Biology subjects

Bu, Z.

Publications and source records attributed to Bu, Z..

3 recordsLinked to original sources

bioRxiv2026

Loss of the mitochondrial redox gene GLRX2 underlies somersaulting behavior in Darwin's pigeons

Darwin described the somersaulting behavior of pigeons as "one of the most remarkable inherited habits ever recorded", yet its molecular basis remained unknown. We show that somersaulting pigeon brains exhibit mitochondrial redox dysfunction and identify an 11-bp frameshifting deletion in GLRX2, a mitochondrial redox enzyme, that abolishes protein function and is highly-enriched in two independently selected breeds. GLRX2 deficiency in mice and zebrafish recapitulates mitochondrial dysfunction, oxidative stress and impaired motor coordination seen in pigeons. Single-nucleus transcriptomics identifies cerebellar Golgi and Purkinje cells as selectively vulnerable, with disrupted inhibitory signaling and synaptic remodeling. These findings demonstrate how relaxation of purifying selection during domestication can expose a deleterious mitochondrial variant to artificial selection, allowing gene loss to serve as a substrate for behavioral evolution.

evolutionary biology↗

bioRxiv2025

STEAP4+ neutrophils: a promising circulating biomarker for lung metastasis

As the leading contributor to cancer-related mortality, metastasis often evades detection until advanced stages, underscoring the critical need for early predictive biomarkers. Neutrophils are naturally circulating sentinels that have been implicated in pioneering pre-metastatic niche formation in distant organs. Nevertheless, their heterogeneity within evolving metastatic microenvironments remains poorly characterized. Here, through dynamically delineating neutrophil subsets via single-cell transcriptomics, we identified a conserved feature of lung metastasis in breast cancer and other cancer models. Among the core genes, a cell surface marker, STEAP4, was selected and validated to indicate lung metastases at both RNA and protein levels. In both humans and mice, these STEAP4+ neutrophils were detectable not only in lung metastatases but also in the circulation. Clinically, the abundance of circulating STEAP4+ neutrophils robustly discriminates patients with lung metastasis from those with localized primary tumor. Our findings uncover STEAP4+ neutrophils as a promising biomarker and lay the groundwork for a non-invasive, blood-based diagnostic strategy for metastatic disease.

cancer biology↗

bioRxiv2022

Development of highly potent non-covalent inhibitors of SARS-CoV-2 3CLpro

The SARS-CoV-2 virus is the causal agent of the ongoing pandemic of coronavirus disease 2019 (COVID-19). There is an urgent need for potent, specific antiviral compounds against SARS-CoV-2. The 3C-like protease (3CLpro) is an essential enzyme for the replication of SARS-CoV-2 and other coronaviruses, and thus is a target for coronavirus drug discovery. Nearly all inhibitors of coronavirus 3CLpro reported so far are covalent inhibitors. Here, we report the development of specific, non-covalent inhibitors of 3CLpro. The most potent one, WU-04, effectively blocks SARS-CoV-2 replications in human cells with EC50 values in the 10-nM range. WU-04 also inhibits the 3CLpro of SARS-CoV and MERS-CoV with high potency, indicating that it is a pan-inhibitor of coronavirus 3CLpro. WU-04 showed anti-SARS-CoV-2 activity similar to that of PF-07321332 (Nirmatrelvir) in K18-hACE2 mice when the same dose was administered orally. Thus, WU-04 is a promising drug candidate for coronavirus treatment. One-Sentence SummaryA oral non-covalent inhibitor of 3C-like protease effectively inhibits SARS-CoV-2 replication.

microbiology↗