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There have been many analytical methods for natural estrogens in commercial dairy milk samples, but in most of which, only four major estrogens (estrone (E1), 17ß-estradiol (E2), estriol (E3), and 17α-estradiol (αE2)) were included. This work developed an effective GC-MS analytical method for simultaneous analysis of twelve natural estrogens in commercial dairy milk sample, in which eight far-less well-known natural estrogens (2-hydroxyestone (2OHE1), 4-hydroxyestrone (4OHE1), 2-hydroxyestradiol (2OHE2), 4-hydroxyestradiol (4OHE2), 16-epiestriol (16epiE3), 16α-hydroxyestrone (16αOHE1), 16-ketoestradiol (16ketoE2) and 17epiestriol (17epiE3)) were included besides the four major natural estrogens. With liquid-liquid extraction and solid phase extraction, twelve natural estrogens in commercial dairy milk could be effectively extracted. The established method showed good linearity (R2 > 0.9991), low limits of detections (LODs, 0.02-0.11 ng/g), as well as excellent recoveries (64-117%) with satisfactory low relative standard deviations (RSDs, 0.8-14.7%). This established method was applied to seven commercial dairy milk samples, and all the twelve natural estrogens were frequently detected except for 4OHE2 without detection in any sample. Our results showed that the concentration contribution ratios of the eight far-less well-known natural estrogens in commercial dairy milk samples contributed to 32-83%, while the corresponding contribution ratios based on estrogen equivalence (EEQ) were 21-62%. This work highlighted the high abundance of the eight far-less well-known natural estrogens in commercial dairy milk based on both concentration and EEQ, which has been neglected for a long time.
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Estrogênios , Leite , Animais , Estrogênios/análise , Cromatografia Gasosa-Espectrometria de Massas , Leite/química , Estradiol/análise , Estriol/análise , Extração em Fase Sólida/métodos , Extração Líquido-Líquido , Cromatografia Líquida de Alta Pressão/métodosRESUMO
Bisphenol analogues (BPs) and natural estrogens (NEs) as two important groups of endocrine-disrupting compounds (EDCs) in drinking water treatment plants (DWTPs) have been hardly investigated except bisphenol A (BPA) and three major NEs including estrone (E1), 17ß-estradiol (E2) and estriol (E3). In this study, a GC-MS analytical method was firstly established and validated for trace simultaneous determination of ten BPs and twelve NEs in drinking water, which included BPA, bisphenol B (BPB), bisphenol C (BPC), bisphenol E (BPE), bsiphenol F (BPF), bsiphenol P (BPP), bisphenol S (BPS), bisphenol Z (BPZ), bisphenol AF (BPAF), bisphenol AP (BPAP), E1, E2, E3, 17α-estradiol (17α-E2), 2-hydroestrone (2OHE1), 16hydroxyestrone (16α-OHE1), 4-hydroestrone (4OHE1), 2-hydroxyesstradiol (2OHE2), 4-hydroxyestradiol (4OHE2), 17-epiestriol (17epiE3), 16-epiestriol (16epiE3) and 16keto-estraiol (16ketoE2). This investigation showed that eighteen out of twenty-two targeted compounds were detected in drinking source waters of eight DWTPs with concentrations ranging from not detected to 142.8 ng/L. Although the conventional treatment process of DWTP could efficiently remove both BPs and NEs with respective removal efficiencies of 74.1%-90.9% and 74.5%-100%, BPA, BPS, BPE, BPZ, E1, 2OHE1, and 2OHE2 were found in the finished drinking waters. Chlorination could remove part of BPs and NEs, but the efficiency varied greatly with DWTP and the reason was unknown. In the finished drinking waters of eight DWTPs, the highest chemically calculated estrogen equivalence (EEQ) derived from BPs and NEs was up to 6.11 ngE2/L, which was over 22 times that could do harm to zebrafish, indicating a potential risk to human health. Given the fact that many chlorination products of BPs and NEs likely have higher estrogenic activities, the estrogenic effect of BPs and NEs in finished drinking water should be accurately examined urgently with the inclusion of BPs, NEs as well as their main chlorinated by-products. This study shed new light on the occurrence, removal, and potential estrogenic effects of BPs and NEs in DWTPs.
