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Proteomic profiling of cerebrospinal fluid in pediatric myelin oligodendrocyte glycoprotein antibody-associated disease

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World Journal of Pediatrics 2024年第3期20卷 259-271页

作者： Yi-Long Wang Meng-Ying Zhu Zhe-Feng Yuan Xiao-Yan Ren Xiao-Tong guo Yi Hua Lu Xu Cong-Ying Zhao Li-Hua jiang Xin Zhang guo-Xia sheng Pei-Fang jiang Zheng-Yan Zhao Feng Gao Department of Neurology Children's HospitalZhejiang University School of MedicineHangzhou 310052China Children's Hospital Zhejiang University School of MedicineHangzhou 310052China Children's Hospital National Clinical Research Center for Child HealthZhejiang University School of MedicineHangzhou 310052China

Background Myelin oligodendrocyte glycoprotein(MOG)antibody-associated disease(MOGAD)is an autoimmune demy-elinating disorder of the central nervous system.Methods Extracted proteins from 34 cerebrospinal fluid(CSF)samples[patients with MOGAD(MOG group,n=12);healthy controls(HC group,n=12);patients with MOG seronegative and metagenomics next-generation sequencing-negative inflammatory neurological diseases(IND group,n=10)]were processed and subjected to label-free quantitative proteomics.Supervised partial least squares-discriminant analysis(PLS-DA)and orthogonal PLS-DA(O-PLS-DA)models were also performed based on proteomics data.Functional analysis of differentially expressed proteins(DEPs)was performed using Gene Ontology,InterPro,and Kyoto Encyclopedia Genes and Genomes.An enzyme-linked immunosorbent assay was used to determine the complement levels in serum from patients with MOGAD.Results Four hundred and twenty-nine DEPs(149 upregulated and 280 downregulated proteins)were identified in the MOG group compared to the HC group according to the P value and fold change(FC).Using the O-PLS-DA model,872 differentially abundant proteins were identified with variable importance projection(VIP)scores>1.Five proteins(gamma-glutamyl hydrolase,cathepsin F,interalpha-trypsin inhibitor heavy chain 5,latent transforming growth factor beta-binding protein 4 and leukocyte-associated immunoglobulin-like receptor 1)overlapping between the top 30 DEPs with top-ranked P value and FC and top 30 proteins in PLS-DA VIP lists were acquired.Functional analysis revealed that the dysregulated proteins in the MOG group were primarily involved in complement and coagulation cascades,cell adhesion,axon guidance,and glycosphingolipid biosynthesis compared to the HC group.Conclusion The proteomic alterations in CSF samples from children with MOGAD identified in the current study might provide opportunities for developing novel biomarker candidates.

关键词： Acute disseminated encephalomyelitis Cerebrospinal fluid Complement cascades Myelin oligodendrocyte glycoprotein-associated disease Proteomics

On the Strong Approximation for a Simple Reentrant Line in Light Traffic Under First-buffer First-served Service Discipline

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Acta Mathematicae Applicatae Sinica 2024年第3期40卷 823-839页

作者： Kai-ming YANG Yong-jiang guo School of Science Beijing University of Posts and TelecommunicationsBeijing 100876China

For a 2-station and 3-class reentrant line under first-buffer first-served(FBFS)service discipline in light traffic,we firstly construct the strong approximations for performance measures including the queue length,workload,busy time and idle time processes.Based on the obtained strong approximations,we use a strong approximation method to find all the law of the iterated logarithms(LILs)for the above four performance measures,which are expressed as some functions of system parameters:means and variances of interarrival and service times,and characterize the fluctuations around their fluid approximations.

