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The quest for sustainable and clean energy sources has intensified research on the Hydrogen Evolution Reaction (HER) in recent decades. In this study, we have presented a novel Ce-doped TiO2 catalyst synthesized through the sol-gel method, showcasing its potential as a superior electrocatalyst for HER in an acidic medium. Comprehensive characterization through X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), Energy dispersive X-ray (EDX), and Raman spectroscopy confirms the successful formation of the catalyst. Electrocatalytic performance evaluation, including open circuit potential (OCP), electrochemical impedance spectroscopy (EIS), and Tafel analysis, demonstrates that GCE-5wt.%CeTiO2 outperforms bare GCE, as well as Ce and TiO2-based electrodes. Kinetic investigations reveal a Tafel slope of 105â mV dec-1, indicating the Volmer step as the rate-determining step. The onset potential for HER at GCE-5wt.%CeTiO2 is -0.16â V vs. RHE, close to the platinum electrode. Notably, the catalyst exhibits a low overpotential of 401â mV to achieve a current density of 10â mA cm-2 with an impressive 95 % Faradaic efficiency. Furthermore, the catalyst demonstrates outstanding durability, maintaining a negligible increase in overpotential during a 14-hour chronoamperometry test. These results have far-reaching implications for the development of cost-effective and efficient electrocatalysts for hydrogen production.
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Cuprous oxide (Cu2O) nanorods have been deposited on soda-lime glass substrates by the modified successive ionic layer adsorption and reaction technique by varying the concentration of NaCl electrolyte into the precursor complex solution. The structural, electrical and optical properties of synthesized Cu2O nanorod films have been studied by a variety of characterization tools. Structural analyses by X-ray diffraction confirmed the polycrystalline Cu2O phase with (111) preferential growth. Raman scattering spectroscopic measurements conducted at room temperature also showed characteristic peaks of the pure Cu2O phase. The surface resistivity of the Cu2O nanorod films decreased from 15 142 to 685 Ω.cm with the addition of NaCl from 0 to 4 mmol and then exhibited an opposite trend with further addition of NaCl. The optical bandgap of the synthesized Cu2O nanorod films was observed as 1.88-2.36 eV, while the temperature-dependent activation energies of the Cu2O films were measured as about 0.14-0.21 eV. Scanning electron microscope morphologies demonstrated Cu2O nanorods as well as closely packed spherical grains with the alteration of NaCl concentration. The Cu2O phase of nanorods was found stable up to 230°C corroborating the optical bandgap results of the same. The film fabricated in presence of 4 mmol of NaCl showed the lowest resistivity and activation energy as well as comparatively uniform nanorod morphology. Our studies demonstrate that the nominal presence of NaCl electrolytes in the precursor solutions has a significant impact on the physical properties of Cu2O nanorod films which could be beneficial in optoelectronic research.
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Herein, we report the encapsulation and release of antimalarial drug quinine (QN) using three nanocarriers, including MCM-41 (1), and its 3-aminopropyl silane (aMCM-41 (2)) and 3-phenylpropyl silane (pMCM-41 (3)) surface functionalized derivatives. The pH and thermal optimization effects on QN adsorption and release from 1, 2 and 3 were investigated.
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Antimaláricos/química , Nanopartículas/química , Quinina/química , Dióxido de Silicio/química , Cápsulas/química , Portadores de Fármacos/química , Sistemas de Liberación de Medicamentos , Estructura Molecular , Tamaño de la Partícula , Porosidad , Propiedades de SuperficieRESUMEN
Protein Kinase CK2 (Casein Kinase 2 or CK2) is a constitutively active serine-threonine kinase overactive in human malignancies. Increased expression and activity of CK2 in Acute Myeloid Leukemia (AML) is associated with a poor outcome. CK2 promotes AML cell survival by impinging on multiple oncogenic signaling pathways. The selective small-molecule CK2 inhibitor CX-4945 has shown in vitro cytotoxicity in AML. Here, we report that CX-4945 has a strong in vivo therapeutic effect in preclinical models of AML. The analysis of genome-wide DNA-binding and gene expression in CX-4945 treated AML cells shows that one mechanism, by which CK2 inhibition exerts a therapeutic effect in AML, involves the revival of IKAROS tumor suppressor function. CK2 phosphorylates IKAROS and disrupts IKAROS' transcriptional activity by impairing DNA-binding and association with chromatin modifiers. Here, we demonstrate that CK2 inhibition decreases IKAROS phosphorylation and restores IKAROS binding to DNA. Further functional experiments show that IKAROS negatively regulates the transcription of anti-apoptotic genes, including BCL-XL (B cell Lymphoma like-2 like 1, BCL2L1). CX-4945 restitutes the IKAROS-mediated repression of BCL-XL in vivo and sensitizes AML cells to apoptosis. Using CX-4945, alongside the cytotoxic chemotherapeutic drug daunorubicin, augments BCL-XL suppression and AML cell apoptosis. Overall, these results establish the in vivo therapeutic efficacy of CX-4945 in AML preclinical models and determine the role of CK2 and IKAROS in regulating apoptosis in AML. Furthermore, our study provides functional and mechanistic bases for the addition of CK2 inhibitors to AML therapy.
