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Poly (ADP-ribose) polymerases (PARP) inhibitors (PARPi) are the first-approved anticancer drug designed to exploit synthetic lethality. PARPi selectively kill cancer cells with homologous recombination repair deficiency (HRD), as a result, PARPi are widely employed to treated BRCA1/2-mutant ovarian, breast, pancreatic and prostate cancers. Currently, four PARPi including Olaparib, Rucaparib, Niraparib, and Talazoparib have been developed and greatly improved clinical outcomes in cancer patients. However, accumulating evidences suggest that required or de novo resistance emerged. In this review, we discuss the molecular mechanisms leading to PARPi resistances and review the potential strategies to overcome PARPi resistance.
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Introduction: Spread effect is one of the aspects on deposition quality evaluation of pesticide droplets. It could be affected by many factors such as the microstructure of the target plant leaf surface, physical features of the droplets, and the concentration of spray additives. Methods: In this study, using a high-speed photography system, 2.3% glyphosate ammonium salt solution with different concentration of the additive was applied to investigate the impact process of single droplet deposition on the plant leaf surface with burrs. Effect of droplet sizes and velocities on spreading area and dynamic deposition procedure was analyzed using image processing programs. Results: The diffusion factor in the process of droplet spreading was changed over time. The occurrence of bubbles in the droplets was observed in the results. With the bubble generation, the droplet diameter expands and a better diffusion effect is obtained. As a result, better spreading effect was obtained as the droplet diameter was expanded with the generation of bubbles. The significant effects of each physical property of droplets on droplet spreading and the interaction effects between the influencing factors were analyzed. A significant correlation was found between additive concentration, droplet impact velocity, droplet diameters and droplet spreading area. All interactions of concentration:velocity, concentration:diameter, velocity:diameter, and concentration:velocity:diameter had a significant effect on the spreading area of droplets. The study of the factors influencing the process of pesticide droplet impact on the leaf surface contributes to the efficient use of pesticides. Thus, the consumption of pesticides and the resulting impact on the environment can be reduced.
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Chlorprenaline hydrochloride (CLOR) is a typical representative of ß-adrenergic agonists that may be used illegally as a livestock feed additive and may have adverse impacts on the environment. In the present study, zebrafish embryos were exposed to CLOR to investigate its developmental toxicity and neurotoxicity. The results demonstrated that CLOR exposure led to adverse effects on developing zebrafish, such as morphological changes, a high heart rate, and increased body length, resulting in developmental toxicity. Moreover, the up-regulation of activities of superoxide dismutase (SOD) and catalase (CAT) and the enhancement of malondialdehyde (MDA) content illustrated that CLOR exposure activated oxidative stress in exposed zebrafish embryos. Meanwhile, CLOR exposure also caused alterations in locomotive behavior in zebrafish embryos, including an increase in acetylcholinesterase (AChE) activity. Quantitative polymerase chain reaction (QPCR) results showed that the transcription of genes related to the central nervous system (CNS) development, namely, mbp, syn2a, α1-tubulin, gap43, shha, and elavl3, indicated that CLOR exposure could lead to neurotoxicity in zebrafish embryos. These results showed that CLOR exposure could cause developmental neurotoxicity in the early stages of zebrafish development and that CLOR might induce neurotoxicity by altering the expression of neuro-developmental genes, elevating AChE activity, and activating oxidative stress.