Recent advances in transcriptome sequencing have made it possible to distinguish ubiquitously expressed long non-coding RNAs (UE lncRNAs) from tissue-specific lncRNAs (TS lncRNAs), thereby providing clues to their cellular functions. Here, we assembled and functionally characterized a consensus lncRNA transcriptome by curating hundreds of RNA-seq datasets across normal human tissues from 16 independent studies. In total, 1,184 UE and 2,583 TS lncRNAs were identified. These different lncRNA populations had several distinct features. Specifically, UE lncRNAs were associated with genomic compaction and highly conserved exons and promoter regions. We found that UE lncRNAs are regulated at the transcriptional level (with especially strong regulation of enhancers) and are associated with epigenetic modifications and post-transcriptional regulation. Based on these observations we propose a novel way to predict the functions of UE and TS lncRNAs through analysis of their genomic location and similarities in epigenetic modifications. Our characterization of UE and TS lncRNAs may provide a foundation for lncRNA genomics and the delineation of complex disease mechanisms.

Adipogenesis is a complex and precisely orchestrated process mediated by a network of adipogenic regulatory factors. Several studies have highlighted the relevance of lncRNAs in adipocyte differentiation, but the precise molecular mechanism has largely remained elusive. In the present study, we performed Ribo-Zero RNA-Seq to investigate both the poly(A)+and poly(A)-lncRNAs of in vitro cultured bovine preadipocytes and differentiated adipocytes. A stringent set of 2882 lncRNAs was finally identified. A comparison of the lncRNAs expression profiles revealed that 16 lncRNAs are differentially expressed during adipocyte differentiation. We focused on the most downregulated lncRNA, which we named adipocyte differentiation-associated long noncoding RNA (ADNCR). Mechanistically, ADNCR inhibited adipocyte differentiation by functioning as a competing endogenous RNA (ceRNA) for miR-204, thereby augmenting the expression of the miR-204 target gene, SIRT1, which is known to inhibit adipocyte differentiation and adipogenic gene expression by docking with NCoR and SMART to repress PPARγ activity. Our data not only provide a valuable genomic resource for the identification of lncRNAs with functional roles in adipocyte differentiation but also reveal new insights into understanding the mechanisms of adipogenic differentiation.

The present study was aimed at exploring the protective effects of Salvianolic acid B (SalB) against paraquat (PQ)-induced lung injury in mice. Lung fibrotic injuries were induced in mice by a single intragastrical administration of 300mg/kg PQ, then the mice were administrated with 200mg/kg, 400mg/kg SalB, 100mg/kg vitamin C (Vit C) and dexamethasone (DXM) for 14days. PQ-triggered structure distortion, collagen overproduction, excessive inflammatory infiltration, pro-inflammatory cytokine release, and oxidative stress damages in lung tissues and mortality of mice were attenuated by SalB in a dose-dependent manner. Furthermore, SalB was noted to enhance the expression and nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2) and reduce expression of the reactive oxygen species-generating enzyme Nox4 [NADPH (reduced form of nicotinamide adenine dinucleotide phosphate) oxidase-4]. SalB also inhibited the increasing expression of transforming growth factor (TGF)-β1 and the phosphorylation of its downstream target Smad3 which were enhanced by PQ. These results suggest that SalB may exert protective effects against PQ-induced lung injury and pulmonary fibrosis. Its mechanisms involve the mediation of Nrf2/Nox4 redox balance and TGF-β1/Smad3 signaling.

Currently, various long noncoding RNAs (lncRNAs) have been identified as key regulators of multiple cancers. However, cancer stem cell (CSC)-related lncRNAs have rarely been reported. In this study, we found an lncRNA that is a promoter upstream transcript of hypoxia-inducible factor-2α (HIF-2α), and we named it "lncRNA-HIF2PUT". The function of HIF-2α is closely connected with "stem cell-like" properties, and the function of PROMPTs is often associated with the adjacent protein-coding transcripts. Herein, we showed that the expression of lncRNA-HIF2PUT was significantly correlated with HIF-2α in colorectal cancer (CRC) tissues. Knockdown of lncRNA-HIF2PUT blocked the HIF-2α expression and inhibited the CSC properties in CRC cell lines DLD-1 and HT29. LncRNA-HIF2PUTsmall interfering RNA transfection resulted in decreased stemness genes expression, impaired colony formation, and spheroid formation ability, retarded migration, and invasion of the cells. These data suggest that lncRNA-HIF2PUT may be a regulator of HIF-2α and a mediator of CSCs in CRC.

