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MiRNAs can be used as promising diagnostic biomarkers of heart failure, while lncRNAs act as competing endogenous RNAs of miRNAs. In this study, we collected peripheral blood monocytes from subjects with or without HF to explore the association between certain lncRNAs, miRNAs and HF. Heart failure patients with preserved or reduced ejection fraction were recruited for investigation. ROC analysis was carried out to evaluate the diagnostic values of certain miRNAs and lncRNAs in HF. Luciferase assays were used to study the regulatory relationship between above miRNAs and lncRNAs. LncRNA overexpression was used to explore the effect of certain miRNAs in H9C2 cells. Expression of miR‐30c was significantly decreased in the plasma and peripheral blood monocytes of patients suffering from heart failure, especially in these with reduced ejection fraction. On the contrary, the expression of lncRNA‐CASC7 was remarkably increased in the plasma and peripheral blood monocytes of patients suffering from heart failure. Both miR‐30c and lncRNA‐CASC7 expression showed a promising efficiency as diagnostic biomarkers of heart failure. Luciferase assays indicated that miR‐30c played an inhibitory role in lncRNA‐CASC7 and IL‐11 mRNA expression. Moreover, the overexpression of lncRNA‐CASC7 suppressed the expression of miR‐30c while evidently increasing the expression of IL‐11 mRNA and protein in H9C2 cells. This study clarified the relationship among miR‐30c, lncRNA‐CASC7 and IL‐11 expression and the risk of heart failure and showed that lncRNA‐CASC7 is potentially involved in the pathogenesis of HF via modulating the expression of miR‐30c.

Coronary microembolization (CME) refers to embolism in the coronary microcirculation. This study showed a reduction in succinyl transferase (CPT1A) and the succinylation substrate (succinyl-CoA) in cardiomyocytes in CME models, suppressing the succinylation of the mitochondrially localized protein TRMT10C. Suppression of succinylation promotes KPNA4 recognition of two nuclear localization signals (NLSs), KAKR and KKK(X) KVKK, in TRMT10C, which induces the transport of TRMT10C from the cytoplasm to the nucleus rather than to the mitochondria. Nuclear TRMT10C induces YTHDF2-mediated decay of TAFAZZIN and NLRX1 through m1A modifications. The reduction in TAFAZZIN and NLRX1 is associated with multiple detrimental effects, such as inflammation mediated by NF-κB and NLRP3, reactive oxygen species (ROS) production, and suppression of mitophagy. TRMT10C knockdown suppressed the accumulation of TRMT10C in the nucleus. It restored NLRX1 and TAFAZZIN protein levels in cardiomyocytes under hypoxia. However, the deficiency of TRMT10C in the mitochondria did not improve-or even worsened-with TRMT10C knockdown. Inducing TRMT10C succinylation via CPT1A overexpression led to the redistribution of TRMT10C to the mitochondria rather than the nucleus, which is likely a better approach for improving cardiomyocyte function under hypoxia than direct TRMT10C knockdown. This study reveals a novel pathological mechanism underlying CME and suggests potential therapeutic targets for this disease.

Coronary microembolization (CME) is a severe medical condition that occurs during acute coronary syndrome, leading to myocardial inflammation, apoptosis, and cardiac dysfunction. The research investigated SRSF1 biological functions during myocardial inflammation caused by CME and its underlying mechanisms. CME models were established in rats injected with microspheres in the left ventricle and oxygen-glucose deprivation (OGD)-exposed cardiomyocytes. RT-qPCR, Western blotting and immunohistochemical staining were used to evaluate the expression of target molecules. Myocardial apoptosis was detected by flow cytometry. The direct binding between SRSF1 and ectonucleotide pyrophosphatase/phosphodiesterase 3 (ENPP3) was verified by RIP and TRAP. Protein interaction was determined by Co-IP. The dual-luciferase reporter assay measured inflammatory cytokine transcription levels. Myocardial injury was assessed by HE staining and ultrasound examinations. The study used ELISA to measure inflammatory cytokines and cardiac troponin I (cTnI) levels. SRSF1 expression was strikingly enhanced in CME models. Knockdown of SRSF1 effectively restrained NF-κB-mediated myocardial inflammation through increasing ENPP3 mRNA/lncRNA ENPP3 ratio by regulating alternative splicing of ENPP3 pre-mRNA. The GlcNAcylation of bromodomain-containing protein 4 (BRD4) was reduced during CME, which increased BRD4 protein level to trigger NF-κB-mediated inflammation. SRSF1/ENPP3 axis inhibited the GlcNAcylation of BRD4 in CME. Myocardial-specific knockout of SRSF1 restored cardiac function and restrained myocardial inflammation in CME rats by inactivation of the ENPP3/BRD4/NF-κB pathway. SRSF1 facilitates CME-induced myocardial inflammation by up-regulating ENPP3/lncRNA ENPP3 ratio to suppress GlcNAcylation of BRD4, suggesting SRSF1 inhibition as a promising therapeutic strategy for CME.

