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Transition metal phosphides (TMPs) have been widely studied for water decomposition for their monocatalytic property for anodic or cathodic reactions. However, their bifunctional catalytic activity still remains a major challenge. Herein, hexagonal nickel-cobalt bimetallic phosphide nanoneedles with 1-3 µm length and 15-30 nm diameter supported on NF (NixCo2-xP NDs/NF) with adjusted electron structure have been successfully prepared. The overall alkaline water electrolyzer composed of the optimal anode (Ni0.67Co1.33P NDs/NF) and cathode (Ni1.01Co0.99P NDs/NF) provide 100 mA cm-2 at 1.62 V. Gibbs Free Energy for reaction paths proves that the active site in the hydrogen evolution reaction (HER) is Ni and the oxygen evolution reaction (OER) is Co in NixCo2-xP, respectively. In the HER process, Co-doping can result in an apparent accumulation of charge around Ni active sites in favor of promoting HER activity of Ni sites, and ΔGH* of 0.19 eV is achieved. In the OER process, the abundant electron transfer around Co-active sites results in the excellent ability to adsorb and desorb *O and *OOH intermediates and an effectively reduced ∆GRDS of 0.37 eV. This research explains the regulation of electronic structure change on the active sites of bimetallic materials and provides an effective way to design a stable and effective electrocatalytic decomposition of alkaline water.
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Endothelial-to-mesenchymal transition (EndMT) was first reported in heart development. Recent studies have shown that EndMT also occurs in the progression of cardiac fibrosis. Herein, we demonstrated a critical role of the Forkhead Box M1 (Foxm1) transcription factor in transforming growth factor beta (TGF-ß)-induced EndMT in endothelial cells (ECs) and a possible underlying molecular mechanism. Foxm1 was induced in ECs following TGF-ß stimulation. Using both pharmacological and molecular approaches to inhibit Foxm1 function can attenuate the TGF-ß-induced EndMT and cell migration. In contrast, lentivirus-mediated overexpression of Foxm1 allowed EndMT to proceed despite the absence of TGF-ß in ECs. Moreover, we found that the activation of the Smad2/3 signaling pathway and EndMT-related transcription factors played important roles in the pathogenesis of Foxm1-mediated EndMT. Further analysis revealed that Foxm1 bound to and increased the promoter activity of the Snail gene encoding a critical transcriptional regulator of EndMT. In conclusion, our results identify FOXM1 as a driver of TGF-ß-induced EndMT and underscore the therapeutic potential of targeting FOXM1 for cardiac fibrosis.
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Células Endoteliais/efeitos dos fármacos , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Proteína Forkhead Box M1/metabolismo , Proteína Smad2/metabolismo , Proteína Smad3/metabolismo , Fatores de Transcrição da Família Snail/metabolismo , Fator de Crescimento Transformador beta1/farmacologia , Fator de Crescimento Transformador beta2/farmacologia , Animais , Sítios de Ligação , Movimento Celular/efeitos dos fármacos , Células Cultivadas , Células Endoteliais/metabolismo , Proteína Forkhead Box M1/genética , Regulação da Expressão Gênica , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Camundongos Endogâmicos C57BL , Regiões Promotoras Genéticas , Transdução de Sinais , Proteína Smad2/genética , Proteína Smad3/genética , Fatores de Transcrição da Família Snail/genéticaRESUMO
N 6-methyladenosine (m6A) is an abundant modification in mammalian mRNAs and plays important regulatory roles in gene expression, primarily mediated through specific recognition by "reader" proteins. YTH family proteins are one major family of known m6A readers, which specifically recognize m6A-modified transcripts via the YTH domains. Despite the significant relevance of YTH-m6A recognition in biology and diseases, few small molecule inhibitors are available for specifically perturbing this interaction. Here we report the discovery of a new inhibitor ("N-7") for YTH-m6A RNA recognition, from the screening of a nucleoside analogue library against the YTH domain of the YTHDF1 protein. N-7 is characterized to be a pan-inhibitor in vitro against five YTH domains from human YTHDF1, YTHDF2, YTHDF3, YTHDC1, and YTHDC2 proteins, with IC50 values in the range of 30-48 µM measured using a fluorescence polarization competition assay. We demonstrated that N-7 directly interacts with the YTH domain proteins via a thermal shift assay. N-7 expands the chemical structure landscape of the m6A YTH domain-containing reader inhibitors and potentiates future inhibitor development for reader functional studies and therapeutic efforts in targeting the epitranscriptome.
