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Esophageal squamous cell carcinoma (ESCC) is one of the most aggressive cancers and is highly resistant to current treatments. ESCC harbors a subpopulation of cells exhibiting cancer stem-like cell (CSC) properties that contribute to therapeutic resistance including radioresistance, but the molecular mechanisms in ESCC CSCs are currently unknown. Here, we report that ribosomal S6 protein kinase 4 (RSK4) plays a pivotal role in promoting CSC properties and radioresistance in ESCC. RSK4 was highly expressed in ESCC CSCs and associated with radioresistance and poor survival in patients with ESCC. RSK4 was found to be a direct downstream transcriptional target of [DELTA]Np63[alpha], the main p63 isoform, which is frequently amplified in ESCC. RSK4 activated the [beta]-catenin signaling pathway through direct phosphorylation of GSK-3[beta] at Ser9. Pharmacologic inhibition of RSK4 effectively reduced CSC properties and improved radiosensitivity in both nude mouse and patient-derived xenograft models. Collectively, our results strongly suggest that the [DELTA]Np63[alpha]/RSK4/GSK-3[beta] axis plays a key role in driving CSC properties and radioresistance in ESCC, indicating that RSK4 is a promising therapeutic target for ESCC treatment., Introduction Esophageal cancer is one of the most frequently occurring cancers and ranks as the seventh leading cause of cancer-related mortality worldwide. Esophageal squamous cell carcinoma (ESCC) is the most [...]

MicroRNAs (miRNAs) are a class of small noncoding RNAs that are approximately 22 nt in length and regulate gene expression post-transcriptionally. miRNAs play a vital role in both physiological and pathological processes and are regarded as promising biomarkers for cancer, cardiovascular diseases, neurodegenerative diseases, and so on. Accurate detection of miRNA expression level in clinical samples is important for miRNA-guided diagnostics. However, the common miRNA detection approaches like RNA sequencing, qRT-PCR, and miRNA microarray are performed in a professional laboratory with complex intermediate steps and are time-consuming and costly, challenging the miRNA-guided diagnostics. Hence, sensitive, highly specific, rapid, and easy-to-use detection of miRNAs is crucial for clinical diagnosis based on miRNAs. With the advantages of being specific, sensitive, efficient, cost-saving, and easy to operate, point-of-care testing (POCT) has been widely used in the detection of miRNAs. For the first time, we mainly focus on summarizing the research progress in POCT of miRNAs based on portable instruments and visual readout methods. As widely available pocket-size portable instruments and visual detection play important roles in POCT, we provide an all-sided discussion of the principles of these methods and their main limitations and challenges, in order to provide a guide for the development of more accurate, specific, and sensitive POCT methods for miRNA detection. [ABSTRACT FROM AUTHOR]

Due to the small size of the annotated corpora and the sparsity of the event trigger words, the event coreference resolver cannot capture enough event semantics, especially the trigger semantics, to identify coreferential event mentions. To address the above issues, this paper proposes a trigger semantics augmentation mechanism to boost event coreference resolution. First, this mechanism performs a trigger-oriented masking strategy to pre-train a BERT (Bidirectional Encoder Representations from Transformers)-based encoder (Trigger-BERT), which is fine-tuned on a large-scale unlabeled dataset Gigaword. Second, it combines the event semantic relations from the Trigger-BERT encoder with the event interactions from the soft-attention mechanism to resolve event coreference. Experimental results on both the KBP2016 and KBP2017 datasets show that our proposed model outperforms several state-of-the-art baselines. [ABSTRACT FROM AUTHOR]

Myocardial infarction is a leading cause of mortality worldwide. Here we report that modulation of microRNA-499 (miR-499) levels affects apoptosis and the severity of myocardial infarction and cardiac dysfunction induced by ischemia-reperfusion. We found that both the α- and β-isoforms of the calcineurin catalytic subunit are direct targets of miR-499 and that miR-499 inhibits cardiomyocyte apoptosis through its suppression of calcineurin-mediated dephosphorylation of dynamin-related protein-1 (Drp1), thereby decreasing Drp1 accumulation in mitochondria and Drp1-mediated activation of the mitochondrial fission program. We also found that p53 transcriptionally downregulates miR-499 expression. Our data reveal a role for miR-499 in regulating the mitochondrial fission machinery and we suggest that modulation of miR-499 levels may provide a therapeutic approach for treating myocardial infarction., MicroRNAs are about 22 nucleotides long and act as negative regulators of gene expression by inhibiting mRNA translation or promoting mRNA degradation (1). A single miRNA can modulate complex physiological [...]

