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Melanoma progression depends on melanoma stem cells (MSCs), which are distinguished by the distinct dysregulated genes. As the key factors in the dysregulation of genes, long non-coding RNAs (lncRNAs) take great effects on MSCs. However, the underlying mechanism of lncRNAs in MSCs has not been extensively characterized. To address the roles of lncRNAs in MSCs, LINC00698 was characterized in this study. The results revealed that LINC00698 was upregulated in MSCs, showing its important role in MSCs. The further data indicated that the LINC00698 silencing triggered cell cycle arrest in the G0/G1 phase and apoptosis of MSCs. LINC00698 could directly interact with miR-3132 to upregulate the expression of TCF7, which was required for sustaining the stemness and the tumorigenic potency of MSCs. At the same time, LINC00698 could bind to the hnRNPM protein to enhance the protein stability, thus suppressing apoptosis and promoting the stemness of MSCs. Furthermore, the in vivo data demonstrated that LINC00698 was essential for tumorigenesis of MSCs via the LINC00698-miR-3132-TCF7/hnRNPM axis. Therefore, our findings contributed novel insights into the underlying mechanism of melanoma progression. [ABSTRACT FROM AUTHOR]

Background: Cerebral stroke (CS) is the leading cause of death in China, and a complex disease caused by both alterable risk factors and genetic factors. This study intended to investigate the association of MMP3, MMP14, and MMP25 single nucleotide polymorphisms (SNPs) with CS risk in a Chinese Han population. Methods: A total of 1,348 Han Chinese were recruited in this case-control study. Four candidate loci including rs520540 A/G and rs679620 T/C of MMP3, rs2236302 G/C of MMP14, and rs10431961 T/C of MMP25 were successfully screened. The correlation between the four SNPs and CS risk was assessed by logistic regression analysis. The results were analyzed by false-positive report probability (FPRP) for chance or significance. The interactions between four SNPs associated with CS risk were assessed by multifactor dimensionality reduction (MDR). Results: rs520540 A/G and rs679620 C/T SNP in MMP3 were associated with risk of CS in allele, codominant, dominant and log-additive models. Ischemic stroke risk were significantly lower in carriers with rs520540-A allele and rs679620-T allele than those with G/G or C/C genotypes. However, rs520540-A allele and rs679620-T allele were associated with higher risk of hemorrhagic stroke. Stratified analysis showed that these two SNPs were associated with reduced risk of CS in aged < 55 years, non-smoking and non-drinking participants, and rs679620 SNP also reduced CS risk in male participants. The levels of uric acid, high-density lipoprotein cholesterol, and eosinophil were different among patients with different genotypes of rs520540 and rs679620. No statistically significant association was found between MMP14 rs2236302 G/C or MMP25 rs10431961 T/C with CS even after stratification by stroke subtypes, age, gender as well as smoking and drinking conditions in all the genetic models. Conclusion: MMP3 rs520540 A/G and rs679620 C/T polymorphisms were associated with CS risk in the Chinese Han population, which provides useful information for the prevention and diagnosis of CS. [ABSTRACT FROM AUTHOR]

Background: The flag leaf of rice (Oryza sativa L.) is an important determinant of plant type characteristics and grain yield. Identification of flag leaf mutants of rice is crucial to elucidate the molecular mechanism of flag-leaf development, and for exploitation of rice germplasm resources. Results: In this study, we describe a mutant designated short and narrow flag leaf 1 (snfl1). Histological analysis showed that the length of epidermal cells and number of longitudinal veins were decreased in the flag leaf of the snfl1 mutant. Map-based cloning indicated that a member of the GATA family of transcription factors is a candidate gene for SNFL1. A single-nucleotide transition at the last base in the single intron of snfl1 led to variation in alternative splicing and early termination of translation. Complemented transgenic plants harbouring the candidate SNFL1 gene rescued the snfl1 mutant. Analysis of RT-PCR and the SNFL1 promoter by means of a GUS fusion expression assay showed that abundance of SNFL1 transcripts was higher in the culm, leaf sheath, and root. Expression of the SNFL1-GFP fusion protein in rice protoplasts showed that SNFL1 was localized in nucleus. Conclusions: We conclude that SNFL1 is an important regulator of leaf development, the identification of which might have important implications for future research on GATA transcription factors. [ABSTRACT FROM AUTHOR]