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The investigation of the implementation effect of the low-carbon city pilot (LCCP) policy in promoting industrial low-carbon development is important for economic growth and carbon reduction in China. This paper takes the industry sector as an independent investigation object, and aims to examine the effectiveness of the policy in improving industrial low-carbon development. The industrial total factor carbon emission efficiency index (ITFCEE) is constructed to measure the level of industrial low-carbon development by the global frontier directional distance function. From the perspective of the multiple participants of the policy, we analyze the mechanisms of the policy, and construct the time-varying difference-in-difference model to test how LCCP policy impacts the ITFCEE. We conclude that (1) LCCP policy improves significantly the ITFCEE. (2) Heterogeneity analysis results show that the positive influence of LCCP policy is significant in cities with high industrial carbon emission intensity, high industrial structure upgrading, and high government expenditure. (3) The result of the mechanism analysis is that LCCP policy can benefit the ITFCEE by promoting enterprise green technology innovation, public environment concern, government technology support, and administrative regulation.
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Carbono , Indústrias , Humanos , Cidades , China , Desenvolvimento Econômico , PolíticasRESUMO
Enhancement of the adsorption performance and recyclability of adsorbents is a crucial aspect of water treatment. Herein, we used one-dimensional porous boron nitride (PBN) as a carrier to load Fe3O4 nanoparticles for the preparation of Fe3O4 nanoparticles-functionalized porous boron nitride (Fe3O4/PBN) via a ball milling method. The high-energy ball milling promoted the creation of a negatively charged PBN surface and facilitated the uniform distribution of Fe3O4 nanoparticles on the surface of PBN. The adsorption performance of Fe3O4/PBN toward cationic dyes could be significantly improved while no enhancement was observed for anionic dyes. The great adsorption performance of Fe3O4/PBN is due to its surface functional groups and surface defects formed in the ball milling process. Moreover, the strong interaction force between Fe3O4/PBN and cationic dyes promotes rapid initial adsorption due to their negatively charged surface. Magnetic measurements demonstrated that Fe3O4/PBN is superparamagnetic. The composites with low loadings of Fe3O4 nanoparticles could be quickly separated from the aqueous solution under a low applied magnetic field, improving their recyclability. This work highlights the role of ball milling in improving the adsorption performance of Fe3O4/PBN and greatly promotes the practical application of Fe3O4/PBN in the field of environmental purification.
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The Yellow River Basin is an energy-rich area. The low-carbon development of the Yellow River Basin is one of the ways to achieve ecological protection and high-quality development. Based on panel data from 2007 to 2019, the dynamic and static carbon emission efficiencies of 98 cities in the Yellow River Basin were calculated using the Undesirable Super Slacks-based model and the Global Malmquist-Luengerber index method, respectively, and the spatial effects of influencing factors were analyzed using the spatial Dubin model. Main conclusions are as follows: (1) The carbon emission efficiency of cities in the Yellow River Basin is different, and only a small numbers of cities have reached the effective state. (2) The main factor for the increase in the overall carbon emission efficiency of the whole Basin is technological progress, and the main factors for the improvement of carbon emission efficiency of different cities are various. (3) The direct effects of economic development level and industrial structure upgrading are significantly positive, the direct effects of technological development level, energy intensity, and opening up are significantly negative, and the indirect effects of population density are positive. The conclusions are of great significance for promoting low-carbon development, ecological protection and high-quality development in the Yellow River Basin.
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Carbono , Rios , Cidades , Desenvolvimento Econômico , Indústrias , China , EficiênciaRESUMO
It is of great significance to study the trends and internal differences of eco-efficiency in the Yellow River Basin for ecological protection and high-quality development of the Yellow River Basin. According to the characteristics of the Yellow River Basin in China, the eco-efficiency evaluation system was constructed, and the super-efficiency slack-based measure (SBM) model and the super-efficiency SBM model of undesired output were used to calculate the eco-efficiency levels of provinces in the Yellow River Basin from 2005 to 2020, and the variation trend and internal differences were analyzed. The results show that when only the expected output was considered, the eco-efficiency of the Yellow River Basin as a whole and each province showed a fluctuating upward trend, but there were obvious differences. Qinghai Province, Sichuan Province, and Ningxia Autonomous Region had high eco-efficiency, while Shaanxi Province, Shanxi Province, and Inner Mongolia Autonomous Region had low eco-efficiency. Compared with only considering the expected outputs, eco-efficiency of Qinghai Province had improved significantly when considering non-expected outputs. The eco-efficiency of Shandong Province and Henan Province had improved significantly after 2016, while the eco-efficiency of the two provinces had decreased significantly before 2016. The eco-efficiency of Shaanxi, Shanxi, Inner Mongolia, Ningxia, and Gansu had declined to varying degrees. Finally, the reasons for the differences in eco-efficiency in various provinces in the Yellow River Basin were analyzed, and suggestions for improving the eco-efficiency of the Yellow River Basin were put forward.
