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Advances in oral mesenchymal stem cell-derived extracellular vesicles in health and disease

Genes & Diseases 2024年第1期11卷 346-357页

作者： Huanyu Luo Anahid Ahmadi Birjandi Feilong Ren tianmeng sun Paul T.Sharpe Hongchen sun Zhengwen An Department of Oral Biology Jilin Provincial Key Laboratory of Tooth Development and Bone RemodelingSchool and Hospital of StomatologyJilin UniversityChangchunJilin 130021China Faculty of Dentistry Oral&Craniofacial SciencesCentre for Craniofacial and Regenerative BiologyKing's College LondonLondonSE19RTUK Department of Oral Pathology Jilin Provincial Key Laboratory of Tooth Development and Bone RemodelingSchool and Hospital of StomatologyJilin UniversityChangchunJilin 130021China

Extracellular vesicles(EVs)are nano-size vesicles secreted naturally by all cells into the extracellular space and have been recognized as important cell-cell mediators in multicel-lular organisms.EVs contain nucleic acids,proteins,lipids,and other cellular components,regulating many basic biological processes and playing an important role in regenerative med-icine and diseases.EVs can be traced to their cells of origin and exhibit a similar function.Moreover,EVs demonstrate low immunogenicity,good biocompatibility,and fewer side ef-fects,compared to their parent cells.Mesenchymal stem cells(MsCs)are one of the most important resource cells for EVs,with a great capacity for self-renewal and multipotent differ-entiation,and play an essential role in stem cell therapy.The mechanism of MsC therapy was thought to be attributed to the differentiation of MsCs after targeted migration,as previously noted.However,emerging evidence shows the previously unknown role of MsC-derived para-crine factors in stem cell therapy.Especially EVs derived from oral tissue MSCs(OMSC-EVs),show more advantages than those of all other MsCs in tissue repair and regeneration,due to their lower invasiveness and easier accessibility for sample collection.Here,we systematically review the biogenesis and biological characteristics of OMSC-EVs,as well as the role of OMsC-EVs in intercellular communication.Furthermore,we discuss the potential therapeutic roles of OMSC-EVs in oral and systemic diseases.We highlight the current challenges and future directions of OMSC-EVs to focus more attention on clinical translation.We aim to provide valuable insights for the explorative clinical application of OMSC-EVs.

关键词： Disease Extracellular vesicles Oral tissue MSC Therapeutic application Tissue regeneration

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Targeted nanostrategies eliminate pre-metastatic niche of cancer

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Nano Research 2024年第6期17卷 5358-5373页

作者： Juan Wang Ning Zhang Xiuping Ding Chengrui Fu Xiaodong Li Baosheng Li Jianxun Ding tianmeng sun Key Laboratory of Organ Regeneration and Transplantation of Ministry of Education Institute of ImmunologyThe First HospitalJilin University1 Xinmin StreetChangchun 130061China Key Laboratory of Polymer Ecomaterials Changchun Institute of Applied ChemistryChinese Academy of Sciences5625 Renmin StreetChangchun 130022China Department of Radiation Oncology Shandong Cancer Hospital and InstituteShandong First Medical University and Shandong Academy of Medical Sciences440 Jiyan RoadJinan 250117China Department of orthopaedics The Second Hospital of Shandong UniversityShandong University247 Beiyuan StreetJinan 250033China State Key Laboratory of Molecular Engineering of Polymers Fudan University220 Handan RoadShanghai 200433China

Establishing a pre-metastatic niche(PMN)in secondary organs is a prerequisite for cancer metastases.Despite advances in cancer therapy,the efficient inhibition of PMN formation remains a clinical challenge.Recent advances in understanding the specific characteristics of PMN and advances in nanotechnology have provided hope for manipulating their microenvironments.A series of nanostrategies have been designed to eliminate the PMN,including the removal of pro-metastatic exosomes from the bloodstream for excretion via the intestines,the targeting and scavenging of myeloid-derived suppressor cells,fibroblasts,and critical extracellular matrix components,and the elimination of circulating tumor cells prior to colonization in distant organs.This review summarizes the underlying mechanisms of PMN formation,highlights the anti-PMN efficacy of currently reported nanostrategies,and underlines the unresolved questions.