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It has been more than 10 months since the first COVID-19 case was reported in Wuhan, China, still menacing the world with a possible second wave. This study aimed to analyze how meteorological variables can affect the spread of local COVID-19 transmission in Bangladesh. Nine spatial units were considered from a meteorological standpoint to characterize COVID-19 transmission in Bangladesh. The daily COVID-19 incidence and meteorological variable (e.g., mean temperature, relative humidity, precipitation, and wind speed) data from April 5 to September 20, 2020, were collected. The Spearman rank correlation, heat maps, and multivariate quasi-Poisson regression were employed to understand their association. The effect of meteorological variables on COVID-19 transmission was modeled using a lag period of 10 days. Results showed that mean temperature, relative humidity, and wind speed are substantially associated with an increased risk of COVID-19. On the other hand, daily precipitation is significantly associated with a decreased risk of COVID-19 incidence. The relative risks (RR) of mean temperature for daily COVID-19 incidences were 1.222 (95% confidence interval [CI], 1.214-1.232). For wind speed, the RR was 1.087 (95% CI, 1.083-1.090). For relative humidity, the RR was 1.027 (95% CI, 1.025-1.029). Overall, this study found the profound effect of meteorological parameters on COVID-19 incidence across selected nine areas in Bangladesh. This study is probably the first study to explore the impact of region-specific meteorological conditions on COVID-19 incidence in Bangladesh. Moreover, adjustments on the areal-aggregated and regional levels were made for three confounding factors, including lockdown, population density, and potential seasonal effects. The study's findings suggest that SARS-CoV-2 can be transmitted in high temperatures and humidity conditions, which contradicts many other countries' prior studies. The research outcomes will provide implications for future control and prevention measures in Bangladesh and other countries with similar climate conditions and population density.
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Here, we report the effect of the substrate, sonication process, and postannealing on the structural, morphological, and optical properties of ZnO thin films grown in the presence of isopropyl alcohol (IPA) at temperature 30-65 °C by the successive ionic layer adsorption and reaction (SILAR) method on both soda lime glass (SLG) and Cu foil. The X-ray diffraction (XRD) patterns confirmed the preferential growth thin films along (002) and (101) planes of the wurtzite ZnO structure when deposited on SLG and Cu foil substrates, respectively. Both XRD and Raman spectra confirmed the ZnO and Cu-oxide phases of the deposited films. The scanning electron microscopy image of the deposited films shows compact and uniformly distributed grains for samples grown without sonication while using IPA at temperatures 50 and 65 °C. The postannealing treatment improves the crystallinity of the films, further evident by XRD and transmission and reflection results. The estimated optical band gaps are in the range of 3.37-3.48 eV for the as-grown samples. Our experimental results revealed that high-quality ZnO thin films could be grown without sonication using an IPA dispersant at 50 °C, which is much lower than the reported results using the SILAR method. This study suggests that in the presence of IPA, the SLG substrate results in better c-axis-oriented ZnO thin films than that of deionized water, ethylene glycol, and propylene glycol at the optimum temperature of 50 °C. Air annealing of the samples grown on Cu foils induced the formation of Cu x O/ZnO junctions, which is evident from the characteristic I-V curve including the structural and optical data.
