Publications by authors named "Jiayu Zhang"

179 Publications

B7-H3 on breast cancer cell MCF7 inhibits IFN-γ release from tumour-infiltrating T cells.

Pathol Res Pract 2021 May 5;224:153461. Epub 2021 May 5.

Department of Oncology, The Second Affiliated Hospital of Soochow University, Suzhou, China. Electronic address:

B7-H3 is a type I membrane protein that has contradictory co-stimulatory and co-inhibitory effects in adaptive and anti-tumour immunity. B7-H3 is up-regulated in many malignant tumours, including breast cancer. Therefore, we hypothesise that B7-H3, which has an immunosuppressive role, suppresses anti-tumour immunity. The aim of this study was to clarify the role of B7-H3 in the tumor microenvironment in breast cancer, explore the possibility of B7-H3 as a target for clinical immunotherapy, and provide reference for clinical work. We knocked down B7-H3 with siRNA in MCF7 breast cancer cells, which we termed MCF7-B7-H3-KD cells, and the expression of B7-H3 was assessed by flow cytometry. GAPDH (glyceraldehyde-3-phosphate dehydrogenase) knockdown was used as a control (MCF7-Gapdh). MCF7-B7-H3-KD and MCF7-Gapdh cells were co-cultured with peripheral blood mononuclear cells (PBMCs) and CD3 T cells from healthy donors to assess the effect of B7-H3 loss. PBMCs cultured with MCF7-Gapdh cells showed decreased activation, proliferation, and function of CD8 T cells, but there was no effect on the proliferation of CD4 T cells. However, when MCF7-B7-H3-KD cells were co-cultured with PBMCs, the proliferation ability of CD4 T cells and CD8 T cells was significantly higher than that observed in MCF7-Gapdh cell co-culture. Additionally, co-culture with MCF7-Gapdh cells decreased the expression of IFN-γ (Interferon-γ). However, after co-culture with MCF7-B7-H3-KD cells, there was an increase in IFN-γ. We further found that this inhibitory effect on IFN-γ was because of decreased mTOR (the mammalian target of rapamycin) phosphorylation in T cells. Treatment of T cells co-cultured with MCF7-B7-H3-KD cells with an mTOR inhibitor blocked the secretion of IFN-γ. B7-H3 on tumour cells inhibits the proliferation of CD4 and CD8 T cells and inhibits the release of IFN-γ by decreasing mTOR signalling. A better understanding of these complex immune regulatory mechanisms should facilitate the generation of more powerful and selective tools to manipulate cancer therapy.
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http://dx.doi.org/10.1016/j.prp.2021.153461DOI Listing
May 2021

High-Throughput Untargeted Serum Metabolomics Analysis of Hyperuricemia Patients by UPLC-Q-TOF/MS.

Evid Based Complement Alternat Med 2021 12;2021:5524772. Epub 2021 Jun 12.

School of Chinese Pharmacy, Beijing University of Chinese Medicine, Beijing 102488, China.

Hyperuricemia (HUA) as a metabolic disease is closely associated with metabolic disorders. The etiology and pathogenesis of HUA are not fully understood, so there is no radical cure so far. Metabolomics, a specialized study of endogenous small molecule substances, has become a powerful tool for metabolic pathway analysis of selected differential metabolites, which is helpful for initially revealing possible development mechanisms of various human diseases. Twenty HUA patients and 20 healthy individuals participated in the experiment, and ultrahigh performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry (UPLC-Q-TOF/MS) was employed to investigate serum samples to find differential metabolites. The statistical techniques used were principal component analysis and orthogonal partial least-squares discriminant analysis. The differences in metabolomics results of samples after pretreatment with different solvents were compared, 38, 20, 26, 28, 33, 50, and 40 potential differential metabolites were found, respectively, in HUA patient samples, and each group involved different metabolic pathways. Repetitive metabolites were removed, 138 differential metabolites in HUA serum were integrated for analysis, and the human body was affected by 7 metabolic pathways of glycerophospholipid metabolism, sphingolipid metabolism, arachidonic acid metabolism, linoleic acid metabolism, phenylalanine metabolism, phenylalanine, tyrosine and tryptophan biosynthesis, and -linolenic acid metabolism. In this work, the metabolomics approach based on UPLC-Q-TOF/MS was employed to investigate serum metabolic changes in HUA patients, 138 potential differential metabolites related to HUA were identified, which provided associations of lipids, amino acids, fatty acids, organic acids, and nucleosides profiles of HUA individuals. Metabolic pathways involved in glycerophospholipid metabolism, sphingolipid metabolism, arachidonic acid metabolism, linoleic acid metabolism, phenylalanine metabolism, phenylalanine, tyrosine and tryptophan biosynthesis, and -linolenic acid metabolism shed light on the understanding of the etiology and pathogenesis process of HUA.
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http://dx.doi.org/10.1155/2021/5524772DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8216829PMC
June 2021

A Reduction Active Theranostic Nanoparticle for Enhanced Near-Infrared Imaging and Phototherapy by Reducing Glutathione Level in Cancer Cells.

J Nanosci Nanotechnol 2021 12;21(12):5965-5971

Key Laboratory for Green Chemical Process of Ministry of Education, Hubei Key Laboratory for Novel Reactor and Green Chemistry Technology, Hubei Engineering Research Center for Advanced Fine Chemicals , School of Chemical Engineering and Pharmacy, Wuhan Institute of Technology, Wuhan, 430205, P. R. China.

