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BACKGROUND: CHD5 is a conventional tumour-suppressing gene in many tumours. The aim of this study was to determine whether CHD5 variants contribute to the risk of hepatocellular carcinoma (HCC). METHODS: Gene variants were identified using next-generation sequencing targeted on referenced mutations followed by TaqMan genotyping in two case-control studies. RESULTS: We discovered a rare variant (haplotype AG) in CHD5 (rs12564469-rs9434711) that was markedly associated with the risk of HCC in a Chinese population. A logistical regression model and permutation test confirmed the association. Indeed, the association quality increased in a gene dose-dependent manner as the number of samples increased. In the stratified analysis, this haplotype risk effect was statistically significant in a subgroup of alcohol drinkers. The false-positive report probability and multifactor dimensionality reduction further supported the finding. CONCLUSIONS: Our results suggest that the rare CHD5 gene haplotype and alcohol intake contribute to the risk of HCC. Our findings can be valuable to researchers of cancer precision medicine looking to improve diagnosis and treatment of HCC.
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Carcinoma Hepatocelular/genética , DNA Helicases/genética , Neoplasias Hepáticas/genética , Proteínas do Tecido Nervoso/genética , Adulto , Idoso , Consumo de Bebidas Alcoólicas/efeitos adversos , Povo Asiático/genética , Estudos de Casos e Controles , Feminino , Interação Gene-Ambiente , Predisposição Genética para Doença , Haplótipos , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo ÚnicoRESUMO
An electrochemiluminescence (ECL) biosensor is described for the detection of microRNA (miRNA-155) based on tris(bipyridine)ruthenium(II) functionalized metal organic framework (RuMOF) materials. The material was prepared by a solvothermal method and was found to be stable even in acidic solution. However, it is selectively and sensitively disassembled by Hg(II) ions, resulting in the release of large quantities of Ru(II)(bpy)3 ions, which produces a strong ECL signal. In view of the ion-selective disassembly and release and strand displacement process, an ultrasensitive ECL sensing method was established for detection of microRNAs. In the presence of the target, the hairpin structure of H1 can open and hybridize with the hairpin probe H2 to form a more stable H1-H2 duplex structure than the H1-target hybrid. The target of hybridization to H1 was immediately freed from the structure and the released target re-entered the new hairpin assembly target recovery process. The remaining H2 single fragment can bind to the I-RuMOFs-conjugates. The more hairpin probes H1, the more I-RuMOFs-conjugates load the DNA fragments, leading to the signal amplification. The method works in the 0.8 f. to 1.0 nM miRNA-155 concentration range and has a detection limit of 0.3 fM. The assay is sensitive, fairly specific and remarkably stable. In our perception, it offers an attractive tool for the sensitive detection of microRNAs in clinical samples. Graphical abstract An electrochemiluminescence (ECL) based biosensor is described for the detection of microRNA (miRNA-155) based on the use of a metal organic framework functionalized with ruthenium(II)tris(bipyridine) that was deposited on a glassy carbon electrode (GCE) modified with gold nanoparticles.
