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The unexpected discovery of hot Jupiters challenged the classical theory of planet formation inspired by our solar system. Until now, the origin and evolution of hot Jupiters are still uncertain. Determining their age distribution and temporal evolution can provide more clues into the mechanism of their formation and subsequent evolution. Using a sample of 383 giant planets around Sun-like stars collected from the kinematic catalogs of the Planets Across Space and Time project, we find that hot Jupiters are preferentially hosted by relatively younger stars in the Galactic thin disk. We subsequently find that the frequency of hot Jupiters declines with age as [Formula: see text]. In contrast, the frequency of warm/cold Jupiters shows no significant dependence on age. Such a trend is expected from the tidal evolution of hot Jupiters' orbits, and our result offers supporting evidence using a large sample. We also perform a joint analysis on the planet frequencies in the stellar age-metallicity plane. The result suggests that the frequencies of hot Jupiters and warm/cold Jupiters, after removing the age dependence are both correlated with stellar metallicities as [Formula: see text] and [Formula: see text], respectively. Moreover, we show that the above correlations can explain the bulk of the discrepancy in hot Jupiter frequencies inferred from the transit and radial velocity (RV) surveys, given that RV targets tend to be more metal-rich and younger than transits.
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As an essential macronutrient, phosphorus (P) is often a limiting nutrient because of its low availability and mobility in soils. Drought is a major environmental stress that reduces crop yield. How plants balance and combine P-starvation responses (PSRs) and drought resistance is unclear. In this study, we identified the transcription factor ZmPHR1 as a major regulator of PSRs that modulates phosphate (Pi) signaling and homeostasis. We found that maize zmphr1 mutants had reduced P concentration and were sensitive to Pi starvation, whereas ZmPHR1-OE lines displayed elevated Pi concentration and yields. In addition, 57% of PSR genes and nearly 70% of ZmPHR1-regulated PSR genes in leaves were transcriptionally responsive to drought. Under moderate and early drought conditions, the Pi concentration of maize decreased, and PSR genes were up-regulated before drought-responsive genes. The ZmPHR1-OE lines exhibited drought-resistant phenotypes and reduced stomatal apertures, whereas the opposite was true of the zmphr1 mutants. ZmPT7-OE lines and zmspx3 mutants, which had elevated Pi concentration, also exhibited drought resistance, but zmpt7 mutants were sensitive to drought. Our results suggest that ZmPHR1 plays a central role in integrating Pi and drought signals and that Pi homeostasis improves the ability of maize to combat drought.
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OBJECTIVES: To investigate the role of circRNA regulators MBNL1 and QKI in the progression of esophageal squamous cell carcinoma. BACKGROUND: MBNL1 and QKI are pivotal regulators of pre-mRNA alternative splicing, crucial for controlling circRNA production - an emerging biomarker and functional regulator of tumor progression. Despite their recognized roles, their involvement in ESCC progression remains unexplored. METHODS: The expression levels of MBNL1 and QKI were examined in 28 tissue pairs from ESCC and adjacent normal tissues using data from the GEO database. Additionally, a total of 151 ESCC tissue samples, from stage T1 to T4, consisting of 13, 43, 87, and 8 cases per stage, respectively, were utilized for immunohistochemical (IHC) analysis. RNA sequencing was utilized to examine the expression profiles of circRNAs, lncRNAs, and mRNAs across 3 normal tissues, 3 ESCC tissues, and 3 pairs of KYSE150 cells in both wildtype (WT) and those with MBNL1 or QKI knockouts. Transwell, colony formation, and subcutaneous tumorigenesis assays assessed the impact of MBNL1 or QKI knockout on ESCC cell migration, invasion, and proliferation. RESULTS: ESCC onset significantly altered MBNL1 and QKI expression levels, influencing diverse RNA species. Elevated MBNL1 or QKI expression correlated with patient age or tumor invasion depth, respectively. MBNL1 or QKI knockout markedly enhanced cancer cell migration, invasion, proliferation, and tumor growth. Moreover, the absence of either MBNL1 or QKI modulated the expression profiles of multiple circRNAs, causing extensive downstream alterations in the expression of numerous lncRNAs and mRNAs. While the functions of circRNA and lncRNA among the top 20 differentially expressed genes remain unclear, mRNAs like SLCO4C1, TMPRSS15, and MAGEB2 have reported associations with tumor progression. CONCLUSIONS: This study underscores the tumor-suppressive roles of MBNL1 and QKI in ESCC, proposing them as potential biomarkers and therapeutic targets for ESCC diagnosis and treatment.