Facile preparation of a tumoral-stimuli-activated theranostic nanoparticle with simple constituents remains a challenge for tumor theranostic nanosystems. Herein we design a simple reductionresponsive turn-on theranostic nanoparticle for achieving fluorescent imaging and phototherapy combination. The theranostic nanoparticle is prepared by a simple one-step dialysis method of reduction active amphiphilic hyperbranched poly(-amidoamines) and a near-infrared (NIR) dye indocyanine green (ICG). The fluorescence of ICG is quenched by the aggregation-caused quenching (ACQ) effect. The fluorescent intensity of free ICG at 816 nm was ∼40 times as high as that of particulate ICG. After reductive nanoparticles incubated with dithiothreitol (DTT), the size of the nanoparticles increased from 160 nm to 610 nm by Dynamic light scattering (DLS). As nanoparticles were internalized by cancer cells, the disulfide bonds would be cleaved by intracellular reduction agents like glutathione (GSH), leading to the release of entrapped ICG. The released ICG regained its fluorescence for self-monitoring the release and therapeutic effect of ICG by fluorescence spectra and the quantitative evaluation of NIR fluorescence intensity. Remarkably, nanoparticles can also reinforce antitumor efficacy through photodynamic therapy and GSH depletion property. This study provides new insights into designing turn-on theranostic systems.
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http://dx.doi.org/10.1166/jnn.2021.19514DOI Listing
December 2021

Fluorescence assay for the sensitive detection of fipronil based on an "on-off" oxidized SWCNH/aptamer sensor.

Anal Methods 2021 Jul 6. Epub 2021 Jul 6.

School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenhe District, Shenyang, Liaoning Province 110016, China.

A simple, quick, effective turn-on fluorescence assay for the determination of fipronil (FIP) was built based on the yellow fluorescence of FAM-aptamer and excellent quenching capability of the oxidized single-walled carbon nanohorns (The oxidized SWCNHs). Oxidized SWCNHs with the great advantage of good dispersibility in solution were generated by link to carboxyl group and were added to a specific FAM-aptamer at an optimal concentration to form an "on-off" oxidized SWCNH/FAM-aptamer fluorescent sensor. The structures of the oxidized SWCNHs were verified, and the comprehensive properties were evaluated by characterization techniques. This paper has exploited oxidized SWCNHs as a quenching agent to detect fipronil for the first time. Under the optimized conditions, the limit of detection (LOD) for fipronil was 3 nM, and the recovery of fipronil varied from 88.6% to 112.7% in different real samples with relative standard deviations (RSDs) not more than 5%. The developed method could be successfully applied for the determination of fipronil in tap water, honey and corn samples.
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http://dx.doi.org/10.1039/d1ay00769fDOI Listing
July 2021

Direct observation Brownian motion of individual nanoparticles in water using microsphere-assisted microscopy.

Opt Lett 2021 Jul;46(13):3099-3102

Observing Brownian motion of nanoscale objects through a traditional optical microscope is still a challenge. Here, we present a method to overcome this challenge by using a traditional optical microscope assisted with a removable microsphere-embedded thin film. The diffusion coefficient of individual unconstrained polystyrene (PS) nanoparticles with a diameter of 300 nm in water is calculated from their respective mean-square displacement versus time curves, and the measured diffusion coefficient shows good agreement with the theoretical Stokes-Einstein one, proving the feasibility of our method. In addition, the experimental results show that the movement of the PS nanoparticles is slowed down near a plane wall, and the diffusion coefficient is consistent with the theoretical constrained diffusion coefficient, which shows that our method can also study the constrained Brownian motion of nanoparticles constrained near a plane wall. Our research results are helpful for the application of microsphere-assisted microscopy in new fields and also provide a new method for nanoparticle tracking.
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http://dx.doi.org/10.1364/OL.427144DOI Listing
July 2021

Necroptotic virotherapy of oncolytic alphavirus M1 cooperated with Doxorubicin displays promising therapeutic efficacy in TNBC.

Oncogene 2021 Jul 21;40(29):4783-4795. Epub 2021 Jun 21.

Department of Pharmacology, Department of Microbiology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, 510080, China.

Triple-negative breast cancer (TNBC) is the most aggressive molecular subtype among breast tumors and remains a challenge even for the most current therapeutic regimes. Here, we demonstrate that oncolytic alphavirus M1 effectively kills both TNBC and non-TNBC. ER-stress and apoptosis pathways are responsible for the cell death in non-TNBC as reported in other cancer types, yet the cell death in TNBC does not depend on these pathways. Transcriptomic analysis reveals that the M1 virus activates necroptosis in TNBC, which can be pharmacologically blocked by necroptosis inhibitors. By screening a library of clinically available compounds commonly used for breast cancer treatment, we find that Doxorubicin enhances the oncolytic effect of the M1 virus by up to 100-fold specifically in TNBC in vitro, and significantly stalls the tumor growth of TNBC in vivo, through promoting intratumoral virus replication and further triggering apoptosis in addition to necroptosis. These findings reveal a novel antitumor mechanism and a new combination regimen of the M1 oncolytic virus in TNBC, and highlight a need to bridge molecular diagnosis with virotherapy.
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http://dx.doi.org/10.1038/s41388-021-01869-4DOI Listing
July 2021

Circulating microRNAs from serum exosomes as potential biomarkers in patients with spontaneous abortion.

Am J Transl Res 2021 15;13(5):4197-4210. Epub 2021 May 15.

Department of Obstetrics and Gynecology, The First Affiliated Hospital of Guangzhou University of Chinese Medicine Guangzhou 510405, China.

Background: Spontaneous abortion (SA) is a common complication in early pregnancy. Nevertheless, SA's etiology is complex, and the underlying molecular mechanisms of the pathogenesis behind SA remains unclear. The present study aims to find the feasibility of using serum exosomal miRNAs as novel biomarkers for SA.

Methods: In our study, we isolated the serum exosomes from the peripheral blood of the subjects. Then transmission electron microscopy (TEM), WB, and in vitro exosome tracing experiments were used. Comprehensive exosomal miRNA sequencing was performed to profile the differentially expressed miRNAs between the SA and normal pregnancy groups. Furthermore, genes targeted by miRNAs were further predicted and verified by TargetScan, miRDB, miRTarBase, miRWalk and HMDD V3.2. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis and pathway category were performed by the DIANA-miRPath v3.0 online tool. We then validated the expression levels of selected miRNAs by qRT-PCR. ROC analysis was performed to explore the clinical utility of the two miRNA as biomarkers for SA.

