Genome-wide expression patterns associated with oncogenesis and sarcomatous transdifferentation of cholangiocarcinoma

BACKGROUND: The molecular mechanisms of CC (cholangiocarcinoma) oncogenesis and progression are poorly understood. This study aimed to determine the genome-wide expression of genes related to CC oncogenesis and sarcomatous transdifferentiation. METHODS: Genes that were differentially expressed between CC cell lines or tissues and cultured normal biliary epithelial (NBE) cells were identified using DNA microarray technology. Expressions were validated in human CC tissues and cells. RESULTS: Using unsupervised hierarchical clustering analysis of the cell line and tissue samples, we identified a set of 342 commonly regulated (>2-fold change) genes. Of these, 53, including tumor-related genes, were upregulated, and 289, including tumor suppressor genes, were downregulated (<0.5 fold change). Expression of SPP1, EFNB2, E2F2, IRX3, PTTG1, PPARγ, KRT17, UCHL1, IGFBP7 and SPARC proteins was immunohistochemically verified in human and hamster CC tissues. Additional unsupervised hierarchical clustering analysis of sarcomatoid CC cells compared to three adenocarcinomatous CC cell lines revealed 292 differentially upregulated genes (>4-fold change), and 267 differentially downregulated genes (<0.25 fold change). The expression of 12 proteins was validated in the CC cell lines by immunoblot analysis and immunohistochemical staining. Of the proteins analyzed, we found upregulation of the expression of the epithelial-mesenchymal transition (EMT)-related proteins VIM and TWIST1, and restoration of the methylation-silenced proteins LDHB, BNIP3, UCHL1, and NPTX2 during sarcomatoid transdifferentiation of CC. CONCLUSION: The deregulation of oncogenes, tumor suppressor genes, and methylation-related genes may be useful in identifying molecular targets for CC diagnosis and prognosis

The LAMOST Survey of Background Quasars in the Vicinity of the Andromeda and Triangulum Galaxies -- II. Results from the Commissioning Observations and the Pilot Surveys

We present new quasars discovered in the vicinity of the Andromeda and Triangulum galaxies with the LAMOST during the 2010 and 2011 observational seasons. Quasar candidates are selected based on the available SDSS, KPNO 4 m telescope, XSTPS optical, and WISE near infrared photometric data. We present 509 new quasars discovered in a stripe of ~135 sq. deg from M31 to M33 along the Giant Stellar Stream in the 2011 pilot survey datasets, and also 17 new quasars discovered in an area of ~100 sq. deg that covers the central region and the southeastern halo of M31 in the 2010 commissioning datasets. These 526 new quasars have i magnitudes ranging from 15.5 to 20.0, redshifts from 0.1 to 3.2. They represent a significant increase of the number of identified quasars in the vicinity of M31 and M33. There are now 26, 62 and 139 known quasars in this region of the sky with i magnitudes brighter than 17.0, 17.5 and 18.0 respectively, of which 5, 20 and 75 are newly-discovered. These bright quasars provide an invaluable collection with which to probe the kinematics and chemistry of the ISM/IGM in the Local Group of galaxies. A total of 93 quasars are now known with locations within 2.5 deg of M31, of which 73 are newly discovered. Tens of quasars are now known to be located behind the Giant Stellar Stream, and hundreds behind the extended halo and its associated substructures of M31. The much enlarged sample of known quasars in the vicinity of M31 and M33 can potentially be utilized to construct a perfect astrometric reference frame to measure the minute PMs of M31 and M33, along with the PMs of substructures associated with the Local Group of galaxies. Those PMs are some of the most fundamental properties of the Local Group.Comment: 26 pages, 6 figures, AJ accepte

Separation and economic recovery of strontium from Nanyishan oil-field water, China

The mass ratio of Ca to Sr is greater than 10 in Nanyishan oil-field water, which causes significant problems during the economic extraction and recovery of selected trace elements in the oil-field water. The oilfield water was isothermally evaporated and various salts such as Li, K, Mg, Ca, Na, Sr, Rb, Cs, Br, and I were obtained from the solution. The Sr content of each phase was determined by ICP-AES, the Sr distribution rule in this process was obtained, and the best separation stage for Sr was identified, to optimize the separation of Sr from Nanyishan oil-field water

