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Abdominal subcutaneous fat deposition (ASFD) is not only related to meat quality in the pig industry but also to human health in medicine. It is of great value to elucidate the potential molecular mechanisms of ASFD. The present study aims to identify obese-specific biomarkers and key pathways correlated with ASFD in pigs. The ASF-related mRNA expression dataset GSE136754 was retrieved from the Gene Expression Omnibus (GEO) database and systematically analyzed using a comprehensive bioinformatics method. A total of 565 differentially expressed genes (DEGs) were identified between three obese and three lean pigs, and these DEGs were mainly involved in the p53 signaling pathway, MAPK signaling pathway and fatty acid metabolism. A protein-protein interaction (PPI) network, consisting of 540 nodes and 1,065 edges, was constructed, and the top ten genes with the highest degree scores—ABL1, HDAC1, CDC42, HDAC2, MRPS5, MRPS10, MDM2, JUP, RPL7L1 and UQCRFS1—were identified as hub genes in the whole PPI network. Especially HDAC1, MDM2, MRPS10 and RPL7L1 were identified as potential robust obese-specific biomarkers due to their significant differences in single gene expression levels and high ROC area; this was further verified by quantitative real-time PCR (qRT-PCR) on abdominal subcutaneous fat samples from obese-type (Saba) and lean-type (Large White) pigs. Additionally, a mRNA-miRNA-lncRNA ceRNA network consisting of four potential biomarkers, 15 miRNAs and 51 lncRNAs was established, and two targeted lncRNAs with more connections, XIST and NEAT1, were identified as potentially important regulatory factors. The findings of this study may provide novel insights into the molecular mechanism involved in ASFD. [ABSTRACT FROM AUTHOR]

The effect of schizophrenia (SCZ) genetic risk on gene expression in brain remains elusive. A popular approach to this problem has been the application of gene co-expression network algorithms (e.g., WGCNA). To improve reliability with this method it is critical to remove unwanted sources of variance while also preserving biological signals of interest. In this WCGNA study of RNA-Seq data from postmortem prefrontal cortex (78 neurotypical donors, EUR ancestry), we tested the effects of SCZ genetic risk on co-expression networks. Specifically, we implemented a novel design in which gene expression was adjusted by linear regression models to preserve or remove variance explained by biological signal of interest (GWAS genomic scores for SCZ risk—(GS-SCZ), and genomic scores- GS of height (GS-Ht) as a negative control), while removing variance explained by covariates of non-interest. We calculated co-expression networks from adjusted expression (GS-SCZ and GS-Ht preserved or removed), and consensus between them (representative of a "background" network free of genomic scores effects). We then tested the overlap between GS-SCZ preserved modules and background networks reasoning that modules with reduced overlap would be most affected by GS-SCZ biology. Additionally, we tested these modules for convergence of SCZ risk (i.e., enrichment in PGC3 SCZ GWAS priority genes, enrichment in SCZ risk heritability and relevant biological ontologies. Our results highlight key aspects of GS-SCZ effects on brain co-expression networks, specifically: 1) preserving/removing SCZ genetic risk alters the co-expression modules; 2) biological pathways enriched in modules affected by GS-SCZ implicate processes of transcription, translation and metabolism that converge to influence synaptic transmission; 3) priority PGC3 SCZ GWAS genes and SCZ risk heritability are enriched in modules associated with GS-SCZ effects. Overall, our results indicate that gene co-expression networks that selectively integrate information about genetic risk can reveal novel combinations of biological pathways involved in schizophrenia. Author summary: Genetic risk for schizophrenia (SCZ) is linked to brain connectivity at multiple levels, from molecular interactions to coherent cognitive processing. Biological mechanisms by which SCZ genetic risk affects brain connectivity are generally unknown. In this study we sought to uncover some of these mechanisms by focusing on gene co-expression networks calculated from RNA-Seq data extracted from postmortem DLPFC. We created co-expression networks from gene expression adjusted to account for, or to remove the likely effects of genomic (polygenic) scores of SCZ risk. We minimized potential confounding effects of illness state or treatment on gene expression by using only brains from donors without a history of mental disorder. We used as a control, co-expression networks from gene expression adjusted to account for effects of genomic scores of height- a normative trait. Our results show subtle and widespread effects of SCZ genomic scores on DLPFC co-expression networks. Gene sets from co-expression modules adjusted for SCZ genetic risk harbor biological significance represented by neuronal functions, but also by interacting pathways of general cellular processes like transcription, translation and metabolism. Our findings highlight possible avenues for identifying regulatory targets of gene expression in schizophrenia. [ABSTRACT FROM AUTHOR]