Results: TEM, NTA measurements and WB analysis showed the successful isolation of exosomes. Exosome labeling by PKH26 proved that exosomes could be efficiently taken up by primary decidual cells. Sequencing data found that with a total of 2,588, there were 189 significantly expressed exosomal miRNAs between the two groups. The most significantly expressed miRNA (miR-371a-5p, miR-206, miR-147b, miR-6859-5p, miR-410-3p, miR-1270 and miR-524-5p) were selected for further analysis. Through KEGG pathway analysis and pathway category, nine risk pathways were revealed. Among them, the Wnt signaling pathway, the Hippo signaling pathway, and the FoxO signaling pathway were pinpointed as major high-risk pathways. As a single marker, miR-371a-5p and miR-206 had a specificity of 83.3% and 70.8% at the sensitivity of 62.5% and 66.7%, respectively. The combined two markers achieved a specificity of 75% at the sensitivity of 79.2%.

Conclusions: Our results suggest that the circulating miRNAs from exosomes are altered in patients with SA. Findings of this exploratory study may provide potential biomarkers for SA.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8205814PMC
May 2021

Comparative methylome reveals regulatory roles of DNA methylation in melon resistance to Podosphaera xanthii.

Plant Sci 2021 Aug 2;309:110954. Epub 2021 Jun 2.

State Key Laboratory of Crop Biology, Shandong Agricultural University, Tai'an, Shandong 271018, China; College of Horticultural Science and Engineering, Shandong Agricultural University, Tai'an, Shandong 271018, China. Electronic address:

Powdery mildew caused by Podosphaera xanthii (P. xanthii) severely endangers melon (Cucumis melo L.) production, while the mechanistic understanding about its resistance to powdery mildew remains largely limited. In this study, we integrated transcriptomic and methylomic analyses to explore whether DNA methylation was involved in modulating transcriptional acclimation of melon to P. xanthii infection. Net photosynthetic rate (Pn), stomatal conductance (Gs), actual photochemical efficiency (ФPSII) and maximum PSII quantum yield (Fv/Fm) were significantly decreased in P. xanthii-infected plants relative to uninfected ones (Control), revealing apparent physiological disorders. Totally 4808 differentially expressed genes (DEGs) were identified by global analysis of gene expression in Control and P. xanthii-infected plants. Comparative methylome uncovered that 932 DEGs were associated with hypermethylation, while 603 DEGs were associated with hypomethylation in melon upon P. xanthii infection. Among these differential methylation-involved DEGs, a set of resistance-related genes including R genes and candidate genes in metabolic and defense pathways were further identified, demonstrating that DNA methylation might function as a new regulatory layer for melon resistance to P. xanthii infection. Altogether our study sheds new insights into the molecular mechanisms of melon against powdery mildew and provides some potential targets for improving melon disease resistance in future.
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http://dx.doi.org/10.1016/j.plantsci.2021.110954DOI Listing
August 2021

Identification of TYR, TYRP1, DCT and LARP7 as related biomarkers and immune infiltration characteristics of vitiligo via comprehensive strategies.

Bioengineered 2021 12;12(1):2214-2227

Department of Dermatology, the First People's Hospital of Yunnan Province, The Affiliated Hospital of Kunming University of Science and Technology, Kunming, Yunnan, China.

This study aims to explore biomarkers associated with vitiligo and analyze the pathological role of immune cell infiltration in the disease. We used the robust rank aggregation (RRA) method to integrate three vitiligo data sets downloaded from gene expression omnibus database, identify the differentially expressed genes (DEGs) and analyze the functional correlation. Then, the comprehensive strategy of combined weighted gene coexpression network analysis (WGCNA) and logical regression of the selection operator (LASSO), support vector machine recursive feature elimination (SVM-RFE), and random forest (RF) machine learning algorithm are employed to screen and biomarkers associated with vitiligo. Finally, the immune cell infiltration of vitiligo was evaluated by CIBERSORT, and the correlation between biomarkers and infiltrating immune cells was analyzed. Herein, we identified 131 robust DEGs, and enrichment analysis results showed that robust DEGs and melanogenesis were closely associated with vitiligo development and progression. TYR, TYRP1, DCT and LARP7 were identified as vitiligo-related biomarkers. Immune infiltration analysis demonstrated that CD4 T Cell, CD8 T Cell, Tregs, NK cells, dendritic cells, and macrophages were involved in vitiligo's pathogenesis. In summary, we adopted a comprehensive strategy to screen biomarkers related to vitiligo and explore the critical role of immune cell infiltration in vitiligo.: TYR, Tyrosinase; TYRP1, Tyrosinase-related protein-1; DCT, dopachrome tautomerase; LARP7, La ribonucleoprotein domain family, member-7; RRA, robust rank aggregation; DEGs, differentially expressed genes; WGCNA, weighted gene coexpression network analysis; LASSO, logical regression of the selection operator; SVM-RFE, support vector machine recursive feature elimination; RF, random forest; GWAS, Genome-wide association study; FasL, Fas-Fas ligand; Tregs, T-regulatory cells; NK, natural killer; GEPCs, gene expression profiling chips; GO, gene ontology; GSEA, gene set enrichment analysis; FDR, false discovery rate; AUC, area under the curve; ROC, receiver-operating characteristic; BP, biological process; CC, cellular component; MF, molecular function.
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http://dx.doi.org/10.1080/21655979.2021.1933743DOI Listing
December 2021

Austrobuxusin N, a new picrotoxane terpenoid glycoside, from the Australian endemic plant (Beuzev. & C.T. White) Airy Shaw.

Nat Prod Res 2021 May 18:1-7. Epub 2021 May 18.

