BackgroundMicroRNAs (miRNAs) are ∼22-nt small non-coding regulatory RNAs that have generally been considered to regulate gene expression at the post-transcriptional level in the cytoplasm. However, recent studies have reported that some miRNAs localize to and function in the nucleus.Methodology/Principal FindingsTo determine the number of miRNAs localized to the nucleus, we systematically investigated the subcellular distribution of small RNAs (sRNAs) by independent deep sequencing sequenced of the nuclear and cytoplasmic pools of 18- to 30-nucleotide sRNAs from human cells. We identified 339 nuclear and 324 cytoplasmic known miRNAs, 300 of which overlap, suggesting that the majority of miRNAs are imported into the nucleus. With the exception of a few miRNAs evidently enriched in the nuclear pool, such as the mir-29b, the ratio of miRNA abundances in the nuclear fraction versus in the cytoplasmic fraction vary to some extent. Moreover, our results revealed that a large number of tRNA 3′trailers are exported from the nucleus and accumulate in the cytoplasm. These tRNA 3′ trailers accumulate in a variety of cell types, implying that the biogenesis of tRNA 3′ trailers is conserved and that they have a potential functional role in vertebrate cells.Conclusion/SignificanceOur results provide the first comprehensive view of the subcellular distribution of diverse sRNAs and new insights into the roles of miRNAs and tRNA 3′ trailers in the cell.

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BackgroundCircular RNAs (circRNAs), a subclass of non-coding RNAs, play essential roles in tumorigenesis and aggressiveness. Our previous study has identified that circAGO2 drives gastric cancer progression through activating human antigen R (HuR), a protein stabilizing AU-rich element-containing mRNAs. However, the functions and underlying mechanisms of circRNAs derived from HuR in gastric cancer progression remain elusive.MethodsCircRNAs derived from HuR were detected by real-time quantitative RT-PCR and validated by Sanger sequencing. Biotin-labeled RNA pull-down, mass spectrometry, RNA immunoprecipitation, RNA electrophoretic mobility shift, and in vitro binding assays were applied to identify proteins interacting with circRNA. Gene expression regulation was observed by chromatin immunoprecipitation, dual-luciferase assay, real-time quantitative RT-PCR, and western blot assays. Gain- and loss-of-function studies were performed to observe the impacts of circRNA and its protein partner on the growth, invasion, and metastasis of gastric cancer cells in vitro and in vivo.ResultsCirc-HuR (hsa_circ_0049027) was predominantly detected in the nucleus, and was down-regulated in gastric cancer tissues and cell lines. Ectopic expression of circ-HuR suppressed the growth, invasion, and metastasis of gastric cancer cells in vitro and in vivo. Mechanistically, circ-HuR interacted with CCHC-type zinc finger nucleic acid binding protein (CNBP), and subsequently restrained its binding to HuR promoter, resulting in down-regulation of HuR and repression of tumor progression.ConclusionsCirc-HuR serves as a tumor suppressor to inhibit CNBP-facilitated HuR expression and gastric cancer progression, indicating a potential therapeutic target for gastric cancer.

Introduction This study explores the preparedness of our emergency department during the COVID-19 outbreak from the nurses’ perspectives, providing a reference and basis for our emergency department’s response to public health emergencies. Methods Using qualitative research methods, semistructured interviews were conducted with 12 emergency nurses who met the inclusion criteria, and Colaizzi analysis was used for data analysis, summary, and induction. Results A cluster of 4 themes that involved preparedness of the emergency department during the COVID-19 outbreak was extracted: organizational preparedness, personal preparedness, patient and family preparedness, and deficiencies and challenges. Discussion Organizations, individuals, patients, and family members were actively prepared to respond to novel coronavirus pneumonia outbreak in the emergency department. The emergency nurses said that the trusted organization guaranteed personal preparedness, and the active cooperation from patients and families was a motivator for personal preparedness. In addition, our study showed that there were deficiencies in both multidisciplinary collaboration efforts and efforts to rapidly diagnose and treat patients with fever in critical condition.

