Biology subjects

Xian, B.

Publications and source records attributed to Xian, B..

3 recordsLinked to original sources

bioRxiv2024

Reduction of DNA Topoisomerase Top2 reprograms the epigenetic landscape and extends health and life span across species

DNA topoisomerases are essential molecular machines that manage DNA topology in the cell and play important roles in DNA replication and transcription. We find that knocking down the enzyme Topoisomerase Top2 or its mammalian homolog Top2b increases the life span of S. cerevisiae, C. elegans, and mice. Top2b reduction also extends the health span of mice and alleviates the pathologies of aging in multiple tissues. At the cellular/molecular level, Top2b reduction attenuates the major hallmarks of aging, such as cellular senescence, de-regulated nutrient sensing, epigenetic alteration, and lysosomal biogenesis. We observed that Top2b reduction significantly changes the epigenetic landscape in various mouse tissues toward those of the young animals, and differentially down-regulates genes with active promoter and high expression. Our observations suggest that Top2 reduction confers longevity effect across species via a conserved mechanism, and may be used as a novel therapeutic strategy for countering aging.

biochemistry↗

bioRxiv2024

ElixirSeeker: A Machine Learning Framework Utilizing Attention-Driven Fusion of Molecular Fingerprints for the Discovery of Anti-Aging Compounds

Despite the growing interest in anti-aging drug development, high cost and low success rate pose a significant challenge. We present ElixirSeeker, a new machine-learning framework designed to help speed up the discovery of potential anti-aging compounds by utilizing the attention-driven fusion of molecular fingerprints. Our approach integrates molecular fingerprints generated by different algorithms and utilizes XGBoost to select optimal fingerprint lengths. Subsequently, we assign weights to the molecular fingerprints and employ Kernel Principal Component Analysis (KPCA) to reduce dimensionality, integrating different attention-driven methods. We trained the algorithm using DrugAge database. Our comprehensive analyses demonstrate that 64-bit Attention-ElixirFP maintains high predictive accuracy and F1 score while minimizing computational cost. Using ElixirSeeker to screen external compound databases, we identified a number of promising candidate anti-aging drugs. We tested top 6 hits and found that 4 of these compounds extend the lifespan of Caenorhabditis elegans, including Polyphyllin , Medrysone, Thymoquinone and Medrysone. This study illustrates that attention-driven fusion of fingerprints maximizes the learning of molecular activity features, providing a novel approach for high-throughput machine learning discovery of anti-aging molecules.

systems biology↗

bioRxiv2023

Identification and Characterization of CtUGT3 as the Key Player of Astragalin Biosynthesis in Safflower

Safflower (Carthamus tinctorius L.) flowers are used as a traditional Chinese medicine for a long history. Flavonoids are the main bioactive components in safflower flowers, and most of them exist in the form of flavonoid glycosides. Only few glycosyltransferases have been identified in safflower. To reveal the uridine diphosphate glycosyltransferase (UGT) involved in flavonoid glycosides biosynthesis in safflower, a metabolomics and transcriptome analysis was performed by using the flowers under different light qualities treatments. Three differentially expressed UGT genes were screened, and their expressions were significantly related with concentrations of 9 flavonoid O-glycosides. Safflower corolla protoplasts were further used to confirm flavonoid O-glycosylation ability of UGT candidates. The astragalin (kaempferol 3-O-glucoside) content was only significantly increased when CtUGT3 was overexpressed in protoplasts. The biochemical properties and kinetic parameters of CtUGT3 were determined. CtUGT3 also showed flavonoid 3-OH and 7-OH glycosylation activities in vitro. Molecular modeling and site-directed mutagenesis revealed that E384 and S276 were critical catalytic residues for the 3-OH glycosylation of CtUGT3. These results demonstrate that CtUGT3 has a flavonoid 3-OH glycosylation function and is involved in the biosynthesis of astragalin in safflower. This study provides insights into the catalytic mechanisms of flavonoid O-glycosyltransferases, and makes a reference for flavonoid biosynthesis genes research in medicinal plants.

plant biology↗