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Traditional fluorescent anti-counterfeiting labels based on "on-off" fluorescence can be easily cloned. It is important to explore advanced anti-counterfeiting fluorescent labels with high-level security. Here, a pioneering ion species- and ion concentration-dependent anti-counterfeiting technique is developed. By successive loading Cu2+ -sensitive yellow emitted carbon dots (Y-CDs) and Cu2+ non-sensitive blue emitted carbon dots (B-CDs) into metal-organic frameworks (MOFs) and followed by electrospinning, the B&Y-CDs@MOF-nanofibrous films are prepared. The results show that the use of MOF not only avoids the fluorescence quenching of CDs but also improves the fluorescence stability. The fluorescence Cu2+ -sensitivity of the CDs@MOF-nanofibrous films can be regulated by polymer coating or lamination. The fluorescent label consisting of different Cu2+ -sensitivity films will show Cu2+ concentration-dependent decryption information. Only at a specific ion species and concentration (Cu2+ solution of 40-90 µm), the true information can be read out. Less or more concentration (<40 or >90 µm) will lead to false information. The identification of the real information depends on both the species and the concentration. After Cu2+ treatment, the fluorescence of the label can be recovered by ethylenediaminetetraacetic acid disodium (EDTA-2Na) for further recycling. This work will open up a new door for designing high-level fluorescent anti-counterfeiting labels.
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Subsidence waterbodies play an important role in carbon cycle in coal mining area. However, little effort has been made to explore the carbon dioxide (CO2) release characteristics and influencing factors in subsidence waterbodies, especially under different restoration modes. Here, we measured CO2 release fluxes (F(CO2)) across Anguo wetland (AW), louts pond (LP), fishpond (FP), fishery-floating photovoltaic wetland (FFPV), floating photovoltaic wetland (FPV) in coal mining subsidence area, with unrestored subsidence waterbodies (SW) and unaffected normal Dasha river (DR) as the control area. We sampled each waterbody and tested which physical, chemical, and biological characteristics of water and sediment related to variability in CO2. The results indicated that F(CO2) exhibited the following patterns: FFPV > FPV > FP > SW > DR > LP > AW. Trophic lake index (TLI) and microbial biomass carbon content (MBC) in sediment had a positive impact on F(CO2). The dominant archaea Euryarchaeota and Thaumarchaeota, and dominant bacteria Proteobacteria promoted F(CO2). This study can help more accurately quantify CO2 emissions and guide CO2 future emission reduction and subsidence waterbodies estoration.
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With the development of intellectual properties, concern about advanced anti-counterfeiting is accumulating, which conventional single-modal luminescence can no longer satisfy. As one of rapidly developing 0D materials, copper-based perovskite shows great potential to realize multiple luminescent centers for complex emissions. In this work, Cd was doped into Cs3 Cu2 I5 and showed resultant emission at 560â nm which surprisingly showed a red-shifted excitation peak from that of intrinsic self-trapped emission, resulting in excitation-wavelength dependent emission. When the excitation wavelength increased from 290â nm to 330â nm, the emission of Cd-doped Cs3 Cu2 I5 changed from deep blue to cold white and finally yellow. Afterwards, Cd-doped Cs3 Cu2 I5 was mixed with polystyrene to prepare anti-counterfeiting ink for silk-screen printing. Meanwhile, Cd-doped Cs3 Cu2 I5 maintains outstanding stability after doping, no matter under ambient, continuous UV radiation or high-temperature environment. The intensity can be almost totally recovered after heating-and-cooling cycles. This study lays groundwork for future research into multiple luminescent center manipulation in 0D materials.
