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Co-culture is known as an efficient way to explore the metabolic potential of fungal strains for new antibiotics and other therapeutic agents that could counter emerging health issues. To study the effect of co-culture on the secondary metabolites and bioactivities of two marine strains, Aspergillus terreus C23-3 and Aspergillus. unguis DLEP2008001, they were co-cultured in live or inactivated forms successively or simultaneously. The mycelial morphology and high-performance thin layer chromatography (HPTLC) including bioautography of the fermentation extracts were recorded. Furthermore, the agar cup-plate method was used to compare the antimicrobial activity of the extracts. Based on the above, liquid chromatography-photodiode array-tandem mass spectrometry (LC-PDA-MS/MS) together with Global Natural Products Social molecular networking (GNPS) and multiple natural products database mining were used to further analyze their secondary metabolite variations. The comprehensive results showed the following trends: (1) The strain first inoculated will strongly inhibit the growth and metabolism of the latter inoculated one; (2) Autoclaved A. unguis exerted a strong inducing effect on later inoculated A. terreus, while the autoclaved A. terreus showed high stability of its metabolites and still potently suppressed the growth and metabolism of A. unguis; (3) When the two strains are inoculated simultaneously, they both grow and produce metabolites; however, the A. terreus seemed to be more strongly induced by live A. unguis and this inducing effect surpassed that of the autoclaved A. unguis. Under some of the conditions, the extracts showed higher antimicrobial activity than the axenic cultures. Totally, A. unguis was negative in response but potent in stimulating its rival while A. terreus had the opposite effect. Fifteen MS detectable and/or UV active peaks showed different yields in co-cultures vs. the corresponding axenic culture. GNPS analysis assisted by multiple natural products databases mining (PubChem, Dictionary of Natural Products, NPASS, etc.) gave reasonable annotations for some of these peaks, including antimicrobial compounds such as unguisin A, lovastatin, and nidulin. However, some of the peaks were correlated with antagonistic properties and remain as possible novel compounds without mass or UV matching hits from any database. It is intriguing that the two strains both synthesize chemical 'weapons' for antagonism, and that these are upregulated when needed in competitive co-culture environment. At the same time, compounds not useful in this antagonistic setting are downregulated in their expression. Some of the natural products produced during antagonism are unknown chlorinated metabolites and deserve further study for their antimicrobial properties. In summary, this study disclosed the different responses of two Aspergillus strains in co-culture, revealed their metabolic variation, and displayed new opportunities for antibiotic discovery.

F. M. Dostoevsky's novel The Devils is an indispensable text for exploring the idea of Russian nihilism. This novel has two threads: one reflects on the nihilistic trend of the 1860s in Russia on the socio-political level, while the other delves into the Russian folk beliefs on the religious and cultural level. These two seemingly opposing threads are, in fact, implicitly intertwined and deeply related by the religious core of Russian nihilism. The "fire" scene in the novel, which revolves around nihilists such as Peter Verkhovensky, seems to resonate with the expectation of the "fire of doom" in Russian folk beliefs, thus hinting at the potential link of Russian nihilism and apocalyptic eschatology. This hint put forth by Dostoevsky in The Devils has been captured and confirmed by later thinkers such as N. Berdyaev. Revisiting history through these lenses reveals that ever since the "Baptism of Rus'," Russian folk interpretations of the Book of Revelation diverged from the official teachings of the Orthodox Church, embodying both a vision of "burning the world" and "universal salvation." This particular apocalyptic thought can be seen as the ideological source of Russian nihilism to a certain extent. [ABSTRACT FROM AUTHOR]