Background: Congenital pulmonary airway malformation (CPAM) is the most frequent pulmonary developmental malformation and the pathophysiology remains poorly understood. This study aimed to identify the characteristic gene expression patterns and the marker genes essential to CPAM. Methods: Tissues from the cystic area displaying CPAM and the area of normal appearance were obtained during surgery. Bulk RNA sequencing (RNA-seq) and single-cell RNA sequencing (scRNA-seq) were performed for integrating analysis. Iterative weighted gene correlation network analysis (iWGCNA) was used to identify specifically expressed genes to CPAM. Results: In total, 2074 genes were significantly differentially expressed between the CPAM and control areas. Of these differentially expressed genes (DEGs), 1675 genes were up-regulated and 399 genes were down-regulated. Gene ontology analysis revealed these DEGs were specifically enriched in ciliated epithelium and involved in immune response. We also identified several CPAM-related modules by iWGCNA, among them, P15_I4_M3 module was the most influential module for distinguishing CPAMs from controls. By combining the analysis of the expression dataset from RNA-seq and scRNA-seq, SPOCK2, STX11, and ZNF331 were highlighted in CPAM. Conclusions: Through our analysis of expression datasets from both scRNA-seq and bulk RNA-seq of tissues obtained from patients with CPAM, we identified the characteristic gene expression patterns associated with the condition. Our findings suggest that SPOCK2 could be a potential biomarker gene for the diagnosis and therapeutic target in the development of CPAM, whereas STX11 and ZNF331 might serve as prognostic markers for this condition. Further investigations with larger samples and function studies are necessary to confirm the involvement of these genes in CPAM. [ABSTRACT FROM AUTHOR]

Nitrate accumulation is a major factor for the secondary salinization of greenhouse soil in China. Our previous study pointed out that a low ratio of red:far-red light (R:FR) can improve salt tolerance in pakchoi under excessive nitrate stress. However, the nitrogen metabolism mechanism is still unclear. To detect the effect of a low R:FR ratio on nitrogen metabolism of pakchoi under excessive nitrate stress, two extra additions of nitrogen of 80 mmol·L−1 NO3− (H80) and 160 mmol·L−1 NO3− (H160) with/without a low R:FR ratio (R:FR = 0.7) were set, and the growth index, chlorophyll content, key enzymes in nitrogen metabolism, nitrate and glutamic acid content and NRT gene expression level of pakchoi leaves were examined. The results indicated that a low ratio of R:FR could alleviate the reduction in growth and chlorophyll content in pakchoi under high-level nitrogen stress (H80 and H160). The activity of nitrate reductase (NR), glutamine synthetase (GS) and glutamine synthetase (GOGAT) decreased under H80 and H160 conditions, except of NR with the H80 treatment. The activity of glutamate dehydrogenase (GDH) increased under H80 treatment, but decreased under H160 treatment. However, the activity of GDH decreased further by reducing the ratio of R:FR. Excessive nitrate stress increased the nitrate content, and a low R:FR ratio could inhibit nitrate accumulation. However, the change in glutamic acid content was significantly increased under a low R:FR ratio without stress. Under the high-nitrogen level treatment (H160), the use of a low ratio of R:FR increased NRT gene expression. Therefore, a low R:FR ratio (R:FR = 0.7) could effectively promote the growth of pakchoi and improve its nitrogen metabolism, thus alleviating the stress effect of a high level of nitrogen in pakchoi. [ABSTRACT FROM AUTHOR]

