Hepatocellular carcinoma (HCC), a common malignancy in China and globally, is primarily treated through surgical resection and liver transplantation, with chemotherapy as a significant synergistic option. Adenine (Ade), a nucleobase, exhibits antitumor effects by blocking human hepatic carcinoma cells in S phase and inhibiting tumor cell proliferation. However, its use is limited owing to its low solubility, poor targeting ability, and nephrotoxicity. Therefore, liver-targeting drug delivery systems have attracted considerable attention for the treatment of HCC. In this study, we explored the liver-targeting efficacy and antitumor effect of adenine-loaded glycyrrhetinic acid-modified hyaluronic acid (Ade/GA-HA) nanoparticles in vitro and in vivo. The GA-HA nanoparticles possessed obvious targeting specificity toward liver cancer cells, which was mainly achieved by the specific binding of the GA ligand to the GA receptor that was highly expressed on the liver cell membrane. In vitro and in vivo results showed that Ade/GA-HA nanoparticles could inhibit liver cancer cell proliferation and migration, promote apoptosis, and significantly inhibit the growth of tumor tissues. Altogether, this study is the first to successfully demonstrate that the targeting activity and antitumor effect of Ade against HCC are enhanced by using GA-HA nanoparticles in vitro and in vivo.
Burst escape speed is an effective and widely used behaviour for evading predators, with burst escape speed relying on several different morphological features. However, we know little about how behavioural and underlying morphological attributes change in concert as a response to changes in selective predation regime. We studied intercorrelated trait differentiation of body shape and burst‐swim‐mediating morphology in response to a habitat shift‐related reduction in burst escape speed using larvae of the dragonfly genusLeucorrhinia. Species in this genus underwent a well‐known habitat shift from predatory fish lakes (fish lakes) to predatory fish‐free lakes dominated by large predatory dragonflies (dragonfly lakes) accompanied by relaxed selection on escape burst speed. Results revealed that species from fish lakes that possess faster burst speed have evolved a suite of functionally intercorrelated traits, expressing a wider abdomen, a higher abdominal muscles mass and a larger branchial chamber compared with species from dragonfly lakes. In contrast, populations within species did not show significant differences in muscle mass and branchial chamber size between lake types in three of the species. High multicollinearity among variables suggests that traits have evolved in concert rather than independently whenLeucorrhiniashifted from fish lakes to dragonfly lakes. Thus, relaxed selection on burst escape speed in dragonfly‐lake species resulted in a correlated reduction of abdominal muscles and a smaller branchial chamber, likely to save production and/or maintenance costs. Our results highlight the importance of studying integrated behavioural and morphological traits to fully understand the evolution of complex phenotypes.
Insects closely interact with plants with multiple genes involved in their interactions. β-glucosidase, constituted mainly by glycoside hydrolase family 1 (GH1), is a crucial enzyme in insects to digest plant cell walls and defend against natural enemies with sequestered plant metabolites. To gain more insights into the role of this enzyme in plant–insect interactions, we analyzed the evolutionary history of the GH1 gene family with publicly available insect genomes. We found that GH1 is widely present in insects, while the gene numbers are significantly higher in insect herbivores directly feeding on plant cell walls than in other insects. After reconciling the insect GH1 gene tree with a species tree, we found that the patterns of duplication and loss of GH1 genes differ among insect orders, which may be associated with the evolution of their ecology. Furthermore, the majority of insects’ GH1 genes were tandem-duplicated and subsequently went through neofunctionalization. This study shows the evolutionary history of an important gene family GH1 in insects and facilitates our understanding of the evolution of insect–plant interactions.