Griffith Institute for Drug Discovery, Griffith University, Nathan, QLD, Australia.

A new picrotoxane terpenoid glycoside, austrobuxusin N (), together with four known compounds, austrobuxusin A-D (-), were isolated from the leaves of the Australian endemic plant (Beuzev. & C.T. White) Airy Shaw. The chemical structure of was elucidated by 1D- and 2D-NMR spectroscopy, along with MS data. The sugar moiety in was determined to be -D-glucose by acid hydrolysis and subsequent comparison of its specific rotation with that of standard. The relative configuration of the aglycone was assigned by ROESY NMR experiment and density functional theory (DFT) calculation of NMR data coupled with DP4 analysis. Cytotoxicity test revealed that compound exhibited 71% inhibition against Caco-2 cell line at the concentration of 166 µM.
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http://dx.doi.org/10.1080/14786419.2021.1923710DOI Listing
May 2021

New Methods and Technology in Drugs Metabolism and Pharmacokinetics (Part-II).

Authors:
Wei Cai Jiayu Zhang

Curr Drug Metab 2021 ;22(3):164

School of Pharmacy, Binzhou Medical University, Yantai, China.

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http://dx.doi.org/10.2174/138920022203210319085656DOI Listing
January 2021

A facile polymer mediated dye incorporation method for fluorescence encoded microbeads with large encoding capacities.

Chem Commun (Camb) 2021 May;57(37):4548-4551

School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, 200030, China.

Here we report a facile dye incorporation method for fluorescence encoded microbeads, which is achieved by tuning the mixed polymer type (blank and dye-labeled polymers) and their doping ratio through electrostatic loading into mesoporous beads. This method is universal to various carriers and could render large encoding capacities.
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http://dx.doi.org/10.1039/d0cc08202cDOI Listing
May 2021

Molecular Targeted Agent and Immune Checkpoint Inhibitor Co-Loaded Thermosensitive Hydrogel for Synergistic Therapy of Rectal Cancer.

Front Pharmacol 2021 16;12:671611. Epub 2021 Apr 16.

Department of Gastrointestinal Colorectal and Anal Surgery, China-Japan Union Hospital of Jilin University, Changchun, China.

Molecular targeted therapy has been proved effective in treatment of rectal cancer. Up-regulated expression of programmed death ligand-1 (PD-L1) was observed after the management of molecular targeted therapy, which made the therapeutic effect discounted. Tumors with higher PD-L1 expression were more sensitive and responsive to treatment of PD-L1 inhibitor. Therefore, the combination of molecular targeted therapy and immune checkpoint blockade makes sense. In this study, the copolymers of poly (ethylene glycol)-block-poly (-leucine) (PEG-PLLeu) were synthesized as a thermosensitive hydrogel composite for consecutive release of regorafenib (REG) and BMS202. The mechanical properties of PEG-PLLeu were investigated, confirming that PEG-PLLeu (5 wt.%) was suitable for injection as drug-delivery composite at low temperature and stable after sol-gel transition at body temperature. Importantly, the double drug loaded hydrogel showed superior antitumour activity over single drugs in an orthotopic rectal cancer model (CT26-Luc). Further analysis of the tumor tissues suggested that REG upregulated the expression of PD-L1 in tumor tissues. In addition, the immunosuppressive tumor microenvironment of CT26-Luc tumor was distinctly relieved under the effect of BMS202, as characterized by increased infiltration of CD8 T cells in tumors and enhanced secretion of antitumour cytokines (IFN-γ and TNF-α). Moreover, the drug-loaded composite showed no obvious toxicity in histological analysis. Taken together, the administration of REG and BMS202 in the PEG-PLLeu composite could induce a synergistic effect in treatment of rectal cancer without obvious toxicity, and thus represented a potential strategy for enhanced therapeutic modality.
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http://dx.doi.org/10.3389/fphar.2021.671611DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8085774PMC
April 2021

Integrative Analysis of TP53INP2 in Head and Neck Squamous Cell Carcinoma.

Front Genet 2021 9;12:630794. Epub 2021 Apr 9.

Hospital of Stomatology, Sun Yat-sen University, Guangzhou, China.

TP53INP2 plays an important role in regulating gene transcription and starvation-induced autophagy, however, its function in head and neck squamous cell carcinoma (HNSCC) remains unclear. Therefore, we assessed the expression and prognostic value of TP53INP2. In addition, RNAseq, miRNAseq, copy number variation, and mutation profiles from The Cancer Genome Atlas (TCGA) dataset were applied to evaluate the distinctive genomic patterns related to TP53INP2 expression. We found that TP53INP2 expression was lower in HNSCC compared with normal controls. Patients with higher TP53INP2 expression had longer survival time. Knockdown of TP53INP2 promoted cell viability. Functional analysis exhibited that TP53INP2 was linked to DNA replication, DNA repair, cell cycle, and multiple metabolic pathways. Moreover, TP53INP2 might affect the expression of multiple genes enhancing the transcriptional activity of nuclear hormone receptors. A competing endogenous RNA (ceRNA) network consisting of 33 lncRNAs, eight miRNAs, and 13 mRNAs was constructed based on the expression of TP53INP2. Taken together, our study highlights the potential value of TP53INP2 in predicting the survival of HNSCC and its important role in the genesis and development of HNSCC.
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http://dx.doi.org/10.3389/fgene.2021.630794DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8062980PMC
April 2021

Regulates the Development of Medullary Thymic Epithelial Cells and Contributes to the Establishment of Central Immune Tolerance.

Front Cell Dev Biol 2021 29;9:655552. Epub 2021 Mar 29.

State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.

