As a new protective and therapeutic fungicide, studies on famoxadone-cymoxanil are rare, and its toxicity to aquatic organisms has not been reported. In the present study, zabrafish embryos were exposed to several concentrations of famoxadone-cymoxanil at 10 hpf. Then, the changes of their shape, heart rate, development and function of innate and adaptive immune cells, oxidative stress, apoptosis, the expression of apoptosis-related genes and immune-related genes, the locomotor behavior were observed and detected in acute toxicity of famoxadone-cymoxanil. Our studies showed that, after exposure to famoxadone-cymoxanil, zebrafish embryos had decreased heart rate, shortened body length, swollen yolk sac. Secondly, the number of innate and adaptive immune cells was significantly reduced; and neutrophil migration and retention at the injury area were inhibited, indicating the developmental toxicity and immunotoxicity of famoxadone-cymoxanil on the zebrafish. We also found that the oxidative stress related indicators of embryos were changed significantly, and apoptosis were substantially increased. Further investigation of changes of some key genes in TLR signaling including TLR4, MYD88 and NF-κB p65 revealed that the mRNA expression of these genes was up-regulated. Meanwhile, the mRNA expression of some proinflammatory cytokines such as TNF-α, IFN-γ, IL6 and IL-1β was also up-regulated. In addition, the activity, the total distance, time and average speed were decreased along with the increase of exposure concentration. The absolute turn angle, sinuosity and the enzymatic activity of acetylcholinesterase (AChE) were also increased. These results suggested that famoxadone-cymoxanil can induce developmental toxicity, immunotoxicity and neurobehavioral toxicity in zebrafish larvae.

中文翻译：

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Famoxadone-cymoxanil诱导的斑马鱼的免疫毒性和神经行为毒性。

作为一种新型的保护性和治疗性杀菌剂，对法莫沙酮-嘧菌胺的研究很少，并且尚未报道其对水生生物的毒性。在本研究中，zabrafish胚胎在10 hpf下暴露于数种浓度的famoxadone-cymoxanil。然后，观察并检测了它们的形状，心率，先天和适应性免疫细胞的发育和功能的变化，氧化应激，凋亡，凋亡相关基因和免疫相关基因的表达，运动行为在急性毒性中的作用。法莫沙酮-cymoxanil。我们的研究表明，暴露于法莫沙酮-cymoxanil后，斑马鱼胚胎的心率降低，体长缩短，卵黄囊肿胀。其次，先天和适应性免疫细胞的数量大大减少。中性粒细胞的迁移和在损伤部位的滞留被抑制，表明法莫沙酮-嘧菌腈对斑马鱼的发育毒性和免疫毒性。我们还发现，与胚胎的氧化应激相关的指标发生了显着变化，并且凋亡显着增加。进一步研究TLR信号中一些关键基因的变化，包括TLR4，MYD88和NF-κBp65，发现这些基因的mRNA表达上调。同时，一些促炎细胞因子如TNF-α，IFN-γ，IL6和IL-1β的mRNA表达也被上调。此外，随着暴露浓度的增加，活性，总距离，时间和平均速度均降低。绝对转角，弯曲度和乙酰胆碱酯酶（AChE）的酶活性也增加了。