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Engineering self-catabolic DNAzyme nanospheres for synergistic anticancer therapy

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Science China Chemistry 2024年第7期67卷 2412-2422页

作者： yu Chen yu Guo Jiaoli Wang Ruiting Liu Xiaohai yang Kemin Wang ying Pu Hui Shi jin Huang Key Laboratory of Chemo/Biosensing and Chemometrics College of Chemistry and Chemical EngineeringKey Laboratory for Bio-Nanotechnology and Molecular Engineering of Hunan ProvinceHunan UniversityChangsha 410082China National Clinical Research Center for Geriatric Disorders Department of GeriatricsXiangya HospitalCentral South UniversityChangsha 410008China

DNAzyme-based gene therapy faces some challenges including cell penetration,activity limitation,and co-delivery ***-assembled DNA nanomedicine has attracted widespread attention due to its many *** is urgent to develop a universal DNA degradation strategy for precise programmable drug ***,we reported a self-catabolic DNAzyme nanospheres(SCNS),which could simultaneously achieve cell penetration,activity enhancement,and co-delivery *** SCNS were assembled through y-DNA stepwise hybridization with each other,which were then loaded with aptamer(Apt),doxorubicin(Dox),and zinc oxide nanoparticles(ZnO NPs).The acid-triggered dissociation of ZnO NPs leads to the generation of Zn^(2+)ions cofactors for immediately self-catabolic DNAzyme *** the disassembly of the SCNS,three types of anticancer treatments would be activated,which include Zn^(2+)involved reactive oxygen species(ROS),Dox-induced chemotherapy,and DNAzyme-based gene *** experimental results show that the nanoplatform(Apt-SCNS-Dox-ZnO)has a good tumor-killing effect and minimal side *** a smart self-driven drug delivery nanoplatform,it is anticipated to displace extraordinary potential in biomedicine and bioengineering.

关键词： DNAzyme nanosphere ZnO NPs ROS Dox anticancer therapy

enOsCas12f1-mediated exon skipping for Duchenne muscular dystrophy therapy in humanized mouse model

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Journal of Genetics and Genomics 2024年第2期51卷 256-259页

作者： ming jin Jiajia Lin yu Zhang Qingquan Xiao Xiangfeng Kong Xiumei Zhang Zhurui Shao yin Wang yuyang yu jinjing Li Wan-jin Chen Guoling Li Hui yang Ning Wang Department of Neurology and Institute of Neurology of First Affiliated Hospital Institute of NeuroscienceFujian Key Laboratory of Molecular NeurologyFujian Medical UniversityFuzhouFujian 350004China HUIDAGENE Therapeutics Co. Ltd.Shanghai 200131China Institute of Neuroscience State Key Laboratory of NeuroscienceKey Laboratory of Primate NeurobiologyCAS Center for Excellence in Brain Science and Intelligence TechnologyShanghai Institutes for Biological SciencesChinese Academy of SciencesShanghai 200031China

Duchenne muscular dystrophy(DMD)is a severe neuromuscular disorder caused by mutations in the dystrophin gene,which encodes the essential protein *** genetic condition,affecting approximately 1 in 5000 male births worldwide(Birnkrant et al.,2018),is characterized by progressive muscle weakness and wasting,leading to premature death in the second or third decade of life(Farini et al.,2016).The absence of dystrophin protein causes instability in the sarcolemma,which predisposes individuals to myonecrosis and activation of inflammatory signaling ***,there is currently no effective cure for DMD,and glucocorticoid steroids are commonly used in clinical settings to delay symptom development(Merlini et al.,2003).

关键词： dystrophy Duchenne

Effect of low-degree astigmatism on the objective visual quality

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International Journal of Ophthalmology(English edition) 2024年第6期17卷 1086-1093页

作者： Ling-ying ye Shu-Feng Li jing-jing Zuo jin Li Hui-Xiang Ma National Clinical Research Center for Ocular Diseases Eye HospitalWenzhou Medical UniversityWenzhou 325027Zhejiang ProvinceChina

