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Schematic illustration of the ROS-responsive on-demand mild photothermal cascade platform for tendon rejuvenation in Achilles tendinopathy. The platform strategically modulates the <t>mitochondrial-cGAS-STING-IRF3/NF-κB</t> signaling axis and induces heat shock protein 70 (HSP70) expression to attenuate oxidative stress and cellular senescence within tendon stem/progenitor cells (TSPCs). Consequently, it promotes tenogenic differentiation while abrogating aberrant osteogenic/chondrogenic lineage commitment. This cascade effect ultimately mitigates heterotopic ossification, enhances structural tendon regeneration, restores biomechanical function, and alleviates pain. Nanoparticle nomenclature: LA-NPs and TPA-TCNQ-NPs denote nanoparticles encapsulating LA or TPA-TCNQ individually; LT-NPs refers to the composite formulation consisting of a mixture of LA-NPs and TPA-TCNQ-NPs; and LT-NPs-NIR represents the LT-NPs mixture following 808 nm near-infrared (NIR) irradiation to activate the photothermal response and controlled payload release.
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Schematic illustration of the ROS-responsive on-demand mild photothermal cascade platform for tendon rejuvenation in Achilles tendinopathy. The platform strategically modulates the <t>mitochondrial-cGAS-STING-IRF3/NF-κB</t> signaling axis and induces heat shock protein 70 (HSP70) expression to attenuate oxidative stress and cellular senescence within tendon stem/progenitor cells (TSPCs). Consequently, it promotes tenogenic differentiation while abrogating aberrant osteogenic/chondrogenic lineage commitment. This cascade effect ultimately mitigates heterotopic ossification, enhances structural tendon regeneration, restores biomechanical function, and alleviates pain. Nanoparticle nomenclature: LA-NPs and TPA-TCNQ-NPs denote nanoparticles encapsulating LA or TPA-TCNQ individually; LT-NPs refers to the composite formulation consisting of a mixture of LA-NPs and TPA-TCNQ-NPs; and LT-NPs-NIR represents the LT-NPs mixture following 808 nm near-infrared (NIR) irradiation to activate the photothermal response and controlled payload release.
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Schematic illustration of the ROS-responsive on-demand mild photothermal cascade platform for tendon rejuvenation in Achilles tendinopathy. The platform strategically modulates the <t>mitochondrial-cGAS-STING-IRF3/NF-κB</t> signaling axis and induces heat shock protein 70 (HSP70) expression to attenuate oxidative stress and cellular senescence within tendon stem/progenitor cells (TSPCs). Consequently, it promotes tenogenic differentiation while abrogating aberrant osteogenic/chondrogenic lineage commitment. This cascade effect ultimately mitigates heterotopic ossification, enhances structural tendon regeneration, restores biomechanical function, and alleviates pain. Nanoparticle nomenclature: LA-NPs and TPA-TCNQ-NPs denote nanoparticles encapsulating LA or TPA-TCNQ individually; LT-NPs refers to the composite formulation consisting of a mixture of LA-NPs and TPA-TCNQ-NPs; and LT-NPs-NIR represents the LT-NPs mixture following 808 nm near-infrared (NIR) irradiation to activate the photothermal response and controlled payload release.
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Schematic illustration of the ROS-responsive on-demand mild photothermal cascade platform for tendon rejuvenation in Achilles tendinopathy. The platform strategically modulates the <t>mitochondrial-cGAS-STING-IRF3/NF-κB</t> signaling axis and induces heat shock protein 70 (HSP70) expression to attenuate oxidative stress and cellular senescence within tendon stem/progenitor cells (TSPCs). Consequently, it promotes tenogenic differentiation while abrogating aberrant osteogenic/chondrogenic lineage commitment. This cascade effect ultimately mitigates heterotopic ossification, enhances structural tendon regeneration, restores biomechanical function, and alleviates pain. Nanoparticle nomenclature: LA-NPs and TPA-TCNQ-NPs denote nanoparticles encapsulating LA or TPA-TCNQ individually; LT-NPs refers to the composite formulation consisting of a mixture of LA-NPs and TPA-TCNQ-NPs; and LT-NPs-NIR represents the LT-NPs mixture following 808 nm near-infrared (NIR) irradiation to activate the photothermal response and controlled payload release.
