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A large body of fungal secondary metabolites has been discovered to exhibit potent antibacterial activities with distinctive mechanisms and has the potential to be an untapped resource for drug discovery. Here, we describe the isolation and characterization of five new antibacterial indole diketopiperazine alkaloids, namely 24,25-dihydroxyvariecolorin G (1), 25-hydroxyrubrumazine B (2), 22-chloro-25-hydroxyrubrumazine B (3), 25-hydroxyvariecolorin F (4), and 27-epi-aspechinulin D (5), along with the known analogue neoechinulin B (6) from a fungal strain of deep-sea cold seep-derived Aspergillus chevalieri. Among these compounds, 3 and 4 represented a class of infrequently occurring fungal chlorinated natural products. Compounds 1–6 showed inhibitory activities against several pathogenic bacteria with MIC values ranging from 4 to 32 μg/mL. It was revealed that compound 6 could induce structural damage to the Aeromonas hydrophila cells based on the observation by scanning electron microscopy (SEM), which led to the bacteriolysis and death of A. hydrophila, suggesting that neoechinulin B (6) might be a potential alternative to novel antibiotics development.

Six new metabolites, including a pair of inseparable mixtures of secofumitremorgins A (1a) and B (1b), which differed in the configuration of the nitrogen atom, 29-hydroxyfumiquinazoline C (6), 10R-15-methylpseurotin A (7), 1,4,23-trihydroxy-hopane-22,30-diol (10), and sphingofungin I (11), together with six known compounds (2–5 and 8–9), were isolated and identified from the deep-sea sediment-derived fungus Aspergillus fumigatus SD-406. Their structures were determined by detailed spectroscopic analysis of NMR and MS data, chiral HPLC analysis of the acidic hydrolysate, X-ray crystallographic analysis, J-based configuration analysis, and quantum chemical calculations of ECD, OR, and NMR (with DP4+ probability analysis). Among the compounds, 1a/1b represent a pair of novel scaffolds derived from indole diketopiperazine by cleavage of the amide bond following aromatization to give a pyridine ring. Compounds 1, 4, 6, 7, 10 and 11 showed inhibitory activities against pathogenic bacteria and plant pathogenic fungus, with MIC values ranging from 4 to 64 μg/mL.

Background: Melatonin (MLT) can improve mitophagy, thereby ameliorating cognitive deficits in Alzheimer's disease (AD) patients. Hence, our research focused on the potential value of MLT-related genes (MRGs) in AD through bioinformatic analysis. Methods: First, the key cells in the single-cell dataset GSE138852 were screened out based on the proportion of annotated cells and Fisher's test between the AD and control groups. The differentially expressed genes (DEGs) in the key cell and GSE5281 datasets were identified, and the MRGs in GSE5281 were selected via weighted gene coexpression network analysis. After intersecting two sets of DEGs and MRGs, we performed Mendelian randomization analysis to identify the MRGs causally related to AD. Biomarkers were further ascertained through receiver operating characteristic curve (ROC) and expression analysis in GSE5281 and GSE48350. Furthermore, gene set enrichment analysis, immune infiltration analysis and correlation analysis with metabolic pathways were conducted, as well as construction of a regulator network and molecular docking. Results: According to the Fisher test, oligodendrocytes were regarded as key cells due to their excellent abundance in the GSE138852 dataset, in which there were 281 DEGs between the AD and control groups. After overlapping with 3,490 DEGs and 550 MRGs in GSE5281, four genes were found to be causally related to AD, namely, G protein-coupled receptor, family C, group 5, member B (GPRC5B), Methyltransferase-like protein 7 A (METTL7A), NF-κB inhibitor alpha (NFKBIA) and RAS association domain family 4(RASSF4). Moreover, GPRC5B, NFKBIA and RASSF4 were deemed biomarkers, except for METTL7A, because of their indistinctive expression between the AD and control groups. Biomarkers might be involved in oxidative phosphorylation, adipogenesis and heme metabolism. Moreover, T helper type 17 cells, natural killer cells and CD56dim natural killer cells were significantly correlated with biomarkers. Transcription factors (GATA2, POU2F2, NFKB1, etc.) can regulate the expression of biomarkers. Finally, we discovered that all biomarkers could bind to MLT with a strong binding energy. Conclusion: Our study identified three novel biomarkers related to MLT for AD, namely, GPRC5B, NFKBIA and RASSF4, providing a novel approach for the investigation and treatment of AD patients. [ABSTRACT FROM AUTHOR]

