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Meningeal lymphatic vessel crosstalk with central nervous system immune cells in aging and neurodegenerative diseases

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Neural Regeneration Research 2025年第3期20卷 763-778页

作者： Minghuang Gao Xinyue Wang Shijie Su Weicheng Feng Yaona Lai Kongli Huang Dandan Cao Qi Wang Science and Technology Innovation Center Guangzhou University of Chinese MedicineGuangzhouGuangdong ProvinceChina institute of Clinical Pharmacology Guangzhou University of Chinese MedicineGuangzhouGuangdong ProvinceChina The Sixth Affiliated Hospital Sun Yat-sen UniversityGuangzhouGuangdong ProvinceChina

Meningeal lymphatic vessels form a relationship between the nervous system and periphery, which is relevant in both health and disease. Meningeal lymphatic vessels not only play a key role in the drainage of brain metabolites but also contribute to antigen delivery and immune cell activation. The advent of novel genomic technologies has enabled rapid progress in the characterization of myeloid and lymphoid cells and their interactions with meningeal lymphatic vessels within the central nervous system. In this review, we provide an overview of the multifaceted roles of meningeal lymphatic vessels within the context of the central nervous system immune network, highlighting recent discoveries on the immunological niche provided by meningeal lymphatic vessels. Furthermore, we delve into the mechanisms of crosstalk between meningeal lymphatic vessels and immune cells in the central nervous system under both homeostatic conditions and neurodegenerative diseases, discussing how these interactions shape the pathological outcomes. Regulation of meningeal lymphatic vessel function and structure can influence lymphatic drainage, cerebrospinal fluid-borne immune modulators, and immune cell populations in aging and neurodegenerative disorders, thereby playing a key role in shaping meningeal and brain parenchyma immunity.

关键词： central nervous system meningeal lymphatic vessels immunity myeloid cells lymphatic cells neurodegenerative disease

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Predicting microbial extracellular electron transfer activity in paddy soils with soil physicochemical properties using machine learning

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Science China(Technological Sciences) 2024年第1期67卷 259-270页

作者： OU JiaJun LUO XiaoShan LIU JunYang HUANG LinYan ZHOU LiHua YUAN Yong School of Automation Guangdong University of TechnologyGuangzhou 510006China Guangdong Key Laboratory of Environmental Catalysis and Health Risk Control Guangzhou Key Laboratory Environmental Catalysis and Pollution ControlSchool of Environmental Science and EngineeringInstitute of Environmental Health and Pollution ControlGuangdong University of TechnologyGuangzhou 510006China School of Biomedical and Pharmaceutical Sciences Guangdong University of TechnologyGuangzhou 510006China

Soil extracellular electron transfer(EET)is a pivotal biological process within the realm of soil.Unfortunately,EET suffers from a lack of predictive models.Herein,an intricately crafted machine learning model has been developed for the purpose of predicting soil EET by using the physicochemical properties of soil as independent input variables and the EET capabilities in terms of current density(j_(max))and Coulombic charge(C_(out))as dependent output variables.An autoencoder ensemble stacking(AES)model was developed to address the aforementioned issue by integrating support vector machine,multilayer perceptron,extreme gradient boosting,and light gradient boosting machine algorithms as the stacking algorithms.With 10-fold crossvalidation,the AES model exhibited notable improvements in predicting j_(max)and C_(out),with average test R^(2)values of 0.83 and 0.84,respectively,surpassing those of single machine learning(ML)models and the basic ensemble model.By utilizing partial correlation plots(PDPs),Shapley Additive explanations(SHAP)values,and SHAP decision plots,we quantitatively explained the impact and contribution of the input molecules on the AES model’s predictions of j_(max)and C_(out).In the context of the SHAP method for the AES model,total carbon(TC)was identified as the most correlated descriptor for j_(max),while total organic carbon(TOC)stood out as the most relevant descriptor for C_(out).In the prediction tasks of j_(max)and C_(out)within the AES model,employing a multitask ML approach allowed the model to benefit from the shared information of input variables,thereby enhancing its overall generalizability.This study provides a feasible tool for the prediction of soil EET from soil physiochemical properties and an advanced understanding of the relationship between soil physiochemical properties and EET capability.