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Schematic illustration of the ROS-responsive on-demand mild photothermal cascade platform for tendon rejuvenation in Achilles tendinopathy. The platform strategically modulates the <t>mitochondrial-cGAS-STING-IRF3/NF-κB</t> signaling axis and induces heat shock protein 70 (HSP70) expression to attenuate oxidative stress and cellular senescence within tendon stem/progenitor cells (TSPCs). Consequently, it promotes tenogenic differentiation while abrogating aberrant osteogenic/chondrogenic lineage commitment. This cascade effect ultimately mitigates heterotopic ossification, enhances structural tendon regeneration, restores biomechanical function, and alleviates pain. Nanoparticle nomenclature: LA-NPs and TPA-TCNQ-NPs denote nanoparticles encapsulating LA or TPA-TCNQ individually; LT-NPs refers to the composite formulation consisting of a mixture of LA-NPs and TPA-TCNQ-NPs; and LT-NPs-NIR represents the LT-NPs mixture following 808 nm near-infrared (NIR) irradiation to activate the photothermal response and controlled payload release.
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Schematic illustration of the ROS-responsive on-demand mild photothermal cascade platform for tendon rejuvenation in Achilles tendinopathy. The platform strategically modulates the <t>mitochondrial-cGAS-STING-IRF3/NF-κB</t> signaling axis and induces heat shock protein 70 (HSP70) expression to attenuate oxidative stress and cellular senescence within tendon stem/progenitor cells (TSPCs). Consequently, it promotes tenogenic differentiation while abrogating aberrant osteogenic/chondrogenic lineage commitment. This cascade effect ultimately mitigates heterotopic ossification, enhances structural tendon regeneration, restores biomechanical function, and alleviates pain. Nanoparticle nomenclature: LA-NPs and TPA-TCNQ-NPs denote nanoparticles encapsulating LA or TPA-TCNQ individually; LT-NPs refers to the composite formulation consisting of a mixture of LA-NPs and TPA-TCNQ-NPs; and LT-NPs-NIR represents the LT-NPs mixture following 808 nm near-infrared (NIR) irradiation to activate the photothermal response and controlled payload release.
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Pinostilbene, identified through screening as a natural STING agonist, activates the <t>STING/TBK1/IRF3</t> pathway in NSCLC cells in a concentration-dependent manner. (A) H1299 cells transfected with an IFNB1 promoter-driven luciferase reporter were stimulated with STING agonists poly(I:C) (1 μg/mL) or poly(dA:dT) (1 μg/mL) for 24 h to assess activation (n = 4). (B) Screening of a natural product library using the assay in (A) (n = 3). (C–J) Western blot analysis of STING, TBK1, and IRF3 phosphorylation in H1299 (C–F) and A549 (G–J) cells treated with Pinostilbene for 24 h (n = 3). (K) Immunofluorescence of p -IRF3 nuclear translocation in H1299 cells (n = 3). Scale bars, 20 μm. (L–R) qPCR analysis of IFNB1 (L), IFIT1 (M), IFIT2 (N), ISG15 (O), CXCL10 (P), IFI44 (Q), and IFI44L (R) mRNA in H1299 cells (n = 3). β-Actin was used as a control. All experiments were independently repeated at least three times. Data are presented as the mean ± SD. Statistical significance was determined by one-way ANOVA followed by Tukey's test. * P < 0.05; ** P < 0.01; *** P < 0.001; ns, not significant.
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Pinostilbene, identified through screening as a natural STING agonist, activates the <t>STING/TBK1/IRF3</t> pathway in NSCLC cells in a concentration-dependent manner. (A) H1299 cells transfected with an IFNB1 promoter-driven luciferase reporter were stimulated with STING agonists poly(I:C) (1 μg/mL) or poly(dA:dT) (1 μg/mL) for 24 h to assess activation (n = 4). (B) Screening of a natural product library using the assay in (A) (n = 3). (C–J) Western blot analysis of STING, TBK1, and IRF3 phosphorylation in H1299 (C–F) and A549 (G–J) cells treated with Pinostilbene for 24 h (n = 3). (K) Immunofluorescence of p -IRF3 nuclear translocation in H1299 cells (n = 3). Scale bars, 20 μm. (L–R) qPCR analysis of IFNB1 (L), IFIT1 (M), IFIT2 (N), ISG15 (O), CXCL10 (P), IFI44 (Q), and IFI44L (R) mRNA in H1299 cells (n = 3). β-Actin was used as a control. All experiments were independently repeated at least three times. Data are presented as the mean ± SD. Statistical significance was determined by one-way ANOVA followed by Tukey's test. * P < 0.05; ** P < 0.01; *** P < 0.001; ns, not significant.
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Image Search Results