Necrosis caused by soybean mosaic virus (SMV) has not been specifically distinguished from susceptible symptoms. The molecular mechanism for the occurrence of necrosis is largely overlooked in soybean genetic research. Field evaluation reveals that SMV disease seriously influences soybean production as indicated by decreasing 22.4% ~ 77.0% and 8.8% ~ 17.0% of yield and quality production, respectively. To expand molecular mechanism behind necrotic reactions, transcriptomic data obtained from the asymptomatic, mosaic, and necrotic pools were assessed. Compared between asymptomatic and mosaic plants, 1689 and 1752 up- and down-regulated differentially expressed genes (DEGs) were specifically found in necrotic plants. Interestingly, the top five enriched pathways with up-regulated DEGs were highly related to the process of the stress response, whereas the top three enriched pathways with down-regulated DEGs were highly related to the process of photosynthesis, demonstrating that defense systems are extensively activated, while the photosynthesis systems were severely destroyed. Further, results of the phylogenetic tree based on gene expression pattern and an amino acid sequence and validation experiments discovered three PR1 genes, Glyma.15G062400, Glyma.15G062500, and Glyma.15G062700, which were especially expressed in necrotic leaves. Meanwhile, exogenous salicylic acid (SA) but not methyl jasmonate (MeJA) could induce the three PR1 gene expressions on healthy leaves. Contrastingly, exogenous SA obviously decreased the expression level of Glyma.15G062400, Glyma.15G062500, and concentration of SMV, but increased Glyma.15G062700 expression in necrotic leaves. These results showed that GmPR1 is associated with the development of SMV-induced necrotic symptoms in soybean. Glyma.15G062400, Glyma.15G062500, and Glyma.15G062700 is up-regulated in necrotic leaves at the transcriptional levels, which will greatly facilitate a better understanding of the mechanism behind necrosis caused by SMV disease. [ABSTRACT FROM AUTHOR]

The polysaccharides found in Lentinula edodes have a variety of medicinal properties, such as anti-tumor and anti-viral effects, but their content in L. edodes sporophores is very low. In this study, Fe2+ was added to the liquid fermentation medium of L. edodes to analyze its effects on mycelial growth, polysaccharide and enzyme production, gene expression, and the activities of enzymes involved in polysaccharide biosynthesis, and in vitro antioxidation of polysaccharides. The results showed that when 200 mg/L of Fe2+ was added, with 7 days of shaking at 150 rpm and 3 days of static culture, the biomass reached its highest value (0.28 mg/50 mL) 50 days after the addition of Fe2+. Besides, Fe2+ addition also enhanced intracellular polysaccharide (IPS) and exopolysaccharide (EPS) productions, the levels of which were 2.98- and 1.79-fold higher than the control. The activities of the enzymes involved in polysaccharides biosynthesis, including phosphoglucomutase (PGM), phosphoglucose isomerase (PGI), and UDPG-pyrophosphorylase (UGP) were also increased under Fe2+ addition. Maximum PGI activity reached 1525.20 U/mg 30 days after Fe2+ addition, whereas PGM and UGP activities reached 3607.05 U/mg and 3823.27 U/mg 60 days after Fe2+ addition, respectively. The Pearson correlation coefficient showed a strong correlation (p < 0.01) between IPS production and PGM and UGP activities. The corresponding coding genes of the three enzymes were also upregulated. When evaluating the in vitro antioxidant activities of polysaccharides, EPS from all Fe2+-treated cultures exhibited significantly better capacity (p < 0.05) for scavenging -OH radicals. The results of the two-way ANOVA indicated that the abilities of polysaccharides to scavenge O2− radicals were significantly (p < 0.01) affected by Fe2+ concentration and incubation time. These results indicated that the addition of iron provided a good way to achieve desirable biomass, polysaccharide production, and the in vitro antioxidation of polysaccharides from L. edodes. [ABSTRACT FROM AUTHOR]

