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BACKGROUND: Abnormal N6-methyladenosine (m6A) modification has become a driving factor in tumour development and progression. The linc00659 is abnormally highly expressed in digestive tract tumours and promotes cancer progression, but there is little research on the mechanism of linc00659 and m6A. METHODS: The expression of linc00659 in colorectal cancer (CRC) tissues and cells was assessed by a quantitative real-time PCR. The proliferative capacity of CRC cells was determined by colony formation, Cell Counting Kit-8 and 5-ethynyl-2 deoxyuridine assays, and the migratory capacity of CRC was determined by wound healing and transwell assays and tube formation. In vivo, a xenograft tumour model was used to detect the effect of linc00659 on tumour growth. The Wnt/ß-catenin signalling pathway and related protein expression levels were measured by western blotting. The binding of linc00659 to insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1) was assessed by RNA pull-down and an immunoprecipitation assay. The effect of IGF2BP1 on FZD6 was detected by an RNA stability assay. RESULTS: The expression of linc00659 was abnormally elevated in CRC tissues and cells compared to normal colonic tissues and cells. We confirm that linc00659 promotes the growth of CRC cells both in vivo and in vitro. Mechanistically, linc00659 binds to IGF2BP1 and specifically enhances its activity to stabilize the target gene FZD6. Therefore, linc00659 and IGF2BP1 activate the Wnt/ß-catenin signalling pathway, promoting cell proliferation in CRC. CONCLUSIONS: Our results show that linc00659 and IGF2BP1 cooperate to promote the stability of the target FZD6 mRNA, thereby facilitating CRC progression, which may represent a potential diagnostic, prognostic and therapeutic target for CRC.
Assuntos
Adenina , Neoplasias Colorretais , RNA Longo não Codificante , Via de Sinalização Wnt , Animais , Humanos , Adenina/análogos & derivados , Linhagem Celular Tumoral , Proliferação de Células , Neoplasias Colorretais/patologia , Modelos Animais de Doenças , Receptores Frizzled/genética , Receptores Frizzled/metabolismo , Regulação Neoplásica da Expressão Gênica , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , RNA MensageiroRESUMO
Benzoylurea (BU) insecticides have been widely used for pest control as third-generation insecticides. Considering that their residues in food may cause adverse effects on human health, the upper limits of BUs remaining in food have been set by the administration. Therefore, it is essential to develop a sensitive and efficient analytical method to determine the residues of BUs in food. Stir bar sorptive extraction (SBSE) is a novel sample preparation technique, and stainless steel wire (SSW) is an ideal substrate for an SBSE device. In this work, a novel SBSE device of SSW jacket-free stir bar with a dumbbell shape was designed and prepared. The conjugated microporous polymer CMP-F6, which possesses a porous structure, high hydrophobicity and rich fluorine-containing functional groups, was immobilized on the surface of SSW by the method of polyacrylonitrile glue adhesion. Compared with previous studies, which used SSW as a substrate, the method of etching partial SSW with hydrochloric acid, on the one hand, made the surface of SSW rough and easy to modify the extraction coating, and on the other hand, converted itself into a dumbbell-shaped structure, which is conducive to improving the extraction efficiency and stability of the SBSE device. The method of SBSE-HPLC-UV was established for determining five BUs. Owing to the hydrophobic interaction and F-F interaction between CMP-F6 and analytes, this method showed good extraction efficiency and had good linearity (R2 ≥ 0.9945) and high sensitivity (LODs in the range of 0.1-0.2 ng mL-1). It was used for the analysis of benzoylurea in an apple juice sample, and the recoveries were 74.3-117.9%.
