Exosomes derived from M1 macrophages inhibit the proliferation of the A549 and H1299 lung cancer cell lines via the miRNA-let-7b-5p-GNG5 axis

Background Almost all cells are capable of secreting exosomes (Exos) for intercellular communication and regulation. Therefore, Exos can be used as a natural therapeutic platform to regulate genes or deliver drugs to treat diseases. M1 macrophages inhibit tumor growth by releasing pro-inflammatory factors. This study explored the applicability of M1 macrophage exosomes (M1-Exos) as gene carriers and the effects on GNG5 protein, and further examined whether macrophage repolarization could inhibit tumor activity. Methods M0 macrophages were polarized toward M1 using vitexin. Exos were obtained from M1 macrophages by ultra-centrifugation. The transwell non-contact co-culture system was used to co-culture M1 macrophages with HLF-α human lung epithelial cells or A549 or H1299 lung cancer cells. MTT, scratch, and transwell assays were used to detect the cell viability, migration, and invasion ability of cells in the four groups. Flow cytometry was used to detect the apoptosis rate of each group, and western blot (WB) analysis was performed to detect the change in the expression of proliferation- and apoptosis-related proteins. We screened the differentially expressed microRNAs using quantitative polymerase chain reaction technology. Luciferase reporter analysis was performed to explore the interaction between miRNA and protein. We used Xenografted A549 tumors in nude mice to study the effect of M1-Exos on tumor cell growth in vivo. Results The results showed that, under the M1 macrophage co-culture system, lung cancer cell viability, invasion, and migration ability decreased, and the number of apoptotic cells increased, will all indicators being statistically significant (P < 0.05). The expression levels of PCNA, KI67, and Bcl-2 decreased significantly, but that of Bax increased (P < 0.05). Exosomes can have the same effect on tumor cells as M1 macrophages. Exosomes can transport miR-let-7b-5p to tumor cells, and miR-let-7b-5p can inhibit tumor cell proliferation and promote tumor cell apoptosis by regulating the GNG5 protein level. Conclusions M1-Exos inhibit the proliferation, invasion, and metastasis of lung cancer cells through miRNA-let-7b-5p and GNG5 signaling pathways and inhibit the anti-apoptotic ability of lung cancer cells

High water uptake ability was associated with root aerenchyma formation in rice: Evidence from local ammonium supply under osmotic stress conditions

Root water uptake is strongly influenced by the morphology and anatomical structure of roots, which are regulated by nitrogen forms and environmental stimuli. To further illustrate the roles of different nitrogen forms on root water uptake under osmotic stress, a split-root system was supplied with different nitrogen forms and osmotic stress simulated by adding 10% (w/v) polyethylene glycol (PEG, 6000). The local effects of nitrogen form and osmotic stress on root morphology, anatomical structure, root lignin content, and water uptake rate were investigated. Under osmotic stress conditions, ammonium markedly promoted the formation and elongation of the lateral root, whereas a significant decrease in numbers of lateral roots was observed under local nitrate supply. Under nitrate supply in split-root systems, osmotic stress significantly promoted root cell death and more aerenchyma formation, as well as accelerated the lignification of the root. However, osmotic stress had no negative effect on the root anatomical structure under ammonium supply. The root water uptake rate was significantly higher in split-root supplied with ammonium than nitrate under osmotic stress conditions. In conclusion, the high water uptake ability in local ammonium supply was associated with the more lateral roots development and the lower cell death, aerenchyma formation and lignification under osmotic stress

Combined utility of Ki-67 index and tumor grade to stratify patients with pancreatic ductal adenocarcinoma who underwent upfront surgery

