Eukaryotic translation initiation factor 2α kinase 2 in pancreatic cancer: An approach towards managing clinical prognosis and molecular immunological characterization.

Most patients with pancreatic cancer are already in the late stages of the disease when they are diagnosed, and pancreatic cancer is a deadly disease with a poor prognosis. With the advancement of research, immunotherapy has become a new focus in the treatment of tumors. To the best of our knowledge, there is currently no reliable diagnostic or prognostic marker for pancreatic cancer; therefore, the present study investigated the potential of eukaryotic translation initiation factor 2α kinase 2 (EIF2AK2) as a predictive and diagnostic marker for pancreatic cancer. Immunohistochemical staining of clinical samples independently verified that EIF2AK2 expression was significantly higher in clinically operated pancreatic cancer tissues than in adjacent pancreatic tissues., and EIF2AK2 expression and differentially expressed genes (DEGs) were identified using downloadable RNA sequencing data from The Cancer Genome Atlas and Genomic Tumor Expression Atlas. In addition, Gene Ontology/Kyoto Encyclopedia of Genes and Genomes analyses and immune cell infiltration were used for functional enrichment analysis of EIF2AK2-associated DEGs. The clinical importance of EIF2AK2 was also determined using Kaplan-Meier survival, Cox regression and time-dependent survival receiver operating characteristic curve analyses, and a predictive nomogram model was generated. Finally, the functional role of EIF2AK2 was assessed in PANC-1 cells using a short hairpin RNA-EIF2AK2 knockdown approach, including CCK-8, wound healing assay, cell cycle and apoptosis assays. The findings suggested that EIF2AK2 may have potential as a diagnostic and prognostic biomarker for patients with pancreatic cancer. Furthermore, EIF2AK2 may provide a new therapeutic target for patients with pancreatic cancer.

The contribution of typhoon local and remote forcings to storm surge along the Makou-Dahengqin tidal reach of Pearl River Estuary.

Due to the interaction between upstream discharge and astronomical tides in tidal reaches, the typhoon-induced storm surge processes are quite different from that in other coastal regions. Investigating the contributions of driving factors is essential to deepen the understanding of storm surges in tidal reaches. In this study, a coupled hydrological-hydrodynamic storm surge model is first developed to explore the main driving factors of storm surges in Makou-Dahengqin tidal reach during the three most influential typhoon events (Hagupit, Hato and Mangkhut). After that, the machine learning method is integrated to assess the water level in response to storm surges. The driving factors of storm surge are decomposed into remote forcing (upstream discharge, astronomical tide) and direct local forcing (wind stress, atmospheric pressure). The relative contributions of remote forcing are the highest near the estuary mouth. The relative contributions of local forcing to water levels are higher in the sections 40-80 km away from the estuary mouth. The most impacting period of the local forcing is about 48 h, while the relative contributions of remote forcing increase before and after the period. The local forcing-induced surges are highest at the upper reach during Hagupit, while it causes extreme surges at the estuary mouth during more powerful typhoons (Hato, Mangkhut). The maximum water levels and remote forcing-induced maximum surges invariably appear at the upper reach. However, when local and remote forcings are in the same phase, the maximum storm surge appears in the lower reaches during Hato. If local and remote forcings are in the same phase, the peak water levels would be amplified by up to 15.04 %, 36.23 % and 40.68 % during Hagupit, Hato and Mangkhut, respectively. Moreover, Remote forcing contributes more to the amplification of peak water levels than local forcing does, accounting for 68.5 % to 100 %.

Light-Induced Structural Dynamic Evolution of Pt Single Atoms for Highly Efficient Photocatalytic CO2 Reduction.