Assuntos
Sucos de Frutas e Vegetais , Polímeros , Aço Inoxidável , Aço Inoxidável/química , Porosidade , Sucos de Frutas e Vegetais/análise , Polímeros/química , Limite de Detecção , Contaminação de Alimentos/análise , Ureia/química , Ureia/análise , Inseticidas/análise , Inseticidas/isolamento & purificação , Inseticidas/química , Extração em Fase Sólida/métodos , Cromatografia Líquida de Alta Pressão/métodos , Adsorção , Resíduos de Praguicidas/análise , Resíduos de Praguicidas/isolamento & purificaçãoRESUMO
Graph data are widely collected and exploited by organizations, providing convenient services from policy formation and market decisions to medical care and social interactions. Yet, recent exposures of private data abuses have caused huge financial and reputational costs to both organizations and their users, enabling designing efficient privacy protection mechanisms a top priority. Local differential privacy (LDP) is an emerging privacy preservation standard and has been studied in various fields, including graph data aggregation. However, existing research studies of graph aggregation with LDP mainly provide single edge privacy for pure graph, leaving heterogeneous graph data aggregation with stronger privacy as an open challenge. In this paper, we take a step toward simultaneously collecting mixed attributed graph data while retaining intrinsic associations, with stronger local differential privacy protecting more than single edge. Specifically, we first propose a moderate granularity attributewise local differential privacy (ALDP) and formulate the problem of aggregating mixed attributed graph data as collecting two statistics under ALDP. Then we provide mechanisms to privately collect these statistics. For the categorical-attributed graph, we devise a utility-improved PrivAG mechanism, which randomizes and aggregates subsets of attribute and degree vectors. For heterogeneous graph, we present an adaptive binning scheme (ABS) to dynamically segment and simultaneously collect mixed attributed data, and extend the prior mechanism to a generalized PrivHG mechanism based on it. Finally, we practically optimize the utility of the mechanisms by reducing the computation costs and estimation errors. The effectiveness and efficiency of the mechanisms are validated through extensive experiments, and better performance is shown compared with the state-of-the-art mechanisms.
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Cotton fiber is a biodegradable material that possesses properties such as high specific area, adjustable shape, and hygroscopicity. In this work, organic polymer was directly in situ grown on the surface of cotton thread and packed into a poly(ether ether ketone) tube for online in-tube solid-phase microextraction. The novel strategy solves the problems like high backpressure and tedious optimization process of normal monolithic polymer-based in-tube solid-phase microextraction capillary. The quaternary ammonium typed ionic liquid of 1-allyl-methylimidazolium chloride, 4-vinylbiphenyl, and ethylene dimethacrylate were co-polymerized and in situ grown on the surface of cotton thread as extraction phase. The solid-phase microextraction tube showed excellent performance for the extraction of three nonsteroidal anti-inflammatory drugs including ketoprofen, naproxen, and flurbiprofen due to the strong ion exchange and hydrophobic interactions. After online coupling with a high-performance liquid chromatography system by six-port valve, the method was applied for the quantitative analysis of nonsteroidal anti-inflammatory drugs in human plasma samples showing good enrichment performance (enrichment factor between 263 and 279), high sensitivity, good linearity, and good reproducibility.
Assuntos
Anti-Inflamatórios não Esteroides/análise , Fibra de Algodão , Líquidos Iônicos/química , Polímeros/química , Microextração em Fase Sólida , Cromatografia Líquida de Alta Pressão , Tamanho da Partícula , Polimerização , Polímeros/síntese química , Propriedades de SuperfícieRESUMO
Findings from observational studies on the associations between vitamin E intake and stroke risk remain controversial, and the dose-response relationship between vitamin E intake and risk of stroke remains to be determined. We conducted a meta-analysis of prospective studies aiming to clarify the relationships between vitamin E intake and risk of stroke. Relevant studies were identified by searching online databases through to June 2018. We computed summary relative risks (RR) with corresponding 95 % CI. Among 3156 articles retrieved from online databases and relevant bibliographies, nine studies involving 3284 events and 220 371 participants were included in the final analyses. High dietary vitamin E intake was inversely associated with the risk of overall stroke (RR=0·83, 95 % CI 0·73, 0·94), and with the risk of stroke for individuals who were followed-up for <10 (RR=0·84, 95 % CI 0·72, 0·91). There was a non-linear association between dietary vitamin E intake and stroke risk (P=0·0249). Omission of any single study did not alter the summary result. In conclusion, this meta-analysis suggests that there is a significant inverse relationship between dietary vitamin E intake and stroke risk. This meta-analysis provides evidence that a higher dietary vitamin E intake is associated with a lower stroke risk.