Background: The simplified International Index of Erectile Function (IIEF-5) is a convenient, reliable and validated diagnostic tool for erectile dysfunction (ED). However, few studies focused on IIEF-5 in ED patients with different pathophysiological causes. ,We aim to compare the IIEF-5 score among ED patients with specific pathophysiologies in this study.Methods: The IIEF-5 score of 3,327 ED patients (median age 39 years) was analyzed. The primary causes of ED were determined by comprehensive diagnostic procedures in the urology/andrology clinics in five training hospitals. Patients with uncertain pathophysiologic cause were excluded.Results: 176 patients were excluded, 3151 patients with ED history between 0.5 year and 20 years, were enrolled. The causes of ED was classified as psychogenic (59.2%), vasoculogenic (21.3%), neurogenic (4.1%), anatomical/structural (2.8%), hormonal (7.1%) or drug-induced (5.5%). A significant difference was detected in the median IIEF-5 score between psychogenic ED and organic ED (15 (IQR 13, 17) versus 12 (IQR 9.5, 14.5), P < 0.001). There was no significant difference of IIEF-5 scores among the organic groups (P = 0.073), or between arteriogenic and venogenic groups (13 (IQR 10.5, 15.5) versus 13 (IQR 11-15), P = 0.912 (adjusted α = 0.017)). However, the median IIEF-5 score of those with a mixed vascular cause was the lowest among vasculogenic patients (11 (IQR 8.5-13.5), scores for the three groups: P = 0.003.).Conclusions: The IIEF-5 scores of men with psychological ED are higher than those with organic causes, but there is no difference among patients with different organic pathophysiologies. Our data indicate that IIEF-5 is not a definitive diagnostic tool to discriminate the pathophysiological causes of ED. [ABSTRACT FROM AUTHOR]

Macrophages are an essential component of innate immunity and play a vital role in inflammation and host defense. Based on immunological responses, the macrophages are classified into "activated" macrophage (M1 macrophages) participating in the responses of type I helper T (Th1) cells to pathogens and "alternatively activated" macrophages (M2 macrophages) in response to interleukin (IL)-4 and IL-13. In this review, we discuss the origin, classification and function of macrophages. We also discuss the mechanisms underlying polarization of different macrophage subtypes, including transcriptional, epigenetic and post-transcriptional regulation.

Background: The macrophage, one of the several key immune cell types, is believed to be involved in tumorigenesis. However, the mechanism of macrophages promoting tumor progression is largely unknown., Methods: The differentially secreted proteins of M1 and M2 macrophages were analyzed by mass spectrometry. We performed GST pull-down assay for the identification of cell-membrane receptors that interact with chitinase 3-like protein 1 (CHI3L1) protein. The mouse model was used to validate the function of CHI3L1 in cancer metastasis in vivo. Protein phosphorylation and gene expression were performed to study the signaling pathway activation of cancer cells after CHI3L1 treatment., Results: M2 macrophage-secreted CHI3L1 promoted the metastasis of gastric and breast cancer cells in vitro and in vivo. The CHI3L1 protein functioned by interacting with interleukin-13 receptor α2 chain (IL-13Rα2) molecules on the plasma membranes of cancer cells. Activation of IL-13Rα2 by CHI3L1 triggered the activation of the mitogen-activated protein kinase signaling pathway, leading to the upregulated expression of matrix metalloproteinase genes, which promoted tumor metastasis. The results of this study indicated that the level of CHI3L1 protein in the sera of patients with gastric or breast cancer was significantly elevated compared with those of healthy donors., Conclusions: Our study revealed a novel aspect of macrophages with respect to cancer metastasis and showed that CHI3L1 could be a marker of metastatic gastric and breast cancer in patients.

