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Gut liver brain axis in diseases:the implications for therapeutic interventions

Signal Transduction and Targeted Therapy 2024年第1期9卷 79-104页

作者： mengyao Yan Shuli Man Benyue sun Long Ma Lanping Guo Luqi Huang Wenyuan Gao State Key Laboratory of Food Nutrition and Safety Key Laboratory of Industrial MicrobiologyMinistry of EducationTianjin Key Laboratory of Industry MicrobiologyNational and Local United Engineering Lab of Metabolic Control Fermentation TechnologyChina International Science and Technology Cooperation Base of Food Nutrition/Safety and Medicinal ChemistryCollege of BiotechnologyTianjin University of Science&Technology300457 TianjinChina National Resource Center for Chinese Materia Medica China Academy of Chinese Medical Sciences100700 BeijingChina Tianjin Key Laboratory for Modern Drug Delivery&High-Efficiency School of Pharmaceutical Science and TechnologyTianjin UniversityWeijin Road300072 TianjinChina

Gut-liver-brain axis is a three-way highway of information interaction system among the gastrointestinal tract,liver,and nervous systems.In the past few decades,breakthrough progress has been made in the gut liver brain axis,mainly through understanding its formation mechanism and increasing treatment strategies.In this review,we discuss various complex networks including barrier permeability,gut hormones,gut microbial metabolites,vagus nerve,neurotransmitters,immunity,brain toxic metabolites,β-amyloid(Aβ)metabolism,and epigenetic regulation in the gut-liver-brain axis.Some therapies containing antibiotics,probiotics,prebiotics,synbiotics,fecal microbiota transplantation(FMT),polyphenols,low FODMAP diet and nanotechnology application regulate the gut liver brain axis.Besides,some special treatments targeting gut-liver axis include farnesoid X receptor(FXR)agonists,takeda G protein-coupled receptor 5(TGR5)agonists,glucagon-like peptide-1(GLP-1)receptor antagonists and fibroblast growth factor 19(FGF19)analogs.Targeting gut-brain axis embraces cognitive behavioral therapy(CBT),antidepressants and tryptophan metabolism-related therapies.Targeting liver-brain axis contains epigenetic regulation and Aβmetabolism-related therapies.In the future,a better understanding of gut-liver-brain axis interactions will promote the development of novel preventative strategies and the discovery of precise therapeutic targets in multiple diseases.

关键词： metabolism therapeutic immunity

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The deteriorated degradation resistance of Mg alloy microtubes for vascular stent under the coupling effect of radial compressive stress and dynamic medium

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Journal of Magnesium and Alloys 2024年第2期12卷 573-585页

作者： mengyao Liu Yabo Zhang Qingyuan Zhang Yan Wang Di Mei Yufeng sun Liguo Wang Shijie Zhu Shaokang Guan School of Materials Science and Engineering Zhengzhou UniversityZhengzhou 450001China Henan Key Laboratory of Advanced Magnesium Alloys Zhengzhou 450002China Key Laboratory of Advanced Materials Processing&Mold Ministry of Education Zhengzhou 450002China

The degradation of Mg alloys relates to the service performance of Mg alloy biodegradable implants.In order to investigate the degradation behavior of Mg alloys as vascular stent materials in the near service environment,the hot-extruded fine-grained Mg-Zn-Y-Nd alloy microtubes,which are employed to manufacture vascular stents,were tested under radial compressive stress in the dynamic Hanks'Balanced Salt Solution(HBSS).The results revealed that the high flow rate accelerates the degradation of Mg alloy microtubes and its degradation is sensitive to radial compressive stress.These results contribute to understanding the service performance of Mg alloys as vascular stent materials.

关键词： Mg alloy Microtubes Degradation behavior Radial compressive stress Dynamic conditions

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Multimodal Nature of the Single-cell Primate Brain Atlas:Morphology,Transcriptome,Electrophysiology,and Connectivity

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Neuroscience Bulletin 2024年第4期40卷 517-532页

作者： Yuhui Shen Mingting Shao Zhao-Zhe Hao mengyao Huang Nana Xu Sheng Liu State Key Laboratory of Ophthalmology Zhongshan Ophthalmic CenterSun Yat-sen UniversityGuangdong Provincial Key Laboratory of Ophthalmology and Visual ScienceGuangzhou510060China Guangdong Province Key Laboratory of Brain Function and Disease Guangzhou510080China