Endothelial progenitor cells (EPCs) contribute to recanalization of deep vein thrombosis (DVT). This study aimed to detect miRNA expression profiles in EPCs from patients with DVT and characterize the role of miRNA in EPCs dysfunction.

The current study aimed to determine whether dietary nucleotides supplementation could improve growth performance, intestinal development and immune function of intra-uterine growth restricted (IUGR) neonate using pig as animal model. A total of 14 pairs of normal birth weight (NBW) and IUGR piglets (7 days old) were randomly assigned to receive a milk-based control diet (CON diet) or diet supplemented with nucleotides (NT diet) for a period of 21 days. Blood samples, intestinal tissues and digesta were collected at necropsy and analyzed for morphology, digestive enzyme activities, microbial populations, peripheral immune cells, expression of intestinal innate immunity and barrier-related genes and proteins. Compared with NBW piglets, IUGR piglets had significantly lower average daily dry matter intake and body weight gain (P<0.05). Moreover, IUGR markedly decreased the villous height and villi: crypt ratio in duodenum (P<0.05), as well as the maltase activity in jejunum (P<0.05). In addition, IUGR significantly decreased the serum concentrations of IgA, IL-1βand IL-10 (P<0.05), as well as the percentage of peripheral lymphocytes (P<0.05). Meanwhile, the down-regulation of innate immunity-related genes such as TOLLIP (P<0.05), TLR-9 (P = 0.08) and TLR-2 (P = 0.07) was observed in the ileum of IUGR relative to NBW piglets. Regardless of birth weight, however, feeding NT diet markedly decreased (P<0.05) feed conversion ratio, increased the villous height in duodenum (P<0.05), activities of lactase and maltase in jejunum (P<0.05), count of peripheral leukocytes (P<0.05), serum concentrations of IgA and IL-1β as well as gene expressions of TLR-9, TLR-4 and TOLLIP in ileum (P<0.05). In addition, expressions of tight junction proteins (Claudin-1 and ZO-1) in ileum were markedly increased by feeding NT diet relative to CON diet (P<0.05). These results indicated that IUGR impaired growth performance, intestinal and immune function, but dietary nucleotides supplementation improved nutrients utilization, intestinal function and immunity.

This study was aimed to investigate the effect of phospholipid transfer protein (PLTP) on cigarette smoke extract (CSE)-induced alteration of the cell cycle and the possible mechanism. Male Wistar rats and the rat alveolar epithelial cell line (RLE-6TN) were exposed to normal air or different concentrations of CSE. Then PLTP siRNA was transfected into cells and an inhibitor of transforming growth factor-β1 (TGF-β1) was administered prior to CSE exposure. Histological changes and cell cycle stage were recorded, as were the expression levels of PLTP, TGF-β1, CyclinD1 and CDK4. Resulting morphological changes included diffuse interstitial substance incrassation and elevated alveolar rupturing. Flow cytometry analysis revealed an increase in the number of cells in the G1 phase in a time- and dose-related manner. Both PLTP and TGF-β1 were up-regulated at protein and mRNA levels, whereas CyclinD1 and CDK4 expression was down-regulated after CSE exposure. Furthermore, PLTP siRNA significantly suppressed CSE-induced TGF-β1 expression, resulting in up-regulation of CyclinD1 and CDK4, but the TGF-β1 inhibitor was not able to abrogate CSE-induced PLTP over-expression. In conclusion, PLTP may operate upstream of the TGF-β1/CyclinD1/CDK4 pathway and may mediate the CSE-induced G1 arrest in RLE-6TN cells. Our work provides some new insight into the relation between PLTP and cell cycle progression.