As a part of the important species that form coral reef ecosystems, stony corals have become a potential source of pharmacologically active lead compounds for an increasing number of compounds with novel chemical structures and strong biological activity. In this study, the secondary metabolites and biological activities are reported for Aspergillus terreus C21-1, an epiphytic fungus acquired from Porites pukoensis collected from Xuwen Coral Reef Nature Reserve, China. This strain was cultured in potato dextrose broth (PDB) media and rice media with different salinities based on the OSMAC strategy. The mycelial morphology and high-performance thin layer chromatographic (HPTLC) fingerprints of the fermentation extracts together with bioautography were recorded. Furthermore, an untargeted metabolomics study was performed using principal component analysis (PCA), orthogonal projection to latent structure discriminant analysis (O-PLSDA), and feature-based molecular networking (FBMN) to analyze their secondary metabolite variations. The comprehensive results revealed that the metabolite expression in A. terreus C21-1 differed significantly between liquid and solid media. The metabolites produced in liquid medium were more diverse but less numerous compared to those in solid medium. Meanwhile, the mycelial morphology underwent significant changes with increasing salinity under PDB cultivation conditions, especially in PDB with 10% salinity. Untargeted metabolomics revealed significant differences between PDB with 10% salinity and other media, as well as between liquid and solid media. FBMN analysis indicated that alkaloids, which might be produced under high salt stress, contributed largely to the differences. The biological activities results showed that six groups of crude extracts exhibited acetylcholinesterase (AChE) inhibitory activities, along with 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical scavenging and antibacterial activities. The results of this study showed that the increase in salinity favored the production of unique alkaloid compounds by A. terreus C21-1. [ABSTRACT FROM AUTHOR]

Neuroinflammation is one of the main mechanisms involved in the progression of neurodegenerative diseases (NDs), and microglial activation is the main feature of neuroinflammation. Polaprezinc (Pol), a chelator of L-carnosine and zinc, is widely used as a clinical drug for gastric ulcers. However, its potential effects on NDs remain unexplored. In LPS-induced BV-2 microglia, we found that Pol reduced the generation of NO and ROS and revealed inhibited expression of iNOS, COX-2, and inflammatory factors such as IL-6, TNF-α, and 1L-1β by Pol using qRT-PCR and Western blotting. These effects were found to be associated with the suppression of the NF-κB signaling pathway. Moreover, we evaluated the potential synergistic effects of aspergillusidone G (Asp G) when combined with Pol. Remarkably, co-treatment with low doses of Asp G enhanced the NO inhibition by Pol from approximately 30% to 80% in LPS-induced BV2 microglia, indicating a synergistic anti-inflammatory effect. A bioinformatics analysis suggested that the synergistic mechanism of Asp G and Pol might be attributed to several targets, including NFκB1, NRF2, ABL1, TLR4, and PPARα. These findings highlight the anti-neuroinflammatory properties of Pol and its enhanced efficacy when combined with Asp G, proposing a novel therapeutic strategy for managing neuroinflammation in NDs. [ABSTRACT FROM AUTHOR]

The secondary metabolites of endophytic fungus Alternaria sp. SK6YW3L were studied. The fungus was isolated from the fresh fruit of mangrove plant Sonneratia apetala collected from Guangxi Shankou Mangrove Nature Reserve. The strain was fermented and cultured with 3% salinity rice medium, and then subjected to silica gel column chromatography, semi-preparative HPLC, Sephadex LH-20, ODS and recrystallization. Thirteen anthraquinones including 7-acetyl-l, 3, 6-trihy-droxyanthracene-9, 10-dione (1), (11S) -1, 3, 6-trihydroxy-7-(1-hydroxyethyl) anthracene-9, 10-dione (2), 7-0-demethyl-6-deoxybostrycoidin (3), altersolanol A (4), dactylariol (5), altersolanol B (6), emodin (7), emodin-3-methyl ether (8), 6-hydroxy -aloeemodin (9), anthraquinone A (10), 1, 5-dihydroxy-7-methoxy-2- methylanthracene-9, 10-dione (11), alterporriol N (12) and alterporriol A (13), were identified using modern spectroscopy techniques such as 1D, 2D NMR and MS, and then comparing with literature data. The single crystal structure of compounds 1 and 4 were analyzed by single-crystal X-Ray diffraction experiment using CuK a radiation. Among them, compound 1 was obtained as a new single crystal and the absolute configuration of compound 4 was determined to be 5R, 6S, 7R, 8S. The absolute configurations of other compounds were determined by comparing optical rotation and CD data. In the bioactivity assay, compounds 1-3 exhibited a-glucosidase inhibitory activity with IC50 values of (210.1 ± 1.2), (125.8 ± 1.5) and (68.7 ± 1.3) ^mol/L, respectively. [ABSTRACT FROM AUTHOR]