zhang, k. | bioRxiv Science

bioRxiv2026

The effect of melittin intervention on murine cervical cancer cells: An in-depth proteomics investigation

Melittin, the principal bioactive peptide of bee venom, exhibits promising antitumor activity, whereas its molecular mechanisms in cervical cancer remain incompletely understood. In this study, the biological effects and molecular responses of melittin in U14 cervical cancer cells were investigated using Astral data-independent acquisition (Astral-DIA)-based quantitative proteomics combined with molecular validation. The effects of melittin on cell migration, invasion, and cell death were evaluated by Transwell assays and PI/Hoechst staining. Differentially expressed proteins (DEPs) were screened and subjected to Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and protein-protein interaction (PPI) analyses. Representative oxidative stress-related genes and proteins were further validated by RT-qPCR and Western blotting. Melittin significantly inhibited the migration and invasion of U14 cervical cancer cells and increased cell death. Quantitative proteomics identified 9,782 protein groups and 187 DEPs, including 71 up- and 116 down-regulated proteins. KEGG pathway enrichment analysis revealed oxidative phosphorylation (OXPHOS) as the most significantly enriched pathway, together with glutathione metabolism, ferroptosis-related pathways, reactive oxygen species signaling, and mitophagy. GO term enrichment analysis indicated that DEGs were mainly engaged in mitochondrial function, electron transport, oxidoreductase activity, and energy metabolism. RT-qPCR assay demonstrated altered expression of Duox1, Gpx4, Gsx2, Nfe2l2, and Gstp2. Additionally, PPI analysis identified Gstp2 and ODC1 as representative hub proteins involved in redox regulation and metabolic adaptation. Furthermore, Western blotting confirmed increased GSTP2 expression following melittin treatment. Overall, these findings provide a comprehensive proteomic landscape of melittin-treated U14 cervical cancer cells and suggest that mitochondrial OXPHOS remodeling and redox-associated pathways may contribute to the antitumor activity of melittin.

cell biology↗

bioRxiv2025

Protenix - Advancing Structure Prediction Through a Comprehensive AlphaFold3 Reproduction

In this technical report, we present Protenix, a comprehensive reproduction of AlphaFold3 (AF3), aimed at advancing the field of biomolecular structure prediction. Protenix tackles the challenges of predicting complex interactions involving proteins, ligands, and nucleic acids, while enhancing accessibility and reproducibility. Across diverse benchmarks, including PoseBusters V2, low-homology PDB sets, and CASP15 RNA, Protenix achieves state-of-the-art performance in protein-ligand, protein-protein, and protein-nucleic acid predictions. We also address limitations, such as potential memorization effects, and outline future directions for improvement. By open-sourcing Protenix, we aim to democratize advanced structure prediction tools and accelerate interdisciplinary research in computational biology and drug discovery.

bioinformatics↗

bioRxiv2024

In vivo multiplex imaging of dynamic neurochemical networks with designed far-red dopamine sensors

Neurochemical signals like dopamine (DA) play a crucial role in a variety of brain functions through intricate interactions with other neuromodulators and intracellular signaling pathways. However, studying these complex networks has been hindered by the challenge of detecting multiple neurochemicals in vivo simultaneously. To overcome this limitation, we developed a single-protein chemigenetic DA sensor, HaloDA1.0, which combines a cpHaloTag-chemical dye approach with the G protein-coupled receptor activation-based (GRAB) strategy, providing high sensitivity for DA, sub-second response kinetics, and an extensive spectral range from far-red to near-infrared. When used together with existing green and red fluorescent neuromodulator sensors, Ca2+ indicators, cAMP sensors, and optogenetic tools, HaloDA1.0 provides high versatility for multiplex imaging in cultured neurons, brain slices, and behaving animals, facilitating in-depth studies of dynamic neurochemical networks.

neuroscience↗