Background:A traditional Chinese medicine (TCM) formula, containing Astragalus membranaceus (Fisch.) Bunge, Aconitum wilsonii Stapf ex Veitch, Curcuma longa L., and Radix ophiopogonis (AACO), has therapeutic value for the treatment of chronic heart failure (CHF). Objective:This study intends to explore the pharmacological mechanism underlying the activity of the AACO formula against CHF. Materials and Methods:Using the TCM Systems Pharmacology database and Bioinformatics Analysis Tool for Molecular Mechanism of TCM, the active ingredients contained in the herbs of the AACO formula were screened. Meanwhile, the target genes related to these active ingredients were identified and genes correlated with CHF were screened. Protein-protein interaction networks were built to elucidate the relationships between the AACO formula and CHF. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) signal pathway enrichment analysis were carried out using the DAVID database. A "drug-component-target-disease" network was constructed with Cytoscape 3.7.0. The therapeutic effect of the AACO formula was proven by hemodynamic study, echocardiography evaluation, and histological analysis in transverse aortic constriction-induced CHF mice and was validated in vitro. Results:A total of 105 active ingredients and 1026 related targets were screened and identified, and 240 related targets overlapping with CHF were selected. According to GO analysis, the enriched genes participated in gene expression and cardiac contraction regulation by Ca2+ regulation. From KEGG analysis, the calcium axis was identified as one of the main mechanisms through which the AACO formula exerts an anti-CHF effect. AACO was validated to significantly improve cardiac diastolic and systolic functions in vivo via an increase in the rate of Ca2+ reuptake of the myocardial sarcoplasmic reticulum and improved myocardial contractility in vitro. Conclusions:Network pharmacology is a convenient method to study the complex pharmacological mechanisms of TCM. The calcium axis likely participates in the anti-CHF mechanism of AACO.

Coronary heart disease remains a major global health challenge, with a clear need for enhanced early risk assessment. This study aimed to elucidate metabolic signatures across various stages of coronary heart disease and develop an effective multiclass diagnostic model. Using metabolomic approaches, gas chromatography-mass and liquid chromatography-tandem mass spectrometry were used to analyze plasma samples from healthy controls, patients with stable angina pectoris, and those with acute myocardial infarction. Pathway enrichment analysis was conducted on metabolites exhibiting significant differences. The key metabolites were identified using Random Forest and Recursive Feature Elimination strategies to construct a multiclass diagnostic model. The performance of the model was validated through 10-fold cross-validation and evaluated using confusion matrices, receiver operating characteristic curves, and calibration curves. Metabolomics was used to identify 1491 metabolites, with 216, 567, and 295 distinctly present among the healthy controls, patients with stable angina pectoris, and those with acute myocardial infarction, respectively. This implicated pathways such as the glucagon signaling pathway, d-amino acid metabolism, pyruvate metabolism, and amoebiasis across various stages of coronary heart disease. After selection, testosterone isobutyrate, N-acetyl-tryptophan, d-fructose, l-glutamic acid, erythritol, and gluconic acid were identified as core metabolites in the multiclass diagnostic model. Evaluating the diagnostic model demonstrated its high discriminative ability and accuracy. This study revealed metabolic pathway perturbations at different stages of coronary heart disease, and a precise multiclass diagnostic model was established based on these findings. This study provides new insights and tools for the early diagnosis and treatment of coronary heart disease.

Polygalacturonases (PGs) are important plant cell wall degrading enzymes that catalyze pectin hydrolysis and are essential during almost all stages of plant development. However, the functional properties of cotton PGs, especially their expression patterns during reproductive organ development, remain elusive. Herein, the systematic and comprehensive identification and analysis of cotton PGs were conducted. The identified PGs were divided into six groups with conserved gene structures and motifs. The purifying selection was their primary evolutionary force. Meanwhile, cis-elements, TFs, and miRNAs related to stress and tissue-specific development, especially anther development, were identified. Transcriptome and qRT-PCR analysis revealed that many GhPGs were expressed in response to environmental stress. They also exhibited tissue specificity, especially at various stages of anther development. Many genes involved in anther development were co-expressed with GhPGs. This study provides valuable information and novel insights for further exploring the function of cotton PGs and their implementation in cotton improvement.