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Progresión de la Enfermedad , Neoplasias Esofágicas , Carcinoma de Células Escamosas de Esófago , ARN Circular , Proteínas de Unión al ARN , Humanos , Proteínas de Unión al ARN/genética , Proteínas de Unión al ARN/metabolismo , Carcinoma de Células Escamosas de Esófago/genética , Carcinoma de Células Escamosas de Esófago/patología , Carcinoma de Células Escamosas de Esófago/metabolismo , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/patología , Neoplasias Esofágicas/metabolismo , ARN Circular/genética , Regulación Neoplásica de la Expresión Génica , Masculino , Proliferación Celular/genética , Línea Celular Tumoral , Femenino , Ratones , Animales , Movimiento Celular/genética , Persona de Mediana Edad , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismoRESUMEN
Phosphorus and nitrogen are essential macronutrients for plant growth and crop production. During phosphate (Pi) starvation, plants enhanced Pi but reduced nitrate (NO3 -) uptake capacity, and the mechanism is unclear. Here, we show that a GARP-type transcription factor NITRATE-INDUCIBLE, GARP-TYPE TRANSCRIPTIOANL REPRESSOR1.2 (NIGT1.2) coordinately modulates Pi and NO3 - uptake in response to Pi starvation. Overexpression of NIGT1.2 increased Pi uptake capacity but decreased NO3 - uptake capacity in Arabidopsis (Arabidopsis thaliana). Furthermore, the nigt1.1 nigt1.2 double mutant displayed reduced Pi uptake but enhanced NO3 - uptake under low-Pi stress. During Pi starvation, NIGT1.2 directly up-regulated the transcription of the Pi transporter genes PHOSPHATE TRANSPORTER1;1 (PHT1;1) and PHOSPHATE TRANSPORTER1;4 (PHT1;4) and down-regulated expression of NO3 - transporter gene NITRATE TRANSPORTER1.1 (NRT1.1) by binding to cis-elements in their promoters. Further genetic assays demonstrated that PHT1;1, PHT1;4, and NRT1.1 were genetically epistatic to NIGT1.2 We also identified similar regulatory pathway in maize (Zea mays). These data demonstrate that the transcription factor NIGT1.2 plays a central role in modulating low-Pi-dependent uptake of Pi and NO3 -, tending toward maintenance of the phosphorus to nitrogen balance in plants during Pi starvation.
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Arabidopsis/metabolismo , Nitratos/metabolismo , Fosfatos/metabolismo , Factores de Transcripción/metabolismo , Zea mays/metabolismo , Proteínas de Transporte de Anión/genética , Proteínas de Transporte de Anión/metabolismo , Arabidopsis/genética , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Epistasis Genética , Regulación de la Expresión Génica de las Plantas , Transportadores de Nitrato , Proteínas de Transporte de Fosfato/genética , Proteínas de Transporte de Fosfato/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Plantas Modificadas Genéticamente , Regiones Promotoras Genéticas , Nicotiana/genética , Factores de Transcripción/genética , Zea mays/genéticaRESUMEN
Designing highly excellent and stable catalysts for alkaline oxygen evolution reaction (OER) is gradually pivotal for clean energy development. In this work, a heterogeneous Fe-doped Ni(OH)2 (Ni/Fe-0.1) was developed via simple one-step electrodeposition onto nickel mesh. The heterogeneous interface structure generates sufficient active sites, significantly improving OER performance with an overpotential of 174â mV at 10â mA cm-2 (η10 ), while Tafel slope is only 43.0â mV dec-1 . In particular, Ni/Fe-0.1 is still able to operate stably at a current density of 1â A cm-2 for 100â h without obvious potential decay. The oxidation of Ni2+ to Ni3+ was detected by X-ray photoelectron spectroscopy, proving that the heterogeneous catalyst could stabilize the high-valence state of nickel as active sites to its superior OER performance. This work provides a convenient synthetic strategy for forming heterogeneous catalysts toward efficient water electrolysis.