Coronary microembolization (CME) is a serious cardiovascular complication that causes severe cardiac dysfunction and arrhythmias. Glutathione (GSH) exhaustion-induced oxidative stress is a key contributor to CME. Here, we explore the molecular mechanisms underlying GSH imbalance during CME. We show that CME induces myocardial injury by disturbing GSH homeostasis, which is ameliorated by glutamate-cysteine ligase modifier subunit (GCLM) or glutaminase (GLS) overexpression. Lysine-specific histone demethylase 1A (KDM1A) removes H3K9me1/2 from the promoter regions of GCLM and GLS to promote their epigenetic expression, thereby maintaining GSH homeostasis in CME. KDM1A is ubiquitinated at the K355 site during CME via inhibiting ubiquitin-specific peptidase 16 (USP16)-mediated deubiquitination. Inducible nitric oxide synthase (iNOS) facilitates S-nitrosylation (SNO) of USP16 at the C731 site, contributing to KDM1A ubiquitination and causing GSH imbalance during CME. Altogether, SNO-USP16 inhibition stabilizes the KDM1A protein to epigenetically activate GCLM and GLS, thus maintaining GSH homeostasis and relieving CME-induced myocardial injury.

Silicosis is a global occupational disease characterized by lung dysfunction, pulmonary inflammation, and fibrosis, for which there is a lack of effective drugs. Pirfenidone has been shown to exert anti-inflammatory and anti-fibrotic properties in the lung. However, whether and how pirfenidone is effective against silicosis remains unknown. Here, we evaluated the efficacy of pirfenidone in the treatment of early and advanced silicosis in an experimental mouse model and explored its potential pharmacological mechanisms. We found that pirfenidone alleviated silica-induced lung dysfunction, secretion of inflammatory cytokines (TNF-α, IL-1β, IL-6) and deposition of fibrotic proteins (collagen I and fibronectin) in both early and advanced silicosis models. Moreover, we observed that both 100 and 200 mg/kg pirfenidone can effectively treat early-stage silicosis, while 400 mg/kg was recommended for advanced silicosis. Mechanistically, antibody array and bioinformatic analysis showed that the pathways related to IL-17 secretion, including JAK-STAT pathway, Th17 differentiation, and IL-17 pathway, might be involved in the treatment of silicosis by pirfenidone. Further in vivo experiments confirmed that pirfenidone reduced the production of IL-17A induced by silica exposure via inhibiting STAT3 phosphorylation. Neutralizing IL-17A by anti-IL-17A antibody improved lung function and reduced pulmonary inflammation and fibrosis in silicosis animals. Collectively, our study has demonstrated that pirfenidone effectively ameliorated silica-induced lung dysfunction, pulmonary inflammation and fibrosis in mouse models by inhibiting the secretion of IL-17A.

Cuticular proteins (CPs) are crucial components of the insect cuticle. Although numerous genes encoding cuticular proteins have been identified in known insect genomes to date, their functions in maintaining insect body shape and adaptability remain largely unknown. In the current study, positional cloning led to the identification of a gene encoding an RR1-type cuticular protein, BmorCPR2, highly expressed in larval chitin-rich tissues and at the mulberry leaf-eating stages, which is responsible for the silkworm stony mutant. In the Dazao-stony strain, the BmorCPR2 allele is a deletion mutation with significantly lower expression, compared to the wild-type Dazao strain. Dysfunctional BmorCPR2 in the stony mutant lost chitin binding ability, leading to reduced chitin content in larval cuticle, limitation of cuticle extension, abatement of cuticle tensile properties, and aberrant ratio between internodes and intersegmental folds. These variations induce a significant decrease in cuticle capacity to hold the growing internal organs in the larval development process, resulting in whole-body stiffness, tightness, and hardness, bulging intersegmental folds, and serious defects in larval adaptability. To our knowledge, this is the first study to report the corresponding phenotype of stony in insects caused by mutation of RR1-type cuticular protein. Our findings collectively shed light on the specific role of cuticular proteins in maintaining normal larval body shape and will aid in the development of pest control strategies for the management of Lepidoptera.

is an opportunistic fungus that can cause severe and potentially fatal pneumonia (PCP) in immunodeficient patients. In this study, we investigated the genetic polymorphisms of at eight different loci, including six nuclear genes (ITS, 26S rRNA, , , and β-Tub) and two mitochondrial genes (mtLSU-rRNA and ) in three PCP cases, including two patients with HIV infection and one without HIV infection in Shanxi Province, P.R. China. The gene targets were amplified by PCR followed by sequencing of plasmid clones. The HIV-negative patient showed a coinfection with two genotypes of at six of the eight loci sequenced. Of the two HIV-positive patients, one showed a coinfection with two genotypes of at the same two of the six loci as in the HIV-negative patient, while the other showed a single infection at all eight loci sequenced. None of the three drug target genes ( and ) showed mutations known to be potentially associated with drug resistance. This is the first report of genetic polymorphisms of in PCP patients in Shanxi Province, China. Our findings expand our understanding of the genetic diversity of in China.

Melanin and cuticular proteins are important cuticle components in insect. Cuticle defects caused by mutations in cuticular protein-encoding genes can hinder melanin deposition. However, the effects of melanin variation on cuticular protein-encoding genes and the corresponding morphological traits associated with these genes are remain largely unknown. Using Bombyx mori as a model, we showed that the melanism levels during larval cuticle pigmentation correlated positively with the expression of cuticular protein-encoding genes. This correlation stemmed from the simultaneous induction of these genes by the melanin precursors. More importantly, the effect of the melanism background on the cuticles induced the up-regulation of other functionally redundant cuticular protein-encoding genes to rescue the morphological and adaptive defects caused by the dysfunction of some mutated cuticular proteins, and the restorative ability increased with increasing melanism levels, which gives a novel evidence that melanism enhances insect adaptability. These findings deepen our understanding of the interactions among cuticle components, as well as their importance in the stabilizing of the normal morphology and function of the cuticle.