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Eficiência , Rios , China , Desenvolvimento EconômicoRESUMO
Reaching the peak of carbon dioxide emissions is the basis and premise of carbon neutrality. In this paper, the factor decomposition model was used to analyze the influencing factors and effects of carbon dioxide emissions. Causal chain model of elastic decoupling was established. The historical decoupling state between carbon dioxide emissions and economic growth and the decoupling effect of its influencing factors were analyzed. The prediction model of carbon dioxide emissions was used to explore the change trend of China's carbon dioxide emissions and its peak in the short and medium term in the future. The elastic decoupling trend between carbon dioxide emissions and economic growth was predicted. The results show that economic growth is the main force driving carbon dioxide emissions. Both energy intensity and energy consumption structure have a strong inhibiting effect on carbon dioxide emissions except for a few years, but the former has a more significant inhibiting effect than the latter. In general, the elastic decoupling between carbon dioxide emissions and economic growth has experienced a state from weak decoupling to growth linkage and then to weak decoupling. And this weak decoupling trend will continue to increase in the short and medium term. During the 14th Five-year and 15th Five-year period, if the average annual economic growth rate will be maintained at 4.61 to 5.85%, energy intensity will be reduced by 16.14 to 18.37%, and the proportion of non-fossil energy in the energy consumption structure at the end of the 14th, 15th, and 16th Five-Year Plan period will be around 19.9%, 23.2%, and 26.1%, respectively, and then the intensity of carbon dioxide emissions will continue to decline. It is expected to reach the peak of carbon dioxide emissions between 10,453 and 10,690 billion tons from 2025 to 2027. And the earlier the peak time is, the smaller the peak is, which would provide valuable time for carbon neutrality and room to reduce carbon dioxide emissions in the medium and long term.
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Dióxido de Carbono , Desenvolvimento Econômico , Dióxido de Carbono/análise , China , Previsões , Modelos TeóricosRESUMO
Continued development of lithium-ion batteries is limited by the shortage of Li element. In this situation, the exploration of high-performance sodium-ion batteries is attracting much attention. In this experimental work, Na2/3Ni1/4Mn34O2 film cathode materials were fabricated by excimer laser deposition at different oxygen partial pressures. X-ray diffraction studies and field emission scanning electron microscopy revealed high c-axis orientation and uniform grain distribution, respectively, in the deposited films. Furthermore, after 30 cycles under a current density of 13 mA g-1, the film samples deposited at an oxygen partial pressure of 65 Pa exhibited a high capacity-retention of 91%. The film structure also had a large-current discharge performance, which makes practical applications possible.
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The N6-methyladenosine (m6A) demethylase FTO is overexpressed in acute myeloid leukemia (AML) cells and promotes leukemogenesis. We previously developed tricyclic benzoic acid FB23 as a highly potent FTO inhibitor in vitro. However, it showed a moderate antiproliferative effect on AML cells. In this work, we performed a structure-activity relationship study of tricyclic benzoic acids as FTO inhibitors. The analog 13a exhibited excellent inhibitory effects on FTO similar to that of FB23 in vitro. In contrast to FB23, 13a exerted a strong antiproliferative effect on AML cells. Like FTO knock down, 13a upregulated ASB2 and RARA expression and increased the protein abundance while it downregulated MYC expression and decreased MYC protein abundance. These genes are key FTO targets in AML cells. Finally, 13a treatment improved the survival rate of MONOMAC6-transplanted NSG mice. Collectively, our data suggest that targeting FTO with tricyclic benzoic acid inhibitors may be a potential strategy for treating AML.
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Ácido Benzoico , Leucemia Mieloide Aguda , Dioxigenase FTO Dependente de alfa-Cetoglutarato/genética , Dioxigenase FTO Dependente de alfa-Cetoglutarato/metabolismo , Animais , Ácido Benzoico/farmacologia , Carcinogênese , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/genética , Camundongos , Relação Estrutura-AtividadeRESUMO
This study examines the sensitivity of daily PM2.5 to NOx emissions and meteorology using in situ observations from main cities of North China (NC). NC cities are divided into low-, medium-, and high-emission groups by the ranking of their 4-year mean NO2. For each emission group, daily NO2 levels are used to divide the days into good-, medium-, and bad-meteorological conditions. Regardless of their emission levels, all cities reveal significant decreases (96%-172%) in daily PM2.5 levels from bad to good meteorological conditions. The largest difference in PM2.5 concentrations between the emissions groups is found under bad meteorological conditions, with 56% higher PM2.5 in high-emission cities than low-emission cities, indicating PM2.5 under bad meteorological conditions has the largest sensitivity to emissions. The high-emission, bad-meteorology group saw a 24% decrease in mean daily PM2.5 levels from 2017, a high-emission year, to 2019, a low-emission year. However, under good meteorological conditions, the high-emissions group shows an increase of 8.8 µg/m3 in mean daily PM2.5 from 2017 to 2019 with a 2.6% increase in the possibility of high PM2.5. These results suggest the current emission reduction measures are more effective in controlling PM2.5 in high-emission cities under bad meteorological conditions than under other meteorological conditions.