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Água Potável , Purificação da Água , Humanos , Animais , Estrogênios/análise , Peixe-Zebra , Estrona , Estradiol , Compostos Benzidrílicos/química , EstriolRESUMO
Saccharomyces cerevisiae var. diastaticus (S. diastaticus) is a major spoilage yeast in brewing. In the present research, the antifungal properties of nerol and the proteome response of S. diastaticus were studied. Results showed nerol can inhibit cell budding and delay yeast fermentation in a dose-depended manner. After 3 d of treatment with 0.25 mg·mL-1 nerol, intracellular ROS levels increased 1.66-fold (P < 0.01), and the cells with damaged membrane increased to 23.2 %. Quantitative proteomic profiles utilizing a capillary-HPLC-MS/MS technology revealed that proteins involved in the metabolism of fermentable sugars were up-regulated in S. diastaticus cells treated with nerol, indicating nerol treatment altered the metabolite pattern of fermentable sugars. Proteins associated with the cell membrane biogenesis, heat shock proteins, amino acid biosynthesis, and glutathione metabolism were similarly up-regulated. These findings revealed the mechanism of nerol-induced yeast cell damage as well as the detoxification response of yeast cells.
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Proteínas de Saccharomyces cerevisiae , Saccharomyces cerevisiae , Saccharomyces cerevisiae/metabolismo , Proteoma/análise , Antifúngicos/farmacologia , Antifúngicos/metabolismo , Proteômica/métodos , Espectrometria de Massas em Tandem , Proteínas de Saccharomyces cerevisiae/metabolismo , Fermentação , Açúcares/metabolismoRESUMO
BACKGROUND: Bitter flavors and antioxidant activities are critical characteristics and indicators, respectively, of beer quality. To gain a better understanding of dry-hopped beer's bitterness, this work comprehensively evaluated the perceived bitterness intensity and bitterness attributes from aspects of beer aroma and non-volatile bitter compounds using sensory analysis under two conditions: (i) with and (ii) without nose clips. To quantify bitter and volatile compounds, the work conducted chromatographic analyses: high-performance liquid chromatography (HPLC), ultra-performance liquid chromatography-mass spectrometry (UPLC-MS) and gas chromatography-mass spectrometry (GC-MS). Simultaneously, this work assessed the antioxidant activity of commercially dry-hopped beers. RESULTS: First, dry-hopped beer in this study contained abundant non-volatile bitter compounds (hop bitter acids, polyphenols and flavonoids), and aroma was validated using HPLC, UPLC-MS and GC-MS methods. Moreover, the bitter-tasting perception test findings demonstrated that many dry-hopped beers had a higher bitterness intensity when evaluated without a nose clip, whereas this phenomenon was adverse in several ale beers. Additionally, the 'lingering' and 'harsh' characteristics were diminished when beer aroma was blocked out (with nose clip) for dry-hopped beer. Meanwhile, most dry-hopped beers had greater antioxidant activity than ale beers (P < 0.05). CONCLUSION: This work revealed the bitterness complexity of dry-hopped beer; besides non-volatile bitter compounds, beer aroma had an impact on the perceived bitterness intensity and attributes, and dry-hopped beer had a relatively intense antioxidant capacity. This study facilitated the development of a detailed knowledge about the assessment of bitter-tasting perceptions in dry-hopped beers and provided a basis for the development of functional beer benefiting human health. © 2022 Society of Chemical Industry.
