HIF-1α Contributes to Hypoxia-induced Invasion and Metastasis of Esophageal Carcinoma via Inhibiting E-cadherin and Promoting MMP-2 Expression

Hypoxia-inducible factor-1α (HIF-1α) has been found to enhance tumor invasion and metastasis, but no study has reported its action in esophageal carcinoma. The goal of this study was to explore the probable mechanism of HIF-1α in the invasion and metastasis of esophageal carcinoma Eca109 cells in vitro and in vivo. mRNA and protein expression of HIF-1α, E-cadherin and matrix metalloproteinase-2 (MMP-2) under hypoxia were detected by RT-PCR and Western blotting. The effects of silencing HIF-1α on E-cadherin, MMP-2 mRNA and protein expression under hypoxia or normoxia were detected by RT-PCR and Western blotting, respectively. The invasive ability of Eca109 cells was tested using a transwell chambers. We established an Eca109-implanted tumor model and observed tumor growth and lymph node metastasis. The expression of HIF-1α, E-cadherin and MMP-2 in xenograft tumors was detected by Western blotting. After exposure to hypoxia, HIF-1α protein was up-regulated, both mRNA and protein levels of E-cadherin were down-regulated and MMP-2 was up-regulated, while HIF-1α mRNA showed no significant change. SiRNA could block HIF-1α effectively, increase E-cadherin expression and inhibit MMP-2 expression. The number of invading cells decreased after HIF-1α was silenced. Meanwhile, the tumor volume was much smaller, and the metastatic rate of lymph nodes and the positive rate were lower in vivo. Our observations suggest that HIF-1α inhibition might be an effective strategy to weaken invasion and metastasis in the esophageal carcinoma Eca109 cell line

Semi-Supervised Specific Emitter Identification Method Using Metric-Adversarial Training

Specific emitter identification (SEI) plays an increasingly crucial and potential role in both military and civilian scenarios. It refers to a process to discriminate individual emitters from each other by analyzing extracted characteristics from given radio signals. Deep learning (DL) and deep neural networks (DNNs) can learn the hidden features of data and build the classifier automatically for decision making, which have been widely used in the SEI research. Considering the insufficiently labeled training samples and large unlabeled training samples, semi-supervised learning-based SEI (SS-SEI) methods have been proposed. However, there are few SS-SEI methods focusing on extracting the discriminative and generalized semantic features of radio signals. In this paper, we propose an SS-SEI method using metric-adversarial training (MAT). Specifically, pseudo labels are innovatively introduced into metric learning to enable semi-supervised metric learning (SSML), and an objective function alternatively regularized by SSML and virtual adversarial training (VAT) is designed to extract discriminative and generalized semantic features of radio signals. The proposed MAT-based SS-SEI method is evaluated on an open-source large-scale real-world automatic-dependent surveillance-broadcast (ADS-B) dataset and WiFi dataset and is compared with state-of-the-art methods. The simulation results show that the proposed method achieves better identification performance than existing state-of-the-art methods. Specifically, when the ratio of the number of labeled training samples to the number of all training samples is 10\%, the identification accuracy is 84.80\% under the ADS-B dataset and 80.70\% under the WiFi dataset. Our code can be downloaded from https://github.com/lovelymimola/MAT-based-SS-SEI.Comment: 12 pages, 5 figures, Journa

Paracrine GABA and insulin regulate pancreatic alpha cell proliferation in a mouse model of type 1 diabetes

Aims/hypothesis: This study aimed to elucidate the mechanism of increased proliferation of alpha cells in recent-onset type 1 diabetes. Pancreatic beta cells express GAD and produce γ-aminobutyric acid (GABA), which inhibits alpha cell secretion of glucagon. We explored the roles of GABA in alpha cell proliferation in conditions corresponding to type 1 diabetes in a mouse model and in vitro. Methods: Type 1 diabetes was induced by injecting the mice with streptozotocin (STZ). Some of the STZ-injected mice were treated with GABA (10 mg/kg daily) for 12 days. Isolated pancreatic islets were treated with STZ or STZ together with GABA for 2 days. The effects of GABA treatment on STZ-induced alpha cell proliferation in vivo and in vitro were assessed. The effect of muscimol, a GABA receptor agonist, on αTC1-6 cell proliferation was also examined. Results: STZ injection substantially decreased levels of GAD, GABA and insulin in pancreatic beta cells 12 h after injection; this was followed by an upsurge of phosphorylated mechanistic target of rapamycin (p-mTOR) in the alpha cells at day 1, and a significant increase in alpha cell mass at day 3. Treating STZ-injected mice with GABA largely restored the immunodetectable levels of insulin and GAD in the beta cells and significantly decreased the number of aldehyde dehydrogenase 1 family, member A3 (ALDH1a3)-positive cells, alpha cell mass and hyperglucagonaemia. STZ treatment also increased alpha cell proliferation in isolated islets, which was reversed by co-treatment with GABA. Muscimol, together with insulin, significantly lowered the level of cytosolic Ca2+ and p-mTOR, and decreased the proliferation rate of αTC1-6 cells. Conclusions/interpretation: GABA signalling critically controls the alpha cell population in pancreatic islets. Low intraislet GABA may contribute to alpha cell hyperplasia in early type 1 diabetes

N6-methyl-adenosine (m6A) in RNA: An Old Modification with A Novel Epigenetic Function

