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The endophytic fungus Neurospora dictyophora 3ZF-02 with a special aroma was isolated from the arils of Torreya grandis. Analysis of volatile organic compounds was done by gas chromatography-mass spectrometry. A total of 46 compounds were identified in the volatile organic compounds by 3ZF-02. In the growth phase, esters, acids, along with some alcohols and ketones were the main components. During the recession period, a large amount of benzene and naphthalene compounds appeared, accompanied by the production of amines. Oleic acid, methyl abietate, terpinen-4-ol were also found. They were the same ingredients in essential oil of Torreya. The antioxidant activity and antifungal activity of all extracts were also evaluated. When cultured for 10 days, it exhibited the most significant antioxidant activity with IC

Eomesodermin (Eomes) is a T‐box transcription factor that drives the differentiation and function of cytotoxic lymphocytes. However, the underlying function and mechanism of Eomes in tumor cells remains elusive. Here, we studied the role of Eomes in human esophageal squamous cell carcinoma (ESCC). Using 2 human ESCC cell lines, we found that Eomes knockdown reduced esophageal cancer cell proliferation and that the esophageal cancer cell cycle was blocked in the G2/M phase. Mechanistically, we identified CCL20 as the main downstream target of Eomes. Furthermore, we found that CCL20 could chemoregulate regulatory T cells (Tregs) through their specific receptor CCR6, then promoting the proliferation of esophageal cancer cells. Eomes knockdown also delayed the growth of human ESCC xenografts in BALB/c nude mice. Importantly, in 133 human ESCC tissues, high Eomes levels were associated with poor clinical prognosis. Overall, our findings suggested that the Eomes‐CCL20‐CCR6 pathway plays a vital role in human ESCC progress. Therefore, targeting this pathway may represent a promising strategy for controlling human ESCC., Lian et al report that the Eomes‐CCL20‐CCR6 pathway plays a vital role in human ESCC progress and that high Eomes levels were associated with poor clinical prognosis. They found that CCL20 could chemoregulate Tregs through their specific receptor CCR6 and then promote the proliferation of esophageal cancer cells. Eomes knockdown also delayed the growth of human ESCC xenografts in BALB/c nude mice.

Longwall face fall in the open face area is one of the most difficult ground control problems in mining thick coal seams in China especially under difficult geological conditions. This paper has proposed a new flexible bolting and grouting technology for face support. The flexible support method includes face support using flexible coir ropes and face grouting with cement and accelerator mixtures. Numerical and laboratory studies of pullout tests are performed to further improve the flexible support performance including optimization of boreholes and flexible bolts diameters, and selection of grouting materials. The results show that (a) The optimized rope‐borehole diameter ratio is around 0.5 to ensure the best face reinforcement; (b) The grouting material (a mixture of ultrafine cement, mineral powder and sodium silicate) shows advantages of low cost, effective waste disposal, reduced setting time, and good pullout limit force and is recommended for industrial application with sodium silicate at a proportion of 10% by weight and mineral powder at 30%. The application of the new flexible bolting and grouting method in Chenmanzhuang mine shows improved face stability and reduced capital cost.

The asymmetric reduction of prochiral carbonyl compounds by NAD(P)H-dependent carbonyl reductases represents a powerful method for the production of optically active alcohols. The stereoselectivity of a series of carbonyl reductases were evaluated toward the reduction of ethyl 2-oxo-4-phenylbutyrate (OPBE). A majority of reductases produced the ethyl (R)-2-hydroxy-4-phenylbutyrate ((R)-HPBE) with low to excellent enantiomeric excess (e.e.), whereas about 30% reductases catalyzed OPBE to form (S)-HPBE. Among them, the carbonyl reductase from Saccharomyces cerevisiae (SeCR) and short-chain dehydrogenase from Gluconobacter oxydans (GoKR) exhibited 100% e.e., yielding the corresponding (R) and (S)-HPBE, respectively. However, the SeCR showed relative higher activity (29.0 U/mg) and affinity (Km of 0.22 mM) than those of GoKR. Docking analysis found that the interaction of OPBE with enzyme-NADPH complex determined the NADPH-provided hydrogen transfer and the configuration of reductive product. These results indicated that the three-dimensional (3D) structure of enzymes controlled the stereoselectivity of the reductive product based on the geometry of the substrate and cofactor.

The transmembrane protein with epidermal growth factor and two follistatin motifs 2 (TMEFF2) is a single-pass transmembrane protein, and it is downregulated in human gastric cancer and levels correlate with tumor progression and time of survival. However, the mechanism of its dysregulation in gastric cancer is little known. Here we investigate its regulatory mechanism and the bidirectional regulation between TMEFF2 and STAT3 in gastric carcinogenesis. TMEFF2 expression was decreased after Helicobacter pylori (H. pylori) infection in vivo and in vitro. STAT3 directly binds to the promoter of TMEFF2 and regulates H. pylori-induced TMEFF2 downregulation in normal gastric GES-1 cells and gastric cancer AGS cells. Conversely, TMEFF2 may suppress the phosphorylation of STAT3 and TMEFF2-induced downregulation of STAT3 phosphorylation may depend on SHP-1. A highly inverse correlation between the expression of TMEFF2 and pSTAT3 was also revealed in gastric tissues. We now show the deregulation mechanism of TMEFF2 in gastric carcinogenesis and identify TMEFF2 as a new target gene of STAT3. The phosphorylation of STAT3 may be negatively regulated by TMEFF2, and the bidirectional regulation between TMEFF2 and STAT3 may contribute to H. pylori-associated gastric carcinogenesis.