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Cerveja , Humulus , Antioxidantes/análise , Cerveja/análise , Cromatografia Líquida , Humanos , Humulus/química , Espectrometria de Massas em TandemRESUMO
Statement of RetractionWe, the Editors and Publisher of the journal Expert Review of Molecular Diagnostics, have retracted the following article:Sen Hong, Zhenkun Yan, YuMei Song, MiaoMiao Bi & Shiquan Li. Down-regulation of lncRNA FEZF1-AS1 mediates regulatory T cell differentiation and further blocks immune escape in colon cancer. Expert Review of Molecular Diagnostics. 2021. DOI: 10.1080/14737159.2022.2012157Since publication, significant concerns have been raised about the integrity of the data and reported results in the article. When approached for an explanation, the authors did not provide their original data or any necessary supporting information. As verifying the validity of published work is core to the integrity of the scholarly record, we are therefore retracting the article. The corresponding author listed in this publication has been informed.We have been informed in our decision-making by our policy on publishing ethics and integrity and the COPE guidelines on retractions.The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as 'Retracted'.
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Hops are abundant in natural bioactive compounds. In this work, nine prenylated bitter compounds from hop were evaluated for their inhibitory activity against α-glucosidase. As a result, four flavonoids and one phloroglucinol (lupulone, LP) outperformed acarbose in inhibiting α-glucosidase. Isoxanthohumol (IX) and LP with two types of structures were selected for inhibition mechanism studies by spectroscopic methods and molecular dynamics simulation (MD). Results showed that IX acted as noncompetitive inhibitor and bound to α-glucosidase in allosteric sites via hydrogen bonds, hydrophobic, van der Waals (vdW), and electrostatic force, whereas LP was uncompetitive inhibitor and bound to catalytic sites via hydrophobic and vdW interactions. Notably, the conformation around binding site of α-glucosidase formed stable α-helix and tightened after binding IX and LP, respectively, which helped to elucidate noncompetitive and uncompetitive inhibitory mechanisms. This work demonstrated that two types of prenylated bitter compounds are discrepant in their mechanisms of interaction with α-glucosidase.
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Humulus , Simulação por Computador , Flavonoides , Paladar , alfa-GlucosidasesRESUMO
BACKGROUND AND AIM: The thymosin beta 10 (TMSB10) was originally identified from the thymus, which plays a key role in the development of many cancers. However, the underlying molecular mechanisms of TMSB10 involved in GC have not been understood. METHODS: We sought to determine the expression of TMSB10 in human GC tissues and illustrate whether it is correlated with the clinical pathologic characteristics and prognosis in GC patients. Its roles and potential mechanisms in regulating tumor growth, invasion, and angiogenesis were evaluated by TMSB10 knockdown/overexpression of GC cells in vitro and ex vivo. RESULTS: Marked overexpression of TMSB10 protein expression was observed in GC cells and tissues, which was associated with the advanced tumor stage and lymph nodes (LN) metastasis of GC patients. Furthermore, prognostic analysis showed that GC patients with high TMSB10 expression had a remarkably shorter survival and acted as an important factor for predicting poor overall survival in GC patients. Moreover, TMSB10 overexpression promoted, while TMSB10 knockdown the proliferation, EMT process, and angiogenesis of GC cells. CONCLUSION: The study highlights that TMSB10 may hold promise as potential prognosis prediction biomarker for the diagnosis of GC and a potential therapeutic target, which will facilitate the development of a novel therapeutic strategy against GC.