Incorporating corporate social responsibility (CSR) into organizational strategies has become essential, demonstrating a dedication to ethical conduct and sustainable practices. This paper investigates how consistency in CSR practices impacts organizational attractiveness. Drawing upon the theory of the continuum model of impression formation, two separate studies were undertaken to investigate the influence of CSR consistency (both consistent and inconsistent CSR) on the appeal of organizations. Besides, these studies aimed to evaluate the mediating roles of conceptual fluency and perceived corporate hypocrisy in this relationship, as well as the moderating effect of two corporate communication strategies (proactive and passive). The study found that perceptions of corporate hypocrisy played a significant mediating role in the link between inconsistent CSR practices and the appeal of an organization. This mediating effect was diminished by the use of proactive communication strategies. In contrast, conceptual fluency was identified as a key mediator in the relationship between consistent CSR practices and organizational attractiveness, with its mediating effect being enhanced by proactive communication strategies. This study makes a novel contribution by focusing on the temporal stability of CSR initiatives and broadens the understanding of whether sustained engagement in CSR activities over time confers greater organizational attractiveness than occasional or random initiatives. This study extends the theory of the relationship between perceived CSR and job seekers and provides guidance and recommendations for CSR activities and HR recruitment practices for companies in the post‐epidemic era. [ABSTRACT FROM AUTHOR]

Chemical elements support various plant functions, and their reutilization is important for plant ecological adaptation. However, there is a lack of studies comparing the elemental concentration and their reutilization in floral petals and leaves of the same plant. To address this research gap, we conducted a comparative study across 38 plant species with diverse life forms in a common garden. Our investigation focused on the nutrient concentration of 10 elements in both petals and leaves and functional traits, including flower lifespan, dry mass per unit area, water concentration, and vein density. We have found that the elements of nitrogen (N), calcium (Ca), magnesium (Mg), iron (Fe), and manganese (Mn) were more abundant in leaves. In contrast, petals contained higher concentrations of phosphorus (P) and potassium (K). N, P, K, Ca, Mg, and sodium (Na) concentrations of petals were positively related to leaves. In herbaceous plants, their petals showed significant resorption of P and K, while N, P, and K were detected with significant resorption in leaves from all life forms. A positive correlation was found between the resorption of P in leaves and petals. From the perspective of the carbon economic spectrum, N and P showed a negative correlation with dry mass per unit area in leaves. Meanwhile, petal dry mass per area and floral longevity were significantly negatively correlated with P. Our findings elucidate the nutritional basis for the functional differentiation between petals and leaves. [ABSTRACT FROM AUTHOR]

Background: The relationship between serum low-density lipoprotein cholesterol (LDL-C) and the risk of relapse in neuromyelitis optica spectrum disorder (NMOSD) remains uncertain. We aimed to examine the association between serum LDL-C level and relapse in NMOSD patients. Methods: We conducted an analysis of the prospective observational NMOSD cohort study with consecutive 184 hospitalized NMOSD patients from department of neurology. Blood samples were collected to measure LDL-C level upon admission. Primary and relapse were evaluated during hospitalization. The relationship between serum LDL-C level and relapse were analyzed by linear curve fitting analyses. Crude and adjusted odds ratios (OR) of LDL-C for relapse with 95% confidence intervals were analyzed using multiple logistic regression models. ROC curve analysis was used to identify the target lipid-lowering value of LDL-C and the probability of relapse was evaluated by the Kaplan–Meier Plot. Results: Over a mean disease course of 100± 87 days, 59.24% (n=109) participants developed relapse with higher LDL-C than the primary group (n=75) (p< 0.001). Adjusted smoothed plots suggested that there were linear relationships between serum LDL-C level and relapse (p< 0.001). The OR (95% CI) between serum LDL-C level and relapse were 2.67 (1.76– 4.04, p< 0.001), and 2.38 (1.48– 3.83, p< 0.001) respectively in NMOSD patients before and after adjusting for potential confounders. The target LDL-C lowering values were 2.795 mmol/L with potential benefits to prevent relapse in NMOSD. Conclusion: In this sample of NMOSD patients, we found that the elevated serum LDL-C was independently and positively associated with the relapse, and serum LDL-C should be well-controlled to prevent the relapse of NMOSD. [ABSTRACT FROM AUTHOR]

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