Although some advances have been made in understanding the molecular regulation of mTEC development, the role of epigenetic regulators in the development and maturation of mTEC is poorly understood. Here, using the TEC-specific knockout mice, we found the deacetylase Sirtuin 6 () is essential for the development of functionally competent mTECs. First of all, TEC-specific deletion dramatically reduces the mTEC compartment, which is caused by reduced DNA replication and subsequent impaired proliferation ability of -deficient mTECs. Secondly, deficiency specifically accelerates the differentiation of mTECs from CD80Aire immature population to CD80Aire intermediate mature population by promoting the expression of . Finally, ablation in TECs markedly interferes the proper expression of tissue-restricted antigens (TRAs) and impairs the development of thymocytes and nTreg cells. In addition, TEC conditional knockout of results in severe autoimmune disease manifested by reduced body weight, the infiltration of lymphocytes and the presence of autoantibodies. Collectively, this study reveals that the expression of epigenetic regulator in TECs is crucial for the development and differentiation of mTECs, which highlights the importance of Sirt6 in the establishment of central immune tolerance.
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http://dx.doi.org/10.3389/fcell.2021.655552DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8044826PMC
March 2021

CD74 regulates cellularity and maturation of medullary thymic epithelial cells partially by activating the canonical NF-κB signaling pathway.

FASEB J 2021 05;35(5):e21535

Laboratory Medicine Center, Nanfang Hospital, Southern Medical University, Guangzhou, China.

Thymic epithelial cells (TECs) are indispensable for T cell development, T cell receptor (TCR) repertoire selection, and specific lineage differentiation. Medullary thymic epithelial cells (mTECs), which account for the majority of TECs in adults, are critical for thymocyte selection and self-tolerance. CD74 is a nonpolymorphic transmembrane glycoprotein of major histocompatibility complex class II (MHCII) that is expressed in TECs. However, the exact role of CD74 in regulating the development of mTEC is poorly defined. In this research, we found that loss of CD74 resulted in a significant diminution in the medulla, a selective reduction in the cell number of mature mTECs expressing CD80 molecules, which eventually led to impaired thymic CD4 T cell development. Moreover, RNA-sequence analysis showed that CD74 deficiency obviously downregulated the canonical nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling pathway in mTECs. Our results suggest that CD74 positively controls mTEC cellularity and maturation partially by activating the canonical NF-κB signaling pathway.
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http://dx.doi.org/10.1096/fj.202100139RDOI Listing
May 2021

Improvement of ECM-based bioroot regeneration via N-acetylcysteine-induced antioxidative effects.

Stem Cell Res Ther 2021 03 22;12(1):202. Epub 2021 Mar 22.

State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, No. 14, 3rd Sec., Ren Min Nan Road, Chengdu, 610041, China.

Background: The low survival rate or dysfunction of extracellular matrix (ECM)-based engineered organs caused by the adverse effects of unfavourable local microenvironments on seed cell viability and stemness, especially the effects of excessive reactive oxygen species (ROS), prompted us to examine the importance of controlling oxidative damage for tissue transplantation and regeneration. We sought to improve the tolerance of seed cells to the transplant microenvironment via antioxidant pathways, thus promoting transplant efficiency and achieving better tissue regeneration.

Methods: We improved the antioxidative properties of ECM-based bioroots with higher glutathione contents in dental follicle stem cells (DFCs) by pretreating cells or loading scaffolds with the antioxidant NAC. Additionally, we developed an in situ rat alveolar fossa implantation model to evaluate the long-term therapeutic effects of NAC in bioroot transplantation.

Results: The results showed that NAC decreased HO-induced cellular damage and maintained the differentiation potential of DFCs. The transplantation experiments further verified that NAC protected the biological properties of DFCs by repressing replacement resorption or ankylosis, thus facilitating bioroot regeneration.

Conclusions: The following findings suggest that NAC could significantly protect stem cell viability and stemness during oxidative stress and exert better and prolonged effects in bioroot intragrafts.
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http://dx.doi.org/10.1186/s13287-021-02237-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7986250PMC
March 2021

High-contrast colourimetric probes for fluoride and trace water based on tautomerization of naphthalimide and application in fingerprint imaging.

Spectrochim Acta A Mol Biomol Spectrosc 2021 Jun 9;254:119674. Epub 2021 Mar 9.

College of Biological and Pharmaceutical Sciences, China Three Gorges University, Yichang, Hubei 443002, PR China. Electronic address:

Three probes for fluoride ion and trace water based on naphthalimide were designed and synthesized. A new sensing mechanism based on naphthalimide tautomerization induced by fluoride ion and water was explored in the aprotic organic solvent. In the fluoride ion sensing process, the probes exhibited a remarkable absorption peak centred at 560 nm in the visible range of 400-700 nm. When trace water presented, the newly formed absorption peak centred at 560 nm gradually disappeared. The sensitive colour variation of the probe also was used in fingerprint imaging. Accordingly, the significant changes in chemical shift of dept135 and HNMR spectrum confirmed the structural transformation of the probes with high contrast. Furthermore, this work also presented an optimization strategy for the sensitivity of the probe based on regulatory tautomerization.
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http://dx.doi.org/10.1016/j.saa.2021.119674DOI Listing
June 2021

Ethnobotanical study on medicinal plants from the Dragon Boat Festival herbal markets of Qianxinan, southwestern Guizhou, China.

Plant Divers 2020 Dec 22;42(6):427-433. Epub 2021 Jan 22.

Key Laboratory of Economic Plants and Biotechnology, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, 650201, China.

