferroptosis and Necroptosis via Lysosomal Ca^(2+) Signaling

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Chinese Journal of Integrative medicine 2024年第6期30卷 525-533页

作者： Lucas dos Santos Zamarioli Michele Rosana Maia Santos Adolfo Garcia Erustes Vanessa Marques Meccatti Thais Cristine Pereira Soraya S Smaili Maria Cristina Marcucci Carlos Rocha Oliveira Gustavo JS Pereira Claudia Bincoletto Department of Pharmacology Paulista School of MedicineFederal University of São PauloSão PauloSP04044-020Brazil research group on Phytocomplexes and cell Signaling School of Health SciencesAnhembi Morumbi UniversitySão PauloSP03164-000Brazil Department of Biosciences and Oral Diagnosis Institute of Science and TechnologySão Paulo State University(ICT-UNESP)São PauloSP12231-280Brazil

Objective To evaluate the chemical composition and effects of Artemisia vulgaris(AV)hydroalcoholic extract(HEAV)on breast cancer cells(MCF-7 and SKBR-3),chronic myeloid leukemia(K562)and NIH/3T3 *** Phytochemical analysis of HEAV was done by high-performance liquid chromatography-mass(HPLC)*** and cell death studies were performed using trypan blue and Annexin/FITC-7AAD,***-1(Fer-1)and necrostatin-1(Nec-1)were used to assess the mode of HEAV-induced cell death and acetoxymethylester(BAPTA-AM)was used to verify the involvement of cytosolic calcium in this *** calcium measurements were made using *** HEAV decreased the viability of MCF-7,SKBR-3 and K562 cells(Pcells was reduced compared to HEAV-exposed fibroblasts(Pcells with HEAV induced cell death primarily by late apoptosis and necrosis in assays using annexin V-FITC/7-AAD(Pcells treated with HEAV relative to cells exposed to HEAV alone(Pcells(Pcellular Ca^(2+)chelator,decreased the number of non-viable cells treated with HEAV(Pcell death,which are partially dependent on lysosomal release of Ca^(2+).These effects may be related to artemisinin and caffeoylquinic acids,the main compounds identified in HEAV.

关键词： Artemisia vulgaris necroptosis ferroptosis late apoptosis Ca^(2+)signaling

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Polysaccharide of Alocasia cucullata Exerts Antitumor Effect by Regulating Bcl-2, Caspase-3 and ERK1/2 Expressions during Long-Time Administration

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Chinese Journal of Integrative medicine 2024年第1期30卷 52-61页

作者： ZHOU Qi-chun XIAO Shi-lin LIN Ru-kun LI Chan CHEN Zhi-jie CHEN Yi-fei LUO Chao-hua MO Zhi-xian LIN Ying-bo School of Traditional Chinese medicine Southern Medical UniversityGuangzhou(510515)China Clinical and Basic research Team of TCM Prevention and Treatment of Non-Small cell Lung Cancer the Second Clinical College of Guangzhou University of Chinese MedicineGuangzhou(510120)China Department of Chinese medicine Zhujiang Hospital Affiliated to Southern Medical UniversityGuangzhou(510282)China Department of Pharmacy Jiangmen Central HospitalJiangmen(529000)China

Objective: To study the in vitro and in vivo antitumor effects of the polysaccharide of Alocasia cucullata(PAC) and the underlying mechanism. Methods: B16F10 and 4T1 cells were cultured with PAC of 40 μg/m L, and PAC was withdrawn after 40 days of administration. The cell viability was detected by cell counting kit-8. The expression of Bcl-2 and Caspase-3 proteins were detected by Western blot and the expressions of ERK1/2 mRNA were detected by quantitative real-time polymerase chain reaction(qRT-PCR). A mouse melanoma model was established to study the effect of PAC during long-time administration. Mice were divided into 3 treatment groups: control group treated with normal saline, positive control group(LNT group) treated with lentinan at 100 mg/(kg·d), and PAC group treated with PAC at 120 mg/(kg·d). The pathological changes of tumor tissues were observed by hematoxylin-eosin staining. The cell apoptosis of tumor tissues was detected by TUNEL staining. Bcl-2 and Caspase-3 protein expressions were detected by immunohistochemistry, and the expressions of ERK1/2, JNK1 and p38 mRNA were detected by qRT-PCR. Results: In vitro, no strong inhibitory effects of PAC were found in various tumor cells after 48 or 72 h of administration. Interestingly however, after 40 days of cultivation under PAC, an inhibitory effect on B16F10 cells was found. Correspondingly, the long-time administration of PAC led to downregulation of Bcl-2 protein(P cells. The above results were verified by in vivo experiments. In addition, viability of B16F10 cells under long-time administration culture in vitro decreased after drug withdrawal, and similar results were also observed in 4T1 cells. Conclusions: Long-time administration of PAC can significantly inhibit viability and promote apoptosis of tumor cells, and had obvious antitumor effect in tumor-bearing mice.

关键词： polysaccharide of Alocasia cucullata tumor cells Bcl-2 Caspase-3 ERK1/2 Chinese medicine

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Demethylase-assisted site-specific detection of N^(1)-methyladenosine in RNA

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Chinese Chemical Letters 2024年第5期35卷 397-401页

作者： Jun Xiong Ke-Ke Chen Neng-Bin Xie Wei Chen Wen-Xuan Shao Tong-Tong Ji Si-Yu Yu Yu-Qi Feng Bi-Feng Yuan College of Chemistry and molecular Sciences Research Center of Public HealthRenmin Hospital of Wuhan UniversitySchool of Public HealthWuhan UniversityWuhan 430071China Department of Laboratory medicine Zhongnan Hospital of Wuhan UniversityWuhan UniversityWuhan 430071China

The dynamic RNA modifications have been viewed as new posttranscriptional regulator in modulating gene expression as well as in a broad range of physiological processes.N^(1)-methyladenosine(m^(1)A)is one of the most prevalent modifications existing in multiple types of ***-depth investigation of the functions of m^(1)A requires the site-specific assessment of m^(1)A stoichiometry in ***,we established a demethylase-assisted method(DA-m^(1)A)for the site-specific detection and quantification of m^(1)A in RNA.N^(1)-methyl group in m^(1)A could result in the stalling of reverse transcription at m^(1)A site,thus producing the truncated *** AlkB is a demethylase that can demethylate m^(1)A to produce adenine in RNA,thus generating full-length cDNA from AlkB-treated *** of the produced amounts of full-length cDNA by quantitative real-time PCR can achieve the site-specific detection and quantification of m^(1)A in *** the DA-m^(1)A method,we examined and successfully confirmed the previously well-characterized m^(1)A sites in various types of RNAs with low false positive *** addition,we found that the level of m^(1)A was significantly decreased at the bromodomain containing 2(BRD2)mRNA position 1674 and CST telomere replication complex component 1(CTC1)mRNA position 5643 in human hepatocellular carcinoma *** results suggest that these two m^(1)A sites in mRNA may be involved in liver *** together,the DA-m^(1)A method is simple and enables the rapid,cost-effective,and site-specific detection and quantification of m^(1)A in RNA,which provides a valuable tool to decipher the functions of m^(1)A in human diseases.

关键词： N^(1)-methyladenosine RNA modification AlkB demethylase RNA epigenetics Quantitative real-time PCR Hepatocellular carcinoma

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