AbstractN6-methyl-adenosine (m6A) is one of the most common and abundant modifications on RNA molecules present in eukaryotes. However, the biological significance of m6A methylation remains largely unknown. Several independent lines of evidence suggest that the dynamic regulation of m6A may have a profound impact on gene expression regulation. The m6A modification is catalyzed by an unidentified methyltransferase complex containing at least one subunit methyltransferase like 3 (METTL3). m6A modification on messenger RNAs (mRNAs) mainly occurs in the exonic regions and 3′-untranslated region (3′-UTR) as revealed by high-throughput m6A-seq. One significant advance in m6A research is the recent discovery of the first two m6A RNA demethylases fat mass and obesity-associated (FTO) gene and ALKBH5, which catalyze m6A demethylation in an α-ketoglutarate (α-KG)- and Fe2+-dependent manner. Recent studies in model organisms demonstrate that METTL3, FTO and ALKBH5 play important roles in many biological processes, ranging from development and metabolism to fertility. Moreover, perturbation of activities of these enzymes leads to the disturbed expression of thousands of genes at the cellular level, implicating a regulatory role of m6A in RNA metabolism. Given the vital roles of DNA and histone methylations in epigenetic regulation of basic life processes in mammals, the dynamic and reversible chemical m6A modification on RNA may also serve as a novel epigenetic marker of profound biological significances

Transcriptome Analysis of Metapenaeus affinis Reveals Genes Involved in Gonadal Development

Metapenaeus affinis is a crustacean with important commercial value in the fishery of the South China Sea. Overfishing has resulted in the decline of the wild population and germplasm degradation. However, there is little background knowledge about its gonadal development, and there is a lack of research on the development of this species. To better understand the molecular regulatory mechanisms during gonadal development, here, we performed RNA-Seq on immature and mature ovaries and compared their transcriptomic signatures. 126,930,488 and 122,677,356 clean sequencing reads were obtained from the Illumina sequencing platform, respectively. 394 differentially expressed genes (DEGs) were identified, of which 136 were up-regulated, and 258 were down-regulated. Further analysis revealed rich transcriptional sequences, which have homology with genes related to reproduction and development. Expression patterns of COX, GPX, E3s, PCNA, STPK, and other genes were changed during ovarian development. Validation by qRT-PCR demonstrated the reliability of RNA-Seq. This study has made a significant contribution to the currently available sequence data of M. affinis and provided reference data for the development of genetic and breeding work

Biochemical properties of mammalian TREX1 and its association with DNA replication and inherited inflammatory disease

Abstract The major DNA-specific 3 -5 exonuclease of mammalian cells is TREX1 (3 repair exonuclease 1; previously called DNase III). The human enzyme is encoded by a single exon and, like many 3 exonucleases, exists as a homodimer. TREX1 degrades ssDNA (single-stranded DNA) more efficiently than dsDNA (double-stranded DNA), and its catalytic properties are similar to those of Escherichia coli exonuclease X. However, TREX1 is only found in mammals and has an extended C-terminal domain containing a leucine-rich sequence required for its association with the endoplasmic reticulum. In normal S-phase and also in response to genotoxic stress, TREX1 at least partly redistributes to the cell nucleus. In a collaborative project, we have demonstrated TREX1 enzyme deficiency in Aicardi-Goutières syndrome. Subsequently, we have shown that AGS1 cells exhibit chronic ATM (ataxia telangiectasia mutated)-dependent checkpoint activation, and these TREX1-deficient cells accumulate ssDNA fragments of a distinct size generated during DNA replication. Other groups have shown that the syndromes of familial chilblain lupus as well as systemic lupus erythematosus, and the distinct neurovascular disorder retinal vasculopathy with cerebral leukodystrophy, can be caused by dominant mutations at different sites within the TREX1 gene

排卵功能障碍性不孕症患者的中医五态人格及焦虑分析

Objective: Finding out the relationship between five-pattern personality and anxiety 、depression characteristics of the DOI patients. Methods: 200 DOI patients were selected in the Infertility Specialist of Guangzhou Liwan District Hospital of Chinese Medicine，at the same time, researchers choose normal women as controls. Respondents filled in the Five-pattern Personality Scales、SAS、SDS and general information questionnaire. Results: The proportion of shaoyin personality of the DOI patients(50%) is significantly higher than the normal women(22%). And no yin and yang personality was observed in patients with DOI. The SAS and SDS score of the DOI patients, listed in descending order, is as follow, taiyin personality、shaoyin personality、taiyang personality、shaoyang personality、yin and yang personality. Conclusion: The main five-pattern personality of DOI is shaoyin personality. The patients of the taiyin and shaoyin personality are more likely to have the characteristics of anxiety and depression.目的  探究排卵功能障碍性不孕症患者不同中医五态人格类型与焦虑、抑郁情绪的关联性。方法  确诊为排卵功能障碍性不孕症患者200例，同时在本院选择正常已育妇女作为对照组。采用《五态人格量表》、《焦虑自评量表（SAS）》、《抑郁自评量表（SDS）》及一般资料问卷进行调查。结果  排卵功能障碍性不孕症组中少阴型中医人格（50%）明显高于正常妇女组（22%），且没有出现阴阳平和型中医人格。不孕症组中太阳、少阳、少阴、太阴型中医人格的焦虑、抑郁总分4组间不全相等（P＜0.001）。结论  排卵功能障碍性不孕症患者以少阴型中医人格为主，且太阴、少阴型中医人格的患者更易出现高焦虑、高抑郁