AIM:To evaluate the effect of low-degree astigmatism on objective visual quality through the Optical Quality Analysis System(OQAS).METHODS:This study enrolled 46 participants(aged 23 to 30y,90 eyes)with normal or corrected-to-normal *** cylindrical lenses(0,0.5,0.75,1.0,and 1.25 D)were placed at the axial direction(180°,45°,90°,and 135°)in front of the eyes with the best correction to form 16 types of regular low-degree *** was used to detect the objective visual quality,recorded as the objective scattering index(OSI),OQAS values at contrasts of 100%,20%,and 9%predictive visual acuity(OV100%,OV20%,and OV9%),modulation transfer function cut-off(MTFcut-off)and Strehl ratio(SR).The mixed effect linear model was used to compare objective visual quality differences between groups and examine associations between astigmatic magnitude and objective visual quality ***:Apparent negative relationships between the magnitude of low astigmatism and objective visual quality were *** increase of OSI per degree of astigmatism at 180°,45°,90°,and 135°axis were 0.38(95%CI:0.35,0.42),0.50(95%CI:0.46,0.53),0.49(95%CI:0.45,0.54)and 0.37(95%CI:0.34,0.41),*** decrease of MTFcut-off per degree of astigmatism at 180°,45°,90°,and 135°axis were-10.30(95%CI:-11.43,-9.16),-12.73(95%CI:-13.62,-11.86),-12.75(95%CI:-13.79,-11.70),and-9.97(95%CI:-10.92,-9.03),*** the same astigmatism degree,OSI at 45°and 90°axis were higher than that at 0°and 135°axis,while MTFcut-off were ***:Low astigmatism of only 0.50 D can significantly reduce the objective visual quality.

关键词： low-degree astigmatism objective visual quality Optical Quality Analysis System

Effect of heat treatment on corrosion behaviors of Mg-6Gd-3y-0.5Zr alloy

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China Foundry 2024年第5期21卷 599-612页

作者： Fei Wang Bin-guo Fu yu-feng Wang Tian-shun Dong Guo-lu Li jin-hai Liu Hebei Key Laboratory of New Functional Materials School of Materials Science and EngineeringHebei University of TechnologyTianjin 300401China Tianjin Institute of Aerospace Mechanical and Electrical Equipment Tianjin 300301China Tianjin Aerospace Long March Technology and Equipment Co. Ltd.Tianjin 300462China

The microstructures and corrosion behaviors of as-cast,T4-treated,and T6-treated Mg-6Gd-3y-0.5Zr alloys were systematically investigated by SEM,TEM,immersion test,and electrochemical corrosion *** results show that the microstructure of the as-cast alloy is composed ofα-Mg and Mg_(24)(Gd,y)_(5)eutectic phase,and in T4-treated alloy,Mg_(24)(Gd,y)_(5)phase dissolves into theα-Mg matrix,leading to an increase in the(y,Gd)H_(2)*** T6 treatment,nanoscale Mg_(24)(Gd,y)_(5)phase dispersedly precipitates from theα-Mg matrix,and exhibits a specific orientation relationship with theα-Mg:(332)Mg_((24)(Gd,y)_(5))//(1011)_(α-Mg),[136]Mg_((24)(Gd,y)_(5))//[1210]_(α-Mg).The corrosion resistance of the Mg-6Gd-3y-0.5Zr alloys can be ranked in the following order:T6-treated alloy exhibits the highest corrosion resistance,followed by the T4-treated alloy,and finally,the as-cast *** corrosion products of the alloys are all composed of MgO,Mg(OH)_(2),Gd_(2)O_(3),y_(2)O_(3),and MgCl_(2).The corrosion behavior of Mg-6Gd-3y-0.5Zr alloy is closely related to the precipitated *** establishing the relationship between corrosion rate,hydrogen evolution rate,and corrosion potential,it is further demonstrated that during the micro galvanic corrosion process,the coarse Mg_(24)(Gd,y)_(5)phase in the as-cast alloy undergoes extensive dissolution,and(y,Gd)H_(2)phase promotes the dissolution of theα-Mg matrix in the T4-treated alloy,intensifying the hydrogen evolution *** T6-treated alloy,with dispersive precipitation of nanoscale Mg_(24)(Gd,y)_(5)phase,exhibits better corrosion resistance performance.

关键词： Mg-6Gd-3y-0.5Zr alloy heat treatment microstructure precipitated phase corrosion resistance

Stereospecific Assembly of Trisubstituted Alkenes via Photoinduced Nitrogen-Centered Radical-Triggered C—C Bond Cleavage/Functionalization of Oxime Esters

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Chinese Journal of Chemistry 2024年第12期42卷 1399-1406页

作者： yu Bao Zhi-Jie Song jin-Long Dai Shenghu yan yue Zhang Jia-yin Wang Guigen Li School of Pharmacy Changzhou UniversityChangzhouJiangsu 213164China Department of Chemistry and Biochemistry Texas Tech University79409USA

Comprehensive Summary A general and convenient photoredox-catalyzed acylation and alkylcyanation of MBH acetates has been established,enabling the assembly of the C(sp2)–C(sp3)bond by a nitrogen-centered radical strategy for the synthesis of trisubstituted alkenes in moderate to excellent chemical yields(48 examples in total).The reaction of MBH acetates with acyl(indanone)oxime esters afforded trisubstituted alkenes containing 1,4-dicarbonyl ***,the use of Eosin y as a photocatalyst in the catalytic system resulted in the formation of distal cyano group-anchored trisubstituted alkenes via deconstructive functionalization of cycloketone oxime ***,these resulting 1,4-dicarbonyl compounds could be applied to late-stage transformations,providing important methods for the synthesis of dihydropyridazin-3(2H)-one.

