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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]

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]

Spatiotemporal distributions of dissolved acrylic acid (AAd) and related biogenic sulfur compounds including dimethylsulfide (DMS) and dissolved and total dimethylsulfoniopropionate (DMSPd and DMSPt) were investigated in the Bohai Sea (BS) and Yellow Sea (YS) during summer and winter. AAd and DMS production from DMSPd degradation and AAd degradation were analyzed. Significant seasonal variations in AAd and DMS(P) were observed. AAd exhibited similar distributions during summer and winter; i.e., relatively high values of AAd occurred in the BS and the northern YS, and the concentrations decreased from inshore to offshore areas in the southern YS. Due to strong biological production from DMSP and abundant terrestrial inputs from rivers in summer, the AAd concentrations in the surface seawater during summer (30.01 nmol L -1) were significantly higher than those during winter (14.98 nmol L -1). The average concentration sequence along the transects during summer (AAd > DMSPt > DMS > DMSPd) showed that particulate DMSP (DMSPp) acted as a DMS producer and that terrestrial sources of AAd were present; in contrast, the sequence in winter was AAd > DMSPt > DMSPd > DMS. High values of AAd and DMS(P) were mostly observed in the upper layers, with occasional high values at the bottom. High AAd concentrations in the porewater, which could be transported to the bottom water, might result from the cleavage of intracellular DMSP and reduce bacterial metabolism in sediments. In addition, the production and degradation rates of biogenic sulfur compounds were significantly higher in summer than in winter, and the removal of AAd was primarily attributed to microbial consumption. Other sources of AAd existed aside from the production from DMSPd. [ABSTRACT FROM AUTHOR]

Nitric oxide (NO) is a short-lived intermediate of the oceanic nitrogen cycle. However, our knowledge about its production and consumption pathways in oceanic environments is rudimentary. In order to decipher the major factors affecting NO photochemical production, we irradiated several artificial seawater samples as well as 31 natural surface seawater samples in laboratory experiments. The seawater samples were collected during a cruise to the western tropical North Pacific Ocean (WTNP, a N–S section from 36 to 2 ∘ N along 146 to 143 ∘ E with 6 and 12 stations, respectively, and a W–E section from 137 to 161 ∘ E along the Equator with 13 stations) from November 2015 to January 2016. NO photoproduction rates from dissolved nitrite in artificial seawater showed increasing trends with decreasing pH, increasing temperature, and increasing salinity. In contrast, NO photoproduction rates (average: 0.5±0.2×10-12 mol L -1 s -1) in the natural seawater samples from the WTNP did not show any correlations with pH, water temperature, salinity, or dissolved inorganic nitrite concentrations. The flux induced by NO photoproduction in the WTNP (average: 13×10-12 mol m -2 s -1) was significantly larger than the NO air–sea flux density (average: 1.8×10-12 mol m -2 s -1), indicating a further NO loss process in the surface layer. [ABSTRACT FROM AUTHOR]

Nitric oxide (NO) is a short-lived compound of the marine nitrogen cycle; however, our knowledge about its oceanic distribution and turnover is rudimentary. Here we present the measurements of dissolved NO in the surface and bottom layers at 75 stations in the Bohai Sea (BS) and the Yellow Sea (YS) in June 2011. Moreover, NO photoproduction rates were determined at 27 stations in both seas. The NO concentrations in the surface and bottom layers were highly variable and ranged from below the limit of detection (i.e., 32 pmol L -1) to 616 pmol L -1 in the surface layer and 482 pmol L -1 in the bottom layer. There was no significant difference (p>0.05) between the mean NO concentrations in the surface (186±108 pmol L -1) and bottom (174±123 pmol L -1) layers. A decreasing trend of NO in bottom-layer concentrations with salinity indicates a NO input by submarine groundwater discharge. NO in the surface layer was supersaturated at all stations during both day and night and therefore the BS and YS were a persistent source of NO to the atmosphere at the time of our measurements. The average flux was about 4.5×10-16 mol cm -2 s -1 and the flux showed significant positive relationship with the wind speed. The accumulation of NO during daytime was a result of photochemical production, and photoproduction rates were correlated to illuminance. The persistent nighttime NO supersaturation pointed to an unidentified NO dark production. NO sea-to-air flux densities were much lower than the NO photoproduction rates. Therefore, we conclude that the bulk of the NO produced in the mixed layer was rapidly consumed before its release to the atmosphere. [ABSTRACT FROM AUTHOR]