Epidermal growth factor receptor (EGFR) has been used as the target in drug design for cancer treatment including the liver cancer. Men and women have different levels of EGFR expression during the life. The whole genome expression profiles of livers of recombinant inbred (RI) strains derived from C57BL/6J (B6) X DBA/2J (D2) were used to compare three major molecular aspects of Egfr gene: the relative expression levels, gene network and eQTLs that regulate the expression of Egfr between female and male mice. Our data suggest that there is a significant difference in the expression levels in the liver between female and male mice. Several important genes in the gene network of Egfr are differentially expressed between female and male mice. The regulatory elements for the expression levels of Egfr between female and male mice are also different. In summary, our data reveals an important sex difference in the Egfr pathways in the liver of the mice. These data may have substantial impact on drug development and dosage determinant for women and men in the clinical trials.

Schizophrenia (SZ) and bipolar disorder (BP) are complex genetic disorders. Their appearance is also likely informed by as yet only partially described epigenetic contributions. Using a sequencing-based method for genome-wide analysis, we quantitatively compared the blood DNA methylation landscapes in SZ and BP subjects to control, both in an understudied population, Hispanics along the US-Mexico border. Remarkably, we identified thousands of differentially methylated regions for SZ and BP preferentially located in promoters 3'-UTRs and 5'-UTRs of genes. Distinct patterns of aberrant methylation of promoter sequences were located surrounding transcription start sites. In these instances, aberrant methylation occurred in CpG islands (CGIs) as well as in flanking regions as well as in CGI sparse promoters. Pathway analysis of genes displaying these distinct aberrant promoter methylation patterns showed enhancement of epigenetic changes in numerous genes previously related to psychiatric disorders and neurodevelopment. Integration of gene expression data further suggests that in SZ aberrant promoter methylation is significantly associated with altered gene transcription. In particular, we found significant associations between (1) promoter CGIs hypermethylation with gene repression and (2) CGI 3'-shore hypomethylation with increased gene expression. Finally, we constructed a specific methylation analysis platform that facilitates viewing and comparing aberrant genome methylation in human neuropsychiatric disorders.

Inflammation and platelet activation are critical phenomena in the setting of decompression sickness. Clopidogrel (Clo) inhibits platelet activation and may also reduce inflammation. The goal of this study was to investigate if Clo had a protective role in decompression sickness (DCS) through anti-inflammation way. Male Sprague-Dawley rats (n=111) were assigned to three groups: control+vehicle group, DCS+vehicle, DCS+Clo group. The experimental group received 50 mg/kg of Clo or vehicle for 3 days, then compressed to 1,600 kPa (150 msw) in 28 s, maintained at 150 msw for 242 s and decompressed to surface at 3m/s. In a control experiment, rats were also treated with vehicle for 3 days and maintained at atmospheric pressure for an equivalent period of time. Clinical assessment took place over a period of 30 min after surfacing. At the end, blood samples were collected for blood cells counts and cytokine detection. The pathology and the wet/dry ratio of lung tissues, immunohistochemical detection of lung tissue CD41 expression, the numbers of P-selectin positive platelets and platelet-leukocyte conjugates in blood were tested. We found that Clo significantly reduced the DCS mortality risk (mortality rate: 11/45 with Clo vs. 28/46 in the untreated group, P<0.01). Clo reduced the lung injury, the wet/dry ratio of lung, the accumulation of platelet and leukocyte in lung, the fall in platelet count, the WBC count, the numbers of activated platelets and platelet-leukocyte complexes in peripheral blood. It was concluded that Clo can play a protective role in decompression sickness through reducing post-decompression platelet activation and inflammatory process.

