Biology subjects

Kong, A. X.

Publications and source records attributed to Kong, A. X..

3 recordsLinked to original sources

bioRxiv2025

Butyrate rescues chlorpyrifos-induced social deficits through inhibition of class I histone deacetylases

Chlorpyrifos (CPF) is a widely used organophosphate pesticide effective through inhibiting acetylcholinesterase, which leads to the accumulation of acetylcholine and continuous nerve stimulation. In addition to its well-known acute toxicity, exposure to CPF has also been linked to chronic conditions such as an increasing risk of autism spectrum disorder (ASD) and adverse effects on gut health, including disturbances to the gut microbiome and metabolism. However, the underlying mechanism of CPFs contribution to ASD remains unclear, and the roles of the gut microbiome and gut metabolites in CPF-induced neurodevelopmental toxicity remain elusive. Using a high-throughput social behavior assay, we found that embryonic exposure to CPF induced lasting social deficits in zebrafish. Through a small-scale screen of common health beneficial gut microbiome metabolites, we discovered that butyrate effectively rescued CPF-induced social deficits. RNA sequencing of zebrafish brain tissues revealed that early exposure to CPF induced a lasting suppression of neuronal genes, including many ASD risk genes, and elevated expression of circadian genes. Butyrate partially reversed the suppression of key neuronal genes. Butyrate is a non-selective inhibitor of histone deacetylases (HDACs). Through a series of loss-of-function experiments utilizing CRISPR-Cas9-induced knockouts and selective chemical inhibitors, we found that the class I HDAC, HDAC1, most likely mediates butyrates rescue effect. Metabolomics analysis detected changes in several nitrogen metabolism-related pathways in the zebrafish gut following CPF exposure. Metagenomics analysis revealed an increase in abundance of the denitrifying bacteria Pseudomonas and a reduction in the nitric oxide-sensitive bacteria Aeromonas in the CPF-exposed zebrafish gut microbiome. Our results connect CPF-exposure with changes in the gut microbiome, metabolome, epigenetics, gene expression, and behavior, inspiring a novel hypothesis for the underlying molecular mechanisms of CPF-induced neurodevelopmental toxicity. In the long run, our findings may help elucidate how CPF exposure contributes to autism risk and inspire therapeutic developments.

neuroscience↗

bioRxiv2025

A searchable database of publications using fluorescent probes and flow cytometry to study antigen-specific B cells

The study of antigen-specific B cells has resulted in important advances in all fields of immunology, the development of experimentally and/or clinically useful antibodies, and as a starting point for rationally designed vaccine antigens. A key innovation allowing for widespread study of antigen-specific B cells was the development of fluorescent antigen probes for use with flow cytometry. Initially these studies were mostly focused upon B cells specific for a variety of model antigens, but over the past decade focus has shifted towards the study of B cells specific for antigens from pathogens such as SARS-CoV-2, HIV, and Influenza virus. Importantly however, these types of approaches have been used for hundreds of different antigens and could be used for thousands more. Unfortunately, studies of B cells specific for an antigen of interest are not easily searchable on current publication databases since these assays are often a small portion of a larger publication. To overcome this, we built a searchable database of studies analyzing antigen-specific B cells by flow cytometry using fluorescent antigen probes that is located at www.immunology.virginia.edu/Taylor/Bcell/Database.php. Using this database, we assessed the number of publications per year revealing rapid growth in the use of this approach in recent years. While much of this rapid growth was focused upon the assessment of B cells specific for SARS-CoV-2, HIV-1, or Influenza virus, studies assessing B cells specific for hundreds of different antigens derived from numerous microbes, animals, plants, or other sources can be found in the database. Combined, the antigen-specific B cell database was built to facilitate identification of studies assessing these cells and for analysis of the field as a whole. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=18 SRC="FIGDIR/small/680531v1_ufig1.gif" ALT="Figure 1"> View larger version (6K): org.highwire.dtl.DTLVardef@f07f5forg.highwire.dtl.DTLVardef@13a3b95org.highwire.dtl.DTLVardef@1dcd79org.highwire.dtl.DTLVardef@9cddaa_HPS_FORMAT_FIGEXP M_FIG C_FIG

immunology↗

bioRxiv2024

Proteome-wide reverse molecular docking reveals folic acid receptor as a mediator of PFAS-induced neurodevelopmental toxicity

Per- and polyfluoroalkyl substances (PFAS) are a class of long-lasting chemicals with widespread use and environmental persistence that have been increasingly studied for their detrimental impacts to human and animal health. Several major PFAS species are linked to neurodevelopmental toxicity. For example, epidemiological studies have associated prenatal exposure to perfluorooctanoate (PFOA) and perfluorononanoate (PFNA) with autism risk. However, the neurodevelopmental toxicities of major PFAS species have not been systematically evaluated in an animal model, and the molecular mechanisms underlying these toxicities have remained elusive. Using a high-throughput zebrafish social behavioral model, we screened six major PFAS species currently under regulation by the Environmental Protection Agency (EPA), including PFOA, PFNA, perfluorooctane sulfonate (PFOS), perfluorohexanesulfonic acid (PFHxS), perfluorobutane sulfonate (PFBS), and hexafluoropropylene oxide dimer acid ammonium salt (GenX). We found that embryonic exposure to PFNA, PFOA, and PFOS induced social deficits in zebrafish, recapitulating one of the hallmark behavioral deficits in autistic individuals. To uncover protein targets of the six EPA-regulated PFAS, we screened a virtual library containing predicted binding pockets of over 80% of the 3D human proteome through reverse molecular docking. The screen predicts that folate receptor beta (FR-{beta}, encoded by the gene FOLR2) interacts strongly with PFNA, PFOA, and PFOS but to a lesser degree with PFHxS, PFBS, and GenX, correlating positively with their in vivo toxicity. These predictions were validated through in silico molecular docking, in vitro protein binding analysis, and in vivo loss-of-function verification. Furthermore, embryonic co-exposure to folic acid effectively rescued social deficits induced by PFAS. The folate pathway has been implicated in autism, indicating a novel molecular mechanism for PFAS in autism etiology.

pharmacology and toxicology↗