Biology subjects

Ran, W.

Publications and source records attributed to Ran, W..

3 recordsLinked to original sources

bioRxiv2026

A polysynaptic hypothalamuspelvic-ganglion circuit regulates prostate tumor growth via WNT3A

Brain-tumor communication is increasingly recognized. Peripheral autonomic nerves regulate prostate cancer progression, yet how the brain influences local nerve-tumor interactions remains unclear. We identify a polysynaptic circuit linking the hypothalamic paraventricular nucleus (PVN), dorsal motor nucleus of the vagus (DMV), major pelvic ganglion (MPG) and prostate tumor in mice. Although both nuclei were activated during tumor growth, PVN activity restrained, whereas DMV activity promoted tumor growth. MPG ablation abolished DMV-induced tumor promotion. Combining LMD with Smart-seq2 revealed transcriptional remodeling and increased Wnt3a expression in tumor-innervating, activated MPG neurons under upstream neural control. MPG explants released WNT3A, whose neutralization suppressed explant-induced cancer-cell proliferation. Together, our findings identify a polysynaptic PVN-DMV-MPG circuit that regulates prostate tumor growth and implicate WNT3A as a mediator of the pro-tumor effects of the MPG, highlighting the therapeutic potential of targeting the neural circuit and downstream molecular pathway.

cancer biology↗

bioRxiv2026

Ribophorin-1 Governs Spike Abundance of Highly Pathogenic Coronaviruses by ER-associated degradation

The spike protein of highly pathogenic coronaviruses is indispensable for viral entry, pathogenesis, and immune evasion. However, specific host factors governing spike protein degradation and abundance on progeny virions remain largely uncharacterized. Here, we identify Ribophorin-1 (RPN1), a non-catalytic subunit of the oligosaccharyltransferase (OST) complex, as an ER-localized host restriction factor that selectively depletes spike to inhibit coronavirus infection. Conditional knockout of Rpn1 in mouse lung markedly exacerbates SARS-CoV-2 pathogenesis, increasing viral load, immune cell infiltration, and syncytium formation. In cells, RPN1 knockdown enhances susceptibility to diverse variants, whereas its overexpression attenuates infection. Nano-flow cytometry, cryo-EM and LSCM show that RPN1 reduces spike abundance on progeny virions, resulting in reduction in subsequent syncytium formation across SARS-CoV, SARS-CoV-2, and MERS-CoV. Mechanistically, RPN1 promotes VCP/p97-dependent retrotranslocation and AMFR-mediated ubiquitination of spike protein. Heterologous expression of RPN1s functional domain (residues 180-307) confers significant protection against SARS-CoV-2 both in vitro and in vivo. Collectively, our findings define an RPN1-initiated ERAD pathway that selectively targets coronavirus spike for proteasomal destruction, and provide proof-of-concept evidence that targeting this RPN1-dependent pathway represents a promising broad-spectrum antiviral strategy.

microbiology↗

bioRxiv2022

Impaired peri-olfactory Cerebrospinal Fluid clearance mediated cognitive decline after dyssomnia

Animal experiments have demonstrated the dependency of CSF clearance function on age and sleep, which partially underlay the cognitive decline in the elderly. However, evidence is lacking in humans mainly due to limited method to assess CSF clearance function. We aimed to image CSF clearance pathways in human brain by dynamic MRI with intrathecal contrast agent as a CSF tracer. We performed T1-weighted and T2-fluid attenuated inversion recovery imaging with equal sequence parameters before and at multiple time points after intrathecal injection of contrast agent to visualize the putative meningeal lymphatic pathway, peri-olfactory nerve pathway and peri-optic nerve pathway. We defined the CSF clearance function as the percentage change in signal unit ratio of critical locations in these pathways from baseline to 39 hours after intrathecal injection. CSF clearance through the putative meningeal lymphatic and peri-neural pathways were clearly visualized in all 85 patients. The CSF clearance function of meningeal lymphatic and peri-neural pathways were reduced with aging (all P < 0.05). The CSF clearance function through peri-olfactory nerve pathway was positive correlated with sleep quality and cognitive function (both P < 0.05). Moreover, the CSF clearance function through peri-olfactory nerve pathway mediated the association of sleep quality with cognitive function (percent change in {beta} [bootstrap 95% confidence interval]: 35% [-0.220, -0.003]). The study shows promise for dynamic MRI with intrathecal injection of contrast agent as a method to assess CSF clearance function through putative peri-neural pathways, and interprets the impaired clearance through putative peri-olfactory nerve pathway may explain the cognitive decline in patients with dyssomnia.

neuroscience↗