Abstract Objective To investigate the prognostic prediction of a new indicator, combined by tumor grade and Ki-67, in patients with resected pancreatic ductal adenocarcinoma (PDAC). Methods Data were retrospectively collected from consecutive patients who underwent primary resection of pancreas from December 2012 to December 2017. Tumor grade and Ki-67 were reviewed from routine pathological reports. G-Ki67 was classified as three categories as I (G1/2 and Ki-67 < 40%), II (G1/2 and Ki-67 ≥ 40%), and III(G3/4 and all Ki-67). Results Cox regression analyses revealed that tumor stage (II vs. I: hazard ratio (HR), 3.781; 95% confidence index (CI), 2.844–5.025; P < 0.001; III vs. I: HR, 7.476; 95% CI, 5.481–10.20; P < 0.001) and G-Ki67 (II vs. I: HR, 1.299; 95% CI, 1.038–1.624; P = 0.022; III vs. I: HR, 1.942; 95% CI, 1.477–2.554; P < 0.001) were independent prognostic factors in the developing cohort. The result was rectified in the validation cohort. In subgroups analysis, G-Ki67 (II vs. I: HR, 1.866 ; 95% CI, 1.045–3.334; P = 0.035; III vs. I: HR, 2.333 ; 95% CI, 1.156–4.705; P = 0.018) also had a high differentiation for survival prediction. Conclusion Our findings indicate that three-categories of G-Ki67 in resectable PDAC according to the routine pathological descriptions provided additional prognostic information complementary to the TNM staging system

The enhanced drought tolerance of rice plants under ammonium is related to aquaporin (AQP).

Previously, we demonstrated that drought resistance in rice seedlings was increased by ammonium (NH4(+)) treatment, but not by nitrate (NO3(-)) treatment, and that the change was associated with root development. To study the effects of different forms of nitrogen on water uptake and root growth under drought conditions, we subjected two rice cultivars (cv. 'Shanyou 63' hybrid indica and cv. 'Yangdao 6' indica, China) to polyethylene glycol-induced drought stress in a glasshouse using hydroponic culture. Under drought conditions, NH4(+) significantly stimulated root growth compared to NO3(-), as indicated by the root length, surface area, volume, and numbers of lateral roots and root tips. Drought stress decreased the root elongation rate in both cultivars when they were supplied with NO3(-), while the rate was unaffected in the presence of NH4(+). Drought stress significantly increased root protoplast water permeability, root hydraulic conductivity, and the expression of root aquaporin (AQP) plasma intrinsic protein (PIP) genes in rice plants supplied with NH4(+); these changes were not observed in plants supplied with NO3(-). Additionally, ethylene, which is involved in the regulation of root growth, accumulated in rice roots supplied with NO3(-) under conditions of drought stress. We conclude that the increase in AQP expression and/or activity enhanced the root water uptake ability and the drought tolerance of rice plants supplied with NH4(+)

Confined Pyrolysis for Simulating Hydrocarbon Generation from Jurassic Coaly Source Rocks in the Junggar Basin, Northwest China

Several oil and gas fields have been found in which oil and gas were mainly derived from the Jurassic coaly source rocks in the Junggar Basin, northwest China. Pyrolysis experiments were performed on two coals (J23C1 and FM1C2) and one type III kerogen of mudstone (Di9S1) from Jurassic strata in the basin at two heating rates of 20 and 2 °C/h in confined systems (gold capsules). Hydrogen indices and H/C atomic ratios of the three samples J23C1, FM1C2, and Di9S1 are 83, 197, and 226 mg/g TOC, and 0.70, 0.86, and 1.01, respectively. The measured maximum oil yields for the three samples are 59.37, 175.75, and 80.75 mg/g TOC, respectively, inconsistent with hydrogen indices and H/C atomic ratios. However, the measured maximum gas yields (∑C_1–5) for the three samples are 90.69, 157.24, and 198.15 mg/g TOC, respectively, consistent with hydrogen indices and H/C atomic ratios. This result is interpreted by kerogen Di9S1 containing mainly crossed alkane moieties with both terminals attached to aromatic rings while coals J23C1 and FM1C2 contain mainly alkane moieties with only one terminal attached to an aromatic ring based on kerogen ¹³C NMR spectra and the oil yield relative to gas yield and compositions of liquid components produced in confined pyrolysis. The crossed alkane moieties were hardly released as liquid alkanes but likely further cracked into gaseous components during pyrolysis. Jurassic strata contain some effective oil source rocks which produced enough amount of oil required for oil expulsion and formation of commercial oil reservoirs in oil generative window (Ro 0.6–1.35%). The amounts of gaseous hydrocarbons generated from the Jurassic coaly source rocks are generally low in oil generative window due to low transformation ratios. Elevated maturity (Ro > 1.35%) is a critical controlling factor to the Jurassic coaly source rocks generating sufficient gaseous hydrocarbons and forming commercial gas reservoirs