Quantitative profiling of m6A at single base resolution across the life cycle of rice and Arabidopsis.

N6-methyladenosine (m6A) plays critical roles in regulating mRNA metabolism. However, comprehensive m6A methylomes in different plant tissues with single-base precision have yet to be reported. Here, we present transcriptome-wide m6A maps at single-base resolution in different tissues of rice and Arabidopsis using m6A-SAC-seq. Our analysis uncovers a total of 205,691 m6A sites distributed across 22,574 genes in rice, and 188,282 m6A sites across 19,984 genes in Arabidopsis. The evolutionarily conserved m6A sites in rice and Arabidopsis ortholog gene pairs are involved in controlling tissue development, photosynthesis and stress response. We observe an overall mRNA stabilization effect by 3' UTR m6A sites in certain plant tissues. Like in mammals, a positive correlation between the m6A level and the length of internal exons is also observed in plant mRNA, except for the last exon. Our data suggest an active m6A deposition process occurring near the stop codon in plant mRNA. In addition, the MTA-installed plant mRNA m6A sites correlate with both translation promotion and translation suppression, depicting a more complicated regulatory picture. Our results therefore provide in-depth resources for relating single-base resolution m6A sites with functions in plants and uncover a suppression-activation model controlling m6A biogenesis across species.

Gallic Acid-Modified Polyethylenimine-Polypropylene Carbonate-Polyethylenimine Nanoparticles: Synthesis, Characterization, and Anti-Periodontitis Evaluation.

The aim of the research was to develop novel gallic acid (GA)-modified amphiphilic nanoparticles of polyethylenimine (PEI)-polypropylene carbonate (PPC)-PEI (PEPE) and comprehensively assess its properties as an antiperiodontitis nanoparticle targeting the Toll-like receptor (TLR). The first step is to evaluate the binding potential of GA to the core trigger receptors TLR2 and TLR4/MD2 for periodontitis using molecular docking techniques. Following this, we conducted NMR, transmission electron microscopy, and dynamic light scattering analyses on the synthesized PEPE nanoparticles. As the final step, we investigated the synthetic results and in vitro antiperiodontitis properties of GA-PEPE nanoparticles. The investigation revealed that GA exhibits potential for targeted binding to TLR2 and the TLR4/MD2 complex. Furthermore, we successfully developed 91.19 nm positively charged PEPE nanoparticles. Spectroscopic analysis indicated the successful synthesis of GA-modified PEPE. Additionally, CCK8 results demonstrated that GA modification significantly reduced the biotoxicity of PEPE. The in vitro antiperiodontitis properties assessment illustrated that 6.25 µM of GA-PEPE nanoparticles significantly reduced the expression of pro-inflammatory factors TNF-α, IL-1ß, and IL-6. The GA-PEPE nanoparticles, with their targeted TLR binding capabilities, were found to possess excellent biocompatibility and antiperiodontitis properties. GA-PEPE nanoparticles will provide highly innovative input into the development of anti- periodontitis nanoparticles.

Crosstalk between endothelial progenitor cells and HCC through periostin/CCL2/CD36 supports formation of the pro-metastatic microenvironment in HCC.

Metastasis causes most cancer-related deaths, and the role and mechanism of periostin (POSTN) in the metastasis of hepatocellular carcinoma (HCC) remain undiscovered. In this study, DEN and HTVi HCC models were performed in hepatic-specific Postn ablation and Postn knock-in mouse to reveal the role of POSTN in HCC metastasis. Furthermore, POSTN was positively correlated with circulating EPCs level and promoted EPC mobilization and tumour infiltration. POSTN also mediated the crosstalk between HCC and EPCs, which promoted metastasis ability and upregulated CD36 expression in HCC through indirect crosstalk. Chemokine arrays further revealed that hepatic-derived POSTN induced elevated CCL2 expression and secretion in EPCs, and CCL2 promoted prometastatic traits in HCC. Mechanistic studies showed that POSTN upregulated CCL2 expression in EPCs via the αvß3/ILK/NF-κB pathway. CCL2 further induced CD36 expression via the CCR2/STAT3 pathway by directly binding to the promoter region of CD36. Finally, CD36 was verified to have a prometastatic role in vitro and to be correlated with POSTN expression, metastasis and recurrence in HCC in clinical samples. Our findings revealed that crosstalk between HCC and EPCs is mediated by periostin/CCL2/CD36 signalling which promotes HCC metastasis and emphasizes a potential therapeutic strategy for preventing HCC metastasis.

Surface Passivation by Embedment of Polyphosphate Inhibits the Aragonite-to-Calcite Thermodynamic Pump.

We monitored the conversion of aragonite to calcite in water by comparing single and mixed polymorph suspensions. We demonstrate that the enhanced aragonite-to-calcite conversion in mixed polymorph suspensions is dramatically inhibited by adding polyphosphate (sodium hexametaphosphate). 13C and 31P solid-state magic angle spinning (MAS) NMR and attenuated total reflectance Fourier transform infrared (ATR-FTIR) spectra allow us to follow quantitatively these effects as imparted by the dissolution-recrystallization processes. 31P{13C} and 13C{31P} rotational echo double resonance (REDOR)NMR experiments reveal coprecipitated phosphate that is embedded only within the surfaces of both polymorphs during the initial dissolution and recrystallization processes, causing passivation that arrests phase conversion.