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Neoplasias Gástricas , Timosina , Biomarcadores Tumorais/biossíntese , Biomarcadores Tumorais/genética , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Humanos , Metástase Linfática , Invasividade Neoplásica , Neovascularização Patológica , Prognóstico , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patologia , Timosina/biossíntese , Timosina/genéticaRESUMO
INTRODUCTION: Dysregulation of microRNAs (miRNAs), which represented a critical level of gene expression modulation, regulated the development of colorectal cancer. However, the functions of numerous miRNAs remain unclear in colorectal cancer. METHODS: The microarray data of GSE115513 were retrieved; subsequently, the differentially expressed miRNAs between 411 colon tumors and 381 normal colon mucosa were analyzed. Real-time PCR (RT-qPCR) and bioinformatic analysis were applied to examine the expression of miR-4449 in collected colorectal tumors and published microarray data. The activity of signal transducer and activator of transcription 3 (STAT3) signaling was detected by Western blotting and RT-qPCR. Dual-Luciferase assay and bioinformatic analysis were used to confirm the interaction between suppressor of cytokine signaling 3 (SOCS3) and miR-4449. Loss of function and rescue assays were performed to study the involvement of miR-4449 and SOCS3 in cell proliferation and apoptosis of colorectal cancer. RESULTS: Herein, we identified miR-4449 as a novel upregulated miRNA in colorectal cancer. Our data suggested that miR-4449 downregulation blocked the proliferation of colorectal cancer cells accompanied with the elevation of cell apoptosis. Decreased expression of miR-4449 led to inactivation of STAT3 pathway as indicated by dephosphorylation of STAT3 and downregulation of STAT3 target genes, including vascular endothelial growth factor (VEGF), c-Myc, baculovirus inhibitor of apoptosis containing 5 (BIRC5). Furthermore, SOCS3, a negative regulator of STAT3 pathway, was found to be a target gene of miR-4449. The data also showed that the inactivation of STAT3 pathway by miR-4449 inhibitor was realized by targeting SOCS3. Moreover, the biological function of miR-4449 downregulation was reversed by SOCS3 knockdown in colorectal cancer cells. CONCLUSION: The current study revealed that miR-4449 promoted cell proliferation of colorectal cancer and was a promising potential therapeutic target for colorectal cancer.
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Eighteen trace elements were analyzed in a 120-year sediment core from Daya Bay. Burial flux history and potential provenance, the relationships among trace elements, and biogenic compositions were analyzed for determining the trend and extent of trace element accumulation and identifying corresponding anthropogenic effects. Additionally, the effects of anthropogenic activities on Daya Bay were reconstructed, and a baseline/background estimation was provided for Daya Bay. The burial fluxes of V, Cr, Cd, Cu, Zn, Mn, Fe, Co, Ni, Pb, Hg, Zn, Mo, Ag, As, Se, and Tl increased from 1960 to 2010, especially after the late 1980s. Our results are useful for understanding pollution and land-sea interactions along the coasts of the South China Sea, especially in the Guangdong-Hong Kong-Macao Greater Bay Area.
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Metais Pesados , Oligoelementos , Poluentes Químicos da Água , China , Monitoramento Ambiental , Sedimentos Geológicos , Hong Kong , Macau , Metais Pesados/análise , Oligoelementos/análise , Poluentes Químicos da Água/análiseRESUMO
To assess the impact of antibiotic pollution to the ecosystem in urban water, the occurrence, seasonal, and spatial distributions, potential sources, and ecological risks of 18 targeted antibiotics in urban river, Pearl River located in Guangzhou city, were investigated. Surface water samples were sampled from 24 sites in Guangzhou center of Pearl River during dry and wet seasons. The results indicated that the concentrations of antibiotic residues were at the nanogram per liter level, except sulfamethazine (SMD) (µg/L). Sulfonamides (SAs) were the dominant antibiotics, contributing 60.4-65.0% to the total antibiotics. The concentrations of SAs, fluoroquinolones (QUs), macrolides (MLs), tetracyclines (TCs), and lincosamides (LCs) were higher in dry season than those in wet season at most sampling sites, which possibly resulted from the dilution effect of heavy rainfall. The concentrations of the antibiotic residues in Guangzhou were comparable or higher than other urban rivers. The calculation on risk quotients indicated that erythromycin-H2O (ETM-H2O) and tetracycline (TC) were of high risks. The source identification by the Pearson correlation analysis and principal component analysis-multiple linear regression (PCA-MLR) method suggested that municipal wastewater treatment plants were primary sources of antibiotics. These results would provide important information for the environmental protect.