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IKAROS, encoded by the IKZF1 gene, is a DNA-binding protein that functions as a tumor suppressor in T cell acute lymphoblastic leukemia (T-ALL). Recent studies have identified IKAROS's novel function in the epigenetic regulation of gene expression in T-ALL and uncovered many genes that are likely to be directly regulated by IKAROS. Here, we report the transcriptional regulation of two genes, phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta (PIK3CD) and phosphoinositide kinase, FYVE-type zinc finger containing (PIKFYVE), by IKAROS in T-ALL. PIK3CD encodes the protein p110δ subunit of phosphoinositide 3-kinase (PI3K). The PI3K/AKT pathway is frequently dysregulated in cancers, including T-ALL. IKAROS binds to the promoter regions of PIK3CD and PIKFYVE and reduces their transcription in primary T-ALL. Functional analysis demonstrates that IKAROS functions as a transcriptional repressor of both PIK3CD and PIKFYVE. Protein kinase CK2 (CK2) is a pro-oncogenic kinase that is overexpressed in T-ALL. CK2 phosphorylates IKAROS, impairs IKAROS's DNA-binding ability, and functions as a repressor of PIK3CD and PIKFYVE. CK2 inhibition results in increased IKAROS binding to the promoters of PIK3CD and PIKFYVE and the transcriptional repression of both these genes. Overall, the presented data demonstrate for the first time that in T-ALL, CK2 hyperactivity contributes to PI3K signaling pathway upregulation, at least in part, through impaired IKAROS transcriptional regulation of PIK3CD and PIKFYVE. Targeting CK2 restores IKAROS's regulatory effects on the PI3K oncogenic signaling pathway.
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Quinasa de la Caseína II/genética , Fosfatidilinositol 3-Quinasa Clase I/genética , Regulación Leucémica de la Expresión Génica , Factor de Transcripción Ikaros/genética , Fosfatidilinositol 3-Quinasas/genética , Leucemia-Linfoma Linfoblástico de Células T Precursoras/genética , Quinasa de la Caseína II/antagonistas & inhibidores , Quinasa de la Caseína II/metabolismo , Línea Celular Tumoral , Ensamble y Desensamble de Cromatina/genética , Fosfatidilinositol 3-Quinasa Clase I/metabolismo , Células HEK293 , Humanos , Factor de Transcripción Ikaros/metabolismo , Naftiridinas/farmacología , Fenazinas/farmacología , Fosfatidilinositol 3-Quinasas/metabolismo , Fosforilación/efectos de los fármacos , Leucemia-Linfoma Linfoblástico de Células T Precursoras/metabolismo , Regiones Promotoras Genéticas/genética , Unión Proteica , Transducción de Señal/genéticaRESUMEN
The key challenges for converting chitin to 5-hydroxymethylfurfural (5-HMF) include the low 5-HMF yield. Moreover, the disadvantages of traditional acid-base catalysts including complex post-treatment processes, the production of by-products, and severe equipment corrosion also largely limit the large-scale conversion of chitin to 5-HMF. In this view, herein we have demonstrated a microwave aided efficient and green conversion of chitin to 5-HMF while using polyoxometalate (POM) as a catalyst and DMSO/water as solvent. Chitin treated with H2SO4 followed by ball-milling (chitin-H2SO4-BM) was selected as the starting compound for the conversion process. Four different POMs including H3[PW12O40], H3[PMo12O40], H4[SiW12O40] and H4[SiMo12O40] were used as catalysts. Various reaction parameters including reaction temperature, amount of catalyst, mass ratios of water/DMSO and reaction time have been investigated to optimize the 5-HMF conversion. The H4[SiW12O40] catalyst exhibited the highest catalytic performance with 23.1% HMF yield at optimum operating conditions which is the highest among the literature for converting chitin to 5-HMF. Significantly, the disadvantages of the state of the art conversion routes described earlier can be overcome using POM-based catalysts, which makes the process more attractive to meet the ever-increasing energy demands, in addition to helping consume crustacean waste.
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The viability of biorefining technology primarily depends on the facile cellulose conversion route with adequate conversion efficiency. Here we have demonstrated the microwave-assisted hydrolysis of cellulose to glucose using polyoxometalate (POM) clusters as acid catalysts. Two different types of POM, including Wells-Dawson and Keggin were justified as catalysts in the cellulose conversion process. In particular, the cellulose to glucose catalytic conversion using Wells-Dawson type POMs has not been reported to date. Also, even though there have been some previous reports about the catalytic biomass conversion of Keggin type POMs, the systematic study to optimize the conversion efficiency in terms of catalyst amount, reaction temperature, reaction time, and the amount of solvent is lacking. Under the experimental conditions employed, the Keggin-type catalyst showed higher cellulose conversion and glucose yield than the Wells-Dawson-type catalyst. Furthermore, the cellulose conversion efficiency and glucose yields were optimized by tuning the reaction conditions including temperature, reaction time, and the amount of solvent. Under optimized conditions, the Keggin-type POM catalyst shows a remarkably high glucose yield of 77.2% and a cellulose conversion of 90.1%. The unique complex properties of the POM catalyst, including being (i) strong acids with extremely high Brønsted and Lewis acidity and (ii) efficient microwave adsorbants which enhanced interaction between substrate and the catalyst can be attributed to the outstanding efficacy of the conversion process.
