Transcriptome-wide 1-methyladenosine functional profiling of messenger RNA and long non-coding RNA in bladder cancer.

Introduction: Post-transcriptional RNA modifications are crucial regulators of tumor development and progression. In many biological processes, N1-methyladenosine (m1A) plays a key role. However, little is known about the links between chemical modifications of messenger RNAs (mRNAs) and long noncoding RNAs (lncRNAs) and their function in bladder cancer (BLCA). Methods: Methylated RNA immunoprecipitation sequencing and RNA sequencing were performed to profile mRNA and lncRNA m1A methylation and expression in BLCA cells, with or without stable knockdown of the m1A methyltransferase tRNA methyltransferase 61A (TRMT61A). Results: The analysis of differentially methylated gene sites identified 16,941 peaks, 6,698 mRNAs, and 10,243 lncRNAs in the two groups. Gene ontology enrichment and Kyoto Encyclopedia of Genes and Genomes pathway analyses of the differentially methylated and expressed transcripts showed that m1A-regulated transcripts were mainly related to protein binding and signaling pathways in cancer. In addition, the differentially genes were identified that were also differentially m1A-modified and identified 14 mRNAs and 19 lncRNAs. Next, these mRNAs and lncRNAs were used to construct a lncRNA-microRNA-mRNA competing endogenous RNA network, which included 118 miRNAs, 15 lncRNAs, and 8 mRNAs. Finally, the m1A-modified transcripts, SCN2B and ENST00000536140, which are highly expressed in BLCA tissues, were associated with decreased overall patient survival. Discussion: This study revealed substantially different amounts and distributions of m1A in BLCA after TRMT61A knockdown and predicted cellular functions in which m1A may be involved, providing evidence that implicates m1A mRNA and lncRNA epitranscriptomic regulation in BLCA tumorigenesis and progression.

Culturing rhodotorula glutinis in fermentation-friendly deep eutectic solvent extraction liquor of lignin for producing microbial lipid.

Currently, deep eutectic solvents (DES) have attracted increasing attention due to their excellent performance in delignification. However, few studies focused on the treatment of DES waste liquid after extraction of lignin. In this work, the fermentation-friendly DES comprised of glycerol, choline chloride (ChCl) and acetic acid (AA) was applied for delignification of lignocellulose. Subsequently, the extraction effects of different DES were investigated, and the DES extraction liquor was used for lipid production. Results shows ChCl made little difference to lipid synthesis, while excessive AA exerted inhibitory effect on the growth of cells. Following pretreatment, the delignification exceeded 63%. When the DES liquid obtained after lignin extraction was used to produce lipid, the delay period was obvious, while the lipid yield and content were unaffected. Not only is the DES prepared in this study effective in delignification of lignocellulose, it is also applicable as raw material to produce lipid.

Non-productive celluase binding onto deep eutectic solvent (DES) extracted lignin from willow and corn stover with inhibitory effects on enzymatic hydrolysis of cellulose.

In this work, deep eutectic solvent (DES) was prepared by mixing choline chloride (ChCl) with lactic acid (LA), and effects of cellulase non-productive binding onto DES-extracted lignin from willow and corn stover on enzymatic hydrolysis of cellulose was investigated. The correlation between hydrolysis yield of cellulose and chemical features of lignin was evaluated, and a potential inhibitory mechanism was proposed. Condensation of lignin was observed during DES treatment, and these condensed aromatic structures had an increased tendency to adsorb enzymes through hydrophobic interactions. As well as hydrophobic interactions mediated by lignin condensation, an increase in phenolic hydroxyl groups resulted in a greater amount of hydrogen bonds between cellulases and lignin that appeared to inhibit enzymatic hydrolysis yields of cellulose (39.96-42.86 % to 31.96-32.68 %). Although large amounts of COOHs were generated, the elevated electrostatic repulsion as a result of ionic groups was insufficient to decrease non-productive adsorption.

The inhibitory effect of melatonin on mammary function of lactating dairy goats†.

The direct role of melatonin in mammary glands of dairy goats has remained obscure. This study aimed to evaluate the expression of melatonin membrane receptors (MT1 and MT2) in the pituitary and mammary glands of dairy goats during lactation, and to investigate the role of melatonin in mammary function. Both MT1 and MT2 were consistently expressed in the pituitary and mammary eight glands throughout the lactation period, and their levels were lower in 9 March (group I), June (group III), and September (group V) than in May (group II) and August (group IV). The expression patterns of pituitary and mammary MT1 and MT2 were consistent with those of blood melatonin during lactation. Furthermore, the mammary prolactin (PRL), and pituitary growth hormone (GH) and PRL mRNA expression showed an inverse trend in relation to blood melatonin levels. In mammary tissues, MT1 and MT2 immunoreactivity was predominantly located in the mammary epithelial cells (MECs). In addition, a dose- and time-dependent inhibition on cell viability was observed in cultured MECs. At the dose of 10 and 100 pg/ml, melatonin decreased mammary ß-casein and PRL expression. Furthermore, the inhibitory effects of melatonin were blocked by luzindole, a nonselective MT1 and MT2 receptor antagonist. In addition, melatonin promoted MT1 and MT2 expression in cultured MECs. In conclusion, the presence of MT1 and MT2 in the pituitary and mammary glands and the inhibitory effects of melatonin on cell viability, ß-casein, and PRL expression in MECs suggest the potential regulation by melatonin in goat mammary function.