Background: The life cycle of a bacteriophage has tightly programmed steps to help virus infect its host through the interactions between the bacteriophage and its host proteins. However, bacteriophage-host protein interactions in high temperature environment remain poorly understood. To address this issue, the protein interaction between the thermophilic bacteriophage GVE2 and its host thermophilic Geobacillus sp. E263 from a deep-sea hydrothermal vent was characterized., Results: This investigation showed that the host's aspartate aminotransferase (AST), chaperone GroEL, and viral capsid protein VP371 formed a linearly interacted complex. The results indicated that the VP371-GroEL-AST complex were up-regulated and co-localized in the GVE2 infection of Geobacillus sp. E263., Conclusions: As reported, the VP371 is a capsid protein of GVE2 and the host AST is essential for the GVE2 infection. Therefore, our study revealed that the phage could use the anti-stress system of its host to protect the virus reproduction in a high-temperature environment for the first time.

Background: MicroRNAs (miRNAs) are key posttranscriptional regulators of gene expression that are implicated in many processes of eukaryotic cells. It is known that the expression profiles of host miRNAs can be reshaped by viruses. However, a systematic investigation of marine invertebrate miRNAs that respond to virus infection has not yet been performed., Results: In this study, the shrimp Marsupenaeus japonicus was challenged by white spot syndrome virus (WSSV). Small RNA sequencing of WSSV-infected shrimp at different time post-infection (0, 6, 24 and 48 h) identified 63 host miRNAs, 48 of which were conserved in other animals, representing 43 distinct families. Of the identified host miRNAs, 31 were differentially expressed in response to virus infection, of which 25 were up-regulated and six down-regulated. The results were confirmed by northern blots. The TargetScan and miRanda algorithms showed that most target genes of the differentially expressed miRNAs were related to immune responses. Gene ontology analysis revealed that immune signaling pathways were mediated by these miRNAs. Evolutionary analysis showed that three of them, miR-1, miR-7 and miR-34, are highly conserved in shrimp, fruit fly and humans and function in the similar pathways., Conclusions: Our study provides the first large-scale characterization of marine invertebrate miRNAs that respond to virus infection. This will help to reveal the molecular events involved in virus-host interactions mediated by miRNAs and their evolution in animals.

Background: Thermostable enzymes from thermophiles have attracted extensive studies. In this investigation, a nuclease-encoding gene (designated as GBSV1-NSN) was obtained from a thermophilic bacteriophage GBSV1 for the first time., Results: After recombinant expression in Escherichia coli, the purified GBSV1-NSN exhibited non-specific nuclease activity, being able to degrade various nucleic acids, including RNA, single-stranded DNA and double-stranded DNA that was circular or linear. Based on sequence analysis, the nuclease shared no homology with any known nucleases, suggesting that it was a novel nuclease. The characterization of the recombinant GBSV1-NSN showed that its optimal temperature and pH were 60 degrees C and 7.5, respectively. The results indicated that the enzymatic activity was inhibited by enzyme inhibitors or detergents, such as ethylene diamine tetraacetic acid, citrate, dithiothreitol, beta-mercaptoethanol, guanidine hydrochloride, urea and SDS. In contrast, the nuclease activity was enhanced by TritonX-100, Tween-20 or chaps to approximately 124.5% - 141.6%. The Km of GBSV1-NSN nuclease was 231, 61 and 92 microM, while its kcat was 1278, 241 and 300 s-1 for the cleavage of dsDNA, ssDNA and RNA, respectively., Conclusion: Our study, therefore, presented a novel thermostable non-specific nuclease from thermophilic bacteriophage and its overexpression and purification for scientific research and applications.