Abstract Background and Objectives: Kanli granule (KG) is a Traditional Chinese Medicine (TCM), which has a significant effect on chronic heart failure (CHF). KG takes "warming and invigorating the heart and kidney Yang Qi, promoting water and blood circulation" as the treatment principle, which can make the heart Yang vibrate, the kidney water transpiration, and the blood promote the circulation of water without the danger of stopping warter blood stasis. However, due to the complexity of TCM, the action mechanism of KG is unclear. In this study, we employed a network pharmacology approach combined with experimental verification to investigate the mechanism of KG in the treatment of CHF. Materials and methods: The active ingredients and targets of KG were searched by TCMSP and TCM database@Taiwan databases, and the CHF-related targets were collected from DisGeNET, OMIM and TTD databases. Gene ontology (GO) analysis and Kyoto Encyclopedia of Gene and Genome (KEGG) signal pathway analysis were carried out through DAVID database. Furthermore, the bubble diagrams of GO analysis and KEGG signal pathway analysis are made on OmicShare platform. The network diagram of "herbs–ingredients–targets–pathways" was constructed by Cytoscape3.7.0 software. We established a TAC induced CHF mice model to verify the protective mechanism of KG. Results: 30 active ingredients of KG were screened for the prevention and treatment of CHF, and 37 targets for the prevention and treatment of CHF by the active components of KG, including SERCA2a, PLB. GO analysis showed that there were 219 items related to biological process, 32 items related to cellular composition and 42 items related to molecular function. There are 81 related KEGG signaling pathways, including calcium signaling pathway. The results of animal experiments showed that KG significantly improved cardiac function in CHF mice by reducing LVEF, FS, NT -proBNP, and KG significantly improved cardiac structure in CHF mice by decreasing LVIDd, LVPWd, and the extent of cardiac fibrosis. Further mechanistic studies revealed that KG upregulated SERCA2a expression and activity to ameliorate CHF. Conclusion: KG may prevent and treat CHF by acting on calcium signaling pathway, increasing SERCA2a expression and improving cardiac function and cardiac structure.

INTRODUCTION:Cotton is a vital industrial crop that is gradually shifting to planting in arid areas. However, tubby-like proteins (TULPs) involved in plant response to various stresses are rarely reported in cotton. The present study exhibited that GhTULP30 transcription in cotton was induced by drought stress.OBJECTIVE:The present study demonstrated the improvement of plant tolerance to drought stress by GhTULP30 through regulation of stomatal movement.METHODS:GhTULP30 response to drought and salt stress was preliminarily confirmed by qRT-PCR and yeast stress experiments. Ectopic expression in Arabidopsis and endogenous gene silencing in cotton were used to determine stomatal movement. Yeast two-hybrid and spilt-luciferase were used to screen the interacting proteins.RESULTS:Ectopic expression of GhTULP30 in yeast markedly improved yeast cell tolerance to salt and drought. Overexpression of GhTULP30 made Arabidopsis seeds more resistant to drought and salt stress during seed germination and increased the stomata closing speed of the plant under drought stress conditions. Silencing of GhTULP30 in cotton by virus-induced gene silencing (VIGS) technology slowed down the closure speed of stomata under drought stress and decreased the length and width of the stomata. The trypan blue and diaminobenzidine staining exhibited the severity of leaf cell necrosis of GhTULP30-silenced plants. Additionally, the contents of proline, malondialdehyde, and catalase of GhTULP30-silenced plants exhibited significant variations, with obvious leaf wilting. Protein interaction experiments exhibited the interaction of GhTULP30 with GhSKP1B and GhXERICO.CONCLUSION:GhTULP30 participates in plant response to drought stress. The present study provides a reference and direction for further exploration of TULP functions in cotton plants.