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Heat stress (HS) induced by high ambient temperatures compromises intestinal epithelial cell. However, the underlying mechanisms by which HS causes intestinal barrier dysfunction remain unclear. In this study, we established an in vitro acute-HS-induced intestinal damage using porcine small intestinal epithelial cell (IPEC-J2) that exposed to the high temperatures (43°C) for 2 h. The cell proliferation, apoptosis, tight junction (TJ) barrier integrity and transcriptomic profiles were measured. The results showed that HS decreased cell viability while increased proapoptotic signaling evidenced by Bax/bcl2 ratio, cytochrome C release to cytosol and active-caspase 3 increases (p < 0.01). HS led to decreased transepithelial electrical resistance, increased cell permeability, and downregulated TJ proteins including ZO1, occludin, and claudin 3 (p < 0.05). Transcriptome sequencing and KEGG pathway analysis revealed HS-induced cell cycle arrest and activation of endoplasmic reticulum stress (ERS) response mediated by a critical transcript eif2α and proapoptotic molecule DDIT3 (known as CHOP). Furthermore, inhibition of ERS by 4-phenylbutyrate (4-PBA) administration and knockdown of eif2α and CHOP significantly attenuated IPEC-J2 cells apoptosis (p < 0.05). Transmission electron microscopy analysis suggested that 4-PBA inhibited HS-induced increase in ER lumen diameter, indicating ultrastructural sign of ERS. In addition, HS-induced impairment of TJs was significantly attenuated by 4-PBA (p < 0.05). Collectively, HS induces ERS and activates the p-eif2α/CHOP signaling pathway to impair epithelial barrier integrity through triggering the intestinal epithelial cell apoptosis.
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Estrés del Retículo Endoplásmico , Factor 2 Eucariótico de Iniciación , Animales , Apoptosis , Respuesta al Choque Térmico , Porcinos , Proteínas de Uniones EstrechasRESUMEN
Water-alkaline electrolysis holds a great promise for industry-scale hydrogen production but is hindered by the lack of enabling hydrogen evolution reaction electrocatalysts to operate at ampere-level current densities under low overpotentials. Here, we report the use of hydrogen spillover-bridged water dissociation/hydrogen formation processes occurring at the synergistically hybridized Ni3S2/Cr2S3 sites to incapacitate the inhibition effect of high-current-density-induced high hydrogen coverage at the water dissociation site and concurrently promote Volmer/Tafel processes. The mechanistic insights critically important to enable ampere-level current density operation are depicted from the experimental and theoretical studies. The Volmer process is drastically boosted by the strong H2O adsorption at Cr5c sites of Cr2S3, the efficient H2O* dissociation via a heterolytic cleavage process (Cr5c-H2O* + S3c(#) â Cr5c-OH* + S3c-H#) on the Cr5c/S3c sites in Cr2S3, and the rapid desorption of OH* from Cr5c sites of Cr2S3 via a new water-assisted desorption mechanism (Cr5c-OH* + H2O(aq) â Cr5c-H2O* + OH-(aq)), while the efficient Tafel process is achieved through hydrogen spillover to rapidly transfer H# from the synergistically located H-rich site (Cr2S3) to the H-deficient site (Ni3S2) with excellent hydrogen formation activity. As a result, the hybridized Ni3S2/Cr2S3 electrocatalyst can readily achieve a current density of 3.5 A cm-2 under an overpotential of 251 ± 3 mV in 1.0 M KOH electrolyte. The concept exemplified in this work provides a useful means to address the shortfalls of ampere-level current-density-tolerant Hydrogen evolution reaction (HER) electrocatalysts.
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INTRODUCTION: Prostate biopsy (PB) is a typical daily practice method for the diagnosis of prostate cancer (PCa). This study aimed to compare the PCa detection rates and peri- and postoperative complications of PB among 3 residents and a consultant. PATIENTS AND METHODS: A total of 343 patients who underwent PB between August 2018 and July 2019 were involved in this study. Residents were systematically trained for 2 weeks by a consultant for performing systematic biopsy (SB) and targeted biopsy (TB). And then, 3 residents and the consultant performed PB independently every quarter due to routine rotation in daily practice. The peri- and postoperative data were collected from a prospectively maintained database (www.pc-follow.cn). The primary outcome and secondary outcome were to compare the PCa detection rates and complications between the residents and consultant, respectively. RESULTS: There was no significant difference between the residents and consultant in terms of overall PCa detection rates of SB and TB or further stratified by prostate-specific antigen value and prostate imaging reporting and data system (PI-RADS) scores. We found the consultant had more TB cores (175 cores vs. 86-114 cores, p = 0.043) and shorter procedural time (mean 16 min vs. 19.7-20.1 min, p < 0.001) versus the residents. The complication rate for the consultant was 6.7% and 5%-8.2% for the residents, respectively (p = 0.875). CONCLUSIONS: The residents could get similar PCa detection and complication rates compared with that of the consultant after a 2-week training. However, the residents still need more cases to shorten the time of the biopsy procedure.