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During the fabrication of lateral-structured photodetectors based on CH3 NH3 PbI3 film, antisolvents represented by toluene are usually used to accelerate the crystallization of perovskite. Using antisolvent not only leads to the formation of shrinkage holes at the bottom of the perovskite layer, but the toxicity of antisolvents would also hinder the industrial preparation of perovskite devices. An antisolvent-free method is a possible solution to avoid these problems. Here, we report a lateral-structured photodetector based on an antisolvent-free method. The lateral photodetector exhibited a high responsivity of 1.75 Aâ W-1 and specific detectivity (D*) of 3.54 × 1012 Jones. In particular, the results indicated that the solvent had an influence on perovskite film morphology, crystallization, and device performance. The prepared CH3 NH3 PbI3 film presented needle-like crystals and low performance with single precursor solvent N,N-dimethylformamide (DMF). In comparison, appropriate mixing of dimethyl sulfoxide (DMSO) could improve the morphology, crystallization, and performance of the film. In addition, the solvent volume ratio of the precursor had a profound effect on the performance of the as-prepared photodetectors. At a DMSO:DMF volume ratio of 5:5, the as-prepared film had massive perovskite crystals and fewer defects, resulting in optimal device performance, which can be explained by Urbach energy.
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The emission wavelength of organic-inorganic hybrid perovskite quantum dots (QDs) can be tuned by controlling reaction time relevant to the halide exchange. It is because halide exchange with different time would lead to different molar ratio of halides in perovskite QDs such as Cl and Br. Here, to research the ligand's effect on the halide exchange, this work synthesized 3-mercaptopropionic acid (MPA)-capped CH3 NH3 PbBrx Cl3-x QDs. It was found that SH- of MPA appeared to inhibit the halide exchange during the reation. Moreover, although the MPA-capped CH3 NH3 PbBrx Cl3-x QDs did not contain the chiral centre, they exhibit the optical rotation. This may provide a method for chirality manipulation of perovskite.
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Ácido 3-Mercaptopropiônico/química , Compostos de Cálcio/química , Óxidos/química , Pontos Quânticos/química , Titânio/química , Estrutura Molecular , Fenômenos Ópticos , Tamanho da Partícula , Propriedades de SuperfícieRESUMO
Gastric cancer was the fifth most common cancer, and its drug treatment mainly included chemotherapy, targeted therapy, and immunotherapy. With the rise of immunotherapy in gastric cancer, small-molecule anti-gastric cancer drugs still have irreplaceable places because of many advantages, such as high stability and mass-productivity, high efficiency, and low cost. At present, the small-molecule anti-gastric cancer drugs in the clinic are constrained by their side effects. So, developing more novel anti-gastric cancer drugs with better efficacy and fewer side effects is urgently needed. Nitrogen-containing heterocycle molecules have attracted much attention from researchers due to their high biocompatibility, activity, and bioavailability, and they even could act with a unique mechanism. This review summarized various types of nitrogen-containing heterocycle antigastric cancer lead compounds from 2017 to 2022 in the last five years. Compared with monocyclic nitrogen-containing heterocycle and bicyclic nitrogen-containing heterocycle, the thick nitrogen-containing heterocycle applied as the skeleton not only showed high efficiency and low toxicity but also, interestingly, may have had some unique mechanism such as inhibition of aurora A and B kinases, etc. We propose two prospective and valuable strategies to develop more efficient candidates for anti-gastric cancer. One strategy was further optimized for some lead compounds mentioned in this review. The other strategy involved utilizing the "pseudo-natural products" concept proposed by Professor Wilhelm Waldmann, combining different nitrogen-containing heterocycle fragments in two and three-dimensional spaces to obtain new thick nitrogen-containing heterocycle skeletons. The strategy will contribute to the expansion of the thick nitrogenous heterocycle's framework, and it was expected that more novel mechanisms and more effective antigastric drugs could be found. These two strategies are expected to help researchers develop more anti-gastric cancer drugs with better potency and lower side effects.