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Técnicas Eletroquímicas , Medições Luminescentes , Mercúrio/farmacologia , Estruturas Metalorgânicas/química , MicroRNAs/análise , Técnicas Biossensoriais/métodos , Eletrodos , Ouro , Humanos , Nanopartículas Metálicas/química , RutênioRESUMO
This paper describes the design and construction of a sudoku-like lab-on-paper platform, in which dual enhancement of reaction intermediates strategy was incorporated for multiplexed competitive electrochemiluminescence (ECL) cyto-assay. Benefiting from the sudoku-like structure, integrated multifunctions were obtained on such an elaborately devised platform, including specific reagents storage, multiple samples immobilization, residual automatic washing, and signal collection. By utilizing semicarbazide (SE) and silver nanoparticles (AgNPs) as dual enhancers, more ECL intermediates could be obtained in the graphene quantum dots (GQDs) and peroxydisulfate system, resulting in the production of more excited-state GQDs to emit light. Moreover, the double-stranded DNA nanowire with multiple branched arms (MBdsDNA) was chosen as an efficient nanocarrier to load more GQDs and AgNPs. Via immobilizing AgNPs on the end of the plentiful branched arms, Ag-MBdsDNA were obtained and trapped on the sensing interface through the valid competitive interactions between target cells and Ag-MBdsDNA. Afterward, abundant GQDs were attached to the three-dimensional (3D) DNA skeleton of the captured Ag-MBdsDNA via π-π stacking. Due to their good self-catalytic activity of labeled AgNPs, more silver was deposited on the Ag-MBdsDNA@GQDs, giving rise to further amplification of expected signal. With four types of cancer cells as models, MCF-7, CCRF-CEM, HeLa, and K562 cells were assayed in the ranges of 1.0 × 102-1.0 × 107, 1.5 × 102-2.0 × 107, 2.0 × 102-5.0 × 106, and 1.2 × 102-2.0 × 106 cells mL-1 with the detection limits of 38, 53, 67, and 42 cells mL-1, respectively. Notably, this strategy supplies a simple and versatile platform for sensitive determination of multiple targeted cells, which would play a crucial role in point-of-care diagnostic fields.
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A novel metal-enhanced ratiometric fluorescence/naked eye bimodal biosensor based on ZnFe2O4@Au-Ag bifunctional nanocomposite and DNA/CeO2 complex for lead ions (Pb2+) has been successfully developed. The nanocomposite probe was composed of a magnetic ZnFe2O4 core and a Au-Ag hollow nanocube shell. Upon bioconjugation, bifunctional magnetic nanocomposites could not only make the probe possess excellent recyclability but also provide an enrichment of "hot spots" for surface enhanced fluorescence detection of Pb2+ by a metal-enhanced fluorescence effect. Typically, the bifunctional nanocomposites conjugated with double-stranded DNA (included Pb2+-specific DNAzyme strand and corresponding substrate strand) to form a Pb2+ biosensor. Nanoceria as a fluorescence quencher strongly adsorbed DNA. Therefore, the formation of double-stranded DNA brought the labeled nitrogen sulfur doped carbon dots (N,S-CDs) and CeO2 into close proximity, which significantly quenched the fluorescence of N,S-CDs. The presence of Pb2+ led to the breakage of the DNAzyme strand, resulting in the fluorescence signal of Cy3 decreasing, while the fluorescence intensity of N,S-CDs aggrandized. First, a preliminary test of Pb2+ was performed by the naked eye. The disengaged DNA/CeO2 complex could result in color change after adding H2O2 because of autocatalysis of CeO2, resulting in real-time visual detection of Pb2+. If further accurate determination was required, the fluorescence intensity ratio of these two fluorescence indicators was measured at 562 and 424 nm (I562/I424). A good linear correlation exists between the log(I562/I424) and the logarithm of Pb2+ concentrations ranging from 10-12 to 3 × 10-6 M. Remarkably, the detection limit of this ratiometric biosensor was 3 × 10-13 M, which ascribed to its superior fluorescence enhancement. Interestingly, the developed bifunctional nanocomposite probe manifests good recyclability and selectivity. More importantly, the biosensor provided potential application of on-site and real-time unknown Pb2+ ions in real systems.
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Técnicas Biossensoriais , Fluorescência , Corantes Fluorescentes/química , Chumbo/análise , Nanocompostos/química , Cério/química , DNA/química , Compostos Ferrosos/química , Corantes Fluorescentes/síntese química , Ouro/química , Íons/análise , Oxigênio/química , Tamanho da Partícula , Porosidade , Prata/química , Propriedades de Superfície , Zinco/químicaRESUMO
Using remote N2 plasma treatment to promote dielectric deposition on the dangling-bond free MoS2 is explored for the first time. The N2 plasma induced damages are systematically studied by the defect-sensitive acoustic-phonon Raman of single-layer MoS2, with samples undergoing O2 plasma treatment as a comparison. O2 plasma treatment causes defects in MoS2 mainly by oxidizing MoS2 along the already defective sites (most likely the flake edges), which results in the layer oxidation of MoS2. In contrast, N2 plasma causes defects in MoS2 mainly by straining and mechanically distorting the MoS2 layers first. Owing to the relatively strong MoS2-substrate interaction and chemical inertness of MoS2 in N2 plasma, single-layer MoS2 shows great stability in N2 plasma and only stable point defects are introduced after long-duration N2 plasma exposure. Considering the enormous vulnerability of single-layer MoS2 in O2 plasma and the excellent stability of single-layer MoS2 in N2 plasma, the remote N2 plasma treatment shows great advantage as surface functionalization to promote dielectric deposition on single-layer MoS2.