Schematic illustration of the ROS-responsive on-demand mild photothermal cascade platform for tendon rejuvenation in Achilles tendinopathy. The platform strategically modulates the mitochondrial-cGAS-STING-IRF3/NF-κB signaling axis and induces heat shock protein 70 (HSP70) expression to attenuate oxidative stress and cellular senescence within tendon stem/progenitor cells (TSPCs). Consequently, it promotes tenogenic differentiation while abrogating aberrant osteogenic/chondrogenic lineage commitment. This cascade effect ultimately mitigates heterotopic ossification, enhances structural tendon regeneration, restores biomechanical function, and alleviates pain. Nanoparticle nomenclature: LA-NPs and TPA-TCNQ-NPs denote nanoparticles encapsulating LA or TPA-TCNQ individually; LT-NPs refers to the composite formulation consisting of a mixture of LA-NPs and TPA-TCNQ-NPs; and LT-NPs-NIR represents the LT-NPs mixture following 808 nm near-infrared (NIR) irradiation to activate the photothermal response and controlled payload release.

Journal: Bioactive Materials

Article Title: On-demand mild photothermal cascade platform reprogramming mitochondrial immunity for tendon rejuvenation

doi: 10.1016/j.bioactmat.2026.01.004

Figure Lengend Snippet: Schematic illustration of the ROS-responsive on-demand mild photothermal cascade platform for tendon rejuvenation in Achilles tendinopathy. The platform strategically modulates the mitochondrial-cGAS-STING-IRF3/NF-κB signaling axis and induces heat shock protein 70 (HSP70) expression to attenuate oxidative stress and cellular senescence within tendon stem/progenitor cells (TSPCs). Consequently, it promotes tenogenic differentiation while abrogating aberrant osteogenic/chondrogenic lineage commitment. This cascade effect ultimately mitigates heterotopic ossification, enhances structural tendon regeneration, restores biomechanical function, and alleviates pain. Nanoparticle nomenclature: LA-NPs and TPA-TCNQ-NPs denote nanoparticles encapsulating LA or TPA-TCNQ individually; LT-NPs refers to the composite formulation consisting of a mixture of LA-NPs and TPA-TCNQ-NPs; and LT-NPs-NIR represents the LT-NPs mixture following 808 nm near-infrared (NIR) irradiation to activate the photothermal response and controlled payload release.

Article Snippet: After blocking for 1 h, membranes were incubated overnight at 4 °C with primary antibodies against STING (13647, CST, USA; A21051, Abclonal, China), p-STING (72971, CST, USA; AF7416, Affinity, China), IRF3 (ab68481, Abcam, UK), p-IRF3 (29047, CST, USA), P65 (A22331, Abclonal, China; 8242, CST, USA), p-P65 (AP0124, Abclonal, China), P53 (10442-1-AP, Proteintech, USA), SOX9 (sc-166505, Santa Cruz, USA), BMP-2 (ab284387, abcam, USA), OCN (sc-390877, Santa Cruz, USA), and iNOS (ab178945, Abcam, USA).

