Porcine skeletal muscle fibres are classified based on their different physiological and biochemical properties. Muscle fibre phenotype is regulated by several independent signalling pathways, including the mitogen-activated protein kinase (MAPK), nuclear factor of activated T cells (NFAT), myocyte enhancer factor 2 (MEF2) and peroxisome proliferator-activated receptor (PPAR) signalling pathways. MicroRNAs are non-coding small RNAs that regulate many biological processes. However, their function in muscle fibre type regulation remains unclear. The aim of our study was to identify miRNAs that regulate muscle fibre type during porcine growth to help understand the miRNA regulation mechanism of fibre differentiation. We performed Solexa/Illumina deep sequencing for the microRNAome during 3 muscle growth stages (63, 98 and 161 d). In this study, 271 mature miRNAs and 243 pre-miRNAs were identified. We detected 472 novel miRNAs in the muscle samples. Among the mature miRNAs, there are 23 highest expression miRNAs (over 10,000 RPM), account for 85.3% of the total counts of mature miRNAs., including 10 (43.5%) muscle-related miRNAs (ssc-miR-133a-3p, ssc-miR-486, ssc-miR-1, ssc-miR-143-3p, ssc-miR-30a-5p, ssc-miR-181a, ssc-miR-148a-3p, ssc-miR-92a, ssc-miR-21, ssc-miR-126-5p). Particularly, both ssc-miR-1 and ssc-miR-133 belong to the MyomiRs, which control muscle myosin content, myofibre identity and muscle performance. The involvement of these miRNAs in muscle fibre phenotype provides new insight into the mechanism of muscle fibre regulation underlying muscle development. Furthermore, we performed cell transfection experiment. Overexpression/inhibition of ssc-miR-143-3p in porcine skeletal muscle satellite cell induced an/a increase/reduction of the slow muscle fibre gene and protein (MYH7), indicating that miR-143 activity regulated muscle fibre differentiate in skeletal muscle. And it regulate MYH7 through the HDAC4-MEF2 pathway.

CpG oligodeoxynucleotides (ODNs) can induce immunological changes in non-obese diabetic (NOD) mice and increase embryo loss, but little is known about the mechanism. This study aimed to determine the role of adiponectin in CpG ODN-induced pregnancy failure.

To provide a comprehensive overview of temporal trends in cancer incidence during 1973-2010 in urban Shanghai.

Increasing evidence suggests that ion channels not only regulate electric signaling in excitable cells but also play important roles in the development of brain tumor. However, the roles of ion channels in glioma remain controversial. In the present study, we systematically analyzed the expression patterns of ion channel genes in a cohort of Chinese patients with glioma using RNAseq expression profiling. First, a molecular signature comprising three ion channel genes (KCNN4, KCNB1 and KCNJ10) was identified using Univariate Cox regression and two-tailed student's t test conducted in overall survival (OS) and gene expression. We assigned a risk score based on three ion channel genes to each primary Glioblastoma multiforme (pGBM) patient. We demonstrated that pGBM patients who had a high risk of unfavorable outcome were sensitive to chemotherapy. Next, we screened the three ion genes-based signature in different molecular glioma subtypes. The signature showed a Mesenchymal subtype and wild-type IDH1 preference. Gene ontology (GO) analysis for the functional annotation of the signature showed that patients with high-risk scores tended to exhibit the increased expression of proteins associated with apoptosis, immune response, cell adhesion and motion and vasculature development. Gene Set Enrichment Analysis (GSEA) results showed that pathways associated with negative regulation of programmed cell death, cell proliferation and locomotory behavior were highly expressed in the high-risk group. These results suggest that ion channel gene expression could improve the subtype classification in gliomas at the molecular level. The findings in the present study have been validated in two independent cohorts.

Numerous population-based studies have suggested that socio-economic status (SES) is associated with cognitive performance, but few nationally representative epidemiological studies on cognitive performance with a large sample of older adults are available in China. And many studies explore the factors associated with cognitive performance, mainly focusing on individual level and more rarely on multiple levels that include the individual and community.

Chronic diseases contribute a large share of disease burden in low- and middle-income countries (LMICs). Chronic diseases have a tendency to occur simultaneously and where there are two or more such conditions, this is termed as 'multimorbidity'. Multimorbidity is associated with adverse health outcomes, but limited research has been undertaken in LMICs. Therefore, this study examines the prevalence and correlates of multimorbidity as well as the associations between multimorbidity and self-rated health, activities of daily living (ADLs), quality of life, and depression across six LMICs.