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The absence of effective active pockets makes traditional molecularly targeted drug strategies ineffective against 80 % of human disease-related proteins. The PROTAC technology effectively makes up for the deficiency of traditional molecular targeted drugs, which produces drug activity by degrading rather than inhibiting the target protein. The degradation of PROTAC is not only affected by POI ligand and E3 ligand, but by the selection of suitable linker which can play an important role in the efficiency and selectivity of the degradation. In the early exploring stage of the PROTAC, flexible chains were priorly applied as the linker of PROTAC. Although PROTAC with flexible chains as linkers sometimes perform well in vitro bioactivity evaluations, the introduction of lipophilic flexible chains reduces the hydrophilicity of these molecules, resulting in generally poor pharmacokinetic characteristics and pharmacological activities in vivo. In addition, recent reports have also shown that some PROTAC with flexible chains have some risks to causing hemolysis in vivo. Therefore, PROTAC with flexible chains show less druggability and large difficulty to entering the clinical trial stage. On the other hand, the application of nitrogen heterocycles in the design of PROTAC linkers has been widely reported in recent years. More and more reports have shown that the introduction of nitrogen heterocycles in the linker not only can effectively improves the metabolism of PROTAC in vivo, but also can enhance the degradation efficiency and selectivity of PROTAC. These PROTAC with nitrogen heterocycle linkers have attracted much attention of pharmaceutical chemists. The introduction of nitrogen heterocycles in the linker deserves priority consideration in the primary design of the PROTAC based on various druggabilities including pharmacokinetic characteristics and pharmacological activity. In this work, we summarized the optimization process and progress of nitrogen heterocyclic rings as the PROTAC linker in recent years. However, there were still limited understanding of how to discover, design and optimize PROTAC. For example, the selection of the types of nitrogen heterocycles and the optimization sites of this linker are challenges for researchers, choosing between four to six-membered nitrogen heterocycles, selecting from saturated to unsaturated ones, and even optimizing the length and extension angle of the linker. There is a truly need for theoretical explanation and elucidation of the PROTAC to guide the developing of more effective and valuable PROTAC.
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Compostos Heterocíclicos , Nitrogênio , Compostos Heterocíclicos/química , Compostos Heterocíclicos/farmacologia , Compostos Heterocíclicos/síntese química , Humanos , Nitrogênio/química , Estrutura Molecular , Animais , LigantesRESUMO
Genomic data is growing exponentially, posing new challenges for sequence analysis and classification, particularly for managing and understanding harmful new viruses that may later cause pandemics. Recent genome sequence classification models yield promising performance. However, the majority of them do not consider the sequential arrangement of nucleotides and amino acids, a critical aspect for uncovering their inherent structure and function. To overcome this, we introduce GenoAnaCla, a novel approach for analyzing and classifying genome sequences, based on sequential pattern mining (SPM). The proposed approach first constructs and preprocesses datasets comprising RNA virus genome sequences in three formats: nucleotide, coding region, and protein. Then, to capture sequential features for the analysis and classification of viruses, GenoAnaCla extracts frequent sequential patterns and rules in three forms and in codons. Eight classifiers are utilized, and their effectiveness is assessed by employing a variety of evaluation metrics. A performance comparison demonstrates that the suggested approach surpasses the current state-of-the-art genome sequence classification and detection techniques with a 3.18% performance increase in accuracy on average.
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PARPi have been explored and applied in the treatment of various cancers with remarkable efficacy, especially BRCA1/2 mutated ovarian, breast, prostate, and pancreatic cancers. However, PARPi renders inevitable drug resistance and showed high toxicity because of PARP-Trapping with long-term clinic tracking. To overcome the drug resistance and the high toxicity of PARPi, many novel methods have been developed including PROTACs. Being an event-driven technology, PROTACs needs a high affinity, low toxicity warhead with no steric hindrance in binding process. Veliparib shows the lowest PARP-Trapping effect but could hardly to be the warhead of PROTACs because of the strong steric hindrance. Other PARP1 inhibitors showed less steric hindrance but owns high PARP-Trapping effect. Thus, the development of novel warhead with high PARP1 affinity, low PARP1-Trapping, and no steric hindrance would be valuable. In this work, we reserved benzimidazole as the motif to reserve the low PARP1-Trapping effect and substituted the pyrrole by aromatic ring to avoiding the steric hindrance in PARP1 binding cave. Thus, a series of benzimidazole derivates were designed and synthesized, and some biological activities in vitro were evaluated including the inhibition for PARP1 enzyme and the PARP-Trapping effect using MDA-MB-436 cell line. Results showed that the compound 19A10 has higher PARP1 affinity(IC50 = 4.62 nM)) and similar low PARP-Trapping effect compared with Veliparib(IC50 (MDA-MB-436) >100 µM). Docking study showed that the compound 19A10 could avoiding the steric hindrance which was much better than Veliparib. So, the compound 19A10 could potentially be a perfect warhead for PARP1 degraders. Besides, because of the depletion of the PARP1 and the decreasing of the binding capability, we suppose that the PROTACs using 19A10 as the warhead would be no-PARP-Trapping effect. Furthermore, QSAR study showed that to develop novel compounds with high PARP1 binding affinity and low PARP-Trapping, we can choose the skeleton with substituent R1H, R2 = piperiazine, and R3 with large tPSA. And, if we want to develop the compounds with high PARP1 binding affinity and high PARP-Trapping which can possibly improve the lethality against tumor cells, we can choose the skeleton with substituent R1F, R2 = 3-methy-piperiazine, and R3 with large tPSA.
