Skin cancer, especially cutaneous squamous cell carcinoma (cSCC), remains a major global health problem. Here, we report a spontaneous macaque cSCC model (5/2752 incidence; 80% mortality) that reproduces key human cSCC features. Tumors show well-differentiated squamous morphology, expression of squamous lineage markers (p63, CK5/6), and elevated Ki-67 proliferation indices. We apply whole-genome sequencing, bulk and single-cell RNA sequencing, proteomics, and functional assays to define tumor biology. Genomes display a high mutational burden with C > T dipyrimidine changes, pervasive chromosomal instability, translocations, and focal copy-number alterations. Integrated analyses reveal NF-κB–mediated inflammatory programs, macrophage-rich immune remodeling, and a shift toward aerobic glycolysis. Cross-platform data nominate MYO10 as recurrently altered and overexpressed. MYO10 knockdown reduces γ-H2AX, micronuclei, and IL-6/TNFα expression, while MYO10 overexpression induces DNA damage and inflammation in primary epithelial cells. Drug screening identifies paclitaxel as the most potent compound (IC₅₀ = 0.011 µM). Paclitaxel triggers apoptosis, G2/M arrest, and reduced migration in vitro. In mouse xenografts, it shrinks tumors by 89.4%. In a treated macaque, it produces 86.6% mean tumor regression, lowers systemic IL-6 and TNFα, and is well tolerated. This spontaneous macaque model links genomic instability to inflammation via MYO10 and offers a translational platform for studying cSCC and testing therapies.

BACKGROUND:Ischemic stroke leads to a long-term disability in humans and no efficient clinical therapy exists to date. The middle cerebral artery occlusion (MCAO) model in non-human primates has shown to be of value for translational stroke research. New method In the current study, a photothrombotic (PT) stroke model was established in rhesus monkeys with either a proximal or distal segment of middle cerebral artery (MCA) thrombosis. This study is the first that compares the two approaches of PT stroke in monkeys using behavioral and physiological measurements and MRI scans.RESULTS:The experiment found that infarct occurred in the MCA target regions, with all monkeys having impaired behavior reflected by deficits in neurologic function, and motor and cognition in object retrieval detour (ORD) task. The monkeys with distal MCA thrombosis developed with sequential photo-irritations of the Sylvian fissure zone, adjacent central anterior gyrus and central posterior gyrus, had similar impairments with respect to behavior and showed a tendency of a small edema volume with proximal MCA thrombosis at days 4 and 7 post PT stroke.COMPARISON WITH EXISTING METHODS:The distal MCA thrombosis developed with sequential photo-irritations might provide a consistent and well-tolerated focal ischemia in rhesus monkeys, compared with other PT stroke models which usually were singly conducted on the animal's motor cortex and had a temporal effect.CONCLUSIONS:The sequentially photo-irritated PT stroke model is a promising ischemic stroke model in rhesus monkey for studying human stroke pathology and physiology and for new therapies development.

Spinal cord injury (SCI) repair is one of the most desirable but extremely challenging clinical problems. Developing suitable animal models and validating the therapeutic interventions in these models is the prerequisite for SCI repair improvement. Non-human primates, closer to humans than other species, are considered to be ideal models for translating laboratory discoveries into human clinical trials. In this study, the acute thoracic (T9) complete transection model in rhesus monkeys was established to evaluate the effects of linear-ordered collagen scaffold (LOCS) and LOCS combined with collagen binding neurotrophin-3 (CBD-NT3), which has been demonstrated to promote axonal regrowth and functional restoration in rodent models. After 10 months post-surgery, the grafted groups dramatically reduced cystic cavity formation and chondroitin sulfate proteoglycans (CSPGs) deposition and facilitated the ingrowth of axonal fibers at the lesion site. Further, the grafted groups displayed more regenerated fibers, exhibiting remyelination and synapse formation. Notably, the LOCS+CBD-NT3 group showed significant locomotor and electrophysiological recovery compared with the Control and LOCS groups. Therefore, LOCS+CBD-NT3 transplantation represents an effective strategy to promote spinal cord repair in non-human primates. More importantly, this complete transection model in non-human primate will contribute to effectively evaluating the potential interventions and accelerating clinical transformation in the future.