The protein kinase C (PKC) activator phorbol 12-myristate 13-acetate (PMA) induces transition of the epithelial MCF-7 cell line to a mesenchymal phenotype. A subset of the resulting mesenchymal cells has surface markers characteristics of a cancer stem cell (CSC) population. We profiled the transcriptome changes associated with the epithelial to mesenchymal transition and those that occurred in the CSC subset. Using a siRNA knockdown strategy, we examined the extent to which these changes were dependent on the PKC family member, PKC-θ. The importance of the cytoplasmic signaling role of this kinase is well established and in this study, we have shown by PKC-θ ChIP-sequencing analysis that this kinase has a dual role with the ability to also associate with chromatin on a subset of PKC-θ dependent genes. In the associated manuscript (Zafar et al., 2014 [5]) we presented evidence for the first time showing that this nuclear role of PKC-θ is also important for gene induction and mesenchymal/CSC phenotype. Here we describe the analysis associated with the transcriptome and ChIP-seq data presented in Zafar et al. (2014) [5] and uploaded to NCBI Gene Expression Omnibus (GSE53335).

Caerulein-induced acute pancreatitis accelerates the progression of pancreatic intraepithelial neoplasia (PanIN) lesions in a pancreas-specific KrasG12D mouse model. The purpose of this study was to explore whether serum microRNAs (miRNAs) can serve as sensitive biomarkers to detect occult PanIN in the setting of acute pancreatitis. Serum miRNA profiles were quantified by an array-based method and normalized by both Variance Stabilization Normalization (VSN) and invariant methods. Individual miRNAs were validated by TaqMan real-time PCR with synthetic spike-in C. elegans miRNAs as external controls. Serum miRNA profiles distinguished KrasG12D mice with pancreatitis from wild-type mice without pancreatitis, but failed to differentiate KrasG12D mice with pancreatitis from wild-type mice with pancreatitis. Most individual miRNAs that increased in KrasG12D mice with pancreatitis were not significantly different between KrasG12D mice without pancreatitis and wild-type mice without pancreatitis. Mechanistically, Gene Set Enrichment Analysis (GSEA) of the mRNA array data and immunohistochemical assays showed that caerulein-induced acute pancreatitis involved acinar cell loss and immune cell infiltration, which might contribute to serum miRNA profile changes. This study highlighted the challenges in using sensitive serum miRNA biomarker screening for the early detection of pancreatic malignancies during acute pancreatitis.

Allergic inflammation and severe allergic reactions (anaphylaxis) are important in allergen induced diseases. Bacterial products such as lipopolysaccharide (LPS) are ubiquitous and can facilitate allergen induced Th2 immune responses. Phosphatase SHP-1 is critical in regulating immunological homeostasis and in allergen induced Th2 immune responses in the lung. However, the mechanisms underlying the initiation of allergic inflammation and allergen induced anaphylaxis are still not completely elucidated and it is unclear whether SHP-1 plays any role in LPS-induced airway inflammation and in allergen-induced anaphylaxis. In this study we tested the hypothesis that phosphatase SHP-1 plays an important role in allergic inflammation and anaphylaxis and determined whether its effects are through regulation of mast cell functions. SHP-1 deficient (mev/+ and mev/mev) and mast cell deficient (Kit(W-sh)) mice were examined in their responses to LPS airway stimulation and to ovalbumin (OVA) allergen induced systemic anaphylaxis. Compared to wild type mice, mev/+ mice had significantly enhanced LPS induced airway inflammation and OVA induced anaphylactic responses, including hypothermia and clinical symptoms. These changes were mast cell dependent as Kit(W-sh) mice had reduced responses whereas adoptive transfer of mast cells restored the responses. However, T and B cells were not involved and macrophages did not play a significant role in LPS induced airway inflammation. Interestingly, basophil differentiation from SHP-1 deficient bone marrow cells was significantly reduced. These findings provided evidence that through regulation of mast cell functions SHP-1 plays a critical role as a negative regulator in allergic inflammation and in allergen induced anaphylaxis. In addition, SHP-1 seems to be required for normal basophil development.

