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Introduction: Liuweizhiji Gegen-Sangshen beverage (LGS) is popular in China, which has been used for alleviating alcohol-mediated discomfort and preventing alcoholic liver disease (ALD). This beverage is consisted of six herbal components that are known as functional foods and fruits. LGS is rich in polysaccharides, however, the activity and quality evaluation of LGS-derived polysaccharides remain unexplored. The purpose of this study is thus to establish a comprehensive quality control methodology for the assessment of LGS polysaccharides (LGSP) and to further explore the anti-oxidant, anti-inflammatory as well as prebiotic effect of LGSP. Methods: LGSP was extracted, followed by analysis of molecular weight distribution, monosaccharide content and structural characterization via integrating the application of high-performance size exclusion chromatography (HPSEC), 1-phenyl-3-methyl-5-pyrazolone-HPLC (PMP-HPLC), fourier transform infrared spectroscopy (FT-IR) as well as nuclear magnetic resonance spectroscopy (NMR) techniques. The anti-oxidation activity of LGSP was determined by DPPH, ABTS, hydroxyl radical scavenging capacity and total antioxidant capacity. The anti-inflammation of LGSP were assessed on the RAW 264.7 cells. The effect of LGSP on growth of Lactobacillus, Bifidobacterium bifidum and Bifidobacterium adolescentis was evaluated. Results: The results demonstrated that LGSP had two molecular weight distribution peaks, with the average molecular weights of (6.569 ± 0.12) × 104 Da and (4.641 ± 0.30) × 104 Da. LGSP was composed of 8 monosaccharides, with galacturonic acid, glucose rhamnose and galactose representing the highest molar ratios. Homogalacturonic acid (HG) type and rhamnosegalacturonic acid glycans I (RG-I) type and α-1,4-glucan were present in LGSP. LGSP concentration in LGS was 17.94 ± 0.28 mg/mL. Furthermore, fingerprint analysis combined with composition quantification of 10 batches of LGSP demonstrated that there was a high similarity among batches. Notably, LGSP exhibited anti-oxidant effect and inhibited expressions of pro-inflammatory factors (TNF-α and IL-6) in LPS-stimulated RAW 264.7 cells. In addition, LGSP remarkably promoted the proliferation of probiotics Lactobacillus, Bifidobacterium bifidum and Bifidobacterium adolescentis, showing good prebiotic activity. Discussion: The results of present study would be of help to gain the understanding of structure-activity relationship of LGSP, provide a reference for quality evaluation of bioactive LGSP, and facilitate development of unique health and functional products in the future.
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INTRODUCTION: Liuweizhiji Gegen-Sangshen (LGS) oral liquid is a Chinese patent medicine that is widely used for the prevention and treatment of alcoholic liver disease in clinical practice. However, the chemical complexity of LGS has not yet been investigated. OBJECTIVE: The aim of this study was to rapidly identify chemical constituents of LGS and establish a quality control method based on fingerprint and quantitative analysis. METHODOLOGY: A comprehensive strategy was used by combining qualitative analysis by ultra-performance liquid chromatography tandem quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) and fingerprint analysis by high-performance liquid chromatography with diode array detection (HPLC-DAD). RESULTS: A total of 162 chemical components in LGS, including 91 flavonoids, 31 organic acids, and 20 phenolic compounds, were identified or preliminarily characterized in both positive and negative ion modes based on the UPLC-Q-TOF-MS results. Of these, 37 were confirmed with the reference standards. In fingerprint analysis, 23 peaks were chosen as common peaks and used to evaluate the similarity of different batches of LGS. Subsequently, a rapid quantification method was optimized and validated for the simultaneous determination of multiple chemical markers in LGS. The validated quantitative method was successfully used to analyze different batches of LGS samples. CONCLUSION: The proposed comprehensive strategy combining HPLC-DAD fingerprinting and multi-component quantification demonstrated satisfactory results with high efficiency, accuracy, and reliability. This can be used as a reference for the overall quality consistency evaluation of Chinese patent medicines.
