783 research outputs found

    A chalcone derivative reactivates latent HIV-1 transcription through activating P-TEFb and promoting Tat-SEC interaction on viral promoter.

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    The principal barrier to the eradication of HIV/AIDS is the existence of latent viral reservoirs. One strategy to overcome this barrier is to use latency-reversing agents (LRAs) to reactivate the latent proviruses, which can then be eliminated by effective anti-retroviral therapy. Although a number of LRAs have been found to reactivate latent HIV, they have not been used clinically due to high toxicity and poor efficacy. In this study, we report the identification of a chalcone analogue called Amt-87 that can significantly reactivate the transcription of latent HIV provirses and act synergistically with known LRAs such as prostratin and JQ1 to reverse latency. Amt-87 works by activating the human transcriptional elongation factor P-TEFb, a CDK9-cyclin T1 heterodimer that is part of the super elongation complex (SEC) used by the viral encoded Tat protein to activate HIV transcription. Amt-87 does so by promoting the phosphorylation of CDK9 at the T-loop, liberating P-TEFb from the inactive 7SK snRNP, and inducing the formation of the Tat-SEC complex at the viral promoter. Together, our data reveal chalcones as a promising category of compounds that should be further explored to identify effective LRAs for targeted reversal of HIV latency

    Light Harvesting Mechanism of Photosystem II in Photosynthesis:

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    As one of the most important chemical reactions on the earth, the photosynthetic reaction has gained much attention. For example, foliage and algae possess superior abilities to harvest luminous energy from sunlight in photosynthetic reactions by capturing lights with the light-harvesting complex (LHC) and transferring the energy from LHC to the reaction center (RC) in Photosystem II (PSII), to realize the continuous and efficient transformation from luminous energy to chemistry energy. In this article, the progresses in the studies on the crystal structure of PSII, the energy and electron transfer mechanism, and artificial simulation on photo-induced electron transfer are reviewed. Additionally, the initiating mechanism of hydrogen-abstraction photoinitiators, and the inspiration of the principles and mechanisms of photo-induced electron transfer in macromolecular photoinitiators were also discussed. It is believed that properly choosing covalent chains of appropriate types and length as the bridge between electron donor and electron acceptor is crucial for improving the initiating efficiency of photoinitiators. Keywords: photosynthesis; photosystem; light harvesting; photoinitiator; electron transfe

    An Extract of Antrodia camphorata Mycelia Attenuates the Progression of Nephritis in Systemic Lupus Erythematosus-Prone NZB/W F1 Mice

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    Antrodia camphorata is used in folk medicine for the treatment of inflammation syndromes and liver-related diseases in Taiwan. The goal of this study was to evaluate the efficacy of the mycelial extract of A. camphorata (ACE) for the treatment of systemic lupus erythematosus (SLE) in SLE-prone NZB/W F1 mice. After antibodies against double-stranded DNA appeared in NZB/W mice, the mice were orally administered varying dosages of ACE (100, 200 and 400 mg kg−1) for 5 consecutive days per week for 12 weeks via gavage. To assess the efficacy of ACE, we measured SLE-associated biochemical and histopathological biomarkers levels of blood urine nitrogen (BUN), blood creatinine, urine protein and urine creatinine and thickness of the kidney glomerular basement membrane by staining with periodic acid-Schiff. Antroquinonol, an active component of ACE, was investigated for anti-inflammation activity in lipopolysaccharide-induced RAW 267.4 cells. ACE at 400 mg kg−1 significantly suppressed urine protein and serum BUN levels and decreased the thickness of the kidney glomerular basement membrane. Antroquinonol significantly inhibited the production of tumor necrosis factor-α and interleukin-1β by 75 and 78%, respectively. In conclusion, ACE reduced urine protein and creatinine levels and suppressed the thickening of the kidney glomerular basement membrane, suggesting that ACE protects the kidney from immunological damage resulting from autoimmune disease

    Orderly arranged NLO materials on exfoliated layeredtemplates based on dendrons with alternating moietiesat the periphery†

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    Nonlinear optical dendrons with alternating terminal groups of the stearyl group (C18) and chromophorewere prepared through a convergent approach. These chromophore-containing dendrons were used asthe intercalating agents for montmorillonite via an ion-exchange process. An orderly exfoliatedmorphology is obtained by mixing the dendritic structure intercalated layered silicates with a polyimide.As a result, optical nonlinearity, i.e. the Pockels effect was observed for these nanocomposites withoutresorting to the poling process. EO coefficients of 9–22 pm V 1 were achieved despite that relativelylow NLO densities were present in the nanocomposites, particularly for the samples comprising thedendrons with alternating moieties. In addition, the hedging effects of the stearyl group on the selfalignmentbehavior, electro-optical (EO) coefficient and temporal stability of the dendron-intercalatedmontmorillonite/polyimide nanocomposites were also investigated

    Assessment of latent tuberculosis infection in psychiatric inpatients: A survey after tuberculosis outbreaks

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    AbstractBackground/PurposeTo investigate risk factors of latent tuberculosis infection (LTBI) among inpatients of chronic psychiatric wards with tuberculosis (TB) outbreaks.MethodsIn April 2013, inpatients of four all-male wards with TB outbreaks were tested for LTBI using the QuantiFERON-TB Gold in Tube (QFT) method. Based on this investigation, a retrospective study was conducted to assess risk factors for LTBI. Inpatients exposed to cluster-A or cluster-B TB cases were defined as contacts of cluster-A or cluster-B, and others, as nonclustered contacts.ResultsAmong 355 inpatients with TB exposure, 134 (38%) were QFT-positive for LTBI. Univariate analysis showed that significant predictors for QFT-positivity were age, case-days of exposure to all TB cases (TB-all) and to sputum smear positive cases, number of source cases with cough, and exposure to cluster-A TB cases. Independent risk factors for LTBI were higher age [adjusted odds ratio (OR) 1.03, 95% confidence intervals (CI: 1.01–1.05)], TB-all exposure case-days ≥ 200 [adjusted OR 2.04 (1.06–3.92)] and exposure to cluster-A TB cases [adjusted OR 2.82 (1.30–6.12)] after adjustment for the sputum smear positivity, and cough variables of the source cases. The contacts of cluster-A had a greater risk of LTBI than did those of cluster-B, especially in the younger population (≤50 years) after adjustment [adjusted OR 2.64 (1.03–6.76)].ConclusionAfter TB outbreaks, more than one third of inpatients were QFT-positive for LTBI. Our findings suggest that, beside the infectiousness of source cases, intensity of exposure, and age of contacts, exposure to TB cases in potential genotyping clusters may be predictive for LTBI in this male psychiatric population
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