Primates exhibit complex brain structures that augment cognitive function.The neocortex fulfills high-cognitive functions through billions of connected neurons.These neurons have distinct transcriptomic,morphological,and electrophysiological properties,and their connectivity principles vary.These features endow the primate brain atlas with a multimodal nature.The recent integration of next-generation sequencing with modified patch-clamp techniques is revolutionizing the way to census the primate neocortex,enabling a multimodal neuronal atlas to be established in great detail:(1)single-cell/single-nucleus RNA-seq technology establishes high-throughput transcriptomic references,covering all major transcriptomic cell types;(2)patch-seq links the morphological and electrophysiological features to the transcriptomic reference;(3)multicell patch-clamp delineates the principles of local connectivity.Here,we review the applications of these technologies in the primate neocortex and discuss the current advances and tentative gaps for a comprehensive understanding of the primate neocortex.

关键词： Neuron Brain atlas Patch-seq Connectivity Primate

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Multi-omics analyses of G6PD deficiency variants in Chinese population

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Journal of Genetics and Genomics 2024年第1期51卷 100-104页

作者： He Ji Jiahuan Chen Peide Huang Zhimin Feng Weining Hu mengyao Dai Xiaohui sun Xiao Jin Guangquan Chen Guang Ning Lin Li Weiqing Wang Yanan Cao Department of Endocrine and Metabolic Diseases Shanghai Institute of Endocrine and Metabolic DiseasesNational Clinical Research Centre for Metabolic DiseasesState Key Laboratory of Medical GenomicsResearch Unit of Clinical and Basic Research on Metabolic Diseases of Chinese Academy of Medical SciencesRuijin Yangtze River Delta Health InstituteWuxi Branch of Ruijin HospitalRuijin HospitalShanghai Jiao Tong University School of MedicineShanghai 200025China National Research Center for Translational Medicine National Key Scientific Infrastructure for Translational MedicineShanghai Jiao Tong UniversityShanghai 200240China SJTU-BGI Innovation Research Center Shanghai 200240China BGI-ShenZhen ShenzhenGuangdong 518083China

Glucose-6-phosphate dehydrogenase(G6PD)deficiency is one of the most prevalent hereditary and X-linked enzyme disorders caused by the pathogenetic G6PD(NM_001042351.2)variants(Yang et al.,2016).The clinical manifestations of G6PD deficiency offer a wide spectrum of diverse disease phenotypes(Hecker et al.,2013).Investigations of prevalence and molecular epidemiology demonstrate that G6PD deficiency affects over 400 milion individuals worldwide and leads to thousands of deaths annually(Mortality and Causes of Death,2015).

关键词： al. G6PD epidemiology

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Mechanistic insight into the controlled synthesis of metal phosphide catalysts from annealing of metal oxides with sodium hypophosphite

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Nano Research 2022年第12期15卷 10134-10141页

作者： Fanpeng Chen Bohang Zhao mengyao sun Cuibo Liu Yanmei Shi Yifu Yu Bin Zhang Department of Chemistry School of ScienceInstitute of Molecular PlusTianjin UniversityTianjin300072China Collaborative Innovation Center of Chemical Science and Engineering Tianjin UniversityTianjin300072China

Understanding and manipulating synthetic progress for precisely controlling the components and defects of nanomaterials is an important and challenging task in materials synthesis and nanocatalysis.Metal phosphides(MPs)have been explored as cheap advanced materials in various catalytic fields.MP materials are usually synthesized through gas-solid phosphorization reaction in a trial-to-error manner,but their formation mechanism and the origin of controlled synthesis remain unclear.Here,we combine in situ thermogravimetrc analysis-mass spectrometry(TG-MS)and quasi-in situ X-ray powder diffraction(XRD)analysis to probe the transformation mechanism from metal oxides(MOs)to MPs during the phosphorization process mediated by hypophosphite.Temperature,time,and the amount of hypophosphite are revealed as the driven forces while oxophilicity and crystallinity as the impeded forces,simultaneously control the component and defect level of a series of MP(M=Ni,Co,W,Mo,and Nb).The as-obtained WO2.9/WP is proved to be an efficient Z-scheme photocatalyst for oxidative coupling of methane with the total C2+production and C2H4 selectivity in C2+products reaching 10.75 pmolg-1 and 98.25%.Our work provides a fundamental understanding of the phosphorization treatment and thereby guides a viable synthetic route to the controlled synthesis of MOx-δ,MP,MOx-δ/MP,and MP/M heterostructured materials.

