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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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Differential distribution of PINK1 and Parkin in the primate brain implies distinct roles

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Neural Regeneration Research 2025年第4期20卷 1124-1134页

作者： Yanting Liu Wei Huang Jiayi wen Xin Xiong Ting Xu Qi wang Xiusheng Chen Xianxian Zhao Shihua Li Xiaojiang Li Weili Yang Guangdong Key Laboratory of Non-human Primate Research Key Laboratory of CNS Regeneration(Ministry of Education)Guangdong-Hongkong-Macao CNS Regeneration Institute of Jinan UniversityJinan UniversityGuangzhouGuangdong ProvinceChina

The vast majority of in vitro studies have demonstrated that PINK1 phosphorylates Parkin to work together in mitophagy to protect against neuronal ***,it remains largely unclear how PINK1 and Parkin are expressed in mammalian *** has been difficult to address because of the intrinsically low levels of PINK1 and undetectable levels of phosphorylated Parkin in small *** this issue is critical for elucidating the in vivo roles of PINK1 and ***,we showed that the PINK1 kinase is selectively expressed as a truncated form(PINK1–55)in the primate *** the present study,we used multiple antibodies,including our recently developed monoclonal anti-PINK1,to validate the selective expression of PINK1 in the primate *** found that PINK1 was stably expressed in the monkey brain at postnatal and adulthood stages,which is consistent with the findings that depleting PINK1 can cause neuronal loss in developing and adult monkey ***1 was enriched in the membrane-bound fractionations,whereas Parkin was soluble with a distinguishable *** double staining experiments showed that PINK1 and Parkin did not colocalize under physiological conditions in cultured monkey astrocytes,though they did colocalize on mitochondria when the cells were exposed to mitochondrial *** findings suggest that PINK1 and Parkin may have distinct roles beyond their well-known function in mitophagy during mitochondrial damage.

关键词： neurodegeneration Parkin Parkinson’s disease PINK1 subcellular distribution

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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

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Unveiling phosphofructokinase as the key target: an innovative strategy combining pull-down assays with optical imaging for snail-killing mechanism exploration

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Science China Chemistry 2025年

作者： Yuxun Lu Weisi wang Le Yu Yuqiang Zhao ying Chen Yunhai Guo Bingrong Luo Yuhua Liu Shizhu Li Liping Duan ying Zhou Yunnan Characteristic Plant Extraction Laboratory College of Chemical Science and Technology Yunnan University College of Biological and Chemical Engineering Guangxi University of Science and Technology National Institute of Parasitic Diseases Chinese Center for Disease Control and Prevention (Chinese Center for Tropical Diseases Research)NHC Key Laboratory of Parasite and Vector Biology WHO Collaborating Centre for Tropical Diseases National Center for International Research on Tropical Diseases School of Chemistry and Environment Yunnan Minzu University Dali Institute of Schistosomiasis Control

The Pomacea canaliculata, also known as apple snail, is an invasive species in China, posing a serious threat to agricultural production and public health. To prevent its rampant infestation, we developed a highly efficient snail-killing lead compound, 1-(4-chlorophenyl)-3-(pyridin-3-yl)urea (PBQ). However, the killing mechanism of PBQ remains unclear. To elucidate this, two novel compounds, B-PBQ and J-PBQ, were developed through structural modification of PBQ and were used, through both protein pull-down assay and confocal laser scanning microscopy imaging, to identify and confirm that phosphofructokinase(PFK) in the apple snail is the primary target protein of PBQ. Further studies revealed that PBQ successfully inhibits the activity,content, and expression of PFK in apple snail, disrupting the glycolysis pathway and leading to abnormal energy *** disruptions impair the snail’s tolerance to low oxygen, resulting in its efficient eradication. These findings offer a promising direction for developing next-generation PFK-targeted snail-killing pesticides. Furthermore, the strategy of combining pull-down assays with optical imaging used in this work provides a novel approach for the exploration of mechanisms of other pesticide candidates.

