RESUMO
Accurate detection of site-specific 5-hydroxymethylcytosine (5hmC) in genomic DNA is of great significance, but it is technically challenging to directly distinguish very low levels of 5hmC from their abundant cytosine/5-methylcytosine (C/5mC) analogues. Herein, we wish to propose a selective ligase-mediated mechanism (SLim) that can directly discriminate 5hmC from C/5mC with a high specificity without the use of any sample processing protocol. In this new design, we discovered that HiFi Taq DNA Ligase can well tolerate the mismatched 5hmC/A base-pairing and then effectively ligate the associated nicking site while the mismatched 5mC/A or C/A pairs cannot be recognized by HiFi Taq DNA Ligase, providing a new way for direct and selective discriminating 5hmC from its similar analogues. Ultrasensitive and selective quantification of site-specific 5hmC is realized by coupling the SLim with polymerase chain reaction (PCR) or loop-mediated isothermal amplification (LAMP).
Assuntos
5-Metilcitosina , DNA Ligases , DNA , 5-Metilcitosina/análogos & derivados , 5-Metilcitosina/análise , 5-Metilcitosina/química , DNA/química , DNA/análise , DNA Ligases/metabolismo , Técnicas de Amplificação de Ácido Nucleico/métodos , Humanos , Reação em Cadeia da PolimeraseRESUMO
We, for the first time, demonstrate high electrocatalytic activity for the hydrogen evolution reaction (HER) on PtFe alloy nanoparticles with stabilized Pt-skin layers supported on carbon black (PtxAL-PtFe/C), which allows the reduction of Pt loading to be lowered to 1/20 compared with a conventional Pt black cathode in proton exchange membrane water electrolysis (PEMWE). The area-specific HER activity of PtxAL-PtFe/C was found to be ca. 2 times higher than that of commercial Pt/C at 80 °C and -0.02 V vs. RHE. PtxAL-PtFe/C exhibited the additional important advantage of suppressed H2O2 production during the HER in the presence of O2, which inevitably diffuses from the anode in PEMWE. Both the excellent HER performance and low H2O2 production are attributed to the lower adsorption energies of atomic hydrogen on Pt-skin surfaces, as revealed by DFT calculations.
RESUMO
The rational design of efficient and low-cost electrocatalysts based on earth-abundant materials is imperative for large-scale production of hydrogen by water electrolysis. Here we present a strategy to prepare highly active catalyst materials through modifying the crystallinity of the surface/interface of strongly coupled transition metal-metal oxides. We have thermally activated the catalysts to construct amorphous/crystalline Ni-Fe oxide interfaced with a conductive Ni-Fe alloy and systematically investigated their electrocatalytic performance toward the hydrogen evolution and oxygen evolution reactions (HER and OER) in alkaline solution. It was found that the Ni-Fe/oxide material with a crystalline surface oxide phase showed remarkably superior HER activity in comparison with its amorphous or poorly crystalline counterpart. In contrast, interestingly, the amorphous/poorly crystalline oxide significantly facilitated the OER activity in comparison with the more crystalline counterpart. On one hand, the higher HER activity can be ascribed to a favorable platform for water dissociation and H-H bond formation, enabled by the unique crystalline metal/oxide structure. On the other hand, the enhanced OER catalysis on the amorphous Ni-Fe oxide surfaces can be attributed to the facile activation to form the active oxyhydroxides under OER conditions. Both are explained based on density functional theory calculations. These results thus shed light onto the role of crystallinity in the HER and OER catalysis on heterostructured Ni-Fe/oxide catalysts and provide guidance for the design of new catalysts for efficient water electrolysis.
