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Gastric cancer (GC) is a common heterogeneous disease. The critical roles of microRNA-340 (miR-340) in the development and progression of GC were emphasized in accumulating studies. This study aims to examine the regulatory mechanism of miR-340 in GC cellular processes. Initially, microarray technology was used to identify differentially expressed genes and regulatory miRs in GC. After that, the potential role of miR-340 in GC was determined via ectopic expression, depletion, and reporter assay experiments. Expression of secreted phosphoprotein 1 (SPP1), miR-340, phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) pathway, and epithelial-mesenchymal transition (EMT)-related genes was measured. Moreover, to further explore the function of miR-340 in vivo and in vitro, proliferation, apoptosis, migration, invasion, and tumorigenic capacity were evaluated. SPP1 was a target gene of miR-340 which could then mediate the PI3K/AKT signaling pathway by targeting SPP1 in GC. Furthermore, miR-340 levels were reduced and SPP1 was enriched in GC tissues and cells, with the PI3K/AKT signaling pathway being activated. Inhibitory effects of upregulated miR-340 on SPP1 and the PI3K/AKT signaling pathway were confirmed in vivo and in vitro. Overexpression of miR-340 or the silencing of SPP1 inhibited GC cell proliferation, invasion, migration, and EMT process, but promoted apoptosis of GC cells. Typically, targeting of SPP1 by miR-340 may contribute to the inhibition of proliferation, migration, invasion, and EMT of GC cells via suppression of PI3K/AKT signaling pathway.

Recently, dedicator of cytokinesis 2 (DOCK2) has been reportedly exhibited high mutation prevalence in the Asian colorectal cancer (CRC) cohort. However, the expression pattern of DOCK2 and its clinical significance in CRC were still unknown. To characterize the role of DOCK2, a tissue microarray (TMA) containing 481 archived paraffin-embedded CRC specimens was performed by immunohistochemistry. Among which, 54 primary CRC tissues showed high expression of DOCK2 protein, while others were negative. Moreover, DOCK2 expression was positively associated with invasion depth (P < .001) and tumor size (P = .016). Significantly, Kaplan-Meier survival analysis revealed that patients with higher DOCK2 expression had a longer overall survival time (P = .017). Furthermore, univariate and multivariate Cox regression analysis confirmed that DOCK2 is an independent prognostic marker in CRC (P = .049,; HR, 0.519; 95% CI, 0.270 to 0.997). In addition, we observed a strong correlation between the infiltration of CD8+ T lymphocytes and DOCK2 expression (P = .0119). Our findings demonstrated that overexpressed DOCK2 might involve in recruiting CD8+ T lymphocytes and serve as a novel prognostic indicator and indicated a potential therapeutic strategy by restoring DOCK2 for CRC.

Objectives Circular RNAs (circRNAs) exist extensively in the eukaryotic genome. The study aimed to identify the role of hsa_circ_0008365 (Circ‐SERPINE2) in gastric carcinoma (GC) cells and its downstream mechanisms. Materials and methods Gene Expression Omnibus (GEO) database was applied to screen differentially expressed circRNAs. CircInteractome, TargetScan and miRecords websites were used to predict target relationships. qRT‐PCR and RNase R treatment were utilised to detect molecule expression and confirm the existence of circ‐SERPINE2. RNA pull‐down assay and dual‐luciferase reporter assay were performed for interaction between circRNA and miRNA or mRNA. EdU assay, colony formation assay, and flow cytometry for apoptosis and cell cycle detections were utilised to assess cell function. Western blot and immunohistochemistry (IHC) assays were applied for detection of proteins in tissues or cells. Results Circ‐SERPINE2 and YWHAZ were upregulated, and miR‐375 was downregulated in GC tissues and cells. Circ‐SERPINE2 and YWHAZ targetedly bound to miR‐375. Circ‐SERPINE2 promoted cell proliferation and cell cycle progress and inhibited cell apoptosis by sponging miR‐375 and regulating YWHAZ expression in vitro. Circ‐SERPINE2 repressed solid tumour growth through enhancing miR‐375 expression and reducing YWHAZ expression in vivo. Conclusions Circ‐SERPINE2 is a novel proliferative promoter through the regulation of miR‐375/YWHAZ. Circ‐SERPINE2/miR‐375/YWHAZ axis might provide a novel therapeutic target of GC.