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玻璃体切割治疗48眼金属球内异物的临床分析

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国际眼科杂志 2014年第8期14卷 1469-1472页

作者：袁冬姜涛王文营赵善瑶王云霄青岛大学附属医院眼科中国山东省青岛市266003

目的:探讨玻璃体手术治疗金属球内异物的临床效果以及影响视力预后的因素。方法:选取我院2010-01/2013-06收治的进行玻璃体切割联合球内异物取出术的球内异物患者47例48眼进行回顾性病例分析,包括视力的变化以及异物大小、术前并发症及... 详细信息

目的:探讨玻璃体手术治疗金属球内异物的临床效果以及影响视力预后的因素。方法:选取我院2010-01/2013-06收治的进行玻璃体切割联合球内异物取出术的球内异物患者47例48眼进行回顾性病例分析,包括视力的变化以及异物大小、术前并发症及就诊时间与视力的关系。结果:所有患者中有46眼成功完整取出异物,2眼为眶内异物未予取出。术后6mo随访最佳矫正视力均有不同程度的提高(P<0.05),球内异物大小、合并视网膜脱离是影响视力的危险因素(P<0.05)。结论:玻璃体切割手术对治疗金属球内异物伤有明显的优越性,及时恰当的玻璃体手术对视功能的恢复尤为重要。

关键词：玻璃体切割术眼球内金属异物临床效果

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玻璃体腔注射雷珠单抗治疗CRVO继发黄斑水肿的有效性和安全性

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国际眼科杂志 2015年第10期15卷 1778-1781页

作者：翟改霞姜涛赵善瑶王文营王云霄青岛大学附属医院眼科中国山东省青岛市266003

目的：观察雷珠单抗对视网膜中央静脉阻塞（ central retinal vein occlusion,CRVO ）继发黄斑水肿治疗的有效性和安全性。方法：根据标准将入组的24例视网膜中央静脉阻塞继发黄斑水肿患者,年龄30~70（平均51.58±10.32）岁,双盲随机... 详细信息

目的：观察雷珠单抗对视网膜中央静脉阻塞（ central retinal vein occlusion,CRVO ）继发黄斑水肿治疗的有效性和安全性。方法：根据标准将入组的24例视网膜中央静脉阻塞继发黄斑水肿患者,年龄30~70（平均51.58±10.32）岁,双盲随机分配到组玉和组Ⅱ。组玉前3mo,每月1次0.5mg雷珠单抗玻璃体腔注射并给予复方血栓通胶囊药物,组Ⅱ前3 mo仅给予复方血栓通胶囊药物。组玉和组Ⅱ从第3 mo起均开始雷珠单抗,PRN（ Prore nata）治疗。两组治疗前最佳矫正视力（ best-corrected visual acuity,BCVA）及中心视网膜厚度（ central retinal thickness,CRT）比较差异无统计学意义（ P〉0.05）。统计分析两组治疗期间的 BCVA、CRT、实验室检查结果、眼部及全身不良反应。结果：组玉治疗前最佳矫正视力（ BCVA ）为52.67±1.78,治疗1wk,1、2、3、4、6、12mo的BCVA分别为63.67±1.61、66.25±1.60、69.58±1.68、70.75±5.22、65.58±4.34、68.92±3.4、70.17±3.7,与治疗前比较有显著统计学差异（P〈0.05）,组玉治疗前 CRT 为539.00±10.94μm,治疗1wk,1、2、3、4、6、12mo 的 CRT 分别是326.67±20.83、264.58±17.11、232.00±13.04、231.25±78.68、316.00±172.48、218.00±105.25、220.58±33.43μm,与治疗前比较有显著统计学差异（P〈0.05）,组Ⅱ治疗前BCVA为52.25±2.83,CRT为539.92±12.21μm,组Ⅱ治疗3mo BCVA 为57.08±3.12,与组玉治疗3mo BCVA比较有统计学差异（ P〈0.05）,组Ⅱ治疗3mo CRT为497.92±11.91μm,与组玉治疗3mo CRT比较有统计学差异（P〈0.05）,治疗访视过程中未发现眼部及全身明显不良反应。结论：玻璃体腔注射雷珠单抗能在短期内能减轻黄斑水肿并提高视力,减少黄斑区荧光渗漏,但在眼内作用的持续时间短,需反复注射。雷珠单抗在CRVO继发黄斑水肿的治疗中具有很好的有效性和安全性。

关键词：雷珠单抗视网膜中央静脉阻塞黄斑水肿血管内皮生长因子有效性安全性

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Deciphering fungal metabolon coupling tandem inverse-electrondemand Diels-Alder reaction and semipinacol rearrangement for the biosynthesis of spiro polycyclic alkaloids

