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The application of combinational therapy breaks the limitation of monotherapy and achieves better clinical benefit for tumor therapy. Herein, a hyaluronic acid/Pluronic F68-based copolymer-mixed micelle was constructed for targeted delivery of chemotherapeutical agent docetaxel (PHDM) in combination with programmed cell death ligand-1(PD-L1) antibody. When PHDM+anti-PDL1 was injected into the blood system, PHDM could accumulate into tumor sites and target tumor cells via CD44-mediated endocytosis and possess tumor chemotherapy. While anti-PDL1 could target PD-L1 protein expressed on surface of tumor cells to the immune checkpoint blockade characteristic for tumor immunotherapy. This strategy could not only directly kill tumor cells but also improve CD8+ T cell level and facilitate effector cytokines release. In conclusion, the rational-designed PHDM+anti-PDL1 therapy strategy creates a new way for tumor immune-chemotherapy.

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Freeze-thaw cycles (FTCs) are an important element of mid and high latitude ecosystems, and significantly influence soil physicochemical properties and microbial activities in the soil active layers. With the global warming, the effects of FTCs on the dissolved organic carbon (DOC) concentration and soil enzyme activity of different types of soil were still uncertain. In this study, soil of undisturbed Deyeuxia angustifolia wetland (UDAW), disturbed Deyeuxia angustifolia wetland (DDAW) and rice paddy field (RP) from three soil layers of (0–10, 10–20 and 20–30 cm) in Sanjiang Plain, Northeast China, were collected, and then subjected to various FTCs with a large (10 to -10℃) and a small (5 to -5℃) amplitudes, respectively. The results indicated that FTCs increased the soil DOC concentration but reduced the concentration of MBC and activities of cellulase, invertase and catalase. Increase in the freeze-thaw frequency, resulted in the DOC concentration increasing initially and then decreasing, and the MBC concentration and soil enzyme activities were opposite. The DOC concentration increment resulting from the freeze-thaw effects was different across different layers and soil type: as the soil depth increased, the average DOC increments decreased, and the average DOC increments varied across different soil types: UDAW > DDAW > RP. The average MBC concentration and soil enzyme activity decreased from 0-10 cm > 10-20 cm > 20-30 cm soil depth; MBC concentration and soil enzyme activities varied across the different soil types: UDAW > DDAW > RP. The freeze-thaw amplitude and soil moisture content interaction had an effect on soil active organic carbon fractions and enzymatic activity. Small amplitude FTCs and higher water content had the greatest effect on DOC concentration, while larger amplitude and higher water content had the greatest effect on MBC concentration and enzymatic activity. In wetland soil, the significant correlations between active organic carbon fractions and enzyme activities indicate that the increased DOC by FTCs plays an important role in soil microbes and enzyme activities. However, active organic carbon fractions and enzyme activities had little correlation in RP, indicating that FTCs has more influence on wetland than farmland.