关键词： extracellular electron transfer paddy soil machine learning prediction autoencoder ensemble stacking model

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Probing valence quark width of the proton in deeply virtual Compton scattering at high energies

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Chinese Physics C 2024年第5期48卷 235-243页

作者：向文昌曹德文周代翠 Physics Division Guangzhou Maritime UniversityGuangzhou 510725China Key Laboratory of Quark and Lepton Physics(MOE) and Institute of Particle PhysicsCentral China Normal UniversityWuhan 430079China

We use the refined hot spot model to study the valence quark shape of the proton with the deeply virtual Compton scattering at high energies in the color glass condensate framework.To investigate the individual valence quark shape,a novel treatment of the valence quark width is employed.We calculate the cross-sections for coherent and incoherent deeply virtual Compton scattering using,for the first time,different widths(Bu and Bd)for the profile density distributions of the up and down quarks instead of using the same width as in the literature.We find that the cross-sections calculated with Bu≥Bd at each collision energy are consistent with each other,which is in agreement with theoretical expectations,whereas those computed with Bu

关键词： gluon saturation physics color glass condensate proton shape fluctuations

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Genome-edited rabbits:Unleashing the potential of a promising experimental animal model across diverse diseases

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Zoological Research 2024年第2期45卷 253-262页

作者： Yang Han Jiale Zhou Renquan Zhang Yuru Liang Liangxue Lai Zhanjun Li Key Laboratory of Zoonosis Research Ministry of EducationCollege of Animal ScienceJilin UniversityChangchunJilin 130062China CAS Key Laboratory of Regenerative Biology Guangdong Provincial Key Laboratory of Stem Cell and Regenerative MedicineSouth China Institute for Stem Cell Biology and Regenerative MedicineGuangzhou Institutes of Biomedicine and HealthChinese Academy of SciencesGuangzhouGuangdong 510530China guangzhou Regenerative Medicine and Health Guang Dong Laboratory(GRMH-GDL) GuangzhouGuangdong 510005China institute for Stem Cell and Regeneration Chinese Academy of SciencesBeijing 100101China

Animal models are extensively used in all aspects of biomedical research,with substantial contributions to our understanding of diseases,the development of pharmaceuticals,and the exploration of gene functions.The field of genome modification in rabbits has progressed slowly.However,recent advancements,particularly in CRISPR/Cas9-related technologies,have catalyzed the successful development of various genome-edited rabbit models to mimic diverse diseases,including cardiovascular disorders,immunodeficiencies,agingrelated ailments,neurological diseases,and ophthalmic pathologies.These models hold great promise in advancing biomedical research due to their closer physiological and biochemical resemblance to humans compared to mice.This review aims to summarize the novel gene-editing approaches currently available for rabbits and present the applications and prospects of such models in biomedicine,underscoring their impact and future potential in translational medicine.

关键词： Genome editing Animal model Rabbit CRISPR/Cas9 Genetic diseases

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Distribution of per-and polyfluoroalkyl substances in blood,serum,and urine of patients with liver cancer and associations with liver function biomarkers

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Journal of Environmental Sciences 2024年第5期139卷 418-427页

作者： Cao Dai Lin Peng Yanjie Li Zhendong Li Da Chen Fei Wang Nan Lin Department of Hepatobiliary Surgery The Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhou 510630China School of Environment Guangdong Key Laboratory of Environmental Pollution and HealthJinan UniversityGuangzhou 510632China State Key Laboratory of Environmental and Biological Analysis Department of ChemistryHong Kong Baptist UniversityHong Kong 999077China South China institute of Environmental Sciences MEEGuangzhou 510655China

Studies have shown that per-and polyfluoroalkyl substances(PFASs)may be hepatotoxic in animals or humans.However,data on clinical epidemiology are very limited.In this study,21PFASs were determined in patients with liver diseases,with the highest median concentrations detected in the serum sample(26.7 ng/mL),followed by blood(10.7 ng/mL)and urine(5.02 ng/mL).Higher total PFAS concentrations were found in hepatocellular carcinoma(HCC)patients compared to non-HCC patients,with significant discrepancies in serum and blood samples.Besides,significant correlations were also found among PFAS concentrations and age,gender,body mass index(BMI),and liver function biomarkers levels.For example,PFAS concentrations are significantly higher in males than in females;Several serum PFASs concentrations increase with age and BMI,while the serum perfluorohexane sulfonic acid(PFHxS)concentrations are negatively correlated with age.In addition,multiple regression models adjusted for age,gender and BMI found that increased serum perfluorobutane sulfonic acid(PFBS),perfluoroheptane sulfonic acid(PFHpS)and perfluorohexylphosphonic acid(PFHxPA)conentrations are correlated with elevated alkaline phosphatase(ALP),aspartate aminotransferase(AST),and alpha-fetoprotein(AFP)(p<0.05).Our results provide epidemiological support for the future study on the potential clinical hepatotoxicity of PFAS.