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Rios , Poluentes Químicos da Água , Antibacterianos/análise , China , Cidades , Ecossistema , Monitoramento Ambiental , Medição de Risco , Água , Poluentes Químicos da Água/análiseRESUMO
Microplastics (MPs) can adsorb toxic chemicals in biological or environmental matrixes and thus influence their behavior and availability. In order to investigate how the combined pollution of MPs and toxic organic chemical influence microbial growth and metabolism, Escherichia coli (E. coli) was grown in a complex, well-defined media and treated with polystyrene microplastics (PS MPs) and dichloro-diphenyl-tricgloroethane (DDT) at human relevant concentration levels. In vivo metabolites captured by a novel solid phase microextraction (SPME) probe, were used to reflect the metabolic dysregulation of E. coli under different pollution stresses. Results showed that the toxic effect of DDT displayed a distinct dose-dependent phenomenon while the existence of PS decreased the growth and metabolic interference effect of DDT on E. coli. Adsorption results revealed a mechanism that PS weakened the adverse impact of DDT by decreasing its free concentration in the treated culture media. Tricarboxylic acid (TCA) cycle related enzymes activities and antioxidant defense related substances of E. coli also proved the mechanism. The current study is believed to broaden our understanding of the ecotoxicity of MPs with toxic organic chemicals on microorganism.
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Microplásticos , Poluentes Químicos da Água , DDT/toxicidade , Escherichia coli , Humanos , Metabolômica , Plásticos , Poliestirenos/toxicidade , Poluentes Químicos da Água/análise , Poluentes Químicos da Água/toxicidadeRESUMO
BACKGROUND: Gastric cancer (GC) has a high rate of metastasis which thereason leading to death. Carnitine palmitoyl transferase 1a (CPT1A) has been reported to play a critical obstacle to various types of cancer progression, which is an attractive focus in anti-cancer therapy. However, the underlying molecular mechanisms of CPT1A involved in GC have not been clarified clear. METHODS: To determine the expression of CPT1A in human GC tissues and cells and illustrate whether it is correlated with the clinical pathologic characteristics and prognosis in GC patients. Its roles and potential mechanisms in regulating tumor growth and invasion were evaluated by CPT1A knockdown/overexpression of GC cells in vitro. RESULTS: Marked upregulation of CPT1A protein expression was observed in GC cells and tissues, which was associated with grade, pathological stage, lymph node metastasis and poor prognosis in patients with GC. CPT1A overexpression also promoted the proliferation, invasion, EMT process of GC cells. In addition, CPT1A upregulation activated GC cell fatty acid oxidation (FAO) via increasing NADP+/NADPH ratio, whereas inhibiting of FAO abolished the effects of CPT1A on GC cell proliferation and migration. CONCLUSION: Our results examine that CPT1A-mediated FAO activation increases GC cell proliferation and migration, supporting that CPT1A is a useful prognostic biomarker and an attractive focus for GC.
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Carnitina O-Palmitoiltransferase/antagonistas & inibidores , Proliferação de Células/fisiologia , Ácidos Graxos/metabolismo , Neoplasias Gástricas/metabolismo , Carnitina O-Palmitoiltransferase/genética , Carnitina O-Palmitoiltransferase/metabolismo , Linhagem Celular Tumoral , Movimento Celular/fisiologia , Ácidos Graxos/química , Regulação Neoplásica da Expressão Gênica/fisiologia , Técnicas de Silenciamento de Genes , Humanos , Oxirredução , Prognóstico , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/patologia , Regulação para CimaRESUMO
Thymic regulatory T cells (tTregs) are potent inhibitors of autoreactive immune responses, and loss of tTreg function results in fatal autoimmune disease. Defects in tTreg number or function are also implicated in multiple autoimmune diseases, leading to growing interest in use of Treg as cell therapies to establish immune tolerance. Because tTregs are present at low numbers in circulating blood and may be challenging to purify and expand and also inherently defective in some subjects, we designed an alternative strategy to create autologous Treg-like cells from bulk CD4+ T cells. We used homology-directed repair (HDR)-based gene editing to enforce expression of FOXP3, the master transcription factor for tTreg Targeted insertion of a robust enhancer/promoter proximal to the first coding exon bypassed epigenetic silencing, permitting stable and robust expression of endogenous FOXP3. HDR-edited T cells, edTregs, manifested a transcriptional program leading to sustained expression of canonical markers and suppressive activity of tTreg Both human and murine edTregs mediated immunosuppression in vivo in models of inflammatory disease. Further, this engineering strategy permitted generation of antigen-specific edTreg with robust in vitro and in vivo functional activity. Last, edTreg could be enriched and expanded at scale using clinically relevant methods. Together, these findings suggest that edTreg production may permit broad future clinical application.
