Two new furan derivatives, hypofurans A and B (1 and 2), and three new cyclopentenone derivatives, hypocrenones A–C (3–5), along with seven known compounds (6–12), were isolated from a marine fungus Hypocrea koningii PF04 associated with the sponge Phakellia fusca. Among them, compounds 10 and 11 were obtained for the first time as natural products. The planar structures of compounds 1–5 were elucidated by analysis of their spectroscopic data. Meanwhile, the absolute configuration of 1 was determined as 2R,3R by the comparison of the experimental and calculated electronic circular dichroism (ECD) spectra. All the isolates were evaluated for their antibacterial and antioxidant activity. Compounds 1, 10, and 12 all showed modest antibacterial activity against Staphylococcus aureus ATCC25923 (MIC, 32 μg/mL). In addition, compounds 1, 10 and 11 exhibited moderate DPPH radical scavenging capacity with IC₅₀ values of 27.4, 16.8, and 61.7 µg/mL, respectively.

Since osteoporosis critically influences the lives of patients with a high incidence, effective therapeutic treatments are important. Quercetin has been well recognized as a bone-sparing agent and thus the underlying mechanisms warrant further investigation. In the current study, the network pharmacology strategy and zebrafish model were utilized to explain the potential pharmacological effects of quercetin on osteoporosis. The potential targets and related signaling pathways were explored through overlapping target prediction, protein–protein interaction network construction, and functional enrichment analysis. Furthermore, we performed docking studies to verify the specific interactions between quercetin and crucial targets. Consequently, 55 targets were related to osteoporosis disease among the 159 targets of quercetin obtained by three database sources. Thirty hub targets were filtered through the cytoNCA plugin. Additionally, the Gene Ontology functions in the top 10 respective biological processes, molecular functions, and cell components as well as the top 20 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were depicted. The most significance difference in the KEGG pathways was the TNF signaling pathway, consisting of the Nuclear Factor Kappa B Subunit (NF-κB), Extracellular Regulated Protein Kinases (ERK) 1/2, Activator Protein 1 (AP-1), Interleukin 6 (IL6), Transcription factor AP-1 (Jun), and Phosphatidylinositol 3 Kinase (PI3K), which were probably involved in the pharmacological effects. Moreover, molecular docking studies revealed that the top three entries were Interleukin 1 Beta (IL1B), the Nuclear Factor NF-Kappa-B p65 Subunit (RelA), and the Nuclear Factor Kappa B Subunit 1 (NFKB1), respectively. Finally, these results were verified by alizarin red-stained mineralized bone in zebrafish and related qPCR experiments. The findings probably facilitate the mechanism elucidation related to quercetin anti-osteoporosis action.

Aristolochic acid (AA) is renowned for engendering nephrotoxicity and teratogenicity. Previous literature has reported that AA treatment resulted in heart failure (HF) via inflammatory pathways. Yet, its implications in HF remain comparatively uncharted territory, particularly with respect to underlying mechanisms. In our study, the zebrafish model was employed to delineate the cardiotoxicity of AA exposure and the restorative capacity of a phytogenic alkaloid palmatine (PAL). PAL restored morphology and blood supply in AA-damaged hearts by o-dianisidine staining, fluorescence imaging, and Hematoxylin and Eosin staining. Furthermore, PAL attenuated the detrimental effects of AA on ATPase activity, implying myocardial energy metabolism recovery. PAL decreased the co-localization of neutrophils with cardiomyocytes, implying an attenuation of the inflammatory response induced by AA. A combination of network pharmacological analysis and qPCR validation shed light on the therapeutic mechanism of PAL against AA-induced heart failure via upregulation of the epidermal growth factor receptor (EGFR) signaling pathway. Subsequent evaluations using a transcriptological testing, inhibitor model, and molecular docking assay corroborated PAL as an IKBKB enzyme activator. The study underscores the possible exploitation of the EGFR pathway as a potential therapeutic target for PAL against AA-induced HF, thus furthering the continued investigation of the toxicology and advancement of protective pharmaceuticals for AA.

Background: Hepatocellular carcinoma (HCC) continues to pose a major health concern for global public health, characterized by pronounced clinical heterogeneity in survival outcomes and therapeutic efficacies. The stromal senescence constitutes a major impediment in constructing robust prognostic models. This study aimed to develop and validate a robust prognostic prediction model to accurately assess the prognostic risk of HCC patients and facilitate personalized precision treatment. Methods: We obtained data from the Gene Expression Omnibus (GEO), The Cancer Genome Atlas (TCGA), and the Clinical Proteomic Tumor Analysis Consortium (CPTAC) databases. Area Under the Curve Cell (AUCell) was used to quantify senescence in single-cell RNA sequencing (scRNA-seq) of HCC. A stromal-senescence prognostic signature was then built by using Cox and least absolute shrinkage and selection operator (LASSO) analyses. High- and low-risk stratification was interrogated with clusterProfiler, maftools, immune-checkpoint analysis, and oncoPredict. Signature expression was cross-validated in scRNA-seq, bulk RNA sequencing (RNA-seq), proteomic, and spatial transcriptomic datasets. Small-molecule ligands targeting DNASE1L3 were identified by virtual screening, and their binding was verified by molecular docking and dynamics simulations. Results: It was found that HCC-associated stromal cells exhibited the most pronounced levels of senescence among cell populations. Using machine-learning algorithms, we successfully established DNASE1L3, NDRG2, ADAM15, IGFBP3, MMP14, and ANGPT2 as a stromal-senescence prognostic signature in HCC. Subsequent comparisons between patient subgroups based on this signature revealed distinct differences in long-term survival outcomes, mutational landscapes, immune checkpoint expression, and responsiveness to chemotherapeutic agents. Further, the stromal-senescence prognostic signature is significantly associated with metabolic reprogramming, immune inflammation, cell proliferation, and metastasis. Multi-omics data analyses were employed to validate the expression levels of this signature in both tumor and normal tissues. In addition, virtual screening identified three potential DNASE1L3 candidates: STL167676, STK598132, and STK119225. Conclusions: This study developed a robust stromal senescence-associated gene signature that accurately predicts survival outcomes in HCC patients and identified candidate stromal senescence-related molecules for more effective personalized therapy.

Two antiepileptic metabolites, nordichloridene (1) and 9-chloro-1,2,3,4-tetrahydroacridine (2), were isolated from the marine algae-derived fungus Chloridium sp. NBU3282. Nordichloridene (1) is a new norditerpenoid featuring a bicyclic 6/6 trans-decalin skeleton conjugated with an α,β-unsaturated methyl vinyl ketone side chain. Its structure was elucidated via comprehensive spectroscopic analysis, and the stereochemical configuration was established by NOESY spectroscopy combined with quantum chemical calculations. Compound 2, previously known only in synthetic chemistry, was identified from a natural source for the first time. Both compounds suppressed pentylenetetrazole-induced hyperactivity in a zebrafish epilepsy model, demonstrating antiepileptic potential via acetylcholinesterase activation and the modulation of epilepsy-associated genes.