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Translational regulation is one of the decisive steps in gene expression, and its dysregulation is closely related to tumorigenesis. Eukaryotic translation initiation factor 3 subunit i (eIF3i) promotes tumor growth by selectively regulating gene translation, but the underlying mechanisms are largely unknown. Here, we show that eIF3i is significantly increased in colorectal cancer (CRC) and reinforces the proliferation of CRC cells. Using ribosome profiling and proteomics analysis, several genes regulated by eIF3i at the translation level were identified, including D-3-phosphoglycerate dehydrogenase (PHGDH), a rate-limiting enzyme in the de novo serine synthesis pathway that participates in metabolic reprogramming of tumor cells. PHGDH knockdown significantly represses CRC cell proliferation and partially attenuates the excessive growth induced by eIF3i overexpression. Mechanistically, METTL3- mediated N6-methyladenosine modification on PHGDH mRNA promotes its binding with eIF3i, ultimately leading to a higher translational rate. In addition, knocking down eIF3i and PHGDH impedes tumor growth in vivo. Collectively, this study not only uncovered a novel regulatory mechanism for PHGDH translation but also demonstrated that eIF3i is a critical metabolic regulator in human cancer. [ABSTRACT FROM AUTHOR]

The hybrid sensor kinase RpfC positively regulates the expression of a range of virulent genes and negatively modulates the synthesis of the quorum sensing signal diffusible signal factor (DSF) in Xanthomonas campestris. Three conserved amino acid residues of RpfC implicated in phosphorelay (His198 in the histidine kinase domain, Asp512 in the receiver domain, and His657 in the histidine phosphotransfer domain) were essential for activation of the production of extracellular enzymes and extracellular polysaccharide (EPS) virulence factors but were not essential for repression of DSF biosynthesis. Domain deletion and subsequent in trans expression analysis revealed that the receiver domain of RpfC alone was sufficient to repress DSF overproduction in an rpfC deletion mutant. Further deletion and alanine scanning mutagenesis analyses identified a peptide of 107 amino acids and three amino acid residues (GIn496, Glu504, and Ile552) involved in modulating DSF production. Co- immunoprecipitation and far Western blot analyses suggested an interaction between the receiver domain and RpfF, the enzyme involved in DSF biosynthesis. These data support a model in which RpfC modulates two different functions (virulence factor synthesis and DSF synthesis) by utilization of a conserved phosphorelay system and a novel domain-specific protein-protein interaction mechanism, respectively. This latter mechanism represents an added dimension to conventional two-component signaling paradigms. [ABSTRACT FROM AUTHOR]

Abstract A study of the hydrodynamic performance of a deep-vee ship was performed to determine the influence of the use of stern flaps and interceptors on drag-resistance, trim, and sinkage properties of the said ship. Factors leading to changes in the resistance and attitude of the ship were analyzed in terms of the stern pressure distribution and transom flow fields. Analysis results demonstrate that both the stern flap and interceptor serve to reduce the amount of drag resistance, running trim, and sinkage of the ship, and that the drag reduction rate attained was of the order of 3–9% in the Froude number (Fr) range of 0.334–0.584. Further, resistance performance of the deep-vee ship equipped with stern flaps was observed to be better in the Fr range of 0.334–0.5; however, when Fr value exceeded 0.5, ship equipped with interceptors demonstrated an superior drag-reduction effect. The study focused on evaluation of the combined effect of the use of stern flaps and interceptors in an attempt to enhance the energy-saving capacity of ships. Results obtained via experimental and numerical analyses demonstrate that deployment of a reasonable combination of stern appendages causes significant improvement in the drag-reduction effect and trim optimization. Highlights • CFD and EFD technologies used to study the influence of the interceptors, stern flaps and their combinations. • The main reason of ship resistance change was obtained. • The action mechanism of appendages was explained from the view of transom stern flow field. • A reasonable combination of stern appendages can improve the effect of drag reduction and trim optimization. [ABSTRACT FROM AUTHOR]

Background Particulate matter 2.5 (PM2.5) has proven to be associated with morbidity and mortality from cardiovascular diseases. However, whether PM2.5 could promote the formation of abdominal aortic aneurysm (AAA) is unclear. Present study aimed to explore the relationship between PM2.5 exposure and AAA development. Methods Ang Ⅱ-infused apoe −/− mice were treated with PM2.5 or saline by intranasal instillation. Four weeks later, histological and immunohistological analyses were used to evaluate the effect of PM2.5 on AAA formation. Human aortic smooth muscle cells (HASMCs) were also employed to further analyze the adverse effect of PM2.5 in vitro. Results We found that PM2.5 could significantly increase the AAA incidence, the maximal abdominal aortic diameter and could promote the degradation of elastin. Additionally, the expression of senescence markers, P21 and P16 were also enhanced after PM2.5 exposure. We also found that PM2.5 significantly increased the AAA related pathological changes, MMP2 and MCP-1 expression in HASMCs. Meanwhile, PM2.5 could increase the expression of senescence markers P21, P16 and SA-β-gal activity, also the reactive oxygen species levels in vitro. Conclusions PM2.5 promoted the formation of AAA in an Ang Ⅱ-induced AAA model. The underlying mechanism might be cellular senescence after PM2.5 exposure. [ABSTRACT FROM AUTHOR]

