The ability of copper to catalyze the electrochemical reduction of CO2 has been shown to greatly depend on its nanoscale surface morphology. While previous studies found evidence of irreversible ...changes of copper nanoparticle and thin film electrodes following electrolysis, we present here the first observation of the reversible reconstruction of electrocatalytic copper surfaces induced by the adsorbed CO intermediate. Using attenuated total internal reflection infrared and surface-enhanced Raman spectroscopies, the reversible formation of nanoscale metal clusters on the electrode is revealed by the appearance of a new CO absorption band characteristic of CO bound to undercoordinated copper atoms and by the strong enhancement of the surface-enhanced Raman effect. Our study shows that the morphology of the catalytic copper surface is not static but dynamically adapts with changing reaction conditions.
Although trastuzumab provides significant clinical benefit for HER2-positive breast cancers, responses are limited by the emergence of resistance. Recent evidence suggests that long noncoding RNAs ...(lncRNAs) play important roles in tumorigenesis and chemoresistance. However, the regulatory mechanism of lncRNAs in trastuzumab resistance is not well established to date. In this research, we identified the differentially expressed lncRNA and investigated its regulatory role in trastuzumab resistance of breast cancer.
LncRNA microarray and qRT-PCR were performed to identify the dysregulated lncRNAs. Transmission electron microscopy, differential ultracentrifugation and qRT-PCR were used to verify the existence of exosomal AFAP1-AS1 (actin filament associated protein 1 antisense RNA 1). Bioinformatics prediction, RNA fluorescence in situ hybridization (RNA-FISH) and immunoprecipitation assays were performed to identify the direct interactions between AFAP1-AS1 and other associated targets, such as AU-binding factor 1 (AUF1) and ERBB2. Finally, a series gain- or loss-functional assays were done to prove the precise role of AFAP1-AS1 in trastuzumab resistance.
AFAP1-AS1 was screened out due to its higher expression in trastuzumab-resistant cells compared to sensitive cells. Increased expression of AFAP1-AS1was associate with poorer response and shorter survival time of breast cancer patients. AFAP1-AS1 was upregulated by H3K27ac modification at promoter region, and knockdown of AFAP1-AS1 reversed trastuzumab resistance. Moreover, extracellular AFAP1-AS1 secreted from trastuzumab resistant cells was packaged into exosomes and then disseminated trastuzumab resistance of receipt cells. Mechanically, AFAP1-AS1 was associated with AUF1 protein, which further promoted the translation of ERBB2 without influencing the mRNA level.
Exosomal AFAP1-AS1 could induce trastuzumab resistance through associating with AUF1 and promoting ERBB2 translation. Therefore, AFAP1-AS1 level may be useful for prediction of trastuzumab resistance and breast cancer treatment.
To investigate molecular mechanisms underlying cell state changes, a crucial analysis is to identify differentially expressed (DE) genes along the pseudotime inferred from single-cell RNA-sequencing ...data. However, existing methods do not account for pseudotime inference uncertainty, and they have either ill-posed p-values or restrictive models. Here we propose PseudotimeDE, a DE gene identification method that adapts to various pseudotime inference methods, accounts for pseudotime inference uncertainty, and outputs well-calibrated p-values. Comprehensive simulations and real-data applications verify that PseudotimeDE outperforms existing methods in false discovery rate control and power.
•A novel coaxial helical gas atmosphere is firstly introduced to extend the stable length of water jet as well as expel the accumulated water layer during the machining of LWJ.•The influences of gas ...component and pressure on the stable length of water jet and accumulated water layer status on substrate surface are revealed.•Scribing and through cutting of CMCs substrates with thickness of 3 mm are realized by CGALWJ machining without the drawing of SiC fibers, formation of recast layer and delamination.
