Genetically engineered pre-microRNA-34a prodrug suppresses orthotopic osteosarcoma xenograft tumor growth via the induction of apoptosis and cell cycle arrest.

Osteosarcoma (OS) is the most common primary malignant bone tumor in children, and microRNA-34a (miR-34a) replacement therapy represents a new treatment strategy. This study was to define the effectiveness and safety profiles of a novel bioengineered miR-34a prodrug in orthotopic OS xenograft tumor mouse model. Highly purified pre-miR-34a prodrug significantly inhibited the proliferation of human 143B and MG-63 cells in a dose dependent manner and to much greater degrees than controls, which was attributed to induction of apoptosis and G2 cell cycle arrest. Inhibition of OS cell growth and invasion were associated with release of high levels of mature miR-34a from pre-miR-34a prodrug and consequently reduction of protein levels of many miR-34a target genes including SIRT1, BCL2, c-MET, and CDK6. Furthermore, intravenous administration of in vivo-jetPEI formulated miR-34a prodrug significantly reduced OS tumor growth in orthotopic xenograft mouse models. In addition, mouse blood chemistry profiles indicated that therapeutic doses of bioengineered miR-34a prodrug were well tolerated in these animals. The results demonstrated that bioengineered miR-34a prodrug was effective to control OS tumor growth which involved the induction of apoptosis and cell cycle arrest, supporting the development of bioengineered RNAs as a novel class of large molecule therapeutic agents

The Application of Theme/rheme Coherence Device in Discourse Teaching under Cognitive Framework

The repetitive coherence of theme and rheme comes through one of the important cohesive devices which make texture coherent and progressing. From cognitive point of view, applying the mode of thematic and rheme into English language teaching can display its tool function for texture. It also contributes to the understanding and interpretation of coherent discourses, and to the way in teaching reading and writing. Therefore，learners will leap forward from their cognitive level. Key words: cognition, coherence of theme and rheme, English language teaching Résumé: Le raccordement répété de thème-rhème est un des moyens importants de réaliser la cohérence et la continuité du texte. Et c’est grâce à ces moyens de cohérence que le texte s’acquiert la cohésion. L’application du système de cohérence à l’enseignement du texte anglais montre son utilité comme instrument textuel, offre de nouvelles perspectives pour l’enseignement de rédaction et de lecture en anglais, et aide les apprenants à approfondir leur compréhension. Mots-clés: cognition, cohérence de thème-rhème, enseignement textuel 摘要：語篇中主述位的反復銜接是實現語篇銜接和連貫的重要手段之一，而正是這些語篇銜接的手段使得主、述位達到層層推進，構成連貫的語篇。從認知的角度將主述位銜接機制應用於英語篇章教學，可展示其作為篇章工具的使用性，也可以為英語寫作和閱讀教學提供更為清新的思路，使英語學習者從認知上達到一個飛躍。 關鍵詞：認知；主述位銜接；篇章教

Expressions of toll-like receptors 2 and 4, and relative cellular factors in HIV patients with tuberculosis infection

Purpose: To investigate the expressions of toll-like receptor 2 (TLR2), toll-like receptor 4 (TLR4), tumor necrosis factor alpha (TNF-α), IFN-γ (IFN- gamma), interleukin 2 (IL-2), interleukin 6 (IL-6) and interleukin 10 (IL-10) in human immunodeficiency virus (HIV) patients with tuberculosis (TB) infection.Methods: Two groups of HIV patients (68 in each group) were used for this study. These were HIV with TB (HIV/TB) group and HIV without TB group. A third group (68 healthy people) served as control. Quantitative polymerase chain reaction (qPCR) was adopted to measure TLR-2 and TLR-4 expressions in peripheral blood mononuclear cells (PBMC), while the serum levels of TNF-α, IFN-γ, IL-2, IL-6 and IL-10 were determined by ELISA.Results: The △Ct values of TLR-2 and TLR-4 in HIV/TB and HIV groups were significantly lower than those in the control group (p < 0.05). Compared to control group, the serum levels of TNF-α, IL-6 and IL-10 significantly increased, while IFN-γ and IL-2 in HIV/TB and HIV groups significantly decreased (p < 0.05). However, IFN-γ and IL-2 decreased significantly in HIV/TB group (p < 0.05). Expression of TLR2 correlated positively with serum levels of TNF-α, IL-6 and IL-10, but negatively with IFN-γ and IL-2 (p < 0.05).Conclusion: TLR2 signal pathway plays a role in HIV patients with TB infection by promoting the expressions of TNF-α, IL-6 and IL-10, while inhibiting IFN-γ and IL-2 cellular factors, and thus may provide a new pathway for the treatment of patients with HIV/TB.Keywords: HIV, Tuberculosis, Toll-like receptor, Cellular factors, Tumor necrosis factor, Interleuki

