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Background and Purpose: Cancer cachexia and cancer‐associated thrombosis are potentially fatal outcomes of advanced cancer. Nevertheless, thrombin expression in non‐small cell lung cancer (NSCLC) primary tumour tissues and the association between prognosis of NSCLC patients remain largely unknown. Experimental Approach Clinical pathological analysis was performed to determine the relationship between thrombin and tumour progression. Effects of r‐hirudin and direct thrombin inhibitor peptide (DTIP) on cancer progression were evaluated. Western blotting, immunohistochemistry, and immunofluorescence were used to explore the inhibition mechanism of r‐hirudin and DTIP. The therapeutic effect of the combination of DTIP and chemotherapy was determined. Key Results: Thrombin expression in NSCLC tissues was closely related to clinicopathological features and the prognosis of patients. Thrombin deficiency inhibited tumour progression. The novel thrombin inhibitors, r‐hirudin and DTIP, inhibited cell invasion and metastasis in vitro. They inhibited tumour growth and metastasis in orthotopic lung cancer model, inhibited cell invasion, and prolonged survival after injection of tumour cells via the tail vein. They also inhibited angiogenesis and spontaneous metastases from subcutaneously inoculated tumours. The promotion by thrombin of invasion and metastasis was abolished in PAR‐1‐deficient NSCLC cells. r‐hirudin and DTIP inhibited tumour progression through the thrombin‐PAR‐1‐mediated RhoA and NF‐κB signalling cascades via inhibiting MMP9 and IL6 expression. DTIP potentiated chemotherapy‐induced growth and metastatic inhibition and inhibited chemotherapy‐induced resistance in mice. Conclusions and Implications: Thrombin makes a substantial contribution, together with PAR‐1, to NSCLC malignancy. The anti‐coagulants, r‐hirudin and DTIP, could be used in anti‐tumour therapy and a combination of DTIP and chemotherapy might improve therapeutic effects. [ABSTRACT FROM AUTHOR]

Forming tight interaction with both Purkinje and granule cells (GCs), Bergmann glia (BG) are essential for cerebellar morphogenesis and neuronal homeostasis. However, how BG act in this process is unclear without comprehensive transcriptome landscape of BG. Here, high temporal‐resolution investigation of transcriptomes with FACS‐sorted BG revealed the dynamic expression of genes within given functions and pathways enabled BG to assist neural migration and construct neuron‐glia network. It is found that the peak time of GCs migration (P7‐10) strikingly coincides with the downregulation of extracellular matrix (ECM) related genes, and the disruption of which by Setdb1 ablation at P7‐10 in BG leads to significant migration defect of GCs emphasizing the criticality of Nfix‐Setdb1 mediated H3K9me3 repressive complex for the precise regulation of GCs migration in vivo. Thus, BG's transcriptomic landscapes offer an insight into the mechanism by which BG are in depth integrated in cerebellar neural network. [ABSTRACT FROM AUTHOR]

Background: Hepatocellular carcinoma (HCC) remains one of the most common cancers worldwide and tends to be detected at an advanced stage. More effective biomarkers for HCC screening and prognosis assessment are needed and the mechanisms of HCC require further exploration. The role of MAOA in HCC has not been intensively investigated. Methods: In‐house tissue microarrays, genechips, and RNAsequencing datasets were integrated to explore the expression status and the clinical value of MAOA in HCC. Immunohistochemical staining was utilized to determine MAOA protein expression. Intersection genes of MAOA related co‐expressed genes and differentially expressed genes were obtained to perform functional enrichment analyses. In vivo experiment was conducted to study the impact of traditional Chinese medicine nitidine chloride (NC) on MAOA in HCC. Results: MAOA was downregulated and possessed an excellent discriminatory capability in HCC patients. Decreased MAOA correlated with poor prognosis in HCC patients. Downregulated MAOA protein was relevant to an advanced TNM stage in HCC patients. Co‐expressed genes that positively related to MAOA were clustered in chemical carcinogenesis, where CYP2E1 was identified as the hub gene. In vivo experiment showed that nitidine chloride significantly upregulated MAOA in a nude mouse HCC model. Conclusions: A decreased MAOA level is not only correlated with aggressive behaviors in males but also serves as a promising biomarker for the diagnosis and prognosis of HCC patients. Moreover, MAOA may play a role in AFB1 toxic transformation through its synergistic action with co‐expressed genes, especially CYP3A4. MAOA also serves as a potential therapy target of NC in HCC patients. [ABSTRACT FROM AUTHOR]