A spontaneous late-ripening mutant of 'Jincheng' (C. sinensis L. Osbeck) sweet orange exhibited a delay of fruit pigmentation and harvesting. In this work, we studied the processes of orange fruit ripening through the comparative analysis between the Jincheng mutant and its wild type. This study revealed that the fruit quality began to differ on 166th days after anthesis. At this stage, fruits were subjected to transcriptome analysis by RNA sequencing. 13,412 differentially expressed unigenes (DEGs) were found. Of these unigenes, 75.8% were down-regulated in the wild type, suggesting that the transcription level of wild type was lower than that of the mutant during this stage. These DEGs were mainly clustered into five pathways: metabolic pathways, plant-pathogen interaction, spliceosome, biosynthesis of plant hormones and biosynthesis of phenylpropanoids. Therefore, the expression profiles of the genes that are involved in abscisic acid, sucrose, and jasmonic acid metabolism and signal transduction pathways were analyzed during the six fruit ripening stages. The results revealed the regulation mechanism of sweet orange fruit ripening metabolism in the following four aspects: First, the more mature orange fruits were, the lower the transcription levels were. Second, the expression level of PME boosted with the maturity of the citrus fruit. Therefore, the expression level of PME might represent the degree of the orange fruit ripeness. Third, the interaction of PP2C, PYR/PYL, and SnRK2 was peculiar to the orange fruit ripening process. Fourth, abscisic acid, sucrose, and jasmonic acid all took part in orange fruit ripening process and might interact with each other. These findings provide an insight into the intricate process of sweet orange fruit ripening.

The development of an effective vaccine is critical for prevention of a Middle East respiratory syndrome coronavirus (MERS-CoV) pandemic. Some studies have indicated the receptor-binding domain (RBD) protein of MERS-CoV spike (S) is a good candidate antigen for a MERS-CoV subunit vaccine. However, highly purified proteins are typically not inherently immunogenic. We hypothesised that humoral and cell-mediated immunity would be improved with a modification of the vaccination regimen. Therefore, the immunogenicity of a novel MERS-CoV RBD-based subunit vaccine was tested in mice using different adjuvant formulations and delivery routes. Different vaccination regimens were compared in BALB/c mice immunized 3 times intramuscularly (i.m.) with a vaccine containing 10 µg of recombinant MERS-CoV RBD in combination with either aluminium hydroxide (alum) alone, alum and polyriboinosinic acid (poly I:C) or alum and cysteine-phosphate-guanine (CpG) oligodeoxynucleotides (ODN). The immune responses of mice vaccinated with RBD, incomplete Freund's adjuvant (IFA) and CpG ODN by a subcutaneous (s.c.) route were also investigated. We evaluated the induction of RBD-specific humoral immunity (total IgG and neutralizing antibodies) and cellular immunity (ELISpot assay for IFN-γ spot-forming cells and splenocyte cytokine production). Our findings indicated that the combination of alum and CpG ODN optimized the development of RBD-specific humoral and cellular immunity following subunit vaccination. Interestingly, robust RBD-specific antibody and T-cell responses were induced in mice immunized with the rRBD protein in combination with IFA and CpG ODN, but low level of neutralizing antibodies were elicited. Our data suggest that murine immunity following subunit vaccination can be tailored using adjuvant combinations and delivery routes. The vaccination regimen used in this study is promising and could improve the protection offered by the MERS-CoV subunit vaccine by eliciting effective humoral and cellular immune responses.

The composition of polyunsaturated fatty acids (PUFAs) in triacylglycerols (TAGs) is key to health benefits and for oil applications, yet the underlying genetic mechanism remains poorly understood. In this study, by in silico, ex vivo, and in vivo profiling of type-2 diacylglycerol acyltransferases (DGAT2s) in Nannochloropsis oceanica we revealed two novel PUFA-preferring enzymes that discriminate individual PUFA species in TAG assembly, with NoDGAT2J for linoleic acid (LA) and NoDGAT2K for eicosapentaenoic acid (EPA). The LA and EPA composition of TAG molecules is mediated in vivo via the functional partitioning between NoDGAT2J and 2K, both of which are localized in the chloroplast envelope. By modulating transcript abundance of the DGAT2s, an N. oceanica strain bank was created, where proportions of LA and EPA in TAG vary by 18.7-fold (between 0.21% and 3.92% dry weight) and 34.7-fold (between 0.09% and 3.12% dry weight), respectively. These findings lay the foundation for producing designer TAG molecules with tailored health benefits or for biofuel applications in industrial microalgae and higher-plant crops.