Leukemia inhibitory factor (LIF), a member of the IL-6 cytokine family, is considered to be a pleiotropic cytokine and functions in both cell proliferation and differentiation. It is widely used in the culture of mouse embryonic stem cells and is implicated in the implantation of mouse model and possibly in humans. Great efforts have been made on the efficient generation of LIF to meet the requirement of this cytokine in biomedical research. However, because of the low expression level in the eukaryotic system and poor purification yields, recombinant human LIF has usually been expressed either as inclusion body or as fusion protein in E. coli (Escherichia coli). Here we introduce a simple method to express hLIF in a soluble form in E. coli and a subsequent purification method. The expression of hLIF was induced at a low temperature (16 °C) and most of the expressed hLIF was observed to be in a soluble form. Then by using three steps of chromatography, which could be easily scaled-up for industrial purposes, active untagged hLIF was purified with similar bioactivity compared to that of the commercial product. The endotoxin level of purified hLIF protein in our method was determined to be lower than 1EU/μg, which was also comparable to the commercial products. Furthermore, as hLIF was expressed in a soluble form, there was no need to develop the denaturation and renaturation methods. The yield of hLIF protein was evaluated to be approximately 0.7 mg hLIF from 1 g wet weight of E.coli in our method.

Increasing evidence has shown that long non-coding RNAs (lncRNAs) are important prognostic biomarkers and epigenetic regulators with critical roles in cancer initiation and progression. However, the expression and clinical prognostic value of antisense lncRNAs in diffuse glioma patients remain unknown.

Royal jelly (RJ) is a secretion of the hypopharyngeal glands (HGs) of honeybee workers. High royal jelly producing bees (RJBs), a stock of honeybees selected from Italian bees (ITBs), have developed a stronger ability to produce RJ than ITBs. However, the mechanism underpinning the high RJ-producing performance in RJBs is still poorly understood. We have comprehensively characterized and compared the proteome across the life span of worker bees between the ITBs and RJBs. Our data uncover distinct molecular landscapes that regulate the gland ontogeny and activity corresponding with age-specific tasks. Nurse bees (NBs) have a well-developed acini morphology and cytoskeleton of secretory cells in HGs to prime the gland activities of RJ secretion. In RJB NBs, pathways involved in protein synthesis and energy metabolism are functionally induced to cement the enhanced RJ secretion compared with ITBs. In behavior-manipulated RJB NBs, the strongly expressed proteins implicated in protein synthesis and energy metabolism further demonstrate their critical roles in the regulation of RJ secretion. Our findings provide a novel understanding of the mechanism consolidating the high RJ-output in RJBs.

Berberine (BBR) is the main active ingredient of a traditional Chinese herb Coptis chinensis. It has been reported to exhibit beneficial effects in treating diabetes and obesity. However, the underlying mechanism has not been fully elucidated. Adipose tissue fibrosis is a hallmark of obesity-associated adipose tissue dysfunction. HIF-1α plays a key role in adipose tissue fibrosis, which closely linked to metabolic dysfunction in obese state. We hypothesized that BBR may alleviate obesity-induced adipose tissue fibrosis and associated metabolic dysfunction through inhibition of HIF-1α. To test this hypothesis, we treated high fat diet (HFD) feeding mice with different dose of BBR (100 mg/kg, 200 mg/kg, and 300 mg/kg) for 8 weeks. We found that BBR treatment greatly decreased the body weight gain and reduced insulin resistance induced by HFD. Data also revealed that BBR improved histologic fibrous of epididymal white adipose tissue (eWAT) and was accompanied with inhibition of the abnormal synthesis and deposition of extracellular matrix (ECM) proteins, such as collagen and fibronectin. We also found that BBR treatment suppressed the expression of HIF-1α and decreased the mRNA expression of LOX in epididymal adipose tissue, which plays a key role in fibrosis development. Taken together, these results suggest that BBR can regulate metabolic homeostasis and suppress adipose tissue fibrosis through inhibiting the expression of HIF-1α.

Acute myocardial infarction (AMI) is one of the leading causes of mortality and morbidity worldwide. Recently, several studies have revealed the diagnostic value of circulating microRNAs (miRNAs) for AMI detection. However, the diagnostic capacity of miRNAs for AMI is still controversial due to the inconsistent results among studies.

In this study, Fe₃O₄/ZnO core⁻shell nanocomposites were synthesized through a chemical method of coating the magnetic core (Fe₃O₄) with ZnO by co-precipitation of Fe₃O₄ with zinc acetate in a basic medium of ammonium hydroxide. The phase structure, morphology and electromagnetic parameters of the Fe₃O₄/ZnO core⁻shell nanocomposites were investigated. The results indicated that the concentration of the solvent was responsible for controlling the morphology of the composites, which further influenced their impedance matching and microwave absorption properties. Moreover, Fe₃O₄/ZnO nanocomposites exhibited an enhanced absorption capacity in comparison with the naked Fe₃O₄ nanospheres. Specifically, the minimum reflection loss value reached −50.79 dB at 4.38 GHz when the thickness was 4.5 mm. It is expected that the Fe₃O₄/ZnO core⁻shell structured nanocomposites could be a promising candidate as high-performance microwave absorbers.