关键词： phosphorization treatment metal phosphides methodology heterostructure oxygen vacancy photocatalysis

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Superhydrophobic Surface-Assisted Preparation of Microspheres and Supraparticles and Their Applications

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Nano-Micro Letters 2024年第4期16卷 110-138页

作者： mengyao Pan Huijuan Shao Yue Fan Jinlong Yang Jiaxin Liu Zhongqian Deng Zhenda Liu Zhidi Chen Jun Zhang Kangfeng Yi Yucai Su Dehui Wang Xu Deng Fei Deng Institute of Fundamental and Frontier Sciences University of Electronic Science and Technology of ChinaChengdu 611731People’s Republic of China School of Materials Science and Engineering Sun Yat-Sen UniversityGuangzhou 510275People’s Republic of China Shenzhen Institute for Advanced Study University of Electronic Science and Technology of ChinaShenzhen 518110People’s Republic of China Pharmaceutical Glass Co.Ltd Zibo 256100People’s Republic of China Department of Nephropathy School of MedicineSichuan Provincial People’s HospitalUniversity of Electronic Science and Technology of ChinaChengduPeople’s Republic of China Department of Nephrology Sichuan Provincial People’s Hospital Jinniu HospitalChengdu Jinniu District People’s HospitalChengduPeople’s Republic of China

Superhydrophobic surface(SHS) has been well developed, as SHS renders the property of minimizing the water/solid contact interface. Water droplets deposited onto SHS with contact angles exceeding 150°, allow them to retain spherical shapes, and the low adhesion of SHS facilitates easy droplet collection when tilting the substrate. These characteristics make SHS suitable for a wide range of applications. One particularly promising application is the fabrication of microsphere and supraparticle materials. SHS offers a distinct advantage as a universal platform capable of providing customized services for a variety of microspheres and supraparticles. In this review, an overview of the strategies for fabricating microspheres and supraparticles with the aid of SHS, including cross-linking process, polymer melting,and droplet template evaporation methods, is first presented. Then, the applications of microspheres and supraparticles formed onto SHS are discussed in detail, for example, fabricating photonic devices with controllable structures and tunable structural colors, acting as catalysts with emerging or synergetic properties, being integrated into the biomedical field to construct the devices with different medicinal purposes, being utilized for inducing protein crystallization and detecting trace amounts of analytes. Finally,the perspective on future developments involved with this research field is given, along with some obstacles and opportunities.

关键词： Superhydrophobic surface Microspheres and supraparticles Photonic devices Catalysts Biomedical and trace detections

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Digital twins in smart farming:An autoware-based simulator for autonomous agricultural vehicles

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International Journal of Agricultural and Biological Engineering 2023年第4期16卷 184-189页

作者： Xin Zhao Wanli Wang Long Wen Zhibo Chen Sixian Wu Kun Zhou mengyao sun Lanjun Xu Bingbing Hu Caicong Wu College of Information and Electrical Engineering China Agricultural UniversityBeijing 100083China Key Laboratory of Agricultural Machinery Monitoring and Big Data Application Ministry of Agriculture and Rural AffairsBeijing 100083China The Bureau of Agriculture and Rural Affairs of Urumchi Xinjiang Uygur Autonomous RegionUrumchi 830000China Research&Advanced Engineering AGCO A/SDK-8930 RandersDenmark Beijing Agricultural Machinery Experiment Appraisal Extension Station Beijing 100079China Kunlun Beidou Intelligence Technologies Co.Ltd. Beijing 102200China

Digital twins can improve the level of control over physical entities and help manage complex systems by integrating a range of technologies.The autonomous agricultural machine has shown revolutionary effects on labor reduction and utilization rate in field works.Autonomous vehicles in precision agriculture have the potential to improve competitiveness compared to current crop production methods and have become a research hotspot.However,the development time and resources required in experiments have limited the research in this area.Simulation tools in unmanned farming that are required to enable more efficient,reliable,and safe autonomy are increasingly demanding.Inspired by the recent development of an open-source virtual simulation platform,this study proposed an autoware-based simulator to evaluate the performance of agricultural machine guidance based on digital twins.Oblique photogrammetry using drones is used to construct threedimensional maps of fields at the same scale as reality.A communication format suitable for agricultural machines was developed for data input and output,along with an inter-node communication methodology.The conversion,publishing,and maintenance of multiple coordinate systems were completed based on ROS(Robot Operating System).Coverage path planning was performed using hybrid curves based on Bézier curves,and it was tested in both a simulation environment and actual fields with the aid of Pure Pursuit algorithms and PID controllers.