SiC/SiC ceramic matrix composites (CMCs) offer an excellent combination of properties at high temperature such as high specific strength, chemical inertness and irradiation tolerance. Those superior properties make CMCs beneficial for use in high-temperature structural applications that are exposed to extreme environments such as aerospace and nuclear energy. However, well machining qualities can hardly be achieved by conventional machining techniques owing to these properties. Laser water jet (LWJ) machining is a promising solution, which is capable of ablating materials with less/no heat defects, well machining precision and consistency. Nevertheless, the machining capacity of LWJ is still limited by the stability of water jet to a great extent. A water layer may form on substrate surface during the impingement of LWJ, which also sets up obstacle for sufficient ablation. Therefore, a novel coaxial helical gas atmosphere is introduced to promote the machining capacity of LWJ in this paper. A theoretical model is established to describe the gas-water two-phase flow field during the ejection and impingement of coaxial gas assisted LWJ (CGALWJ). The influences of gas component and pressure on the stable length of water jet and surface water layer status are analyzed based on numerical simulations and experiments. Scribing experiments are further carried out on CMCs substrates with thickness of 3 mm. Groove with maximum depth-to-width ratio of 13.6 as well as through cutting are realized without the drawing of SiC fibers, formation of recast layer and delamination. The theoretical and experimental results provide solid foundation for the high-quality machining of ceramic matrix composites and other hard-to-process materials.
Rosai-Dorfman disease is a histiocytic disorder with a poorly defined pathogenesis. Recent molecular studies have revealed recurrent mutations involving genes in the MAPK/ERK pathway in Langerhans ...cell histiocytosis and Erdheim-Chester disease. However, cases of Rosai-Dorfman disease have rarely been assessed. We performed next-generation sequencing to assess 134 genes on 21 cases of Rosai-Dorfman disease, including 13 women and 8 men with a median age of 43 years (range, 3-82). In all, 13 had extranodal, 5 had nodal, and 3 had coexistent nodal and extranodal disease. The head and neck region was the most common area involved (n=7). Mutation analysis detected point mutations in 7 (33%) cases, including KRAS (n=4) and MAP2K1 (n=3). No mutations were identified in ARAF, BRAF, PIK3CA, or any other genes assessed. Immunohistochemistry demonstrated p-ERK overexpression in 3 cases, all harboring MAP2K1 mutations. Patients carrying mutated genes were younger (median age, 10 vs 53 years, P=0.0347) with more pediatric patients (4/7 vs 1/14, P=0.0251). The presence of mutations correlated with location being more common in the head and neck region; 6/7 (86%) mutated vs 1/14 (7%) unmutated cases (P=0.0009). All 5 (100%) mutated cases with available staging information had a multifocal presentation, whereas only 3/11 (27%) unmutated patients had multifocal disease (P=0.0256). Treatment information was available in 10 patients, including radical resection (n=4), resection and radiation (n=3), and cladribine-based chemotherapy (n=3). With a median follow-up of 84 months (range, 7-352), 7 remained in clinical remission and 3 had persistent disease. No correlation between mutation status and clinical outcome was noted. In summary, we detected mutually exclusive KRAS and MAP2K1 mutations in one-third of cases of Rosai-Dorfman disease suggesting this subgroup are clonal and involve activation of MAPK/ERK pathway. Our data contribute to the understanding of the biology of Rosai-Dorfman disease and point to potential diagnostic and therapeutic targets.
Text summarization is an information compression technology to extract important information from long text, which has become a challenging research direction in the field of natural language ...processing. At present, the text summary model based on deep learning has shown good results, but how to more effectively model the relationship between words, more accurately extract feature information and eliminate redundant information is still a problem of concern. This paper proposes a graph neural network model GA-GNN based on gated attention, which effectively improves the accuracy and readability of text summarization. First, the words are encoded using a concatenated sentence encoder to generate a deeper vector containing local and global semantic information. Secondly, the ability to extract key information features is improved by using gated attention units to eliminate local irrelevant information. Finally, the loss function is optimized from the three aspects of contrastive learning, confidence calculation of important sentences, and graph feature extraction to improve the robustness of the model. Experimental validation was conducted on a CNN/Daily Mail dataset and MR dataset, and the results showed that the model in this paper outperformed existing methods.