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Fatores de Transcrição Forkhead , Edição de Genes , Animais , Fatores de Transcrição Forkhead/genética , Humanos , Tolerância Imunológica , Camundongos , Fenótipo , Linfócitos T ReguladoresRESUMO
To explore the role of long-chain non-coding RNA (lncRNA) taurine up-regulated gene 1 (TUG1) in the development of colorectal cancer (CRC) via the miR-138-5p/zinc finger E-box-binding homeobox 2 (ZEB2) axis. Eighty-four CRC tissue specimens and 84 corresponding paracancerous tissue specimens were sampled from 84 patients with CRC admitted to the First Hospital of Jilin University from January 2018 to September 2019. The TUG1 expression in the specimens was determined, and its value in diagnosis and prognosis of CRC was analyzed. Additionally, constructed stable and transient overexpresison vectors and inhibition vectors were transfected into CRC cells. The MTT, transwell, and flow cytometry were adopted for analysis on the proliferation, invasion, and apoptosis of transfected cells, respectively, and a dual luciferase reporter (DLR) assay was carried out for correlation determination between TUG1 and miR-138-5p and between miR-138-5p and ZEB2. TUG1 was up-regulated in CRC, and serum TUG1 could be adopted as a diagnostic marker of CRC, with area-under-the-curve (AUC) larger than 0.8. In addition, siRNA-TUG1, shRNA-TUG1, miR-138-5p-mimics, and miR-138-5p-inhibitor were transfected into cells, and it turned out that overexpressing miR-138-5p and inhibiting ZEB2 exerted the same effects. The DLR assay revealed that TUG1 was able to targetedly regulate miR-138-5p, and miR-138-5p could targetedly regulate ZEB2, and in vitro experiments revealed that TUG1 could affect the epithelial-to-mesenchymal transition (EMT) of CRC via the miR-138-5p/ZEB2 axis. TUG1 could promote the development of CRC via the miR-138-5p/ZEB2 axis.
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Neoplasias Colorretais/metabolismo , RNA Longo não Codificante/metabolismo , Homeobox 2 de Ligação a E-box com Dedos de Zinco/metabolismo , Apoptose , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Progressão da Doença , Transição Epitelial-Mesenquimal , Regulação Neoplásica da Expressão Gênica , Humanos , MicroRNAs/genética , Invasividade Neoplásica , RNA Longo não Codificante/genética , Transdução de Sinais , Homeobox 2 de Ligação a E-box com Dedos de Zinco/genéticaRESUMO
BACKGROUND: Most recently, long non-coding RNAs (lncRNAs) emerge as crucial modulators in many biological processes, such as embryonic development, cell growth, and tumorigenesis. However, the correlations between lncRNAs and colorectal cancer (CRC) cell proliferation, metastasis, and gemcitabine resistance are not well understood. RESULTS: The expression of AGAP2-AS1 was overexpressed in CRC tissues and negatively correlated with the survival of patients with CRC. AGAP2-AS1 promoted CRC cell proliferation and inhibited apoptosis. Moreover, AGAP2-AS1 enhanced the chemoresistance of CRC cells to gemcitabine. In addition, AGAP2-AS1 enhanced the migration and invasion of CRC cells. Mechanistic studies showed that AGAP2-AS1 regulated fibroblast growth factor receptor 1 (FGFR1) expression by sponging miR-497 in CRC progression. CONCLUSION: We identified an oncogenic role of AGAP2-AS1 in the development and progression of CRC. METHODS: qRT-PCR was used to measure the expression of AGAP2 Antisense RNA 1 (AGAP2-AS1) in 116 cases of CRC and adjacent normal tissues. Luciferase reporter assays was used to detect the interaction between AGAP2-AS1 and miR-497. The xenograft tumor experiment was used to study the in vivo function of AGAP2-AS1.
