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Abstract Nanogels offer hope for precise drug delivery, while addressing drug delivery hurdles is vital for effective prostate cancer (PCa) management. We developed an injectable elastin nanogels (ENG) for efficient drug delivery system to overcome castration-resistant prostate cancer (CRPC) by delivering Decursin, a small molecule inhibitor that blocks Wnt/βcatenin pathways for PCa. The ENG exhibited favourable characteristics such as biocompatibility, flexibility, and low toxicity. In this study, size, shape, surface charge, chemical composition, thermal stability, and other properties of ENG were used to confirm the successful synthesis and incorporation of Decursin (DEC) into elastin nanogels (ENG) for prostate cancer therapy. In vitro studies demonstrated sustained release of DEC from the ENG over 120 h, with a pH-dependent release pattern. DU145 cell line induces moderate cytotoxicity of DEC-ENG indicates that nanomedicine has an impact on cell viability and helps strike a balance between therapeutics efficacy and safety while the EPR effect enables targeted drug delivery to prostate tumor sites compared to free DEC. Morphological analysis further supported the effectiveness of DEC-ENG in inducing cell death. Overall, these findings highlight the promising role of ENG-encapsulated decursin as a targeted drug delivery system for CRPC.

Xylanase plays a key role in degrading plant cell wall during pathogenic fungi infection. Here, we identified a xylanase gene, VmXyl2 from the transcriptome of Valsa mali and examined its function. VmXyl2 has highly elevated transcript levels during the infection process of V. mali, with 15.02-fold increase. Deletion mutants of the gene were generated to investigate the necessity of VmXyl2 in the development and pathogenicity of V. mali. The VmXyl2 deletion mutant considerably reduced the virulence of V. mali in apple leaves and in twigs, accompanied by 41.22% decrease in xylanase activity. In addition, we found that VmXyl2 induces plant cell necrosis regardless of its xylanase activity, whereas promoting the infection of V. mali in apple tissues. The cell death-inducing activity of VmXyl2 dependent on BRI1-associated kinase-1 (BAK1) but not Suppressor of BIR1-1 (SOBIR1). Furthermore, VmXyl2 interacts with Mp2 in vivo, a receptor-like kinase with leucine-rich repeat. The results offer valuable insights into the roles of VmXyl2 in the pathogenicity of V. mali during its infection of apple trees.

Emerging evidence has linked arsenic exposure and metabolic homeostasis, but the mechanism is incompletely understood, especially at relatively low concentrations. In this study, we used a mouse model to evaluate the health impacts and metabolic toxicity of arsenic exposure in drinking water at environmentally relevant levels (0.25 and 1.0 ppm). Our results indicated that arsenic damaged intestinal barrier and induced arsenic accumulation, oxidative stress, and pathological changes in the liver and illum. Interestingly, arsenic increased the hepatic triglyceride (TG) and total cholesterol (TC), while reduced serum TG and TC levels. The liver transcriptome found that arsenic exposure caused transcriptome perturbation and promoted hepatic lipid accumulation by regulating the exogenous fatty acids degradation and apolipoproteins related genes. The serum metabolomics identified 74 and 88 differential metabolites in 0.25 and 1.0 ppm, respectively. The KEGG disease and subcellular location analysis indicated that arsenic induced liver and intestinal diseases, and the mitochondrion might be the target organelle for arsenic-induced toxicity. Co-enrichment of transcriptome and metabolome identified 24 metabolites and 9 genes as metabolic toxicity biomarkers. Moreover, 40 male (20 nonalcoholic fatty liver disease (NAFLD) cases and 20 healthy controls) was further selected to validate our findings. Importantly, the significantly changed L-palmitoylcarnitine, 3-hydroxybutyric acid, 2-hydroxycaproic acid and 6 genes of Hadha, Acadl, Aldh3a2, Cpt1a, Cpt2, and Acox1 were found in the NAFLD cases. The results from integrated multi-omics and chemical-protein network analysis indicated that L-palmitoylcarnitine played a critical role in metabolic toxicity by regulating mitochondrial fatty acids β-oxidation genes (Cpt1a, Cpt2). In conclusion, these findings provided new clues for the metabolic toxicity of arsenic exposure at environmentally relevant levels, which involved in the late-life NAFLD development. Our results also contribute to understanding the human responses and phenotypic changes to this hazardous material exposure in the environment.

Climate change and human activities have caused various ecological risks to coastal urban agglomerations. Ecological security refers to the state of health of an ecosystem and its integrity. An objective and comprehensive evaluation of ecological security is significant for protecting the structure and function of coastal ecosystems. The driving force–pressure–state–impact–response (DPSIR) model was used to construct a dynamic simulation model of ecological security in the Xiamen–Zhangzhou–Quanzhou region (XZQR), located on the eastern coast of China. The ecological security level (ESL) characteristics of the spatial and temporal patterns were evaluated by calculating the ecological security index (ESI). Obstacle factors were analyzed as well. The results show the following: (1) From 2011 to 2021, the average ESI rose from 0.238 to 0.686 and went through a relatively insecure stage (2011–2015), a critical stage (2016–2019), and a relatively secure stage (2020–2021). (2) The ESI level in Quanzhou was higher in the early stage, and the level of ecological security in Zhangzhou showed a significant rising trend, increasing by 0.541. Its increase depended on increases in the impact layer. (3) The impact layer is the main obstacle layer affecting the ESL, and the main obstacles include CO2 emissions (0.117), annual rainfall (0.091), general public budget expenditures (0.082), GDP growth rates (0.082), and green coverage in built-up areas (0.075). Therefore, we recommend promoting the complementary advantages of the XZQR and implementing ecological restoration projects.