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Próstata , Neoplasias de la Próstata , Consultores , Humanos , Biopsia Guiada por Imagen/métodos , Imagen por Resonancia Magnética/métodos , Masculino , Estudios Prospectivos , Próstata/patología , Neoplasias de la Próstata/diagnóstico , Neoplasias de la Próstata/patología , Ultrasonografía Intervencional , UrólogosRESUMEN
Oleanolic acid has previously been shown to possess PI3K inhibitory activity, thus, the purpose of this work was to generate a series of derivatives that improve the potency. Twenty rationally designed oleanolic acid derivatives were synthesized and tested the cytotoxicity and PI3K inhibitory activity. The results suggested that attachment of additional structural elements such as association of thiazole group to A ring and insertion of phenylurea group was important for increasing activities. The most active derivative was compound II2, which exhibited PI3K inhibitory activity (IC50 = 58.42 nmol/l) and improved interaction with activity site of PI3K according with docking studies.
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For our interest in the potential biologically active and structurally unique steroidal glycosides, continued phytochemical investigation of Cynanchum taihangense was carried out; twelve new seco-pregnane glycosides, cynataihosides I-L (1-4), M-T (7-14), and two known glycosides, glaucoside A (5) and atratcynoside F (6), were isolated from the 95% ethanol extract of Cynanchum taihangense. Two new aglycones were found among compounds 10, 11, 13, and 14. The structures of the glycosides were elucidated based on 1D and 2D NMR spectroscopic data, HR-ESI-MS analysis, and chemical evidence. The cytotoxicity of compounds against three human tumor cell lines (HL-60, THP-1, and PC-3) were evaluated by MTT assay. Compound 11 displayed significant cytotoxicity against THP-1 and PC-3 cell line with IC50 values of 5.08 and 22.75 µm, respectively. Compounds 3 and 14 exhibited moderate and selective cytotoxicity on HL-60 and THP-1 with IC50 values of 17.78 and 16.02 µm, respectively.
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Cynanchum , Cynanchum/química , Glicósidos/química , Humanos , Estructura Molecular , Raíces de Plantas/química , Pregnanos/química , Pregnanos/farmacologíaRESUMEN
This study analyzed the outcome indicators in randomized controlled trial(RCT) on Chinese medicine as adjuvant therapy for severe pneumonia in the past years, laying a foundation for the design of clinical trials on and construction of core outcome set(COS) for severe pneumonia. To be specific, related RCT was retrieved from CNKI, Wanfang, VIP, SinoMed, PubMed, EMbase, Cochrane Library, Web of Science, Chinese Clinical Trial Registry, and ClinicalTrials.gov(from January 1,2011 to April 9,2022). Then data in the trials were extracted, and the quality of included RCT was assessed according to Cochrane handbook, followed by descriptive analysis of the use of outcome indicators. A total of 11 833 articles were screened out, and finally 34 RCTs were included(2 were protocols). The included trials involved 109 outcome indicators with emergence frequency of 320, which were mainly classified into 9 categories: physicochemical indicators(54, frequency 167), time to achieve the efficacy(15, frequency 38), clinical effective rate(10, frequency 36), quality of life(11, frequency 35), symptoms and signs(7, frequency 18), traditional Chinese medicine(TCM) syndrome(4, frequency 13), safety(3, frequency 8), economic evaluation(1, frequency 1), other indicators(4, frequency 4). The indicators with high frequency followed the order: total effective rate, arterial oxygen partial pressure, C-reactive protein, white blood cell count, arterial blood carbon dioxide partial pressure. A total of 5 articles(14.71%) reported the main outcome indicators and 11 articles(32.35%) adopted the efficacy on TCM syndromes as the outcome indicator. There are many problems in the selection of outcome indicators in RCT on the treatment of severe pneumonia with Chinese medicine, mainly manifested as the disregard of clinical endpoint indicators, the inappropriate selection of surrogate indicators, and the non-standard evaluation criteria for the efficacy on TCM syndrome. It is suggested that the evaluation system for the efficacy of Chinese medicine on severe pneumonia should be established in accordance with the method for international COS to improve the quality of clinical trials.
