The molecular mechanism of sepsis-induced diaphragm dysfunction.

Background: No effective drugs for the treatment of sepsis-induced diaphragm dysfunction are currently available. Therefore, it is particularly important to clarify the molecular regulatory mechanism of this condition and subsequently implement effective treatment and prevention of sepsis-induced diaphragm dysfunction. Methods: A mouse model of diaphragm dysfunction was established via injection of lipopolysaccharide (LPS). An RNA-sequencing (RNA-seq) technique was used to detect the differentially expressed genes (DEGs) in the diaphragms of mice. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed for functional analysis of DEGs. The protein-protein interaction network obtained from the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) website was imported into Cytoscape, the key molecular regulatory network was constructed with CytoNCA, the ClueGo plugin was further used to analyze the core regulatory pathways of key molecular, and finally, the iRegulon plugin was used to the identify key transcription factors. Results: The genes upregulated after LPS treatment were involved in biological processes and pathways related to immune response; the genes downregulated after LPS treatment were mainly correlated with the muscle contraction. The expressions of several inflammation-related genes were upregulated after LPS treatment, of which tumor necrosis factor (Tnf), interleukin (Il)-1ß, and Il-6 assumed a core regulatory role in the network; meanwhile, the downregulated key genes included Col1a1, Uqcrfs1, Sdhb, and ATP5a1, among others. These key regulatory factors participated in the activation of Toll-like receptor (TLR) signaling pathway, nuclear factor (NF)-κB signaling pathway, and TNF signaling pathway as well as the inhibition of oxidative phosphorylation pathway, cardiac muscle contraction pathway, and citrate cycle pathway. Finally, RelA, IRF1, and STAT3, were identified as the key regulators in the early stage of diaphragmatic inflammatory response. Conclusions: Sepsis-induced diaphragm dysfunction in mice is closely correlated with the activation of TLR signaling pathway, NF-κB signaling pathway, and TNF signaling pathway and the inhibition of oxidative phosphorylation pathway, cardiac muscle contraction pathway, and citrate cycle pathway. Our findings provide insight into the molecular mechanism of sepsis-induced diaphragm dysfunction in mice and provide a promising new strategy for targeted treatment of diaphragm dysfunction.

The Effect of Stray Current on Calcium Leaching of Cement-Based Materials.

The metro engineering is in an environment rich in stray current and groundwater, which will accelerate concrete corrosion. In this study, the corrosion of cement-based materials, under stray current, consisting of direct current, was investigated, and the effects of stray current magnitude, water-binder ratio, fly ash, and silica fume on its corrosion were analyzed. The results show that, as the energisation duration of the stray current increases, the mass of the cathode side leachables increases, and the compressive strength of the cement-based materials decreases overall; at 120 d of stray current, the water-binder ratio of 0.50 shows the least reduction in strength, compared to the others; the mass of cathode side leachables decrease significantly with the increase in fly ash content; when fly ash content is 15%, the mass of cathode side leachables is the least, and the decrease in the compressive strength at 120 d of stray current is the smallest. At 10% silica fume content, the mass of the cathode side leachables is the least, and the decrease in the compressive strength of the cement-based materials at 120 d of stray current is the smallest. In general, the corrosion resistance is relatively good at 15% fly ash content and 10% silica fume content under stray current.

MiR-202-3p inhibits the proliferation and metastasis of lung adenocarcinoma cells by targeting RRM2.

Background: Lung adenocarcinoma (LUAD) is the most common type of lung cancer, and its pathogenesis is still unclear. The present study aimed to investigate the role of miR-202-3p and its downstream target gene, ribonucleotide reductase regulatory subunit M2 (RRM2), in the occurrence and development of LUAD and elucidate the correlation between RRM2 and the clinicopathological stage and prognosis of LUAD. Methods: The expression of miR-202-3p was analyzed using the CancerMIRNome database and quantitative polymerase chain reaction (qPCR). The effects of miR-202-3p and RRM2 on the proliferation, migration, and invasion of A549 cells were analyzed. A dual luciferase reporter assay was used to verify the targeting of miR-202-3p and RRM2. Additionally, the correlation between RRM2 expression and clinicopathology was analyzed. Results: (I) MiR-202-3p was lowly expressed in LUAD and the LUAD cell lines. qPCR confirmed that microRNA (miRNA) transfection was effective and sufficient for subsequent experiments. (II) MiR-202-3p inhibited the proliferation, invasion, and migration of LUAD cells. (III) There was a targeting relationship between miR-202-3p and RRM2, and miR-202-3p affected the expression of the RRM2 protein. RRM2 was highly expressed in lung cancer tissue. (IV) RRM2 was associated with the clinicopathological staging of lung cancer. The prognosis of patients with low RRM2 expression was better, and the prognostic sensitivity of RRM2 to lung cancer was high. RRM2 may exert its effects via the Notch pathway. (V) Si-RRM2 inhibited the expression of the RRM2 protein. RRM2 promoted the proliferation, migration, and invasion of LUAD cells. A miR-202-3p inhibitor restored the inhibitory effect of si-RRM2 on LUAD cells. Conclusions: MiR-202-3p was lowly expressed in lung cancer tissue. MiR-202-3p overexpression inhibited the proliferation and metastasis of lung cancer cells. RRM2 was highly expressed in lung cancer tissue and promoted the proliferation and metastasis of lung cancer cells. MiR-202-3p targeted and inhibited RRM2, thereby reducing the proliferation and metastasis of LUAD cells. LUAD patients with low RRM2 expression had a better prognosis, and the expression level of RRM2 was correlated with the clinical characteristics of lung cancer patients.

