Abstract
5-Methylcytosine (m5C) plays an extremely important role in the basic biochemical process. With the great increase of identified m5C sites in a wide variety of organisms, their epigenetic ...roles become largely unknown. Hence, accurate identification of m5C site is a key step in understanding its biological functions. Over the past several years, more attentions have been paid on the identification of m5C sites in multiple species. In this work, we firstly summarized the current progresses in computational prediction of m5C sites and then constructed a more powerful and reliable model for identifying m5C sites. To train the model, we collected experimentally confirmed m5C data from Homo sapiens, Mus musculus, Saccharomyces cerevisiae and Arabidopsis thaliana, and compared the performances of different feature extraction methods and classification algorithms for optimizing prediction model. Based on the optimal model, a novel predictor called iRNA-m5C was developed for the recognition of m5C sites. Finally, we critically evaluated the performance of iRNA-m5C and compared it with existing methods. The result showed that iRNA-m5C could produce the best prediction performance. We hope that this paper could provide a guide on the computational identification of m5C site and also anticipate that the proposed iRNA-m5C will become a powerful tool for large scale identification of m5C sites.
This study explores the role of the long noncoding RNA (LncRNA) CRNDE in cisplatin (CDDP) resistance of gastric cancer (GC) cells. Here, we show that LncRNA CRNDE is upregulated in carcinoma tissues ...and tumor‐associated macrophages (TAMs) of GC patients. In vitro experiments show that CRNDE is enriched in M2‐polarized macrophage‐derived exosomes (M2‐exo) and is transferred from M2 macrophages to GC cells via exosomes. Silencing CRNDE in M2‐exo reverses the promotional effect of M2‐exo on cell proliferation in CDDP‐treated GC cells and homograft tumor growth in CDDP‐treated nude mice. Mechanistically, CRNDE facilitates neural precursor cell expressed developmentally downregulated protein 4‐1 (NEDD4‐1)‐mediated phosphatase and tensin homolog (PTEN) ubiquitination. Silencing CRNDE in M2‐exo enhances the CDDP sensitivity of GC cells treated with M2‐exo, which is reduced by PTEN knockdown. Collectively, these data reveal a vital role for CRNDE in CDDP resistance of GC cells and suggest that the upregulation of CRNDE in GC cells may be attributed to the transfer of TAM‐derived exosomes.
SYNOPSIS
LncRNA CRNDE is transferred from M2‐polarized macrophages to GC cells via exosomes, suppressing PTEN expression in GC cells. The latter leads to a reduced sensitivity of GC cells to cisplatin.
LncRNA CRNDE is enriched in TAMs of GC patients.
LncRNA CRNDE is transferred from M2‐polarized macrophages to GC cells via exosomes in vitro.
CRNDE facilitates NEDD4‐1‐mediated PTEN ubiquitination in GC cells.
Exosomal transfer of LncRNA CRNDE is linked to cisplatin resistance in GC cells caused by reduced PTEN levels.
LncRNA CRNDE is transferred from M2‐polarized macrophages to GC cells via exosomes, suppressing PTEN expression in GC cells. The latter leads to a reduced sensitivity of GC cells to cisplatin.
Helium (He) bubbles are typical radiation defects in structural materials in nuclear reactors after high dose energetic particle irradiation. In the past decades, extensive studies have been ...conducted to explore the dynamic evolution of He bubbles under various conditions and to investigate He-induced hardening and embrittlement. In this review, we summarize the current understanding of the behavior of He bubbles in metals; overview the mechanisms of He bubble nucleation, growth, and coarsening; introduce the latest methods of He control by using interfaces in nanocrystalline metals and metallic multilayers; analyze the effects of He bubbles on strength and ductility of metals; and point out some remaining questions related to He bubbles that are crucial for design of advanced radiation-tolerant materials.
Cancer stem cells are undifferentiated cancer cells that have self‐renewal ability, a high tumorigenic activity, and a multilineage differentiation potential. MicroRNAs play a critical role in ...regulating gene expression during carcinogenesis. Here, we investigated the role of miR‐7 and the mechanism by which it is dysregulated in gastric cancer stem cells (GCSCs). The stem cell marker, CD44, was used to sort GCSCs by fluorescence‐activated cell sorting. We found that CD44 (+) cells have higher invasiveness and form more number of sphere colonies than CD44 (−) cells. Quantitative real‐time polymerase chain reaction (PCR) revealed that the miR‐7‐5p expression was remarkably downregulated in GCSCs but was significantly increased in the methionine‐deprived medium. The downregulation of miR‐7‐5p results from the increased DNA methylation in the promoter region using the methylation‐specific PCR. Overexpression of miR‐7‐5p reduced the formation of colony and decreased the invasion of GCSCs through targeting Smo and Hes1 and subsequent repressing Notch and Hedgehog signaling pathways in vitro. Notably, upregulating miR‐7‐5p inhibited the growth of tumor in the xenograft model. Hence, these data demonstrated that miR‐7‐5p represses GCSC invasion through inhibition of Smo and Hes1, which provides a potential therapeutic target of gastric cancer treatment.
