The fluid seepage in local-saturated zone of subgrade promotes the migration of fine particles in the filler, resulting in the change of pore structure and morphology of the filler and the deformation of solid skeleton, which affects the fluid seepage characteristics. Repeatedly, the muddy interlayer, mud pumping and other diseases are finally formed. Based on the theory of two-phase seepage, the theory of porous media seepage, and the principle of effective stress in porous media, a two-phase fluid-solid coupling mathematical model in local-saturated zone of subgrade considering the effect of fine particles migration is established. The mathematical model is numerically calculated with the software COMSOL Multiphysics○R, the two-phase seepage characteristics and the deformation characteristics of the solid skeleton in local-saturated zone of the subgrade are studied. The research results show that due to the continuous erosion and migration of fine particles in local-saturated zone of the subgrade, the volume fraction of fine particles first increases then decreases and finally becomes stable with the increase of time. And the volume fraction of fine particles for the upper part of the subgrade is larger than that for the lower part of the subgrade. The porosity, the velocity of fluid, the velocity of fine particles, and the permeability show a trend of increasing first and then stabilizing with time; the pore water pressure has no significant changes with time. The vertical displacement increase first and then decrease slightly with the increase of time, and finally tend to be stable. For a filler with a larger initial volume fraction of fine particles, the maximum value of the volume fraction of fine particles caused by fluid seepage is larger, and the time required to reach the maximum value is shorter. It can be concluded that in actual engineering, the volume fraction of fine particles in the subgrade filler should be minimized on the premise that the filler gradation meets the requirements of the specification.

Under the pressure of fluoroquinolones, Pasteurella multocida (PM) can easily develop resistance to fluoroquinolones mediated by QRDR target mutation. It is imperative to find new drug resistance inhibitor targets to combat the rapid development of drug resistance. In order to overcome these problems, we sequenced the transcriptome of PM with different levels of resistance to ENR(0.03 μg/mL; 8 μg/mL; 32μg/Ml, Enrofloxacin). The results showed that with the increase of resistance to fluoroquinolones, the expression of satP gene was significantly up-regulated. The satP gene deletion strain and replenishment strain were constructed, and their drug resistance and tolerance were determined. The results showed that the deletion of satP gene did not affect the resistance of PM to fluoroquinolones, rather affected the time when PM developed resistance to fluoroquinolones. After 10 generations of drug induction, the MIC (minimum inhibitory concentration) of fluoroquinolones for wild strain was 64 μg/mL, while the MIC for satP gene deletion strain was only 8 μg/mL. The MDK99 test (time to kill 99% bacteria),agar diffusion test and mutation frequency test showed that the tolerance of satP gene deletion strain was significantly lower than that of wild strain. At the same time, the virulence of gene deletion strain and wild strain was tested, and about 400 times decreased virulence was observed for satP gene deletion strain. The mouse infection model confirmed that mice infected with satP gene deletion strains were more likely to be treated with ENR than mice infected with wild-type bovine PM strains. The results show that satP has potential to be a target of fluoroquinolone resistance inhibitors.

Breast cancer is the most common malignancies in women and the second leading cause of cancer death in women. Triple negative breast cancer (TNBC) subtype is a breast cancer subset without ER, PR and HER2 expression, limiting treatment options and presenting a poorer survival rate. Thus, we investigated whether HDACi would be used as potential anti-cancer therapy on breast cancer cells. In this study, we found TNBC and HER2-enrich breast cancers are extremely sensitive to Panobinostat, Belinostat of HDACi via experiments of cell viability assay, apoptotic marker identification and flow cytometry measurement. On the other hand, we developed a bioluminescence based live cell non-invasive apoptosis detection sensor (IADS) detection system to evaluate the quantitative and kinetic analyses of apoptotic cell death by HDAC treatment on breast cancer cells. In addition, the use of HDACi may also be accompanied with chemotherapeutic agent such as doxorubicin to synergic drug sensitivity on TNBC cell (MDA-MB-231), but not in breast normal epithelia cells (MCF-10A), providing therapeutic benefits against breast tumor in clinic.