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Metabolic reprogramming: a new option for the treatment of spinal cord injury

Neural Regeneration Research 2025年第4期20卷 1042-1057页

作者： Jiangjie Chen Jinyang Chen Chao Yu Kaishun Xia Biao Yang Ronghao Wang Yi Li Kesi Shi Yuang Zhang Haibin Xu Xuesong Zhang Jingkai Wang Qixin Chen chengzhen liang Department of Orthopedics The Second Affiliated Hospital of Zhejiang University School of MedicineHangzhouZhejiang ProvinceChina Orthopedics Research Institute of Zhejiang University Zhejiang UniversityHangzhouZhejiang ProvinceChina Key Laboratory of Motor System Disease Research and Precision Therapy of Zhejiang Province HangzhouZhejiang ProvinceChina Clinical Research Center of Motor System Disease of Zhejiang Province HangzhouZhejiang ProvinceChina Qiandongnan Prefecture People’s Hospital KailiGuizhou ProvinceChina Department of Orthopedics Fourth Medical CenterChinese PLA General HospitalBeijingChina

Spinal cord injuries impose a notably economic burden on society,mainly because of the severe after-effects they cause.Despite the ongoing development of various therapies for spinal cord injuries,their effectiveness remains unsatisfactory.However,a deeper understanding of metabolism has opened up a new therapeutic opportunity in the form of metabolic reprogramming.In this review,we explore the metabolic changes that occur during spinal cord injuries,their consequences,and the therapeutic tools available for metabolic reprogramming.Normal spinal cord metabolism is characterized by independent cellular metabolism and intercellular metabolic coupling.However,spinal cord injury results in metabolic disorders that include disturbances in glucose metabolism,lipid metabolism,and mitochondrial dysfunction.These metabolic disturbances lead to corresponding pathological changes,including the failure of axonal regeneration,the accumulation of scarring,and the activation of microglia.To rescue spinal cord injury at the metabolic level,potential metabolic reprogramming approaches have emerged,including replenishing metabolic substrates,reconstituting metabolic couplings,and targeting mitochondrial therapies to alter cell fate.The available evidence suggests that metabolic reprogramming holds great promise as a next-generation approach for the treatment of spinal cord injury.To further advance the metabolic treatment of the spinal cord injury,future efforts should focus on a deeper understanding of neurometabolism,the development of more advanced metabolomics technologies,and the design of highly effective metabolic interventions.

关键词： axons glycolysis metabolic reprogramming metabolism mitochondria neural regeneration neuroprotection oxidative phosphorylation spinal cord injury therapy

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A conductive supramolecular hydrogel creates ideal endogenous niches to promote spinal cord injury repair

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Bioactive Materials 2022年第9期7卷 103-119页

作者： Biao Yang chengzhen liang Di Chen Feng Cheng Yuang Zhang Shaoke Wang Jiawei Shu Xianpeng Huang Jingkai Wang Kaishun Xia Liwei Ying Kesi Shi Chenggui Wang Xuhua Wang Fangcai Li Qian Zhao Qixin Chen Department of Orthopedics Surgery The Second Affiliated HospitalSchool of MedicineZhejiang UniversityHangzhou310009ZhejiangChina Orthopedics Research Institute of Zhejiang University Hangzhou310009ZhejiangChina Key Laboratory of Motor System Disease Research and Precision Therapy of Zhejiang Province Hangzhou310009ZhejiangChina Ningbo Research Institute of Zhejiang University Ningbo315100ZhejiangChina State Key Laboratory of Chemical Engineering College of Chemical and Biological EngineeringZhejiang UniversityHangzhou310027ZhejiangChina NHC and CAMS Key Laboratory of Medical Neurobiology MOE Frontier Science Center for Brain Research and Brain-Machine IntegrationSchool of Brain Science and Brain MedicineZhejiang UniversityHangzhou310003ZhejiangChina