The D-wave heavy-light mesons from QCD sum rules

We study the D-wave c_bar s heavy meson doublets (1^-,2^-) and (2^-,3^-) using the method of QCD sum rule in the framework of heavy quark effective theory. Choosing the same threshold values omega_c around 2.7 Gev, we calculate the masses of the 1^- and 3^- states. They are m_{D*_{s1}} = 2.81 \pm 0.10 GeV and m_{D*_{s3}} = 2.85 \pm 0.08 GeV, consistent with the newly observed D*_{s1}(2860) and D*_{s3}(2860) states by LHCb. The masses of their 2^- partners are calculated to be 2.82 \pm 0.10 and 2.81 \pm 0.08 GeV. The mass splittings within the same doublet are calculated to be m_{D_{s2}} - m_{D*_{s1}} = 0.016 \pm 0.007 GeV and m_{D*_{s3}} - m_{D'_{s2}} = 0.039 \pm 0.014 GeV.Comment: 8 pages, 6 figures, accepted by PR

Genomewide association study of leprosy.

BACKGROUND: The narrow host range of Mycobacterium leprae and the fact that it is refractory to growth in culture has limited research on and the biologic understanding of leprosy. Host genetic factors are thought to influence susceptibility to infection as well as disease progression. METHODS: We performed a two-stage genomewide association study by genotyping 706 patients and 1225 controls using the Human610-Quad BeadChip (Illumina). We then tested three independent replication sets for an association between the presence of leprosy and 93 single-nucleotide polymorphisms (SNPs) that were most strongly associated with the disease in the genomewide association study. Together, these replication sets comprised 3254 patients and 5955 controls. We also carried out tests of heterogeneity of the associations (or lack thereof) between these 93 SNPs and disease, stratified according to clinical subtype (multibacillary vs. paucibacillary). RESULTS: We observed a significant association (P<1.00x10(-10)) between SNPs in the genes CCDC122, C13orf31, NOD2, TNFSF15, HLA-DR, and RIPK2 and a trend toward an association (P=5.10x10(-5)) with a SNP in LRRK2. The associations between the SNPs in C13orf31, LRRK2, NOD2, and RIPK2 and multibacillary leprosy were stronger than the associations between these SNPs and paucibacillary leprosy. CONCLUSIONS: Variants of genes in the NOD2-mediated signaling pathway (which regulates the innate immune response) are associated with susceptibility to infection with M. leprae

Effect of Low Power Laser Irradiation on the Ability of Cell Growth and Myogenic Differentiation of Myoblasts Cultured In Vitro

As a therapeutic modality, low power laser irradiation (LPLI) has been used clinically in the treatment of skeletal muscle injuries and other myopathic conditions, but the cellular and molecular mechanisms attributed to this therapy were still unclear. Myoblasts are a type of myogenic stem cells quiescence in mature skeletal muscle fibers and are considered as the source cells during the regenerating process. The purpose of this paper was to investigate the effects of LPLI on the proliferation and myogenic differentiation of the cultured myoblasts and to find out the major candidates responsible for LPLI-induced muscle regeneration in vivo. In this study, primary rat myoblasts were exposed to helium-neon (He-Ne) laser. Cell proliferation, differentiation, and the cellular responses to LPLI were monitored by using morphological observation and molecular biological methods. It was found that LPLI at a certain fluence could increase the cell growth potential for myoblasts and further induce more cells entering into S phase of the mitotic cycle as indicated by high levels of bromodeoxyuridine (BrdU) incorporation, while at the same time inhibiting their in vitro differentiation and decreasing the expression of myogenic regulatory genes to a certain extent. Taken together, these results provide experimental evidence for the clinical applications of LPLI in regenerating skeletal muscle

Stimulative Effects of Low Intensity He-Ne Laser Irradiation on the Proliferative Potential and Cell-Cycle Progression of Myoblasts in Culture

Low intensity laser irradiation (LILI) was found to promote the regeneration of skeletal muscle in vivo but the cellular mechanisms are not fully understood. Myoblasts, normally quiescent and inactivated in adult skeletal muscle, are a type of myogenic progenitor cells and considered as the major candidates responsible for muscle regeneration. The aim of the present study was to study the effect of LILI on the growth potential and cell-cycle progression of the cultured myoblasts. Primary myoblasts isolated from rat hind legs were cultured in nutrient-deficient medium for 36 hours and then irradiated by helium-neon laser at a certain energy density. Immunohistochemical and flow cytometric analysis revealed that laser irradiation could increase the expression of cellular proliferation marker and the amount of cell subpopulations in the proliferative phase as compared with the nonirradiated control group. Meanwhile, the expressions of cell-cycle regulatory proteins in the laser-treated myoblasts were markedly upregulated as compared to the unirradiated cells, indicating that LILI could promote the reentry of quiescent myoblasts into the cell division cycle. These results suggest that LILI at certain fluences could promote their proliferation, thus contributing to the skeletal muscle regeneration following trauma and myopathic diseases