Topological quantum transition driven by charge-phonon coupling in higher-order topological insulators

We investigate a second-order topological quantum transition of a modified Kane-Mele model driven by electron-phonon interaction. The results show that the system parameters of the bare modified Kane-Mele model are renormalized by the electron-phonon interaction. Starting from the second-order topological phase for the bare model, the increasing electron-phonon coupling strength can drive the second-order topological insulator into a semimetal phase. Such a secondorder topological phase transition is characterized by the band-gap closing, discontinuity of averaged ferminoic number and topological invariant.Comment: 8 pages,6 figure

Prognostic value of vitamin D in patients with pneumonia: A systematic review and meta-analysis

Purpose: To investigate the prognostic role of vitamin D in pneumonia patients  through meta-analysis.Methods: PubMed and Embase were systematically searched for relevant studies that assessed the impact of vitamin D on the risk of adverse outcomes among patients with pneumonia. Risk ratios (RR) with 95 % confidence intervals (95 % CI) were pooled using meta-analysis. Q-test and I2 statistics were used to evaluate between-study heterogeneity.Results: Six studies were finally included in the meta-analysis. The results of meta-analysis of these studies indicated that low vitamin D status was associated with higher risk of mortality among pneumonia patients (RR = 2.59, 95 % CI = 1.32-5.08; p = 0.005). Results from meta-analysis of studies with adjusted estimates suggest that low vitamin D status was independently associated with higher risk of mortality among pneumonia patients (RR = 3.15, 95 % CI 1.54-6.44, p = 0.002). There was no significant risk of bias in the meta-analysis.Conclusion: This study demonstrates that low vitamin D level is associated with a higher risk of adverse outcomes in patients with pneumonia.Keywords: Pneumonia, Vitamin D, Prognosis, Meta-analysis, Systematic revie

Timing of Drought Affected the Growth, Physiology, and Mortality of Mongolian Pine Saplings

Background and Objectives: More frequent and severe droughts are occurring due to climate change in northern China. In addition to intensity and duration, the timing of droughts may be decisive for its impacts on tree growth, mortality, and the whole forest ecosystem. The aim of this study was to compare the effect of drought occurring in the early- and mid-growing season on the growth and physiology of Mongolian pine (Pinus sylvestris var. mongolica Litv.) saplings. Materials and Methods: Four-year-old container saplings that were about to sprout were exposed to three treatments: (i) regular irrigation throughout the growing season (CTRL), (ii) no irrigation in the early growing season (weeks 1–5) followed by regular irrigation (EGD), (iii) no irrigation in the mid growing season (weeks 5–10), and regular irrigation in the early and late growing season (MGD). We measured the root and shoot growth, sapling mortality, and the physiological changes in the roots and needles periodically. Results: Drought in the mid growing season was more harmful than in the early growing season in terms of chlorophyll fluorescence, electrolyte leakage of needles, needle length, stem diameter increment, and sapling mortality. The high mortality in the mid growing season might be attributed to the joint effect of drought and high temperature. Drought in the early growing season decreased root growth, and the starch and soluble sugars in roots as much as the drought in the mid growing season. Abscisic acid concentration increased in fine roots, but decreased in old needles after drought. Conclusions: Special attention should be paid on forest sites susceptible to drought during afforestation in the face of ongoing climate change

Timing of Drought Affected the Growth, Physiology, and Mortality of Mongolian Pine Saplings

Background and Objectives: More frequent and severe droughts are occurring due to climate change in northern China. In addition to intensity and duration, the timing of droughts may be decisive for its impacts on tree growth, mortality, and the whole forest ecosystem. The aim of this study was to compare the effect of drought occurring in the early- and mid-growing season on the growth and physiology of Mongolian pine (Pinus sylvestris var. mongolica Litv.) saplings. Materials and Methods: Four-year-old container saplings that were about to sprout were exposed to three treatments: (i) regular irrigation throughout the growing season (CTRL), (ii) no irrigation in the early growing season (weeks 1–5) followed by regular irrigation (EGD), (iii) no irrigation in the mid growing season (weeks 5–10), and regular irrigation in the early and late growing season (MGD). We measured the root and shoot growth, sapling mortality, and the physiological changes in the roots and needles periodically. Results: Drought in the mid growing season was more harmful than in the early growing season in terms of chlorophyll fluorescence, electrolyte leakage of needles, needle length, stem diameter increment, and sapling mortality. The high mortality in the mid growing season might be attributed to the joint effect of drought and high temperature. Drought in the early growing season decreased root growth, and the starch and soluble sugars in roots as much as the drought in the mid growing season. Abscisic acid concentration increased in fine roots, but decreased in old needles after drought. Conclusions: Special attention should be paid on forest sites susceptible to drought during afforestation in the face of ongoing climate change