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Medicamentos Herbarios Chinos , Neumonía , Humanos , Medicina Tradicional China , Medicamentos Herbarios Chinos/uso terapéutico , Calidad de Vida , Terapia Combinada , Neumonía/tratamiento farmacológicoRESUMEN
Network Meta-analysis was conducted to compare the efficacy and safety of different Chinese medicine injections combined with conventional therapy in the treatment of stroke-associated pneumonia. CNKI, Wanfang, VIP, PubMed, Web of Science, and Cochrane Library were searched for the relevant literature pubslished from inception to April 1, 2022. Stata 17 was used for data analysis. After screening of 1 189 papers, 72 studies were finally selected, which involved 5 819 patients and 6 Chinese medicine injections(Tanreqing Injection, Xingnaojing Injection, Xuebijing Injection, Xiyanping Injection, Shenfu Injection, and Shenmai Injection). The network Meta-analysis ranked the injections as follows.(1) In terms of improving the total clinical effective rate, the surface under the cumulative ranking curve(SUCRA) followed the order of Xiyanping Injection + conventional therapy > Xuebijing Injection + conventional therapy > Tanreqing Injection + conventional therapy > Shenmai Injection + conventional therapy > Xingnaojing Injection + conventional therapy > Shenfu Injection + conventional therapy > conventional therapy.(2) In terms of recovering the National Institute of Health stroke scale(NIHSS) scores, the SUCRA followed the order of Xuebijing Injection + conventional therapy > Xingnaojing Injection + conventional therapy > Tanreqing Injection + conventional therapy > Shenfu Injection + conventional therapy > conventional therapy.(3) In reducing the average time to abatement of fever, the SUCRA followed the order of Xiyanping Injection + conventional therapy > Tanreqing Injection + conventional therapy > Xuebijing Injection + conventional therapy > conventional therapy.(4) In terms of reducing the mean hospital stay, the SUCRA followed the order of Xiyanping Injection + conventional therapy > Xubijing Injection + conventional therapy > Tanreqing Injection + conventional therapy > Shenmai Injection + conventional therapy > conventional therapy. The clinical efficacy of Tanreqing Injection, Xuebijing Injection, Xiyanping Injection, Xingnaojing Injection, Shenmai Injection, or Shenfu Injection combined with conventional therapy was superior to that of conventional therapy alone. However, due to the limitations of the quality and methodology of different intervention measures, this conclusion needs to be verified by more high-quality and rigorously designed randomized controlled trial.
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Medicamentos Herbarios Chinos , Neumonía , Accidente Cerebrovascular , Humanos , Medicina Tradicional China , Metaanálisis en Red , Medicamentos Herbarios Chinos/uso terapéutico , Neumonía/tratamiento farmacológico , Inyecciones , Accidente Cerebrovascular/complicaciones , Accidente Cerebrovascular/tratamiento farmacológicoRESUMEN
Copper-based materials are efficient electrocatalysts for the conversion of CO2 to C2+ products, and most these materials are reconstructed in situ to regenerate active species. It is a challenge to precisely design precatalysts to obtain active sites for the CO2 reduction reaction (CO2 RR). Herein, we develop a strategy based on local sulfur doping of a Cu-based metal-organic framework precatalyst, in which the stable Cu-S motif is dispersed in the framework of HKUST-1 (S-HKUST-1). The precatalyst exhibits a high ethylene selectivity in an H-type cell with a maximum faradaic efficiency (FE) of 60.0 %, and delivers a current density of 400â mA cm-2 with an ethylene FE up to 57.2 % in a flow cell. Operando X-ray absorption results demonstrate that Cuδ+ species stabilized by the Cu-S motif exist in S-HKUST-1 during CO2 RR. Density functional theory calculations indicate the partially oxidized Cuδ+ at the Cu/Cux Sy interface is favorable for coupling of the *CO intermediate due to the modest distance between coupling sites and optimized adsorption energy.
