Acetylcytidine modification of Amotl1 by N-acetyltransferase 10 contributes to cardiac fibrotic expansion in mice after myocardial infarction.

Cardiac fibrosis is a pathological scarring process that impairs cardiac function. N-acetyltransferase 10 (Nat10) is recently identified as the key enzyme for the N4-acetylcytidine (ac4C) modification of mRNAs. In this study, we investigated the role of Nat10 in cardiac fibrosis following myocardial infarction (MI) and the related mechanisms. MI was induced in mice by ligation of the left anterior descending coronary artery; cardiac function was assessed with echocardiography. We showed that both the mRNA and protein expression levels of Nat10 were significantly increased in the infarct zone and border zone 4 weeks post-MI, and the expression of Nat10 in cardiac fibroblasts was significantly higher compared with that in cardiomyocytes after MI. Fibroblast-specific overexpression of Nat10 promoted collagen deposition and induced cardiac systolic dysfunction post-MI in mice. Conversely, fibroblast-specific knockout of Nat10 markedly relieved cardiac function impairment and extracellular matrix remodeling following MI. We then conducted ac4C-RNA binding protein immunoprecipitation-sequencing (RIP-seq) in cardiac fibroblasts transfected with Nat10 siRNA, and revealed that angiomotin-like 1 (Amotl1), an upstream regulator of the Hippo signaling pathway, was the target gene of Nat10. We demonstrated that Nat10-mediated ac4C modification of Amotl1 increased its mRNA stability and translation in neonatal cardiac fibroblasts, thereby increasing the interaction of Amotl1 with yes-associated protein 1 (Yap) and facilitating Yap translocation into the nucleus. Intriguingly, silencing of Amotl1 or Yap, as well as treatment with verteporfin, a selective and potent Yap inhibitor, attenuated the Nat10 overexpression-induced proliferation of cardiac fibroblasts and prevented their differentiation into myofibroblasts in vitro. In conclusion, this study highlights Nat10 as a crucial regulator of myocardial fibrosis following MI injury through ac4C modification of upstream activators within the Hippo/Yap signaling pathway.

Genomic Analyses for Selective Signatures and Genes Involved in Hot Adaptation Among Indigenous Chickens From Different Tropical Climate Regions.

Climate change, especially weather extremes like extreme cold or extreme hot, is a major challenge for global livestock. One of the animal breeding goals for sustainable livestock production should be to breed animals with excellent climate adaptability. Indigenous livestock and poultry are well adapted to the local climate, and they are good resources to study the genetic footprints and mechanism of the resilience to weather extremes. In order to identify selection signatures and genes that might be involved in hot adaptation in indigenous chickens from different tropical climates, we conducted a genomic analysis of 65 indigenous chickens that inhabit different climates. Several important unique positively selected genes (PSGs) were identified for each local chicken group by the cross-population extended haplotype homozygosity (XP-EHH). These PSGs, verified by composite likelihood ratio, genetic differentiation index, nucleotide diversity, Tajima's D, and decorrelated composite of multiple signals, are related to nerve regulation, vascular function, immune function, lipid metabolism, kidney development, and function, which are involved in thermoregulation and hot adaptation. However, one common PSG was detected for all three tropical groups of chickens via XP-EHH but was not confirmed by other five types of selective sweep analyses. These results suggest that the hot adaptability of indigenous chickens from different tropical climate regions has evolved in parallel by taking different pathways with different sets of genes. The results from our study have provided reasonable explanations and insights for the rapid adaptation of chickens to diverse tropical climates and provide practical values for poultry breeding.

Metal organic framework MIL-53(Fe) as an efficient artificial oxidase for colorimetric detection of cellular biothiols.

Biothiols play critical roles in many biological processes and their aberrant is related to a variety of syndromes. A simple and reliable colorimetric method is developed in this work for biothiols detection based on an oxidase mimic, a metal organic framework (MOF) MIL-53(Fe), and a peroxidase substrate 3,3',5,5'-tetramethylbenzidine (TMB). In this design, MIL-53(Fe) is utilized to catalyze the conversion of TMB to a blue colored 3,3',5,5'-tetramethylbenzidine diimine, which can be read on a spectrophotometer at 652 nm. The oxidation-induced blue color generation can be efficiently inhibited by biothiols, thus a colorimetric analytical method is proposed for biothiols detection based on the above system. Under optimal conditions, a linear relationship in a range from 1 to 100 µM and a limit of detection (LOD) at 120 nM are achieved with Cys as a model target. The developed platform is further applied to evaluate cellular biothiols in normal (RWPE-1) and cancer (LNCap) cell lines, revealing that the overall biothiols level in LNCap is much higher than that in RWPE-1. This work renders a powerful tool for identifying cancer cells in a simple manner for biomedical diagnosis associated with biothiols.