MicroRNA-24 (miR‐24), a member of the miRNA family, functions as an oncogene in various types of human cancer. However, the underlying mechanisms of miR‐24 involvement in the development and progression of hepatocellular carcinoma (HCC) remain poorly understood. The present study revealed that miRNA-24 down-regulates p53 through binding to the 3′-UTR of p53 mRNA based on a luciferase reporter assay, and that the expression level of miR-24 could affect the invasion of HCC lines via p53. Down-regulation of p53 significantly attenuated the inhibitory effects of miR-24 knockdown on the invasion of HCC cells, suggesting that miR-24 could be a potential target for HCC treatment. Moreover, our results revealed that miR-24 expression was significantly increased in HCC metastatic tumor tissues compared with matched non-metastatic tumor tissues, and that the up-regulation of miR-24 was significantly associated with down-regulation of p53 in the HCC tissues. In conclusion, this study demonstrates that miR-24 functions as an oncogene in HCC, at least partly by promoting cell invasion through down-regulation of p53. Therefore, miR-24 may be a potential therapeutic target for treatment of HCC. [ABSTRACT FROM AUTHOR]

The close relationship between intestinal microflora and immune system has been confirmed, stimulus from intestinal flora plays an important role in the development of the immune system and its dynamic balance. Current research is still inadequate to determine how local bacteria in gut influence the whole body. In this study, influence of ceftriaxone sodium induced intestinal dysbacteriosis on local and overall immune function was investigated. We found that the beneficial bacteria decreased significantly compared with control after oral administration of ceftriaxone; Moreover, the proportion of T cells are higher and B cells are lower in the dysbacteriosis mice, activation and proliferation of T and B cells was decreased significantly in gut-associated lymphoid tissues (GALTs), such as Peyer's patches (PPs) and mesenteric lymph nodes(MLNs)with ceftriaxone treatment; The secreted sIgA in intestinal was reduced in dysbacteriosis mice than that of control as well. The similar results above are also shown on the spleen. In addition, the delayed type hypersensitivity (DTH) reaction decreased in dysbacteriosis mice. The present data suggested that intestinal microflora had impact on immune system by influencing the proportion and function of lymphocytes in PPS-MLN-spleen. [ABSTRACT FROM AUTHOR]

S-type peraluminous granite can crop out in various tectonic settings. The Paleozoic Piaochi granitic intrusion is a large S-type peraluminous intrusion located in the North Qinling orogen, and has important implication for its tectonic evolution. Though intensively studied, the age and tectonic setting of this intrusion are still controversial. In this study, we carried out an integrated study of zircon U-Pb age, major and trace elements, and Sr-Nd-Hf-O isotope compositions for the Piaochi intrusion, with aims to constrain its petrogenesis and tectonic significance. SIMS and LA-ICPMS U-Pb zircon data obtained from magmatic zircons indicate that the Piaochi intrusion was emplaced at 473 ± 4 Ma, and contained ca. 490 Ma inherited zircons. The granite samples from the Piaochi intrusion show typical S-type characteristics, such as the relatively moderate aluminum saturation index (1.00-1.08), low zirconium saturation temperatures, occurrences of muscovite, and high zircon δ18O values (8.70 to 9.54‰). The relatively low Sm/Nd (0.13-0.20) and FeOT/MgO ratios (2.21-3.9) suggest that the granites are unfractionated. The geochemical compositions reveal that they were derived from partial melting of a clay-poor, but plagioclase- and biotite-rich psammitic source, similar to metasedimentary rocks outcropping in the North Qinling unit. Moreover, the Piaochi granites are moderately depleted in Eu and heavy rare earth elements, and have relatively high (La/Yb)N values (22.8-56.8), implying a high-pressure, plagioclase-poor and garnet-rich residual assemblage. The Piaochi granites have high and variable initial 87Sr/86Sr ratios (0.72167-0.72511) and low εNd (t) (from - 10.23 to - 8.71) values with two-stage Nd model ages (TDM2) of 1.91-2.03 Ga, which are comparable with those of supracrustal materials in the North Qinling unit. In addition, our results show that the ca. 470 Ma magmatic zircons display a narrow εHf (t) array within those of the inherited cores. These imply that the Piaochi granites inherited their isotopic characteristics wholly from their sources, and the Hf isotopes might have been differently homogenized during the partial melting. Our new zircon U-Pb ages indicate that the Piaochi granites were emplaced after the climax of the UHP metamorphism, coeval with later retrograde metamorphism during exhumation. Therefore, we suggest that the formation of the early Paleozoic Piaochi intrusion was triggered by the exhumation of the UHP rocks. [ABSTRACT FROM AUTHOR]

• Ultrasound increased the secondary structure stability of SPI-HF. • Ultrasound decreased the zeta potential, particle size, and turbidity of complexes. • Ultrasound treatment enhanced the emulsifying properties of SPI-HF. In recent years, more and more attention had been paid to the combination of proteins and flavonoids, and several flavonoids had been reported to improve the physicochemical and emulsifying properties of proteins. This study investigated the effects of ultrasonic treatment (450 W for 10 min, 20 min, and 30 min) on the physicochemical properties, antioxidant activity, and emulsifying properties of soy protein isolate (SPI) -hawthorn flavonoids (HF) non-covalent complexes. The results showed that the addition of HF to SPI and 20 min of ultrasound could reduce α-helix and random coil, increase β-sheet and β-turn, and enhance fluorescence quenching. In addition, it decreased the particle size, zeta potential, surface hydrophobicity, and turbidity to 88.43 or 95.27 nm, −28.80 mV, 1250.42, and 0.23, respectively. The protein solubility, free sulfhydryl group, antioxidant activity, emulsifying activity index, and emulsifying stability index all increased to 73.93%, 15.07 μmol/g, 71.00 or 41.91%, 9.81 m2/g, and 67.71%, respectively. Moreover, high-density small and low-flocculation droplets were formed. Therefore, the combined ultrasound treatment and addition of HF to SPI is a more effective method for protein modification compared to ultrasound treatment alone. It provides a theoretical basis for protein processing and application in the future. [ABSTRACT FROM AUTHOR]