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Antineoplásicos , Benzimidazóis , Ensaios de Seleção de Medicamentos Antitumorais , Poli(ADP-Ribose) Polimerase-1 , Inibidores de Poli(ADP-Ribose) Polimerases , Benzimidazóis/química , Benzimidazóis/farmacologia , Benzimidazóis/síntese química , Humanos , Poli(ADP-Ribose) Polimerase-1/metabolismo , Poli(ADP-Ribose) Polimerase-1/antagonistas & inibidores , Inibidores de Poli(ADP-Ribose) Polimerases/farmacologia , Inibidores de Poli(ADP-Ribose) Polimerases/química , Inibidores de Poli(ADP-Ribose) Polimerases/síntese química , Relação Estrutura-Atividade , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/síntese química , Estrutura Molecular , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Simulação de Acoplamento MolecularRESUMO
Refractory materials are an important pillar for the stable development of the high-temperature industry. A large amount of waste refractories needs to be further disposed of every year, so it is of great significance to carry out research on the recycling of used refractories. In this work, lightweight composite aggregate was prepared by using discarded Al2O3-ZrO2-C refractories as the main raw material, and the performance of the prepared lightweight aggregate was improved by adjusting the calcination temperature and introducing light calcined magnesia additives. The results showed that the cold compressive strength and thermal shock resistance of the lightweight aggregates were significantly improved with increasing calcination temperature. Moreover, the introduction of light calcined magnesia can effectively improve the apparent porosity, cold compressive strength, and thermal shock resistance of the prepared lightweight aggregates at the calcination temperature of 1400 °C. Consequently, this work provides a useful reference for the resource utilization of used refractories, while the prepared lightweight aggregates are expected to be applied in the field of high-temperature insulation.
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It is crucial for effectively controlling potentially toxic element (PTE) pollution to understand the pollution situation, ecological risks, health risks, and migration patterns of PTEs. However, currently, no research has been conducted on the migration patterns of soil PTEs from coal mining subsidence areas to waterlogged areas under different restoration modes. In this study, a total of 15 sediment samples and 60 soil samples were collected from landscaped wetlands, aquaculture wetland, fish-photovoltaic complementary wetland, photovoltaic wetland, and waterlogged areas with untreated coal mining subsidence. The PTE pollution status, ecological risks, health risks, migration patterns, and the important factors influencing the migration were analyzed. The results indicated that the comprehensive pollution level of PTEs in waterlogged areas with coal mining subsidence can be reduced by developing them into landscaped wetlands, aquaculture wetlands, fish-photovoltaic complementary wetlands, and photovoltaic wetlands. Additionally, the closer to the waterlogged area, the higher the Cu content in the subsidence area soil is, reaching its peak in the waterlogged area. The Cd was influenced positively by SOC and pH. The research results were of great significance for formulating reclamation plans for waterlogged areas and controlling PTE pollution.
