Previous studies have revealed the critical roles of N6-methyladenosine (m6A) modification of mRNA in embryonic stem cells (ESCs), but the biological function of m6A in large intergenic noncoding RNA (lincRNA) is unknown. Here, we showed that the internal m6A modification of linc1281 mediates a competing endogenous RNA (ceRNA) model to regulate mouse ESC (mESC) differentiation. We demonstrated that loss of linc1281 compromises mESC differentiation and that m6A is highly enriched within linc1281 transcripts. Linc1281 with RRACU m6A sequence motifs, but not an m6A-deficient mutant, restored the phenotype in linc1281-depleted mESCs. Mechanistic analyses revealed that linc1281 ensures mESC identity by sequestering pluripotency-related let-7 family microRNAs (miRNAs), and this RNA-RNA interaction is m6A dependent. Collectively, these findings elucidated the functional roles of linc1281 and its m6A modification in mESCs and identified a novel RNA regulatory mechanism, providing a basis for further exploration of broad RNA epigenetic regulatory patterns.
Recent data suggests that abnormal maternal pre-pregnancy body mass index (BMI) or gestational weight gain (GWG) is associated with unfavorable delivery outcomes. However, limited clinical evidence is available to support this correlation in China. Participating 510 mother-infant pairs were recruited from the Shanghai First Maternity and Infant Hospital, China, between January 1st and 30th 2016. Maternal pre-pregnancy BMI was categorized according to the China’s classification and GWG according to the 2009 Institute of Medicine recommendations (IOM). Linear regression tested the associations between pre-pregnancy BMI or GWG and length of gestation, birthweight, length, and head circumference. Logistic regression assessed the associations between pre-pregnancy BMI or GWG and macrosomic, small- (SGA) and large- (LGA) for-gestational-age infants. Overweight/obese women showed increased length of gestation and birthweight, but did not have a higher risk of macrosomic and LGA infants compared with normal weight women. Women with excessive GWG showed increased length of gestation, birthweight, length, and head circumference, and were more likely to deliver macrosomic and LGA infants compared with women with adequate GWG. Although a relatively low proportion of women from Shanghai area are overweight/obese or exhibit excessive GWG, both high pre-pregnancy BMI and excessive GWG influence perinatal outcomes.
Molecular hydrogen (H2) is a colorless and odorless gas. Studies have shown that H2 inhalation has the therapeutic effects in many animal studies and clinical trials, and its application is recommended in the novel coronavirus pneumonia treatment guidelines in China recently. H2 has a relatively small molecular mass, which helps it quickly spread and penetrate cell membranes to exert a wide range of biological effects. It may play a role in the treatment and prevention of a variety of acute and chronic inflammatory diseases, such as acute pancreatitis, sepsis, respiratory disease, ischemia reperfusion injury diseases, autoimmunity diseases, etc.. H2 is primarily administered via inhalation, drinking H2-rich water, or injection of H2 saline. It may participate in the anti-inflammatory and antioxidant activity (mitochondrial energy metabolism), immune system regulation, and cell death (apoptosis, autophagy, and pyroptosis) through annihilating excess reactive oxygen species production and modulating nuclear transcription factor. However, the underlying mechanism of H2 has not yet been fully revealed. Owing to its safety and potential efficacy, H2 has a promising potential for clinical use against many diseases. This review will demonstrate the role of H2 in antioxidative, anti-inflammatory, and antiapoptotic effects and its underlying mechanism, particularly in coronavirus disease-2019 (COVID-19), providing strategies for the medical application of H2 for various diseases.
A previous NMR structure of the duplex 5'GGU GGA GGCU/PCCG AAG CCG5' revealed an unusually stable RNA internal loop with three consecutive sheared GA pairs. Here, we report NMR studies of two duplexes, 5'GGU GGA GGCU/PCCA AAG CCG5' (replacing the UG pair with a UA closing pair) and 5'GGU GAA GGCU/PCCG AAG CCG5' (replacing the middle GA pair with an AA pair). An unusually stable loop with three consecutive sheared GA pairs forms in the duplex 5'GGU GGA GGCU/PCCA AAG CCG5'. The structure contrasts with that reported for this loop in the crystal structure of the large ribosomal subunit of Deinococcus radiodurans [Harms, J., Schluenzen, F., Zarivach, R., Bashan, A., Gat, S., Agmon, I., Bartels, H., Franceschi, F., and Yonath, A. (2001) Cell 107, 679-688]. The middle AA pair in the duplex 5'GGU GAA GGCU/PCCG AAG CCG5' rapidly exchanges orientations, resulting in alternative base stacking and pseudosymmetry with exclusively sheared pairs. The U GAA G/G AAG C internal loop is 2.1 kcal/mol less stable than the U GGA G/G AAG C internal loop at 37 degrees C. Structural, energetic, and dynamic consequences upon functional group substitutions within related 3 x 3 and 3 x 6 internal loops are also reported.
Synthetic high polymer flocculants, frequently utilized for flocculating efficiency and low cost, recently have been discovered as producing increased risk to human health and the environment. Development of a more efficient and environmentally sound alternative flocculant agent is investigated in this paper. Bioflocculants are produced by microorganisms and may exhibit a high rate of flocculation activity. The bioflocculant ETH-2, with high flocculating activity (2849 mg Kaolin particle/mg ETH-2), produced by strain Enterobacter sp. isolated from activated sludge, was systematically investigated with regard to its production, characterization, and flocculation mechanism. Analyses of microscopic observation, zeta potential and ETH-2 structure demonstrates the bridging mechanism, as opposed to charge neutralization, was responsible for flocculation of the ETH-2. ETH-2 retains high molecular weight (603 to 1820 kDa) and multi-functional groups (hydroxyl, amide and carboxyl) that contributed to flocculation. Polysaccharides mainly composed of mannose, glucose, and galactose, with a molar ratio of 1∶2.9∶9.8 were identified as the active constituents in bioflocculant. The structure of the long backbone with active sites of polysaccharides was determined as a primary basis for the high flocculation activity. Bioflocculant ETH-2 is cation independent, pH tolerant, and thermally stable, suggesting a potential fit for industrial application.
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