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Science China Chemistry 2025年第01期 288-296页

作者： Shuai Liu wen-Qiang Xu ying-Tong Di Man-Cheng Tang Ding-Kang Chen Ming-Ming Cao Yao-wen Chang Hong-Yu Tang Chun-Mao Yuan Jun-Bo Yang Zhi-Li Zuo Han Guo Zi-Fei Xu ying Zeng Yun-Dong Wu Xiao-Jiang Hao Key Laboratory of Phytochemistry and Natural Medicines (Chinese Academy of Sciences) Kunming Institute of Botany Chinese Academy of Sciences University of Chinese Academy of Sciences Lab of Computational Chemistry and Drug Design State Key Laboratory of Chemical Oncogenomics Peking University Shenzhen Graduate School Shenzhen Bay Laboratory State Key Laboratory of Microbial Metabolism School of Life Sciences & Biotechnology Shanghai Jiao Tong University State Key Laboratory of Functions and Applications of Medicinal Plants Guizhou Medical University Molecular Biology Experimental Center Germplasm Bank of Wild Species in Southwest China Kunming Institute of Botany Chinese Academy of Sciences Yunnan Key Laboratory for Wild Plant Resources Kunming Institute of Botany Chinese Academy of Sciences Research Unit of Chemical Biology of Natural Anti-Virus Products Chinese Academy of Medical Sciences

In the intricate process of natural product biosynthesis, a metabolon can enhance metabolic flux by associating sequential enzymes. A fungal metabolon, comprising of flavin-dependent monooxygenase Spe F and P450 monooxygenase Spe G, is identified in the biosynthesis of spiro polycyclic alkaloids(+)-notoamide B and its diastereomer(+)-versicolamide B. Using notoamide E as a substance, Spe F/Spe G metabolon can control the stereoselectivity of its 2,3-epoxidation, followed by hydrogen atom ion at C-17 to generate reactive epoxide tau-m A with dienyl iminium unit. Subsequently,(+)-notoamide B and(+)-versicolamide B are produced via tandem nonenzymatic inverse-electron-demand Diels-Alder reaction and semipinacol rearrangement. This provides the first example of metabolon in the biosynthesis of spiro-prenylated indole alkaloids.

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Heating effect and biocompatibility of bacterial magnetosomes as potential materials used in magnetic fluid hyperthermia

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Progress in Natural Science:Materials International 2012年第1期22卷 31-39页

作者： Rui-ting Liu a,Jie Liu a,c,Jie-qiong Tong a,c,Tao Tang a,b,Wei-Chao Kong a,c,Xiao-wen wang a,ying Li b,Jin-tian Tang a a Key Laboratory of Particle & Radiation Imaging(Tsinghua University),Ministry of Education,Department of Engineering Physics,Tsinghua University,Beijing 100084,China b State Key Laboratories for Agrobiotechnology and College of Biological Sciences,China Agricultural University,Beijing 100083,China c Department of Pharmaceutics,Beijing University of Chinese Medicine,Beijing 100102,China [a] Key Laboratory of Particle & Radiation Imaging (Tsinghua University) Ministry of Education Department of Engineering Physics Tsinghua University Beijing 100084 China [b] State Key Laboratories for Agrobiotechnology and College of Biological Sciences China Agricultural University Beijing 100083 China [c] Department of Pharmaceutics Beijing University of Chinese Medicine Beijing 100102 China

Magnetic fluid hyperthermia(MFH) promises to be a viable alternative in the treatment of localized cancerous *** treatment consists of introducing nanoparticles as energy absorbent agents in tumor tissue under an oscillating magnetic field,where nanoparticles dissipate energy in the form of heat,causing a localized rise in the temperature and tumor cell *** magnetic fluid under study is artificial magnetic *** work seeks to introduce the new natural biologic magnetic material bacterial magnetosomes(BMs) to be used in *** of magnetosomes and chemically synthesized magnetic nanoparticles(MNPs),such as morphology,magnetic properties and their heating effects under magnetic field were *** studies using human breast cancer cells MCF-7 indicated that cell viability could be significantly decreased by the heat derived from BMs and MNPs under alternative magnetic *** of BMs and MNPs was compared in terms of evaluating their acute toxicity in mice and their decomposition abilities in vitro,and it showed that magnetosomes exhibit a lower *** findings provide evidence for beneficial activities of magnetosomes in MFH and support the continued investigation of it to be applied in biomedicine.

