Novel meta-diamide insecticide, broflanilide, suppresses the population of common cutworm Spodoptera litura through its lethal and sublethal effects.

BACKGROUND: Broflanilide has been registered in China for the control of Lepidoptera and Coleoptera pests, and is widely used to control the target pests at lethal and sublethal levels. The lethal and sublethal effects of broflanilide on the common cutworm (CCW) Spodoptera litura Fabricius, a representative Lepidopteran pest in agricultural crops, were examined to explore its ecological influence on pests. RESULTS: In F0 , broflanilide had little influence on the hatchability of eggs, but significantly reduced the neonate survival rate. The lethal activity of broflanilide towards third-instar larvae and adults was 0.13 mg kg-1 (LD50 ) and 3.59 mg L-1 (LC50 ) respectively at 48 h. After being treated with a sublethal dose (LD10 and LD30 ) of broflanilide, the duration of third- to sixth-instar larvae and the mean fecundity of reproductive females were significantly increased, but pupation rate, weight of pupae and life-cycle rate were significantly decreased. In F1 , the duration of F1 larvae and the doubling time were prolonged, whereas the rates of pupation and the life cycle were decreased by 14.92% and 18.00%, respectively. The intrinsic rate of increase, finite rate of increase and net reproductive rate in the sublethal group were lower than in the control group. The relative fitness of F1 treated by LD10 and LD30 was 0.81 and 0.66, respectively. CONSLUSION: Broflanilide not only has highly lethal activity, but also suppresses the population growth and progeny of CCW, as a critical factor for guidelines of its usage in the field.

ZNRF1 Mediates Epidermal Growth Factor Receptor Ubiquitination to Control Receptor Lysosomal Trafficking and Degradation.

Activation of the epidermal growth factor receptor (EGFR) is crucial for development, tissue homeostasis, and immunity. Dysregulation of EGFR signaling is associated with numerous diseases. EGFR ubiquitination and endosomal trafficking are key events that regulate the termination of EGFR signaling, but their underlying mechanisms remain obscure. Here, we reveal that ZNRF1, an E3 ubiquitin ligase, controls ligand-induced EGFR signaling via mediating receptor ubiquitination. Deletion of ZNRF1 inhibits endosome-to-lysosome sorting of EGFR, resulting in delayed receptor degradation and prolonged downstream signaling. We further demonstrate that ZNRF1 and Casitas B-lineage lymphoma (CBL), another E3 ubiquitin ligase responsible for EGFR ubiquitination, mediate ubiquitination at distinct lysine residues on EGFR. Furthermore, loss of ZNRF1 results in increased susceptibility to herpes simplex virus 1 (HSV-1) infection due to enhanced EGFR-dependent viral entry. Our findings identify ZNRF1 as a novel regulator of EGFR signaling, which together with CBL controls ligand-induced EGFR ubiquitination and lysosomal trafficking.

Preparation of pingyangmycin PLGA microspheres and related in vitro/in vivo studies.

Using a multiple emulsion solvent evaporation method, pingyangmycin was entrapped in poly(lactic-co-glycolic acid) (PLGA) to prepare a long-acting pingyangmycin PLGA microsphere formulation that can be sustainably released with high entrapment efficiency. Meanwhile, the effects of stirring speed during the multiple emulsion solvent evaporation process were also taken into consideration. Investigation of the in vitro release properties showed that the microsphere formulations could sustainably release the drug over nearly 28 d, and, moreover, it could stably control pingyangmycin release over nearly 24 d when intramuscularly injected into dogs. No serious toxic effect was observed in an acute toxicity test in mice. A subcutaneous xenotransplant model of hepatoma H(22) in mice was established for pharmacodynamic studies and the results showed that the process of preparing pingyangmycin PLGA microsphere formulations was feasible and that intramuscular injection of this microsphere formulation resulted in anti-tumor activity in vivo.