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Objectives To assess the benefits of Zhuang medicine in treating rheumatoid arthritis (RA), with a focus on cardiac tricuspid annulus displacement and heart rate variability (HRV), thereby providing evidence supporting Zhuang medicine theories. METHODS: This retrospective study analyzed echocardiographic data and HRV of 30 healthy subjects and 60 RA patients. RA patients were divided into two groups for a 6-month treatment: 30 received iguratimod (control group), and 30 underwent combined Zhuang medicine and needle-pricking therapy (test group). Echocardiographic assessments and HRV measures were recorded both before and after treatment. RESULTS: Compared to the healthy group, RA patients showed increased late diastolic tricuspid annular velocity. However, early diastolic tricuspid annular velocity to late diastolic tricuspid annular velocity ratios, tricuspid annular plane systolic excursion (TAPSE), and the standard deviation of average normal RR intervals (SDANN) were significantly lower (all P<0.05). After treatment, the test group exhibited higher clinical efficacy (90% vs. 56.67% in the control group). Significant improvements were observed in TAPSE and HRV indices [SDANN, standard deviation of the RR intervals (SDNN), root mean square of successive RR interval differences (RMSSD), and the percentage of adjacent RR interval differences greater than 50 milliseconds (PNN50)] in the test group (all P<0.05). Additionally, a positive correlation was noted among these measurments. CONCLUSION: Zhuang medicine significantly enhances right ventricular function and autonomic balance in RA patients, thus affirming its therapeutic potential.
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The forthcoming wearable health care devices garner considerable attention because of their potential for monitoring, treatment, and protection applications. Herein, a self-powered triboelectric patch was developed using polytetrafluoroethylene rubbed with nylon fabric. The triboelectric patch can maintain a stable electrostatic field, due to the excess electrification on the surface of the triboelectric layer. The designed triboelectric nanogenerator (TENG) output watt density can reach about 485 mW/m2 with added resistance of 11 kΩ. Additionally, the performance of the triboelectric patch allowed eye movement monitoring. The maximum voltage could reach 80 V at the vertical distance of 20 mm between the frictional layer and collector. The triboelectric patch not only can power a digital watch for potential wearable applications but also can be integrated to monitor eye movements during sleep. This work proposed a mechanism for human movement energy harvesting, which may be used for self-powered smart wearable health equipment and Maxwell displacement current wireless sensors.
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Fontes de Energia Elétrica , Dispositivos Eletrônicos Vestíveis , Humanos , Nanotecnologia , Movimentos Oculares , Monitorização FisiológicaRESUMO
Hepatocellular carcinoma (HCC) is one of the leading causes of cancer death worldwide. Consequently, it is essential to identify biomarkers for treatment response and the prognosis prediction. We investigated whether ABL1 can function as a biomarker or a drug target for HCC. We assessed the ABL1 expression, genetic alterations and patients' survival from LinkedOmics, GEO, TCGA and Human Protein Atlas. We analyzed PPI, GO and KEGG pathways. GSEA was analyzed for functional comparison. The current drugs targeting ABL1 were statistically analyzed using DRUGSURV and DGIdb database. We found ABL1 is overexpressed in HCC and its higher expression reduces survival probability. Genetic changes of ABL1 are not frequent. We screened out 25 differentially expressed genes correlated with ABL1. The top functions of ABL1 are biological regulation, metabolic process, protein-containing, and protein binding. KEGG pathways showed that ABL1 and correlated with ABL1 significantly genes markedly enriched in the ErbB signaling pathway, and pathways in cancer. We counted the existing drugs targeting ABL1, which indicates that inhibiting ABL1 expression may improve the survival probability of HCC. In conclusion, ABL1 plays a crucial role in the development and progression of this cancerization and is a potential drug target.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Biologia Computacional , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Redes Reguladoras de Genes , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Prognóstico , TranscriptomaRESUMO