Carnitine palmitoyltransferase 1 (Cpt1a) is a rate-limiting enzyme that mediates the transport of fatty acids into the mitochondria for subsequent beta-oxidation. The objective of this study was to uncover how diet mediates the transcriptional regulation of Cpt1a. Pregnant Sprague Dawley rats were exposed to either a high-fat (HF) or low-fat control diet during gestation and lactation. At weaning, male offspring received either a HF or control diet, creating 4 groups: lifelong control diet (C/C; n = 12), perinatal HF diet (HF/C; n = 9), post-weaning HF diet (C/HF; n = 10), and lifelong HF diet (HF/HF; n = 10). Only HF/HF animals had higher hepatic Cpt1a mRNA expression than C/C. Epigenetic analysis revealed reduced DNA methylation (DNAMe) and increased histone 3 lysine 4 dimethylation (H3K4Me2) upstream and within the promoter of Cpt1a in the HF/HF group. This was accompanied by increased peroxisome proliferator activated receptor alpha (PPARα) and CCAAT/enhancer binding protein beta (C/EBPβ) binding directly downstream of the Cpt1a transcription start site within the first intron. Findings were confirmed in rat hepatoma H4IIEC3 cells treated with non-esterified fatty acid (NEFA). After 12 h of NEFA treatment, there was an enrichment of SWI/SNF related matrix associated actin dependent regulator of chromatin subfamily D member 1 (BAF60a or SMARCD1) in the first intron of Cpt1a. We conclude that dietary fat elevates hepatic Cpt1a expression via a highly coordinated transcriptional mechanism involving increased H3K4Me2, reduced DNAMe, and recruitment of C/EBPβ, PPARα, PGC1α, and BAF60a to the gene.

In Drosophila, a complex consisting of Calypso and ASX catalyzes H2A deubiquitination and has been reported to act as part of the Polycomb machinery in transcriptional silencing. The mammalian homologs of these proteins (BAP1 and ASXL1/2/3, respectively), are frequently mutated in various cancer types, yet their precise functions remain unclear. Using an integrative approach based on isogenic cell lines generated with CRISPR/Cas9, we uncover an unanticipated role for BAP1 in gene activation. This function requires the assembly of an enzymatically active BAP1-associated core complex (BAP1.com) containing one of the redundant ASXL proteins. We investigate the mechanism underlying BAP1.com-mediated transcriptional regulation and show that it does not participate in Polycomb-mediated silencing. Instead, our results establish that the function of BAP1.com is to safeguard transcriptionally active genes against silencing by the Polycomb Repressive Complex 1.

Intraparenchymal transplantation of neural stem/progenitor cells (NSPCs) has been extensively investigated in animal models of ischemic stroke. However, the reported therapeutic efficacy was inconsistent among studies. To evaluate this situation, PubMed, Embase, and Web of Science databases were searched for preclinical studies using NSPC intraparenchymal transplantation in ischemic stroke animals. Data of study quality score, neurobehavioral (mNSS, rotarod test, and cylinder test) and histological (infarct volume) outcomes, cell therapy-related serious adverse events, and related cellular mechanisms were extracted for meta-analysis and systematic review. A total of 62 studies containing 73 treatment arms were included according to our criterion, with a mean quality score of 5.10 in 10. Among these studies, almost half of the studies claimed no adverse events of tumorigenesis. The finally pooled effect sizes for neurobehavioral and histological assessments were large (1.27 for mNSS, 1.63 for the rotarod test, 0.71 for the cylinder test, and 1.11 for infarct volume reduction). With further analysis, it was found that the administration time poststroke, NSPC donor species, and transplantation immunogenicity had close correlations with the degree of infarct volume reduction. The NSPC dosage delivered into the brain parenchyma was also negatively correlated with the effect of the cylinder test. Intriguingly, endogenous apoptosis inhibition and axonal regeneration played the most critical role in intraparenchymal NSPC transplantation among the cellular mechanisms. These results indicate that intraparenchymal NSPC transplantation is beneficial for neurobehavioral and histological improvement and is relatively safe for ischemic stroke animals. Therefore, intraparenchymal NSPC transplantation is a promising treatment for stroke patients.