Dissolved oxygen (DO) is an important influencing factor in the process of aerobic microbial fermentation. Spinosad is an aerobic microbial-derived secondary metabolite. In our study, spinosad was used as an example to establish a DO strategy by multi-scale analysis, which included a reactor, cell and gene scales. We changed DO conditions that are related to the characteristics of cell metabolism (glucose consumption rate, biomass accumulation and spinosad production). Consequently, cell growth was promoted by maintaining DO at 40% in the first 24 h and subsequently increasing DO to 50% in 24 h to 96 h. In an in-depth analysis of the key enzyme genes (gtt, spn A, spn K and spn O), expression of spinosad and specific Adenosine Triphosphate (ATP), the spinosad yield was increased by regulating DO to 30% within 96 h to 192 h and then changing it to 25% in 192 h to 240 h. Under the four-phase DO strategy, spinosad yield increased by 652.1%, 326.1%, 546.8%, and 781.4% compared with the yield obtained under constant DO control at 50%, 40%, 30%, and 20% respectively. The proposed method provides a novel way to develop a precise DO strategy for fermentation.

For a complementary hydrogen-bonded complex, when every hydrogen-bond acceptor is on one side and every hydrogen-bond donor is on the other, all secondary interactions are attractive and the complex is highly stable. AAA-DDD (A=acceptor, D=donor) is considered to be the most stable among triply hydrogen-bonded sequences. The easily synthesized and further derivatized AAA-DDD system is very desirable for hydrogen-bonded functional materials. In this case, AAA and DDD, starting from 4-methoxybenzaldehyde, were synthesized with the Hantzsch pyridine synthesis and Friedländer annulation reaction. The association constant determined by fluorescence titration in chloroform at room temperature is 2.09×10(7) M(-1) . The AAA and DDD components are not coplanar, but form a V shape in the solid state. Supramolecular polymers based on AAA-DDD triply hydrogen bonded have also been developed. This work may make AAA-DDD triply hydrogen-bonded sequences easily accessible for stimuli-responsive materials.

B-lymphoma mouse Moloney leukemia virus insertion region 1 (Bmi1), a member of the polycomb group, has elevated expression and is involved in the pathogenesis of various aggressive cancers, including nasopharyngeal carcinoma (NPC). To date, the mechanisms underlying the high expression of Bmi1 in NPC remain obscure. To gain new insights into the transcriptional regulation of BMI1, we cloned and characterized the promoter region of BMI1. Luciferase reporter assays demonstrated that the region from -783 to +375 showed significant promoter activity. With the use of a series of 5'-deletion and 3'-deletion promoter constructs in luciferase reporter assays, the +167/+232 and -536/-134 regions were found to be sufficient for full promoter activity. Transcriptional activity of the BMI1 promoter was dependent on the Sp1 binding site cluster (+181/+214) as well as the E-box elements (-181), and was abolished after mutation of the two cis-elements. Electrophoretic mobility shift assays and chromatin immunoprecipitation assays demonstrated that Sp1 bound to the region from +181 to +214 within the BMI1 promoter. In addition, gain-of-function and loss-of-function analyses revealed that Sp1 augmented Bmi1 expression. Further investigations using immunohistochemistry and quantitative RT-PCR disclosed a significant positive correlation between the expression of Sp1 and Bmi1 in normal nasopharyngeal epithelial cells, NPC cells, and NPC tissue specimens. In addition, Myc, the known transcription factor for BMI1 in neuroblastomas, also activated the transcription of BMI1 through binding to the E-box element (-181) within its promoter, and showed a positive correlation with the mRNA level of BMI1 in NPC. In conclusion, these findings provide valuable mechanistic insights into the role of Sp1 and c-Myc in BMI1 transcription in NPC, and suggest that targeting of Sp1 or c-Myc may be a potential therapeutic strategy for NPC.

A simple and versatile method for highly efficient synthesis of various polysubstituted indoles via a sequential one-pot Rh(III)-catalyzed direct C2–H and C7–H alkylation with diazo compounds has been developed. This process features with mild reaction conditions, wide substrate scope, and good functional group tolerance (24 examples, up to 96% yield).