Study on the Frost Resistance of Concrete Modified with Steel Balls Containing Phase Change Material (PCM).

In order to investigate the effect of phase change materials on the frost resistance of concrete in cold regions, hollow steel balls were used in this paper for the macroscopic encapsulation of the phase change material to replace some of the coarse aggregates in the preparation of phase change concrete. On the premise of ensuring reasonable mechanical properties, concrete mixed with different contents and different surface treatments of grouting steel balls were tested for the compressive strength and splitting tensile strength to determine the optimum content of phase change steel balls and investigate the frost resistance of phase change concrete. At the same time, industrial CT was used to explore the internal pore evolution pattern of concrete during the freeze-thaw period. The test results show that the optimum content of steel balls is 75%; during the freeze-thaw process, the mass loss, relative dynamic elastic modulus loss, and strength loss of phase change concrete are all lower than those of ordinary concrete, and the increase in porosity of phase change concrete is also significantly lower than that of ordinary concrete; the addition of phase change materials can optimise the distribution of the internal pore in concrete, improve its internal pore structure, and enhance its frost resistance.

The predictive prognostic values of CBFA2T3, STX3, DENR, EGLN1, FUT4, and PCDH7 in lung cancer.

BACKGROUND: Lung cancer is one of the most malignant tumors. However, neither the pathogenesis of lung cancer nor the prognosis markers are completely clear. The purpose of this study is to screen the diagnostic or prognostic markers of lung cancer. METHODS: TCGA and GEO datasets were used to analyze the relationship between lung cancer-related genes and lung cancer samples. Common differential genes were screened, and a univariate Cox regression analysis was used to screen survival related genes. A univariable Cox proportional hazards regression analysis was used to verify the genes and construct risk model. The key factors affecting the prognosis of lung cancer were determined by univariate and multivariate regression analyses. The ROC curve, AUC and the survival of each risk gene was analyzed. Finally, the biological functions of high- and low-risk patients were explored by GSEA and an immune-infiltration analysis. RESULTS: Based on the common differential genes, 13 genes significantly related to lung cancer survival were identified. Eight risk genes (CBFA2T3, DENR, EGLN1, FUT2, FUT4, PCDH7, PHF14, and STX3) were screened out. The results showed that risk status may be an independent prognostic factor, and the risk score predicted the prognosis of lung cancer. CBFA2T3 and STX3 are protective genes, while DENR, EGLN1, FUT4 and PCDH7 are dangerous genes. These 6 genes can be used as independent lung cancer prognosis markers. The corresponding biological functions of genes expressed in high-risk patients were mostly related to tumor proliferation and inflammatory infiltration. Neutrophil, CD8+T, Macrophage M0, Macrophage M1- and mDC-activated cells were high in high-risk status samples. CONCLUSIONS: CBFA2T3, STX3, DENR, EGLN1, FUT4, and PCDH7 are important participants in the occurrence and development of lung cancer. High-risk patients display serious inflammatory infiltration. This study not only provides insight into the mechanism of occurrence and development of lung cancer, but also provides potential targets for targeted therapy of lung cancer.

Experimental Investigation on the Freeze-Thaw Resistance of Steel Fibers Reinforced Rubber Concrete.

The reuse of rubber in concrete results in two major opposing effects: an enhancement in durability and a reduction in mechanical strength. In order to strengthen the mechanical properties of rubber concrete, steel fibers were added in this research. The compressive strength, the four-point bending strength, the mass loss rate, and the relative dynamic elastic modulus of steel fiber reinforced rubber concrete, subjected to cyclic freezing and thawing, were tested. The effects of the content of steel fibers on the freeze-thaw resistance are discussed. The microstructure damage was captured and analyzed by Industrial Computed Tomography (ICT) scanning. Results show that the addition of 2.0% steel fibers can increase the compressive strength of rubber concrete by 26.6% if there is no freeze-thaw effect, but the strengthening effect disappears when subjected to cyclic freeze-thaw. The enhancement of steel fibers on the four-point bending strength is effective under cyclic freeze-thaw. The effect of steel fibers is positive on the mass loss rate but negative on the relative dynamic elastic modulus.

Autogenous Shrinkage Property of High-Performance Graphenes Cement-Based Composites.

At present, high-performance cement-based composites are widely used, and they are prone to early cracking due to their high autogenous shrinkage stress. In this research, the uniformly dispersed GNPs were added into high-performance cementitious materials. The autogenous shrinkage of high-performance cementitious matrix materials with different incorporation of GNPs was also researched with water to cement ratio of 0.25, 0.30 and 0.35. According to hydration heat, hydration products, microstructure and porosity of GNPs cementitious matrix materials, the microcosmic mechanism for autogenous shrinkage was also investigated. It was testified that moderate addition of GNPs decreased the autogenous shrinkage of cement-based composites. Moreover, the autogenous shrinkage value was minimal after treatment with 0.10 wt% GNPs cement paste sample for 7 days, at the water to cement ratio of 0.35, and the depressed percentage of autogenous shrinkage reached 81.60% compared with the blank sample.