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Considering practical application and commercialization, the research of non-toxic and stable halide perovskite and its application in the field of photoelectric detection have received great attention. However, there are relatively few studies on deep ultraviolet photodetectors, and the perovskite films prepared by traditional spin-coating method have disadvantages such as uneven grain size and irregular agglomeration, which limit their device performance. Herein, uniform and ordered Cs3Cu2I5 nanonet arrays are fabricated based on monolayer colloidal crystal (MCC) templates prepared with 1 µm polystyrene (PS) spheres, which enhance light-harvesting ability. Furthermore, the performance of the lateral photodetector (PD) is significantly enhanced when using Cs3Cu2I5 nanonet compared to the pure Cs3Cu2I5 film. Under deep ultraviolet light, the Cs3Cu2I5 nanonet PD exhibits a high light responsivity of 1.66 AW-1 and a high detection up to 2.48 × 1012 Jones. Meanwhile, the unencapsulated PD has almost no response to light above 330 nm and shows remarkable stability. The above results prove that Cs3Cu2I5 nanonet can be a great potential light-absorbing layer for solar-blind deep ultraviolet PD, which can be used as light absorption layer of UV solar cell.
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All-inorganic cesium lead halide perovskite nanocrystals (NCs) are quite promising materials for emission-based applications. However, the intrinsic toxicity of lead, as well as the weak stability, remains to be resolved. Exploring more and more types of lead-free NCs with high photoluminescence quantum yields (PLQYs) and high stability is a fundamental task. This work gave the first example of copper doped cesium halide (Cu:CsX, X = Br, Cl/Br, Br/I) NCs with good stability and high PLQYs (â¼31.2%), which could act as a new member of the lead-free NC family. A simple single-step ultrasonic method was applied for the synthesis of environmentally friendly Cu:CsX NCs. By varying the halide composition, the emission wavelength of Cu:CsX can be shifted within 450-505 nm. The as-prepared NCs show highly uniform size and excellent stability. Finally, UV pumped light-emitting diodes are demonstrated by using Cu:CsX NCs as a color conversion layer.
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The growing demands for optical anti-counterfeiting technology require the development of new environmentally friendly materials with single component, multimodal fluorescence and high stability. Herein, the Bi/Sb codoped Cs2Ag0.1Na0.9InCl6 lead-free double perovskite material is reported as an efficient multimodal luminescence material with excitation-wavelength-dependent emission. When excited by 360 nm UV light, dual-emission is observed at 455 and 560 nm, which comes from the 3P1-1S0 transition of Sb3+ ions and self-trapped excitons (STEs), respectively. Under the 320 nm UV lamp, the microcrystals show only a blue emission centered at 455 nm. Therefore, the Bi/Sb codoped Cs2Ag0.1Na0.9InCl6 double perovskite emits blue and yellow lights under the 320 and 360 nm UV lamp, respectively. Moreover, the obtained double perovskite shows a high PLQY up to 41% and excellent stability against both air and high temperature, which make it a promising anti-counterfeiting material.
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Toxic pollutants are affecting the environment on a global scale. To quantify the extent of the elemental pollution in Peixian, a typical Chinese city, we collected 332 soil samples from agricultural, residential, woodland, and hydrological environments. Using multivariate statistical and geostatistical analyses, the results indicate that contaminants including chromium (Cr), zinc (Zn), copper (Cu), lead (Pb), cadmium (Cd), and arsenic (As) may share common sources such as commercial activities, coal mining activities, water transportation, power generation, and livestock manure. The presence of mercury (Hg) in the southern part of the study area, however, is almost entirely attributed to nearby mining activities. The value of contamination index was the highest in hydrological environments. Health exposure risk assessments of the elements were also investigated. With the exception of Pb, the potentially toxic elements in the study area do not pose a severe non-carcinogenic health risk. At the levels observed in our study, however, Pb may pose a non-carcinogenic risk to children. Based on these results, the area's livability is assessed. The urban livability analysis shows that the livability level is higher in the western part of the study area than it is in the eastern part.