Dragon Boat Festival herbal markets in the Qianxinan Buyi and Miao Autonomous Prefecture of southwestern Guizhou have a long well-conserved history. These markets, which are a feature of Buyi and Miao traditional medicines, contain a rich diversity of medicinal plants and traditional medical knowledge. Today, people in southwestern Guizhou still believe that using herbs during the Dragon Boat Festival prevents and can treat disease. In this study, we identified the fresh herbal plants sold at the herbal markets of Xingren City and Zhenfeng County in Qianxinan Buyi and Miao Autonomous Prefecture and quantified their importance. We identified 141 plant species (belonging to 114 genera and 61 families). The plant family with the most species was Asteraceae (14 species). Informants reported that most medicinal plants are herbaceous, with 95.7% of plants used for decoction and 30.5% used for medicinal baths. Medicinal plants are most commonly used to treat rheumatism, injury, and abdominal diseases. The utilization frequency index and relative importance values indicated that and are the most important plants sold at herbal markets during the Dragon Boat Festival. The price of medicinal materials sold in the market may serve as an indicator of the conservation status of species in the region. These findings indicate that the Dragon Boat Festival herbal markets in the Qianxinan Buyi and Miao Autonomous Prefecture fully embodies the characteristics of indigenous ethnomedicine and culture, and also exhibits the diversity of plant resources. We recommend that rare and endangered plants in this region be domesticated and protected.
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http://dx.doi.org/10.1016/j.pld.2020.12.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7936108PMC
December 2020

The proximity of the G-quadruplex to hemin impacts the intrinsic DNAzyme activity in mitochondria.

Chem Commun (Camb) 2021 Mar 24;57(24):3038-3041. Epub 2021 Feb 24.

CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, Multi-disciplinary Research Division, Institute of High Energy Physics and University of Chinese Academy of Sciences (UCAS), Chinese Academy of Sciences (CAS), Beijing 100049, P. R. China.

The DNAzyme activity of G-quadruplex/hemin in mitochondria has not been characterized. Herein, we report an unexpected difference in the DNAzyme activity between in vitro assays and in mitochondria. Molecular dynamic simulations illustrate how the interaction of the G-quadruplex with hemin may modulate the DNAzyme activity. These results might facilitate a better understanding of the catalytic mechanism of the DNAzyme and help the rational design of stable and active DNAzymes suitable for intracellular catalysis.
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http://dx.doi.org/10.1039/d0cc08316jDOI Listing
March 2021

Facile preparation of novel nickel sulfide modified KNbO heterojunction composite and its enhanced performance in photocatalytic nitrogen fixation.

J Colloid Interface Sci 2021 May 1;590:548-560. Epub 2021 Feb 1.

Department of Materials Science and Engineering, Zhejiang Normal University, Jinhua 321004, China; Key Laboratory of the Ministry of Education for Advanced Catalysis Materials, Institute of Physical Chemistry, Zhejiang Normal University, Jinhua 321004, China. Electronic address:

This work was designed to prepare a novel NiS/KNbO p-n heterojunction composite for efficient photocatalytic nitrogen fixation under simulated sunlight. The NiS/KNbO photocatalyst was prepared through a two-step hydrothermal method. X-ray diffraction, Raman spectroscopy, X-ray photoelectron spectroscopy, scanning electron microscopy, and transmission electron microscopy analyses proved that NiS nanoparticles were closely decorated on the surface of KNbO nanorods, to facilitate the migration of electrons between the two semiconductors. Mott-Schottky analysis indicated that the Femi level of KNbO is higher than that of NiS. Thus, the electron migration from KNbO to NiS occurs naturally. This migration elevates the band potential of NiS, makes NiS/KNbO form a type-II photocatalyst, and generates an internal electric field in the composite. The synergetic effect of the internal electric field and the type-II band structure endows NiS/KNbO with high efficiency in the spatial separation of photogenerated electron-hole pairs, verified by electrochemical impedance spectroscopy and transient photocurrent experiments. Therefore, NiS/KNbO presents good efficiency in photocatalytic N reduction with an NH production rate of 155.6 μmol·L·g·h, which is 1.9 and 6.8 times higher than those of KNbO and NiS, respectively. UV-visible diffuse reflectance spectroscopy and N-adsorption experiments were also performed to investigate the effect of light absorption and surface area on the photocatalytic reaction. Nevertheless, compared with the great promotion effect in charge separation, the contribution of the two factors can be ignored.
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http://dx.doi.org/10.1016/j.jcis.2021.01.086DOI Listing
May 2021

Theoretical and Experimental Study on Nonlinear Failure of an MEMS Accelerometer under Dual Frequency Acoustic Interference.

Sensors (Basel) 2021 Jan 31;21(3). Epub 2021 Jan 31.

Beijing Institute of Aerospace Control Device, Beijing 100094, China.

In order to quantitatively study the interfered output of the accelerometer under an acoustic injection attack, a mathematical model for fitting and predicting the accelerometer output was proposed. With ADXL103 as an example, an acoustic injection attack experiment with amplitude sweeping and frequency sweeping was performed. In the mathematical model, the R-squared coefficient was = 0.9990 in the acoustic injection attack experiment with amplitude sweeping, and = 0.9888 with frequency sweeping. Based on the mathematical model, the dual frequency acoustic injection attack mode was proposed. The difference frequency signal caused by the nonlinear effect was not filtered by the low-pass filter. At a 115 dB sound pressure level, the maximum acceleration bias of the output was 4.4 m/s and the maximum amplitude of fluctuation was 4.97 m/s. Two kinds of methods of prevention against acoustic injection attack were proposed, including changing the damping ratio of the accelerometer and adding a preposition low-pass filter.
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http://dx.doi.org/10.3390/s21030945DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7867008PMC
January 2021

Real-Time Visualization and Quantification of Oncolytic M1 Virus and .

Hum Gene Ther 2021 Feb;32(3-4):158-165

Department of Pharmacology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.

Alphavirus M1 is a promising oncolytic virus for cancer therapy. Here, we constructed a fluorescent reporter virus for real-time visualization and quantification of M1 virus both and . The reporter-encoding M1 virus maintained the characteristics of parental virus in the aspects of structure, replication capacity, the feature to induce cytopathic cell death, and the property of tumor targeting. The fluorescence is positively correlated with virus replication both and . More importantly, the reporter can be stably expressed for at least 10 generations in a serial passage assay. In summary, we successfully constructed stable and authentic reporter viruses for studying M1 virus and provided a feasible technical route for gene modification of oncolytic virus M1.
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http://dx.doi.org/10.1089/hum.2020.273DOI Listing
February 2021

Different Dose Regimens of Intravenous Tranexamic Acid in Adolescent Spinal Deformity Surgery: A Systematic Review and Meta-Analysis.

