Using confocal microscopy, X-ray microanalysis and the scanning ion-selective electrode technique, we investigated the signalling of H₂O₂, cytosolic Ca²⁺ (Ca²⁺cyt) and the PM H⁺-coupled transport ...system in K⁺/Na⁺ homeostasis control in NaCl-stressed calluses of Populus euphratica. An obvious Na⁺/H⁺ antiport was seen in salinized cells; however, NaCl stress caused a net K⁺ efflux, because of the salt-induced membrane depolarization. H₂O₂ levels, regulated upwards by salinity, contributed to ionic homeostasis, because H₂O₂ restrictions by DPI or DMTU caused enhanced K⁺ efflux and decreased Na⁺/H⁺ antiport activity. NaCl induced a net Ca²⁺ influx and a subsequent rise of Ca²⁺cyt, which is involved in H₂O₂-mediated K⁺/Na⁺ homeostasis in salinized P. euphratica cells. When callus cells were pretreated with inhibitors of the Na⁺/H⁺ antiport system, the NaCl-induced elevation of H₂O₂ and Ca²⁺cyt was correspondingly restricted, leading to a greater K⁺ efflux and a more pronounced reduction in Na⁺/H⁺ antiport activity. Results suggest that the PM H⁺-coupled transport system mediates H⁺ translocation and triggers the stress signalling of H₂O₂ and Ca²⁺, which results in a K⁺/Na⁺ homeostasis via mediations of K⁺ channels and the Na⁺/H⁺ antiport system in the PM of NaCl-stressed cells. Accordingly, a salt stress signalling pathway of P. euphratica cells is proposed.
Bisphenol S (BPS) is an environmental pollutant that can accumulate in the human body and cause harm. Puerarin (PUE) is a flavonoid with anti-inflammatory and antioxidant effects. In this study, we ...used 50 mg/kg/d BPS as a poison and PUE as an intervention for model mice for 42 d. BPS exposure significantly increased the levels of the impairment of the mice’s liver function, T-CHO, TG, LDL-C, ALT, and AST in the BPS group were significantly increased (p < 0.05). Additionally, BPS exposure caused inflammatory cell infiltration in the mice liver tissue and enhanced oxidative stress response, the level of MDA was significantly increased (p < 0.05). The expression of CD36 and pparγ was stimulated after BPS exposure. Moreover, the expression of cpt1a and cpt1b, which promote fatty acid oxidation, was downregulated. After PUE intervention, the levels of genes and proteins involved in lipid synthesis (PPARγ, SREBP1C, and FASN) and metabolism (Cpt1a, Cpt1b, and PPARα) in mice returned to those of the control group, or much higher than those in the BPS group. Therefore, we hypothesized that BPS causes lipid accumulation in the liver by promoting lipid synthesis and reducing lipid metabolism, whereas PUE reduces lipid synthesis and promotes lipid metabolism. Conclusively, our results imply that long-term exposure to BPS in mice affects liver lipid metabolism and that PUE intervention could maintain the liver function of mice at normal metabolic levels.
Abstract
Alanyl-tRNA synthetases (AlaRSs) from three domains of life predominantly rely on a single wobble base pair, G3-U70, of tRNAAla as a major determinant. However, this base pair is divergent ...in human mitochondrial tRNAAla, but instead with a translocated G5-U68. How human mitochondrial AlaRS (hmtAlaRS) recognizes tRNAAla, in particular, in the acceptor stem region, remains unknown. In the present study, we found that hmtAlaRS is a monomer and recognizes mitochondrial tRNAAla in a G3-U70-independent manner, requiring several elements in the acceptor stem. In addition, we found that hmtAlaRS misactivates noncognate Gly and catalyzes strong transfer RNA (tRNA)-independent pre-transfer editing for Gly. A completely conserved residue outside of the editing active site, Arg663, likely functions as a tRNA translocation determinant to facilitate tRNA entry into the editing domain during editing. Finally, we investigated the effects of the severe infantile-onset cardiomyopathy-associated R592W mutation of hmtAlaRS on the canonical enzymatic activities of hmtAlaRS. Overall, our results provide fundamental information about tRNA recognition and deepen our understanding of translational quality control mechanisms by hmtAlaRS.
The novel quaternary ammonium modified magnetic carboxyl-carbon nanotubes (QA-Mag-CCNTs) have been synthesised and characterized. QA-Mag-CCNTs were applied in magnetic dispersive solid phase ...extraction (Mag-dSPE) for preconcentration of perchlorate from tea leaves prior to liquid chromatography-tandem quadrupole mass spectrometry (LC-MS/MS) analysis. The Mag-dSPE procedure for preconcentration of perchlorate succeed in overcoming the flaw (containing target analyte randomly) of commercially available SPE cartridge. Under optimal conditions, the results showed higher extraction efficiency of QA-Mag-CCNTs, with recoveries between 85.2% and 107%. And the satisfactory precision with inter-day and intra-day RSD values were lower than 8.0%. Furthermore, QA-Mag-CCNTs were evaluated for reuse up to 20 times. The limit of quantification (LOQ) for perchlorate was 8.21 ng kg−1. The developed method was successfully applied in tea leaves for food-safety risk monitoring in Zhejiang province, China. The results showed the concentrations of perchlorate in 229 out of 240 collected samples were in the range of 0.082–988 μg kg−1. It was confirmed that QA-Mag-CCNTs were highly effective materials used for preconcentration of perchlorate.
