The interactions of derivatives of lumisterol (L3) and vitamin D3 (D3) with liver X receptors (LXRs) were investigated. Molecular docking using crystal structures of the ligand binding domains (LBDs) ...of LXRα and β revealed high docking scores for L3 and D3 hydroxymetabolites, similar to those of the natural ligands, predicting good binding to the receptor. RNA sequencing of murine dermal fibroblasts stimulated with D3-hydroxyderivatives revealed LXR as the second nuclear receptor pathway for several D3-hydroxyderivatives, including 1,25(OH)
D3. This was validated by their induction of genes downstream of LXR. L3 and D3-derivatives activated an LXR-response element (LXRE)-driven reporter in CHO cells and human keratinocytes, and by enhanced expression of LXR target genes. L3 and D3 derivatives showed high affinity binding to the LBD of the LXRα and β in LanthaScreen TR-FRET LXRα and β coactivator assays. The majority of metabolites functioned as LXRα/β agonists; however, 1,20,25(OH)
D3, 1,25(OH)
D3, 1,20(OH)
D3 and 25(OH)D3 acted as inverse agonists of LXRα, but as agonists of LXRβ. Molecular dynamics simulations for the selected compounds, including 1,25(OH)
D3, 1,20(OH)
D3, 25(OH)D3, 20(OH)D3, 20(OH)L3 and 20,22(OH)
L3, showed different but overlapping interactions with LXRs. Identification of D3 and L3 derivatives as ligands for LXRs suggests a new mechanism of action for these compounds.
paradoxical teratogenic mechanism for retinoic acid Lee, Leo M. Y; Leung, Chun-Yin; Tang, Walfred W. C ...
Proceedings of the National Academy of Sciences - PNAS,
08/2012, Letnik:
109, Številka:
34
Journal Article
Recenzirano
Odprti dostop
Retinoic acid, an active metabolite of vitamin A, plays essential signaling roles in mammalian embryogenesis. Nevertheless, it has long been recognized that overexposure to vitamin A or retinoic acid ...causes widespread teratogenesis in rodents as well as humans. Although it has a short half-life, exposure to high levels of retinoic acid can disrupt development of yet-to-be formed organs, including the metanephros, the embryonic organ which normally differentiates into the mature kidney. Paradoxically, it is known that either an excess or a deficiency of retinoic acid results in similar malformations in some organs, including the mammalian kidney. Accordingly, we hypothesized that excess retinoic acid is teratogenic by inducing a longer lasting, local retinoic acid deficiency. This idea was tested in an established in vivo mouse model in which exposure to excess retinoic acid well before metanephric rudiments exist leads to failure of kidney formation several days later. Results showed that teratogen exposure was followed by decreased levels of Raldh transcripts encoding retinoic acid-synthesizing enzymes and increased levels of Cyp26a1 and Cyp26b1 mRNAs encoding enzymes that catabolize retinoic acid. Concomitantly, there was significant reduction in retinoic acid levels in whole embryos and kidney rudiments. Restoration of retinoic acid levels by maternal supplementation with low doses of retinoic acid following the teratogenic insult rescued metanephric kidney development and abrogated several extrarenal developmental defects. This previously undescribed and unsuspected mechanism provides insight into the molecular pathway of retinoic acid-induced teratogenesis.
We report the first results of a light weakly interacting massive particles (WIMPs) search from the CDEX-10 experiment with a 10 kg germanium detector array immersed in liquid nitrogen at the China ...Jinping Underground Laboratory with a physics data size of 102.8 kg day. At an analysis threshold of 160 eVee, improved limits of 8×10^{-42} and 3×10^{-36} cm^{2} at a 90% confidence level on spin-independent and spin-dependent WIMP-nucleon cross sections, respectively, at a WIMP mass (m_{χ}) of 5 GeV/c^{2} are achieved. The lower reach of m_{χ} is extended to 2 GeV/c^{2}.