Background. Myasthenia gravis (MG) is a rare autoimmune disease with clinical symptoms of fluctuating muscle weakness. Due to the side effects of current therapies, there is an urgent need for a new medication for MG treatment. Nux vomica is a traditional Chinese medicine used in various diseases. However, the mechanism of action of Nux vomica against MG remains unclear. Methods. Network pharmacology was used to explore the underlying mechanisms of Nux vomica in MG treatment, which was validated using molecular docking and in vivo experiments in mice. Results. Twelve bioactive compounds and 72 targets in Nux vomica were screened. Seventy-nine myasthenia-related targets were obtained from the GENECARD and DisGeNET databases. PPI networks of Nux vomica- and myasthenia-related targets were constructed using Bisogenet, and these two networks were subsequently merged into an intersection to establish a core-target PPI network that consisted of 204 nodes and 4,668 edges. KEGG enrichment analysis indicated that 132 pathways were enriched in 204 core targets. In addition, we obtained 50 docking pairs via molecular docking. In vivo experiments revealed that Nux vomica can improve the symptoms of MG. Conclusion. Nux vomica is involved in the pathogenesis of MG through the "multicomponent-target-pathway" mechanism. [ABSTRACT FROM AUTHOR]

Objectives: Long non-coding RNAs (lncRNAs) are key regulators involved in the progression of glioma, and many functional lncRNAs are yet to be identified. This study aimed to explore the function of CHRM3-AS2, a rarely reported lncRNA, in glioma, as well as the underlying mechanisms involving miR-370-5p/KLF4. Methods: Differentially expressed RNAs (DERs) were screened from two gene expression profiles of glioblastoma (GBM). Fluorescence in situ hybridisation was performed to determine the subcellular localisation of CHRM3-AS2. Cell viability, colony formation, apoptosis, migration, and invasion were evaluated using cell counting kit-8, colony counts, flow cytometry, wound healing, and Transwell assays, respectively. mRNA and protein expression of specific genes were measured using quantitative real-time polymerase chain reaction and western blotting, respectively. Dual luciferase reporter gene, RNA immunoprecipitation, and RNA pull-down assays were performed to identify the target relationships. A mouse xenograft model was established for in vivo validation. Results: CHRM3-AS2 was screened as a prognosis-associated DER in GBM. CHRM3-AS2 expression was up-regulated in glioma cells, and CHRM3-AS2 was localised in the cytoplasm. Silencing of CHRM3-AS2 expression inhibited cell viability, colony formation, migration, and invasion and promoted apoptosis of U251 and SHG-44 cells. In addition, CHRM3-AS2 targeted miR-370-5p/KLF4 in glioma cells. The anti-tumour effect of CHRM3-AS2 silencing was weakened by miR-370-5p silencing or KLF4 overexpression. In vivo , silencing of CHRM3-AS2 expression inhibited tumour growth and Ki67 expression in mice. Overexpression of KLF4 also weakened the anti-tumour effect of CHRM3-AS2 silencing in mice. Conclusions: Silencing of CHRM3-AS2 expression inhibited the malignant progression of glioma by regulating miR-370-5p/KLF4 expression. [ABSTRACT FROM AUTHOR]

Background: Long noncoding RNAs (lncRNAs) are closely related to the occurrence and development of cancer. Gastric adenocarcinoma-associated, positive CD44 regulator, long intergenic noncoding RNA (GAPLINC) is a recently identified lncRNA that can actively participate in the tumorigenesis of various cancers. Here, we investigated the functional roles and mechanism of GAPLINC in renal cell carcinoma (RCC) development. Methods: Differentially expressed lncRNAs between RCC tissues and normal kidney tissues were detected by using a microarray technique. RNA sequencing was applied to explore the mRNA expression profile changes after GAPLINC silencing. After gain- and loss-of-function approaches were implemented, the effect of GAPLINC on RCC in vitro and in vivo was assessed by cell proliferation and migration assays. Moreover, rescue experiments and luciferase reporter assays were used to study the interactions between GAPLINC, miR-135b-5p and CSF1. Results: GAPLINC was significantly upregulated in RCC tissues and cell lines and was associated with a poor prognosis in RCC patients. Knockdown of GAPLINC repressed RCC growth in vitro and in vivo , while overexpression of GAPLINC exhibited the opposite effect. Mechanistically, we found that GAPLINC upregulates oncogene CSF1 expression by acting as a sponge of miR-135b-5p. Conclusion: Taken together, our results suggest that GAPLINC is a novel prognostic marker and molecular therapeutic target for RCC. [ABSTRACT FROM AUTHOR]