Biology subjects

YU, X.

Publications and source records attributed to YU, X..

6 recordsLinked to original sources

bioRxiv2026

MXRA7 Alleviates Epididymitis from Exercise-Induced Fatigue by Inhibiting Pyroptosis

AimsTo explore exercise-induced fatigue (EIF)s effects on the male reproductive system and MXRA7s regulatory role herein. MethodsWe recruited EIF volunteers for semen/serum tests, established a mouse EIF model via weight-loaded swimming to assess epididymal segmental injury, and constructed pyroptosis models of PC-1/DC-2 cells. Public database transcriptomic analysis identified MXRA7 expression and enriched pathways in epididymitis; MXRA7s function was verified via its knockdown/overexpression in DC-2 cells. PKC-MXRA7 association was explored by phosphorylation assays and CO-IP, and sperm incubation experiments evaluated MXRA7s effect on sperm function. ResultsEIF impaired human sperm motility, reduced mouse sperm quality and induced epididymitis with segment-specific pyroptosis. MXRA7 expression differed in PC-1/DC-2 cells and correlated with pyroptosis; it was phosphorylated by PKC, inhibited the NF-{kappa}B pathway to alleviate inflammation, and mitigated pyroptosis-induced sperm motility damage. ConclusionEIF induces epididymal epithelial pyroptosis and epididymitis, and MXRA7 exerts a protective effect mainly in caudal epididymal cells by alleviating pyroptosis, thus reducing sperm quality damage.

molecular biology↗

bioRxiv2025

EPEPDI: prediction of binding free energy changes from missense mutations in double and single-stranded DNA-binding proteins

Predicting changes in binding free energy due to missense mutations (MMs) in protein-DNA interactions (PDIs) is vital for understanding disease mechanisms and advancing therapeutic strategies. However, many existing models fail to account for the unique characteristics of MMs in double-stranded DNA binding proteins (DSBs) and single-stranded DNA binding proteins (SSBs). To address this, we constructed a comprehensive dataset from diverse sources, clearly distinguishing between DSBs and SSBs. Using sequence-based embeddings from pre-trained protein language models, including ESM2, ProtTrans, and ESM1v, we developed EPEPDI, a deep learning framework that integrates these embeddings through a multi-channel architecture. To refine predictive accuracy, we introduced an information entropy-based algorithm, determining 181 residues as the optimal sequence length where amino acid contributions and entropy dynamics balance. This approach boosts both precision and computational efficiency, enabling scalable analysis of mutation impacts on DNA-binding proteins. Ablation studies validated optimal feature combinations, demonstrating that EPEPDI outperforms existing approaches, achieving an average Pearson correlation coefficient of 0.755 on the MPD276 dataset via ten-fold cross-validation and 0.632 on independent tests for both DSBs and SSBs. This work highlights the importance of distinguishing DSBs and SSBs in PDIs and shows the potential of advanced machine learning in biological research.

bioinformatics↗

bioRxiv2025

Immunogenicity of Rabies Virus G-Protein mRNA Formulated with Muscle Targeting Lipid Nanoparticles in Mice

Rabies is a preventable zoonotic disease caused by the rabies virus (RABV) with a high mortality rate. Most vaccines on the market or under development have issues such as a low single-dose neutralization titer, complex processes, and high costs. During the COVID-19 pandemic, the successful development of mRNA vaccines has opened up a new avenue for preventive vaccines. As a new technology, mRNA has higher scalability. In this study, we designed an mRNA encoding the RV-G protein, encapsulated by our own muscle targeting lipid nanoparticles (LNP), and evaluated the expression of the RV-G protein in vitro, its immunogenicity, and its protection against virus infection in vivo. The results showed that RV-G mRNA was significantly expressed in vitro. High Virus-IgG binding titers and Virus-neutralizing antibody titers (VNT) were induced by immunization with RV-G mRNA-LNP. Additionally, our results show that the RV-G mRNA vaccine is better than commercially available vaccines in mice.

pharmacology and toxicology↗

bioRxiv2024

Replication stress increases de novo CNVs across the malaria parasite genome

Changes in the copy number of large genomic regions, termed copy number variations (CNVs), contribute to important phenotypes. CNVs are readily identified using conventional approaches when present in a large fraction of the cell population. However, CNVs in only a few genomes are often overlooked but important; if beneficial, a de novo CNV that arises in a single genome can expand during selection to create a population of cells with novel characteristics. While single cell methods for studying de novo CNVs are increasing, we continue to lack information about CNV dynamics in rapidly evolving microbial populations. Here, we investigated de novo CNVs in the genome of the Plasmodium parasite that causes human malaria. The highly AT-rich P. falciparum genome readily accumulates CNVs that facilitate rapid adaptation. We employed low-input genomics and specialized computational tools to evaluate the impact of sub-lethal stress on the de novo CNV rate. We observed a significant increase in genome-wide de novo CNVs following treatment with an antimalarial compound that inhibits replication. De novo CNVs encompassed genes from various cellular pathways participating in human infection. This snapshot of CNV dynamics emphasizes the connection between replication stress, DNA repair, and CNV generation in this important microbial pathogen.

genomics↗

bioRxiv2023

OSCAA: A Two-Dimensional Gaussian Mixture Model for Copy Number Variation Association Analysis

Copy number variants (CNVs) are prevalent in the human genome which provide profound effect on genomic organization and human diseases. Discovering disease associated CNVs is critical for understanding the pathogenesis of diseases and aiding their diagnosis and treatment. However, traditional methods for assessing the association between CNVs and disease risks adopt a two-stage strategy conducting quantitative CNV measurements first and then testing for association, which may lead to biased association estimation and low statistical power, serving as a major barrier in routine genome wide assessment of such variation. In this article, we developed OSCAA, a flexible algorithm to discover disease associated CNVs for both quantitative and qualitative traits. OSCAA employs a two-dimensional Gaussian mixture model that is built upon the principal components from copy number intensities, accounting for technical biases in CNV detection while simultaneously testing for their effect on outcome traits. In OSCAA, CNVs are identified and their associations with disease risk are evaluated simultaneously in a single step, taking into account the uncertainty of CNV identification in the statistical model. Our simulations demonstrated that OSCAA outperformed the existing one-stage method and traditional two-stage methods by yielding a more accurate estimate of the CNV-disease association, especially for short CNVs or CNVs with weak signal. In conclusion, OSCAA is a powerful and flexible approach for CNV association testing with high sensitivity and specificity, which can be easily applied to different traits and clinical risk predictions.

genomics↗

bioRxiv2020

Fast and easy single-molecule pulldown assay based on agarose microbeads

The recently developed single-molecule pulldown (SiMPull) assay by Jain and colleagues is a highly innovative technique but its wide application is hindered by the high technical barrier and time consumption. We report an innovative, agarose microbead-based approach for SiMPull. We used commercially available, pre-surface-functionalized agarose microbeads to capture the protein of interest together with its binding partners specifically from cell extracts and observed these interactions under a microscope at the single-molecule level. Relative to the original method, microbead-based SiMPull is considerably faster, easier to use, and more reproducible and yet provides similar sensitivity and signal-to-noise ratio; specifically, with the new method, sample-preparation time is substantially decreased (from [~]10 to [~]3 h). These crucial features should facilitate wide application of powerful and versatile SiMPull in common biological and clinical laboratories. Notably, by exploiting the simplicity and ultrahigh sensitivity of microbead-based SiMPull, we used this method in the study of rare auditory hair cells for the first time.

biochemistry↗