Background: Histone deacetylase 3 (HDAC3) plays an important role in the development and progression of a variety of cancers, but its regulatory mechanism in acute myeloid leukemia (LAML) is not entirely understood. Methods: We analyzed the expression of HDAC3 in normal and cancerous tissues using Oncomine, UALCAN, and GEO databases. Changes of the HDAC3 gene were analyzed by cBioPortal. The genes coexpressed with HDAC3 were analyzed by WebGestalt, and the predicted signaling pathways in KEGG were discussed. Results: We discovered that the expression of HDAC3 was elevated in some types of acute myeloid leukemia. The HDAC3 gene has a strong positive correlation with SLC25A5, NDUFA2, Cox4I1, and EIF3K, which regulate cell growth and development. HDAC3 transcription is higher in patients with FLT3 mutation than in healthy people. HDAC3 can be directly involved in regulating the thyroid hormone signaling pathway. MEF2D is directly involved in the cGMP-PKG signaling pathway, and the HDAC3 gene has a strong synergistic relationship with MEF2D. HDAC3 is indirectly involved in the cGMP-PKG signaling pathway, thereby indirectly regulating the expression levels of p53 and p21 genes in patients with LAML. Genomics of Drug Sensitivity in Cancer (GDSC) database analysis revealed that the application of the HDAC3 inhibitor can inhibit the proliferation of leukemia cells. Conclusions: Therefore, our data suggest that HDAC3 may be a possible therapeutic target for acute myeloid leukemia.
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Histona Desacetilases , Leucemia Mieloide Aguda , Mineração de Dados , Histona Desacetilases/genética , Histona Desacetilases/metabolismo , Humanos , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/genética , Transdução de SinaisRESUMO
zMicroRNAs (miRNAs) are endogenously expressed small noncoding RNAs that regulate approximately one-third of human genes at post-transcription level. Previous studies have shown that miRNAs were implicated in many cellular processes and participated in the progress of various tumors including hepatocellular carcinoma (HCC). Among all miRNAs, the let-7 family is well recognized to play pivotal roles in tumorigenesis by functioning as potential growth suppressor. In the present study, we aimed to investigate the role of let-7 family, particularly the hsa-let-7g, in the molecular pathogenesis of HCC. By use of MTT, qPCR, Western blotting and 2-dimensional electrophoresis (2-DE), over-expression of hsa-let-7g was found to inhibit the proliferation of HCC cell line via negative and positive regulations of c-Myc and p16(INK4A) , respectively. The expression of hsa-let-7g was noted to be markedly lowered in the HepG2, Hep3B and Huh7 cells, yet higher in the Bel-7404 HCC cell line. Proliferation of HCC cell line was significantly inhibited after the transfection of hsa-let-7g mimics, while hsa-let-7g inhibitor transfection exerted an opposite effect. Concurrently, the mRNA and protein levels of c-Myc were found significantly decreased in HepG2 cells after transfection of hsa-let-7g mimics, but obviously increased in Bel-7404 cells after transfection of hsa-let-7g inhibitor. As revealed by 2-DE, a significant upregulation of p16(INK4A) was revealed after the gain-of-function study using hsa-let-7g. Therefore, we suggest that hsa-let-7g may act as a tumor suppressor gene that inhibits HCC cell proliferation by downregulating the oncogene, c-Myc, and upregulating the tumor suppressor gene, p16(INK4A) .
