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Hypoxia can aggravate tumor occurrence, development, invasion, and metastasis, and greatly inhibit the photodynamic therapy (PDT) effect. Herein, carbon nitride (CNs)‐based DNA and photosensitizer co‐delivery systems (BPSCNs) with oxygen‐producing functions are developed to address this problem. Selenide glucose (Seglu) is used as the dopant to prepare red/NIR‐active CNs (SegluCNs). The tumor‐targeting unit Bio‐PEG2000is utilized to construct BPSCNs nanoparticles through esterification reactions. Furthermore, DNA hydrophobization is realized via mixing P53 gene with a positively charged mitochondrial‐targeted near‐infrared (NIR) emitting photosensitizer (MTTPY), which is encapsulated in non‐cationic BPSCNs for synergistic delivery. Ester bonds in BPSCNs@MTTPY‐P53 complexes can be disrupted by lipase in the liver to facilitate P53 release, upregulated P53 expression, and promoted HIF‐1α degradation in mitochondria. In addition, the oxygen produced by the complexes improved the hypoxic microenvironment of hepatocellular carcinoma (HCC), synergistically downregulated HIF‐1α expression in mitochondria, promoted mitochondrial‐derived ferroptosis and enhanced the PDT effect of the MTTPY unit. Both in vivo and in vitro experiments indicated that the transfected P53‐DNA, produced O2and ROS by these complexes synergistically led to mitochondrial‐derived ferroptosis in hepatoma cells through the HIF‐1α/SLC7A11 pathway, and completely avoiding PDT resistance caused by hypoxia, exerting a significant therapeutic role in HCC treatment. BPSCNs@MTTPY‐P53 complexes can be disrupted by lipase in the liver to facilitate P53 release, upregulated P53 expression, and promoted HIF‐1c degradation in mitochondria. After laser irradiation, the oxygen produced by the complexes improved the hypoxic microenvironment of HCC, synergistically downregulated HIF‐1α expression in mitochondria, promoted mitochondrial‐derived ferroptosis, and enhanced the PDT effect of tumors.

An ultrasound-triggered sonodynamic therapy has shown great promise for cancer therapy. However, its clinical applications are very limited because the traditional sonosensitizers tend to suffer from very poor efficiency combined with low retention in cancer cells and low tumor selectivity. Therefore, sonosensitizers with higher effectivity, higher tumor cell retention, and higher tumor cell specificity are highly required. Herein, we constructed a Ti2C(OH)Xnanosheet, which was a poor sonosensitizer but had a long circulation in the blood system. However, it was very interesting to find that the tumor microenvironment could in situturn Ti2C(OH)Xnanosheet into a novel and excellent sonosensitizer with a nanofiber structure in tumors, exhibiting excellent ability to generate reactive oxygen species (ROS) under ultrasound. Moreover, the nanofiber structure made it very difficult to get out of cancer cells, highly enhancing the retention of the sonosensitizer in the tumor, thereby enabling it to effectively and selectively kill cancer cells in vivo. Our findings demonstrate that the strategy of the tumor microenvironment triggering the in situsynthesis of an effective sonosensitizer in tumor provided a promising means to simultaneously increase the efficiency, sonosensitizer retention in cancer cells, and cancer selectivity, thereby effectively killing cancer cells but causing little damage to healthy tissues via the sonodynamic therapy.

Response surface methodology was applied to investigate the optimum degradation conditions of paracetamol using Ag/BiVO4 photocatalysts under the visible light irradiation. Experimental results show that the optimum degradation conditions were: catalyst dosage quantity was 80 mg, Ag-catalyst loading was 5%, and the initial pH value of the solution was 6, respectively. Under this condition, the degradation efficiency of paracetamol was 77.9% within 5 h under the visible light irradiation.

ABSTRACTPseudomonas aeruginosacan employ many distinct mechanisms of resistance to aminoglycoside antibiotics; however, in cystic fibrosis patients, more than 90% of aminoglycoside-resistantP. aeruginosaisolates are of the impermeability phenotype. The precise molecular mechanisms that produce aminoglycoside impermeability-type resistance are yet to be elucidated. A subtractive hybridization technique was used to reveal gene expression differences between PAO1 and isogenic, spontaneous aminoglycoside-resistant mutants of the impermeability phenotype. Among the many genes found to be up-regulated in these laboratory mutants were the amrABgenes encoding a recently discovered efflux system. TheamrABgenes appear to be the same as the recently describedmexXYgenes; however, the resistance profile that we see inP. aeruginosais very different from that described forEscherichia coliwith mexXY. Direct evidence for AmrAB involvement in aminoglycoside resistance was provided by the deletion of amrBin the PAO1-derived laboratory mutant, which resulted in the restoration of aminoglycoside sensitivity to a level nearly identical to that of the parent strain. Furthermore, transcription of the amrABgenes was shown to be up-regulated in P. aeruginosaclinical isolates displaying the impermeability phenotype compared to a genotypically matched sensitive clinical isolate from the same patient. This suggests the possibility that AmrAB-mediated efflux is a clinically relevant mechanism of aminoglycoside resistance. Although it is unlikely that hyperexpression of AmrAB is the sole mechanism conferring the impermeability phenotype, we believe that the Amr efflux system can contribute to a complex interaction of molecular events resulting in the aminoglycoside impermeability-type resistance phenotype.