•The influence of red mud on mechanical and durability properties of SCC were studied.•High superplasticiser dosages required for red mud concrete to meet the SCC requirements.•Mechanical strengths ...of SCC particularly at early age increased with increasing red mud content.•Corrosion potential of reinforced SCC samples decreased with increasing red mud content.•Presence of red mud in SCC did not make negative influence on the leaching of metals.
Red mud is a hazardous waste material produced during alkaline leaching of bauxite in the Bayer process. This study proposed the use of red mud to replace fly ash in self-compacting concrete (SCC) and the influences of red mud on fresh and hardened properties, and durability performances of SCC were studied. The fresh concrete results show that red mud had a slight negative impact on the fresh properties of SCC. The hardened concrete results show that the mechanical strength of concrete increased with increasing of red mud content. The half-cell potential test results indicated that red mud had a significant effect on restraining the corrosion process in SCC. Compared to the control sample, the red mud samples suffered less corrosion. Cracks associated with corrosion of reinforcement were observed in RMC0 and RMC100 samples after 28 day accelerated corrosion test. The ICP-MS results showed that there’s no significant difference in metal elements among the solutions regardless the red mud content in concrete.The relative corrosion rate test results suggested that red mud can suppress the corrosion current. The SCC samples consisting 75% red mud performed the best resistance to corrosion according to the results of half-cell potentials and mass loss of rebar.
The durability of concrete has attracted significant attention over the past several decades and is still a research hotspot until now. This paper reviews and discusses recent research activities on ...the durability of concrete, including: 1) major durability problems such as alkali aggregate reaction, sulfate attack, steel corrosion and freeze–thaw; 2) durability of concrete in marine environment; and 3) coupling effects of mechanical load and environmental factors on durability of concrete. Moreover, the consideration of durability in concrete structure design (DuraCrete and performance-based specifications) is also briefly reviewed.
Bacillus subtilis var. natto N21 (Bac; for greater proteolytic capacity) and Saccharomyces cerevisiae Y10 (Sac; for greater acidic capacity) were applied to produce a 2-stage combined fermentation ...feed. This study investigated whether the enhancement of Bac+Sac fermented feed on broiler growth performance was due to the probiotics per se or due to the fermentation process. Trial 1 included 1-d-old broiler chicks (n =144) randomly assigned to control, water added (same as in the fermentation feed, 23%), and Bac+Sac fermented feed (FBac+Sac) treatments with 4 replicates. Trial 2 included 21-d-old broiler chickens (n = 12) assigned into control and FBac+Sac groups for a metabolic trial for nutrient availability. Trial 3 included 1-d-old male broiler chicks (n = 216) randomly assigned into 6 treatments with 3 replicates. Treatments included a control, Sac fermented feed (FSac), FBac+Sac, Bac powder (PBac), Sac powder (PSac), and Bac+Sac powder (PBac+Sac). The results from trial 1 showed that FBac+Sac increased BW and feed intake (P < 0.05) in 21- and 39-d-old chickens. The water-added group showed decreased BW, weight gain, and feed intake (P < 0.05). Trial 2 showed that FBac+ Sac increased gross energy availability (P < 0.05). Trial 3 showed that FBac+Sac increased 21- and 39-d-old BW and weight gain (P < 0.05). Diets supplemented with probiotic powder or fermented with Sac did not improve broiler growth performance (P > 0.05). The growth performance improvement of the FBac+Sac treatment was probably not due to the added water, probiotic powder inclusion, or through single-strain fermentation, but due to the 2-stage fermentation process using Bac and Sac strains.