Techniques: Expressing, Formulation, Irradiation

LT-NPs-NIR regulate the mtDNA-STING-IRF3/NF-κB pathway in macrophages. (A) Principal component analysis (PCA) of transcriptomic data from RAW 264.7 cells under different treatments. (B) Volcano plots comparing H 2 O 2 vs. Control (left) and LT-NPs-NIR vs. H 2 O 2 (right). (C) Heatmap of differentially expressed genes (DEGs) with hierarchical clustering. (D, E) Gene Ontology (GO), KEGG, and Gene Set Enrichment Analysis (GSEA) for H 2 O 2 vs. Control (D) and LT-NPs-NIR vs. H 2 O 2 (E). (F) Multi-SIM imaging showing mtDNA (magenta) and the mitochondrial outer membrane protein TOMM20 (green), with quantification of their colocalization. (G) Western blot analysis of key proteins in the cGAS-STING-NF-κB axis. Scale bar: 5 μm (F). Significance: ns, not significant; ∗p < 0.05, ∗∗p < 0.01, ∗∗∗p < 0.001.

Journal: Bioactive Materials

Article Title: On-demand mild photothermal cascade platform reprogramming mitochondrial immunity for tendon rejuvenation

doi: 10.1016/j.bioactmat.2026.01.004

Figure Lengend Snippet: LT-NPs-NIR regulate the mtDNA-STING-IRF3/NF-κB pathway in macrophages. (A) Principal component analysis (PCA) of transcriptomic data from RAW 264.7 cells under different treatments. (B) Volcano plots comparing H 2 O 2 vs. Control (left) and LT-NPs-NIR vs. H 2 O 2 (right). (C) Heatmap of differentially expressed genes (DEGs) with hierarchical clustering. (D, E) Gene Ontology (GO), KEGG, and Gene Set Enrichment Analysis (GSEA) for H 2 O 2 vs. Control (D) and LT-NPs-NIR vs. H 2 O 2 (E). (F) Multi-SIM imaging showing mtDNA (magenta) and the mitochondrial outer membrane protein TOMM20 (green), with quantification of their colocalization. (G) Western blot analysis of key proteins in the cGAS-STING-NF-κB axis. Scale bar: 5 μm (F). Significance: ns, not significant; ∗p < 0.05, ∗∗p < 0.01, ∗∗∗p < 0.001.

Article Snippet: After blocking for 1 h, membranes were incubated overnight at 4 °C with primary antibodies against STING (13647, CST, USA; A21051, Abclonal, China), p-STING (72971, CST, USA; AF7416, Affinity, China), IRF3 (ab68481, Abcam, UK), p-IRF3 (29047, CST, USA), P65 (A22331, Abclonal, China; 8242, CST, USA), p-P65 (AP0124, Abclonal, China), P53 (10442-1-AP, Proteintech, USA), SOX9 (sc-166505, Santa Cruz, USA), BMP-2 (ab284387, abcam, USA), OCN (sc-390877, Santa Cruz, USA), and iNOS (ab178945, Abcam, USA).

Techniques: Control, Imaging, Membrane, Western Blot

LT-NPs-NIR attenuate oxidative stress, preserve mitochondrial integrity, and suppress senescence in TSPCs by inhibiting the mtDNA-STING-NF-κB axis. (A) Schematic of the experimental design. (B) TSPC proliferation assessed by CCK-8 assay. (C, E) Immunofluorescence staining and quantification of HSP70 (n = 3). (D, F) Mitochondrial membrane potential (ΔΨm) visualized by JC-1 staining (red: high potential; green: low potential) and quantification. (G) Multi-SIM of mtDNA (magenta) and TOMM20 (green) with colocalization analysis. (H) Western blot of cGAS-STING-IRF3-NF-κB pathway proteins. (I, K) Colony-forming unit fibroblast (CFU-F) assay and quantification of self-renewal capacity (n = 3). (J) Senescence-associated β-galactosidase (SA-β-gal) activity. (L, M) Apoptosis analysis by Annexin V/PI flow cytometry and quantification (n = 3). Scale bars: 100 μm (C); 5 μm (D, G); 200 μm (J). Significance: ns, not significant; ∗p < 0.05, ∗∗p < 0.01, ∗∗∗p < 0.001.