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Electrochemical CO2 -to-CO conversion provides a possible way to address problems associated with the greenhouse effect; however, developing low-cost electrocatalysts to mediate high-efficiency CO2 reduction remains a challenge on account of the limited understanding of the nature of the real active sites. Herein, we reveal the Znδ+ metalloid sites as the real active sites of stable nonstoichiometric ZnOx structure derived from Zn2 P2 O7 through operando X-ray absorption fine structure analysis in conjunction with evolutionary-algorithm-based global optimization. Furthermore, theoretical and experimental results demonstrated that Znδ+ metalloid active sites could facilitate the activation of CO2 and the hydrogenation of *CO2 , thus accelerating the CO2 -to-CO conversion. Our work establishes a critical fundamental understanding of the origin of the real active center in the zinc-based electrocatalysts for CO2 reduction reaction.
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Detailed information about the influences of the cooperative motion of water and methanol molecules on practical solid-liquid heterogeneous photocatalysis reactions is critical for our understanding of photocatalytic reactions. The present work addresses this issue by applying operando nuclear magnetic resonance (NMR) spectroscopy, in conjunction with density functional theory (DFT) calculations and ab initio molecular dynamics (AIMD) simulations, to investigate the dynamic behaviors of heterogeneous photocatalytic systems with different molar ratios of water to methanol on rutile-TiO2 photocatalyst. The results demonstrate that methanol and water molecules are involved in the cooperative motions, and the cooperation often takes the form of methanol-water clusters that govern the number of methanol molecules reaching to the active sites of the photocatalyst per unit time, as confirmed by the diffusion coefficients of the methanol molecule calculated in the binary methanol-water solutions. Nuclear Overhauser effect spectroscopy experiments reveal that the clusters are formed by the hydrogen bonding between the -OH groups of CH3OH and H2O. The formation of such methanol-water clusters is likely from an energetic standpoint in low-concentration methanol, which eventually determines the yields of methanol reforming products.
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The potential distribution at the electrode interface is a core factor in electrochemistry, and it is usually treated by the classic Gouy-Chapman-Stern (G-C-S) model. Yet the G-C-S model is not applicable to nanosized particles collision electrochemistry as it describes steady-state electrode potential distribution. Additionally, the effect of single nanoparticles (NPs) on potential should not be neglected because the size of a NP is comparable to that of an electrode. Herein, a theoretical model termed as Metal-Solution-Metal Nanoparticle (M-S-MNP) is proposed to reveal the dynamic electrode potential distribution at the single-nanoparticle level. An explicit equation is provided to describe the size/distance-dependent potential distribution in single NPs stochastic collision electrochemistry, showing the potential distribution is influenced by the NPs. Agreement between experiments and simulations indicates the potential roles of the M-S-MNP model in understanding the charge transfer process at the nanoscale.
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Photocatalytic water splitting provides an economically feasible way for converting solar energy into hydrogen. Great efforts have been devoted to developing efficient photocatalysts; however, the surface catalytic reactions, especially for the sluggish oxygen evolution reaction (OER), still remain a challenge, which limits the overall photocatalytic energy efficiency. Herein, we design a Rhn cluster cocatalyst, with Rh0 -Rh3+ sites anchoring the Mo-doped BiVO4 model photocatalytic system. The resultant photocatalyst enables a high visible-light photocatalytic oxygen production activity of 7.11â mmol g-1 h-1 and an apparent quantum efficiency of 29.37 % at 420â nm. The turnover frequency (TOF) achieves 416.73â h-1 , which is 378 times higher than that of the photocatalyst only with Rh3+ species. Operando X-ray absorption characterization shows the OER process on the Rh0 -Rh3+ sites. The DFT calculations further illustrate a bifunctional OER mechanism over the Rh0 -Rh3+ sites, in which the oxygen intermediate attacks the Rh3+ sites with assistance of a hydrogen atom transfer to the Rh0 sites, thus breaking the scaling relationship of various oxygen intermediates.