关键词： Per-and polyfluoroalkyl substances(PFASs) Liver cancer Serum Blood Urine Liver function biomarkers

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The evolution,pathogenicity and transmissibility of quadruple reassortant H1N2 swine influenza virus in China:A potential threat to public health

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Virologica Sinica 2024年第2期39卷 205-217页

作者： Xinxin Cui Jinhuan Ma Zifeng Pang Lingzhi Chi Cuishan Mai Hanlin Liu Ming Liao Hailiang Sun College of Veterinary Medicine South China Agricultural UniversityGuangzhou510642China Key Laboratory of Zoonosis Control and Prevention of Guangdong Province South China Agricultural UniversityGuangzhou510642China National and Regional Joint Engineering Laboratory for Medicament of Zoonosis Prevention and Control South China Agricultural UniversityGuangzhou510642China Shandong Vocational Animal Science and Veterinary College Weifang261061China institute of Animal Health Guangdong Academy of Agricultural SciencesGuangzhou510640China

Swine are regarded as“intermediate hosts”or“mixing vessels”of influenza viruses,capable of generating strains with pandemic potential.From 2020 to 2021,we conducted surveillance on swine H1N2 influenza(swH1N2)viruses in swine farms located in Guangdong,Yunnan,and Guizhou provinces in southern China,as well as Henan and Shandong provinces in northern China.We systematically analyzed the evolution and pathogenicity of swH1N2 isolates,and characterized their replication and transmission abilities.The isolated viruses are quadruple reassortant H1N2 viruses containing genes from pdm/09 H1N1(PB2,PB1,PA and NP genes),triple-reassortant swine(NS gene),Eurasian Avian-like(HA and M genes),and recent human H3N2(NA gene)lineages.The NA,PB2,and NP of SW/188/20 and SW/198/20 show high gene similarities to A/Guangdong/Yue Fang277/2017(H3N2).The HA gene of swH1N2 exhibits a high evolutionary rate.The five swH1N2 isolates replicate efficiently in human,canine,and swine cells,as well as in the turbinate,trachea,and lungs of mice.A/swine/Shandong/198/2020 strain efficiently replicates in the respiratory tract of pigs and effectively transmitted among them.Collectively,these current swH1N2 viruses possess zoonotic potential,highlighting the need for strengthened surveillance of swH1N2 viruses.

关键词： Swine influenza virus(SIV) H1N2 Evolution Replication Pathogenicity Zoonotic potential

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Des-Arg(9)bradykinin as a causal metabolite for autism spectrum disorder

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World Journal of Psychiatry 2024年第1期14卷 88-101页

作者： Zhong-Yu Huang Zi-Pan Lyu Hong-Gui Li Hua-Zhi You Xiang-Na Yang Cai-Hui Cha Center for Medical Research on Innovation and Translation Institute of Clinical MedicineGuangzhou First People’s HospitalSchool of MedicineSouth China University of TechnologyGuangzhou 510000Guangdong ProvinceChina School of Biological Sciences Nanyang Technological UniversityNanyang Ave 639798Singapore Department of Pediatrics First Affiliated Hospital of Guangzhou University of Chinese MedicineGuangzhou 510405Guangdong ProvinceChina Department of Nutrition First Affiliated Hospital of Guangzhou University of Chinese MedicineGuangzhou 510405Guangdong ProvinceChina Department of Pediatric Traditional Chinese Medicine Clinic Guangzhou Women and Children's Medical CenterGuangzhou 510632Guangdong ProvinceChina Department of Psychology Guangzhou Women and Children's Medical CenterGuangzhou 510632Guangdong ProvinceChina