Journal: Bioactive Materials

Article Title: On-demand mild photothermal cascade platform reprogramming mitochondrial immunity for tendon rejuvenation

doi: 10.1016/j.bioactmat.2026.01.004

Figure Lengend Snippet: LT-NPs-NIR attenuate oxidative stress, preserve mitochondrial integrity, and suppress senescence in TSPCs by inhibiting the mtDNA-STING-NF-κB axis. (A) Schematic of the experimental design. (B) TSPC proliferation assessed by CCK-8 assay. (C, E) Immunofluorescence staining and quantification of HSP70 (n = 3). (D, F) Mitochondrial membrane potential (ΔΨm) visualized by JC-1 staining (red: high potential; green: low potential) and quantification. (G) Multi-SIM of mtDNA (magenta) and TOMM20 (green) with colocalization analysis. (H) Western blot of cGAS-STING-IRF3-NF-κB pathway proteins. (I, K) Colony-forming unit fibroblast (CFU-F) assay and quantification of self-renewal capacity (n = 3). (J) Senescence-associated β-galactosidase (SA-β-gal) activity. (L, M) Apoptosis analysis by Annexin V/PI flow cytometry and quantification (n = 3). Scale bars: 100 μm (C); 5 μm (D, G); 200 μm (J). Significance: ns, not significant; ∗p < 0.05, ∗∗p < 0.01, ∗∗∗p < 0.001.

Article Snippet: After blocking for 1 h, membranes were incubated overnight at 4 °C with primary antibodies against STING (13647, CST, USA; A21051, Abclonal, China), p-STING (72971, CST, USA; AF7416, Affinity, China), IRF3 (ab68481, Abcam, UK), p-IRF3 (29047, CST, USA), P65 (A22331, Abclonal, China; 8242, CST, USA), p-P65 (AP0124, Abclonal, China), P53 (10442-1-AP, Proteintech, USA), SOX9 (sc-166505, Santa Cruz, USA), BMP-2 (ab284387, abcam, USA), OCN (sc-390877, Santa Cruz, USA), and iNOS (ab178945, Abcam, USA).

Techniques: CCK-8 Assay, Immunofluorescence, Staining, Membrane, Western Blot, Activity Assay, Flow Cytometry

Pinostilbene, identified through screening as a natural STING agonist, activates the STING/TBK1/IRF3 pathway in NSCLC cells in a concentration-dependent manner. (A) H1299 cells transfected with an IFNB1 promoter-driven luciferase reporter were stimulated with STING agonists poly(I:C) (1 μg/mL) or poly(dA:dT) (1 μg/mL) for 24 h to assess activation (n = 4). (B) Screening of a natural product library using the assay in (A) (n = 3). (C–J) Western blot analysis of STING, TBK1, and IRF3 phosphorylation in H1299 (C–F) and A549 (G–J) cells treated with Pinostilbene for 24 h (n = 3). (K) Immunofluorescence of p -IRF3 nuclear translocation in H1299 cells (n = 3). Scale bars, 20 μm. (L–R) qPCR analysis of IFNB1 (L), IFIT1 (M), IFIT2 (N), ISG15 (O), CXCL10 (P), IFI44 (Q), and IFI44L (R) mRNA in H1299 cells (n = 3). β-Actin was used as a control. All experiments were independently repeated at least three times. Data are presented as the mean ± SD. Statistical significance was determined by one-way ANOVA followed by Tukey's test. * P < 0.05; ** P < 0.01; *** P < 0.001; ns, not significant.

Journal: Redox Biology

Article Title: Identification of Pinostilbene as a natural STING agonist that triggers FTH1 degradation via K48-ubiquitination to induce ferroptosis in non-small cell lung cancer

doi: 10.1016/j.redox.2026.104099

Figure Lengend Snippet: Pinostilbene, identified through screening as a natural STING agonist, activates the STING/TBK1/IRF3 pathway in NSCLC cells in a concentration-dependent manner. (A) H1299 cells transfected with an IFNB1 promoter-driven luciferase reporter were stimulated with STING agonists poly(I:C) (1 μg/mL) or poly(dA:dT) (1 μg/mL) for 24 h to assess activation (n = 4). (B) Screening of a natural product library using the assay in (A) (n = 3). (C–J) Western blot analysis of STING, TBK1, and IRF3 phosphorylation in H1299 (C–F) and A549 (G–J) cells treated with Pinostilbene for 24 h (n = 3). (K) Immunofluorescence of p -IRF3 nuclear translocation in H1299 cells (n = 3). Scale bars, 20 μm. (L–R) qPCR analysis of IFNB1 (L), IFIT1 (M), IFIT2 (N), ISG15 (O), CXCL10 (P), IFI44 (Q), and IFI44L (R) mRNA in H1299 cells (n = 3). β-Actin was used as a control. All experiments were independently repeated at least three times. Data are presented as the mean ± SD. Statistical significance was determined by one-way ANOVA followed by Tukey's test. * P < 0.05; ** P < 0.01; *** P < 0.001; ns, not significant.