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OBJECTIVE: We attempt to investigate the biological function of the discoidin, complement C1r/C1s,Uegf, and Bmp1 and Limulus factor C, Coch, and Lgl domain-containing 2 (DCBLD2) in glioblastoma, as well as its effect on the epithelial-mesenchymal transition (EMT) process. METHODS: The public expression data of glioblastoma samples and normal brain samples from The Cancer Genome Atlas database, Genotype-Tissue Expression database and Chinese Glioma Genome Atlas database were used to analyze the expression of DCBLD2 and its relationship with the survival of patients with glioblastoma. Quantitative real-time PCR and western blot were used to evaluate mRNA and protein levels of DCBLD2. Cell viabilities were tested using Cell Counting Kit-8 and clone formation assays. Cell invasive and migratory abilities were measured by transwell assays. RESULTS: DCBLD2 expression was upregulated in glioblastoma and has a significantly positive correlation with the WHO classification. In addition, high expression of DCBLD2 was closely correlated with poor prognosis in primary and recurrent patients with glioblastoma. What is more, we found that knockdown of DCBLD2 notably reduced the cell proliferative, invasive and migratory capacities by elevating the expression of E-cadherin and inhibiting the expression of vimentin, snail, slug and twist. However, overexpression of DCBLD2 presented the opposite results. CONCLUSION: The current study reveals that high expression of DCBLD2 is closely related to poor prognosis in glioblastoma and can significantly enhance the tumor cell viability and metastasis by activating the EMT process, suggesting that DCBLD2 may be a possible biomarker for glioblastoma treatment.
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Neoplasias Encefálicas/genética , Transição Epitelial-Mesenquimal/genética , Glioblastoma/genética , Proteínas de Membrana/genética , Antígenos CD/genética , Antígenos CD/metabolismo , Western Blotting , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patologia , Caderinas/genética , Caderinas/metabolismo , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Sobrevivência Celular/genética , Bases de Dados Genéticas , Técnicas de Silenciamento de Genes , Glioblastoma/metabolismo , Glioblastoma/patologia , Humanos , Proteínas de Membrana/metabolismo , Invasividade Neoplásica , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Prognóstico , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase em Tempo Real , Fatores de Transcrição da Família Snail/genética , Fatores de Transcrição da Família Snail/metabolismo , Taxa de Sobrevida , Proteína 1 Relacionada a Twist/genética , Proteína 1 Relacionada a Twist/metabolismo , Regulação para Cima , Vimentina/genética , Vimentina/metabolismoRESUMO
This study attempted to research the molecular mechanism underlying the inhibitory role of miR-1225-5p in the malignant progression of glioblastoma. Bioinformatics analyses based on the gene expression omnibus (GEO) and Chinese glioma genome atlas (CGGA) databases showed that miR-1225-5p, as a favorable prognostic factor, was expressed at low levels in glioblastoma, and its expression was also related to WHO grade and age. The subsequent CCK-8 assay indicated that miR-1225-5p might prevent the malignant progression of glioblastoma, which was represented by that miR-1225-5p mimic reduced the viability of glioblastoma cells. Then, we predicted that FNDC3B might be a potential target gene of miR-1225-5p, and it was negatively correlated with the level of miR-1225-5p, which were confirmed by dual-luciferase reporter assay, qRT-PCR and western blot assays. Moreover, based on the analyses of the cancer genome atlas (TCGA), Oncomine and CGGA databases, FNDC3B was enriched in glioblastoma and high expression of FNDC3B led to poor prognosis. Finally, CCK8 and transwell experiments showed that the ability of miR-1225-5p to inhibit glioblastoma cell viability, invasion and migration was at least partially achieved by targeting FNDC3B. In general, these results revealed that the miR-1225-5p/FNDC3B axis contributes to inhibiting the malignant phenotype of glioblastoma cells, which lays a foundation for molecular diagnosis and treatment of glioblastoma.
