Biomedical subjects

Jiayu Zhang

Publications and source records attributed to Jiayu Zhang.

4 recordsLinked to original sources

PubMed2026

Deciphering the effects of sulfonamide antibiotics on denitrification from a metagenomic perspective: Inhibition of nitrite reduction and succession patterns of functional microorganisms.

Limited research has thoroughly elucidated the impact mechanisms of antibiotics on the denitrification process at the genomic and gene levels, which has hindered the optimization and development of nitrogen removal technology for antibiotic-containing swine wastewater. Lab-scale sequencing batch reactors were constructed in this study to treat synthetic wastewater containing different sulfonamides and nitrate. Investigations were carried out on denitrification performance, microbial community diversity, denitrifier succession patterns, and functional gene distribution. The stress of sulfonamides inhibited the nitrite reduction process, transforming complete denitrification into partial denitrification and causing significant nitrite accumulation. The average nitrogen removal efficiency in the treatment groups decreased from 81.0% ± 2.2-40.1% ± 6.1%. Alicycliphilus and Thauera were identified as the key taxa, accounting for 32.2% and 16.9% of all potential denitrifying bacteria, respectively. Although metagenome-assembled genomes (MAGs) from Thauera were enriched with genes encoding nitrate reductases (nap, nar) and nitrite reductases (nir), this genus preferentially utilized nitrate as an electron acceptor, resulting in the preferential nitrate reduction and subsequent nitrite accumulation. In contrast, Alicycliphilus MAGs developed tolerance to the sulfonamides stress during later stages, with concomitant enrichment of associated functional genes. They replaced Thauera to reemerge as the dominant group, thereby restoring complete denitrification. This study provides new insights into the regulatory mechanisms governing complete versus partial denitrification in nitrogen removal from antibiotic-containing wastewater.

Denitrifier succession↗

PubMed2026

Discovery of novel quinazoline-containing ATR inhibitor for treatment of acute myeloid leukemia.

ATR is a core kinase in the DNA damage response pathway, primarily sensing replication pressure and double strand breaks, initiating cell cycle arrest, DNA repair, and apoptosis programs, and maintaining genomic stability. In this work, we validated that intervention in ATR function might regulate the progression of AML through bioinformatics analysis. And a series of novel ATR inhibitors based on quinazoline moiety were obtained. The promising compound C7 achieved effective enzyme level and cellular level inhibitory activities, and exhibited acceptable liver S9 stability and oral bioavailability, with no high risk of drug-drug interactions. Research on the underlying mechanism indicated that compound C7 could inhibit the development of MOLM-13 through a dual mechanism of rapidly inducing cell apoptosis and exacerbating DNA damage levels. In brief, compound C7 might be a promising candidate or lead compound for the discovery of novel ATR inhibitors and the treatment of AML.

Quinazolines↗

PubMed2026

hnRNPC facilitates coronavirus replication by directly binding the frameshift-stimulatory element of viral genomic RNA.

Translation of key viral replicative proteins in coronaviruses requires a programmed -1 ribosomal frameshifting (-1 PRF) event controlled by the viral frameshift-stimulatory element (FSE). Although previous studies have analyzed host factor dependencies of coronaviruses, how host cellular factors alter -1 PRF efficiency and affect viral replication remains poorly understood. Here, using RNA pull-down combined with LC-MS/MS analysis, we identified heterogeneous nuclear ribonucleoprotein C (hnRNPC) as a major interacting protein of FSE RNA. Coronavirus infection triggers hnRNPC mRNA decay, alters hnRNPC protein levels, and induces its cytoplasmic relocalization, where it appears to bind directly to FSE RNA through residues Asn7 and Asn83. This binding is associated with increased -1 PRF efficiency and may facilitate coronavirus replication. Deletion mapping analysis shows that hnRNPC preferentially binds U-rich regions of the FSE RNA. Finally, we demonstrated that the small molecule Elbasvir directly binds hnRNPC, disrupting the interaction between hnRNPC and FSE RNA and inhibiting coronavirus replication by decreasing -1 PRF efficiency. Collectively, our study identifies hnRNPC as a key host cofactor for coronaviruses and provides a novel target for broad-spectrum antiviral drug development.

RNA, Viral↗

PubMed2026

Cross-kingdom genomic variation in chicken gut microbiomes: insights from China's diverse local breeds.

BACKGROUND: The gut microbiome possesses substantial genetic diversity that supports microbial adaptation, but the genomic variation patterns across its prokaryotic and viral populations remain incompletely characterized. RESULTS: Through integrated metagenomic and metatranscriptomic analysis of ten indigenous chicken breeds from China, we recovered 1527 representative prokaryotic MAGs, 37,555 representative DNA viral contigs, and 1867 representative RNA viral contigs (primarily comprising Bacillota/Bacteroidota, Uroviricota, and Lenarviricota/Pisuviricota, respectively). By integrating complementary short-read and long-read metagenomics with metatranscriptomics, we identified structural variants (SVs) and single-nucleotide variants (SNVs) in these cross-kingdom genomes. Positive SV-SNV density correlations occurred consistently across all microbial groups, indicating coordinated mutational processes. DNA viruses exhibited the highest variant prevalence (86.9% SNVs, 47.7% SVs), with temperate phages accumulating significantly more variants than virulent phages. Functionally, prokaryotic variants accumulated in carbohydrate metabolism and amino acid metabolism, while viral variants demonstrated broad metabolic hijacking. Horizontal gene transfer (HGT) was characterized by a strong virus-associated signature (69.40% of 536 events) and marked by an asymmetric pattern, with phage-to-bacteria (P-to-B) flow alone constituting 37.50% of all events. Random forest analysis revealed a strong bidirectional predictive relationship between SV and SNV densities across prokaryotic, DNA viral, and RNA viral populations, suggesting coupled genomic instability. Niche breadth emerged as a major driver of SNVs across kingdoms and was positively correlated with variant density. In prokaryotes, HGT events significantly shaped variant patterns. For viruses, genomic GC content was an important factor and consistently showed a negative correlation with SNV density in both DNA and RNA viruses. CONCLUSIONS: These findings demonstrate that coordinated mutational processes and kingdom-specific intrinsic factors drive genomic variation, with viruses serving as key genetic exchange vectors in chicken gut ecosystems. Video Abstract.

Animals↗