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Carcinoma Hepatocelular/prevenção & controle , Regulação Neoplásica da Expressão Gênica , Neoplasias Hepáticas/prevenção & controle , MicroRNAs/fisiologia , Proteínas de Neoplasias/genética , Proteínas Proto-Oncogênicas c-myc/genética , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Proliferação de Células , Inibidor p16 de Quinase Dependente de Ciclina , Humanos , Neoplasias Hepáticas/patologia , MicroRNAs/genética , Biossíntese de Proteínas , Transcrição GênicaRESUMO
OBJECTIVE: To investigate the gene diagnosis and phenotypes analysis for a couple with ß-thalassemia suspected from of blood routine test and hemoglobin electrophoresis, as well as the prenatal gene diagnosis of the fetus. METHODS: The gene mutation of ß-globin in the samples of peripheral blood of pregnant woman and her husband, as well as amniotic fluid of pregnant woman were analyzied and identified by using PCR-RDB and Sanger sequencing. RESULTS: The detection showed that the heterozygote mutation of IVS-â ¡-654 (C>T), which is common mutation of ß-globin gene, existed in pregnant woman, while her husband carried a rare mutation CD29 (c.90 C>T) of ß-globin gene. The prenatal diagnosis indicated that the fetus inherited with mutation from the parents, fetus genotype was ßIVS-â ¡-6541/ßCD29. CONCLUSION: The CD29(C>T) mutation of ß-globin gene has been identified in Chinese population first. Although this mutation type is symonymous mutation, but its carrier displays phenotype of ß-thalaessmia. Therefore, the attention to this mutation should be paid considering the genetic risk. It contributes to genetic counseling and prenatal gene diagnosis.
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Talassemia beta , Análise Mutacional de DNA , Feminino , Heterozigoto , Humanos , Fenótipo , Gravidez , Mutação Silenciosa , Globinas betaRESUMO
Chemical energy conversion/storage through water splitting for hydrogen production has been recognized as the ideal solution to the transient nature of renewable energy sources. Solid polymer electrolyte (SPE) water electrolysis is one of the most practical ways to produce pure H2 . Electrocatalysts are key materials in the SPE water electrolysis. At the anode side, electrode materials catalyzing the oxygen evolution reaction (OER) require specific properties. Among the reported materials, only iridium presents high activity and is more stable. In this Minireview, an application overview of single iridium metal and its oxide catalysts-binary, ternary, and multicomponent catalysts of iridium oxides and supported composite catalysts-for the OER in SPE water electrolysis is presented. Two main strategies to improve the activity of an electrocatalyst system, namely, increasing the number of active sites and the intrinsic activity of each active site, are reviewed with detailed examples. The challenges and perspectives in this field are also discussed.
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In this paper, the mechanical properties and minimum thermal conductivity of ZnZr, Zn2Zr, Zn2Zr3, and MgZn2 are calculated from first principles. The results show that the considered Zn-Zr intermetallic compounds are effective strengthening phases compared to MgZn2 based on the calculated elastic constants and polycrystalline bulk modulus B, shear modulus G, and Young's modulus E. Meanwhile, the strong Zn-Zr ionic bondings in ZnZr, Zn2Zr, and Zn2Zr3 alloys lead to the characteristics of a higher modulus but lower ductility than the MgZn2 alloy. The minimum thermal conductivity of ZnZr, Zn2Zr, Zn2Zr3, and MgZn2 is 0.48, 0.67, 0.68, and 0.49 W m-1 K-1, respectively, indicating that the thermal conductivity of the Mg-Zn-Zr alloy could be improved as the precipitation of Zn atoms from the α-Mg matrix to form the considered Zn-Zr binary alloys. Based on the analysis of the directional dependence of the minimum thermal conductivity, the minimum thermal conductivity in the direction of [110] can be identified as a crucial short limit for the considered Zn-Zr intermetallic compounds in Mg-Zn-Zr alloys.