Pitaya is rich in nutrition and unique in function and contains vegetable albumin, anthocyanins, rich vitamins, and water soluble dietary fiber, which are rare in fruits and vegetables. However, researches mostly focused on pitaya cultivation, biological characteristics, fresh‐keeping, and lacked analyses about chemical composition of pitaya. Therefore, ethanol extraction and GC/MS were used to extract and identify the bioactive components in pulp and pericarp of red pitaya and white pitaya. The extracting results showed that percentages of ethanol extracts from pulp and pericarp of red pitaya were 14.5% and 12%, whereas those of white pitaya were 16% and 12%. The GC/MS results showed that different kinds of bioactive constituents were identified in fresh pericarp and pulp of red pitaya and white pitaya. In the four ethanol extracts, there are rich polysiloxane plant organosilicon with total contents of 10.09%, 24.21%, 25.77%, and 23.25%. Meanwhile, there are many heterocyclic substances, and the content of pericarp is much higher than that of pulp. The four ethanol extracts also contain some other bioactive ingredients, such as esters, hydrocarbons, alcohols, amides, halides, and fatty acids, which can be used as raw materials for biomedicine, advanced cosmetics, and skin care products. [ABSTRACT FROM AUTHOR]

Lung squamous cell carcinoma (LUSC) is the main pathological type of pulmonary malignant tumors; at present, less than 10% of patients with advanced metastatic LUSC live for more than 5 years. We previously reported that low expression of miRNA‐126‐3p is associated with the occurrence and progression of lung adenocarcinoma (LUAD). Here, we examined expression of miRNA‐126‐3p in 23 samples from patients with LUSCs and 23 normal control specimens by quantitative real‐time PCR (RT‐qPCR). Associations between miRNA‐126‐3p expression and clinical features were studied from materials derived from Gene Expression Omnibus (GEO) chips and The Cancer Genome Atlas (TCGA) database. Twelve online platforms were used to identify candidate target genes of miRNA‐126‐3p. Further analyses of the Kyoto Encyclopedia of Genes and Genomes (KEGG), Gene Ontology (GO), and protein–protein interaction (PPI) network were performed on the target genes. GEO microarray analysis, TCGA data mining, RT‐qPCR, and integration analysis consistently reported low expression of miRNA‐126‐3p in LUSC. A total of 42 genes were identified as potential target genes of miRNA‐126‐3p from online platforms, GEO microarrays, and the TCGA database. GO and KEGG analyses demonstrated that the target genes are involved in several biological processes that promote the progression of LUSC. SOX2, E2F2, and E2F3 were selected as hub genes from the PPI network for further analysis. In summary, our results suggest that the low expression of miRNA‐126‐3p may play a role in promoting the development of LUSC and miRNA‐126‐3p may be a biomarker for LUSC early diagnosis and prognosis. [ABSTRACT FROM AUTHOR]

