Gene Ontology graph embeddings with Dynamic Thresholding based Deep Neural Networks for Multi-label protein subcellular localization prediction.

DJ-1 deficiency in SH-SY5Y cells reveals dysregulated networks of genes and pathways involved in neuronal function and disease.

Transcriptomic analysis reveals the regulatory role of LIPE in lipid metabolism and tumor-associated macrophage polarization in breast cancer.

Genetic interactions between bioactive ingredients in traditional Chinese medicine and major depressive disorder, bipolar disorder, and schizophrenia.

The present study aimed to investigate the therapeutic effects and underlying mechanism of oridonin (ORI) in ulcerative colitis (UC) using the lipopolysaccharide (LPS)‑induced macrophage inflammatory model in vitro and the dextran sulfate sodium (DSS)‑induced mouse UC model in vivo. Cell Counting Kit‑8 assay was used to determine the appropriate drug concentrations for the in vitro experiments. Western blotting and reverse transcription‑quantitative polymerase chain reaction were performed to evaluate the expression levels of proteins and mRNAs related to signaling pathways, autophagy and inflammatory cytokines. The autophagy inhibitor 3‑methyladenine was applied to verify the role of the PI3K/AKT/mTOR pathway. In vivo, the disease activity index (DAI) was recorded and colon tissue damage was assessed by hematoxylin and eosin staining. Serum inflammatory cytokines were measured using an enzyme‑linked immunosorbent assay. Network pharmacology based on GeneCards and Traditional Chinese Medicine Systems Pharmacology databases, along with Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis, predicted involvement of the PI3K/AKT/mTOR pathway in the pathogenesis of UC, which was further validated by the immunohistochemistry, immunofluorescence and western blotting of colon tissues. The results indicated that ORI significantly reduced the expression of pro‑inflammatory cytokines and increased the anti‑inflammatory cytokine interleukin‑10 in LPS‑stimulated macrophages. In DSS‑induced colitis mice, ORI treatment alleviated body weight loss, decreased DAI scores, improved colon shortening and upregulated the expression of intestinal tight junction proteins. Mechanistically, ORI inhibited the PI3K/AKT/mTOR pathway and altered autophagy‑related molecular markers, as evidenced by increased levels of autophagy‑related (ATG)13, beclin‑1, ATG12, ATG7 and ATG5 as well as decreased expression of p62. In conclusion, ORI alleviates inflammatory responses in vitro and mitigates UC‑related pathological changes in vivo, which may be associated with suppression of the PI3K/AKT/mTOR pathway and modulation of autophagy‑associated protein markers.

Discovery of shared molecular signatures and their functions associated with type-2 diabetes and myocardial infarction, and repurposing common drugs.

In silico transcriptomic analysis for biomarker discovery in TB and HIV co-infection.

In silico discovery of selective TPX2 and BUB1B inhibitors as novel antimitotic agents in breast cancer therapy.

Oxidative stress inhibits milk fat production by p38 MAPK-Cebpα-Acsl6 axis in mouse mammary gland.

Dynamic exosomal proteomic response of the sea cucumber Apostichopus japonicus to Vibrio splendidus challenge.

Investigating the potential risk of nicotine exposure on glioblastoma: Integrating Mendelian randomization and network toxicology analysis.

mRNA and lncRNA expression profiles as potential targets for diagnosis and treatment of oral lichen planus.

Fusing serum peptidome profiles with clinical variables via machine learning for pulmonary embolism risk assessment.

Immunomodulatory and cellular effects of Aeromonas salmonicida melanin in Atlantic salmon (Salmo salar).

Mechanistic insights into the anticancer potential of bergapten in non-small cell lung cancer: A network pharmacology, in-silico molecular docking and dynamics simulation study.

Adipose tissue is not only the primary site of energy storage but also an essential metabolic organ for maintaining energy homeostasis to regulate adipogenesis, metabolism, and chronic inflammation in mammals. However, the cross-species conservation and divergence of its cellular composition and transcriptional features remain unclear. To address this, we analyzed single-cell RNA sequencing datasets from cattle, pigs, and humans. Conserved cell types, including adipocytes, adipose stem and progenitor cells (ASPCs), macrophages, endothelial cells, and T cells, were identified across all three species. In contrast, pigs uniquely contained mesenchymal cells (COL1A1, COL1A2) and B cells (CD37), cattle possessed distinct preadipocyte populations (COL3A1, PNPLA2, GPAM), and humans exhibited abundant dendritic (HLA-DRA, HLA-DRB1) and mast cells (KIT). Focusing on adipocytes, we identified 537, 160, and 73 species-specific DEGs in cattle, pigs, and humans, respectively. Gene Ontology enrichment analysis of adipocyte-specific DEGs revealed that genes enriched in cattle were primarily involved in cytoskeletal organization and triglyceride biosynthesis (LPIN1, DGAT2), those enriched in pigs in oxidative phosphorylation and thermogenesis (LIPE, CIDEA), and those enriched in humans in lipid transport and immune signaling (ADIPOQ, LPL). Overall, this study establishes a cross-species single-cell atlas of subcutaneous adipose tissue, providing insights into conserved architectures and species-specific adaptations, and serving as a valuable resource for comparative biology and livestock research.