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In this manuscript, a disposable paper-based analytical device comprised of a closed bipolar electrode (BPE) was fabricated for the ultrasensitive electrochemiluminescence (ECL) detection of intracellular H2O2 and the number of cancer cells. In this approach, wax printing was used to fabricated reaction zone, and carbon ink-based BPE and driving electrodes were screen-printed into the paper. AuPd nanoparticles (NPs), which served as a carrier of the capture aptamer and as the catalyst for the ECL reaction of luminol and H2O2, were used to modify the BPE. Luminol/Au NPs were attached to the surface of the captured cells via hybridation chain reaction with two hairpin structure DNA labelled luminol/Au NPs. In the stimulation of phorbol myristate acetate, The coreactant H2O2 was released from the target cells. The ECL response of the luminol-H2O2 system was related to the number of cancer cells in the testing buffer, which served as a quantitative signal for the determination of cancer cells and the concentration of H2O2. In order to decrease the external voltage, K3[Fe(CN)6] was introduced in the cathode resevoir of BPE because it gained electrons at the cathode more easily than oxygen. The ECL intensity was quantitatively related to the concentration of MCF-7 in the range of 1.0 × 102-1.0 × 107 cells/mL. The detection limit was 40 cells/mL and it showed good specificity for cells with high overexpression of mucin-1 receptor, it was concluded that the developed protocol could be effectively utilized for the detection of MCF-7 cells.
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Técnicas Biossensoriais , Contagem de Células , Técnicas Eletroquímicas , Peróxido de Hidrogênio/isolamento & purificação , Carbono , Regulação Neoplásica da Expressão Gênica , Ouro/química , Humanos , Peróxido de Hidrogênio/química , Hibridização In Situ , Limite de Detecção , Medições Luminescentes , Células MCF-7 , Mucina-1/genética , Paládio/químicaRESUMO
MicroRNAs (miRNAs) are a class of significant biomarkers; however, it is still a huge challenge to express them accurately. Herein, a fluorescent/colorimetric dual-model biosensor based upon the quenching effect of graphitic carbon nitride on palladium nanoclusters (Pd NCs) on the platform of a microfluidic paper-based analytical device was built for the detection of miRNAs. On the one hand, Pd NCs could catalyze a chromogenic reaction so that preliminary detection was achieved by the naked eye. On the other hand, the fluorescence analysis combined with nucleic acid cycle signal amplification was required to get precise result and the detection limit is 3 fM, which was superior to the previous method. What's more, this biosensor could be designed to detect other miRNAs via changing the corresponding aptamer sequences. Therefore, the as-constructed biosensor supplies a versatile platform to conduct point-of-care detection of miRNAs with outstanding performance.
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As a two-dimensional semiconductor, WS2 has attracted great attention due to its rich physical properties and potential applications. However, it is still difficult to synthesize monolayer single-crystalline WS2 at larger scale. Here, we report the growth of large-scale triangular single-crystalline WS2 with a semi-sealed installation by chemical vapor deposition (CVD). Through this method, triangular single-crystalline WS2 with an average length of more than 300 µm was obtained. The largest one was about 405 µm in length. WS2 triangles with different sizes and thicknesses were analyzed by optical microscope and atomic force microscope (AFM). Their optical properties were evaluated by Raman and photoluminescence (PL) spectra. This report paves the way to fabricating large-scale single-crystalline monolayer WS2, which is useful for the growth of high-quality WS2 and its potential applications in the future.
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In this work, an electrochemical biosensor based on Au nanorods (NRs) modified microfluidic paper-based analytical devices (µPADs) were constructed for sensitive detection of microRNA (miRNA) by using cerium dioxide - Au@glucose oxidase (CeO2-Au@GOx) as an electrochemical probe for signal amplification. Au NRs were synthesized by in-situ growth method in µPADs surface to enhance the conductivity and modified hairpin probe through Au-S bonds. The construction of "the signal transducer layer" was carried out by GOx catalyzing glucose to produce H2O2, which was further electrocatalyzed by CeO2. After the biosensor was constructed, an obvious electrochemical signal was observed from the reduction of H2O2. In order to make the detection more convincing, the visual detection was performed based on the oxidation of 3,3',5,5'-tetramethylbenzidine by H2O2 with the help of Exonuclease I. The electrochemical biosensor provided a wide linear range of 1.0fM to 1000fM with a relatively low detection limit of 0.434fM by the electrochemical measurement. Linear range of 10fM to 1000fM with a relatively low detection limit of 7.382fM was obtained by visual detection. The results indicated the proposed platform has potential utility for detection of miRNA.