B-cell maturation antigen (BCMA) fused at the C-terminus to the Fc portion of human IgG1 (BCMA-Fc) blocks B-cell activating factor (BAFF) and proliferation-inducing ligand (APRIL)-mediated B-cell activation, leading to immune disorders. The fusion protein has been cloned and produced by several engineering cell lines. To reduce cost and enhance production, we attempted to express recombinant human BCMA-Fc (rhBCMA-Fc) in Pichia pastoris under the control of the AOX1 methanol-inducible promoter. To produce the target protein with uniform molecular weight and reduced immunogenicity, we mutated two predicted N-linked glycosylation sites. The secretory yield was improved by codon optimization of the target gene sequence. After fed-batch fermentation under optimized conditions, the highest yield (207 mg/L) of rhBCMA-Fc was obtained with high productivity (3.45 mg/L/h). The purified functional rhBCMA-Fc possessed high-binding affinity to APRIL and dose-dependent inhibition of APRIL-induced proliferative activity in vitro through three-step purification. Thus, this yeast-derived expression method could be a low-cost and effective alternative to the production of rhBCMA-Fc in mammalian cell lines. [ABSTRACT FROM AUTHOR]

Accumulating evidence suggests the immunosuppressive microenvironments created by malignant tumors represent a major obstacle for effective anti-tumor immunity. A better understanding of the suppressive mechanisms mediated by tumor microenvironments and the development of strategies to reverse the immune suppression are major challenges for the success of tumor immunotherapy. Here, we report that human tumor cells can induce senescence in naïve/effector T cells, exhibiting potent suppressive function in vitro and in vivo. We further show that tumor-derived endogenous cyclic adenosine monophosphate ( cAMP) is responsible for the induction of T-cell senescence. Importantly, activation of TLR8 signaling in tumor cells can block the induction and reverse the suppression of senescent naïve and tumor-specific T cells in vitro and in vivo, resulting in enhanced anti-tumor immunity. These studies identify a novel mechanism of human tumor-mediated immune suppression and provide a new strategy to reverse tumor immunosuppressive effects for tumor immunotherapy. [ABSTRACT FROM AUTHOR]

Z-source inverters are inverters with buck-boost capability that traditional inverters cannot match. Despite this ability, present Z-source topologies are burdened by some limitations such as chopping input current, high-voltage stress and poor spectral performance at high gain. To improve their performances, a number of asymmetrical transformer-based embedded Z-source inverters are proposed. Through theoretical derivation and experiments, the proposed inverters have been shown to draw a smooth input current and produce a high gain by varying the transformer turns ratio n. The range of variation for n depends on the inverter topology chosen, which in turn depends on the application under consideration. [ABSTRACT FROM AUTHOR]

The article presents a study which synthesized a silicone-containing polymer by addition polymerization between 1,12-bis(3-methyl-3-oxetanyl)-2,5,8,11-tetraoxadodecane and dichloridedimethylsilane catalyzed by tetrabutylammonium bromide. The polymer was also characterized by Fourier transform infrared spectroscopy, gel permeation chromatography, and differential scanning calorimetry analyses. Results showed that the polymer electrolyte was electrochemical stable until 4.3 V.

Abstract: Previous studies have illustrated that hnRNP K, which could be methylated at arginine residues, plays a key role in coordinating transcriptional responses to DNA damage as a cofactor for p53. In this study, we observed that hnRNP K was markedly arginine methylated in response to UV radiation. Furthermore, arginine methylation of hnRNP K enhanced its affinity with p53. Inhibition of methylation in hnRNP K attenuated the recruitment of p53 to p21 promoter, and reduced p53 transcriptional activity. These data suggested that arginine methylation of hnRNP K is a key element for p53 transcriptional activity. [Copyright &y& Elsevier]