The current effective method for treatment of spinal cord injury(SCI)is to reconstruct the biological microenvironment by filling the injured cavity area and increasing neuronal differentiation of neural stem cells(NSCs)to repair SCI.However,the method is characterized by several challenges including irregular wounds,and mechanical and electrical mismatch of the material-tissue interface.In the current study,a unique and facile agarose/gelatin/polypyrrole(Aga/Gel/PPy,AGP3)hydrogel with similar conductivity and modulus as the spinal cord was developed by altering the concentration of Aga and PPy.The gelation occurred through non-covalent interactions,and the physically crosslinked features made the AGP3 hydrogels injectable.In vitro cultures showed that AGP3 hydrogel exhibited excellent biocompatibility,and promoted differentiation of NSCs toward neurons whereas it inhibited over-proliferation of astrocytes.The in vivo implanted AGP3 hydrogel completely covered the tissue defects and reduced injured cavity areas.In vivo studies further showed that the AGP3 hydrogel provided a biocompatible microenvironment for promoting endogenous neurogenesis rather than glial fibrosis formation,resulting in significant functional recovery.RNA sequencing analysis further indicated that AGP3 hydrogel significantly modulated expression of neurogenesis-related genes through intracellular Ca2+signaling cascades.Overall,this supramolecular strategy produces AGP3 hydrogel that can be used as favorable biomaterials for SCI repair by filling the cavity and imitating the physiological properties of the spinal cord.

关键词： Conducting polymer Supramolecular hydrogels Biomimetic scaffolds Nerve regeneration Spinal cord injury

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A backbone parent contributes core genomic architecture to pedigree breeding of early-season indica rice

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Journal of Genetics and Genomics 2021年第11期48卷 1040-1043页

作者： Junyu Chen Huali Zhang Shuhan Deng Huilong Du Zhuo Chen Yuhui Zhao Dongqing Dai chengzhen liang Ximing Li Chengzhi liang Rui Zhang liangyong Ma State Key Laboratory of Rice Biology and Chinese National Center for Rice Improvement China National Rice Research InstituteHangzhou 311400China Novogene Bioinformatics Institute Beijing 100083China State Key Laboratory of Plant Genomics Institute of Genetics and Developmental BiologyInnovation Academy for Seed DesignChinese Academy of SciencesBeijing 100101China Biotechnology Research Institute Chinese Academy of Agricultural SciencesBeijing 100081China

Due to the capacity to deliver favorable target traits to offspring via breeder selection,backbone parents carrying accumulated favorable agronomic traits have been used widely in breeding programs in crop species,such as rice,wheat,cotton,and maize(Zhou et al.,2016;Fradgley et al.,2019;Li et al.,2019;Ma et al.,2019;Han et al.,2020).It is estimated that 3656(~70%)of the major Chinese rice varieties released from the year 1950e2008 were found to be derived from as few as 35 backbone parents(Tang et al.,2012).Large-scale genome sequencing of diverse rice accessions has been emerged as a promising technology for the identification of key genomic regions or loci under selection during rice domestication(Huang et al.,2012;Wang et al.,2018)and genetic improvement(Xie et al.,2015).On the other hand,sequence information derived from breeding pedigrees could also help to unravel how favorable genomic regions were transmitted from parents to their offspring,as demonstrated by the researches on the pedigrees of the wellknown rice varieties Minghui 63 and Huanghuazhan(Zhou et al.,2016;Chen et al.,2017;Huang et al.,2018).These researches enhanced the understanding of the cumulative effects of beneficial alleles at limited loci in selected offspring varieties.A few examples include IPA1,Gn1a,GW5,GS3,and GS5 for high grain yield,Waxy for good grain eating quality,and Xa21 for high adversity adaptability.

关键词： breeding backbone season

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Significant Improvement of Cotton Verticillium Wilt Resistance by Manipulating the Expression of Gastrodia Anlffungal Proteins

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Molecular Plant 2016年第10期9卷 1436-1439页

作者： Yiqin Wang chengzhen liang Shenjie Wu Xueyan Zhang Jiuyou Tang Guijiang Jian Gaili Jiao Fuguang Li Chengcai Chu State Key Laboratory of Plant Genomics and National Center for Plant GeneResearch (Beijing) Institute of Genetics and Developmental Biology Chinese Academy of Sciences Beijing 100101 China Biotechnology Research Institute Chinese Academy of Agricultural Sciences Beijing 100081 China Institute of Economic Crops Shanxi Academy of Agricultural Sciences Yuncheng Shanxi Province 044000 China Institute of Cotton Research Chinese Academy of Agricultural Sciences Anyang Henan Province 455000 China Institute of Plant Protection Chinese Academy of Agricultural Sciences Beijing 100193 China