Revealing the structural evolution of the real active site during photocatalysis is very important for understanding the catalytic mechanism, but it remains a great challenge. By employing single atoms (SAs) as the mechanism research platform, we investigated the variation of the SA structure under light and the corresponding reaction pathway controlment mechanism. In particular, taking the defect anchoring strategy, Pt SAs are anchored on the metal ion vacancy-rich ZnNiTi layered double hydroxide-etched (ZnNiTi-LDHs-E) support. It is proved by CO-Fourier transform infrared and X-ray absorption fine structure characterization methods that the Pt SAs could gain photoelectrons to form cationic Pt(IV), electron-rich Pt(II), and near-neutral Ptδ+ species at different light intensities. By in situ inducing the above different Pt SAs in photocatalytic CO2 reduction, a dramatic product distribution is observed: (1) under weak light, Pt(IV) SAs cannot activate CO, so CO cannot be further transformed into hydrocarbons; (2) under the moderate light, electron-rich Pt(II) SAs could cooperate with adjacent LDH surface sites (Ni2+/Ti4+) to open up the C-C coupling route for C2H6 generation; and (3) Pt SAs in the state of near-neutral Ptδ+ could directly hydrogenate CO into CH4. This work reveals the structural evolution of Pt SAs in photocatalysis and the corresponding effect on catalytic performance, which provides a new idea for the construction of highly efficient photocatalysts.

TLR2 inhibition ameliorates the amplification effect of LPS on lipid accumulation and lipotoxicity in hepatic cells.

BACKGROUND: Gut microbiome dysbiosis is related to the pathogenesis of nonalcoholic fatty liver disease (NAFLD), and the role of toll-like receptor 2 (TLR2) in its molecular mechanism is controversial. Here, we investigated the effects and mechanisms of Escherichia coli-derived lipopolysaccharide (LPS) on lipid accumulation and lipotoxicity in palmitic acid (PA)-treated L02 cell as an NAFLD cell model, and the role of TLR2 in this process. METHODS: Oil red O staining assay and free fatty acid (FFA) content test were performed to determine the effects of LPS on lipid accumulation in a PA-induced NAFLD cell model with or without TLR2 inhibition. The levels of IL-6 and TNF-α were measured to investigate inflammation conditions. Hoechst 33342 staining assay and Caspase-3 activity assay were used to test cell apoptosis, and the expression levels of proteins in the IRS1/PI3K/AKT signaling pathway, TLR2/MyD88/IKKα/NF-κB signaling pathway, and mitochondrion-dependent apoptotic signaling pathway were detected using Western blot. RESULTS: Lipid accumulation, pro-inflammatory cytokine release, and cell apoptosis with high levels were observed in the PA-induced NAFLD cell model, and LPS aggravated these processes. Whereas TLR2 inhibition could significantly ameliorate PA-induced and LPS-amplified lipid accumulation, inflammatory, and cell apoptosis, it had no significant effect on L02 cells treated with LPS alone. CONCLUSIONS: These results were confirmed by activation or inhibition of the IRS1/PI3K/AKT signaling pathway, TLR2/MyD88/IKKα/NF-κB signaling pathway, and mitochondrion-dependent apoptotic signaling pathway, and were reflected by changes on their proteins expression. TLR2 is involved in PA-induced lipid accumulation and lipotoxicity in L02 cells, which could be aggravated by LPS, although LPS-induced amplification might not be through direct interaction with TLR2.

Drinking Warm Water Improves Growth Performance and Optimizes the Gut Microbiota in Early Postweaning Rabbits during Winter.

Accumulating evidence indicates that cold exposure changes the composition of the gut microbiota and reduces intestinal immunity in early postweaning livestock. However, little is known about the effects of drinking warm water (WW) on gut microbiota during winter. In this study, we investigated the effects of drinking WW in winter on the growth performance and gut microbiota structure of rabbits raised in poorly insulated housing from the early postweaning period (day 46) to the subadult period (day 82). The average daily gain and feed conversion ratio in rabbits drinking WW were significantly improved compared to those of the rabbits drinking cold water (CW) during 47-58 days. In addition, rabbits drinking WW had a significantly decreased the risk of diarrhea during 71-82 days. 16S rRNA sequence analysis revealed that the alpha diversity of the cecal microbiota was not significantly different between the WW and CW groups, but significantly increased with age. The relative abundance of cecal microorganisms, such as Coprococcus spp. was considerably increased at day 70 in the group drinking WW. Correlation analysis indicated that Coprococcus spp. was negatively associated with pro-inflammatory factors. In conclusion, our results suggest that drinking WW has a positive effect on growth performance and gut microbiota in rabbits during the early postweaning stage in winter.