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Flash floods cause damage to engineering structures and buildings mainly due to their huge impact force. Scientific investigation of the impact process of flash floods has significant theoretical and engineering implications in ensuring the safety of flood-resistant structures and human life. In this experimental study, the impact pressure and flow velocity in the flow field were measured synchronously using the impact detection system and a particle image velocimetry system in a water channel and the effects of the turbulence structure on the impact process of flash flood were investigated. As shown by the experimental measurements, the large-scale coherent structure in the flow field reached six times the boundary layer thickness. The turbulence and impact force energy spectra were very similar in the low-frequency, large-scale wave band, indicating that the large-scale turbulence structure dominated the impact process. Both the mean and maximum impact pressures increased with the turbulence kinetic energy. An equation for impact force characterization that considers the effects of turbulence and thus was more accurate was given, providing a theoretical basis for the protection of engineering structures from the damage by flash floods.

Additional file 1. Additional materials and methods. Figure S1. MMAE inhibits the growth of pancreatic cancer cells. Figure S2. Effect of Mc-vc-PABC linker on growth of pancreatic cancer cells. Figure S3. Expression of the MUC1 protein in Capan-2 and CFPAC-1 xenograft tumor tissues.

Trastuzumab-resistance is still a major challenge in treating patients with HER2 positive breast cancer. In this study, we tried to overcome transtuzumab-resistance by examining the therapeutic efficacy of third generation anti-HER2 chimeric antigen receptor (CAR)-T cells alone and in combination with PD1 blockade against HER2 positive and trastuzumab-resistance breast cancer cells in vitro and xenograft model. The anti-HER2 CAR-T cells were generated by infecting CD3/CD28 activated peripheral blood mononuclear cells with lentivirus expressing third generation anti-HER2 CAR. Anti-HER2 CAR-T cells were specifically targeted to HER2 positive BT474 and trastuzumab resistant HCC1954 cells compared with HER2 negative breast cancer cells. Results from ELISA revealed that the secretion of IL-2 and IFN-γ was increased in anti-HER2 CAR-T cells after being co-cultured with HCC1954 cells, and was further increased with the addition of anti-PD1 antibody in the co-culture system. Furthermore, data from lactate dehydrogenase assay showed that anti-HER2 CAR-T cells displayed a potent cytotoxicity against HCC1954 and BT474 cells. Addition of anti-PD1 antibody further enhanced the cytotoxicity of anti-HER2 CAR-T cells against HCC1954 cells. Lastly, injection of anti-HER2 CAR-T cells significantly reduced the growth of HCC1954 xenograft tumors. Combining anti-HER2 CAR-T cells with anti-PD1 antibody further impaired the growth of HCC1954 tumors. The present results indicate that anti-HER2 CAR-T cells have therapeutic efficacy against trastuzumab resistant breast tumors and addition of the PD1 antibody can further enhance the therapeutic effect of anti-HER2 CAR-T cells. Thus, third generation anti-HER2 CAR-T cells along with PD1 blockade is a potential therapy to overcome trastuzumab resistance of breast cancer.

p38 MAPK has been strongly implicated in the development of atherosclerosis, but its role in cholesterol ester accumulation in macrophages and formation of foam cells, an early step in the development of atherosclerosis, has not been investigated. We addressed this issue and made some brand new observations. First, elevated intracellular cholesterol level induced by the exposure to LDL-activated p38 MAPK and activation of p38 MAPK with anisomycin increased the ratio of cholesterol esters over free cholesterol, whereas inhibition of p38 MAPK with SB203580 or siRNA reduced the LDL loading-induced intracellular accumulation of free cholesterol and cholesterol esters in macrophages. Second, exposure to LDL cholesterol inhibited autophagy in macrophages, and inhibition of autophagy with 3-methyladenine increased intracellular accumulation of cholesterol (free cholesterol and cholesterol esters), whereas activation of autophagy with rapamycin decreased intracellular accumulation of free cholesterol and cholesterol esters induced by the exposure to LDL cholesterol. Third, LDL cholesterol loading-induced inhibition of autophagy was prevented by blockade of p38 MAPK with SB203580 or siRNA. Neutral cholesterol ester hydrolase was co-localized with autophagosomes. Finally, LDL cholesterol loading and p38 activation suppressed expression of the key autophagy gene, ulk1, in macrophages. Together, our results provide brand new insight about cholesterol ester accumulation in macrophages and foam cell formation.