关键词： nanoparticle controlled drug delivery pre-metastatic niche elimination metastasis suppression cancer therapy

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Organic thin-film transistors and related devices in life and health monitoring

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Nano Research 2024年第2期17卷 426-444页

作者： Chenfang sun Tie Wang Tianjin Key Laboratory of Drug Targeting and Bioimaging Life and Health Intelligent Research InstituteTianjin University of TechnologyTianjin 300384China

The early determination of disease-related biomarkers can significantly improve the survival rate of patients.Thus,a series of explorations for new diagnosis technologies,such as optical and electrochemical methods,have been devoted to life and health monitoring.Organic thin-film transistor(OTFT),as a state-of-the-art nano-sensing technology,has attracted significant attention from construction to application owing to the merits of being label-free,low-cost,facial,and rapid detection with multi-parameter responses.Nevertheless,interference from non-specific adsorption is inevitable in complex biological samples such as body liquid and exhaled gas,so the reliability and accuracy of the biosensor need to be further improved while ensuring sensitivity,selectivity,and stability.Herein,we overviewed the composition,mechanism,and construction strategies of OTFTs for the practical determination of disease-related biomarkers in both body fluids and exhaled gas.The results show that the realization of bio-inspired applications will come true with the rapid development of high-effective OTFTs and related devices.

关键词： organic thin-film transistors biosensors biomarkers organic bioelectronics organic semiconductors healthcare

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Pretreating and normalizing metabolomics data for statistical analysis

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Genes & Diseases 2024年第3期11卷 188-205页

作者： Jun sun Yinglin Xia Division of Gastroenterology and Hepatology Department of MedicineDepartment of Microbiology/ImmunologyUIC Cancer CenterUniversity of Illinois ChicagoJesse Brown VA Medical Center Chicago(537)ChicagoIL 60612USA Division of Gastroenterology and Hepatology Department of MedicineUniversity of Illinois ChicagoChicagoIL 60612USA

Metabolomics as a research field and a set of techniques is to study the entire small molecules in biological samples.Metabolomics is emerging as a powerful tool generally for pre-cision medicine.Particularly,integration of microbiome and metabolome has revealed the mechanism and functionality of microbiome in human health and disease.However,metabo-lomics data are very complicated.Preprocessing/pretreating and normalizing procedures on metabolomics data are usually required before statistical analysis.In this review article,we comprehensively review various methods that are used to preprocess and pretreat metabolo-mics data,including MS-based data and NMR-based data preprocessing,dealing with zero and/or missing values and detecting outliers,data normalization,data centering and scaling,data transformation.We discuss the advantages and limitations of each method.The choice for a suitable preprocessing method is determined by the biological hypothesis,the characteristics of the data set,and the selected statistical data analysis method.We then provide the perspective of their applications in the microbiome and metabolome research.

关键词： Data centering and scaling Data normalization Data transformation Missing values MS-Baseddata preprocessing NMRData preprocessing Outliers Preprocessing/pretreatment

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Gold Nanoparticle Enantiomers and Their Chiral-Morphology Dependence of Cellular Uptake

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CCS Chemistry 2022年第2期4卷 660-670页

作者： Ning-Ning Zhang Hao-Ran sun Shuhan Liu Yu-Chen Xing Jun Lu Fei Peng Cheng-Long Han Zhonglin Wei tianmeng sun Bai Yang Kun Liu State Key Laboratory of Supramolecular Structure and Materials College of ChemistryJilin UniversityChangchun 130012 Key Laboratory of Organ Regeneration and Transplantation of Ministry of Education Institute of ImmunologyThe First HospitalJilin UniversityChangchun 130012 National-Local Joint Engineering Laboratory of Animal Models for Human Diseases Changchun 130012 Department of Chemical Engineering University of MichiganAnn ArborMI 48109 Department of Organic Chemistry College of ChemistryJilin UniversityChangchun 130012 International Center of Future Science Jilin UniversityChangchun 130012 Chiral Nanomaterial Research Center International Center of Future ScienceJilin UniversityChangchun 130012

Chiral molecules are widely prevalent in nature and biological systems,and artificial chiral nanoparticles have drawn enormous interest owing to their unique optical and physical properties.However,nanoparticles with chiral morphologies and their potential role in biology have been rarely explored.Herein,we report a seed-mediated synthesis of enantiomorphic Au nanooctopods(NOPs)and their chiralmorphology dependence of cellular uptake.With a high yield(∼80%),the chiral NOPs possess eight uniform arms that bend fromtodirections,like a propeller structure.The chiral NOPs synthesized with L-or D-glutathione(GSH)have opposite handedness,resulting in opposite circular dichroism signals,which is consistent with finite-difference time-domain simulations.D-GSH NOPs demonstrate greater than 30%(ca.15%)enhanced cellular uptake in GL261 and bEnd.3 cells compared with L-GSH NOPs(racemic NOPs).Moreover,D-GSH NOPs modified with poly(ethylene glycol)or L-GSH are also preferred by the cells,proving the chiral-morphology dependence of cellular uptake.Our study develops the exploration of the chiral-specific interaction in biological systems,providing potential applications for drug delivery,biosensing,and tumor detection.