Article Snippet: Antibodies against STING, TBK1, and IRF3 were purchased from Proteintech (Wuhan, China).

Techniques: Concentration Assay, Transfection, Luciferase, Activation Assay, Western Blot, Phospho-proteomics, Immunofluorescence, Translocation Assay, Control

Pinostilbene activates the STING/ferroptosis pathway to exert antitumor effects in vivo . Lewis lung carcinoma-bearing mice were administered Pinostilbene (10 mg/kg, i.p., every two days) or vehicle control for 24 days, during which tumor volume was measured every other day prior to euthanasia (n = 6). (A) Tumor growth curve (n = 6). (B) Excised tumors (n = 6). (C) Tumor weight (n = 6). (D) H&E staining of major organs (n = 3). Scale bars, 50 μm. (E–H) Western blot of p-STING (E, F), p -TBK1 (E, G), and p -IRF3 (E, H) in tumors (n = 3). (I–M) qPCR of IFNB1 (I), IFIT1 (J), ISG15 (K), USP18 (L), and CXCL10 (M) mRNA in tumors (n = 3). (N–Q) FTH1 expression by IHC (n = 5) and Western blot (n = 3). Scale bars, 100 μm. (R, S) 4-HNE levels by IHC (n = 5). Scale bars, 100 μm. (T, U) Ki67 IHC for proliferation (n = 5). Scale bars, 100 μm. (V–X) qPCR of IL-1β (V), IL-6 (W), and TNF-α (X) mRNA in tumors (n = 3). (Y) Representative images of immunofluorescence for CD8 + and CD4 + T cell infiltration (n = 3). Scale bars, 100 μm. All experiments were independently repeated at least three times. Data are presented as the mean ± SD. Significance was determined by Student's t -test. ** P < 0.01; *** P < 0.001.

Journal: Redox Biology

Article Title: Identification of Pinostilbene as a natural STING agonist that triggers FTH1 degradation via K48-ubiquitination to induce ferroptosis in non-small cell lung cancer

doi: 10.1016/j.redox.2026.104099

Figure Lengend Snippet: Pinostilbene activates the STING/ferroptosis pathway to exert antitumor effects in vivo . Lewis lung carcinoma-bearing mice were administered Pinostilbene (10 mg/kg, i.p., every two days) or vehicle control for 24 days, during which tumor volume was measured every other day prior to euthanasia (n = 6). (A) Tumor growth curve (n = 6). (B) Excised tumors (n = 6). (C) Tumor weight (n = 6). (D) H&E staining of major organs (n = 3). Scale bars, 50 μm. (E–H) Western blot of p-STING (E, F), p -TBK1 (E, G), and p -IRF3 (E, H) in tumors (n = 3). (I–M) qPCR of IFNB1 (I), IFIT1 (J), ISG15 (K), USP18 (L), and CXCL10 (M) mRNA in tumors (n = 3). (N–Q) FTH1 expression by IHC (n = 5) and Western blot (n = 3). Scale bars, 100 μm. (R, S) 4-HNE levels by IHC (n = 5). Scale bars, 100 μm. (T, U) Ki67 IHC for proliferation (n = 5). Scale bars, 100 μm. (V–X) qPCR of IL-1β (V), IL-6 (W), and TNF-α (X) mRNA in tumors (n = 3). (Y) Representative images of immunofluorescence for CD8 + and CD4 + T cell infiltration (n = 3). Scale bars, 100 μm. All experiments were independently repeated at least three times. Data are presented as the mean ± SD. Significance was determined by Student's t -test. ** P < 0.01; *** P < 0.001.

Article Snippet: Antibodies against STING, TBK1, and IRF3 were purchased from Proteintech (Wuhan, China).

Techniques: In Vivo, Control, Staining, Western Blot, Expressing, Immunofluorescence