Dear Editor Verticillium wilt caused by Verticillium dahliae Kleb. is the most destructive disease in cotton-growing areas around the world. The infection significantly reduces cotton yield and fiber quality due to leaf chlorosis, necrosis or wilting, leaf or boll abscission, and even plant death. The losses may reach up to 80% of lint cotton yield （Wei et al., 2015）.

关键词： GASTRODIA elata VERTICILLIUM wilt of cotton DISEASE resistance of plants

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Increased lateral root formation by CRISPR/Cas9-mediated editing of arginase genes in cotton

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Science China(Life Sciences) 2017年第5期60卷 524-527页

作者： Yanling Wang Zhigang Meng chengzhen liang Zhaohong Meng Yuan Wang Guoqing Sun Tao Zhu Yongping Cai Sandui Guo Rui Zhang Yi Lin School of Life Science Anhui Agricultural University Biotechnology Research Institute Chinese Academy of Agricultural Sciences

Dear Editor,Proper development of plant roots is critical for primary physiological functions,including water and nutrient absorption and uptake,physical support,and carbohydrate storage(Zhang et al.,2010).Crop root systems act as the key organ for sensing and response to abiotic and biotic stresses.Previous studies of crop root system development suggest that increased lateral root formation(LRF)could

关键词：酶基因精氨酸棉花编辑介导根形养分吸收碳水化合物

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红蓝光促进陆地棉愈伤组织诱导和增殖

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中国农业科学 2024年第4期57卷 638-649页

作者：李凯利魏云晓种智力孟志刚王远梁成真陈全家张锐新疆农业大学农学院/棉花教育部工程研究中心/农业生物技术重点实验室中国农业科学院生物技术研究所

【目的】陆地棉（Gossypium hirsutum）的遗传转化技术存在转化周期长、转化效率低等问题，其中，愈伤组织增殖速度慢是导致棉花转化周期长的关键因素。探究陆地棉愈伤组织增殖的最适光照条件，为缩短棉花转化周期提供技术基础。【方法... 详细信息

【目的】陆地棉（Gossypium hirsutum）的遗传转化技术存在转化周期长、转化效率低等问题，其中，愈伤组织增殖速度慢是导致棉花转化周期长的关键因素。探究陆地棉愈伤组织增殖的最适光照条件，为缩短棉花转化周期提供技术基础。【方法】以陆地棉受体品种WC的下胚轴为外植体诱导愈伤组织，设置红光、蓝光、红蓝光（1﹕1）和白光（CK）4种不同光照处理，研究不同光质下愈伤组织的增殖速度、形态特征，以及相关基因表达水平和相关酶活性的差异，解析光照对愈伤组织增殖的影响并获得最优光照条件。【结果】不同光质对诱导棉花外植体出愈和愈伤组织生长具有明显影响。在4种不同光照处理下，红蓝光相较其他光质具有更显著地促进外植体出愈和愈伤组织增殖的效果，表现为愈伤组织分化时间更短，7—15 d，即与其他处理存在明显表型差异，7 d愈伤组织鲜重红蓝光（0.39 g）>蓝光（0.34 g）>白光（0.24 g）>红光（0.23 g）,15 d时，红蓝光（1.15 g）>蓝光（0.98 g）>白光（0.69 g）>红光（0.51 g），红蓝光照射下的愈伤组织鲜重是白光对照的1.65倍，比单一蓝光或红光照射下的愈伤组织鲜重增加16.5%或125.5%；与此相一致的是，红蓝光处理下，第二周的愈伤增殖率也最高，达14.67%，比红光处理（7.17%）增加1倍多。4种光质下，愈伤增殖及体胚再生相关基因的表达量，红蓝光处理均显示最高。此外，红蓝光处理下愈伤组织的过氧化氢酶（CAT）活性显著提高，活性氧（ROS）含量低于白光对照。【结论】不同光质条件下，棉花外植体的愈伤组织增殖速度不同，红蓝光（1﹕1）促进外植体出愈和愈伤增殖表现最优，其次为蓝光，再次为白光，单独的红光不利于棉花出愈和愈伤增殖。红蓝光（1﹕1）处理诱导光受体及其互作因子、愈伤增殖等相关基因的表达，增强愈伤组织内过氧化氢酶的活性，降低活性氧含量，促进细胞分裂，进而促进愈伤增殖。