关键词： reentrant line queueing network FBFS service discipline strong approximation LIL Brownian motion

Designing salt stress-resilient crops:Current progress and future challenges

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Journal of Integrative Plant Biology 2024年第3期66卷 303-329页

作者： Xiaoyan Liang Jianfang Li Yongqing Yang Caifu jiang Yan guo State Key Laboratory of Plant Environmental Resilience College of Biological SciencesChina Agricultural UniversityBeijing 100094China State Key Laboratory of Nutrient Use and Management College of Resources and Environmental SciencesChina Agricultural UniversityBeijing 100194China Center for Crop Functional Genomics and Molecular Breeding China Agricultural UniversityBeijing 100094China Frontiers Science Center for Molecular Design Breeding China Agricultural UniversityBeijing 100193China

Excess soil salinity affects large regions of land and is a major hindrance to crop production worldwide.Therefore,understanding the molecular mechanisms of plant salt tolerance has scientific importance and practical significance.In recent decades,studies have characterized hundreds of genes associated with plant responses to salt stress in different plant species.These studies have substantially advanced our molecular and genetic understanding of salt tolerance in plants and have introduced an era of molecular design breeding of salt-tolerant crops.This review summarizes our current knowledge of plant salt tolerance,emphasizing advances in elucidating the molecular mechanisms of osmotic stress tolerance,salt-ion transport and compartmentalization,oxidative stress tolerance,alkaline stress tolerance,and the trade-off between growth and salt tolerance.We also examine recent advances in understanding natural variation in the salt tolerance of crops and discuss possible strategies and challenges for designing salt stress-resilient crops.We focus on the model plant Arabidopsis(Arabidopsis thaliana)and the four most-studied crops:rice(Oryza sativa),wheat(Triticum aestivum),maize(Zea mays),and soybean(Glycine max).

关键词： molecular design breeding salt stress-resilient crop salt tolerance

Exploiting sound for emerging applications of extracellular vesicles

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Nano Research 2024年第2期17卷 462-475页

作者： Zhuhao Wu Hongwei Cai Chunhui Tian Zheng Ao Lei jiang Feng guo Department of Intelligent Systems Engineering Indiana UniversityBloomingtonIN 47405USA

Extracellular vesicles are nano-to micro-scale,membrane-bound particles released by cells into extracellular space,and act as carriers of biomarkers and therapeutics,holding promising potential in translational medicine.However,the challenges remain in handling and detecting extracellular vesicles for disease diagnosis as well as exploring their therapeutic capability for disease treatment.Here,we review the recent engineering and technology advances by leveraging the power of sound waves to address the challenges in diagnostic and therapeutic applications of extracellular vesicles and biomimetic nanovesicles.We first introduce the fundamental principles of sound waves for understanding different acoustic-assisted extracellular vesicle technologies.We discuss the acoustic-assisted diagnostic methods including the purification,manipulation,biosensing,and bioimaging of extracellular vesicles.Then,we summarize the recent advances in acoustically enhanced therapeutics using extracellular vesicles and biomimetic nanovesicles.Finally,we provide perspectives into current challenges and future clinical applications of the promising extracellular vesicles and biomimetic nanovesicles powered by sound.

关键词： extracellular vesicles exosomes biomimetic nanovesicles acoustics disease diagnostics therapeutics

Traditional Chinese medicine for the treatment of immune-related nephropathy:A review

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Acta Pharmaceutica Sinica B 2024年第1期14卷 38-66页

作者： Pu jiang Changliang Yao De-an guo School of Pharmacy Nanjing University of Chinese MedicineNanjing 210023China Shanghai Research Center for Modernization of Traditional Chinese Medicine National Engineering Research Center of TCM Standardization TechnologyShanghai Institute of Materia MedicaChinese Academy of SciencesShanghai 201203China

Immune-related nephropathy(IRN)refers to immune-response-mediated glomerulonephritis and is the main cause of end-stage renal failure.The pathogenesis of IRN is not fully understood;therefore,treatment is challenging.Traditional Chinese medicines(TCMs)have potent clinical effects in the treatment of the IRN conditions immunoglobulin A nephropathy,lupus nephropathy,and diabetic nephropathy.The underlying mechanisms mainly include its inhibition of inflammation;improvements to renal interstitial fibrosis,oxidative stress,autophagy,apoptosis;and regulation of immunity.In this review,we summarize the clinical symptoms of the three IRN subtypes and the use of TCM prescriptions,herbs,and bioactive compounds in treating IRN,as well as the potential mechanisms,intending to provide a reference for the future study of TCM as IRN treatments.