To investigate epigenetic and transcriptional alterations in children with Wiedemann-Steiner syndrome (WDSTS) due to variants of KMT2A gene using genome-wide DNA methylation array and RNA sequencing (RNA-seq), and identify the key pathways and candidate genes. A retrospective study was carried out for 16 children with WDSTS and 10 healthy controls who visited Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine between November 2016 and December 2024. Peripheral blood samples were collected. Genomic DNA and total RNA were extracted using commercially made kits. Genome-wide DNA methylation profiling was conducted to identify differentially methylated positions (DMPs) and annotated genes, followed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. RNA-seq was performed to identify differentially expressed genes (DEGs) and conduct GO/KEGG functional annotation. Methylation and expression data were integrated to identify overlapping genes showing significant changes at both levels, followed by GO, KEGG and gene-pathway network analyses. This study was approved by the Ethics Committee of the hospital (Ethics No.: GKLW-A-2024-006-01). A total of 2 652 DMPs corresponding to 1 262 genes were identified, which included 833 hypermethylated genes (66%) and 429 hypomethylated genes (34%). Hypermethylated genes were mainly enriched for functions related to cell junctions, while hypomethylated genes were significantly involved in nervous system development and morphogenesis. RNA-seq identified 2 627 DEGs, including 765 up-regulated genes (29%) and 1 862 down-regulated genes (71%). Up-regulated genes were mainly associated with immune-related processes, and down-regulated genes were mainly related to substance transport. Integrative analysis identified 93 overlapping genes with significant changes in both methylation and expression. And these genes were enriched in extracellular matrix-related processes, calcium ion binding, neurodevelopment, and cell adhesion. Key candidate genes, including LAMB1, LAMB2 and NID1, were further prioritized. Integrated analysis of DNA methylation and transcriptome data reveals WDSTS-related epigenetic-transcriptional alterations and provides clues for exploring disease mechanisms and optimizing diagnostic strategies.

Olfactory dysfunction is a debilitating condition with no established treatment. This study evaluated the efficacy of intranasal (i.n.) NAD administration in restoring olfactory function. Cultured human olfactory stem cells (hOSCs) were treated with NAD and assessed by immunofluorescence staining, PCR, and western blot analyses. In vivo, mice with ZnSO4-induced anosmia were treated with i.n. NAD, intraperitoneal dexamethasone, or PBS and evaluated by histological analysis, behavioral tests, bulk RNA-sequencing (RNA-seq), and in situ hybridization. NAD promoted hOSC differentiation into olfactory sensory neurons (OSNs), evidenced by increased stem cell (SOX2 and nestin) and OSN markers (Tuj1 and OMP) expression, and upregulated neuronal differentiation-related genes (SOX2, NESTIN, NEUROD1, NEUROG1, and OMP). In vivo, the NAD group showed significant olfactory function improvement and marked olfactory epithelium repair. Bulk RNA-seq of the olfactory turbinate tissue identified 113 differentially expressed genes (cluster T1) upregulated in control and NAD groups. The Gene Ontology (GO) term "modulation of chemical synaptic transmission" was associated with cluster T1, and 25 genes implicated in this GO were upregulated in the NAD group. Integration with publicly available single-cell RNA-seq data identified six neuronal marker genes - ABHD2, DLGAP2, FOXO3, HIPK2, KCNMA1, and PCDH17 - upregulated by NAD. Protein expression of DLGAP2 and PCDH17 was higher in differentiated hOSCs treated with NAD. In situ hybridization confirmed that Dlgap2, Foxo3, and Pcdh17 expression was restored in anosmic mice treated with i.n. NAD. The potential therapeutic efficacy of i.n. NAD administration was demonstrated by showing regeneration of OSNs in hOSCs and restoring olfactory function in an anosmia mouse model.

Compound Shougong Powder (CSP) is composed of six Chinese herbal medicines and exerts effects in reducing swelling and relieving pain. It is mainly applied in clinical practice as an adjuvant therapy for various malignant tumors; however, its chemical constituents and the material basis of its efficacy have not been fully clarified. This study aimed to clarify the chemical constituents, their migration and distribution invivo, and the pharmacodynamic material basis and anti-tumor mechanism of CSP. Ultrahigh-performance liquid chromatography (UHPLC) combined with high-resolution mass spectrometry (HRMS) was employed to identify the chemical constituents of CSP and their migration and distribution in mouse serum and tissues; network pharmacology was integrated to explore the potential anti-tumor mechanism of the stably distributed constituents. A total of 3645 chemical constituents were identified under both positive- and negative-ion modes. Following oral administration, 611 constituents derived from the formulation were detected in mouse serum. In tissues, 1187, 1020, 618, and 401 prototype constituents were identified in the stomach, esophagus, liver, and lungs, respectively. Systematic analysis of all identified constituents revealed 95 that were stably distributed across the original formulation, serum, and the liver, lung, esophagus, and stomach. These 95 constituents stably present in the formula, serum, and target tissues may act synergistically to contribute to the antitumor and analgesic efficacy of CSP. Furthermore, network pharmacology was integrated to explore the potential mechanism of these constituents. A total of 152 overlapping targets between CSP and cancer were identified by Venn diagram analysis. Protein-protein interaction (PPI) network analysis revealed hub genes such as ALB, PTGS2, EGFR, CXCL8, and GSK3B. Gene Ontology (GO) enrichment showed involvement in apoptotic regulation, cell proliferation, and kinase activity, while Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis highlighted key pathways including cancer, PI3K-Akt, TNF, and MAPK signaling pathways. These findings clarify the chemical constituents and invivo distribution of CSP, confirm that the 95 stably distributed constituents are the potential pharmacodynamic material basis, and suggest that CSP exerts anti-tumor effects through a multicomponent, multi-target, and multi-pathway regulatory network, providing a basis for further investigation into the pharmacodynamic material foundation of CSP in the treatment of malignant tumors.

HPLC-PDA and LC-HRMS/MS-based quantitative and qualitative analysis of Glycosmis pentaphylla alkaloids, and investigation of their anticancer potential through network pharmacology.