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[Display omitted] • Overexpressed DNMT1 drives PTX resistance and immune escape by EMT process in TNBC. • The combination of αPD-L1, DEX and PTX achieve a high quality synergistic anti-tumor effect. • DEC/PTX NPs@αPD-L1 achieve multiple tumor selection. • DEC/PTX NPs@αPD-L1 induced robust anti-tumor immunity via multilayered immunity effects. Triple-negative breast cancer (TNBC) is one of the major clinical problems to be solved urgently, because of its high malignancy, poor targeted therapy effect and easy occurrence of drug resistance and metastasis. Here, methyltransferase DNMT1 was identified as a key factor mediating PTX resistance for TNBC. Decitabine (DEC), an inhibitor of DNMT1, can inhibit the proliferation and metastasis of TNBC cells and reverse PTX resistance. In this study, we reported a new delivery system (DEC/PTX NPs@αPD-L1) co-loaded with DEC and PTX modified by anti-PD-L1 monoclonal antibody (αPD-L1), which can overcome drug resistance and metastasis through multi-mode synergistic effect. αPD-L1 increases the enrichment of nanoparticles in tumor tissue through active targeting effect, and blocks PD-L1 on the surface of TNBC cells, thereby activating anti-tumor immune while enhancing internalization of nanoparticles by tumor cells. Inside tumor cells, DEC inhibits EMT process and cancer stem cells to overcome PTX resistance and metastasis. PTX can not only exerts direct tumor killing effect, but also inhibit Treg cells from remodeling immune microenvironment, and induces efficient immunogenic death in cooperation with DEC. This delivery system, realizing tumor-specific synchronized chemoimmunotherapy, represents a promising therapeutic platform for TNBC. [ABSTRACT FROM AUTHOR]

Strain localization influenced by microstructural features has an important effect on mechanical properties of α + β titanium alloy. To address the effect, a microstructure-based finite element model is established. In this model, regions for primary α (αp) and transformed β matrix (βt) are generated from real microstructures of a two-phase titanium alloy (TA15 alloy); the plastic flow behaviors of these two features are determined directly rather than from single phase alloy. A constitutive equation of αp is developed with consideration of dislocation-obstacle interaction, whereas the constitutive equation of βt is determined by nanoindentation tests. Finally, the calculated stress-strain responses of the alloy are verified by experiments. The simulated results show that strain localization bands (SLBs) have two morphologies: short and long-continuous SLBs. Lots of short SLBs appear mainly in βt and αp when the volume fraction of αp is small and moderate, respectively. Long-continuous SLBs appear mainly in αp when the volume fraction of αp is large. With the increase of αp in SLBs, the strength of the alloy decreases while the ductility increases. By decreasing the disparity of strength between αp and βt, the strain gradient in SLBs reduces and the ductility of the alloy increases. [ABSTRACT FROM AUTHOR]