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Small extracellular vesicles from hypoxia-preconditioned bone marrow mesenchymal stem cells attenuate spinal cord injury via miR-146a-5p-mediated regulation of macrophage polarization

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Neural Regeneration Research 2024年第10期19卷 2259-2269页

作者： Zeyan Liang Zhelun Yang Haishu Xie Jian Rao Xiongjie Xu Yike Lin Chunhua Wang chunmei chen Department of Neurosurgery Fujian Medical University Union HospitalFuzhouFujian ProvinceChina Fujian Neurosurgical Institute FuzhouFujian ProvinceChina

Spinal cord injury is a disabling condition with limited treatment options.Multiple studies have provided evidence suggesting that small extracellular vesicles(SEVs)secreted by bone marrow mesenchymal stem cells(MSCs)help mediate the beneficial effects conferred by MSC transplantation following spinal cord injury.Strikingly,hypoxia-preconditioned bone marrow mesenchymal stem cell-derived SEVs(HSEVs)exhibit increased therapeutic potency.We thus explored the role of HSEVs in macrophage immune regulation after spinal cord injury in rats and their significance in spinal cord repair.SEVs or HSEVs were isolated from bone marrow MSC supernatants by density gradient ultracentrifugation.HSEV administration to rats via tail vein injection after spinal cord injury reduced the lesion area and attenuated spinal cord inflammation.HSEVs regulate macrophage polarization towards the M2 phenotype in vivo and in vitro.Micro RNA sequencing and bioinformatics analyses of SEVs and HSEVs revealed that mi R-146a-5p is a potent mediator of macrophage polarization that targets interleukin-1 receptor-associated kinase 1.Reducing mi R-146a-5p expression in HSEVs partially attenuated macrophage polarization.Our data suggest that HSEVs attenuate spinal cord inflammation and injury in rats by transporting mi R-146a-5p,which alters macrophage polarization.This study provides new insights into the application of HSEVs as a therapeutic tool for spinal cord injury.

关键词： bone marrow mesenchymal stem cells hypoxia preconditioning interleukin-1 receptor-associated kinase 1 macrophages mesenchymal stem cells small extracellular vesicles spinal cord injury

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Interplay between microglia and environmental risk factors in Alzheimer's disease

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Neural Regeneration Research 2024年第8期19卷 1718-1727页

作者： Miaoping Zhang chunmei Liang Xiongjin chen Yujie Cai Lili Cui Guangdong Key Laboratory of Age-Related Cardiac and Cerebral Diseases Affiliated Hospital of Guangdong Medical UniversityZhanjiangGuangdong ProvinceChina

Alzheimer s disease,among the most common neurodegenerative disorders,is chara cterized by progressive cognitive impairment.At present,the Alzheimer’s disease main risk remains genetic ris ks,but major environmental fa ctors are increasingly shown to impact Alzheimer’s disease development and progression.Microglia,the most important brain immune cells,play a central role in Alzheimer’s disease pathogenesis and are considered environmental and lifestyle"sensors."Factors like environmental pollution and modern lifestyles(e.g.,chronic stress,poor dietary habits,sleep,and circadian rhythm disorde rs)can cause neuroinflammato ry responses that lead to cognitive impairment via microglial functioning and phenotypic regulation.However,the specific mechanisms underlying interactions among these facto rs and microglia in Alzheimer’s disease are unclear.Herein,we:discuss the biological effects of air pollution,chronic stress,gut micro biota,sleep patterns,physical exercise,cigarette smoking,and caffeine consumption on microglia;consider how unhealthy lifestyle factors influence individual susceptibility to Alzheimer’s disease;and present the neuroprotective effects of a healthy lifestyle.Toward intervening and controlling these environmental risk fa ctors at an early Alzheimer’s disease stage,understanding the role of microglia in Alzheimer’s disease development,and to rgeting strategies to to rget microglia,co uld be essential to future Alzheimer’s disease treatments.

关键词： Alzheimer’s disease chronic stress environmental factor gut microbiota microglia particulate matter with diameter<2.5μm

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A hybrid CNN-LSTM model for diagnosing rice nutrient levels at the rice panicle initiation stage

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Journal of Integrative Agriculture 2024年第2期23卷 711-723页

作者： Fubing Liao Xiangqian Feng Ziqiu Li Danying Wang chunmei Xu Guang Chu Hengyu Ma Qing Yao Song chen School of Computer Science and Technology Zhejiang Sci-Tech UniversityHangzhou 310018China China National Rice Research Institute Chinese Academy of Agricultural SciencesHangzhou 310006China School of Agriculture Yangtze UniversityJingzhou 434025China