Assuntos
Dieta , Acidente Vascular Cerebral/prevenção & controle , Vitamina E/administração & dosagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Índice de Massa Corporal , Suplementos Nutricionais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Dinâmica não Linear , Estado Nutricional , Estudos Observacionais como Assunto , Estudos Prospectivos , Fatores de RiscoRESUMO
Redox imbalance has been regarded as the key limitation for anaerobic isobutanol production in metabolically engineered Escherichia coli strains. In this work, the ethanol synthetic pathway was recruited to solve the NADH redundant problem while the pentose phosphate pathway was modulated to solve the NADPH deficient problem for anaerobic isobutanol production. Recruiting the ethanol synthetic pathway in strain AS108 decreased isobutanol yield from 0.66 to 0.29 mol/mol glucose. It was found that there was a negative correlation between aldehyde/alcohol dehydrogenase (AdhE) activity and isobutanol production. Decreasing AdhE activity increased isobutanol yield from 0.29 to 0.6 mol/mol. On the other hand, modulation of the glucose 6-phosphate dehydrogenase gene of the pentose phosphate pathway increased isobutanol yield from 0.29 to 0.41 mol/mol. Combination of these two strategies had a synergistic effect on improving isobutanol production. Isobutanol titer and yield of the best strain ZL021 were 53 mM and 0.74 mol/mol, which were 51 % and 12 % higher than the starting strain AS108, respectively. The total alcohol yield of strain ZL021 was 0.81 mol/mol, which was 23 % higher than strain AS108.
Assuntos
Butanóis/metabolismo , Proteínas de Escherichia coli/genética , Escherichia coli/genética , Engenharia Metabólica , Via de Pentose Fosfato , Álcool Desidrogenase/genética , Álcool Desidrogenase/metabolismo , Aldeído Oxirredutases/genética , Aldeído Oxirredutases/metabolismo , Meios de Cultura/química , Escherichia coli/metabolismo , Proteínas de Escherichia coli/metabolismo , Microbiologia Industrial , NADP/metabolismo , Plasmídeos/genética , Plasmídeos/metabolismoRESUMO
Hemophagocytic lymphohistiocytosis (HLH), also known as hemophagocytic syndrome (HPS), is a benign histiocytosis with hyperreactive proliferation of the mononuclear phagocyte system caused by immune function abnormalities, which often occurs under the background of genetic mutations, inflammation, infection or tumors. Because the research on malignancy-associated HLH (M-HLH) is focused on hematological malignancies, reports on HLH secondary to solid tumors are rare. In this case, we report a 14-year-old girl who developed HLH during treatment for intracranial multifocal germinoma, and the disease was controlled after hormone combined with etoposide(VP-16) and other related treatments. To our knowledge, there have been no documented cases of HLH caused by intracranial multifocal germinoma.
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BACKGROUND: Non-small cell lung cancer (NSCLC) is a malignant form of lung cancer, and its prognosis could be improved by identifying key therapeutic targets. Thus, this study investigates the potential role of F-box Only Protein 33 (FBXO33) in NSCLC. METHODS: The expression levels of FBXO33 in NSCLC were determined using University of Alabama at Birmingham Cancer Data Analysis Portal (UALCAN) prediction, and its correlation with overall survival (OS) was analyzed via Kaplan-Meier survival analysis. These results were validated through quantitative polymerase chain reaction (qPCR), western blot (WB), and immunofluorescence (IF). We modulated FBXO33 expression by overexpression or knockdown and analyzed its effects on cell growth, proliferation, migration, invasion, and stemness characteristics in NSCLC cell lines. Additionally, the interaction between FBXO33 and Myelocytomatosis (Myc) and its impact on Myc ubiquitination were examined. An in vivo NSCLC xenograft model was used to corroborate the in vivo experimental results. RESULTS: The study found an inverse correlation between FBXO33 expression in NSCLC and OS. Lower FBXO33 expression enhanced the growth, proliferation, migration, invasion, and stemness characteristics of NSCLC cell lines. FBXO33 interacted with Myc to promote its ubiquitination and subsequent degradation, which suppressed NSCLC development. CONCLUSION: FBXO33 is expressed at low levels in NSCLC and correlates with lower OS. Overexpression of FBXO33 promotes Myc ubiquitination and degradation and inhibits tumor cell proliferation, migration and stemness characteristics, thereby impeding NSCLC progression.
