AP39 through AMPK-ULK1-FUNDC1 pathway regulates mitophagy, inhibits pyroptosis, and improves doxorubicin-induced myocardial fibrosis.

Doxorubicin induces myocardial injury and fibrosis. Still, no effective interventions are available. AP39 is an H2S donor that explicitly targets mitochondria. This study investigated whether AP39 could improve doxorubicin-induced myocardial fibrosis. Doxorubicin induced significant myocardial fibrosis while suppressing mitophagy-related proteins and elevating pyroptosis-related proteins. Conversely, AP39 reverses these effects, enhancing mitophagy and inhibiting pyroptosis. In vitro experiments revealed that AP39 inhibited H9c2 cardiomyocyte pyroptosis, improved doxorubicin-induced impairment of mitophagy, reduced ROS levels, ameliorated the mitochondrial membrane potential, and upregulated AMPK-ULK1-FUNDC1 expression. In contrast, AMPK inhibitor (dorsomorphin) and ULK1 inhibitor (SBI-0206965) reversed AP39 antagonism of doxorubicin-induced FUNDC1-mediated impairment of mitophagy and secondary cardiomyocyte pyroptosis. These results suggest that mitochondria-targeted H2S can antagonize doxorubicin-induced pyroptosis and impaired mitophagy in cardiomyocytes via AMPK-ULK1-FUNDC1 and ameliorated myocardial fibrosis and remodeling.

Erratum: Corrigendum: Hu H et al. (2023) Taxonomic and phylogenetic characterisations of six species of Pleosporales (in Didymosphaeriaceae, Roussoellaceae and Nigrogranaceae) from China. MycoKeys 100: 123-151. https://doi.org/10.3897/mycokeys.100.109423.

[This corrects the article DOI: 10.3897/mycokeys.100.109423.].

Taxonomic and phylogenetic characterisations of six species of Pleosporales (in Didymosphaeriaceae, Roussoellaceae and Nigrogranaceae) from China.

Pleosporales comprise a diverse group of fungi with a global distribution and significant ecological importance. A survey on Pleosporales (in Didymosphaeriaceae, Roussoellaceae and Nigrogranaceae) in Guizhou Province, China, was conducted. Specimens were identified, based on morphological characteristics and phylogenetic analyses using a dataset composed of ITS, LSU, SSU, tef1 and rpb2 loci. Maximum Likelihood (ML) and Bayesian analyses were performed. As a result, three new species (Neokalmusiakarka, Nigrogranaschinifolium and N.trachycarpus) have been discovered, along with two new records for China (Roussoellaneopustulans and R.doimaesalongensis) and a known species (Roussoellapseudohysterioides). Morphologically similar species and phylogenetically close taxa are compared and discussed. This study provides detailed information and descriptions of all newly-identified taxa.

Correction: Wu et al. Rust Fungi on Medicinal Plants in Guizhou Province with Descriptions of Three New Species. J. Fungi 2023, 9, 953.

Error in Figure [...].

Rust Fungi on Medicinal Plants in Guizhou Province with Descriptions of Three New Species.

During the research on rust fungi in medicinal plants of Guizhou Province, China, a total of 9 rust fungal species were introduced, including 3 new species (Hamaspora rubi-alceifolii, Nyssopsora altissima, and Phragmidium cymosum), as well as 6 known species (Melampsora laricis-populina, Melampsoridium carpini, Neophysopella ampelopsidis, Nyssopsora koelrezidis, P. rosae-roxburghii, P. tormentillae). Notably, N. ampelopsidis and P. tormentillae were discovered for the first time in China, while M. laricis-populina, Me. carpini, and Ny. koelreuteriae were first documented in Guizhou Province. Morphological observation and molecular phylogenetic analyses of these species with similar taxa were compared to confirm their taxonomic identities, and taxonomic descriptions, illustrations and host species of those rust fungi on medicinal plant are provided.

Diversity, morphology, and molecular phylogeny of Diatrypaceae from southern China.

During an investigation of Diatrypaceae from southern China, 10 xylariales-like taxa have been collected. Morphological and multi-gene analyses confirmed that these taxa reside in Diatrypaceae and represent eight novel taxa and two new records belonging to six genera (viz., Allocryptovalsa, Diatrype, Diatrypella, Paraeutypella, Peroneutypa, and Vasilyeva gen. nov.). Vasilyeva gen. nov. was proposed to accommodate Vasilyeva cinnamomi sp. nov. Among the other collections, seven new species were introduced (viz., Diatrype camelliae-japonicae sp. nov., Diatrype rubi sp. nov., Diatrypella guiyangensis sp. nov., Diatrypella fatsiae-japonicae sp. nov., Paraeutypella subguizhouensis sp. nov., Peroneutypa hainanensis sp. nov., and Peroneutypa qianensis sp. nov.), while two were reported as new records from China (Allocryptovalsa rabenhorstii and Diatrype enteroxantha). For Diatrypaceae, the traditional taxonomic approach based on morphology may not be applicable.

Insights into the Cytochrome P450 Monooxygenase Superfamily in Osmanthus fragrans and the Role of OfCYP142 in Linalool Synthesis.