Comparison of four types of energy grasses as lignocellulosic feedstock for the production of bio-ethanol.

In order to utilize energy grasses as substrates for production of biofuels and expand the diversity of lignocellulosic feedstocks, this work developed an evaluation system considering 16 kinds of parameters related to the contents of three main compositions (cellulose, hemicellulose and lignin), inhibitors generated from the pretreatment, the extent of enzymatic hydrolysis and microbial fermentation. Giant reed, corn stalks, switch grass, pennisetum and silvergrass were investigated. Comprehensive utilization indexes of giant reed (55.0) and corn stalks (40.6) revealed that giant reed had the potential for producing biofuels but corn stalks, widely used in bio-ethanol and xylitol production, possessed high contents of inhibitors which were harmful to microbial fermentation.

Using a combined hydrolysis factor to balance enzymatic saccharification and the structural characteristics of lignin during pretreatment of Hybrid poplar with a fully recyclable solid acid.

In this study, a new pretreatment strategy for lignocellulosic was developed using a fully recyclable solid acid, Toluenesulfonic acid (p-TsOH). A combined hydrolysis factor (CHF) as a pretreatment severity was used to balance enzymatic saccharification and the structural characteristics of lignin. The results from degradation of carbohydrates, enzymatic hydrolysis of cellulose and characterization of lignin by FT-IR, 31P NMR, GPC, 2D-HSQC NMR indicated that a CHF of approximately 3.90 was the optimal pretreatment severity to facilitate enzymatic saccharification and the potential serviceability of lignin. Then approximately 90% of the xylan was removed to result in a reasonable sugar yield of 76%. Residual lignin showed low molecular weight (Mw, 5783g/mol), narrow polydispersities (Mw/Mn, 1.10) and high content of phenolic hydroxyl groups (3.702mmol/g); it may be a potential feedstock for phenol monomer and polymeric materials production. In short, this process was regarded as a promising approach to achieve an efficient conversion of lignocellulosic biomass to sugar products and lignin-based materials.

The correlation between cellulose allomorphs (I and II) and conversion after removal of hemicellulose and lignin of lignocellulose.

H2SO4, NaOH and H3PO4 were applied to decompose lignocellulose samples (giant reeds, pennisetum and cotton stalks) to investigate the correlation between cellulose allomorphs (cellulose I and II) and conversion of cellulose. The effect of removal of hemicellulose and lignin on the surface morphology, crystallinity index (CrI), cellulose allomorphs (cellulose I and II), and enzymatic hydrolysis under different pretreatments was also studied. CrI caused by H3PO4 pretreatment reached 11.19%, 24.93% and 8.15% for the three samples, respectively. Corn stalk showed highest conversion of cellulose among three samples, irrespective of the pretreatment used. This accounted for the widely use of corn stalk as the renewable crop substrate to synthesize biofuels like ethanol. CrI of cellulose I (CrI-I) negatively affects cellulose conversion but CrI of cellulose II (CrI-II) positively affects cellulose conversion. It contributes to make the strategy to transform cellulose I to cellulose II and enhancing enzymatic hydrolysis of lignocellulose.

Pharmacokinetics of simvastatin lactone and its active metabolite simvastatin hydroxy acid in healthy Chinese male and female volunteers.

BACKGROUND: Gender differences in pharmacokinetics have been reported to have important clinical consequences; however, no information about differences in the pharmacokinetics of the cholesterol-lowering drug simvastatin lactone and its metabolite, simvastatin hydroxy acid, in males and females is available. OBJECTIVE: The aim of this study was to investigate the effect of gender on the pharmacokinetics of simvastatin lactone and simvastatin hydroxy acid in healthy Han Chinese volunteers. METHODS: 16 healthy volunteers (8 males and 8 females) were orally administered a single dose of 40 mg simvastatin lactone after an overnight fast. Plasma was then collected 24 hours after simvastatin lactone administration. Concentrations of simvastatin lactone and simvastatin hydroxy acid were measured by high performance liquid chromatography/mass spectrometry/mass spectrometry (HPLC/MS/MS). RESULTS: There were no significant associations between the pharmacokinetic parameters of simvastatin lactone and gender. For simvastatin hydroxy acid, peak plasma concentrations (Cmax) and dose-normalized by the subject weight Cmax (NCmax) were higher in females than in males. Furthermore, NCmax and dose-normalized by the subject weight AUC (NAUC0-24h, NAUC0-∞) ratios of simvastatin hydroxy acid to simvastatin lactone in females were higher than in males. CONCLUSION: This study indicates that gender affects the plasma concentrations of active simvastatin hydroxy acid, but has no significant effect on parent simvastatin lactone. Raised plasma concentrations of simvastatin hydroxy acid in females may enhance the risk of systemic adverse effects during simvastatin lactone treatment.