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IBNtxA (3-iodobenzoyl naltrexamine) is a novel µ-opioid receptor (MOR) agonist which is structurally related to the MOR antagonist naltrexone. Recent studies suggest IBNtxA preferentially signals through truncated MOR splice variants, resulting in anti-nociception with reduced side effects, including no conditioned place preference (CPP) when tested at a single dose. IBNtxA represents an intriguing lead compound for preclinical drug development targeting truncated MOR splice variants, but further evaluation of its in vivo pharmacological profile is necessary. The purpose of this study was to independently verify the antinociceptive properties of IBNtxA and to examine more completely the rewarding properties and discriminative stimulus effects of IBNtxA, allowing broader assessment of IBNtxA as a candidate for further medications development. A dose of 3 mg/kg IBNtxA was equipotent to 10 mg/kg morphine in a hot-plate analgesia assay. In drug discrimination testing using mice trained to discriminate between 3 mg/kg IBNtxA and vehicle, the κ-agonist U-50488 fully substituted for IBNtxA. MOR agonist morphine, δ-agonist SNC162, NOP agonist SCH 221510, and MOR/NOP partial agonist buprenorphine each partially substituted for IBNtxA. IBNtxA up to 3 mg/kg did not produce a place preference in CPP. Pretreatment with 3 mg/kg IBNtxA but not 1 mg/kg IBNtxA attenuated acquisition of place preference for 10 mg/kg morphine. A dose of 3 mg/kg IBNtxA attenuated morphine-induced hyperlocomotion but did not alter naloxone-precipitated morphine withdrawal. Overall, IBNtxA has a complicated opioid receptor pharmacology in vivo. These results indicate that IBNtxA produces potent anti-nociception and has low abuse liability, likely driven by substantial κ agonist signaling effects.
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Cyclooxygenase-2 (COX-2) inhibitors are regarded as potentially important in strategies for cancer treatment. however, the precise mechanisms of these anti-inflammatory drugs as anti-cancer therapy are still unknown. In this study, we examined the effect of DFU both in vitro on MCF-7 cell growth, as well as in vivo on tumor growth produced by MCF-7 cell injection in mice. DFU has growth inhibitory effects on tumor growth in mice compared to the control group. We examined the tumor tissues for apoptosis and angiogenesis by immunostaining. Apoptosis was detected only in the treatment group. DFU treatment also resulted in the inhibition of angiogenesis, as well as decreased COX-2 expression. Results of this study suggest that inhibitory effects of DFU might be COX-2 dependent.
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Inhibidores Enzimáticos/farmacología , Furanos/farmacología , Isoenzimas/antagonistas & inhibidores , Animales , Apoptosis , Línea Celular Tumoral , Proliferación Celular , Ciclooxigenasa 2 , Humanos , Inmunohistoquímica , Masculino , Proteínas de la Membrana , Ratones , Ratones SCID , Trasplante de Neoplasias , Neovascularización Patológica , Molécula-1 de Adhesión Celular Endotelial de Plaqueta/biosíntesis , Prostaglandina-Endoperóxido Sintasas , Factores de TiempoRESUMEN
PTEN, a novel tumor suppressor, functions as a regulator of both cell cycle progression and apoptosis. PTEN gene is frequently mutated or deleted in several malignancies including human hepatocellular carcinoma (HCC). The clinical significance and prognostic value of PTEN expression in HCC or in the surrounding non-cancerous parenchyma remain obscure. Using immunohistochemistry, we analyzed the PTEN protein expression in 46 tissue sections collected from surgically resected hepatitis C virus (HCV)-positive cirrhotic HCC patients. Although the surrounding normal liver tissue was strongly expressing PTEN in 42 cases (91.3%), the immunostaining intensity was low in 29 (63.1%) and high in 17 (36.9%) of the HCCs. Additionally a significant positive correlation was identified between low PTEN expression in the HCC and increased expression of iNOS and COX II in the surrounding liver. The overall survival was significantly longer for the HCC-patients with high PTEN expression than patients with low PTEN expression. Univariate analysis revealed PTEN expression as an independent prognostic factor for patients survival. By Western blot analysis we also found that the Akt/PKB signaling, which is negatively regulated by PTEN, was upregulated in the HCCs in comparison to its expression in the surrounding liver tissue. These results demonstrate that downregulation of PTEN in the tumor is an important step in HCV-positive cirrhotic hepatocarcinogenesis and might result in concomitant upregulation of iNOS and COX II in the surrounding liver in favor of tumor promotion.