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Breast cancer is a malignant tumor with the highest incidence in women of the world. CXCR4 and Skp2 are highly expressed in breast cancer cells and CXCR4 was positively correlated with Skp2 by interference or overexpression. The microRNA array was used to detect the differentially expressed spectrum of micro RNAs in breast cancer cells the changes of miR-7-5p after CXCR4 inhibitor (NT21MP) treatment to block the CXCR4/SDF-1 pathway was founded. MiR-7-5p has been found to be correlated with Skp2 in various tumors in the literature, and Skp2 expression can be regulated by transfection with miR-7-5p mimics or inhibitors. The expression level of miR-7-5p was upregulated or downregulated after CXCR4 interference or overexpression. Combined with the correlation between CXCR4 and miR-7-5p in the chip results, CXCR4 may regulate Skp2 through miR-7-5p. Epithelial cells have the morphological characteristics of mesenchymal cells for some reason called epithelial-mesenchymal transformation (EMT). Transfection of miR-7-5p mimics into drug-resistant cells reduced Skp2 levels, decreased the expression of Vimentin, Snail, and slug, and increased the expression of E-cadherin. CXCR4 inhibitor (NT21MP) can reverse the EMT changes caused by miR-7-5p inhibitor. Similarly, in vivo results suggesting that CXCR4 inhibitors can reverse the EMT phenotype of drug-resistant breast cancer cells through the CXCR4/miR-7-5p/Skp2 pathway. In summary, the CXCR4/miR-7-5p/Skp2 signaling pathway plays an important role in the progression of breast cancer. This study provides a theoretical basis for the treatment of breast cancer by targeting the CXCR4 pathway.
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Transición Epitelial-Mesenquimal/genética , MicroARNs/genética , Receptores CXCR4/antagonistas & inhibidores , Transducción de Señal/efectos de los fármacos , Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Quimiocinas , Regulación hacia Abajo/efectos de los fármacos , Femenino , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Receptores CXCR4/metabolismoRESUMEN
Acute pancreatitis (AP) is known worldwide as one of the most common gastrointestinal diseases, prospectively leading to hospitalization coupled with increasing incidence. Several microRNAs (miRNAs) have been reported to be potential biomarkers for pancreatitis. In this study, we verified the hypothesis that miR-92a-3p is implicated in the development of AP by controlling the proliferation and apoptosis of pancreatic acinar cells (PACs) through the modulation of the Kruppel-like factor 2 (KLF2) and inflammatory factors in rats. Initially, we established a rat model of AP and extracted the pancreatic tissues. Then, the positive rate of KLF2 was measured using immunohistochemistry, and the expression of the related genes was determined by rReverse transcription quantitative polymerase chain reaction and Western blot analysis. The cell proliferation and apoptosis were measured by 5-ethynyl-2'-deoxyuridine assay and flow cytometry, and the contents of inflammatory factors were measured using enzyme-linked immunosorbent assay. AP rats presented with increased miR-92a-3p expression as well as decreased KLF2 expression in PACs. The downregulation of miR-92a-3p and overexpression of KLF2 led to decline in expression of nuclear factor-κB (NF-κB), survivin, tumor necrosis factor-α, and Bax as well as extent of NF-κB phosphorylation, contents of inflammatory factors, and apoptosis rate of PACs, but to increased KLF2 and B-cell lymphoma-2 levels and proliferation rate of PACs. Collectively, the data obtained from the present study demonstrated that reduced miR-92a-3p expression may relieve AP through its suppressive effects on cell apoptosis, inflammatory factors, and facilitatory effects on cell proliferation by enhancing KLF2 expression.
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Phosphorus, an essential mineral macronutrient, is a major constituent of fertilizers for maize (Zea mays L.) production. However, the molecular mechanisms of phosphate (Pi) acquisition in maize plants and its redistribution remain unclear. This study presents the functional characterization of ZmPT7 in Pi uptake and redistribution in maize. The ZmPT7 was expressed in roots and leaves, and induced during Pi starvation. The ZmPT7 complemented the Pi-uptake deficiency of yeast mutant phoΔnull and Arabidopsis mutant pht1;1Δ4Δ, indicating that ZmPT7 functioned as a Pi transporter. We generated zmpt7 mutants by CRISPR/Cas9 and ZmPT7-overexpressing lines. The zmpt7 mutants showed reduced, whereas the ZmPT7-overexpressing lines displayed increased Pi-uptake capacity and Pi redistribution from old to young leaves, demonstrating that ZmPT7 played central roles in Pi acquisition and Pi redistribution from old to young leaves. The ZmCK2 kinases phosphorylated ZmPT7 at Ser-521 in old maize leaves, which enhanced transport activity of ZmPT7. The Ser-520 of Arabidopsis AtPHT1;1, a conserved residue of ZmPT7 Ser-521, was also phosphorylated by AtCK2 kinase, and the mutation of Ser-520 to Glu (phosphorylation mimic) yielded enhanced transport activity of AtPHT1;1. Taken together, these results indicate that ZmPT7 plays important roles in Pi acquisition and redistribution, and its transport activity is modulated by phosphorylation.