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BackgroundFerroptosis has been proven to contribute to the progression of myocardial ischemia/reperfusion (I/R) injury and can be inhibited or promoted by ATF3. Short-chain fatty acids (SCFAs) have shown benefits in various cardiovascular diseases with anti-inflammatory and antioxidant effects. However, the impact of SCFAs on ferroptosis in ischemic-stimulated cardiomyocytes remains unknown. This study aimed to investigate the effect of SCFAs on cardiomyocyte ferroptosis, the expression of ATF3, and its potential upstream regulators.Methods and resultsThe expression of ATF3, ferroptosis pathway geneset (FPG), and geneset of potential regulators for ATF3 (GPRA, predicted by the PROMO database) was explored in the public human myocardial infarction single-cell RNA-seq (sma) dataset. Cardiomyocyte data was extracted from the dataset and re-clustered to explore the FPG, ATF3, and GPRA expression patterns in cardiomyocyte subclusters. A dose-dependent toxic experiment was run to detect the suitable dose for SCFA treatment. The erastin-induced ferroptosis model and hypoxia-reoxygenation (H/R) model (10 h of hypoxia followed by 6 h of reoxygenation) were adopted to assess the effect of SCFAs via the CCK8 assay. Gene expression was examined via RT-PCR and western blot. Ferroptosis markers, including lipid peroxides and Fe2+, were detected using the liperfluo and ferroOrange probes, respectively. In the sma dataset, upregulated ferroptosis pathway genes were mainly found in the infarction-stimulated cardiac cells (border zone and fibrotic zone), particularly the cardiomyocytes and adipocytes. The ATF3 and some of its potential transcription factors (VDR, EGR3, PAX5, and SP1) can be regulated by SCFA. SCFA can attenuate erastin-induced lipid peroxidation in cardiomyocytes. SCFA treatment can also reverse erastin-induced Fe2+ increase but may strengthen the Fe2+ in the H/R model. We also precisely defined a ferroptosis subcluster of cardiomyocytes (CM09) that highly expressed FPG, ATF3, and GPRA.ConclusionThe ATF3 and the ferroptosis pathway are elevated in cardiomyocytes of injury-related cardiac regions (border zone, ischemic zone, and fibrotic zone). SCFA can attenuate cardiomyocyte ferroptosis and regulate the expression of ATF3. Our study offers novel insights into the potential targets of SCFAs in the cardiovascular system.

Abstract Myocardial infarction (MI) is a major cause of mortality worldwide. The major limitation of regenerative therapy for MI is poor cardiac retention of therapeutics, which results from an inefficient vascular network and poor targeting ability. In this study, a two‐layer intrinsically magnetic epicardial patch (MagPatch) prepared by 3D printing with biocompatible materials like poly (glycerol sebacate) (PGS) is designed, poly (ε‐caprolactone) (PCL), and NdFeB. The two‐layer structure ensured that the MagPatch multifariously utilized the magnetic force for rapid vascular reconstruction and targeted drug delivery. MagPatch accumulates superparamagnetic iron oxide (SPION)‐labelled endothelial cells, instantly forming a ready‐implanted organization, and rapidly reconstructs a vascular network anastomosed with the host. In addition, the prefabricated vascular network within the MagPatch allowed for the efficient accumulation of SPION‐labelled therapeutics, amplifying the therapeutic effects of cardiac repair. This study defined an extendable therapeutic platform for vascularization‐based targeted drug delivery that is expected to assist in the progress of regenerative therapies in clinical applications.

A survey was carried out on forest soils and grassland soils from Hebei and Sichuan provinces using Tenebrio molitor larvae as a bait, and high-throughput DNA sequencing (HTS) of the fungal internal transcribed spacer-2 ribosomal DNA was used to monitor the natural distribution of three leading hypocrealean families of insect fungal pathogens (Clavicipitaceae, Cordycipitaceae, and Ophiocordycipitaceae). The occurrence of insect fungal pathogens in soil samples from 98 different sites was compared. The use of insect bait indicated that entomopathogenic fungi of the genus Metarhizium were predominant, followed by Beauveria and Isaria. Molecular characterization using the Mz_FG543 intergenic region revealed that the Metarhizium species pool was phylogenetically composed of three closely related species as follows; Metarhizium pingshaense (n = 74), Metarhizium robertsii (n = 51), and Metarhizium brunneum (n = 26), as well as one isolate which clustered with Metarhizium flavoviride. Nine potentially new phylogenetic species were delimited within the M. flavoviride species complex by sequencing of the 5′ elongation factor-1 alpha region locus. The Beauveria (n = 64) and Isaria (n = 5) isolates were characterized via sequence analyses of the Bloc region. An intergenic spacer phylogeny of the Beauveria isolate assemblage revealed the phylogenetic species within the Beauveria bassiana clade. Interestingly, the individuals of M. pingshaense (n = 18) and M. brunneum (n = 12) exhibited the presence of both mating types in Sichuan Province. Similarly, for the Beauveria isolates, reproductive mode assays demonstrated that all four B. bassiana subclades possessed bipolar outcrossing mating systems. Of these, 19 isolates contained two mating types, and the rest were fixed for single mating types, revealing opportunities for intra-lineage heterothallic mating. The HTS results showed a significantly higher occurrence of the Clavicipitaceae family and the Metarhizium genus in the soil samples. The Venn diagram showed Metarhizium anisopliae (senso lato), Isaria farinose, and B. bassiana as frequently abundant fungal pathogen operational taxonomic units (core) across sampling sites, while the baiting method showed that the genus of Isaria was isolated locally. The Mantel test verified that community dissimilarity increased significantly with geographical distance, suggesting that geographical coordinates are possible factors that influence the insect fungal pathogen community composition in the studied sites. This study is the first to highlight the usefulness of utilizing soil baiting and deep sequencing to investigate the population dynamics of entomopathogens in soil.