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BackgroundHomoharringtonine (HHT) is a kind of cephalotaxus alkaloid used in traditional Chinese medicine. Although HHT has been successfully used as a therapeutic agent for leukemia, the drug resistance and toxicity are major concerns. MicroRNAs (miRNAs) have been identified to modulate cellular sensitivity to anticancer drugs. We examined the synergistic action between miR-370 and HHT in vitro and in vivo.MethodsThe synergistic action between miR-370 and HHT was examined by flow cytometry. The effect of HHT on miR-370 expression was determined by quantitative RT-PCR (qRT-PCR). The expression of miR-370 and Forkhead box M1 (FoxM1) in 23 patients with newly diagnosed chronic-phase chronic myeloid leukemia (CML-CP) and 10 patients with blast-crisis CML (CML-BP) as well as miR-370–targeted FoxM1 was determined by qRT-PCR and western blot analysis.ResultsEctopic expression of miR-370 sensitized the CML K562 cell line to HHT by targeting FoxM1, the major regulator in cell proliferation and apoptosis. miR-370 significantly promoted HHT-mediated cell apoptosis and miR-370 and HHT cooperated in affecting FoxM1 expression. As well, miR-370 was moderately upregulated after HHT treatment in K562 cells. In addition, the expression of miR-370 was significantly reduced in CML patients as compared with healthy controls. Furthermore, the expression of miR-370 was lower in CML-BP than CML-CP patients.ConclusionsMiR-370 sensitized K562 cells to HHT by inducing apoptosis in part by downregulation of FoxM1 expression. These findings may provide further information for CML treatment with HHT.

A nutrient-phytoplankton model with multiple delays is studied analytically and numerically. The aim of this paper is to study how the delay factors influence dynamics of interaction between nutrient and phytoplankton. The analytical analysis indicates that the positive equilibrium is always globally asymptotically stable when the delay does not exist. On the contrary, the positive equilibrium loses its stability via Hopf instability induced by delay and then the corresponding periodic solutions emerge. Especially, the stability switches for positive equilibrium occur as the delay is increased. Furthermore, the numerical simulations show that periodic-2 and periodic-3 solutions can appear due to the existence of delays. Numerical results are consistent with the analytical results. Our results demonstrate that the delay has a great impact on the nutrient-phytoplankton dynamics.

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H. pylori can survive under a nutrition-deficient environment. During infection and transmission, H. pylori is confronted with nutrient limitation and the bacterium requires rapid alteration in gene expression for survival under stress conditions. However, the mechanism underlining this regulation remains unknown. A previous study showed that σ54 is an important regulation factor for H. pylori survival in the nutrition-deficient environment. Our results show that the expression of σ54 (rpoN) is significantly induced in the stationary phase (nutrition deficiency) and the rpoN mutant showed a significantly lower viability than wild-type H. pylori in the late stationary phase. Thus, σ54 is involved in H. pylori survival during nutrient limitation. We used comparative proteomics to analyze the protein differentiation between wild-type and rpoN mutant during the stationary phase. With depleted nutrients, σ54 can slow the process of proliferation by negatively regulating genes involved in energy metabolism and biosynthesis and enhance stress-resistant ability by positively regulating genes involved in protein fate and redox reaction. Especially, NapA positively regulated by σ54 plays an important function in H. pylori survival both in the stationary phase and in water, and the latter situation would be beneficial for bacterial in vitro transmission. Our investigations give new light on the adaptive regulation of H. pylori under stress conditions.

We proposed a nutrient‐phytoplankton interaction model with a discrete and distributed time delay to provide a better understanding of phytoplankton growth dynamics and nutrient‐phytoplankton oscillations induced by delay. Standard linear analysis indicated that delay can induce instability of a positive equilibrium via Hopf bifurcation. We derived the conditions guaranteeing the existence of Hopf bifurcation and tracked its direction and the stability of the bifurcating periodic solutions. We also obtained the sufficient conditions for the global asymptotic stability of the unique positive steady state. Numerical analysis in the fully nonlinear regime showed that the stability of the positive equilibrium is sensitive to changes in delay values under select conditions. Numerical results were consistent with results predicted by linear analysis.

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In this paper, the dynamics and stability of multi-span pipe conveying fluid embedded in Pasternak foundation is studied. Based on Euler-Bernoulli beam theory, the dynamics of multi-span pipe conveying fluid embedded in two parameters Pasternak foundation is analyzed. The dynamic stiffness method (DSM) is used to solve the control equation. A seven span pipe is calculated. The affection of two parameters of Pasternak foundation is mainly studied. Along with increasing the elastic stiffness K and shear stiffness G, the frequency is also increasing.