Cardiovascular disease (CVD) is one of the leading causes of death worldwide. Our study aimed to investigate the prevalence of two conditions, angina and stroke, and relevant risk factors among older adults in six low- and middle- income countries(LMICs).

Lipid metabolism reprogramming plays important role in cell growth, proliferation, angiogenesis and invasion in cancers. However, the diverse lipid metabolism programmes and prognostic value during glioma progression remain unclear. Here, the lipid metabolism-related genes were profiled using RNA sequencing data from The Cancer Genome Atlas (TCGA) and Chinese Glioma Genome Atlas (CGGA) database. Gene ontology (GO) and gene set enrichment analysis (GSEA) found that glioblastoma (GBM) mainly exhibited enrichment of glycosphingolipid metabolic progress, whereas lower grade gliomas (LGGs) showed enrichment of phosphatidylinositol metabolic progress. According to the differential genes of lipid metabolism between LGG and GBM, we developed a nine-gene set using Cox proportional hazards model with elastic net penalty, and the CGGA cohort was used for validation data set. Survival analysis revealed that the obtained gene set could differentiate the outcome of low- and high-risk patients in both cohorts. Meanwhile, multivariate Cox regression analysis indicated that this signature was a significantly independent prognostic factor in diffuse gliomas. Gene ontology and GSEA showed that high-risk cases were associated with phenotypes of cell division and immune response. Collectively, our findings provided a new sight on lipid metabolism in diffuse gliomas.

To explore the molecular mechanism of the response of Masson pine (Pinus massoniana), the main coniferous tree in southern China, to high CO2 stress, transcriptome sequencing was carried out to analyze the genome-wide responses of annual seedlings under different durations (0 h, 6 h, 12 h and 24 h) of high CO2 stress. The results showed that a total of 3080/1908, 3110/2115 and 2684/1483 genes were up-/down-regulated after 6 h, 12 h and 24 h of treatment, respectively, compared with control check group (CK, 0 h). Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that most of these differentially expressed genes (DEGs) were enriched in energy metabolism, carbohydrate synthesis, cell wall precursor synthesis and hormone regulation pathways. For energy metabolism, the expression of most genes involved in photosynthesis (including the light reaction and Calvin cycle) was generally inhibited, while the expression of genes related glycolysis, the tricarboxylic acid (TCA) cycle and PPP pathway was up-regulated. In addition, the increase in the CO2 concentration induced the up-regulation of gene expression in the sucrose synthesis pathway. Among all starch synthesis genes, GBSS (granule-bound starch synthase) had the highest expression level. On the other hand, during the synthesis of hemicellulose and pectin (cell wall precursor substances), the expression levels of GMD (GDP-mannose 4,6-dehydratase), MGP (Mannose-1-phosphate guanylyl transferase) and RHM (Rhamnose biosynthetic enzyme) were the highest, suggesting that the synthesis of the raw materials hemicellulose and pectin in Masson pine under stress were mainly supplied by GDP-Man, GDP-Fuc and UDP-Rha. Finally, stress inhibited gene expression in the ABA (Abscisic Acid) synthesis pathway and induced gene expression in the GA (Gibberellin), SA (Salicylic acid), BR(Brassinolide) and MeJA (Methyl Jasmonate) pathways. Stomatal switches were regulated by hormonal interactions. This experiment elaborated on the response and molecular mechanism of Masson pine to CO2 stress and aided in screening carbon sequestration genes for the corresponding molecular research of Masson pine in the future.

Old age has been demonstrated to be a risk factor for GBM, but the underlying biological mechanism is still unclear. We designed this study intending to determine a mechanistic explanation for the link between age and pathogenesis in GBM.

Mutations in the pioneer transcription factor FOXA1 are a hallmark of estrogen receptor-positive (ER+) breast cancers. Examining FOXA1 in ∼5,000 breast cancer patients identifies several hotspot mutations in the Wing2 region and a breast cancer-specific mutation SY242CS, located in the third β strand. Using a clinico-genomically curated cohort, together with breast cancer models, we find that FOXA1 mutations associate with a lower response to aromatase inhibitors. Mechanistically, Wing2 mutations display increased chromatin binding at ER loci upon estrogen stimulation, and an enhanced ER-mediated transcription without changes in chromatin accessibility. In contrast, SY242CS shows neomorphic properties that include the ability to open distinct chromatin regions and activate an alternative cistrome and transcriptome. Structural modeling predicts that SY242CS confers a conformational change that mediates stable binding to a non-canonical DNA motif. Taken together, our results provide insights into how FOXA1 mutations perturb its function to dictate cancer progression and therapeutic response.