We recently isolated an exon-4-deleted epidermal growth factor receptor (EGFR) variant, termed de4 EGFR. Because the extracellular domain alteration of receptors often influences the antitumor effect of therapeutic antibodies, it is essential to test the sensitivity of de4 EGFR(+) tumors to anti-EGFR antibodies. Therefore, in this study, the antitumor activities of mAb CH12, an anti-EGFRvIII antibody developed in our laboratory, as well as a U.S. Food and Drug Administration-approved anti-EGFR antibody, cetuximab (C225), were characterized on de4 EGFR(+) models. The results of FACS assays showed that CH12 bound to de4 EGFR with a higher avidity than did C225. Interestingly, CH12, but not C225, significantly inhibited the metastasis and growth of U87MG-de4 EGFR xenografts, with a growth-inhibition ratio of 46.48% in vivo, and prolonged the survival of the tumor-bearing mice by 37.2%. Treatment with CH12 significantly suppressed tumor proliferation and angiogenesis with increased tumor apoptosis. Mechanistically, de4 EGFR protein expression was virtually undetectable in the U87MG-de4 EGFR xenografts treated with CH12. This may account for the observed reduction of Akt and Erk phosphorylation, cyclin D1, Bcl-2, and Bcl-x(L) expression and the increase of p27 and E-cadherin expression. Intriguingly, LAMP-1, a major component of the lysosome, was significantly up-regulated in the CH12-treated group but not in the C225-treated group, suggesting its contribution to the degradation of de4 EGFR. Taken together, our data demonstrated that mAb CH12 is a promising therapeutic agent for treating de4 EGFR(+) gliomas.

Background: Delta-like 1 (DLK1), a fetal liver stem cell marker, is strongly expressed in human and rodent fetal liver, but not in adult liver. Notably, dysregulation of DLK1 was found in some human hepatocellular carcinomas (HCC). However, the effect of DLK1 on HCC cell growth and its underlying mechanism are still largely unknown. Aims: To (i) assess the expression of DLK1 in human HCC and adjacent liver tissues and human HCC cell lines; (ii) evaluate the effect of DLK1 on SMMC-7721, Huh7 HCC cell growth in vitro and in vivo; and (iii) explore the potential mechanism of DLK1 that regulates HCC cell growth. Methods: The expression of DLK1 mRNA and protein were detected using reverse transcriptase-polymerase chain reaction and immunohistochemistry respectively. The effect of DLK1 on the proliferation of SMMC-7721 and Huh7 cells was evaluated by colony formation and tumour xenograft assay. The differential expression profiles of DLK1-overexpressing SMMC-7721 cells and control cells were compared using HG-U133 Plus 2 Genechip. The cell cycle distribution of DLK1 forced expressing cells was comparatively analysed. Results: Upregulation of DLK1 was observed in 41 of 57 (71.9%) human HCC samples. Ectopic expression of DLK1 promoted cell proliferation, colony formation and tumorigenicity in SMMC-7721 and Huh7 cells. DLK1 upregulated the expression of interferon-inducible protein 16 (IFI16) and its promoter transcriptional activity, decreased p21waf1/cip1 and induced cell cycle acceleration. However, silencing of IFI16 using small interfering RNA abrogated DLK1-induced proliferation in these cells. Conclusions: IFI16 may be an essential downstream target of DLK1 in HCC cells and required for DLK1-induced cell proliferation.

MicroRNAs (miRNAs) are important gene regulators, which are often deregulated in cancers. In this study, the authors analyzed the microRNAs profiles of 78 matched cancer/noncanerous liver tissues from HCC patients and 10 normal liver tissues and found that 69 miRNAs were differentially expressed between hepatocellular carcinoma (HCC) and corresponding noncancerous liver tissues (N). Then the expressions of 8 differentially expressed miRNAs were validated by real time RT PCR. The set of differentially expressed miRNAs could distinctly classify HCC, N and normal liver tissues (NL). Moreover, some of these differentially expressed miRNAs were related to the clinical factors of HCC patients. Most importantly, Kaplan-Meier estimates and the log-rank test showed that high expression of hsa-miR-125b was correlated with good survival of HCC patients (hazard ratio, 1.787, 95% confidence interval, 1.020-3.133, p = 0.043). The transfection assay showed that overexpression of miR-125b in HCC cell line could obviously suppress the cell growth and phosporylation of Akt. In conclusion, the authors have demonstrated the diagnostic miRNA profile for HCC, and for the first time, identified the miR-125b with predictive significance for HCC prognosis.

Genetic manipulation can be used to solve some traditional chemical engineering problems in biochemical engineering such as in poly(β-hydroxybutyrate) (PHB) production. To reduce the high production costs of PHB resulting from expensive raw materials, low productivity of the process and complexity of recovery steps, PHB biosynthetic genes (phbCAB), Vitreoscilla globin gene (vgb) and lytic genes of phage λ with an S amber mutation (S - RRz) were simultaneously introduced into the same recombinant Escherichia coli, VG1 (pTU14). This will have the advantages of using phbCAB with cheap raw materials and accumulating a high content of PHB, with the ability of vgb to enable a higher specific oxygen uptake rate by the cells, and the characteristics of S - RRz to realize controllable cell lysis. In the fermentation of VG1 (pTU14), starch hydrolysate was used in place of glucose as a cheaper carbon source, and a PHB concentration and productivity as high as 167.6g dm -3 and 3.05 g dm -3 h -1 were easily realized at almost zero levels of dissolved oxygen (DO), and with a simple temperature-inducing treatment for recovery PHB with a purity of at least 95% was easily harvested.