Revealing the Preventable Effects of Fu-Zheng-Qu-Xie Decoction against Recurrence and Metastasis of Postoperative Early-Stage Lung Adenocarcinoma Based on Network Pharmacology Coupled with Metabolomics Analysis.

Fu-Zheng-Qu-Xie (FZQX) decoction is a traditional Chinese herbal prescription for the treatment of lung cancer and exerts proapoptotic and immunomodulatory effects. It has been clinically suggested to be effective in improving the survival of postoperative early-stage lung adenocarcinoma (LUAD), but the mechanism remains unclear. In this study, we used network pharmacology coupled with metabolomics approaches to explore the pharmacological action and effective mechanism of FZQX against the recurrence and metastasis of postoperative early-stage LUAD. Network pharmacology analysis showed that FZQX could prevent the recurrence and metastasis of postoperative early-stage LUAD by regulating a series of targets involving vascular endothelial growth factor receptor 2, estrogen receptor 1, sarcoma gene, epidermal growth factor receptor, and protein kinase B and by influencing the Ras, PI3K-Akt, and mitogen-activated protein kinase signaling pathways. In liquid chromatography-mass spectrometry analysis, 11 differentially expressed metabolites, including PA(12:0/18:4(6Z,9Z,12Z,15Z)), PC(16:0/0:0)[U], LysoPC(18:1(11Z)), and LysoPC(18:0), were discovered in the FZQX-treated group compared to those in the model group before treatment or normal group. They were enriched in cancer metabolism-related signaling pathways such as central carbon metabolism in cancer, choline metabolism, and glycerol phospholipid metabolism. Collectively, our results suggest that the multicomponent and multitarget interaction network of FZQX inhibits the recurrence and metastasis of postoperative early-stage LUAD by activating the receptor signal transduction pathway to inhibit proliferation, induce cell apoptosis, inhibit aerobic glycolysis, and reprogram tumor lipid metabolism.

Cuticular compounds inhibit cannibalism of early-instar spiderlings by pulli-carrying Pardosa pseudoannulata females.

Cannibalism is common in spiders. Wolf spider (Lycosidae) females, which exhibit extensive maternal care, have been reported to cannibalize less when they are carrying egg sacs and juveniles. In a laboratory experiment, we demonstrated that cannibalism of early-instar spiderlings (EIS) by a wolf spider (Pardosa pseudoannulata) mother was almost completely inhibited when she was carrying spiderlings. Compared with virgin and mated-females, mother spiders tolerated more and predated fewer spiderlings, including gregarious pulli and newly dispersed spiderlings (NDS). Cannibalism of EIS by females during their reproductive period exhibited a V-shaped pattern, with a gradual decrease from the egg sac-carrying to pulli-carrying (PC) stage, and a recovery from the PC stage to post-reproductive (PR) stage. Notably, there was 0 cannibalism at the PC stage. PC females exhibited no interest in pulli, while PR females were attracted to and predated pulli and NDS as they did their natural prey, Nilaparvata lugens. Interestingly, PC females captured and released NDS in a foraging assay, although attraction was observed from olfactometer measurements. PC mothers possessed a cuticular volatile profile that was closer to that of pulli and NDS than to that of PR females. Moreover, NDS cuticular extract provoked an electrophysiological response in legs of PC females. Therefore, cuticular compound-mediated chemical communication may be involved in inhibiting cannibalism of EIS by spider mothers, and especially in eliminating cannibalism by PC mothers. Future studies will aim to characterize the specific cuticular compounds and chemoreception mechanism in females, which will facilitate our understanding of intraspecific recognition and cannibalism in spiders.

Identification of polymorphisms in Cyrtorhinus lividipennis RDL subunit contributing to fipronil sensitivity.

As one of the most important predatory enemies, the miridbug, Cyrtorhinus lividipennis, plays an important role in rice planthoppers control, such as Nilaparvata lugens (brown planthopper). In order to compare insecticide selectivity between C. lividipennis and N. lugens, the contact acute toxicities of six insecticides (diazoxon, paraoxon, carbaryl, fenobucarb, fipronil and ethofenprox) were monitored. The results showed that all tested insecticides were more toxic to C. lividipennis than to N. lugens and fipronil had the biggest difference. The RDL subunit (Cl-RDL) was cloned from C. lividipennis and a RDL isoform (Cl-RDL-In) was also found with 31 amino acids insertion in RDL intracellular region. In order to understand the role of the insertion on insecticide sensitivities, three subunits (Nl-RDL, Cl-RDL and Cl-RDL-In) were constructed to obtain the functional receptors in Xenopus oocytes and the fipronil sensitivities were detected by the voltage-clamp technique. Nl-RDL (IC50=32.36 ± 4.07 µM) was more insensitive to fipronil than Cl-RDL (IC50=6.47 ± 1.12 µM). The insertion in Cl-RDL significantly reduced fipronil sensitivity with IC50 value in Cl-RDL-In of 16.83 ± 2.30 µM. Interestingly, after the elution of fipronil, the current response of Cl-RDL-In appeared obvious recovery, which were not observed in Cl-RDL and Nl-RDL. It might imply that the insertion played a special role in fipronil sensitivity.