Aims To investigate the association of CYP2C9* 3 and * 6 with hyperlipidaemia in Chinese. Methods Four hundred and seventy-six Chinese participated in the study, including 211 uncomplicated hyperlipidaemic patients and 265 healthy controls. PCR-RFLP was used to identify CYP2C9* 3 and * 6. Results CYP2C9* 6 was not detected in this study. The allelic frequency of CYP2C9* 3 was 0.039 (95% CI 0.022, 0.056). A nonsignificant difference existed in CYP2C9* 3 frequencies between males and females ( P = 0.605, OR = 1.194, 95% CI 0.610, 2.336), patients and controls ( P = 0.063, OR = 0.506, 95% CI 0.244, 1.049) in the total population. However, in the female group, CYP2C9* 3 frequency in patients with hyperlipidaemia was significantly lower than that in controls ( P < 0.0001, OR = 0.062, 95% CI 0.008, 0.476). Conclusions The association of CYP2C9* 3 with hyperlipidaemia was specific for females in this Chinese population. [ABSTRACT FROM AUTHOR]

In the title compound, C18H22O4, the cyclo-hexane and cyclo-hexa-none rings adopt normal chair and half-chair conformations, respectively. The dioxolane ring is almost planar, with an r.m.s. deviation of 0.094 (3) Å. In the crystal, mol-ecules are connected by O-H⋯O hydrogen bonds, forming 21 helical chains along the a-axis direction. The chains are further connected by C-H⋯O hydrogen bonds.

The title compound, C(11)H(10)Cl(2), is a useful inter-mediate for the synthesis of 1H-cyclo-propa[b]naphthalene. Strain in the mol-ecule is evidenced by the fact that the cyclo-hexane ring is essentially planar and nearly coplanar with the benzene ring [dihedral angle 1.87 (18)°], and the cyclo-propyl ring is almost perpendicular to the cyclo-hexane ring [dihedral angle 70.99 (12)°]. The mol-ecules are loosely connected into one-dimensional chains by inter-molecular Cl⋯Cl inter-actions with a distance of 3.571 (1) Å. The centroid-to-centroid distance between stacked benzene rings is ca 5.89 Å, indicating that no π-π stacking exists in the crystal structure.

DGR [staphylokinase (Sak) variant K35R, in which lysine (K) at position 35 is replaced by arginine (R)], a recombinant mutant of the Staphylococcus aureus enzyme, is a promising drug for thrombotic disorders. In the present work, DGR was successfully overexpressed by the plasmid JF1125[pST-DGR] as a soluble cytoplasmic protein in a 30-litre fermentor that accounted for more than 50% of the total cellular protein. The expressed DGR was subsequently purified by using a simple three-step chromatographic purification process developed at a pilot scale. The clearance of host-cell-protein contaminants in the protein purification process was confirmed by SDS/PAGE and Western blotting, using rabbit antisera raised against Escherichia coli JF1125 cell proteins. SDS/PAGE, isoelectric focusing and HPLC-MS analysis indicated that the purified DGR is almost completely homogeneous. The purification process resulted in greater-than-98% pure DGR and yielded up to 25.0 mg/g wet weight of cells. The effect of pH and temperature on the stability of DGR was investigated further. The results showed that DGR was highly stable at neutral pH and more stable than two other wild-type Saks, SakSTAR and Sak42D, when submitted to high temperatures.

Aims: To investigate the association of CYP2C9*3 and *6 with hyperlipidaemia in Chinese., Methods: Four hundred and seventy-six Chinese participated in the study, including 211 uncomplicated hyperlipidaemic patients and 265 healthy controls. PCR-RFLP was used to identify CYP2C9*3 and *6., Results: CYP2C9*6 was not detected in this study. The allelic frequency of CYP2C9*3 was 0.039 (95% CI 0.022, 0.056). A nonsignificant difference existed in CYP2C9*3 frequencies between males and females (P = 0.605, OR = 1.194, 95% CI 0.610, 2.336), patients and controls (P = 0.063, OR = 0.506, 95% CI 0.244, 1.049) in the total population. However, in the female group, CYP2C9*3 frequency in patients with hyperlipidaemia was significantly lower than that in controls (P < 0.0001, OR = 0.062, 95% CI 0.008, 0.476)., Conclusions: The association of CYP2C9*3 with hyperlipidaemia was specific for females in this Chinese population.