RESUMO
High dust concentration produced in the fully mechanized longwall mining face is a significant threat to the front-line workers. It is critical to discover the potential safety zone to ensure routine personnel operation. Fluent 2020 R1 is employed to reappear the spatial dust distribution based on the gas-solid coupling theory. The dust migration behavior and safety regional division are illuminated in the spatial longwall mining face. The formation of dust concentration trigonum is introduced with the particle diffusion force analyzed. The YZ plane safety zone area shows an increasing trend at X = 70-95 m. The respirable dust concentration decreases from the peak value to the safe value at sidewalk 4.0-4.6 m. The safety zone area and length both pose a linear growth with the increasing wind velocity. In the XY plane, the safety zone area and length extend by 1.26 times and 1.33 times, respectively. The horizontal plane creates a greater growth rate of safety zone than the vertical plane. The drum rotation creates a wind circumfluence that exerts an obvious effect on the dust distribution around the coal cutter. The sidewalk region mainly situates in the safety zone for the personal squat down, while it is gradually exposed to the dangerous dust pollution situation as the breathing height rises.
Assuntos
Minas de Carvão , Exposição Ocupacional , Carvão Mineral/análise , Poeira/análise , Humanos , Exposição Ocupacional/análise , VentoRESUMO
AIM: The IRE1 signaling pathway is implicated in I/R injury. However, little is known about the involvement of this pathway in low-dose LPS treatment of myocardial I/R injury. Thus, an attempt was made to determine the relationship between the IRE1 pathway and I/R injury using rats or in vitro H9C2 cell myocardial I/R injury models. MAIN METHODS: Sprague-Dawley rats and cultured H9C2 cells were pretreated with low-dose LPS and subjected to myocardial I/R injury models. KEY FINDINGS: Low-dose LPS did not affect normal rat or cellular function. Compared with the I/R group, treatment with LPS attenuated myocardial apoptosis, decreased plasma LDH and CK-MB activities, reduced myocardium infarct size, and downregulated caspase-3 expression. Moreover, the protein or mRNA expression levels of the IRE1 signaling pathway-related proteins Grp78, IRE1, p-ASK1, ASK1, p-JNK, and JNK were notably increased during I/R injury but significantly decreased by low-dose LPS treatment both in rats and in H9C2 cells. SIGNIFICANCE: Low-dose LPS exhibited therapeutic effects in myocardial I/R injury. Most importantly, the cardioprotective mechanism of low-dose LPS may be associated with the IRE1 signaling pathway.
Assuntos
Proteínas de Membrana/metabolismo , Isquemia Miocárdica/tratamento farmacológico , Proteínas Serina-Treonina Quinases/metabolismo , Traumatismo por Reperfusão/tratamento farmacológico , Animais , Apoptose/efeitos dos fármacos , Modelos Animais de Doenças , Chaperona BiP do Retículo Endoplasmático , Proteínas de Choque Térmico/metabolismo , Lipopolissacarídeos/farmacologia , MAP Quinase Quinase Quinase 5/metabolismo , Sistema de Sinalização das MAP Quinases/fisiologia , Masculino , Infarto do Miocárdio/metabolismo , Isquemia Miocárdica/metabolismo , Isquemia Miocárdica/fisiopatologia , Traumatismo por Reperfusão Miocárdica/metabolismo , Miocárdio/metabolismo , Miócitos Cardíacos/metabolismo , Substâncias Protetoras/farmacologia , Ratos , Ratos Sprague-Dawley , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/fisiopatologia , Transdução de Sinais/efeitos dos fármacosRESUMO
BACKGROUND: Previous studies demonstrate that T-cadherin is a candidate tumor suppressor in several types of human tumors, including non-small cell lung cancer (NSCLC). Lack of protein expression of T-cadherin by hypermethylation has been found to play an important role in lung alveolar differentiation regulation and epithelial tumorigenesis. However, the correlation between T-cadherin hypermethylation and clinicopathological characteristics of NSCLC remains unclear. Here we conducted a systematic review and meta-analysis to quantitatively evaluate the effects of T-cadherin hypermethylation on the incidence of NSCLC and clinicopathological characteristics. METHODS: A detailed literature search was carried out for related research