Biomed Res Int 2020 28;2020:3101358. Epub 2020 Nov 28.

Department of Spine Surgery, China-Japan Friendship Hospital, Beijing, China.

Objective: To evaluate the efficacy and safety of different dose regimens of intravenous (IV) tranexamic acid (TXA) in adolescent spinal deformity surgery.

Methods: Two researchers independently searched multiple databases, including PubMed, Embase, Cochrane Library, and Web of Science to find studies that met the inclusion criteria. A meta-analysis was performed based on the guidelines of the .

Results: Six randomized controlled trials (RCTs) and eleven non-RCTs were identified, including 1148 patients. According to different dose regimens of IV TXA, the included studies were divided into the high-dose group and the low-dose group. Compared with placebo, both groups had less total blood loss (TBL) (high dose: WMD = -1737.55, 95% CI: (-2247.16, -1227.94), < 0.001, = 0%; low dose: WMD = -528.67, 95% CI: (-666.06, -391.28), < 0.001, = 0%), intraoperative blood loss (IBL) (high dose: WMD = -301.48, 95% CI: (-524.3, -78.66), = 0.008, = 60.3%; low dose: WMD = -751.14, 95% CI: (-967.21, -535.08), < 0.001, = 0%), and blood transfusion rates (high dose: RR = 0.19, 95% CI: (0.1, 0.37), < 0.001, = 0%; low dose: RR = 0.4, 95% CI: (0.18, 0.91), = 0.029, = 57%). High-dose IV TXA use was associated with more vertebral fusion segments (WMD = 0.53, 95% CI: (0.23, 0.82), < 0.001, = 31.2%). Low-dose IV TXA use was associated with shorter operative time (WMD = -18.43, 95% CI: (-26.68, -10.17), < 0.001, = 0%).

Conclusion: High-dose and low-dose IV TXA were effective in reducing TBL, IBL, and blood transfusion rates without increasing complications in adolescent patients undergoing spinal deformity surgery. Low-dose IV TXA was effective in reducing the operative time. Both the high-dose and low-dose groups had similar preoperative and postoperative Hb levels compared to the control group.
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http://dx.doi.org/10.1155/2020/3101358DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7803096PMC
May 2021

Long non-coding RNA CASC9 promotes the progression and development of gastric cancer via regulating miR-370/EGFR axis.

Dig Liver Dis 2021 Apr 18;53(4):509-516. Epub 2021 Jan 18.

Department of Gastrointestinal Colorectal and Anal surgery, China-Japan Union Hospital of Jilin University, NO.126 Xiantai Street, Changchun, Jilin 130033, China. Electronic address:

lncRNA cancer susceptibility 9 (CASC9) is a pivotal modulator in various cancers, such as colorectal cancer, breast cancer and esophageal cancer. However, its exact role in gastric cancer (GC) has not been systematically studied. Here, using a combination of molecular and cell biology approaches, we found that CASC9 also acts as a factor promoting the progression of GC. First, mRNA and protein expression levels were quantified by real-time quantitative reverse transcription PCR (qRT-PCR) and western blot, respectively. Second, CCK-8 assay, colony formation assay and cell cycle analysis were performed to compare the cell growth abilities when CASC9 was knocked down. Third, the proliferative cells were determined by labeling Edu and the regulatory effect of CASC9 on miR-370 was detected by RNA-protein pull-down and luciferase reporter assays. Finally, in vivo mice model was established to verify the role of CASC9 in promoting GC progression. Our results showed that CASC9 was up-regulated significantly in both GC tissues and cell lines. Conversely, CASC9 knockdown inhibited GC growth in vitro. Further analysis indicated that CASC9 directly targeted miR-370 and negatively regulated miR-370 expression in GC. Besides, EGFR (epidermal growth factor receptor) was identified as a direct target gene of miR-370. Taken together our results support a model in which CASC9 promotes GC progression through miR-370/EGFR/ERK/AKT pathway. Finally, in vivo CASC9 knockdown resulted in impaired GC growth. In sum, this study firstly demonstrates that lncRNA CASC9 acts as an oncogene through altering EGFR expression level via negatively regulating miR-370 expression.
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http://dx.doi.org/10.1016/j.dld.2020.12.115DOI Listing
April 2021

The application of a new clear removable appliance with an occlusal splint in early anterior crossbite.

BMC Oral Health 2021 01 21;21(1):36. Epub 2021 Jan 21.

State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, No. 14, 3rd Sec. Ren Min Nan Road, Chengdu, 610041, Sichuan Province, People's Republic of China.

Background: The effectiveness of anterior crossbite treatment in preschool-aged children depends on the treatment design and patient compliance. Common early treatment appliances with steel wires and acrylic resin can bring about numerous problems, such as toothache, sore gums and mucous membrane injury. The aim of this study was to propose a new clear removable appliance to provide preschool-age children with an improved experience of early occlusal interference treatment.

Methods: Appliances were designed with the help of 3-dimensional (3D) digital reconstruction oral models and fabricated using 3D printing technology and the pressed film method. Then, the mechanical properties of the original dental coping sheet and thermoformed aligners were assessed in a simulated intraoral environment. Preschool-age participants who displayed anterior crossbite were recruited in this study. Records (photographs and impressions) were taken before the treatment (T1), during the treatment (T2) and at the end of the treatment (T3). The effects of treatment were evaluated by clinical examination and questionnaires.

Results: Normal degrees of overbite and overjet in the primary dentition were achieved using this new appliance. Dental and soft tissue relationships were improved. Questionnaires showed that the safety evaluation, degree of comfort and convenience grades of the appliance were all relatively high.