By analyzing the sequencing results, we found that PKM2 was significantly enriched in the KEGG pathway associated with muscle development and was screened as a hub gene in the fast-growing group; hence, we speculate that PKM2 may be associated with the growth and development of Bian chickens. Keywords: miRNA-seq; skeletal muscle; Bian chicken; growth and development EN miRNA-seq skeletal muscle Bian chicken growth and development N.PAG N.PAG 15 04/26/22 20220415 NES 220415 1. Apart from research on genes related to Bian chicken growth, there are few studies on miRNA functions in Bian chicken growth. miRNA is a noncoding sequence with a length of approximately 22 nt, which inhibits the expression of target genes by binding to the 3'UTR region of mRNA [[5]]. In order to further explore the key DEMs and predicted target genes, we performed an interaction network analysis of genes enriched in KEGG pathways associated with muscle growth and development. [Extracted from the article]

Environmental context: Blooms of Ulva prolifera have recurred annually in the Yellow Sea since 2007, causing economic losses and severe ecological problems. We conducted laboratory incubation experiments to examine the effects of temperature and nutrients on its biogenic sulfur emissions during its decline period. Increasing temperature and nutrients affected the decay of U. prolifera, resulting in respective decreased and increased emission of biogenic sulfur compounds. The Ulva prolifera blooms have recurred annually in the Yellow Sea (YS) since 2007, causing huge economic losses and severe ecological problems. So far, few studies have investigated the release of volatile biogenic sulfur compounds by the U. prolifera blooms. In this study, laboratory incubation experiments were conducted to examine the effects of temperature and nutrient concentrations on the emissions of biogenic sulfur compounds during the green tide decline period. Under simulated conditions, higher incubation temperatures and nutrient concentrations promoted the decay of U. prolifera. When the incubation temperature was increased from 20 #176;C to 25 #176;C, the mean concentrations of dimethylsulfide (DMS), dissolved dimethylsulfoniopropionate (DMSPd) and particulate dimethylsulfoniopropionate (DMSPp) in the culture medium decreased by ~20 %, 55 % and 20 % respectively; in addition, these values increased by ~40 %, 70 % and 240 % respectively when exogenous nutrients were added to the culture medium. Moreover, a high concentration of nitrate (NO3-) (>50 μM) could promote the release of biogenic sulfur by U. prolifera in the absence of other nutrients. The findings of this study provide insight into the roles of macroalgae on changes to the environment and shed light on the potential impact of DMSP and other degradation products of DMS produced by the green tide on the environment and ecosystem. [ABSTRACT FROM AUTHOR]

Plexin D1 (PLXND1), which was previously thought to mediate semaphorin signalling, belongs to the Plexin family of transmembrane proteins. PLXND1 cooperates mostly with the coreceptor neuropilin and participates in many aspects of axonal guidance. PLXND1 can also act as both a tumour promoter and a tumour suppressor. Emerging evidence suggests that mutations in PLXND1 or Semaphorin 3E, the canonical ligand of PLXND1, can lead to serious cardiovascular diseases, such as congenital heart defects, CHARGE syndrome and systemic sclerosis. Upon ligand binding, PLXND1 can act as a GTPase‐activating protein (GAP) and modulate integrin‐mediated cell adhesion, cytoskeletal dynamics and cell migration. These effects may play regulatory roles in the development of the cardiovascular system and disease. The cardiovascular effects of PLXND1 signalling have gradually been elucidated. PLXND1 was recently shown to detect physical forces and translate them into intracellular biochemical signals in the context of atherosclerosis. Therefore, the role of PLXND1 in cardiovascular development and diseases is gaining research interest because of its potential as a biomarker and therapeutic target. In this review, we describe the cardiac effects, vascular effects and possible molecular mechanisms of PLXND1 signalling. [ABSTRACT FROM AUTHOR]

This study aimed to evaluate the effects of in vitro‐induced drug resistance on the virulence of Streptococcus. Micro‐dilution method was used to determine the minimal inhibitory concentration (MIC). In vitro‐induced drug resistance was conducted for S. agalactiae (CVCC1886) and S. dysgalactiae (CVCC3701) by gradually increasing the antimicrobial concentration (strains were from IVDC, China). PCR was used to detect the resistance and virulence genes of the strains before and after resistance induction. Colony morphology was observed to compare the physiological and biochemical properties of the strains. A total of 88 clean‐grade Kunming mice (obtained from Inner Mongolia University, Hohhot, China) were used in half of the lethal dose (LD50) test for detecting the changes in virulence of strains. The results showed that S. agalactiae (CVCC1886) and S. dysgalactiae (CVCC3701) developed resistance against seven kinds of antibiotics, respectively. Resistance and virulence genes of CVCC3701 were changed when treated by the Penicillin‐inducing. The growth of the CVCC3701‐PEN was decreased compared to the CVCC3701. Virulence test in mice indicated that the LD50 of CVCC3701 before induction and CVCC3701‐PEN after induction were 5.45 × 106 and 5.82 × 108 CFU/ml, respectively. Compared with the untreated bacteria, the bacterial virulence was reduced 1.1 × 102 times after resistance induction. In conclusion, S. dysgalactiae (CVCC3701) is a susceptible strain of drug resistance to antibiotics, in vitro‐induced drug resistance reduced the virulence of CVCC3701, but the virulence is still existing and also could result in the death of mice. For public health safety, it must be alert to the emergence of drug resistance of Streptococcus in animal production. [ABSTRACT FROM AUTHOR]