BACKGROUND Early diagnosis and therapeutic interventions can greatly enhance the developmental trajectory of children with autism spectrum disorder(ASD).However,the etiology of ASD is not completely understood.The presence of confounding factors from environment and genetics has increased the difficulty of the identification of diagnostic biomarkers for ASD.AIM To estimate and interpret the causal relationship between ASD and metabolite profile,taking into consideration both genetic and environmental influences.METHODS A two-sample Mendelian randomization(MR)analysis was conducted using summarized data from large-scale genome-wide association studies(GWAS)including a metabolite GWAS dataset covering 453 metabolites from 7824 European and an ASD GWAS dataset comprising 18381 ASD cases and 27969 healthy controls.Metabolites in plasma were set as exposures with ASD as the main outcome.The causal relationships were estimated using the inverse variant weight(IVW)algorithm.We also performed leave-one-out sensitivity tests to validate the robustness of the results.Based on the drafted metabolites,enrichment analysis was conducted to interpret the association via constructing a protein-protein interaction network with multi-scale evidence from databases including Infinome,SwissTargetPrediction,STRING,and Metascape.RESULTS Des-Arg(9)-bradykinin was identified as a causal metabolite that increases the risk of ASD(β=0.262,SE=0.064,P_(IVW)=4.64×10^(-5)).The association was robust,with no significant heterogeneity among instrument variables(P_(MR Egger)=0.663,P_(IVW)=0.906)and no evidence of pleiotropy(P=0.949).Neuroinflammation and the response to stimulus were suggested as potential biological processes mediating the association between Des-Arg(9)bradykinin and ASD.CONCLUSION Through the application of MR,this study provides practical insights into the potential causal association between plasma metabolites and ASD.These findings offer perspectives for the discovery of diagnostic or predictive biomarkers to support clinical

关键词： Des-Arg(9)bradykinin Autism spectrum disorder Mendelian randomization Metabolite Enrichment analysis

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Two-photon live imaging of direct glia-to-neuron conversion in the mouse cortex

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Neural Regeneration Research 2024年第8期19卷 1781-1788页

作者： Zongqin Xiang Shu He Rongjie Chen Shanggong Liu Minhui Liu Liang Xu Jiajun Zheng Zhouquan Jiang Long Ma Ying Sun Yongpeng Qin Yi Chen Wen Li Xiangyu Wang Gong Chen Wenliang Lei Guangdong-Hong Kong-Macao institute of CNS Regeneration(GHMICR) Jinan UniversityGuangzhouGuangdong ProvinceChina Department of Neurosurgery The First Affiliated HospitalJinan UniversityGuangzhouGuangdong ProvinceChina Laboratory for Neuroimmunology in Health and Diseases Guangzhou First People’s HospitalSchool of MedicineSouth China University of TechnologyGuangzhouGuangdong ProvinceChina VIB-KU Leuven Center for Brain&Disease Research LeuvenFlemish RegionBelgium

Over the past decade,a growing number of studies have reported transcription factor-based in situ reprogramming that can directly conve rt endogenous glial cells into functional neurons as an alternative approach for n euro regeneration in the adult mammalian central ne rvous system.Howeve r,many questions remain regarding how a terminally differentiated glial cell can transform into a delicate neuron that forms part of the intricate brain circuitry.In addition,concerns have recently been raised around the absence of astrocyte-to-neuron conversion in astrocytic lineage-tra cing mice.In this study,we employed repetitive two-photon imaging to continuously capture the in situ astrocyte-to-neuron conversion process following ecto pic expression of the neural transcription factor NeuroD1 in both prolife rating reactive astrocytes and lineage-tra ced astrocytes in the mouse cortex.Time-lapse imaging over several wee ks revealed the ste p-by-step transition from a typical astrocyte with numero us short,tapered branches to a typical neuro n with a few long neurites and dynamic growth cones that actively explored the local environment.In addition,these lineage-converting cells were able to migrate ra dially or to ngentially to relocate to suitable positions.Furthermore,two-photon Ca2+imaging and patch-clamp recordings confirmed that the newly generated neuro ns exhibited synchronous calcium signals,repetitive action potentials,and spontaneous synaptic responses,suggesting that they had made functional synaptic connections within local neural circuits.In conclusion,we directly visualized the step-by-step lineage conversion process from astrocytes to functional neurons in vivo and unambiguously demonstrated that adult mammalian brains are highly plastic with respect to their potential for neuro regeneration and neural circuit reconstruction.