The overexpression of centromere protein H (CENPH), one of the fundamental components of the human active kinetochore, has been shown to be closely associated with human cancers. However, the mechanism of its transcriptional regulation has not been reported. The aim of the present study was to investigate the regulatory elements for the transcriptional regulation of CENPH in nasopharyngeal carcinoma cells. To characterize the CENPH promoter and identify regulatory elements, we cloned 1015 bp (−975/+40 bp) of the 5′-flanking region of the CENPH gene from immortalized normal nasopharyngeal epithelial cells (Bmi-1/NPEC). Functional analysis established a minimal region (−140/−87 bp) involved in the regulation of human CENPH promoter activity. Through site-directed mutagenesis, a transactivation assay, chromatin immunoprecipitation, and electrophoretic mobility shift assay, we found that the Sp1/Sp3 transcription factors could bind to the CENPH promoter in vitro and in vivo, and that they regulated CENPH promoter activation in human nasopharyngeal carcinoma cells. Furthermore, Sp1 and Sp3 were highly expressed in nasopharyngeal carcinoma cells. Knockdown of Sp1 and Sp3 by small interfering RNA or inhibition of Sp1 and Sp3 activity by mithramycin A decreased CENPH mRNA expression, whereas the exogenous expression of Sp1 and Sp3 upregulated CENPH mRNA expression. Taken together, our results indicate that Sp1 and Sp3 bind to the CENPH minimal promoter and function as a regulator of the transcription of CENPH in human nasopharyngeal carcinomas.

In order to investigate the paleoclimatic changes in S China during the late Quaternary and their influence on pedogenesis and soil classification, a yellow-brown earth (YBE)-red clay (RC) profile in Langxi County, Anhui Province was studied. The grain-size distribution and the major- and trace-element compositions of the profile indicate that the YBE of the profile shares the same origin with the YBE in Jiujiang and Xuancheng and the Xiashu loess in Zhenjiang, and the underlying RC also has aeolian characteristics and shares the same origin with the Xiashu loess. Grain-size characteristics, molecular ratios of SiO 2 /Al 2 O 3 , SiO 2 /(Al 2 O 3 +Fe 2 O 3 ), and BA ([CaO+MgO+K 2 O+Na 2 O]/Al 2 O 3 ) and other weathering indices (CaO/TiO 2 , MgO/TiO 2 , K 2 O/TiO 2 , Na 2 O/TiO 2 , and Rb/Sr) of the profile indicate that the RC is more strongly weathered than the YBE. Magnetic susceptibility (Χ lf ) of the uniform red clay (URC) of the profile is significantly enhanced. However, that of the underlying reticulate red clay (RRC) is significantly decreased because of the paleogroundwater movement and cannot indicate its strong weathering properties. The YBE-RC profile in Langxi County recorded a great climatic change during late Quaternary: At that time, the pedogenic development of the RC was terminated and widespread dust deposition occurred. The parent material of the RC may be aeolian deposits which were accumulated before the last interglacial and were strongly weathered and rubified under the subsequent interglacial climate. It is observed that red soils, derived from the RC, and yellow-brown soils, derived from the YBE, coexist in the study area, which is contradictive to the theory of the zonal distribution of soils. Therefore, it is necessary to take into account the history of Quaternary climatic changes when studying pedogenesis.

Tryptophan-thymine dimer model compounds used to mimic the repair reaction of DNA photolyase have been synthesized. The photosensitized cleavage of the dimer by the covalently linked tryptophan is strongly solvent-dependent with the reaction rates increasing in increasingly polar solvents, for example, the quantum yield Φ = 0.004 in THF/hexane (5:95) and 0.093 in water. The fluorescence of the tryptophan residue is quenched by the dimer moiety by electron transfer from the excited tryptophan to the dimer. Fluorescence-quenching studies indicated that the electron transfer was efficient in polar solvents. The splitting efficiency of the dimer radical anion within the tryptophan·+–dimer·– species is also remarkably solvent-dependent and increases with the polarity of the solvents. The back-electron-transfer reaction in the charge-separated species, which competes with cleavage, was suppressed in polar solvents. These results are in contrast to those of earlier solvent-dependent studies of indole-dimer systems, but they can be rationalized in terms of the differences in the distances between the chromophore unit and the attached dimer. The pH-dependent measurements of the splitting reaction and the deuterium isotope effect showed that the tryptophan radical cation within the charge-separated species does not deprotonate prior to the cleavage of the dimer radical anion. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)