The abundant extracellular matrix (ECM) in solid tumors causes limited drug penetration and hypoxia-mediated chemoresistance, which lead to poor chemotherapy outcomes. To solve this problem, a biomimetic metal-organic framework nanodrug (ZIF-8-DOX-LY-RM) is developed with red blood cell membrane (RM) camouflage and encapsulation of type 1 transforming growth factor β receptor (TGFBR1) inhibitor and doxorubicin (DOX) for efficient chemotherapy. Based on the biomimetic properties of the erythrocyte membrane, ZIF-8-DOX-LY-RM can effectively accumulate in tumor tissues with immune escape and prolonged blood circulation. Then, the enriched nanodrug ZIF-8-DOX-LY-RM releases the TGFBR1 to remove collagen, subsequently leading to enhanced nanodrug penetration and increased oxygen supply. The abundant oxygen supply then relieves hypoxia-mediated chemoresistance of DOX through increased cellular uptake and elevated reactive oxygen species production. The in vivo studies demonstrate the outstanding performance of ZIF-8-DOX-LY-RM nanoparticles in chemotherapy of cancer. This work presents an ECM normalization strategy for the synergistic collagen depletion and hypoxia alleviation and opens a promising avenue for effective chemotherapy of solid tumors.

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Advancement of bioorthogonal chemistry in molecular optical imaging lies in expanding the repertoire of fluorophores that can undergo fluorescence signal changes upon bioorthogonal ligation. However, most available bioorthogonally activatable fluorophores only emit shallow tissue-penetrating visible light via an intramolecular charge transfer mechanism. Herein, we report a serendipitous “torsion-induced disaggregation (TIDA)” phenomenon in the design of near-infrared (NIR) tetrazine (Tz)-based cyanine probe. The TIDA of the cyanine is triggered upon Tz-transcyclooctene ligation, converting its heptamethine chain from S-trans to S-cis conformation. Thus, after bioorthogonal reaction, the tendency of the resulting cyanine towards aggregation is reduced, leading to TIDA-induced fluorescence enhancement response. This Tz-cyanine probe sensitively delineates the tumor in living mice as early as 5 min post intravenous injection. As such, this work discovers a design mechanism for the construction of bioorthogonally activatable NIR fluorophores and opens up opportunities to further exploit bioorthogonal chemistry in in vivo imaging.

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The behavior of power transmission tower-line system subjected to spatially varying base excitations is studied in this paper. The transmission towers are modeled by beam elements while the transmission lines are modeled by cable elements that account for the nonlinear geometry of the cables. The real multistation data from SMART-1 are used to analyze the system response subjected to spatially varying ground motions. The seismic input waves for vertical and horizontal ground motions are also generated based on the Code for Design of Seismic of Electrical Installations. Both the incoherency of seismic waves and wave travel effects are accounted for. The nonlinear time history analytical method is used in the analysis. The effects of boundary conditions, ground motion spatial variations, the incident angle of the seismic wave, coherency loss, and wave travel on the system are investigated. The results show that the uniform ground motion at all supports of system does not provide the most critical case for the response calculations.