关键词： astrocyte-to-neuron conversion Ca2+imaging direct lineage conversion glia astrocyte in vivo reprogramming lineage-tracing mice NeuroD1 neuron two-photon imaging

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Identification of fangchinoline as a broad-spectrum enterovirus inhibitor through reporter virus based high-content screening

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Virologica Sinica 2024年第2期39卷 301-308页

作者： Qiu-Yan Zhang Jia-Qi Li Qi Li Yang Zhang Zhe-Rui Zhang Xiao-Dan Li Hong-Qing Zhang Cheng-Lin Deng Feng-Xia Yang Yi Xu Bo Zhang The Joint Center of Translational Precision Medicine Department of Infections and DiseasesGuangzhou Institute of PediatricsGuangzhou Women and Children's Medical CenterGuangzhou510623China Key Laboratory of Special Pathogens and Biosafety Wuhan Institute of VirologyCenter for Biosafety Mega-ScienceChinese Academy of SciencesWuhan430071China University of Science and Technology of China Department of Life Sciences and MedicineHefei230026China Hunan Normal University School of MedicineChangsha410081China

Hand,foot,and mouth disease(HFMD)is a common pediatric illness mainly caused by enteroviruses,which are important human pathogens.Currently,there are no available antiviral agents for the therapy of enterovirus infection.In this study,an excellent high-content antiviral screening system utilizing the EV-A71-eGFP reporter virus was developed.Using this screening system,we screened a drug library containing 1042 natural compounds to identify potential EV-A71 inhibitors.Fangchinoline(FAN),a bis-benzylisoquinoline alkaloid,exhibits potential inhibitory effects against various enteroviruses that cause HFMD,such as EV-A71,CV-A10,CV-B3 and CV-A16.Further investigations revealed that FAN targets the early stage of the enterovirus life cycle.Through the selection of FAN-resistant EV-A71 viruses,we demonstrated that the VP1 protein could be a potential target of FAN,as two mutations in VP1(E145G and V258I)resulted in viral resistance to FAN.Our research suggests that FAN is an efficient inhibitor of EV-A71 and has the potential to be a broad-spectrum antiviral drug against human enteroviruses.

关键词： Hand,foot,and mouth disease(HFMD) Enterovirus EV-A71 High-content screening Fangchinoline(FAN)

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Performance and mechanism of CO_(2) absorption during the simultaneous removal of SO_(2) and NO_(x) by wet scrubbing process

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Journal of Environmental Sciences 2024年第1期135卷 534-545页

作者： Peng Lu Xianhui Yan Lyumeng Ye Dingsheng Chen Dongyao Chen Jianhang Huang Chaoping Cen Guangdong Province Engineering Laboratory for Air Pollution Control South China Institute of Environmental SciencesMinistry of Ecology and EnvironmentGuangzhou 510655China Guangdong Provincial Key Laboratory of Water and Air Pollution Control Guangzhou 510655China School of Environmental Science and Engineering Sun Yat-sen UniversityGuangzhou 510275China

The co-removal of CO_(2)while removing SO_(2)and NOxfrom industrial flue gas has great potential of carbon emission reduction but related research is lacking.In this study,a wet scrubbing process with various urea solutions for desulfurization and denitrification was explored for the possibility of CO_(2)absorption.The results showed that the urea-additive solutions were efficient for NOxand SO_(2)abatement,but delivered<10%CO_(2)absorption efficiency.The addition of Ca(OH)_(2)dramatically enhanced the CO_(2)absorption,remained the desulfurization efficiency,unfortunately restricted the denitrification efficiency.Among various operating parameters,pH of solution played a determining role during the absorption.The contradictory pH demands of CO_(2)absorption and denitrification were observed and discussed in detail.A higher pH of solution than 10 was favorable for CO_(2)absorption,while the oxidizing of NO to NO_(2),NO_(2)^(-)or NO_(3)^(-)by NaClO_(2)was inhibited in this condition.When7

关键词： CO_(2)absorption Synergistic desulfurization and denitrification Wet scrubbing process Urea-NaClO_(2)-Ca(OH)_(2)absorbent Carbonation reaction

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