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Técnicas Biossensoriais/instrumentação , Cério/química , Dispositivos Lab-On-A-Chip , MicroRNAs/sangue , Catálise , Técnicas Eletroquímicas/instrumentação , Desenho de Equipamento , Glucose/química , Glucose Oxidase/química , Ouro/química , Humanos , Peróxido de Hidrogênio/química , Limite de Detecção , PapelRESUMO
Previous studies showed that the low expressions of chromodomain-helicase-DNA-binding protein 5 (CHD5) were intensively associated with deteriorative biologic and clinical characteristics as well as outcomes in many tumors. The aim of this study is to determine whether CHD5 single nucleotide polymorphisms (SNPs) contribute to the prognosis of hepatocellular carcima (HCC). The SNPs were selected according to their linkage disequilibrium (LD) in the targeted next-generation sequencing (NGS) and then genotyped with TaqMan probers. We revealed a rare haplotype AG in CHD5 (SNPs: rs12564469-rs9434711) was markedly associated with HCC prognosis. The univariate and multivariate regression analyses revealed the patients with worse overall survival time were those with tumor metastasis and haplotype AG, as well as cirrhosis, poor differentiation and IV-TNM stage. Based on the available public databases, we discovered the significant association between haplotype AG and CHD5 mRNA expressions only existed in Chinese. These data proposed that the potentially genetic haplotype might functionally contribute to HCC prognosis and CHD5 mRNA expressions.
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Convenient biosensor for simultaneous multi-analyte detection was increasingly required in biological analysis. A novel flower-like silver (FLS)-enhanced fluorescence/visual bimodal platform for the ultrasensitive detection of multiple miRNAs was successfully constructed for the first time based on the principle of multi-channel microfluidic paper-based analytical devices (µPADs). Fluorophore-functionalized DNA1 (DNA1-N-CDs) was combined with FLS, which was hybridized with quencher-carrying strand (DNA2-CeO2) to form FLS-enhanced fluorescence biosensor. Upon the addition of the target miRNA, the fluorescent intensity of DNA1-N-CDs within the proximity of the FLS was strengthened. The disengaged DNA/CeO2 complex could result in color change after joining H2O2, leading to real-time visual detection of miRNA firstly. If necessary, then the fluorescence method was applied for a accurate determination. In this strategy, the growth of FLS in µPADs not only reduced the background fluorescence but also provided an enrichment of "hot spots" for surface enhanced fluorescence detection of miRNAs. Results also showed versatility of the FLS in the enhancement of sensitivity and selectivity of the miRNA biosensor. Remarkably, this biosensor could detect as low as 0.03fM miRNA210 and 0.06fM miRNA21. Interestingly, the proposed biosensor also possessed good capability of recycling in three cycles upon change of the supplementation of DNA2-CeO2 and visual substitutive device. This method opened new opportunities for further studies of miRNA related bioprocesses and will provide a new instrument for simultaneous detection of multiple low-level biomarkers.
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Técnicas Biossensoriais , Dispositivos Lab-On-A-Chip , MicroRNAs/isolamento & purificação , DNA/química , Peróxido de Hidrogênio/química , Nanopartículas Metálicas , MicroRNAs/genética , PapelRESUMO
Recently, paper substrates have attracted tremendous interest from both academia and industry. Not only is paper highly abundant and portable, it is lightweight, disposable, easy-to-use, and can be rolled or folded into 3D configurations. More importantly, with a unique porous bulk structure and rough and absorptive surface properties, the construction of nanomaterials-functionalized cellulose has enabled cellulose paper to be applied for point-of-care (POC) paper devices with reasonably good performance at low cost. In this review, the latest advances in the modification of nanomaterials on paper cellulose are summed up. To begin with, the attractive properties of paper-based analytical devices are described. Then, fabricating methods for the functionalization of cellulose with diverse materials, including noble metals, bimetals, metal oxides, carbon nanomaterials, and molecular imprinting polymer nanoparticles, as well as their applications, are introduced in detail. Finally, the current critical issues, challenges, and future prospectives for exploring a paper-based analytical system based on nanomaterials-modified cellulose are discussed. It is believed that more strategies will be developed in the future to construct nanomaterials-functionalized cellulose, paving the way for the mass production of POC paper devices with a satisfactory performance.