Osmanthus fragrans flowers have long been used as raw materials in food, tea, beverage, and perfume industries due to their attractive and strong fragrance. The P450 superfamily proteins have been reported to widely participate in the synthesis of plant floral volatile organic compounds (VOCs). To investigate the potential functions of P450 superfamily proteins in the fragrance synthesis of O. fragrans, we investigated the P450 superfamily genome wide. A total of 276 P450 genes were identified belonging to 40 families. The RNA-seq data suggested that many OfCYP genes were preferentially expressed in the flower or other organs, and some were also induced by multiple abiotic stresses. The expression patterns of seven flower-preferentially expressed OfCYPs during the five different flower aroma content stages were further explored using quantitative real-time PCR, showing that the CYP94C subfamily member OfCYP142 had the highest positive correlation with linalool synthesis gene OfTPS2. The transient expression of OfCYP142 in O. fragrans petals suggested that OfCYP142 can increase the content of linalool, an important VOC of the O. fragrans floral aroma, and a similar result was also obtained in flowers of OfCYP142 transgenic tobacco. Combined with RNA-seq data of the transiently transformed O. fragrans petals, we found that the biosynthesis pathway of secondary metabolites was significantly enriched, and many 2-C-methyl-D-erythritol 4-phosphate (MEP) pathway genes were also upregulated. This evidence indicated that the OfCYP proteins may play critical roles in the flower development and abiotic response of O. fragrans, and that OfCYP142 can participate in linalool synthesis. This study provides valuable information about the functions of P450 genes and a valuable guide for studying further functions of OfCYPs in promoting fragrance biosynthesis of ornamental plants.

Exploration of the Potential Transcriptional Regulatory Mechanisms of DNA Methyltransferases and MBD Genes in Petunia Anther Development and Multi-Stress Responses.

Cytosine-5 DNA methyltransferases (C5-MTases) and methyl-CpG-binding-domain (MBD) genes can be co-expressed. They directly control target gene expression by enhancing their DNA methylation levels in humans; however, the presence of this kind of cooperative relationship in plants has not been determined. A popular garden plant worldwide, petunia (Petunia hybrida) is also a model plant in molecular biology. In this study, 9 PhC5-MTase and 11 PhMBD proteins were identified in petunia, and they were categorized into four and six subgroups, respectively, on the basis of phylogenetic analyses. An expression correlation analysis was performed to explore the co-expression relationships between PhC5-MTases and PhMBDs using RNA-seq data, and 11 PhC5-MTase/PhMBD pairs preferentially expressed in anthers were identified as having the most significant correlations (Pearson's correlation coefficients > 0.9). Remarkably, the stability levels of the PhC5-MTase and PhMBD pairs significantly decreased in different tissues and organs compared with that in anthers, and most of the selected PhC5-MTases and PhMBDs responded to the abiotic and hormonal stresses. However, highly correlated expression relationships between most pairs were not observed under different stress conditions, indicating that anther developmental processes are preferentially influenced by the co-expression of PhC5-MTases and PhMBDs. Interestingly, the nuclear localization genes PhDRM2 and PhMBD2 still had higher correlations under GA treatment conditions, implying that they play important roles in the GA-mediated development of petunia. Collectively, our study suggests a regulatory role for DNA methylation by C5-MTase and MBD genes in petunia anther maturation processes and multi-stress responses, and it provides a framework for the functional characterization of C5-MTases and MBDs in the future.

Consensus guidelines for the detection of immunogenic cell death.

Apoptotic cells have long been considered as intrinsically tolerogenic or unable to elicit immune responses specific for dead cell-associated antigens. However, multiple stimuli can trigger a functionally peculiar type of apoptotic demise that does not go unnoticed by the adaptive arm of the immune system, which we named "immunogenic cell death" (ICD). ICD is preceded or accompanied by the emission of a series of immunostimulatory damage-associated molecular patterns (DAMPs) in a precise spatiotemporal configuration. Several anticancer agents that have been successfully employed in the clinic for decades, including various chemotherapeutics and radiotherapy, can elicit ICD. Moreover, defects in the components that underlie the capacity of the immune system to perceive cell death as immunogenic negatively influence disease outcome among cancer patients treated with ICD inducers. Thus, ICD has profound clinical and therapeutic implications. Unfortunately, the gold-standard approach to detect ICD relies on vaccination experiments involving immunocompetent murine models and syngeneic cancer cells, an approach that is incompatible with large screening campaigns. Here, we outline strategies conceived to detect surrogate markers of ICD in vitro and to screen large chemical libraries for putative ICD inducers, based on a high-content, high-throughput platform that we recently developed. Such a platform allows for the detection of multiple DAMPs, like cell surface-exposed calreticulin, extracellular ATP and high mobility group box 1 (HMGB1), and/or the processes that underlie their emission, such as endoplasmic reticulum stress, autophagy and necrotic plasma membrane permeabilization. We surmise that this technology will facilitate the development of next-generation anticancer regimens, which kill malignant cells and simultaneously convert them into a cancer-specific therapeutic vaccine.

Anti-tumor efficacy of a hepatocellular carcinoma vaccine based on dendritic cells combined with tumor-derived autophagosomes in murine models.

The majority of hepatocellular carcinoma (HCC) patients have a poor prognosis with current therapies, and new approaches are urgently needed. We have developed a novel therapeutic cancer vaccine platform based on tumor cell derived autophagosomes (DRibbles) for cancer immunotherapy. We here evaluated the effectiveness of DRibbles-pulsed dendritic cell (DC) immunization to induce anti-tumor immunity in BALB/c mouse HCC and humanized HCC mouse models generated by transplantation of human HCC cells (HepG2) into BALB/c-nu mice. DRibbles were enriched from H22 or BNL cells, BALB/c-derived HCC cell lines, by inducing autophagy and blocking protein degradation. DRibbles-pulsed DC immunization induced a specific T cell response against HCC and resulted in significant inhibition of tumor growth compared to mice treated with DCs alone. Anti- tumor efficacy of the DCs-DRibbles vaccine was also demonstrated in a humanized HCC mouse model. The results indicated that HCC/DRibbles-pulsed DCs immunotherapy might be useful for suppressing the growth of residual tumors after primary therapy of human HCC.