关键词： chirality branched nanoparticles chiral morphology selective cellular uptake surface plasmonic resonance

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Fossil Equidae in the Linxia Basin with Biostratigraphic and Paleozoogeographic Significance

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Acta Geologica Sinica(English Edition) 2024年第1期98卷 1-9页

作者： sun Boyang Key Laboratory of Vertebrate Evolution and Human Origins of the Chinese Academy of Sciences Institute of Vertebrate Paleontology and PaleoanthropologyChinese Academy of SciencesBeijing 100044China

The Linxia Basin is characterized by an abundance of Cenozoic sediments,that contain exceptionally rich fossil resources.Equids are abundant in the Linxia Basin,the fossil record of equids in this region including 16 species that represent 10 genera.In comparison to other classic late Cenozoic areas in China,the Linxia Basin stands out,because the fauna and chronological data accompanying Linxia equids render them remarkably useful for biostratigraphy.The anchitheriines in the region,such as Anchitherium and Sinohippus,represent early equids that appeared in the late stages of the middle and late Miocene,respectively.Among the equines,most species of Chinese hipparions have been identified in the Linxia Basin and some species of the genera Hipparion and Hippotherium have FAD records for China.Furthermore,Equus eisenmannae is one of the earliest known species of Equus in the Old World and is well-represented at the Longdan locality.Some species with precise geohistorical distributions can serve as standards for high-resolution chronological units within this framework.Located at the eastern margin of the Tibetan Plateau and subject to considerable uplift,the Linxia Basin has served as a biogeographic transition area for equids throughout the late Cenozoic.

关键词： Equidae Cenozoic biostratigraphy paleozoogeography Linxia Basin

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NADPH oxidase 4(NOX4)as a biomarker and therapeutic target in neurodegenerative diseases

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Neural Regeneration Research 2024年第9期19卷 1961-1966页

作者： Napissara Boonpraman sun Shin Yi BK21 four Program Department of Medical SciencesSoonchunhyang UniversityAsanSouth Korea Department of Biomedical Laboratory Science Soonchunhyang UniversityAsanSouth Korea iConnectome Co.Ltd.CheonanSouth Korea

Diseases like Alzheimer’s and Parkinson’s diseases are defined by inflammation and the damage neurons undergo due to oxidative stress. A primary reactive oxygen species contributor in the central nervous system, NADPH oxidase 4, is viewed as a potential therapeutic touchstone and indicative marker for these ailments. This in-depth review brings to light distinct features of NADPH oxidase 4, responsible for generating superoxide and hydrogen peroxide, emphasizing its pivotal role in activating glial cells, inciting inflammation, and disturbing neuronal functions. Significantly, malfunctioning astrocytes, forming the majority in the central nervous system, play a part in advancing neurodegenerative diseases, due to their reactive oxygen species and inflammatory factor secretion. Our study reveals that aiming at NADPH oxidase 4 within astrocytes could be a viable treatment pathway to reduce oxidative damage and halt neurodegenerative processes. Adjusting NADPH oxidase 4 activity might influence the neuroinflammatory cytokine levels, including myeloperoxidase and osteopontin, offering better prospects for conditions like Alzheimer’s disease and Parkinson’s disease. This review sheds light on the role of NADPH oxidase 4 in neural degeneration, emphasizing its drug target potential, and paving the path for novel treatment approaches to combat these severe conditions.

关键词： Alzheimer’s disease astrocytes mitochondrial dysfunction myeloperoxidase NADPH oxidase 4 NADPH oxidase 4 inhibitors neurodegenerative diseases osteopontin Parkinson’s disease reactive oxygen species

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Lupenone improves motor dysfunction in spinal cord injury mice through inhibiting the inflammasome activation and pyroptosis in microglia via the nuclear factor kappa B pathway

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Neural Regeneration Research 2024年第8期19卷 1802-1811页

作者： Fudong Li Xiaofei sun Kaiqiang sun Fanqi Kong Xin Jiang Qingjie Kong Department of Orthopedics Shanghai General HospitalShanghai Jiao Tong University School of MedicineShanghaiChina Department of Orthopedic Surgery Spine CenterShanghai Changzheng HospitalNaval Medical UniversityShanghaiChina Department of Orthopedic Surgery Naval Medical CenterNaval Medical UniversityShanghaiChina Department of Anesthesiology Shanghai Changzheng HospitalNaval Medical UniversityShanghaiChina