Nitrogen(N)and potassium(K)are two key mineral nutrient elements involved in rice growth.Accurate diagnosis of N and K status is very important for the rational application of fertilizers at a specific rice growth stage.Therefore,we propose a hybrid model for diagnosing rice nutrient levels at the early panicle initiation stage(EPIS),which combines a convolutional neural network(CNN)with an attention mechanism and a long short-term memory network(LSTM).The model was validated on a large set of sequential images collected by an unmanned aerial vehicle(UAV)from rice canopies at different growth stages during a two-year experiment.Compared with VGG16,AlexNet,GoogleNet,DenseNet,and inceptionV3,ResNet101 combined with LSTM obtained the highest average accuracy of 83.81%on the dataset of Huanghuazhan(HHZ,an indica cultivar).When tested on the datasets of HHZ and Xiushui 134(XS134,a japonica rice variety)in 2021,the ResNet101-LSTM model enhanced with the squeeze-and-excitation(SE)block achieved the highest accuracies of 85.38 and 88.38%,respectively.Through the cross-dataset method,the average accuracies on the HHZ and XS134 datasets tested in 2022 were 81.25 and 82.50%,respectively,showing a good generalization.Our proposed model works with the dynamic information of different rice growth stages and can efficiently diagnose different rice nutrient status levels at EPIS,which are helpful for making practical decisions regarding rational fertilization treatments at the panicle initiation stage.

关键词： dynamic model of deep learning UAV rice panicle initiation nutrient level diagnosis image classification

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On-line Recognition of Abnormal Patterns in Bivariate Autocorrelated Process Using Random Forest

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Computers, Materials & Continua 2022年第10期73卷 1707-1722页

作者： Miao Xu Bo Zhu chunmei chen Yuwei Wan College of Mechanical and Electrical Engineering Kunming University of Science&TechnologyKunming650500China School of Engineering Cardiff UniversityCardiffCF243AAUK

It is not uncommon that two or more related process quality characteristics are needed to be monitored simultaneously in production process for most of time.Meanwhile,the observations obtained online are often serially autocorrelated due to high sampling frequency and process dynamics.This goes against the statistical I.I.D assumption in using the multivariate control charts,which may lead to the performance of multivariate control charts collapse soon.Meanwhile,the process control method based on pattern recognition as a non-statistical approach is not confined by this limitation,and further provide more useful information for quality practitioners to locate the assignable causes led to process abnormalities.This study proposed a pattern recognition model using Random Forest(RF)as pattern model to detect and identify the abnormalities in bivariate autocorrelated process.The simulation experiment results demonstrate that the model is superior on recognition accuracy(RA)(97.96%)to back propagation neural networks(BPNN)(95.69%),probability neural networks(PNN)(94.31%),and support vector machine(SVM)(97.16%).When experimenting with simulated dynamic process data flow,the model also achieved better average running length(ARL)and standard deviation of ARL(SRL)than those of the four comparative approaches in most cases of mean shift magnitude.Therefore,we get the conclusion that the RF model is a promising approach for detecting abnormalities in the bivariate autocorrelated process.Although bivariate autocorrelated process is focused in this study,the proposed model can be extended to multivariate autocorrelated process control.

关键词： Random Forest bivariate autocorrelated process pattern recognition average run length

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Morphological evolution and flow conduction characteristics of fracture channels in fractured sandstone under cyclic loading and unloading

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International Journal of Mining Science and Technology 2023年第12期33卷 1527-1540页

作者： Quanle Zou Zihan chen Jinfei Zhan chunmei chen Shikang Gao Fanjie Kong Xiaofeng Xia State Key Laboratory of Coal Mine Disaster Dynamics and Control School of Resources and Safety EngineeringChongqing UniversityChongqing 400044China School of Mining Guizhou UniversityGuiyang 550025China

In coal mining,rock strata are fractured under cyclic loading and unloading to form fracture channels.Fracture channels are the main flow narrows for gas.Therefore,expounding the flow conductivity of fracture channels in rocks on fluids is significant for gas flow in rock strata.In this regard,graded incremental cyclic loading and unloading experiments were conducted on sandstones with different initial stress levels.Then,the three-dimensional models for fracture channels in sandstones were established.Finally,the fracture channel percentages were used to reflect the flow conductivity of fracture channels.The study revealed how the particle size distribution of fractured sandstone affects the formation and expansion of fracture channels.It was found that a smaller proportion of large blocks and a higher proportion of small blocks after sandstone fails contribute more to the formation of fracture channels.The proportion of fracture channels in fractured rock can indicate the flow conductivity of those channels.When the proportion of fracture channels varies gently,fluids flow evenly through those channels.However,if the proportion of fracture channels varies significantly,it can greatly affect the flow rate of fluids.The research results contribute to revealing the morphological evolution and flow conductivity of fracture channels in sandstone and then provide a theoretical basis for clarifying the gas flow pattern in the rock strata of coal mines.