关键词：陆地棉红光蓝光愈伤组织增殖速度活性氧

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A bioactive injectable self-healing anti-inflammatory hydrogel with ultralong extracellular vesicles release synergistically enhances motor functional recovery of spinal cord injury

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Bioactive Materials 2021年第8期6卷 2523-2534页

作者： Chenggui Wang Min Wang Kaishun Xia Jingkai Wang Feng Cheng Kesi Shi Liwei Ying Chao Yu Haibin Xu Shining Xiao chengzhen liang Fangcai Li Bo Lei Qixin Chen Department of Orthopedics Surgery 2nd Affiliated HospitalSchool of MedicineZhejiang UniversityHangzhou310009ZhejiangPR China Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research College of StomatologyFrontier Institute of Science and TechnologyXi’an Jiaotong UniversityXi’an710054PR China

The repair and motor functional recovery after spinal cord injury(SCI)remains a worldwide challenge.The inflammatory microenvironment is one of main obstacles on inhibiting the recovery of SCI.Using mesenchymal stem cells(MSCs)derived extracellular vesicles to replace MSCs transplantation and mimic cell paracrine secretions provides a potential strategy for microenvironment regulation.However,the effective preservation and controlled release of extracellular vesicles in the injured spinal cord tissue are still not satisfied.Herein,we fabricated an injectable adhesive anti-inflammatory F127-polycitrate-polyethyleneimine hydrogel(FE)with sustainable and long term extracellular vesicle release(FE@EVs)for improving motor functional recovery after SCI.The orthotopic injection of FE@EVs hydrogel could encapsulate extracellular vesicles on the injured spinal cord,thereby synergistically induce efficient integrated regulation through suppressing fibrotic scar formation,reducing inflammatory reaction,promoting remyelination and axonal regeneration.This study showed that combining extracellular vesicles into bioactive multifunctional hydrogel should have great potential in achieving satisfactory locomotor recovery of central nervous system diseases.

关键词： Bioactive biomaterials Multifunctional hydrogel Extracellular vesicles release Spinal cord injury repair

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Injectable kartogenin and apocynin loaded micelle enhances the alleviation of intervertebral disc degeneration by adipose-derived stem cell

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Bioactive Materials 2021年第10期6卷 3568-3579页

作者： Chao Yu Dongdong Li Chenggui Wang Kaishun Xia Jingkai Wang Xiaopeng Zhou Liwei Ying Jiawei Shu Xianpeng Huang Haibin Xu Bin Han Qixin Chen Fangcai Li Jianbin Tang chengzhen liang Nigel Slater Department of Orthopedics Surgery The Second Affiliated HospitalZhejiang University School of MedicineHangzhou CityZhejiang ProvincePR China Orthopedics Research Institute of Zhejiang University Hangzhou CityZhejiang ProvincePR China Key Laboratory of Motor System Disease Research and Precision Therapy of Zhejiang Province Hangzhou CityZhejiang ProvincePR China Key Laboratory of Biomass Chemical Engineering of Ministry of Education Center for Bionanoengineeringand College of Chemical and Biological EngineeringZhejiang UniversityHangzhouZhejiang310027China Department of Chemical Engineering and Biotechnology University of CambridgeCambridgeUnited Kingdom