关键词： Magnetosome Synthesized magnetic nanoparticles Magnetic fluid hyperthermia Properties Biocompatibility

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Moment Redistribution Effect of the Continuous Glass Fiber Reinforced Polymer-Concrete Composite Slabs Based on Static Loading Experiment

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Structural Durability & Health Monitoring 2025年第1期19卷 105-123页

作者： Zhao-Jun Zhang wen-Wei wang Jing-Shui Zhen Bo-Cheng Li De-Cheng Cai Yang-Yang Du Hui Huang Offshore Oil Engineering Co.Ltd. Tianjin300461China Department of Bridge Engineering School of TransportationSoutheast UniversityNanjing211189China

This study aimed to investigate the moment redistribution in continuous glass fiber reinforced polymer(GFRP)-concrete composite slabs caused by concrete cracking and steel bar yielding in the negative bending moment *** experimental bending moment redistribution test was conducted on continuous GFRP-concrete composite slabs,and a calculation method based on the conjugate beam method was *** composite slabs were formed by combining GFRP profiles with a concrete layer and supported on steel beams to create two-span continuous composite slab *** methods,epoxy resin bonding,and stud connection,were used to connect the composite slabs with the steel *** experimental findings showed that the specimen connected with epoxy resin exhibited two moments redistribution phenomena during the loading process:concrete cracking and steel bar yielding at the internal *** contrast,the composite slab connected with steel beams by studs exhibited only one-moment redistribution phenomenon throughout the loading *** the concrete at the internal support cracked,the bending moment decreased in the internal support section and increased in the midspan *** the steel bars yielded,the bending moment further decreased in the internal support section and increased in the mid-span *** GFRP profiles do not experience cracking,there was no significant decrease in the bending moment of the mid-span *** test specimens experienced compressive failure of concrete at the mid-span *** results showed good agreement between the calculated and experimental values of bending moments in the mid-span section and internal support *** proposed model can effectively predict the moment redistribution behavior of continuous GFRP-concrete composite slabs.

关键词： Moment redistribution GFRP-concrete composite slabs bending moment experimental study analysis model

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NOX4 exacerbates Parkinson's disease pathology by promoting neuronal ferroptosis and neuroinflammation

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Neural Regeneration Research 2025年第7期20卷 2038-2052页

作者： Zhihao Lin Changzhou ying Xiaoli Si Naijia Xue Yi Liu Ran Zheng ying Chen Jiali Pu Baorong Zhang Department of Neurology The Second Affiliated HospitalZhejiang University School of MedicineHangzhouZhejiang ProvinceChina

Parkinson's disease is primarily caused by the loss of dopaminergic neurons in the substantia nigra ***,a novel form of regulated cell death characterized by iron accumulation and lipid peroxidation,plays a vital role in the death of dopaminergic ***,the molecular mechanisms underlying ferroptosis in dopaminergic neurons have not yet been completely *** oxidase 4 is related to oxidative stress,however,whether it regulates dopaminergic neuronal ferroptosis remains *** aim of this study was to determine whether NADPH oxidase 4 is involved in dopaminergic neuronal ferroptosis,and if so,by what *** found that the transcriptional regulator activating transcription factor 3 increased NADPH oxidase 4 expression in dopaminergic neurons and astrocytes in an 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine-induced Parkinson's disease *** oxidase 4 inhibition improved the behavioral impairments observed in the Parkinson's disease model animals and reduced the death of dopaminergic ***,NADPH oxidase 4 inhibition reduced lipid peroxidation and iron accumulation in the substantia nigra of the Parkinson's disease model ***,we found that NADPH oxidase 4 interacted with activated protein kinase Cαto prevent ferroptosis of dopaminergic ***,by lowering the astrocytic lipocalin-2 expression,NADPH oxidase 4 inhibition reduced 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine-induced *** findings demonstrate that NADPH oxidase 4 promotes ferroptosis of dopaminergic neurons and neuroinflammation,which contribute to dopaminergic neuron death,suggesting that NADPH oxidase 4 is a possible therapeutic target for Parkinson's disease.

关键词： dopaminergic neuron ferroptosis NADPH oxidase 4(NOX4) neuroinflammation Parkinson's disease

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