关键词： IgA nephropathy Diabetic nephropathy Lupus nephritis Traditional Chinese medicine Immunity Pathogenesis Mechanism Pathophysiology

Mechanical Modeling and Analysis of Stability Deterioration of Production Well During Marine Hydrate Depressurization Production

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China Ocean Engineering 2024年第2期38卷 338-351页

作者： SUN Huan-zhao CHANG Yuan-jiang SUN Bao-jiang WANG Kang CHEN guo-ming LI Hao DAI Yong-guo Centre for Offshore Engineering and Safety Technology China University of Petroleum(East China)Qingdao 266580China School of Petroleum Engineering China University of Petroleum(East China)Qingdao 266580China jiangsu Shuguang Oil Tools Co. LtdTaizhou 225532China

Different from oil and gas production,hydrate reservoirs are shallow and unconsolidated,whose mechanical properties deteriorate with hydrate decomposition.Therefore,the formations will undergo significant subsidence during depressurization,which will destroy the original force state of the production well.However,existing research on the stability of oil and gas production wells assumes the formation to be stable,and lacks consideration of the force exerted on the hydrate production well by formation subsidence caused by hydrate decomposition during production.To fill this gap,this paper proposes an analytical method for the dynamic evolution of the stability of hydrate production well considering the effects of hydrate decomposition.Based on the mechanical model of the production well,the basis for stability analysis has been proposed.A multi-field coupling model of the force state of the production well considering the effect of hydrate decomposition and formation subsidence is established,and a solver is developed.The analytical approach is verified by its good agreement with the results from the numerical method.A case study found that the decomposition of hydrate will increase the pulling-down force and reduce the supporting force,which is the main reason for the stability deterioration.The higher the initial hydrate saturation,the larger the reservoir thickness,and the lower the production pressure,the worse the stability or even instability.This work can provide a theoretical reference for the stability maintaining of the production well.

关键词： natural gas hydrate production well depressurization production formation deformation stability deterioration

The lysine methyltransferase SMYD2 facilitates neointimal hyperplasia by regulating the HDAC3-SRF axis

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Acta Pharmaceutica Sinica B 2024年第2期14卷 712-728页

作者： Xiaoxuan Zhong Xiang Wei Yan Xu Xuehai Zhu Bo Huo Xian guo Gaoke Feng Zihao Zhang Xin Feng Zemin Fang Yuxuan Luo Xin Yi Ding-sheng jiang Division of Cardiovascular Surgery Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030China Key Laboratory of Organ Transplantation Ministry of EducationNHC Key Laboratory of Organ TransplantationChinese Academy of Medical SciencesWuhan 430030China School of Life Science and Technology Key Laboratory of Developmental Genes and Human DiseaseSoutheast UniversityNanjing 210096China Department of Cardiology Renmin Hospital of Wuhan UniversityWuhan 430060China

Coronary restenosis is an important cause of poor long-term prognosis in patients with coronary heart disease.Here,we show that lysine methyltransferase SMYD2 expression in the nucleus is significantly elevated in serum-and PDGF-BB-induced vascular smooth muscle cells(VSMCs),and in tissues of carotid artery injury-induced neointimal hyperplasia.Smyd2 overexpression in VSMCs(Smyd2-vTg)facilitates,but treatment with its specific inhibitor LLY-507 or SMYD2 knockdown significantly inhibits VSMC phenotypic switching and carotid artery injury-induced neointima formation in mice.Transcriptome sequencing revealed that SMYD2 knockdown represses the expression of serum response factor(SRF)target genes and that SRF overexpression largely reverses the inhibitory effect of SMYD2 knockdown on VSMC proliferation.HDAC3 directly interacts with and deacetylates SRF,which enhances SRF transcriptional activity in VSMCs.Moreover,SMYD2 promotes HDAC3 expression via tri-methylation of H3K36 at its promoter.RGFP966,a specific inhibitor of HDAC3,not only counteracts the pro-proliferation effect of SMYD2 overexpression on VSMCs,but also inhibits carotid artery injury-induced neointima formation in mice.HDAC3 partially abolishes the inhibitory effect of SMYD2 knockdown on VSMC proliferation in a deacetylase activity-dependent manner.Our results reveal that the SMYD2-HDAC3-SRF axis constitutes a novel and critical epigenetic mechanism that regulates VSMC phenotypic switching and neointimal hyperplasia.