Soil chemical fumigation is an effective and popular method to increase agricultural productivity. However, the broad-spectrum bioactivity of fumigants causes harm to soil beneficial microorganisms ...involved in the soil phosphorous cycle, such as soil phosphorus solubilizing microorganisms (PSMs). We review the effects of soil chemical fumigation on soil phosphorus cycling, and the potential underlying mechanisms that ultimately lead to altered phosphorus availability for crops. These complex processes involve the highly diverse PSM community and a plethora of soil phosphorus forms. We discuss phosphatizing amendments aimed at counteracting the possible negative effects of fumigation on phosphorus availability, phosphorus use efficiency, and crop yields. We also emphasize distinguishing between the effects on soil phosphorus cycling caused by the chemical fumigants, and those caused by the fumigation process (e.g. plastic mulching). These are typically conflated in the literature; distinguishing them is critical for identifying appropriate amendments to remediate possible post-fumigation soil phosphorus deficiencies.
Talaromyces marneffei
(
T. marneffei
) can cause talaromycosis, a fatal systemic mycosis, in patients with AIDS. With the increasing number of talaromycosis cases in Guangdong, China, we aimed to ...investigate the susceptibility of 189
T. marneffei
clinical strains to eight antifungal agents, including three echinocandins (anidulafungin, micafungin, and caspofungin), four azoles (posaconazole, itraconazole, voriconazole, and fluconazole), and amphotericin B, with determining minimal inhibition concentrations (MIC) by Sensititre YeastOne™ YO10 assay in the yeast phase. The MICs of anidulafungin, micafungin, caspofungin, posaconazole, itraconazole, voriconazole, fluconazole, and amphotericin B were 2 to > 8 μg/ml, >8 μg/ml, 2 to > 8 μg/ml, ≤ 0.008 to 0.06 μg/ml, ≤ 0.015 to 0.03 μg/ml, ≤ 0.008 to 0.06 μg/ml, 1 to 32 μg/ml, and ≤ 0.12 to 1 μg/ml, respectively. The MICs of all echinocandins were very high, while the MICs of posaconazole, itraconazole, and voriconazole, as well as amphotericin B were comparatively low. Notably, fluconazole was found to have a higher MIC than other azoles, and exhibited particularly weak activity against some isolates with MICs over 8 μg/ml. Our data in vitro support the use of amphotericin B, itraconazole, voriconazole, and posaconazole in management of talaromycosis and suggest potential resistance to fluconazole.
Background
Various methods are used for cervical ripening during the induction of labour. It is still debatable which of these methods of treatment is optimal.
Objective
To compare treatment ...techniques for cervical ripening in the induction of labour.
Search strategy
Medline, Embase, and the Cochrane Collaboration databases were searched using the keywords ‘cervical ripening’, ‘labour induced’, ‘misoprostol’, ‘dinoprostone’, and ‘Foley catheter’.
Selection criteria
Randomised controlled trials (RCTs) of cervical ripening during the induction of labour, evaluating rates of failure to achieve vaginal delivery within 24 hours, incidence of uterine hyperstimulation with fetal heart rate (FHR) changes, and rates of caesarean section. Studies including women with prelabour rupture of membranes were excluded.
Data collection and analysis
Outcome data were collected and analysed through pairwise meta‐analysis and network meta‐analysis within a Bayesian framework.
Main results
A total of 96 RCTs (17 387 women) were included in the meta‐analysis. Vaginal misoprostol was the most effective cervical ripening method to achieve vaginal delivery within 24 hours, but had the highest incidence of uterine hyperstimulation with FHR changes. The use of a Foley catheter to induce labour was associated with the lowest rate of uterine hyperstimulation accompanied by FHR changes. The caesarean section rate was lowest using oral misoprostol for the induction of labour.
Author's conclusions
No method of labour induction demonstrated overall superiority when considering all three clinical outcomes. Decisions regarding the choice of induction method will depend upon the relative preference for effecting vaginal delivery within 24 hours, minimising the incidence of uterine hyperstimulation with adverse FHR changes and avoiding caesarean section.
Tweetable
Oral misoprostol for the induction of labour is safer than vaginal misoprostol and has the lowest rate of caesarean section.
Tweetable
Oral misoprostol for the induction of labour is safer than vaginal misoprostol and has the lowest rate of caesarean section.
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