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Antimetabólitos Antineoplásicos/uso terapêutico , Movimento Celular/genética , Neoplasias Colorretais/genética , Resistencia a Medicamentos Antineoplásicos/genética , MicroRNAs/genética , RNA Longo não Codificante/genética , Apoptose/genética , Carcinogênese/genética , Linhagem Celular Tumoral , Proliferação de Células , Sobrevivência Celular/genética , Desoxicitidina/análogos & derivados , Desoxicitidina/uso terapêutico , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Oncogenes , Prognóstico , Regulação para Cima , GencitabinaRESUMO
MiR-663b has been demonstrated to be abnormally expressed in several cancer types and was involved in the progression of cancer. Although overexpression of miR-663b in colorectal cancer was observed, the role of miR-663b in colorectal cancer cells has not been identified yet. In this study, we analyzed expression of miR-663b in colorectal tumors and explored the molecular mechanism of miR-663b in colorectal cancer cells. MiR-663b was significantly overexpressed in colorectal tumors and cell lines. Downregulation of miR-663b inhibited cell proliferation and sphere forming ability in colorectal cancer cells. In addition, miR-663b downregulation inactivated Ras/Raf signaling activity and subsequently decreased YAP1 and CD44 expression in colorectal cancer cells. Using TargetScan software, TNK1, a negative regulator of Ras/Raf signaling, was predicted to be a target gene of miR-663b. Western blotting and RT-qPCR showed that TNK1 expression was negatively regulated by miR-663b. In addition, the direct binding of miR-663b to TNK1 mRNA was proved by dual luciferase reporter assay. Furthermore, downregulation of miR-663b inhibited colorectal cancer cell proliferation and stemness, which was reversed after siRNA-mediated silencing of TNK1. In conclusion, the current study revealed a pivotal role of miR-663b in the progression of colorectal cancer.
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Neoplasias Colorretais/genética , Regulação para Baixo , Proteínas Fetais , MicroRNAs/genética , Proteínas Tirosina Quinases , Transdução de Sinais/genética , Neoplasias Colorretais/patologia , Progressão da Doença , HumanosRESUMO
Flavor stability is a significant concern to brewers as the staling compounds impart unpleasant flavor to beer. Thus, yeasts with antistaling ability have been engineered to produce beer with improved flavor stability. Here, we proposed that increasing the NADH availability of yeast could improve the flavor stability of beer. By engineering endogenous pathways, we obtained an array of yeast strains with a higher reducing activity. Then, we carried out beer fermentation with these strains and found that the antistaling capacities of the beer samples were improved. For a better understanding of the underlying mechanism, we compared the flavor profiles of these strains. The production of staling components was significantly decreased, whereas the content of antistaling components, such as SO2, was increased, in line with the increased antistaling ability. The other aroma components were marginally changed, indicating that this concept was useful for improving the antistaling stability without changing the flavor of beer.