关键词： autoware simulation platform autonomous agricultural vehicle digital twin autonomous robots

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Preclinical evaluation of cyclophosphamide and fludarabine combined with CD19 CAR-T in the treatment of B-cell hematologic malignancies in vivo

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Oncology Research 2024年第6期32卷 1109-1118页

作者： ZHIGANG XIA mengyao TIAN YUCAI CHENG WENFANG YI ZEFAN DU TIANWEN LI YUCHEN WEN LINDI LI YONG LIU CHUN CHEN Pediatric Hematology Laboratory Division of Hematology/OncologyDepartment of PediatricsThe Seventh Affiliated Hospital of Sun Yat-sen UniversityShenzhen518107China Scientific Research Center The Seventh Affiliated Hospital of Sun Yat-sen UniversityShenzhen518107China

Background:Chimeric antigen receptor T(CAR-T)cell therapy has achieved marked therapeutic success in ameliorating hematological malignancies.However,there is an extant void in the clinical guidelines concerning the most effective chemotherapy regimen prior to chimeric antigen receptor T(CAR-T)cell therapy,as well as the optimal timing for CAR-T cell infusion post-chemotherapy.Materials and Methods:We employed cell-derived tumor xenograft(CDX)murine models to delineate the optimal pre-conditioning chemotherapy regimen and timing for CAR-T cell treatment.Furthermore,transcriptome sequencing was implemented to identify the therapeutic targets and elucidate the underlying mechanisms governing the treatment regimen.Results:Our preclinical in vivo evaluation determined that a combination of cyclophosphamide and fludarabine,followed by the infusion of CD19 CAR-T cells five days subsequent to the chemotherapy,exerts the most efficacious therapeutic effect in B-cell hematological malignancies.Concurrently,RNA-seq data indicated that the therapeutic efficacy predominantly perturbs tumor cell metabolism,primarily through the inhibition of key mitochondrial targets,such as C-Jun Kinase enzyme(C-JUN).Conclusion:In summary,the present study offers critical clinical guidance and serves as an authoritative reference for the deployment of CD19 CAR-T cell therapy in the treatment of B-cell hematological malignancies.

关键词： CD19 CAR-T B-cell hematologic malignancies Metabolism In vivo

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Inhibition of PRMT5 by market drugs as a novel cancer therapeutic avenue

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Genes & Diseases 2023年第1期10卷 267-283页

作者： Lakshmi Prabhu Matthew Martin Lan Chen Ozlem Demir Jiamin Jin Xiumei Huang Aishat Motolani mengyao sun Guanglong Jiang Harikrishna Nakshatri Melissa L.Fishel Steven sun Ahmad Safa Rommie E.Amaro Mark R.Kelley Yunlong Liu Zhong-Yin Zhang Tao Lu Department of Pharmacology and Toxicology Indiana University School of MedicineIndianapolisIN 46202USA Chemical Genomics Core Facility Indiana University School of MedicineIndiana University School of MedicineIndianapolisIN 46202USA Department of Biochemistry and Molecular Biology Indiana University School of MedicineIndiana University School of MedicineIndianapolisIN46202USA Department of Chemistry and Biochemistry University of CaliforniaSan DiegoCA 92093USA Department of Radiation Oncology Indiana University School of MedicineIndianapolisIN 46202USA Department of Medical and Molecular Genetics Indiana University School of MedicineIndianapolisIN 46202USA Department of Medicine Indiana University School of MedicineIndianapolisIN 46202USA Department of Pediatrics Herman B Wells Center for Pediatric ResearchIndianapolisiN 46202USA Indiana University Simon Comprehensive Cancer Center Indiana University School of MedicineIndianapolisIN46202USA