Assuntos
Carcinoma Pulmonar de Células não Pequenas , Proliferação de Células , Proteínas F-Box , Neoplasias Pulmonares , Células-Tronco Neoplásicas , Proteínas Proto-Oncogênicas c-myc , Ubiquitinação , Humanos , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/genética , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/metabolismo , Animais , Proteínas F-Box/metabolismo , Proteínas F-Box/genética , Células-Tronco Neoplásicas/metabolismo , Células-Tronco Neoplásicas/patologia , Linhagem Celular Tumoral , Proteínas Proto-Oncogênicas c-myc/metabolismo , Proteínas Proto-Oncogênicas c-myc/genética , Proliferação de Células/genética , Movimento Celular/genética , Camundongos Nus , Camundongos , Ubiquitina-Proteína Ligases/metabolismo , Ubiquitina-Proteína Ligases/genética , Regulação Neoplásica da Expressão Gênica , Feminino , Proteólise , MasculinoRESUMO
The determination of blood concentration of non-steroidal anti-inflammatory drugs (NSAIDs) is highly desired in clinical practice. In this work, three amino bearing metal-organic frameworks (amino-MOFs) coated cotton fibers were prepared using a facile cysteine-triggered in situ growth strategy and proposed as in-tip solid-phase microextraction (in-SPME) adsorbents for efficient extraction of non-steroidal anti-inflammatory drugs from human plasma. The self-made adsorbents exhibited satisfactory extraction performance toward three NSAIDs including diclofenac sodium, ketoprofen and flurbiprofen. Under the optimized conditions, the established method exhibited satisfactory enrichment performance, low limits of detection and excellent extraction efficiency. Good reproducibility, wide linear range, excellent linearity and satisfactory sensitivity were obtained in the experiment. The method was also used for the enrichment and determination of NSAIDs in human plasma samples. Good recoveries were obtained, ranging from 66.5% to 98.9% with relative standard deviations less than 6.62%. The good performance of amino-MOFs was due to the synergistic effects arising from grafted charged amino groups within ordered pores of suitable size, leading to strong affinity towards guest molecules. Electrostatic interaction, hydrogen bond and π-π interaction played a vital role in the extraction of NSAIDs. This report indicated the potential of amino-MOFs as efficient adsorbents for the determination of NSAIDs from human plasma.
Assuntos
Estruturas Metalorgânicas , Humanos , Estruturas Metalorgânicas/química , Reprodutibilidade dos Testes , Fibra de Algodão , Cromatografia Líquida de Alta Pressão/métodos , Anti-Inflamatórios não Esteroides , Extração em Fase Sólida/métodos , Microextração em Fase Sólida/métodos , Limite de DetecçãoRESUMO
Development of high-throughput and rapid screening analytical method is in high demand for anti-doping and clinical point-of-care (POC) analysis. Solid-phase microextraction and mass spectrometry direct coupling (SPME-MS) has been proved as a rapid and effective way for target analysis in complex sample matrixes. An online direct coupling of in-tube SPME (IT-SPME) with MS using polymer coated open-tubular column has been developed in this work. A sharp stainless-steel needle was attached at the end of the SPME column, which enables the direct ionization of the analytes after elution from the IT-SPME column. Itaconic acid-benzene co-polymer was in-situ grown on the inner surface of the fused silica capillary and used as extraction phase. This column has low backpressure and provides both hydrophobic and weak cationic exchange interaction with the target analytes due to the chemical properties. The developed online IT-SPME-MS method showed good extraction performance towards various target analytes and good reusability at least for 60 times. As a proof-of-concept application, the above method was applied for the analysis of antiepileptic drugs (AEDs) in both plasma and urine samples with linear range (1 ng/mL-200 ng/mL), good linearity (R2 ≥ 0.99), and good reproducibility (intra-day RSDs less than 4.36%, inter-day RSDs less than 6.55%). The method exhibited high enrichment factors between 187 and 204 for the two AEDs and high sensitivity for the analysis of human plasma samples and urine samples.