publications. Analyses of pooled data were performed. Odds ratio (OR) and hazard ratio (HR) were calculated and summarized, respectively. RESULTS: Final analysis of 1,172 NSCLC patients from 15 eligible studies was performed. T-cadherin hypermethylation was observed to be significantly higher in NSCLC than in normal lung tissue, based on the pooled OR from nine studies including 532 NSCLC and 372 normal lung tissue samples (OR=8.19, 95% confidence interval [CI]=5.41-12.39, P<0.00001). T-cadherin hypermethylation may also be associated with pathological types. The pooled OR was obtained from four studies including 111patients with squamous cell carcinoma and 106 with adenocarcinoma (OR=0.35, 95% CI=0.19-0.66, P=0.001), which indicated that T-cadherin hypermethylation plays a more important role in the pathogenesis of adenocarcinoma. We did not find that T-cadherin hypermethylation was correlated with the sex or smoking status, clinical stages, or epidermal growth factor receptor (EGFR) mutation status. However, T-cadherin hypermethylation was found to be significantly higher in poorly differentiated NSCLC than in moderately and highly differentiated NSCLC, and NSCLC patients with T-cadherin hypermethylation had a lower survival rate than those without T-cadherin hypermethylation. CONCLUSION: The results of this meta-analysis suggest that T-cadherin hypermethylation is associated with an increased risk and worse survival in NSCLC. T-cadherin hypermethylation, which induces the inactivation of T-cadherin gene, plays an important role in the carcinogenesis, cancer progression, as well as clinical outcome.
Assuntos
Antineoplásicos/farmacologia , Caderinas/antagonistas & inibidores , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/metabolismo , Terapia de Alvo Molecular , Antineoplásicos/química , Caderinas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/patologia , Humanos , Neoplasias Pulmonares/patologia , Metilação/efeitos dos fármacosRESUMO
A novel kind of molecular imprinted polymers based on ionic liquid-functionalized graphene (MIPs/IL/GR) was prepared by electro-polymerization, which was applied as a molecular recognition element to modify glassy carbon electrode (GCE) to construct an electrochemical sensor (MIPs/IL/GR/GCE) for sensitive detection of bovine hemoglobin (BHb). The fabrication conditions that affect the performance of the imprinted sensor, such as pyrrole concentration, scan cycles and scan rates, have been discussed. Under the optimized conditions, the prepared molecular imprinting electrochemical sensor showed a fast rebinding dynamics, which was successfully applied to BHb detection with a wide linear range from 1.0 × 10(-10) to 1.0 × 10(-3)g/L (R=0.998) and a detection limit of 3.09 × 10(-11)g/L. Moreover, the fabricated sensor possessed a good selectivity and stability, providing a promising tool for immunoassays and clinical applications.
Assuntos
Técnicas Biossensoriais/instrumentação , Técnicas Eletroquímicas/instrumentação , Grafite/química , Hemoglobinas/análise , Líquidos Iônicos/química , Impressão Molecular , Animais , Carbono/química , Bovinos , Eletrodos , Desenho de Equipamento , Limite de Detecção , PolimerizaçãoRESUMO
A zirconia/multi-walled carbon nanotube (ZrO2/MWCNT) mesoporous composite was fabricated via a simple method using a hydrothermal process with the aid of the cationic surfactant cetyltrimethylammonium bromide (CTAB). Transmission electron microscopy (TEM), N2 adsorption-desorption, Fourier transform infrared spectroscopy (FT-IR) and X-ray diffraction (XRD) techniques were used to characterize the as-made samples. The cubic ZrO2 nanocrystallites were observed to overlay the surface of MWCNTs, which resulted in the formation of a novel mesoporous-nanotube composite. On the basis of a TEM analysis of the products from controlled experiment, the role of the acid-treated MWCNTs and CTAB was proposed to explain the formation of the mesoporous-nanotube structure. The as-made composite possessed novel properties, such as a high surface area (312 m(2)·g(-1)) and a bimodal mesoporous structure (3.18 nm and 12.4 nm). It was concluded that this composite has important application value due to its one-dimensional hollow structure, excellent electric conductivity and large surface area.