In vivo assembly enhanced binding effect augments tumor specific ferroptosis therapy.

Emerging evidence indicates that the activation of ferroptosis by glutathione peroxidase 4 (GPX4) inhibitors may be a prominent therapeutic strategy for tumor suppression. However, the wide application of GPX4 inhibitors in tumor therapy is hampered due to poor tumor delivery efficacy and the nonspecific activation of ferroptosis. Taking advantage of in vivo self-assembly, we develop a peptide-ferriporphyrin conjugate with tumor microenvironment specific activation to improve tumor penetration, endocytosis and GPX4 inhibition, ultimately enhancing its anticancer activity via ferroptosis. Briefly, a GPX4 inhibitory peptide is conjugated with an assembled peptide linker decorated with a pH-sensitive moiety and ferriporphyrin to produce the peptide-ferriporphyrin conjugate (Gi-F-CAA). Under the acidic microenvironment of the tumor, the Gi-F-CAA self-assembles into large nanoparticles (Gi-F) due to enhanced hydrophobic interaction after hydrolysis of CAA, improving tumor endocytosis efficiency. Importantly, Gi-F exhibits substantial inhibition of GPX4 activity by assembly enhanced binding (AEB) effect, augmenting the oxidative stress of ferriporphyrin-based Fenton reaction, ultimately enabling antitumor properties in multiple tumor models. Our findings suggest that this peptide-ferriporphyrin conjugate design with AEB effect can improve the therapeutic effect via induction of ferroptosis, providing an alternative strategy for overcoming chemoresistance.

[Risk Assessment and Sources of Heavy Metals in Farmland Soils of Yellow River Irrigation Area of Ningxia].

The farmland environment is directly related to the quality and safety of agricultural products. In order to understand the characteristics and main influencing factors of heavy metals in farmland soil in the Yellow River irrigation area of Ningxia, sampling and monitoring were conducted for five consecutive years from 2017 to 2021, and the distribution characteristics and correlation of heavy metals were analyzed. The pollution status and potential ecological risks of heavy metals were evaluated, and the main sources of heavy metals in farmland were analyzed. The results showed that the average values of Pb, As, Zn, Ni, Cu, Hg, Cr, and Cd in the soil of the Ningxia Yellow River irrigation area were 19.74, 11.67, 66.88, 29.09, 22.55, 0.03, 62.27, and 0.19 mg·kg-1, respectively, which were enriched to some extent compared with the background values of the soil environment in Ningxia. Among them, Hg and Cd had middle- and high-grade ecological risk points; however, none of them exceeded the control value of agricultural land soil pollution risk, and all sampling sites had no high-risk or extremely high-risk levels. The results of source analysis based on positive matrix factorization (PMF) and correlation analysis showed that there were five main sources of heavy metals in farmland soil in the study area: natural sources, mixed sources of industrial and mining activities and the production and life of residents, transportation sources, agricultural production activities sources, and industrial sources, with contribution rates of 26.54%, 25.59%, 22.52%, 15.63%, and 9.72%, respectively. On the whole, the heavy metals in farmland soil in the Ningxia Yellow River irrigation area did not exceed the standard, and there was no high-level ecological risk. The production environment of the farmland soil was good, but the contribution rate of human activities to soil heavy metals was large.

[Soil enzyme activities and their stoichiometry at different altitudes in Helan Mountains, Northwest China]. / è´ºå °å±±ä¸åŒæµ·æ‹”åœŸå£¤é ¶æ´»æ€§åŠå ¶åŒ–å­¦è®¡é‡ç‰¹å¾.

Understanding altitudinal variation characteristics and driving mechanism of soil enzyme activities and their stoichiometry is of great significance for studying nutrient cycling in fragile mountain forest ecosystems. In this study, we collected soil samples from different altitudes (1380-2438 m) in Helan Mountains to analyze the altitudinal changes in soil physicochemical properties, soil enzyme activities and their stoichiometry and its influencing factors. The results showed that the activities of ß-glucosidase (ßG) and ß-N-acetylglucosaminidase (NAG) and the enzyme activities ratios of soil C/N and soil C/P firstly increased and then decreased with increasing altitude, which all peaked at 2139 m. Alkaline phosphatase (AKP) activities increased with the increases of altitude, with the maximum being found at 2438 m. However, L-leucine aminopeptidase (LAP) activities and soil N/P enzyme activities ratios did not change with increasing altitude. Compared with the soil enzyme stoichiometry in other regions of the world, Helan Mountains showed a certain degree of N limitation. Except for LAP, the activities of the other three enzymes were significantly positively correlated with the ratios of soil organic carbon/total nitrogen, soil organic carbon/total phosphorus, and total nitrogen/total phosphorus, and negatively correlated with pH. The LAP, soil C/P enzyme activities ratios and soil N/P enzyme activities ratios showed significant negative correlation with TP. In addition, AKP was significantly negatively correlated with soil bulk density.