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Cerveja/análise , Aromatizantes/metabolismo , NAD/metabolismo , Saccharomyces/metabolismo , Fermentação , Engenharia Genética , Odorantes/análise , Saccharomyces/genéticaRESUMO
Trace polycyclic aromatic hydrocarbons (PAHs) in drinking water sources have significant harmful effects on human health. Water and sediment samples from water source regions of three water treatment plants in Guangzhou were collected and the distributions of 16 kinds of PAHs were analyzed. The human risk of PAHs in the water samples was also evaluated using the Risk Assessment Guidance for Superfund (RAGS) of the United States Environmental Protection Agency (USEPA). The results showed that PAHs in the samples from the three water source regions did not exceed the corresponding standard limit for water quality, and the content of ΣPAHs in suspended solids and sediments was below the medium level. The non-carcinogenic risks (HQ and HI) of PAHs in the water samples were less than 1, and the non-carcinogenic risk was negligible. In addition, Riskingest, Riskdermal, and RiskT for the waters were all in range of 5.53×10-7 to 5.34×10-6, indicating that a carcinogen risk was possible but acceptable. The results of the isomer ratio method indicated that the PAHs in the water sources of the three water plants had a mixed input of pollution, including petroleum discharge, petroleum combustion, and incomplete combustion of wood, coal, and biomass. The total organic carbon (TOC) content of the water and sediment samples was positively correlated with the accumulation and enrichment of low-ring PAHs, and there was a significant positive correlation between PAHs and similar molecules in the sediments. The ΣPAHs in the water and sediment samples were also strongly correlated.
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Saúde Ambiental , Hidrocarbonetos Policíclicos Aromáticos , Medição de Risco , Poluentes Químicos da Água , China , Monitoramento Ambiental , Sedimentos Geológicos , Humanos , Abastecimento de ÁguaRESUMO
Developing efficient and durable catalysts for methanol oxidation is of great significance for direct methanol fuel cells. Herein, we realized the deposition of ultra-trace Pt nanoparticles by atomic layer deposition (ALD) onto a three-dimensional (3D) titanium nitride (TiN) nanowire array grown on carbon cloth (CC), in which the 3D TiN nanowires provide a stable platform for the Pt nanoparticles, besides the inherent properties of high corrosion resistance and conductivity. Owing to the superior characteristics of the 3D TiN nanostructure as the support material and the strong interaction between Pt and TiN, the Pt nanoparticles on the TiN nanowire array show an enhanced electrocatalytic activity toward methanol oxidation compared to a commercial Pt/C catalyst. This work provides an effective strategy to fabricate 3D high-performance electrocatalysts for future energy applications.
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In this article, an ambient mass spectrometric method with molecularly imprinted polymer (MIP)-coated wooden tips was developed for sensitive analysis of trace macrolide antibiotics in complex food samples. A novel solid-phase microextraction (SPME) probe was prepared, via the modification of a layer MIP coating (with roxithromycin as template molecule) on the surface of wooden tips. The obtained MIP-coated wooden-tip SPME probe can be applied directly to enrich trace macrolide antibiotics from complex food samples, with enrichment factors of 244-1604, 72-370, and 12-82 folds for analysis of five investigated macrolide antibiotics in drinking water, honey, and milk samples, respectively. After extraction, a high voltage and some spray solvent were applied on the loaded SPME probe to desorb and ionize analytes enriched on the probe surface for electrospray ionization mass spectrometric (ESI-MS) analysis under ambient and open-air conditions. The method showed good linearity, with correlation coefficient values (r2) no less than 0.9904, and the calibration function was verified via Mandel's fitting test (pâ¯>â¯0.063). The limits of detection were in the range of 0.003-0.05, 1.1-5.1, and 1.9-15.8â¯ng/g for analysis of drinking water, honey, and milk samples, respectively. Recoveries of the five targeted macrolide antibiotics in honey and milk samples ranged from 73.4% to 98.1%, with the standard deviations no higher than 8.6%. As a result, MIP-coated wooden-tip ESI-MS method could be feasibly used as a sensitive method for determination of trace macrolide antibiotics in complex food samples.