On the basis of first-principles density functional calculations, we predict that Li-decorated graphyne can serve as a promising candidate for hydrogen storage, with a largest storage capacity of 18.6 wt %. The average adsorption energy of hydrogen is about −0.27 eV/H 2 , indicating that the doped system is an ideal hydrogen storage material at ambient conditions. It is proposed that the polarization mechanism, which stems from the electric field induced by the ionic Li coated on the graphyne, plays a key role in the adsorption of H 2 molecules. Furthermore, the formation of the hydrogen−hydrogen complex also stabilizes the adopted hydrogen molecules.

Skeletal muscle differentiation is controlled by multiple cell signaling pathways, however, the JNK/MAPK signaling pathway dominating this process has not been fully elucidated. Here, we report that the JNK/MAPK pathway was significantly downregulated in the late stages of myogenesis, and in contrast to P38/MAPK pathway, it negatively regulated skeletal muscle differentiation. Based on the PAR-CLIP-seq analysis, we identified six elevated miRNAs (miR-1a-3p, miR-133a-3p, miR-133b-3p, miR-206-3p, miR-128-3p, miR-351-5p), namely myogenesis-associated miRNAs (mamiRs), negatively controlled the JNK/MAPK pathway by repressing multiple factors for the phosphorylation of the JNK/MAPK pathway, including MEKK1, MEKK2, MKK7, and c-Jun but not JNK protein itself, and as a result, expression of transcriptional factor MyoD and mamiRs were further promoted. Our study revealed a novel double-negative feedback regulatory pattern of cell-specific miRNAs by targeting phosphorylation kinase signaling cascade responsible for skeletal muscle development.

Belite (C 2 S, CCaO, SSiO 2 ) based cements are promising low-CO 2 substitutes of ordinary Portland cement. The main drawback is their low hydration rates, which makes them unpractical for construction. Yet more disconcerting is the different reactivity between polymorphs of belite: while β-C 2 S reacts slowly with water, γ-C 2 S is almost inert. Due to the demand of improving C 2 S reactivity, in this work we aim to understand the hydration mechanism of belite polymorphs by density functional theory and molecular dynamics simulations methods. We calculated the low-index cleavage energies, and the thermodynamic equilibrium structures were constructed through Wulff shape constructing method. We built the adsorption energy surface (AES) maps and found out the transition state structures for (chemi)sorption of water molecules. Finally molecular dynamics were employed to simulate the reactions taking place during 2 ns at room temperature. We found that water dissociation consists of three steps, rotation, dissociation, and diffusion, with different energy barriers. Considering the AES, DFT energy barriers, and the molecular dynamics simulations, the number of reactive sites is the key aspect that controls hydration; even though water reacts preferentially in γ-C 2 S surfaces over in β-C 2 S in terms of energy, a considerably lower number of reactive points in γ-C 2 S would limit the surface hydration and dissolution.

Aerobic glycolysis is a hallmark of metabolic reprogramming in tumor progression. However, the mechanisms regulating glycolytic gene expression remain elusive in neuroblastoma (NB), the most common extracranial malignancy in childhood. Herein, we identify that CUT‐like homeobox 1 (CUX1) and CUX1‐generated circular RNA (circ‐CUX1) contribute to aerobic glycolysis and NB progression. Mechanistically, p110 CUX1, a transcription factor generated by proteolytic processing of p200 CUX1, promotes the expression of enolase 1, glucose‐6‐phosphate isomerase, and phosphoglycerate kinase 1, while circ‐CUX1 binds to EWS RNA‐binding protein 1 (EWSR1) to facilitate its interaction with MYC‐associated zinc finger protein (MAZ), resulting in transactivation of MAZ and transcriptional alteration of CUX1 and other genes associated with tumor progression. Administration of an inhibitory peptide blocking circ‐CUX1‐EWSR1 interaction or lentivirus mediating circ‐CUX1 knockdown suppresses aerobic glycolysis, growth, and aggressiveness of NB cells. In clinical NB cases, CUX1 is an independent prognostic factor for unfavorable outcome, and patients with high circ‐CUX1 expression have lower survival probability. These results indicate circ‐CUX1/EWSR1/MAZ axis as a therapeutic target for aerobic glycolysis and NB progression.