Spinal cord injury-induced motor dysfunction is associated with neuroinflammation.Studies have shown that the triterpenoid lupenone,a natural product found in various plants,has a remarkable anti-inflammatory effect in the context of chronic inflammation.However,the effects of lupenone on acute inflammation induced by spinal cord injury remain unknown.In this study,we established an impact-induced mouse model of spinal cord injury,and then treated the injured mice with lupenone(8 mg/kg,twice a day)by intrape ritoneal injection.We also treated BV2 cells with lipopolysaccharide and adenosine5’-triphosphate to simulate the inflammatory response after spinal cord injury.Our res ults showed that lupenone reduced IKBa activation and p65 nuclear translocation,inhibited NLRP3 inflammasome function by modulating nuclear factor kappa B,and enhanced the conve rsion of proinflammatory M1 mic roglial cells into anti-inflammatory M2 microglial cells.Furthermore,lupenone decreased NLRP3 inflammasome activation,NLRP3-induced mic roglial cell polarization,and microglia pyroptosis by inhibiting the nuclear factor kappa B pathway.These findings suggest that lupenone protects against spinal cord injury by inhibiting inflammasomes.

关键词： inflammasome inflammation lupenone microglia polarization pyroptosis spinal cord injury

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Rational surface charge engineering of haloalkane dehalogenase for boosting the enzymatic performance in organic solvent solutions

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Chinese Journal of Chemical Engineering 2024年第1期65卷 276-285页

作者： Yin Wu Yan sun Department of Biochemical Engineering School of Chemical Engineering and Technology and Key Laboratory of Systems Bioengineering and Frontiers Science Center for Synthetic Biology(Ministry of Education)Tianjin UniversityTianjin 300350China

Biocatalysis in organic solvents(OSs)has numerous important applications,but native enzymes in OSs often exhibit limited catalytic performance.Herein,we proposed a computation-aided surface charge engineering strategy to improve the catalytic performance of haloalkane dehalogenase DhaA in OSs based on the energetic analysis of substrate binding to the DhaA surface.Several variants with enhanced OS resistance were obtained by replacing negative charged residues on the surface with positive charged residue(Arg).Particularly,a four-substitution variant E16R/E93R/E121R/E257R exhibited the best catalytic performance(five-fold improvement in OS resistance and seven-fold half-life increase in 40%(vol)dimethylsulfoxide).As a result,the overall catalytic performance of the variant could be at least 26 times higher than the wild-type DhaA.Fluorescence spectroscopy and molecular dynamics simulation studies revealed that the residue substitution mainly enhanced OS resistance from four aspects:(a)improved the overall structural stability,(b)increased the hydrophobicity of the local microenvironment around the catalytic triad,(c)enriched the hydrophobic substrate around the enzyme molecule,and(d)lowered the contact frequency between OS molecules and the catalytic triad.Our findings validate that computationaided surface charge engineering is an effective and ingenious rational strategy for tailoring enzyme performance in OSs.

关键词： Surface charge engineering Organic solvent resistance Molecular dynamics simulation Haloalkane dehalogenase

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Study on Coded Permutation Entropy of Finite Length Gaussian White Noise Time Series

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Chinese Journal of Electronics 2024年第1期33卷 185-194页

作者： Huihui sun Xiaofeng ZHANG School of Physics and Information Technology Shaanxi Normal University

As an extension of permutation entropy(PE), coded permutation entropy(CPE) improves the performance of PE by making a secondary division for ordinal patterns defined in PE. In this study, we provide an exploration of the statistical properties of CPE using a finite length Gaussian white noise time series theoretically. By means of the Taylor series expansion, the approximate expressions of the expected value and variance of CPE are deduced and the Cramér-Rao low bound(CRLB) is obtained to evaluate the performance of the CPE estimator. The results indicate that CPE is a biased estimator, but the bias only depends on relevant parameters of CPE and it can be easily corrected for an arbitrary time series. The variance of CPE is related to the encoding patterns distribution,and the value converges to the CRLB of the CPE estimator when the time series length is large enough. For a finitelength Gaussian white noise time series model, the predicted values can match well with the actual values, which further validates the statistic theory of CPE. Using the theoretical expressions of CPE, it is possible to better understand the behavior of CPE for most of the time series.

关键词： Coded permutation entropy Gaussian white noise Finite-length time series Cramér-Rao low bound

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