Market drugs,suchas Foodand Drug Administration(FDA)or European Medicines Agency(EMA)-approved drugs for specific indications provide opportunities for repurposing for newer therapeutics.This potentially saves resources invested in clinical trials that verify drug safety and tolerance in humans prior to alternative indication approval.Protein arginine methyltransferase 5(PRMT5)overexpression has been linked to promoting the tumor phenotype in several cancers,including pancreatic ductal adenocarcinoma(PDAC),colorectal cancer(CRC),and breast cancer(BC),making PRMT5 an important target for cancer therapy.Previously,we showed that PRMT5-mediated methylation of the nuclear factor(NF)-kB,partially contributes to its constitutive activation observed in cancers.In this study,we utilized an AlphaLiSA-based high-throughput screening method adapted in our lab,and identified one FDA-approved drug,Candesartan cilexetil(Can,used in hypertension treatment)and one EMA-approved drug,Cloperastine hydrochloride(Clo,used in cough treatment)that had significant PRMT5-inhibitory activity,and their anti-tumor properties were validated using cancer phenotypic assays in vitro.Furthermore,PRMT5 selective inhibition of methyltransferase activity was confirmed by reduction of both NF-kB methylation and its subsequent activation upon drug treatment.Using in silico prediction,we identified critical residues on PRMT5 targeted by these drugs that may interfere with its enzymatic activity.Finally,Clo and Can treatment have exhibited marked reduction in tumor growth in vivo.Overall,we provide basis for pursuing repurposing Clo and Can as anti-PRMT5 cancer therapies.Our study offers potential safe and fast repurposing of previously unknown PRMT5 inhibitors into clinical practice.

关键词： Cancer Research NF-kB Pharmacology PRMT5 PRMT5 inhibitors

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A discovery of two slow pulsars with FAST:“Ronin”from the globular cluster M15

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Science China(Physics,Mechanics & Astronomy) 2024年第6期67卷 166-180页

作者： Dengke Zhou Pei Wang Di Li Jianhua Fang Chenchen Miao Paulo CCFreire Lei Zhang Dandan Zhang Huaxi Chen Yi Feng Yifan Xiao Jintao Xie Xu Zhang Chenwu Jin Han Wang Yinan Ke Xuerong Guo Rushuang Zhao Chenhui Niu Weiwei Zhu mengyao Xue Yabiao Wang Jiafu Wu Zhenye Gan Zhongyi sun Chengjie Wang Jie Zhang Junshuo Zhang Jinhuang Cao Wanjin Lu Research Center for Astronomical Computing Zhejiang LaboratoryHangzhou 311121China National Astronomical Observatories Chinese Academy of SciencesBeijing 100101China Institute for Frontiers in Astronomy and Astrophysics Beijing Normal UniversityBeijing 102206China University of Chinese Academy of Sciences Beijing 100049China New Cornerstone Science Laboratory Shenzhen 518054China Max Planck Institut f¨ur Radioastronomie Bonn 53121Germany Centre for Astrophysics and Supercomputing Swinburne University of TechnologyHawthorn 3122Australia School of Mathematical Sciences School of Physics and Electronic SciencesGuizhou Normal UniversityGuiyang 550001China Guizhou Provincial Key Laboratory of Radio Astronomy and Data Processing Guiyang 550001China School of Physics and Electronic Engineering Qilu Normal UniversityJinan 250200China School of Physics and Electronic Science Guizhou Normal UniversityGuiyang 550001China College of Physical Science and Technology Central China Normal UniversityWuhan 430079China Tencent Youtu Lab Shanghai 201103China

Globular clusters harbor numerous millisecond pulsars,but long-period pulsars(P 100 ms)are rarely found.In this study,we employed a fast folding algorithm to analyze observational data from multiple globular clusters obtained by the Five-hundredmeter Aperture Spherical radio Telescope(FAST),aiming to detect the existence of long-period pulsars.We estimated the impact of the median filtering algorithm in eliminating red noise on the minimum detectable flux density(S_(min))of pulsars.Subsequently,we successfully discovered two isolated long-period pulsars in M15 with periods approximately equal to 1.928451 and3.960716 s,respectively.On the P-˙P diagram,both pulsars are positioned below the spin-up line,suggesting a possible history of partial recycling in X-ray binary systems disrupted by dynamical encounters later on.According to timing results,these two pulsars exhibit remarkably strong magnetic fields.If the magnetic fields were weakened during the accretion process,then a short duration of accretion might explain the strong magnetic fields of these pulsars.

关键词： pulsar globular cluster FAST

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