No abstract

Neuroblastoma has obvious heterogeneity. It is one of the few undifferentiated malignant tumors that can spontaneously degenerate into completely benign tumors. However, for its high-risk type, even with various intensive treatment options, the prognosis is still unsatisfactory. At the same time, a large number of research data show that the abnormal amplification and high-level expression of the MYCN gene are positively correlated with the malignant progression, poor prognosis, and mortality of neuroblastoma. In this context, this article explores the role of the N-Myc, MYCN gene expression product on its target genes related to the cell cycle and reveals its regulatory network in promoting tumor proliferation and malignant progression. We hope it can provide ideas and direction for the research and development of drugs targeting N-Myc and its downstream target genes.

Introduction: Climate change not only directly affects the phenotype of organisms but also indirectly impacts their physiology, for example, by altering their susceptibility to insecticides. Changed diurnal temperature fluctuations are an important aspect of climate change; ignoring the impact of these fluctuations on the biological effects of various chemical insecticides can lead to inaccurate assessments of insecticide risk under the current and future climate change scenarios.Methods: In this study, we studied effects of different temperature amplitudes (± 0, ± 6, ± 12°C) at the same mean temperature (22°C) on the life history traits of a globally distributed pest (Sitobion avenae, wheat aphid), in response to low doses of two insecticides. The first, imidacloprid shows a positive temperature coefficient; the second, beta-cypermethrin has a negative temperature coefficient.Results: Compared with the results seen with the constant temperature (22°C), a wide temperature amplitude (± 12°C) amplified the negative effects of imidacloprid on the survival, longevity, and fecundity of S. avenae, but significantly increased the early fecundity of the wheat aphid. Beta-cypermethrin positively impacted the wheat aphid at all temperature amplitudes studied. Specifically, beta-cypermethrin significantly increased the survival, longevity, and fecundity of S. avenae under medium temperature amplitude (± 6°C). There were no significant differences in the survival, longevity, and the early fecundity of S. avenae when it was treated with beta-cypermethrin at the wide temperature amplitude (± 12°C). However, the negative effect of beta-cypermethrin on the intrinsic rate of increase of S. avenae decreased gradually with the increase in temperature amplitude.Discussion: In conclusion, the response of S. avenae to positive temperature coefficient insecticides was markedly affected by temperature amplitude, while negative temperature coefficient insecticides increased the environmental adaptability of S. avenae to various temperature amplitudes. Our results highlight the importance of the integrated consideration of diurnal temperature fluctuations and different temperature coefficient insecticide interactions in climate-change-linked insecticide risk assessment; these results emphasize the need for a more fine-scale approach within the context of climate change and poison sensitivity.

Novel chiral ionone alkaloid derivatives were synthesized and their antimetastatic effects were evaluated in human breast cancer cells using chemotaxis assay. Compared with positive control LY294002, a PI3 K inhibitor, derivatives 10 a, 11 a, 11 c, 11 g, 11 j, 11 k and 11 w exhibited significant inhibitory effects against cancer cell migration. Especially, the IC50 for compound 11 g was as low as 0.035±0.004 μM. Further investigations on compound 11 g revealed that it could exert inhibitory effects on the adhesion, migration and invasion of MDA‐MB‐231 cells. The mechanisms for the antitumor metastatic effects of 11 g might be through the inhibition of HIF‐1α/VEGF/VEGFR2/Akt pathway, which suppressed the downstream signaling molecules, including Akt1/mTOR/p70S6K and Akt2/PKCζ/integrin β1 pathways. Taken together, chiral ionone alkaloid derivative 11 g has the potential to be developed into an antitumor metastatic agent for breast cancer.