Alterations in platelet proteome signature and impaired platelet integrin αIIbß3 activation in patients with COVID-19.

BACKGROUND: Patients with COVID-19 are at increased risk of thrombosis, which is associated with altered platelet function and coagulopathy, contributing to excess mortality. OBJECTIVES: To characterize the mechanism of altered platelet function in COVID-19 patients. METHODS: The platelet proteome, platelet functional responses, and platelet-neutrophil aggregates were compared between patients hospitalized with COVID-19 and healthy control subjects using tandem mass tag proteomic analysis, Western blotting, and flow cytometry. RESULTS: COVID-19 patients showed a different profile of platelet protein expression (858 altered of the 5773 quantified). Levels of COVID-19 plasma markers were enhanced in the platelets of COVID-19 patients. Gene ontology pathway analysis demonstrated that the levels of granule secretory proteins were raised, whereas those of platelet activation proteins, such as the thrombopoietin receptor and protein kinase Cα, were lowered. Basally, platelets of COVID-19 patients showed enhanced phosphatidylserine exposure, with unaltered integrin αIIbß3 activation and P-selectin expression. Agonist-stimulated integrin αIIbß3 activation and phosphatidylserine exposure, but not P-selectin expression, were decreased in COVID-19 patients. COVID-19 patients had high levels of platelet-neutrophil aggregates, even under basal conditions, compared to controls. This association was disrupted by blocking P-selectin, demonstrating that platelet P-selectin is critical for the interaction. CONCLUSIONS: Overall, our data suggest the presence of 2 platelet populations in patients with COVID-19: one of circulating platelets with an altered proteome and reduced functional responses and another of P-selectin-expressing neutrophil-associated platelets. Platelet-driven thromboinflammation may therefore be one of the key factors enhancing the risk of thrombosis in COVID-19 patients.

Surface-applied insecticide treatments for quarantine control of Japanese beetle, Popillia japonica Newman (Coleoptera: Scarabaeidae), larvae in field-grown nursery plants.

BACKGROUND: Japanese beetles, Popillia japonica Newman, are a quarantine challenge for nursery shipments from infested to non-infested states. Marathon (imidacloprid) and Discus (imidacloprid + cyfluthrin) are approved preharvest nursery treatments (US Domestic Japanese Beetle Harmonization Plan; DJHP). This study evaluated approved and non-approved (acephate, carbaryl, clothianidin, dinotefuran, halofenozide, thiamethoxam, trichlorfon) preharvest treatments, optimal rates (labeled 1x, 0.3-0.75 x or 2-3 x) and optimal timings (June, July, August and September) to control early-instar (grubs) P. japonica in field nurseries. RESULTS: Most insecticides effectively reduced grub densities, except for acephate, carbaryl and trichlorfon. Clothianidin, thiamethoxam and halofenozide provided grub control equivalent to DJHP standards during most years. Across all test years and timings, percentage grub reductions were: Marathon (1x: 59.2-100; 3 x: 78.9-100), Discus (1x: 60.7-100), clothianidin (1x: 96.1-100; 3 x: 97.4-100), thiamethoxam (1x: 75.0-100; 3 x: 80.0-100), halofenozide (1x: 70.0-100; 3 x: 90.0-100) and dinotefuran (1x: 13.2-88.2; 3 x: 71.1-93.4). CONCLUSIONS: July application was more consistent and effective than other timings, and higher rates (2x and 3 x) did not generally improve grub control. Overall, clothianidin, thiamethoxam and halofenozide (and dinotefuran applied in August) were equivalent to current DJHP standards. These insecticides may be suitable for DJHP Category 2 states, potentially lowering grower costs.