关键词： Photocatalysis Radical reactions MBH acetates Oxime esters Stereoselectivity Acylation Alkylation Green chemistry

NF-κB in biology and targeted therapy:new insights and translational implications

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Signal Transduction and Targeted Therapy 2024年第4期9卷 1322-1358页

作者： Qing Guo yizi jin Xinyu Chen Xiaomin ye Xin Shen mingxi Lin Cheng Zeng Teng Zhou Jian Zhang Department of Medical Oncology Fudan University Shanghai Cancer CenterNo.270Dong'an RoadShanghai 200032China Department of Oncology Shanghai Medical CollegeFudan UniversityShanghaiChina State Key Laboratory of Oncogenes and Related Genes Renj-Med-X Stem Cell Research CenterShanghai Cancer Institute&Department of UrologyRen Ji HospitalSchool of Medicine and School of Biomedical EngineeringShanghai Jiao Tong UniversityShanghai 200127PR China Department of Cardiology the First Affiliated Hospital of Sun Yat-Sen University58 Zhongshan 2nd RoadGuangzhou 510080China Department of Neurology Rujin HospitalShanghai JiaoTong University Schoolof MedicineShanghaiChina

NF-κB signaling has been discovered for nearly 40 ***,NF-κB signaling was identified as a pivotal pathway in mediating inflammatory ***,with extensive and in-depth investigations,researchers have discovered that its role can be expanded to a variety of signaling mechanisms,biological processes,human diseases,and treatment *** this review,we first scrutinize the research process of NF-κB signaling,and summarize the composition,activation,and regulatory mechanism of NF-κB *** investigate the interaction of NF-κB signaling with other important pathways,including PI3K/AKT,MAPK,JAK-STAT,TGF-β,Wnt,Notch,Hedgehog,and TLR *** physiological and pathological states of NF-κB signaling,as well as its intricate involvement in inflammation,immune regulation,and tumor microenvironment,are also ***,we illustrate how NF-κB signaling is involved in a variety of human diseases,including cancers,inflammatory and autoimmune diseases,cardiovascular diseases,metabolic diseases,neurological diseases,and ***,we discuss the therapeutic approaches targeting NF-κB signaling,including IKK inhibitors,monoclonal antibodies,proteasome inhibitors,nuclear translocation inhibitors,DNA binding inhibitors,TKls,non-coding RNAs,immunotherapy,and ***,we provide an outlook for research in the field of NF-κB *** hope to present a stereoscopic,comprehensive NF-κB signaling that will inform future research and clinical practice.

关键词： PI3K/AKT diseases involvement

Effect of navigation endoscopy combined with threedimensional printing technology in the treatment of orbital blowout fractures

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International Journal of Ophthalmology(English edition) 2024年第3期17卷 570-576页

作者： jin-Hai yu yao-Hua Wang Qi-Hua Xu Chao Xiong An-An Wang Hong-Fei Liao School of Optometry Jiangxi Medical CollegeNanchang UniversityNanchang 330006Jiangxi ProvinceChina The Affiliated Eye Hospital Jiangxi Medical CollegeNanchang UniversityNanchang 330006Jiangxi ProvinceChina Jiangxi Clinical Research Center for Ophthalmic Disease Nanchang 330006Jiangxi ProvinceChina Jiangxi Research Institute of Ophthalmology and Visual Science Nanchang 330006Jiangxi ProvinceChina Jiangxi Provincial Key Laboratory for Ophthalmology Nanchang 330006Jiangxi ProvinceChina

●AIM:To explore the combined application of surgical navigation nasal endoscopy(NNE)and three-dimensional printing technology(3DPT)for the adjunctive treatment of orbital blowout fractures(OBF).●METHODS:Retrospective analysis was conducted on the data of patients with OBF who underwent surgical treatment at the Affiliated Eye Hospital of Nanchang University between July 2012 and November *** control group consisted of patients who received traditional surgical treatment(n=43),while the new surgical group(n=52)consisted of patients who received NNE with *** difference in therapeutic effects between the two groups was evaluated by comparing the duration of the operation,best corrected visual acuity(BCVA),enophthalmos difference,recovery rate of eye movement disorder,recovery rate of diplopia,and incidence of postoperative complications.●RESULTS:The study included 95 cases(95 eyes),with 63 men and 32 *** patients’age ranged from 5 to 67y(35.21±15.75y).The new surgical group and the control group exhibited no statistically significant differences in the duration of the operation,BCVA and enophthalmos *** recovery rates of diplopia in the new surgical group were significantly higher than those in the control group at 1mo[OR=0.03,95%CI(0.01–0.15),Py rates of eye movement disorders at 1 and 3mo after surgery were OR=0.08,95%CI(0.03–0.24),Py time of diplopia and eye movement disorder in patients with OBF.

