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. 2023 Jul 6;3(7):829–845. doi: 10.1038/s43587-023-00442-w

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© The Author(s) 2023

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Fig. 5 — Aged hamsters and young hamsters were treated (or not) with ABT-263 and then infected with SARS-CoV-2. Animals were euthanized at 7 dpi and 22 dpi. a, Left: histopathological examination of lung sections (H&E staining, 7 dpi). The sum of the subscores is shown (n = 11–12 aged and n = 6 young). Right: photomicrographs showing lower alveolar destruction in ABT-263-treated aged hamsters (but not ABT-263-treated young hamsters). Arrowhead: inflammatory cell infiltrate; star: alveolar wall rupture; sun: type II pneumocyte hyperplasia; thunderbolt: necrosis; arrow: activated blood vessel. Scale bars, 50 μm. b, Heat maps of the differential expressed prothrombotic and inflammatory factors in the serum of vehicle-treated and ABT-263-treated aged hamsters, in a mass spectrometry analysis of the proteome (fold change in protein level > 1.2, P < 0.05) (n = 5–6). c, Histopathological examination of lung sections (H&E staining, 22 dpi). Lower panels: The total histology score (left) and the numbers of inflammatory foci (inflammation and type II hyperplasia) per lung section (right) are shown (n = 4–6). d, Sirius Red labeling in the lungs of vehicle-treated and ABT-263-treated aged hamsters and young hamsters at 22 dpi. Top: representative images showing (stars) the destructured basal membranes in vehicle-treated aged animals. Bottom: the percentages of Sirius Red labeling are shown (n = 4–6). e, TMT-based proteomic analysis of lung extracts (vehicle-treated and ABT-263-treated aged hamsters). Heat maps of the differentially expressed components, in a mass spectrometry analysis of the proteome, are depicted (fold change in protein abundance > 2, P < 0.05) (n = 4). For all graphs, errors indicate mean ± s.d. Pooled results from two independent experiments (a, left) and one of two representative experiments (a, right, and b–e) are shown. Significant differences were determined using the two-tailed Mann–Whitney U-test (a,b,e) and one-way ANOVA Kruskal–Wallis test (non-parametric), followed by Dunn’s post test (c,d). *P < 0.05, **P < 0.01, ***P < 0.001.