The amphibian metamorphosis assay (AMA) was proposed by the Organization for Economic Cooperation and Development (OECD) to screen thyroid disruptors of vertebrate species. The general experimental design of the AMA exposes Nieuwkoop and Faber (NF) stage 51 Xenopus laevis tadpoles to test chemical concentrations for 21 d. However, recent studies demonstrated that thyroid gland began to function after NF stage 45 in X. laevis. Thus, in this study, we initiated exposure with NF stage 48 tadpoles when the thyroid gland is still in a preliminary development period, to compare the sensitivity of the AMA with NF 48 stage and NF 51 stage tadpoles. Further, the application and sensitivity of the optimized AMA were evaluated and validated by two known thyroid toxicants methimazole (MMI) and sodium perchlorate (SP). The observational endpoints are developmental stage, hind limb length (HLL), snout–vent length (SVL), wet weight, and daily observations of mortality. The results were as follows. Although the sensitivity to endpoint of growth, such as wet weight and SVL was similar between the two assays, our optimized AMA detected delaying effects of 1 mg/L MMI and 32 μg/L SP on metamorphosis development both on day 7 and at test termination, which were lower than those in AMA. Additionally, it is easier to get a large number of animals at NF stage 48 than NF stage 51 in a short time. Thus, it is suggested that the NF stage 48 tadpoles might be applied to the AMA for efficiently screening the thyroid-active substances. [ABSTRACT FROM AUTHOR]

Abstract: The distributions of dimethylsulfide (DMS), dimethylsulfoniopropionate (DMSP), and acrylic acid (AA) were investigated in the Changjiang Estuary during winter (dry season) and summer (wet season) 2014 and in the East China Sea (ECS) during summer 2015. The rates of dissolved DMSP (DMSPd) degradation with DMS and AA production, DMS degradation, and AA degradation in the ECS were also studied. Significant seasonal variations in DMS(P) and AA concentrations were observed in the Changjiang Estuary with higher values during the wet season than during the dry season. The maximum ratio of AA/chlorophyll a (Chl a) occurred at the mouth of the Changjiang Estuary due to the combined effects of production from DMSP and terrestrial inputs from the Changjiang Estuary. The distributions of DMS(P) and AA in the ECS were dramatically influenced by the Kuroshio Current and the upwelling caused by the Taiwan Warm Current. The ratios of DMS(P)/Chl a and AA/Chl a exhibited similar patterns in the surface seawater of the ECS, which indicated that phytoplankton species and biomass might play important roles in controlling the distributions of DMS(P) and AA. In vertical profiles, high values of AA emerged in the upper water column and bottom seawater of the Changjiang Estuary. Meanwhile, the maxima of DMS(P) and AA generally appeared in the surface or euphotic layer, whereas their minima arose in the bottom seawater of the ECS. The degradation rates of DMSPd, DMS, and AA in the inshore waters were higher than those in the open sea. [ABSTRACT FROM AUTHOR]

Approximately 2% of the human genome consists of protein-coding regions. Therefore, the majority of transcripts are noncoding RNAs, such as microRNA (miRNA) and long noncoding RNAs (lncRNAs). In ischemic heart disease, the majority of miRNAs are repressors or destabilizers of target messenger RNAs. The lncRNAs are a second class of noncoding RNAs that have recently gained attention for their roles in heart disease and in regulating the functions of miRNA. In this review, we summarize the role of miRNA in pathological cardiac hypertrophy and myocardial infarction. In addition, we discuss the functional interactions of miRNA and lncRNA and its impact on these ischemic heart diseases. [ABSTRACT FROM AUTHOR]

Production of dimethylsulfoniopropionate (DMSP), dimethylsulfide (DMS), and acrylic acid (AA) from 22 marine microalgae representing six phyla were examined at different growth stages. The concentrations of DMSP, DMS, and AA per cell in the media showed significant changes during the whole growth period, and the highest concentrations were found at the stationary growth phase or the senescent phase. Different species had different concentration levels of DMSP, DMS, and AA, among which Pyrrhophyta, Bacillariophyte, and Chrysophyta had relatively large release. The highest concentrations of DMSP, DMS, and AA were 56.70, 0.86, and 44.60 fmol cell−1 in Scrippsiella trochoidea , Prymnesiacee , and Karenia mikimotoi , respectively. The ratios of DMS/DMSP and AA/(DMSP+AA) in the 22 marine microalgae differed dramatically over the growth cycle. The DMS/DMSP ratios were <25%, indicating that only a small fraction of DMSP was converted to DMS by enzymatic cleavage. Moreover, there was a higher ratio of enzymatic degradation of DMSP in the senescent growth stage. The AA/(DMSP+AA) ratio, representing the degradation ratio of DMSP, increased significantly at the beginning of growth period and then decreased. Hence, the changes in these ratios could approximately illustrate the degradation mechanism of DMSP among diverse species at different growth phases. • High DMSP, DMS and AA concentrations were detected in Pyrrophyta and Bacillariophyta. • The maximum concentrations of DMSP and DMS appeared in the stationary growth stage. • The highest release of AA was observed in the early exponential growth period. • The maximum value of DMSP enzymatic degradation appeared in late growth phase. [ABSTRACT FROM AUTHOR]