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In this paper, the performance of three microtextured tools in machining Inconel 718 high-temperature alloy under two different coating conditions was investigated using the finite element method. Firstly, the theoretical tool-chip contact length model of the microtextured tool is established. Secondly, the theoretical model of cutting force and cutting the heat of the surface weave tool is established using the theoretical tool-chip contact length model. The theoretical analysis of cutting force and cutting temperature of the microtextured tool is carried out according to the variation law of the theoretical tool-chip contact length. And finally, the finite element simulation model is established. The effect of changing the coating material on the machining performance of microtextured tools is discussed by changing the coating material on the tool surface. By establishing the simulation model, the changing patterns of cutting force, cutting temperature and effective stress of the three microtextured tools are compared under different coating materials. Adding coating materials to the tool surface can effectively improve machining efficiency. In addition, it is proposed that different microtexture shapes produce different degrees of secondary cutting during the turning of microtextured tools.

ABSTRACTN6-methyladenosine (m6A) mRNA modifications play critical roles in various biological processes. However, no study addresses the role of m6A in macroautophagy/autophagy. Here, we show that m6A modifications are increased in H/R-treated cardiomyocytes and ischemia/reperfusion (I/R)-treated mice heart. We found that METTL3 (methyltransferase like 3) is the primary factor involved in aberrant m6A modification. Silencing METTL3 enhances autophagic flux and inhibits apoptosis in H/R-treated cardiomyocytes. However, overexpression of METTL3 or inhibition of the RNA demethylase ALKBH5 has an opposite effect, suggesting that METTL3 is a negative regulator of autophagy. Mechanistically, METTL3 methylates TFEB, a master regulator of lysosomal biogenesis and autophagy genes, at two m6A residues in the 3ʹ-UTR, which promotes the association of the RNA-binding protein HNRNPD with TFEBpre-mRNA and subsequently decreases the expression levels of TFEB. Further experiments show that autophagic flux enhanced by METTL3 deficiency is TFEB dependent. In turn, TFEB regulates the expression levels of METTL3 and ALKBH5 in opposite directions: it induces ALKBH5 and inhibits METTL3. TFEB binds to the ALKBH5promoter and activates its transcription. In contrast, inhibition of METTL3 by TFEB does not involve transcriptional repression but rather downregulation of mRNA stability, thereby establishing a negative feedback loop. Together, our work uncovers a critical link between METTL3-ALKBH5 and autophagy, providing insight into the functional importance of the reversible mRNA m6A methylation and its modulators in ischemic heart disease.AbbreviationsACTB, actin beta; ALKBH5, alkB homolog 5, RNA demethylase; ANXA5, annexin A5; ATG, autophagy-related; BafA, bafilomycin A1; CASP3, caspase 3; ELAVL1, ELAV like RNA binding protein 1; FTO, FTO, alpha-ketoglutarate dependent dioxygenase; GFP, green fluorescent protein; GST, glutathione S-transferase; HNRNPD, heterogeneous nuclear ribonucleoprotein D; H/R, hypoxia/reoxygenation; I/R, ischemia/reperfusion; LAD, left anterior descending; m6A, N6-methyladenosine; MEFs, mouse embryo fibroblasts; Mer, mutated estrogen receptor domains; METTL3, methyltransferase like 3; METTL14, methyltransferase like 14; mRFP, monomeric red fluorescent protein; MTORC1, mechanistic target of rapamycin kinase complex 1; NMVCs, neonatal mouse ventricular cardiomyocytes; PCNA, proliferating cell nuclear antigen; PE, phosphatidylethanolamine; PI, propidium iodide; PTMs, post-translational modifications; PVDF, polyvinylidenedifluoride; RIP, RNA-immunoprecipitation; siRNA, small interfering RNA; SQSTM1, sequestosome 1; TFEB, transcription factor EB; TUBA: tublin alpha; WTAP, WT1 associated protein; YTHDF, YTH N6-methyladenosine RNA binding protein

In plants, the vesicle fusion process plays a vital role in pathogen defence. However, the importance of the vesicle fusion process in apple ring rot has not been studied. Here, we isolated and characterised the apple syntaxin gene MdSYP121. Silencing the MdSYP121gene in transgenic apple calli increased tolerance to Botryosphaeria dothideainfection; this increased tolerance was correlated with salicylic acid (SA) synthesis-related and signalling-related gene transcription. In contrast, overexpressing MdSYP121in apple calli resulted in the opposite phenotypes. In addition, the results of RNA sequencing (RNA-Seq) and quantitative real-time PCR (qRT-PCR) assays suggested that MdSYP121plays an important role in responses to oxidation–reduction reactions. Silencing MdSYP121in apple calli enhanced the expression levels of reactive oxygen species (ROS)-related genes and the activity of ROS-related enzymes. The enhanced defence response status in MdSYP121-RNAi lines suggests that syntaxins are involved in the defence response to B. dothidea. More importantly, we showed that MdSYP121 forms a soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complex with MdSNAP33, and the complex may participate in regulating resistance to B. dothidea. In conclusion, by regulating the interaction of SA pathway and oxidation–reduction process, MdSYP121can influence the pathogen infection process in apple. A gene with multiple functions in defense against apple ring rot may provide a target for breeding apple varieties resistant to this devastating and enigmatic fungal disease. In China, the world’s greatest producer of apples, apple ring rot poses a severe challenge to growers. A Chinese team led by Shujing Wu and Xuesen Chen, of Shandong Agricultural University, explored the role of a gene, MdSYP121, thought to provide resistance to ring rot. A combination of genetic, genomic, and transgenic experiments showed that MdSYP121does indeed confer resistance to the disease, and may do this both by regulating hormonal pathways of defense and by stimulating enzymes involved in defensive oxidation/reduction reactions. Overall, their results suggest potential foci for breeding programmes aimed at reducing the susceptibility of apple cultivars to the ring rot fungus.