关键词： CT imaging Flow conductivity Three-dimensional reconstruction Proportion of fracture channels Cyclic loading and unloading

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Efect of the Gad system on Actinobacillus succinogenes during acid stress

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Systems Microbiology and Biomanufacturing 2022年第1期2卷 177-185页

作者： chunmei chen Qun Zhang Junzhu Qian Dan Wu Pengcheng chen Pu Zheng The Key Laboratory of Industrial Biotechnology Ministry of EducationSchool of BiotechnologyJiangnan UniversityWuxi 214122China

The glutamate decarboxylase(Gad)system is an important amino acid-dependent acid resistance system commonly found in microorganisms.Actinobacillus succinogenes is one of the best natural producers of succinic acid(SA)but lacks glutamate decarboxylase.This study assessed the efects of Gad system introduction into A.succinogenes.The recombinant strains gadB-SW and gadBC-SW were constructed by heterologous expression of gadB alone,or gadB together with gadC,respectively.After 1.0 and 1.5 h of acid stress at pH 4.6,cell survival of gadBC-SW was greater than gadB-SW.The growth of gadB-SW and gadBC-SW was both afected by the expression of heterologous proteins and byγ-aminobutyric acid,with gadBC-SW growth reduced at a neutral pH.SA production in acidic conditions was evaluated by a shake fask and by 3-L bioreactor fermentation.The results showed gadBC-SW to increase SA production by 8.4%in shake fask compared to the parent strain,SW.For a 3-L bioreactor batch fermentation under acidic environment,the highest conversion rate of sugar to SA was observed for gadBC-SW,reaching 96%.However,SA concentration by gadBC-SW was only 47 g/L and 31 g/L at pH 6.5 and pH 6.0,respectively.In summary,the introduction of heterologous gadB and gadC into A.succinogenes not only improved acid tolerance but also infuenced the synthesis of SA and added a metabolic burden.

关键词： Actinobacillus succinogenes Acid stress Glutamate decarboxylase Succinic acid Glutamate

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miRNA-148b-3p targeting SOCS3 inhibits macrophage M2 polarization by JAK2/STAT3 pathway in immune thrombocytopenia

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BIOCELL 2022年第5期46卷 1319-1328页

作者： YANG YANG LIJUAN FU chunmei chen MEIWEI HU Department of Hematology The Second Hospital Affiliated to Zhejiang Chinese Medical UniversityHangzhou310005China

Aberrant expression of miRNAs is significantly correlated with the occurrence of immune thrombocytopenic purpura(ITP).The immune imbalance of M1/M2 macrophage contributes to the development of ITP.However,the role of miR-148b-3p in macrophage phenotype imbalance remains unknown in ITP.In this study,we aimed to explore whether miR-148b-3p inhibits M2 macrophage polarization in ITP and to investigate the underlying mechanism.Peripheral blood from 22 ITP patients were collected,and real-time PCR confirmed that miR-148b-3p was upregulated and Western blot analyses detected the expression of SOCS3 was down-regulated.Subsequent dualluciferase reporter gene assay indicated that miR-148b-3p could bind to SOCS3.Furthermore,we found significant correlation between miR-148b-3p expression and platelet count.Applying gain and lose the function experiments of miR-148b-3p and SOCS3,we demonstrated that suppression of miR-148b-3p or up-regulation of SOCS3 promoted macrophage M2 polarization by inhibiting JAK2/STAT3 pathway.Together,our findings demonstrate that that miR-148b-3p targeting SOCS3 inhibits M2 macrophage polarization via JAK2/STAT3 signaling in ITP.

关键词： ITP miR-148b Macrophage SOCS3

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Mesenchymal stem cell-derived extracellular vesicles therapy in traumatic central nervous system diseases:a systematic review and meta-analysis

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Neural Regeneration Research 2023年第11期18卷 2406-2412页

作者： Zhelun Yang Zeyan Liang Jian Rao Fabin Lin Yike Lin Xiongjie Xu Chunhua Wang chunmei chen Department of Neurosurgery Fujian Medical University Union HospitalFuzhouFujian ProvinceChina