Researchers view vast zeros in single-cell RNA-seq data differently: some regard zeros as biological signals representing no or low gene expression, while others regard zeros as missing data to be ...corrected. To help address the controversy, here we discuss the sources of biological and non-biological zeros; introduce five mechanisms of adding non-biological zeros in computational benchmarking; evaluate the impacts of non-biological zeros on data analysis; benchmark three input data types: observed counts, imputed counts, and binarized counts; discuss the open questions regarding non-biological zeros; and advocate the importance of transparent analysis.
The high-speed growth of China's large-scale new economy indicates that innovation has become the most important economic growth pole. The study aims to explore the structure of the path to ...innovation, in which we focus on the mediating effect of organizational character.
Considering the indigenous context of China's new economy, the study divides innovation into two types: technological innovation and business model innovation. Then, we build a path model to achieve the innovation by taking intellectual capital and organizational character as antecedents. Finally, a structural equation model is built to measure the path on the basis of sample data collected via a questionnaire survey.
The results indicate that intellectual capital has a significant positive direct effect on technological innovation, but its direct effect on business model innovation is not significant. Organizational character not only mediates the relationship between the intellectual capital and technological innovation, but also plays a mediating role in the effect path from the intellectual capital to business model innovation. In addition, technological innovation has a positive impact on the business model innovation, and mediates the relationship between the intellectual capital and business model innovation.
The study takes intellectual capital and organizational character as the common antecedents of innovation and breaks down the content of innovation research into technological innovation and business model innovation. Thus, it establishes a new theoretical analysis framework for dual innovation research and enriches the related theories. The framework would have stronger explanatory power for revealing the innovation strategy and behavior carried out by a large number of corporate organizations in China and the boom of new economy. Furthermore, it would lead enterprises to organize innovation activities more effectively and improve their innovation performances.
Secondary organic aerosol (SOA) produced by atmospheric oxidation of primary emitted precursors is a major contributor to fine particulate matter (PM
) air pollution worldwide. Observations during ...winter haze pollution episodes in urban China show that most of this SOA originates from fossil-fuel combustion but the chemical mechanisms involved are unclear. Here we report field observations in a Beijing winter haze event that reveal fast aqueous-phase conversion of fossil-fuel primary organic aerosol (POA) to SOA at high relative humidity. Analyses of aerosol mass spectra and elemental ratios indicate that ring-breaking oxidation of POA aromatic species, leading to functionalization as carbonyls and carboxylic acids, may serve as the dominant mechanism for this SOA formation. A POA origin for SOA could explain why SOA has been decreasing over the 2013-2018 period in response to POA emission controls even as emissions of volatile organic compounds (VOCs) have remained flat.
Abstract
Severe events of wintertime particulate air pollution in Beijing (winter haze) are associated with high relative humidity (RH) and fast production of particulate sulfate from the oxidation ...of sulfur dioxide (SO
2
) emitted by coal combustion. There has been considerable debate regarding the mechanism for SO
2
oxidation. Here we show evidence from field observations of a haze event that rapid oxidation of SO
2
by nitrogen dioxide (NO
2
) and nitrous acid (HONO) takes place, the latter producing nitrous oxide (N
2
O). Sulfate shifts to larger particle sizes during the event, indicative of fog/cloud processing. Fog and cloud readily form under winter haze conditions, leading to high liquid water contents with high pH (>5.5) from elevated ammonia. Such conditions enable fast aqueous-phase oxidation of SO
2
by NO
2
, producing HONO which can in turn oxidize SO
2
to yield N
2
O.This mechanism could provide an explanation for sulfate formation under some winter haze conditions.
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