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Poluentes Ambientais , Metais Pesados/análise , Poluentes do Solo/análise , Criança , China , Cidades , Monitoramento Ambiental , Humanos , Medição de Risco , SoloRESUMO
Non-small cell lung cancer (NSCLC) is the major type of lung malignancy with increasing incidence worldwide. Despite progression in diagnosis and management of NSCLC, the patients' survival rate is still unfavorable. Accumulating data have shown that circular RNAs (circRNAs) act as key roles in oncogenesis. In this project, circ_0026134 expression in NSCLC tissue specimens and cells was measured by RT-qPCR. The functional roles (cell growth, apoptosis, migration, and invasion) of circ_0026134 were investigated by gain and loss-of-function assays. In addition, luciferase reporter assay was used to uncover the mechanisms of circ_0026134. Circ_0026134 was frequently upregulated in NSCLC samples and cell lines. Furthermore, we observed that downregulation of circ_0026134 attenuated NSCLC cell proliferation and metastatic properties and induced cell apoptosis. The overexpression of circ_0026134 in NSCLC cells caused the opposite effect. For the part of mechanism exploration, miR-1256 and miR-1287 were proved to be sponged by circ_0026134. Rescue experiments further indicated that the oncogenic role of circ_0026134 was dependent on its regulation of miR-1256 and miR-1287. Taken together, this study may provide a new insight and treatment target for NSCLC.
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Carcinoma Pulmonar de Células não Pequenas/genética , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Neoplasias Pulmonares/genética , MicroRNAs/metabolismo , RNA/genética , Células A549 , Apoptose/genética , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/patologia , Linhagem Celular Tumoral , Proliferação de Células/genética , Células Epiteliais/metabolismo , Células Epiteliais/patologia , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Invasividade Neoplásica , RNA Circular , Regulação para CimaRESUMO
Agricultural multifunctionality is increasing interest and importance under the environmental change, which influences the sustainability of agricultural systems. However, research on how the agricultural multifunctionality is being temporally adjusted under the process of rapid urbanization remains limited. Here, we use the Yangtze River Delta, one of the newest metropolitan agglomerations globally, as study area to investigate the threats of modern urbanization to traditional agriculture. This study assessed changes to farmland area and the agricultural multifunctionality of 16 cities in the delta during 1995-2015. The results show that: (1) 87.1% (690, 200â¯hm2) of farmland area was lost because of urban sprawl over the last 20â¯years; (2) the total value of agricultural multifunctionality in the delta had increased by 23.2%, which was mainly attributed to a significant increase in food provision and cultural leisure values; (3) the key factor affecting the spatial differentiation of agricultural multifunctionality changed from agricultural labour in 1995 to gross domestic product in 2005 and 2015; and (4) Socio-economic conditions and natural resources determined the adaptive change model of agricultural multifunctionality in different groups of cities. These results illustrate that agricultural multifunctionality is being adjusted to rapid urbanization through the intensification and trade-off of the multiple functions in agricultural system. Therefore, to foster the sustainable development of agriculture in metropolitan agglomerations, future land use policy should focus on both urban control and promoting agricultural multifunctionality. Ongoing transformation practices, such as land consolidation, should aim to improve the bio-physical and socio-economic functions of farmland in the delta. Future research should focus on developing locally suitable strategies based on the adaptive mechanisms of agricultural multifunctionality under changing environments in different cities.
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This work investigated the influences of citric acid and methyl-ß-cyclodextrin (MCD) as enhancing agents during the electrokinetics (EK)-persulfate process on the remediation of soil artificially contaminated with decabromodiphenyl ether (BDE-209) and copper (Cu) with an initial concentration of 50 and 1000 mg/kg, respectively. The results clearly demonstrate the efficiency of the process while at the same time, the distribution of the residual contaminants in soil and the EK parameters were greatly influenced by the presence of persulfate, MCD and citric acid. The results show that there was significant removal of BDE-209 and Cu from the soil. MCD-assisted process gave the highest BDE-209 removal (88.6%) and the third largest Cu removal (54.3%) from the soil. Comparatively, the highest Cu removal (92.5%) and the second largest BDE-209 removal (85.6%) were achieved by the joint application of MCD and citric acid in anolyte during the EK-persulfate treatment. MCD and citric acid could increase soil electrical current and electroosmotic flow during EK. The alkalization of soil near cathode was alleviated by the acidic byproducts of persulfate decomposition which could be transported to the soil by electroosmosis and electromigration. This integration process may provide a green efficient technology for remediating co-contaminated soil.