RBFOX2 recognizes N6-methyladenosine to suppress transcription and block myeloid leukaemia differentiation.

N6-methyladenosine (m6A) methylation can be deposited on chromatin-associated RNAs (caRNAs) by the RNA methyltransferase complex (MTC) to regulate chromatin state and transcription. However, the mechanism by which MTC is recruited to distinct genomic loci remains elusive. Here we identify RBFOX2, a well-studied RNA-binding protein, as a chromatin factor that preferentially recognizes m6A on caRNAs. RBFOX2 can recruit RBM15, an MTC component, to facilitate methylation of promoter-associated RNAs. RBM15 also physically interacts with YTHDC1 and recruits polycomb repressive complex 2 (PRC2) to the RBFOX2-bound loci for chromatin silencing and transcription suppression. Furthermore, we found that this RBFOX2/m6A/RBM15/YTHDC1/PRC2 axis plays a critical role in myeloid leukaemia. Downregulation of RBFOX2 notably inhibits survival/proliferation of acute myeloid leukaemia cells and promotes their myeloid differentiation. RBFOX2 is also required for self-renewal of leukaemia stem/initiation cells and acute myeloid leukaemia maintenance. Our study presents a pathway of m6A MTC recruitment and m6A deposition on caRNAs, resulting in locus-selective chromatin regulation, which has potential therapeutic implications in leukaemia.

Anti-inflammatory effect and mechanism of catalpol in various inflammatory diseases.

Catalpol is a kind of iridoid glucoside, widely found in a variety of plants, mostly extracted from the rhizome of the traditional medicinal herb rehmanniae. It has various biological activities such as anti-inflammatory, antioxidant, and antitumor. The anti-inflammatory effects of catalpol have been demonstrated in a variety of diseases, such as neurological diseases, atherosclerosis, renal diseases, respiratory diseases, digestive diseases, bone and joint diseases, eye diseases, and periodontitis. The purpose of this review is to summarize the existing literature on the anti-inflammatory effects of catalpol in a variety of inflammatory diseases over the last decade and to focus on the anti-inflammatory mechanisms of catalpol.

RBM33 is a unique m6A RNA-binding protein that regulates ALKBH5 demethylase activity and substrate selectivity.

Regulation of RNA substrate selectivity of m6A demethylase ALKBH5 remains elusive. Here, we identify RNA-binding motif protein 33 (RBM33) as a previously unrecognized m6A-binding protein that plays a critical role in ALKBH5-mediated mRNA m6A demethylation of a subset of mRNA transcripts by forming a complex with ALKBH5. RBM33 recruits ALKBH5 to its m6A-marked substrate and activates ALKBH5 demethylase activity through the removal of its SUMOylation. We further demonstrate that RBM33 is critical for the tumorigenesis of head-neck squamous cell carcinoma (HNSCC). RBM33 promotes autophagy by recruiting ALKBH5 to demethylate and stabilize DDIT4 mRNA, which is responsible for the oncogenic function of RBM33 in HNSCC cells. Altogether, our study uncovers the mechanism of selectively demethylate m6A methylation of a subset of transcripts during tumorigenesis that may explain demethylation selectivity in other cellular processes, and we showed its importance in the maintenance of tumorigenesis of HNSCC.

Transport of Microplastic and Dispersed Oil Co-contaminants in the Marine Environment.

Microplastics (MPs) and oil pollution are major concerns in oceans. Although their coexistence in oceans and the associated MP-oil-dispersant agglomerates (MODAs) have been reported, limited attention is given to the behavior of the co-contaminants. This study investigated MODA transport in a simulated ocean system and explored related mechanisms under various oil types, salinities, and mineral concentrations. We found that more than 90% of the heavy oil-formed MODAs stayed at the seawater surface, while the light oil-formed MODAs were widely distributed throughout the seawater column. The increased salinity promoted MODAs formed by 7 and 90 µm MPs to transport from the seawater surface to the column. This was elucidated by the Derjaguin-Landau-Verwey-Overbeek theory as more MODAs formed under higher salinities and dispersants kept them stable in the seawater column. Minerals facilitated the sinking of large MP-formed MODAs (e.g., 40 µm) as minerals were adsorbed on the MODA surface, but their impact on small MP-formed MODAs (e.g., 7 µm) was negligible. A MODA-mineral system was proposed to explain their interaction. Rubey's equation was recommended to predict the sinking velocity of MODAs. This study is the first attempt to reveal MODA transport. Findings will contribute to the model development to facilitate their environmental risk evaluation in oceans.

FTO mediates LINE1 m6A demethylation and chromatin regulation in mESCs and mouse development.

N6-methyladenosine (m6A) is the most abundant internal modification on mammalian messenger RNA. It is installed by a writer complex and can be reversed by erasers such as the fat mass and obesity-associated protein FTO. Despite extensive research, the primary physiological substrates of FTO in mammalian tissues and development remain elusive. Here, we show that FTO mediates m6A demethylation of long-interspersed element-1 (LINE1) RNA in mouse embryonic stem cells (mESCs), regulating LINE1 RNA abundance and the local chromatin state, which in turn modulates the transcription of LINE1-containing genes. FTO-mediated LINE1 RNA m6A demethylation also plays regulatory roles in shaping chromatin state and gene expression during mouse oocyte and embryonic development. Our results suggest broad effects of LINE1 RNA m6A demethylation by FTO in mammals.