Cell transplantation has been proved the promising therapeutic effects on intervertebral disc degeneration(IVDD).However,the increased levels of reactive oxygen species(ROS)in the degenerated region will impede the efficiency of human adipose-derived stem cells(human ADSCs)transplantation therapy.It inhibits human ADSCs proliferation,and increases human ADSCs apoptosis.Herein,we firstly devised a novel amphiphilic copolymer PEG-PAPO,which could self-assemble into a nanosized micelle and load lipophilic kartogenin(KGN),as a single complex(PAKM).It was an injectable esterase-responsive micelle,and showed controlled release ability of KGN and apocynin(APO).Oxidative stimulation promoted the esterase activity in human ADSCs,which accelerate degradation of esterase-responsive micelle.Compared its monomer,the PAKM micelle possessed better bioactivities,which were attributed to their synergistic effect.It enhanced the viability,autophagic activation(P62,LC3 II),ECM-related transcription factor(SOX9),and ECM(Collagen II,Aggrecan)maintenance in human ADSCs.Furthermore,it is demonstrated that the injection of PAKM with human ADSCs yielded higher disc height and water content in rats.Therefore,PAKM micelles perform promoting cell survival and differentiation effects,and may be a potential therapeutic agent for IVDD.

关键词： Intervertebral disc degeneration Polymer-drug conjugates Mesenchymal stem cell Reactive oxygen species Stem cell therapy

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Towards understanding abscisic acid-mediated leaf senescence

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Science China(Life Sciences) 2015年第5期58卷 506-508页

作者： liang chengzhen CHU Chengcai State Key Laboratory of Plant Genomics and National Center for Plant Gene Research (Beijing) Institute of Genetics and Developmental Biology Chinese Academy of Sciences

Senescence is a necessary part of most complex organisms that controlled by many complicated genetic programs.However,unlike animals and humans,leaf senescence has a great impact on nutrient recycling from source to s... 详细信息

关键词：叶片衰老脱落酸介导植物适应性组成部分遗传程序养分循环品质育种

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Impact assessment of genetically modified herbicide-tolerant cotton on arthropod communities

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Journal of Cotton Research 2022年第2期5卷 164-172页

作者： LI Dongyang ZHU Xiangzhen ZHANG Kaixin WANG Li ZHANG Rui liang chengzhen LUO Junyu CUI Jinjie State Key Laboratory of Cotton Biology Institute of Cotton ResearchChinese Academy of Agricultural SciencesAnyangHenan 455000 China Biotechnology Research Institute Chinese Academy of Agricultural SciencesBeijing 100081China.

Background:Cotton(Gossypium spp.)is one of the most important economic crops worldwide,and its production plays an important role in the economy of many countries.Genetically modified herbicide-tolerant(GMHT)crops,which were developed to minimize the losses caused by weeds,have gradually become the most widely adopted genetically modified crops in the world due to their economic and environmental benefits.However,the potential ecological and environmental risks of GMHT crops have attracted extensive attention and controversy.Arthropod communities form a promine nt part of the biodiversity of agroecosystems and are important indicators of environmental health.Elucidating the effects of GMHT crops on the diversity of arthropod communities is necessary to ensure the safety of GMHT crops.Result:In this 2-year study,we investigated the potential impact of GMHT crops on arthropod communities.The GMHT cotton variety GGK2 with glyphosate tolerance and its near-isogenic non-GMHT variety K312 were used for the experimental groups.The Shannon diversity index(H),Simpson diversity index(D),Pielou evenness index(J),and principal co-ordinates analysis(PCoA)of the Bray-Curtis distance were used to evaluate the population dynamics and biodiversity of arthropods in cotton fields.No significant differences were found between GGK2 and K312 in their total abundance of arthropod communities,and biodiversity indexes on most sampling dates.The arthropod composition in the GGK2 and K312 plots was similar.Sampling elates had a significant effect on biodiversity indexes,whereas no clear tendencies related to cotton variety or cotton variety x sampling elates interaction were recorded.In addition,PCoA revealed high similarity between the arthropod communities in the plots of the GMHT cotton variety GGK2 and its near-isogenic variety K312.Conclusion:There was no obvious difference in abundance,diversity indexes of arthropod communities between GMHT cotto n variety GGK2 and its near-isogenic variety K312 under the small-scale plan ting regime

关键词： GMHT crops Cotton Arthropod communities Biodiversity Diversity index PCoA

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