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PURPOSE: The purpose of this study was to investigate the biological role and mechanism of miR-373 targeting of TFIIB-related factor 2 (BRF2) in the regulation of non-small cell lung cancer (NSCLC) cells. MATERIALS AND METHODS: miRNA microarray chip analysis of four paired NSCLC and adjacent non-tumor tissues was performed. Quantitative real-time polymerase chain reaction (qRT-PCR) andwestern blotting were used to detect the expression levels of miR-373 and BRF2 in NSCLC tissues and cell lines. The dual-luciferase reporter method was performed to determine if BRF2 is a target of miR-373. MTT, wound-healing, Transwell, and flow cytometric assays were conducted to examine the proliferation, migration, invasion, and cell cycle progression of NSCLC A549 cells, respectively; western blotting was used to detect the expression of epithelial-mesenchymal transition (EMT)-related proteins. RESULTS: The miRNA microarray chip analysis demonstrated that miR-373 was down-regulated in NSCLC tissues, and this result was confirmed by qRT-PCR. Additionally, miR-373 was confirmed to target BRF2. Moreover, miR-373 expression was inversely correlated with BRF2 expression in NSCLC tissues and cell lines; both miR-373 down-regulation and BRF2 up-regulation were strongly associated with the clinicopathological features and prognosis of NSCLC patients. In vitro, overexpression of miR-373 markedly inhibited cell proliferation, migration, and invasion; up-regulated the expression of E-cadherin; and down-regulated the expression of N-cadherin and Snail in A549 cell. Knockdown BRF2 by siRNA resulted in effects similar to those caused by overexpression of miR-373. CONCLUSION: MiR-373 is decreased in NSCLC, and overexpression of miR-373 can suppress cell EMT, and inhibit the proliferation, migration, and invasion of NSCLC A549 cells by targeting BRF2.
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Carcinoma Pulmonar de Células não Pequenas/genética , Regulação para Baixo , Neoplasias Pulmonares/genética , MicroRNAs/genética , Fator de Transcrição TFIIIB/genética , Regiões 3' não Traduzidas , Células A549 , Adulto , Idoso , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Movimento Celular , Proliferação de Células , Transição Epitelial-Mesenquimal , Feminino , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Pulmonares/metabolismo , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Análise de Sequência com Séries de Oligonucleotídeos , Prognóstico , Fator de Transcrição TFIIIB/metabolismoRESUMO
OBJECTIVE: MicroRNAs have been found to be deregulated in lung cancers, which play crucial roles in tumorigenesis and progression. FBXW7 and FBXW11, two important F-box proteins of the ubiquitin-proteasome system (UPS), can target multiple substrates for degradation, in order to regulate cell proliferation and survival in cancers. In the present study, we aimed to explore the potential role and regulating mechanism of miR-182 in non-small cell lung cancer (NSCLC). METHODS: MiRNA expression was evaluated by quantitative reverse-transcription polymerase chain reaction (qRT-PCR). FBXW7, FBXW11, c-Jun, c-Myc and cyclin D protein levels were detected by western blot. Cell growth was determined using cell counting kit (CCK)-8 reagent and colony formation experiment. Then, cell apoptosis and the cell cycle were analyzed on flow cytometry. The target binding activity of miR-182 with FBXW7 or FBXW11 was evaluated through the Dual-Luciferase Reporter Assay System. RESULTS: It was confirmed that miR-182 was significantly upregulated in tumor tissues, compared with adjacent normal tissues, and this was inversely correlated to the protein levels of FBXW7 and FBXW11. The overexpression of miR-182 in NSCLC cells dramatically promoted cell growth, colony formation capacity and cell cycle progression, and inhibited apoptosis in NSCLC cells. In contrast, the downregulation of miR-182 significantly alleviated these properties in vitro. Furthermore, we demonstrated that miR-182 exerted an oncogenic role in NSCLC by directly targeting FBXW7 and FBXW11. CONCLUSION: These results bring new insights into the oncogenic role of miR-182 in NSCLC, indicating that miR-182 might be a novel biomarker for the diagnosis and prognosis of NSCLC.