NOLC1 suppresses immunochemotherapy by inhibiting p53-mediated ferroptosis in gastric cancer

Human gastric cancer (GC) is one of the most malignant cancers, and cisplatin (Cis)-based chemotherapy remains the main clinical treatment for GC. However, Cis resistance often occurs, largely limiting its therapeutic efficacy in tumors. Therefore, a better understanding of the drug resistance mechanism could reveal new approaches for improving GC treatment efficacy. Here, we define the integrative role of nucleolar and coiled-body phosphoprotein 1 (NOLC1), a molecular chaperone that is significantly upregulated in GC tissues and Cis-resistant GC cells. Knocking down NOLC1 increased GC sensitivity to Cis by regulating ferroptosis. Mechanistically, NOLC1 binds to the p53 DNA-binding domain (DBD), decreasing p53 nuclear accumulation stimulated by Cis and suppressing p53 transcriptional functions. Then, the p53-mediated ferroptosis is suppressed. Furthermore, the silence of NOLC1 promoted ferroptosis-induced immunogenic cell death (ICD) and reprogrammed the immunosuppressive tumor microenvironment, thereby increasing sensitivity to anti-programmed cell death-1 (PD-1) therapy plus Cis. The combination of anti-PD-1 plus Cis effectively inhibited GC growth without significant side effects. In summary, our findings reveal that targeting NOLC1 may be a novel therapeutic strategy for GC and may increase the efficacy of chemotherapy combined with immune checkpoint inhibitor (ICI) therapy

Relationships between athletic ability and academic performance in primary school students: A 3-year follow-up study

BackgroundThe aim of this study was to examine whether academic performance is associated with students' athletic ability in primary school.MethodsA 3-year follow-up study was conducted among 1,136 Chinese students. Sit-up and jump rope testers were used to measure 1-min sit-ups and 1-min jump ropes, respectively. Meanwhile, the Pittsburgh Sleep Quality Scale and the Beck Depression Inventory were used to estimate sleep quality and depression levels. The end-of-semester examinations were used to evaluate students' academic performance during the follow-up period.ResultsAfter adjusting for confounders, the mean change in Chinese language performance for participants stratified by 1-min sit-ups at baseline was 0.35 (95% CI: −0.37 to 0.76) for level 1 (slowest), 0.52 (95% CI: −0.54 to 1.08) for level 2, and 1.72 (95% CI: 1.14 to 2.30) for level 3 (fastest) (P for trend = 0.003); the mean change in math scores was 0.28 (95% CI: −0.50 to 0.95) for level 1 (slowest), 0.95 (95% CI: 0.38 to 1.52) for level 2, and 1.41 (95% CI: 0.82 to 1.99) for level 3 (fastest) (P for trend = 0.048). The mean change in foreign language scores was −0.45 (95% CI: −0.99 to −0.93) for level 1 (slowest), −0.14 (95% CI: −0.44 to 0.41) for level 2, and 0.69 (95% CI: 0.25 to 1.13) for level 3 (fastest) (P for trend = 0.004). The mean change in Chinese language performance for participants stratified by 1-min jump ropes at the baseline was 0.30 (95% CI: −0.16 to 0.76) for level 1 (slowest), 1.09 (95% CI: 0.42 to 1.76) for level 2, and 1.74 (95% CI: 1.14 to 2.35) for level 3 (fastest) (P for trend = 0.001). The mean change in math scores was 0.41 (95% CI: −0.11 to 0.92) for level 1 (slowest), 1.44 (95% CI: 0.69 to 2.19) for level 2, and 1.43 (95% CI: 0.76 to 2.10) for level 3 (fastest) (P for trend = 0.019). The mean change in foreign language performance was −0.71 (95% CI: −1.08 to −0.33) for level 1 (slowest), 0.95 (95% CI: −0.40 to 1.50) for level 2, and 0.91 (95% CI: 0.41 to 1.41) for level 3 (fastest) (P for trend &lt; 0.001).ConclusionThis study suggests that participation in jump rope and sit-up exercises may positively affect students' academic performance