To ascertain the role of the solidification cell structures on the mechanical performance of Al-Si-(Mg) alloys processed using the laser powder bed fusion (LPBF) technique, micropillar compression ...tests were performed on LPBF Al-10Si-0.3Mg (AlSi10Mg). The alloy's microstructure consists of submicron-scale cellular structures, dense dislocation networks, and dispersed nanoscale Si precipitates. The stress-strain responses of the micropillars are devoid of pronounced serrations and the yield strength and work hardening behaviors are size-independent. A comparison of the micropillar compression responses of the LPBF AlSi10Mg, 316 L stainless steel and Inconel 718 alloy, and nano-and micro-crystalline alloys is made. In LPBF AlSi10Mg, the combination of dislocation networks and shear-resistant Si particles resist the dislocation motion significantly and enhance dislocation storage. This results in the cellular structure dominating the strength and plastic flow. These results show a pathway for designing high strength alloys via additive manufacturing.
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Background
With the onset of the coronavirus disease 2019 (COVID‐19) pandemic, many experts expected that asthma‐associated morbidity because of severe acute respiratory syndrome coronavirus 2 ...infection would dramatically increase. However, some studies suggested that there was no apparent increasing in asthma‐related morbidity in children with asthma, it is even possible children may have improved outcomes. To understand the relationship between the COVID‐19 pandemic and asthma outcomes, we performed this article.
Methods
We searched PubMed, Embase, and Cochrane Library to find literature from December 2019 to June 2021 related to COVID‐19 and children's asthma control, among which results such as s, comments, letters, reviews, and case reports were excluded. The level of asthma control during the COVID‐19 pandemic was synthesized and discussed by outcomes of asthma exacerbation, emergency room visit, asthma admission, and childhood asthma control test (c‐ACT).
Results
A total of 22,159 subjects were included in 10 studies. Random effect model was used to account for the data. Compared with the same period before the COVID‐19 pandemic, asthma exacerbation reduced (odds ratio OR = 0.26, 95% confidence interval CI = 0.14–0.48, Z = 4.32, p < 0.0001), the odds of emergency room visit decreased as well (OR = 0.11, 95% CI = 0.04–0.26, Z = 4.98, p < 0.00001). The outcome of asthma admission showed no significant difference (OR = 0.84, 95% CI = 0.32–2.20, Z = 0.36, p = 0.72). The outcome of c‐ACT scores were not analyzed because of the different manifestations used. Overall, c‐ACT scores reduced during the pandemic.
Conclusion
Compared to the same period before the COVID‐19 pandemic, the level of asthma control has been significantly improved. We need to understand the exact factors leading to these improvements and find methods to sustain it.
This paper mainly talks about the Cauchy two-matrix model and its corresponding integrable hierarchy with the help of orthogonal polynomial theory and Toda-type equations. Starting from the symmetric ...reduction in Cauchy biorthogonal polynomials, we derive the Toda equation of CKP type (or the C-Toda lattice) as well as its Lax pair by introducing time flows. Then, matrix integral solutions to the C-Toda lattice are extended to give solutions to the CKP hierarchy which reveals the time-dependent partition function of the Cauchy two-matrix model is nothing but the
τ
-function of the CKP hierarchy. At last, the connection between the Cauchy two-matrix model and Bures ensemble is established from the point of view of integrable systems.
Circular RNAs (circRNAs) is one type of important non-coding RNAs that participate in tumorigenesis and cancer progression. In our previous study, we performed a microarray analysis of circRNAs ...between the tumor tissues and the adjacent normal tissues of hepatocellular carcinoma (HCC) patients, and found that the circRNA hsa_circ_0007456 is significantly downregulated in the tumor tissues and correlated with the prognosis of HCC. We further investigated the relationship between the expression levels of hsa_circ_0007456 in HCC and the susceptibility of NK cells, and found that the expression levels of hsa_circ_0007456 in HCC cell lines significantly influenced their susceptibility to NK cells. Through a series of screening and validation, we found that hsa_circ_0007456 mainly functioned through sponging miR-6852-3p and regulating the expression of intercellular adhesion molecule-1 (ICAM-1) in HCC. The miR-6852-3p/ICAM-1 axis is essential for the NK cytotoxicity toward HCC mediated by hsa_circ_0007456. In conclusion, we identify here hsa_circ_0007456 as a promising biomarker of HCC, and highlight hsa_circ_0007456/miR-6852-3p/ICAM-1 axis as an important signaling pathway in the process of tumor immune evasion and the tumorigenesis of HCC.
Background
Autophagy plays an important role in regulating cisplatin (CDDP) resistance in gastric cancer cells. However, the underlying mechanism of methioninase (METase) in the regulation of ...autophagy and CDDP resistance of gastric cancer cells is still not clear.
Materials and methods
Western blot was used to detect the levels of autophagy-related proteins, multidrug-resistant 1 (MDR-1), and FoxM1 protein. LncRNA HULC was detected by qRT-PCR. Cell viability was detected using CCK-8 assay. The interaction between lncRNA HULC and FoxM1 was confirmed by RNA pull-down and RIP assay.
Results
Lentiviral vector carrying METase (LV-METase) suppressed autophagy and CDDP resistance of drug-resistant gastric cancer cells. LncRNA HULC was significantly downregulated in drug-resistant gastric cancer cells transfected with LV-METase. Besides, we found that lncRNA HULC interacted with FoxM1. In addition, METase suppressed autophagy to reduce CDDP resistance of drug-resistant gastric cancer cells through regulating HULC/FoxM1, and interfering HULC suppressed autophagy to reduce CDDP resistance of drug-resistant gastric cancer cells through regulating FoxM1. Finally, interfering HULC inhibited tumor growth in vivo.
Conclusion
METase suppressed autophagy to reduce CDDP resistance of drug-resistant gastric cancer cells through regulating HULC/FoxM1 pathway.
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