关键词： Neointimaformation Histonemethylation Histoneacetylation SRFacetylation SMYD2 HDAC3 LLY-507 RGFP966

Targeting the adenosine A2A receptor for neuroprotection and cognitive improvement in traumatic brain injury and Parkinson's disease

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Chinese Journal of Traumatology 2024年第3期27卷 125-133页

作者： Yan Zhao Yuan-guo Zhou jiang-Fan Chen Department of Army Occupational Disease State Key Laboratory of TraumaBurns and Combined InjuryResearch Institute of SurgeryDaping HospitalArmy Medical University.Chongqing400042China The Molecular Neuropharmacology Laboratory and the Eye-Brain Research Center The State Key Laboratory of OphthalmologyOptometry and Vision ScienceWenzhou Medical UniversityWenzhou325035Zhejiang ProvinceChina Oujiang Laboratory(Zhejiang Lab for Regenerative Medicine Vision and Brain Health)Wenzhou325035Zhejiang ProvinceChina

Adenosine exerts its dual functions of homeostasis and neuromodulation in the brain by acting at mainly 2 G-protein coupled receptors,called A1 and A2A receptors.The adenosine A2A receptor(A2AR)antagonists have been clinically pursued for the last 2 decades,leading to final approval of the istradefylline,an A2AR antagonist,for the treatment of OFF-Parkinson's disease(PD)patients.The approval paves the way to develop novel therapeutic methods for A2AR antagonists to address 2 major unmet medical needs in PD and traumatic brain injury(TBI),namely neuroprotection or improving cognition.In this review,we first consider the evidence for aberrantly increased adenosine signaling in PD and TBI and the sufficiency of the increased A2AR signaling to trigger neurotoxicity and cognitive impairment.We further discuss the increasing preclinical data on the reversal of cognitive deficits in PD and TBI by A2AR antagonists through control of degenerative proteins and synaptotoxicity,and on protection against TBI and PD pathologies by A2AR antagonists through control of neuroinflammation.Moreover,we provide the supporting evidence from multiple human prospective epidemiological studies which revealed an inverse relation between the consumption of caffeine and the risk of developing PD and cognitive decline in aging population and Alzheimer's disease patients.Collectively,the convergence of clinical,epidemiological and experimental evidence supports the validity of A2AR as a new therapeutic target and facilitates the design of A2AR antagonists in clinical trials for disease-modifying and cognitive benefit in PD and TBI patients.

关键词： Receptor,Adenosine A2A Adenosine A2 receptor antagonists Parkinson's disease Brain injuries,traumatic

Ergodicity of 3D Stochastic Burgers Equation

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Acta Mathematica Sinica,English Series 2024年第2期40卷 498-510页

作者： Zhao DONG jiang Lun WU guo Li ZHOU RCSDS Academy of Mathematics and Systems ScienceChinese Academy of SciencesBeijing 100190P.R.China Department of Mathematics Computational FoundrySwansea UniversitySwansea SA18ENUK College of Mathematics and Statistics Chongqing UniversityChongqing 400044P.R.China

3D Burgers equation is an important model for turbulence.It is natural to expect the long-time behaviour for this hydrodynamics equation.However,there is no result about the long-time behaviour for this deterministic model.Surprisingly,if the system is perturbed by stochastic noise,we establish the existence and uniqueness of invariant measure for 3D stochastic Burgers equation.

关键词： 3D stochastic Burgers equations maximum principle ergodicity