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Medicamentos de Ervas Chinesas , Controle de Qualidade , Cromatografia Líquida de Alta Pressão/métodos , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/análise , Flavonoides/análise , Espectrometria de Massas/métodos , Reprodutibilidade dos Testes , Administração Oral , Fenóis/análiseRESUMO
Aging entails gradual functional decline influenced by interconnected factors. Multiple hallmarks proposed as common and conserved underlying denominators of aging on the molecular, cellular and systemic levels across multiple species. Thus, understanding the function of aging hallmarks and their relationships across species can facilitate the translation of anti-aging drug development from model organisms to humans. Here, we built AgeAnnoMO (https://relab.xidian.edu.cn/AgeAnnoMO/#/), a knowledgebase of multi-omics annotation for animal aging. AgeAnnoMO encompasses an extensive collection of 136 datasets from eight modalities, encompassing 8596 samples from 50 representative species, making it a comprehensive resource for aging and longevity research. AgeAnnoMO characterizes multiple aging regulators across species via multi-omics data, comprehensively annotating aging-related genes, proteins, metabolites, mitochondrial genes, microbiotas and age-specific TCR and BCR sequences tied to aging hallmarks for these species and tissues. AgeAnnoMO not only facilitates a deeper and more generalizable understanding of aging mechanisms, but also provides potential insights of the specificity across tissues and species in aging process, which is important to develop the effective anti-aging interventions for diverse populations. We anticipate that AgeAnnoMO will provide a valuable resource for comprehending and integrating the conserved driving hallmarks in aging biology and identifying the targetable biomarkers for aging research.
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Envelhecimento , Bases de Conhecimento , Multiômica , Animais , Humanos , Envelhecimento/genética , Biomarcadores , Longevidade/genéticaRESUMO
As a ligand-dependent transcription factor, retinoid-associated orphan receptor γt (RORγt) that controls T helper (Th) 17 cell differentiation and interleukin (IL)-17 expression plays a critical role in the progression of several inflammatory and autoimmune conditions. An emerging novel approach to the therapy of these diseases thus involves controlling the transcriptional capacity of RORγt to decrease Th17 cell development and IL-17 production. Several RORγt inhibitors including both antagonists and inverse agonists have been discovered to regulate the transcriptional activity of RORγt by binding to orthosteric- or allosteric-binding sites in the ligand-binding domain. Some of small-molecule inhibitors have entered clinical evaluations. Therefore, in current review, the role of RORγt in Th17 regulation and Th17-related inflammatory and autoimmune diseases was highlighted. Notably, the recently developed RORγt inhibitors were summarized, with an emphasis on their optimization from lead compounds, efficacy, toxicity, mechanisms of action, and clinical trials. The limitations of current development in this area were also discussed to facilitate future research.
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Lung adenocarcinoma (LUAD) is a deadly tumor with dynamic evolutionary process. Although much endeavors have been made in identifying the temporal patterns of cancer progression, it remains challenging to infer and interpret the molecular alterations associated with cancer development and progression. To this end, we developed a computational approach to infer the progression trajectory based on cross-sectional transcriptomic data. Analysis of the LUAD data using our approach revealed a linear trajectory with three different branches for malignant progression, and the results showed consistency in three independent cohorts. We used the progression model to elucidate the potential molecular events in LUAD progression. Further analysis showed that overexpression of BUB1B, BUB1 and BUB3 promoted tumor cell proliferation and metastases by disturbing the spindle assembly checkpoint (SAC) in the mitosis. Aberrant mitotic spindle checkpoint signaling appeared to be one of the key factors promoting LUAD progression. We found the inferred cancer trajectory allows to identify LUAD susceptibility genetic variations using genome-wide association analysis. This result shows the opportunity for combining analysis of candidate genetic factors with disease progression. Furthermore, the trajectory showed clear evident mutation accumulation and clonal expansion along with the LUAD progression. Understanding how tumors evolve and identifying mutated genes will help guide cancer management. We investigated the clonal architectures and identified distinct clones and subclones in different LUAD branches. Validation of the model in multiple independent data sets and correlation analysis with clinical results demonstrate that our method is effective and unbiased.
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Adenocarcinoma de Pulmão , Adenocarcinoma , Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Transcriptoma/genética , Adenocarcinoma/genética , Estudo de Associação Genômica Ampla , Estudos Transversais , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/patologiaRESUMO
Alternative polyadenylation (APA) is a widespread posttranscriptional regulation process. APA generates diverse mRNA isoforms with different 3' UTR lengths, affecting mRNA expression, miRNA binding regulation and alternative splicing events. Previous studies have demonstrated the important roles of APA in tumorigenesis and cancer progression through diverse aspects. Thus, a comprehensive functional landscape of diverse APA events would aid in a better understanding of the underlying mechanisms related to APA in human cancers. Here, we built CAFuncAPA (https://relab.xidian.edu.cn/CAFuncAPA/) to systematically annotate the functions of 15478 APA events in human pan-cancers. Specifically, we first identified APA events associated with cancer survival and tumor progression. We annotated the potential downstream effects of APA on genes/isoforms expression, regulation of miRNAs, RNA binding proteins (RBPs) and alternative splicing events. Moreover, we also identified up-regulators of APA events, including the effects of genetic variants on poly(A) sites and RBPs, as well as the effect of methylation phenotypes on APA events. These findings suggested that CAFuncAPA can be a helpful resource for a better understanding of APA regulators and potential functions in cancer biology.