关键词： orbital blowout fracture three-dimensional printing endoscopy surgical navigation

Ketogenic diet therapy in children with epilepsy caused by SLC2A1 mutations:a single-center single-arm retrospective study

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World Journal of Pediatrics 2024年第5期20卷 517-524页

作者： ying-yan Wang yun-Qing Zhou Li-Juan Luo Cui-jin Wang Nan Shen Hao Li Ji-Wen Wang Department of Neurology Shanghai Children’s Medical CenterSchool of MedicineShanghai Jiao Tong UniversityShanghaiChina Department of Infectious Diseases Shanghai Children’s Medical CenterSchool of MedicineShanghai Jiao Tong UniversityShanghaiChina Clinical Research Ward Clinical Research CenterShanghai Children’s Medical CenterSchool of MedicineShanghai Jiao Tong UniversityShanghaiChina

Background This retrospective study assessed the efficacy and safety of ketogenic diet therapies in children with epilepsy caused by SLC2A1 genetic mutations and glucose transporter type 1 deficiency *** Pediatric patients with epilepsy symptoms admitted to our medical center between January 2017 and October 2021 were included if they presented with an SLC2A1 genetic mutation on whole-exome *** analyzed the patients’convulsions and treatment with antiepileptic *** patients were followed up at different time periods after ketogenic diet *** Six patients with SLC2A1 mutations were included in this *** patients had seizures of different types and frequencies,and they took antiepileptic drugs to relieve their *** were then treated with a ketogenic diet for at least four *** analyzed epilepsy control rates at 1,2,3,6,and 12 months after ketogenic diet *** patients were seizure-free within a month of receiving the diet *** patients were followed up for six months,three were followed up for 12 months after the treatment,and there was no recurrence of epilepsy during this *** antiepileptic drug withdrawal,none of the patients experienced seizure relapse when receiving ketogenic diet treatment *** severe adverse events occurred during the *** Ketogenic diet therapy is very effective and safe for the treatment of epilepsy caused by SLC2A1 ***,patients with glucose transporter type 1 deficiency syndrome caused by SLC2A1 mutations should begin ketogenic diet treatment as soon as possible.

关键词： Epilepsy Glucose transporter type 1 Ketogenic diet SLC2A1

A mutation in TBXT causes congenital vertebral malformations in humans and mice

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Journal of Genetics and Genomics 2024年第4期51卷 433-442页

作者： Shuxia Chen yunping Lei yajun yang Chennan Liu Lele Kuang Li jin Richard HFinnell Xueyan yang Hongyan Wang Obstetrics and Gynecology Hospital State Key Laboratory of Genetic Engineering at School of Life SciencesKey Laboratory of Reproduction Regulation of NPFPCInstitute of Reproduction and DevelopmentFudan UniversityShanghai 200438China Shanghai Key Laboratory of Metabolic Remodeling and Health Institute of Metabolism and Integrative BiologyFudan UniversityShanghai 200438China Center for Precision Environmental Health Department of Molecular and Cellular BiologyBaylor College of MedicineHoustonTX 77030USA MOE Key Laboratory of Contemporary Anthropology School of Life SciencesFudan UniversityShanghai 200438China Department of Assisted Reproduction Xinhua HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghai 200092China Children’s Hospital Fudan University399 Wanyuan RoadShanghai 201102China

T-box transcription factor T(TBXT;T)is required for mesodermal formation and axial skeletal *** it has been extensively studied in various model organisms,human congenital vertebral malformations(CVMs)involving T are not well ***,we report a family with 15 CVM patients distributed across 4 *** affected individuals carry a heterozygous mutation,T c.596A>G(p.Q199R),which is not found in unaffected family members,indicating co-segregation of the genotype and *** vitro assays show that T p.Q199R increases the nucleocytoplasmic ratio and enhances its DNA-binding affinity,but reduces its transcriptional activity compared to the *** determine the pathogenicity of this mutation in vivo,we generated a Q199R knock-in mouse model that recapitulates the human CVM *** heterozygous Q199R mice show subtle kinked or shortened tails,while homozygous mice exhibit tail filaments and severe vertebral ***,we show that the Q199R mutation in T causes CVM in humans and mice,providing previously unreported evidence supporting the function of T in the genetic etiology of human CVM.

关键词： Congenital vertebral malformation TBXT T gene Loss-of-function mutation