High Expression of Cancer-IgG Is Associated With Poor Prognosis and Radioresistance via PI3K/AKT/DNA-PKcs Pathway Regulation in Lung Adenocarcinoma.

BACKGROUND: Lung adenocarcinoma (LUAD) is the dominant type of lung neoplasms, and radiotherapy is its mainstay treatment, yet poor prognosis caused by radioresistance remains problematic. Cancer-derived immunoglobulin G (cancer-IgG) has been detected in multiple cancers and plays important roles in carcinogenesis. This study aimed to demonstrate that cancer-IgG is associated with poor prognosis of LUAD and to identify its role in radioresistance. METHODS: Cancer-IgG expression was detected by immunohistochemistry from 56 patients with stage III LUAD and by western blot and immunofluorescence in LUAD cell lines and in a human bronchial epithelial cell line. The effects of cancer-IgG silencing on the proliferation and apoptosis of PC9 and H292 cells were evaluated by plate cloning and apoptosis assay; the effects of cancer-IgG silencing on DNA damage repair ability and radiosensitivity were evaluated by colony-forming assay, γH2AX immunofluorescence, and neutral comet assay. Finally, we used the protein phosphorylation microarray and western blot to explore mechanisms involving cancer-IgG that increased radioresistance. RESULTS: Cancer-IgG is widely expressed in stage III LUAD, and the overall survival and disease-free survival of patients with positive expression are notably lower than those of patients with negative expression, indicating the associations between cancer-IgG and poor prognosis as well as radioresistance. The expression of cancer-IgG in the four LUAD cell lines was located mainly on the cell membrane and cytoplasm and not in the normal lung epithelial cell. Knockdown of cancer-IgG in PC9 and H292 cells resulted in increased apoptosis and negatively affected cancer cell proliferation. After irradiation, silencing of cancer-IgG showed a decrease in colonies as well as increases in the Olive tail moment and γH2AX foci in nucleus, indicating that the knockdown of cancer-IgG resulted in a decrease in the damage repair ability of DNA double-strand breaks in LUAD cells and an enhanced radiosensitivity. The expression of p-AKT, p-GSK3ß, and p-DNA-PKcs decreased in the knockdown group after radiotherapy, suggesting that cancer-IgG could affect radiotherapy resistance by mediating double-strand breaks damage repair in LUAD cells through the PI3K/AKT/DNA-PKcs pathway. CONCLUSIONS: This study revealed that cancer-IgG regulates PI3K/AKT/DNA-PKcs signaling pathways to affect radioresistance of LUAD and associated with poor prognosis.

Filler improvement and purification effects of constructed rapid infiltration facility.

Purification effects of constructed rapid infiltration system with two main fillers (coarse sand or medium coarse sand) and different addition proportion (5%, 10%, or 15%) modifiers (sponge iron, blast furnace slag, or zeolite) on rainwater runoff were studied through filter column tests. A set of constructed rapid infiltration system test device was designed, which included 9 rainwater filter columns. The test results showed that the permeability of artificial fillers blended with modifiers could have the promotion with varying degrees. There were differences in the characteristics of the modifiers, so the artificial fillers blended with different modifiers had a significant difference for the purification effects on each pollutant. In view of the overall situations, the pollutant removal effects of artificial fillers with two or more modifiers had a smaller gap, and the reduction effects were good, ranging from 38.95 to 46.25% when the main filler is coarse sand and from 46.29 to 49.46% while main filler is medium coarse sand. It was worth noting that the artificial fillers blended with sponge iron showed a slight harden after prolonged used; however, it had little influence on the permeability and water purification effects.

Modeling the effects of parameter optimization on three bioretention tanks using the HYDRUS-1D model.

The operation effects of bioretention on different tanks were investigated through tests and simulations. Three layered bioretention tanks, namely, #1, #2, and #3, were selected for intermittent operation tests. The artificial filler layers of the tanks consisted of mixed fillers of fly ash and sand, blast furnace slag, and planting soil. Models were established by using HYDRUS-1D software based on test results. The sensitivity of model parameters was analyzed through Morris screening method. Results showed that return period, thickness of media layer, and solute concentration in the liquid phase were the parameters that significantly influenced the operation effects. The Nash-Sutcliffe efficiency coefficients of the models were greater than 0.85. The simulation results showed that the reduction effects at different inflow loads were better under low loads than under high loads. The comprehensive reduction rate of pollutant load was 5.22% less under high concentrations than under low concentrations. The comprehensive reduction rates of water and pollutant loads were 35.97% and 20.68% greater, correspondingly, in the 1 year return period than in the 10 year return period. The artificial fillers comprising a mixture of fly ash and sand also showed the optimal reduction effects, with comprehensive reduction rates of 69.33% and 83.08% for water and pollutant load, respectively. The reduction effects of water and pollutants for the #1 tank presented an upward trend, whereas those for the #2 tank showed a downward trend given an increase in planting soil thickness. An increase in media thickness enhanced the reduction effects. The media with 60 cm thickness demonstrated the optimal effect.