Assuntos
Anticonvulsivantes , Polímeros , Humanos , Polímeros/química , Microextração em Fase Sólida/métodos , Reprodutibilidade dos Testes , Espectrometria de Massas/métodosRESUMO
Electrochemical deposition has been proposed as a promising approach for in situ immobilization of metal-organic framework (MOF) on conductive surfaces. It is favorable as it is time-saving, green, and does not require vigorous reaction conditions, which can be applied to the synthesis and immobilization of extraction materials for fiber in-tube solid phase microextraction. In this work, PPF-1 was immobilized on the surface of the carbon fibers by electrochemical method. The novel method overcame the problems including strict conditions and time-consuming operation. The modified carbon fibers were packed into the PEEK tube for extraction and analysis of three non-steroidal anti-inflammatory drugs (NSAIDs), which performed good extraction efficiency due to strong hydrogen bonding, hydrophobic interaction and π-π interaction between PPF-1 and analytes. The established method obtained good enrichment performance (enrichment factor between 230-540), low limits of detection (between 0.01-0.03 ng/mL), good linearity and good reproducibility (RSDs≤4.93%), which was successfully applied for the quantitative analysis of NSAIDs in human plasma samples.
Assuntos
Estruturas Metalorgânicas , Microextração em Fase Sólida , Anti-Inflamatórios não Esteroides/análise , Fibra de Carbono , Cromatografia Líquida de Alta Pressão/métodos , Humanos , Limite de Detecção , Reprodutibilidade dos Testes , Microextração em Fase Sólida/métodosRESUMO
Polypropylene hollow fiber is a kind of ideal material for stir bar sorptive extraction (SBSE) which possesses the advantages of porous structure, large specific surface area, high mechanical strength, and good solvent resistance. In this work, a novel SBSE device using the polypropylene hollow fiber-based stir bar with the detachable dumbbell-shaped structure was designed and prepared. Covalent organic framework-V (COF-V), which possesses porous structure, sphere shape with large specific surface area, was synthesized at room temperature and grown on polypropylene hollow fiber by polydopamine modification method. Compared with previous studies which used etched poly(ether ether ketone) as supporting material, polypropylene hollow fiber omitted the complicated, difficult and dangerous pretreatment process with high concentrated sulfuric acid. The immobilization of COF-V on the polypropylene hollow fiber significantly endows them with multiple interaction abilities including hydrophobic interaction and π-π interaction. The stir bar showed good performance and stability for the extraction of four benzophenones including BP-1, BP-6, BP-3 and Ph-BP. By coupling with HPLC-UV, the COF-V@polypropylene hollow fiber based SBSE method showed wide linear range (0.1-200 ng/mL), excellent linearity (R2 ≥ 0.9979), high sensitivity (LODs in the range of 0.02-0.03 ng/mL), and good repeatability (RSD ≤ 5.21%). This method was successfully applied to the analysis of benzophenones in soil and sunscreen samples.
Assuntos
Estruturas Metalorgânicas , Benzofenonas , Cromatografia Líquida de Alta Pressão , Polipropilenos , Porosidade , Reprodutibilidade dos TestesRESUMO
Online coupling in-tube solid-phase microextraction (SPME) with mass spectrometry (MS) was achieved by directly utilizing a monolithic SPME capillary as the electrospray emitter. A porous organic polymer with a highly porous structure can not only provide excellent extraction efficiency due to its high specific surface area but also increase the ionization efficiency and stability by producing smaller electrospray droplets. This online coupling strategy significantly simplifies the device as well as the operation process. The whole analytical process only takes about 12 min with a sample amount of 100 µL. By choosing an ionic liquid-based organic polymer with high extraction ability and good stability and adjusting a suitable porous structure for better electrospray, the developed in-tube SPME-MS method showed excellent extraction performance and good reusability without clogging events. As a proof of concept, the proposed method was applied for the analysis of non-steroid anti-inflammatory drugs in plasma and urine samples. The method showed a wide linear range (0.1-200 ng/mL), good linearity (R2 ≥ 0.99), and good reproducibility (intra-day relative standard deviations (RSDs) <3.00% and inter-day RSDs <6.29%).