Introduction: Progression and chemoresistance of acute myeloid leukemia (AML) contribute to most of the treatment failure. Notch pathway has been proven to be involved in many biological processes and diseases, especially AML. In this study, we aimed to explore genes correlated with Notch1 pathway in AML and determine their roles in the regulation of AML progression and chemoresistance. Methods: TCGA database was used to explore Notch1 associated genes. Kaplan-Meier survival analysis was performed to evaluate the prognostic significance of genes. Quantitative RT-PCR (qRT-PCR) and Western blot were performed to examine the expression of genes. The expression of PRKD2 was up-regulated or knocked down in AML cell lines by lentivirus or siRNAs. CCK-8 and flow cytometry were used to analyze the effect of PRKD2 on cell proliferation and chemoresistance. Results: Based on TCGA database, PRKD2 was found to be positively correlated with Notch1 expression, cytogenetic risk status and poorer prognosis in AML. Moreover, the expression level of PRKD2 was higher in AML chemo-resistant cells than in chemo-sensitive cells. Functionally, knockdown of PRKD2-induced apoptosis and increased chemosensitivity of AML cells. PRKD2 overexpression promoted proliferation and chemoresistance of AML cells. Furthermore, we found PRKD2 could regulate Notch1 pathway. Besides, high PRKD2 expression was correlated with higher risk group of AML patients which indicated that PRKD2 was an independent prognostic marker for AML. Conclusion: Taken together, our results showed that PRKD2 could promote the proliferation and chemoresistance of AML cells by regulating Notch1 pathway. The study broadened our insights into the underlying mechanisms in chemoresistance and proliferation of AML, and provided a new prognostic marker and treatment target for AML.
We study the propagation of femtosecond laser pulses with a single (front or rear) edge or dual edge through turbid media via Monte Carlo simulation. The results show that both the transmitted pulses spread on the basis of the incident pulse width
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, arising from the scattering effect. Further, the broadening width of the incident laser with a dual-edge pulse is wider than that of the incident laser width a single-edge pulse. The effect of the scattering particles on the front edge and the rear edge of the femtosecond laser can be distinguished in the time domain for femtosecond laser pulses through turbid media with the optical depth (OD) less than 10. In this scattering regime, the front-edge pulse scattered by the particles contributes more to diffused photons, but the effect of the scattering particles on the front edge and the rear edge of the femtosecond laser cannot be discriminated in turbid media with the OD more than 10, where the scattering is dominated by multiple scattering.
We study the transition from the ballistic to the snake regime of a femtosecond laser through a turbid medium via Monte Carlo simulation. The results show that the transition depth of the ballistic to the snake regime of a femtosecond laser through a turbid medium is close to the surface of the scattering volume. The transition process depends on the scattering coefficient of the turbid medium. Unlike the decay of the intensities of the ballistic photons governed by Beer–Lambert law, the intensities of the snake photons first increase with an increase of the thickness of the turbid medium and then decrease with a further increase of the thickness, for all scattering coefficients ranging from 10 to 20 cm−1. Further, we study the balance point of the intensity of the ballistic photons and the snake photons, which also depends on the scattering coefficient and the half-acceptance angle. The transmission depth corresponding to the transition balance point decreases with an increase of the scattering coefficient. In addition, for the transition balance point, the product of the transmission depth and scattering coefficient is approximately a constant (∼2) for a specific simulation configuration.
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