Although there are challenges in treating traumatic central nervous system diseases,mesenchymal stem cell-de rived extracellular vesicles(MSC-EVs) have recently proven to be a promising non-cellular the rapy.We comprehensively evaluated the efficacy of mesenchymal stem cell-de rived extracellular vesicles in traumatic central nervous system diseases in this meta-analysis based on preclinical studies.Our meta-analysis was registered at PROSPERO(CRD42022327904,May 24,2022).To fully retrieve the most relevant articles,the following databases were thoro ughly searched:PubMed,Web of Science,The Cochrane Library,and Ovid-Embase(up to April 1,2022).The included studies were preclinical studies of mesenchymal stem cell-derived extracellular vesicles for traumatic central nervous system diseases.The Systematic Review Centre for Laboratory Animal Experimentation(SYRCLE)’s risk of bias tool was used to examine the risk of publication bias in animal studies.After screening 2347studies,60 studies were included in this study.A meta-analysis was conducted for spinal co rd injury(n=52) and traumatic brain injury(n=8).The results indicated that mesenchymal stem cell-derived extracellular vesicles treatment prominently promoted motor function recovery in spinal co rd injury animals,including rat Basso,Beattie and Bresnahan locomotor rating scale scores(standardized mean difference [SMD]:2.36,95% confidence interval [CI]:1.96-2.76,P <0.01,I2=71%) and mouse Basso Mouse Scale scores(SMD=2.31,95% CI:1.57-3.04,P=0.01,I2=60%) compared with controls.Further,mesenchymal stem cell-de rived extracellular vesicles treatment significantly promoted neurological recovery in traumatic brain injury animals,including the modified N eurological Severity Score(SMD=-4.48,95% CI:-6.12 to-2.84,P <0.01,I2=79%) and Foot Fault Test(SMD=-3.26,95% CI:-4.09 to-2.42,P=0.28,I2=21%) compared with controls.Subgroup analyses showed that characteristics may be related to the therapeutic effect of mesenchymal stem cell-de rived extra cellular vesicles.For Basso,Bea

关键词： animals central nervous system diseases extracellular vesicles mesenchymal stromal cell meta-analysis spinal cord injury traumatic brain injury

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Natural Sesquiterpenoids, Diterpenoids, Sesterterpenoids, and Triterpenoids with Intriguing Structures from 2017 to 2022

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Chinese Journal of Chemistry 2023年第22期41卷 3115-3132页

作者： Xiaotian Zhang Meijia Zheng Aimin Fu Qin Li chunmei chen Hucheng Zhu Yonghui Zhang Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation School of PharmacyTongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubei 430030China

This review covers the isolation,structural determination,plausible biosynthetic pathways,and biological activities of 166 natural terpenoids including 57 sesquiterpenoids,65 diterpenoids,15 sesterterpenoids,and 29 tr... 详细信息

关键词： Sesquiterpenoids Diterpenoids Sesterterpenoids Triterpenoids Structura scaffolds Biosynthetic pathways Structure elucidation Drug discovery

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Chemistry,Biosynthesis,and Biological Activity of Halogenated Compounds Produced by Marine Microorganisms

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Chinese Journal of Chemistry 2022年第14期40卷 1729-1750,I0002页

作者： Jiamin Wang Xiaoyan Pang chunmei chen chenghai Gao Xuefeng Zhou Yonghong Liu Xiaowei Luo CAS Key Laboratory of Tropical Marine Bio-resources and Ecology/Guangdong Key Laboratory of Marine Materia Medica South China Sea Institute of OceanologyChinese Academyof SciencesGuangzhouGuangdong 510301China Institute of Marine Drugs Guangxi University of Chinese MedicineNanningGuangxi 530200China Southern Marine Science and Engineering Guangdong Laboratory(Guangzhou) GuangzhouGuangdong 511458China University of Chinese Academy of Sciences 19Yuquan RoadBejing 100049China

Natural products derived from marine microorganisms have been received great attention as a potential source of new compound entities for drug discovery.The unique marine environment brings us a large group of halogen-containing natural products with abundant biological functionality and good drugability.Meanwhile,biosynthetically halogenated reactions are known as a significant strategy used to increase the pharmacological activities and pharmacokinetic properties of compounds.Given that a tremendous increase in the number of new halogenated compounds from marine microorganisms in the last five years,it is necessary to summarize these compounds with their diverse structures and promising bioactivities.In this review,we have summarized the chemistry,biosynthesis(related halogenases),and biological activity of a total of 316 naturally halogenated compounds from marine microorganisms covering the period of 2015 to May 2021.Those reviewed chlorinated and brominated compounds with the ratio of 9:1 were predominantly originated from 36 genera of fungi(62%)and 9 bacterial strains(38%)with cytotoxic,antibacterial,and enzyme inhibitory activities,structural types of which are polyketides(38%),alkaloids(27%),phenols(11%),and others.This review would provide a plenty variety of promising lead halogenated compounds for drug discovery and inspire the development of new pharmaceutical agents.

关键词： Marine microorganisms Natural products Halogenated compounds Biological activity Biosynthesis

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