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In recent years, the explosive growth of spatial technologies has enabled the characterization of spatial heterogeneity of tissue architectures. Compared to traditional sequencing, spatial transcriptomics reserves the spatial information of each captured location and provides novel insights into diverse spatially related biological contexts. Even though two spatial transcriptomics databases exist, they provide limited analytical information. Information such as spatial heterogeneity of genes and cells, cell-cell communication activities in space, and the cell type compositions in the microenvironment are critical clues to unveil the mechanism of tumorigenesis and embryo differentiation. Therefore, we constructed a new spatial transcriptomics database, named SPASCER (https://ccsm.uth.edu/SPASCER), designed to help understand the heterogeneity of tissue organizations, region-specific microenvironment, and intercellular interactions across tissue architectures at multiple levels. SPASCER contains datasets from 43 studies, including 1082 sub-datasets from 16 organ types across four species. scRNA-seq was integrated to deconvolve/map spatial transcriptomics, and processed with spatial cell-cell interaction, gene pattern and pathway enrichment analysis. Cell-cell interactions and gene regulation network of scRNA-seq from matched spatial transcriptomics were performed as well. The application of SPASCER will provide new insights into tissue architecture and a solid foundation for the mechanistic understanding of many biological processes in healthy and diseased tissues.
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Bases de Dados Genéticas , Perfilação da Expressão Gênica , Humanos , Carcinogênese , Comunicação Celular , Diferenciação Celular , Análise de Célula Única , Transcriptoma , Microambiente TumoralRESUMO
Photovoltaic energy as one of the important alternatives to traditional fossil fuels has always been a research hot spot in the field of renewable and clean solar energy. Very recently, the anomalous ferroelectric photovoltaic effect in multiferroic bismuth ferrite (BiFeO3) has attracted much attention due to the above-bandgap photovoltage and switchable photocurrent. However, its photocurrent density mostly in the magnitudes of µA/cm2 resulted in a poor power conversion efficiency, which severely hampered its practical application as a photovoltaic device. In this case, a novel approach was designed to improve the photocurrent density of BiFeO3 through the cooperative effect of the gradient distribution of oxygen vacancies and consequently induced the flexoelectric effect realized in the (La, Co) gradient-doped BiFeO3 multilayers. Subsequent results and analysis indicated that the photocurrent density of the gradient-doped multilayer BiFeO3 sample was nearly 3 times as much as that of the conventional doped single-layer sample. Furthermore, a possible mechanism was proposed herein to demonstrate roles of band engineering and the flexoelectric effect on the photovoltaic performance of the gradient-doped BiFeO3 film.
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A monoclonal antibody (mAb) and an indirect competitive enzyme-linked immunosorbent assay (ic-ELISA) for ornidazole (ONZ) detection were developed. ONZ was conjugated with cationic bovine serum albumin as a hapten to generate the artificial immunogens and coating antigens. BALB/c mice were immunized, and mAbs were obtained. The competitive inhibition curve of ic-ELISA was y=0.0438x2-0.2101x+0.2925, with R2=0.9941. The 50% inhibition concentration, the limit of detection, and limit of quality for ONZ were 0.15, 0.01, and 0.05µg/kg, respectively. The cross-reactivity of the mAbs to secnidazole was 0.33%. The recoveries were from 89.18% to 101.63% and the coefficient of variation was less than 7.15% in chicken, chicken liver, and honey samples, all of which had ONZ concentrations of 0.05 and 0.1µg/kg. Results showed that the ic-ELISA based on mAb could be used for the rapid detection for ONZ.
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Anticorpos Monoclonais , Ensaio de Imunoadsorção Enzimática/métodos , Ornidazol/análise , Animais , Reações Cruzadas , Feminino , Limite de Detecção , Camundongos , Camundongos Endogâmicos BALB C , Ornidazol/imunologiaRESUMO
Two novel immunizing haptens of 3-methyl-quinoxaline-2-carboxylic acid (MQCA) were synthesized and conjugated with cationized bovine serum albumin. Female BALB/c mice were immunized with above conjugates, splenocytes were fused with Sp2/0 cells to produce monoclonal antibody. Compared with previous studies, antibodies raised in this work showed higher sensitivity. Meantime, a novel heterologous coating hapten was also prepared. The indirect competitive enzyme-linked immunosorbent assay (icELISA) based on the optimum condition showed an IC50 of 3.1µg/kg (ppb), and the linear range of 0.46-10.5ppb for MQCA. The limit of detect (LOD) of MQCA in swine muscle, swine liver and chicken was 0.32, 0.54, and 0.28ppb, respectively. The LOD of this assay can satisfy the minimum required performance levels (4ppb) for MQCA. These results indicated that the proposed ELISA, with high sensitivity and specificity, as well as good reproducibility and accuracy, is suitable for determination of MQCA residues in food samples.