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Microstructures of fullerene derivatives formed via self-assembly strategy facilitate the versatile applications of these zero-dimensional molecules. However, the accurate elucidation of formation mechanism of fullerene microstructures is a challenge issue. A novel fullerene derivative 2 with rigid pyridine substituent was synthesized and characterized by X-ray crystallography. Using the strategy of liquid-liquid interfacial precipitation, self-assembly of 2 affords a micrometer-sized flowerlike and a discoid morphology. Based on the crystal packing of 2, the proper formation mechanism of different morphologies was proposed. Meanwhile, the photoelectrochemical properties of different morphologies of 2 was also unveiled.
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Atherosclerosis is one of the most common type of cardiovascular disease and the prime cause of mortality in the aging population worldwide. However, the detail mechanisms and special biomarkers of atherosclerosis remain to be further investigated. Lately, long non-coding RNAs (lncRNAs) has attracted much more attention than other types of ncRNAs. In our work, we found and confirmed differently expressed lncRNAs and mRNAs in atherosclerosis by analyzing GSE28829. We performed the weighted gene co-expression network analysis (WGCNA) by analyzing GSE40231 to confirm highly correlated genes. Gene Ontology (GO) analysis were utilized to assess the potential functions of differential expressed lncRNAs in atherosclerosis. Co-expression networks were also constructed to confirm hub lncRNAs in atherosclerosis. A total of 5784 mRNAs and 654 lncRNAs were found to be dysregulated in the progression of atherosclerosis. A total of 15 lncRNA-mRNA co-expression modules were identified in this study based on WGCNA analysis. Moreover, a few lncRNAs, such as ZFAS1, LOC100506730, LOC100506691, DOCK9-AS2, RP11-6I2.3, LOC100130219, were confirmed as important lncRNAs in atherosclerosis. Taken together, bioinformatics analysis revealed these lncRNAs were involved in regulating the leukotriene biosynthetic process, gene expression, actin filament organization, t-circle formation, antigen processing, and presentation, interferon-gamma-mediated signaling pathway, and activation of GTPase activity. We believed that this study would provide potential novel therapeutic and prognostic targets for atherosclerosis.
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Delayed administration of kallikrein after cerebral infarction can improve neurological function. However, the appropriate kallkrein treatment time after ischemic stroke has not been illuminated. In this study, we compared the long-term outcome among three kallikrein therapeutic regimens starting at different time points following mouse cerebral ischemia. Furthermore, the protective mechanisms involving neurogenesis, angiogenesis, and AKT-GSK3ß-VEGF signaling pathway were analyzed. Human tissue kallikrein was injected through the tail vein daily starting at 8 h, 24 h, or 36 h after right middle cerebral artery occlusion (MCAO) until the 28th day. Three therapeutic regimens all protected against neurological dysfunction, but kallikrein treatment starting at 8 h after MCAO had the best efficacy. Additionally, kallikrein treatment at 8 h after MCAO significantly enhanced cell proliferation including neural stem cell and induced differentiation of neural stem cell into mature neuron. Kallikrein treatment starting at 8 h also promoted more angiogenesis than other two treatment regimens, which was associated with AKT-GSK3ß-VEGF signaling pathway. Thus, we confirm that three delayed kallikrein treatments provide protection against cerebral infarction and furthermore suggest that kallikrein treatment starting at 8 h had a better effect than that at 24 h and 36 h. These findings provide the experimental data contributing to better clinical application of exogenous kallikrein.
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Preparation of efficient and reusable adsorption materials for water treatment and purification is still remarkably challenging. In this paper, three dimensional porous boron nitride nanosheets (3D porous BNNSs) with high chemical stability and excellent adsorption capacity for organic dyes have been successfully synthesized through a template-free route. The 3D porous BNNSs consist of uniform nanosheets with average diameter of about 200 nm and thickness of about 3 nm. The adsorption conditions have been optimized by varying the experimental parameters such as initial dye concentration, solution pH, contact time, etc. As expected, the 3D porous BNNSs exhibit superior adsorption activity toward methylene blue (MB) in aqueous solution: more than 95.3% of the dye can be removed within 5 min compared with the adsorption efficiency of 10% for conventional activated carbon and 67.5% for the 3D porous BNNSs reported previously at pH 8.0 and 30 °C. The unique 3D structure and high density adsorption sites are believed to play a key role in the efficient removal performance. Moreover, about 94.5% of the starting adsorption capacity is maintained after ten adsorption-regeneration cycles. With the high adsorption efficiency and reusability performance, the 3D porous BNNSs are suitable for water cleaning and meet the requirement of mass production.