Conclusion: This explorative study demonstrates that our new clear removable appliance is able to correct early-stage anterior crossbite in a safe, comfortable, convenient and efficient way. Thus, it is a promising method to correct a certain type of malocclusion, and its clinical use should be promoted in the future.
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http://dx.doi.org/10.1186/s12903-021-01393-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7818763PMC
January 2021

D-arginine-loaded metal-organic frameworks nanoparticles sensitize osteosarcoma to radiotherapy.

Biomaterials 2021 02 2;269:120642. Epub 2021 Jan 2.

CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, Institute of High Energy Physics and University of Chinese Academy of Sciences (UCAS), Chinese Academy of Sciences (CAS), Beijing, 100049, PR China. Electronic address:

Osteosarcoma is a common type of bone cancers with a high rate of pulmonary recurrence. High-dose radiation therapy is useful for the ablation of unresectable osteosarcoma. However, it may cause severe adverse effects. To address this problem, we developed D-arginine-loaded metal-organic frameworks (MOF) nanoparticles for improving the radiosensitivity of osteosarcoma. D-arginine, a metabolically inert enantiomer of L-arginine, could produce nitric oxide and down-regulate hypoxia-inducible factor-1alpha (HIF-1α) to alleviate tumor hypoxia. In addition, MOF could also generate free radicals to kill the tumor cells. Results demonstrate that D-arginine-loaded nanoparticles enhanced tumor ablation and prevented the lung metastasis in mice upon radiation therapy. Furthermore, the nanoparticles or radiation alone had relatively low toxicity in cells and mice. Therefore, D-arginine-loaded MOF nanoparticles are relatively safe and highly effective in sensitizing osteosarcoma to radiotherapy.
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http://dx.doi.org/10.1016/j.biomaterials.2020.120642DOI Listing
February 2021

Shifts in composition and function of soil fungal communities and edaphic properties during the reclamation chronosequence of an open-cast coal mining dump.

Sci Total Environ 2021 May 6;767:144465. Epub 2021 Jan 6.

State Key Laboratory of Coal Resources and Safe Mining, China University of Mining and Technology, Beijing 100083, China.

The diversity, composition and ecological guilds of soil fungal communities in relation to revegetation were assessed during an open-cast mining dump reclamation chronosequence of the soil <1, 5, 10, 15 and 20 years after the start of reclamation. Soil pH and electrical conductivity, total nitrogen (TN), soil organic carbon (SOC), available potassium (AK), and available phosphorus (AP) contents, and soil phosphatase (Pha), urease (U) and invertase (INV) activities were measured. Using high-throughput sequence analysis on internal transcribed spacer (ITS) sequences, 1059 soil fungal operational taxonomic units (OTUs) were identified belonging to 64 orders and these were further categorized by ecological guild. Soil fungal diversity indices were significantly different between the early (<1 year) and later reclamation communities. Nonmetric multidimensional scaling (NMDS) analysis indicates that the composition and ecological guilds of soil fungal communities were significantly different early in the process and at the end of reclamation (P < 0.05). Co-occurrence network and structural equation model analyses show that soil fungal community structure and ecological guilds were correlated with edaphic properties and had an indirect effect on soil available nutrients through direct action on soil enzymes. Overall, the data suggest that soil fungal community composition and function within an open-cast coal mining dump reclamation chronosequence changed during the period following artificial re-vegetation, with interactions between edaphic properties and soil fungal communities associated with these changes.
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http://dx.doi.org/10.1016/j.scitotenv.2020.144465DOI Listing
May 2021

New Methods and Technology in Drugs Metabolism and Pharmacokinetics.

Authors:
Jiayu Zhang Wei Cai

Curr Drug Metab 2020;21(12):959

School of Pharmaceutical Sciences, Hunan University of Medicine, Huaihua, 41800, China.

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http://dx.doi.org/10.2174/138920022112201207111132DOI Listing
January 2020

Rapid Profiling and Identification of Vitexin Metabolites in Rat Urine, Plasma and Faeces after Oral Administration Using a UHPLC-Q-Exactive Orbitrap Mass Spectrometer Coupled with Multiple Data-mining Methods.

Curr Drug Metab 2021 ;22(3):185-197

School of Pharmacy, Bin Zhou Medical University, Yantai 260040, China.

Background: Vitexin is a natural flavonoid compound with multiple pharmacological activities and is extracted from the leaves and seeds of Vitex negundo L. var. cannabifolia (Sieb. et Zucc.) Hand.-Mazz. However, the metabolite characterization of this component remains insufficient.

Objective: To establish a rapid profiling and identification method for vitexin metabolites in rat urine, plasma and faeces after oral administration using a UHPLC-Q-Exactive orbitrap mass spectrometer were coupled with multiple data-mining methods.

Methods: In this study a simple and rapid systematic strategy for the detection and identification of constituents was proposed based on UHPLC-Q-Exactive Orbitrap mass spectrometry in parallel reaction monitoring mode combining diagnostic fragment ion filtering techniques.

Results: A total of 49 metabolites were fully or partially characterized based on their accurate mass, characteristic fragment ions, retention times, corresponding ClogP values, and so on. It is obvious that C-glycosyl flavonoids often display an [M+H-120] ion that represents the loss of CHO. As a result, these metabolites were presumed to be generated through glucuronidation, sulfation, deglucosylation, dehydrogenation, methylation, hydrogenation, hydroxylation, ring cleavage and their composite reactions. Moreover, the characteristic fragmentation pathways of flavonoids, chalcones and dihydrochalcones were summarized for the subsequent metabolite identification.

Conclusion: The current study provided an overall metabolic profile of vitexin which will be of great help in predicting the in vivo pharmacokinetic profiles and understanding the action mechanism of this active ingredient.
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http://dx.doi.org/10.2174/1389200221999210101232841DOI Listing
January 2021