Fig 2: TLN1 upregulation is associated with poor disease-free survival (DFS) in triple-negative breast cancer (TNBC).(A) The expression of ITGB1, ITGB3, and ITGA5 in breast cancer subclasses and normal breast tissue using The Cancer Genome Atlas (TCGA) samples (n = 114 of normal samples, n = 556, 37, and 116 of luminal, human epidermal growth factor receptor 2 [HER2] positive and TNBC samples, respectively; p-value is the result of comparison with normal samples, respectively). (B) Representative immunohistochemistry images of TLN1 expression in TNBC tissue, chest wall recurrence, lymphatic metastasis, and intestinal metastasis (scale bar, 100 µm). (C) Western blot analysis of TLN1 expression in fresh TNBC and para-cancerous tissues (n = 4, p = 0.009). (D) The DFS of 171 TNBC patients in the cohort was estimated by the Kaplan-Meier method, and the difference between groups with high and low TLN1 expression was compared within each set of patients listed and analysed by log-rank analysis (HR = 3.19, p < 0.001). (E) Chi-square analysis of high or low TLN1 expression with T-stage, N-stage, and Ki67 index. Data are either presented as representative images or expressed as the mean ± standard error of the mean (SEM) of each group. p < 0.01 was indicated by **. Figure 1—source data 1.TLN1 upregulation is associated with poor DFS in TNBC.

Fig 3: Western blot analysis of expression of core targets of DMAG. The expressions of ITGA2B, ITGB3, VWF, PLEK and p-Akt were detected by western blot after HEL cells were treated with DMAG (10, 20 and 40 µM) for 4 days. The data represent the mean ± SD of three independent experiments; *p < 0.05, **p < 0.01, ***p < 0.001, compared to the control group

Fig 4: DMAG administration enhances recovery of platelet level and function in mice with thrombocytopenia. a The KM mice were irradiated by X-ray (4 Gy) and then treated with normal saline, TPO (3000 U/kg), or DMAG (5 mg/kg) for 14 days, respectively. The number of platelets were counted on day 0, 3, 7, 10, and 14. Each group contains 12 mice (6 male mice and 6 female mice). The data represent the mean ± SD of three independent experiments; *p < 0.05, **p < 0.01, ***p < 0.001, compared to the corresponding model group. b MPV was measured on day 0, 3, 7, 10, and 14 in each group. c Representative images of H&E staining of BM from normal, model, TPO and DMAG groups. The yellow circles indicate megakaryocytes. Scale bar: 100 µm. The histogram indicates the number of megakaryocytes in each group. The data represent the mean ± SD of three independent experiments; *p < 0.05, **p < 0.01, compared to the model group. d Immunohistochemical analysis of the expression of VWF in BM cells of each group. Blue represents cell nucleus. Brownness represents the expression of VWF. The histogram indicates the number of megakaryocytes in each group. The data represent the mean ± SD of three independent experiments; **p < 0.01, ***p < 0.001, compared to the model group. e The expression of CD41 and CD61 was detected by flow cytometry in BM cells of each group. The histogram indicates the percentage of CD41+CD61+ cells in each group. The data represent the mean ± SD of three independent experiments; ***p < 0.001, compared to the model group. f Tail bleeding time was measured after the distal tail was cut in each group. The data represent the mean ± SD of three independent experiments; **p < 0.01, compared to the model group. g Under the stimulation of ADP, platelet aggregation was measured by a turbidimetric aggregation-monitoring device. The histogram shows the maximum aggregation amplitude of platelets in each group. The data represent the mean ± SD of three independent experiments; **p < 0.01, compared to the model group. h Micrographs of collagen-coated slides with the same number of platelets perfused. The red represents platelets. The histogram shows the average coverage of red fluorescence on the whole surface by ImageJ software. The data represent the mean ± SD of three independent experiments; ***p < 0.001, compared to the model group

Fig 5: Preparation and characterization of PPHNs. (A) Prolonged blood circulation for PBC-bound phage. BCP1-BGL or BGL phages (1 × 109 pfu each), either unbound or pre-bound to PBC, were separately injected into rats and the phage titer in the blood at various time points was determined. Mean ± S.E.M., n = 3, *p < 0.05, **p < 0.01, with BCP1-BGL prebound compared to BCP1-BGL and BGL prebound compared to BGL. (B) Schematic illustration of PPHNs. PLTs extracted from 1 mL of rat blood were used to prepare platelet membrane nanoparticles (PMNs), followed by incubation with 5.2 × 1012 pfu of phages. PPHNs were isolated through centrifugation, followed by several washes with PBS. (C) TEM images of PMNs (left) and PPHNs (right) negatively stained with uranyl acetate. Scale bar, 100 nm. (D) Detection of expressed CD41, CD42b, CD61 and P8 in PMNs and PPHNs by western blotting with specific antibodies. (E) Dynamic light scattering analysis of PMNs, PPHNs in water. (F) Zeta potential distribution of phage, PMNs and PPHNs. Mean ± S.E.M., n = 3. (G) Release study of phage bound on PPHNs. Mean ± S.E.M., n = 3. (H) Binding of BCP1-BGL phage to PMNs in the presence of increasing concentration of BCP1 peptide. The number of unbound phages was determined after centrifugation. Mean ± S.E.M., n = 3. (I) Thermal stability of PPHNs. Mean ± S.E.M., n = 3.