This data is generated from the analysis of similarities and differences in gene expression levels and pathways among genes (VegfA, VegfB, VegfC, and Pgf) in Vegf family using whole genome expression data generated from normal retina of eighty strains of mice. The results have been published in doi:10.1016/j.exer.2018.06.024 (Cui et al., 2018) [1]. Fig. 1 shows the expression quantitative trait loci (eQTL) that regulate the expression level of each gene in the Vegf family. The other three figure show the overlapped genes among the top 500 genes that their expression levels are most closely correlated to each of the Vegf genes. The four tables contain the information of top 50 genes that their expression levels are most closely correlated to each of the Vegf genes, and the correlation of the top 50 genes from one gene to the other genes in the Vegf family.

Growth differentiation factor 9 (GDF9) gene is an effective intra-ovarian regulator; it plays a crucial role in early folliculogenesis in female mammals. The non synonymous mutations: g.3905A > C (also known as p.Gln320Pro/Q320P) and g.4135G > A (also know as p.Val397Ile/V397I), are two well-known and controversial single nucleotide polymorphisms (SNPs) within GDF9 gene in goats with different prolificacy, and so far, there were no studies on linkage between Q320P and V397I. Therefore, the aim of this work was to study whether Q320P and V397I mutations have a significant effect on litter size, in Shaanbei white cashmere goats (SBWC, n = 1511), and to explore the specific relationship between these two SNPs. The results showed that both of Q320P and V397I mutations exhibited three genotypes; the minor allele frequencies (MAF) of the SNPs were 0.286 and 0.477, respectively; and these two SNPs were in strong linkage disequilibrium (D' = 0.976, r2 = 0.348) in the studied goats. Moreover, association analyses revealed that Q320P was significantly associated with the first-born litter size in goats irrespective of the sample size (n = 1511; P = 0.008), while V397I significantly affected litter size until the sample size crossed 1300 (P = 0.015). Meanwhile, the diplotypes PP-II and QP-VI were observed to have a superior effect on litter size (P = 3.78 × 10-5) to that of the haplotypes (P = 1.12 × 10-7). Thus, the findings led us to assume that Q320P mutation was the major SNP affecting goat litter size. These findings can provide useful DNA markers for selecting superior individuals in marker-assisted selection (MAS) for breeding in relation to fecundity in goats.

Immune-enhancing effects of three kinds of purple sweet potato polysaccharides (PSPPs) including water-soluble polysaccharide (WSP), dilute alkali-soluble polysaccharide (DASP) and concentrated alkali-soluble polysaccharide (CASP) were evaluated. Scanning electron microscope analysis showed that all PSPPs could stimulate the formation of microvilli-like structures in cellular surfaces, which was possibly related to activation of macrophages. Neutral red uptake assay showed that PSPPs could increase the phagocytic activity of cells. High dose (400 μg/mL) of PSPPs could notably augment the level of nitric oxide (NO). ELISA analysis revealed that 200 and 400 μg/mL of PSPPs distinctly elevated the production of IL-1β. Cells received 200 and 400 μg/mL of WSP as well as 400 μg/mL of DASP exhibited higher level of IL-6. Results of animal experiments showed that WSP treatment (400 mg/kg) could promote the secretions of IgA, IgG, IgM and sIgA in both normal and immunosuppressed mice. Moreover, CASP treatment (400 mg/kg) elevated the production of IgM in the serum of normal and immunosuppressive mice, while DASP (400 mg/kg) only improved the secretion of IgM in normal mice. In summary, all three polysaccharides can stimulate immune responses of macrophages and positively regulate adaptive immunity by enhancing the production of immunoglobulins in mice.

Frequent somatic mutations of BRAF and CTNNB1 were identified in both histological subtypes of craniopharyngioma (adamantinomatous and papillary) which shed light on target therapy to cure this oncogenic disease. The aim of this study was to investigate the noninvasive MRI-based radiomics diagnosis to detect BRAF and CTNNB1 mutations in craniopharyngioma patients.