Dental pulp inflammation is a widespread public health problem caused by oral bacterial infections and can progress to pulp necrosis and periapical diseases. N6‐methyladenosine (m6A) is a prevalent epitranscriptomic modification in mRNA. Previous studies have demonstrated that m6A methylation plays important roles in cell differentiation, embryonic development and stress responses. However, whether m6A modification affects dental pulp inflammation remains unknown. To address this issue, we investigated the expression of m6A and N6‐adenosine methyltransferase (METTL3, METTL14) as well as demethylases (FTO, ALKBH5) and found that the levels of m6A and METTL3 were up‐regulated in human dental pulp cells (HDPCs) stimulated by lipopolysaccharide (LPS). Furthermore, we knocked down METTL3 and demonstrated that METTL3 depletion decreased the expression of inflammatory cytokines and the phosphorylation of IKKα/β, p65 and IκBα in the NF‐κB signalling pathway as well as p38, ERK and JNK in the MAPK signalling pathway in LPS‐induced HDPCs. The RNA sequencing analysis revealed that the vast number of genes affected by METTL3 depletion was associated with the inflammatory response. Previous research has shown that METTL3‐dependent N6‐adenosine methylation plays an important role in mRNA splicing. In this study, we found that METTL3 knockdown facilitated the expression of MyD88S, a splice variant of MyD88 that inhibits inflammatory cytokine production, suggesting that METTL3 might inhibit the LPS‐induced inflammatory response of HDPCs by regulating alternative splicing of MyD88. These data shed light on new findings in epitranscriptomic regulation of the inflammatory response and open new avenues for research into the molecular mechanisms of dental pulp inflammation.
Ac omprehensive study unveiling the impacto f heterovalent doping with Bi 3 + on the structural,s emiconductive, and photoluminescent properties of as ingle crystal of lead halide perovskites (CH 3 NH 3 PbBr 3 )i sp resented.A si ndicatedb ys ingle-crystal XRD, ap erfect cubic structure in Bi 3 + -doped CH 3 NH 3 PbBr 3 crystals is maintainedina ssociation with as light lattice contraction. Time-resolved andp owerdependent photoluminescence( PL) spectroscopy illustrates ap rogressivelyq uenched PL of visible emission, alongside the appearance of an ew PL signal in the near-infrared( NIR) regime,w hich is likely to be due to energy transfer to the Bi sites. These optical characteristics indicatet he role of Bi 3 + dopants as nonradiative recombination centers, which explains the observed transition from bimolecular recombina-tion in pristine CH 3 NH 3 PbBr 3 to ad ominant trap-assisted monomolecular recombination with Bi 3 + doping. Electrically, it is found that the mobility in pristine perovskite crystals can be boosted with al ow Bi 3 + concentration,w hich may be related to atrap-filling mechanism.Aided by temperature (T)-dependentm easurements, two temperature regimes are observed in association with differenta ctivation energies (E a ) for electrical conductivity.T he reduction of E a at lower T may be ascribed to suppression of ionic conduction induced by doping. The modified electrical properties and NIR emission with the control of Bi 3 + concentration shed light on the opportunity to apply heterovalent doping of perovskite single crystals forN IR optoelectronic applications.
Osteoclast differentiation and function are crucial for maintaining bone homeostasis and preserving skeletal integrity. N6-methyladenosine (m6A) is an abundant mRNA modification that has recently been shown to be important in regulating cell lineage differentiation. Nevertheless, the effect of m6A on osteoclast differentiation remains unknown. In the present study, we observed that the m6A level and methyltransferase METTL3 expression increased during osteoclast differentiation. Mettl3 knockdown resulted in an increased size but a decreased bone-resorbing ability of osteoclasts. The expression of osteoclast-specific genes (Nfatc1, c-Fos, Ctsk, Acp5 and Dcstamp) was inhibited by Mettl3 depletion, while the expression of the cellular fusion-specific gene Atp6v0d2 was upregulated. Mechanistically, Mettl3 knockdown elevated the mRNA stability of Atp6v0d2 and the same result was obtained when the m6A-binding protein YTHDF2 was silenced. Moreover, the phosphorylation levels of key molecules in the MAPK, NF-κB and PI3K-AKT signaling pathways were reduced upon Mettl3 deficiency. Depletion of Mettl3 maintained the retention of Traf6 mRNA in the nucleus and reduced the protein levels of TRAF6. Taken together, our data suggest that METTL3 regulates osteoclast differentiation and function through different mechanisms involving Atp6v0d2 mRNA degradation mediated by YTHDF2 and Traf6 mRNA nuclear export. These findings elucidate the molecular basis of RNA epigenetic regulation in osteoclast development.
Understanding the factors that limit the performance of perovskite solar cells (PSCs) can be enriched by detailed temperature (T)-dependent studies. Based on p-i-n type PSCs with prototype methylammonium lead triiodide (MAPbI 3 ) perovskite absorbers, T-dependent photovoltaic properties are explored and negative T-coefficients for the three device parameters (V OC , J SC , and FF) are observed within a wide low T-range, leading to a maximum power conversion efficiency (PCE) of 21.4% with an impressive fill factor (FF) approaching 82% at 220 K. These T-behaviors are explained by the enhanced interfacial charge transfer, reduced charge trapping with suppressed nonradiative recombination and narrowed optical bandgap at lower T. By comparing the T-dependent device behaviors based on MAPbI 3 devices containing a PASP passivation layer, enhanced PCE at room temperature is observed but different tendencies showing attenuating T-dependencies of J SC and FF, which eventually leads to nearly T-invariable PCEs. These results indicate that charge extraction with the utilized all-organic charge transporting layers is not a limiting factor for low-T device operation, meanwhile the trap passivation layer of choice can play a role in the T-dependent photovoltaic properties and thus needs to be considered for PSCs operating in a temperature-variable environment.
BackgroundSmarthouses capable of non-destructive, high-throughput plant phenotyping collect large amounts of data that can be used to understand plant growth and productivity in extreme environments. The challenge is to apply the statistical tool that best analyzes the data to study plant traits, such as salinity tolerance, or plant-growth-related traits.ResultsWe derive family-wise salinity sensitivity (FSS) growth curves and use registration techniques to summarize growth patterns of HEB-25 barley families and the commercial variety, Navigator. We account for the spatial variation in smarthouse microclimates and in temporal variation across phenotyping runs using a functional ANOVA model to derive corrected FSS curves. From FSS, we derive corrected values for family-wise salinity tolerance, which are strongly negatively correlated with Na but not significantly with K, indicating that Na content is an important factor affecting salinity tolerance in these families, at least for plants of this age and grown in these conditions.ConclusionsOur family-wise methodology is suitable for analyzing the growth curves of a large number of plants from multiple families. The corrected curves accurately account for the spatial and temporal variations among plants that are inherent to high-throughput experiments.Electronic supplementary materialThe online version of this article (doi:10.1186/s13007-017-0165-7) contains supplementary material, which is available to authorized users.
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