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•QA-Mag-CCNTs have been synthesised and characterized by SEM, VSM and XPS.•QA-Mag-CCNTs are evaluated in Mag-dSPE for preconcentration of perchlorate from tea leaves.•It succeeds in overcoming the flaw (containing perchlorate randomly) of SPE cartridge.•The Mag-dSPE procedure is environmental friendly and effective to remove matrix.•Mag-dSPE LC-MS/MS method is efficient and promising for food-safety risk monitoring.
Abstract
Background
The mortality rate remains high among patients with coinfection with
Pneumocystis
pneumonia (PCP) and HIV. The timing for initiation of antiretroviral therapy (ART) after a ...diagnosis of moderate to severe PCP remains controversial, however. We therefore designed the present study to determine the optimal timing for ART initiation in AIDS-associated PCP (AIDS/PCP) patients.
Methods
This was a multicenter, observational, prospective clinical trial. Eligible participants were recruited from 14 hospitals in mainland China, and assigned to an Early ART arm (initiation of ART ≤ 14 days after PCP diagnosis) and a Deferred ART arm (initiation of ART > 14 days after PCP diagnosis). The primary outcomes were death and the incidence of AIDS-defining events at week 48. The secondary outcomes were the changes in CD4+ T-cell counts from baseline values at weeks 12, 24, and 48, the virological suppression rate at week 24 and week 48, the rate of development of PCP-associated immune reconstitution inflammatory syndrome (PCP/IRIS), and the rate of adverse events over 48 weeks.
Results
The present study was performed using the data of 363 participants, with 169 participants in the Early ART arm, and 194 participants in the Deferred ART arm. Immunological and virological outcomes were found to be similar in both treatment arms. At week 48, there were no significant differences for the incidence of mortality (20 vs. 26,
p
= 0.860), and AIDS-defining events (17 vs. 26,
p
= 0.412). Over 48 weeks, the rates of PCP/IRIS (2 vs. 3,
p
= 1.000), adverse events (70 vs. 72,
p
= 0.465), and grade 3 or 4 adverse events (28 vs. 34,
p
= 0.919) did not reach statistical significance. A significant difference observed between two study arms was that 11 participants (55.0%) in the Early ART arm compared to 23 participants (88.5%) in the Deferred ART arm (
p
= 0.026) succumbed before ART had ever been started.
Conclusions
Early ART initiation results in no increase in mortality, AIDS-defining events, IRIS, adverse events, and immunological or virological outcomes. These results support the early initiation of ART in patients with moderate to severe AIDS/PCP.
Clinical trial registration
The present trial was registered at Chinese Clinical Trial Registry (ChiCTR1900021195). Registered 1 February 2019,
http://www.chictr.org.cn/showproj.aspx?proj=35362
.
Objectives To investigate the antidepressant effects of Xiaoyaosan (XYS) in a chronic unpredictable mild stress (CUMS) depression model.
Methods The changes in behaviour and plasma metabolic ...profiles were investigated after four‐week CUMS exposure and treatment. Drugs were administered during the four‐week period of CUMS, with the healthy group serving as negative controls, and the fluoxetine and venlafaxine groups serving as positive controls. Plasma samples were collected at 28th day, and the plasma metabolic profiling was measured using NMR, followed by multivariate analysis.
Key findings Exposure to CUMS for four weeks caused depression‐like behaviour in rats, as indicated by significant decreases in weight gain, sucrose consumption and locomotor activity. Eleven potential biomarkers, including seven in the Carr–Purcell–Meiboom–Gill spectra, five in the diffusion‐edited spectra, and one in both were identified. It was found that trimethylamine‐N‐oxide, alanine, β‐hydroxybutyrate, valine, leucine/isoleucine, low‐density lipoprotein/very low‐density lipoprotein and lipids were lower and phosphatidylcholine, high‐density lipoprotein, choline and N‐acetyl glycoproteins were higher in CUMS‐treated rats, as compared with controls. XYS significantly suppressed behavioural changes and attenuated plasma metabolite changes.
Conclusions XYS produced an obvious antidepressant effect, and the metabonomic approach benefits estimation of the pharmacodynamic action of traditional Chinese medicine prescriptions.
WC-8Co hardmetals with different proportions of prismatic WC grains and plate-like WC grains were directly produced through sintering the W-C-8Co ele- mental powder mixture which was fabricated by ...dielectric barrier discharge plasma （DBDP）-assisted milling. The morphology of prepared WC-8Co hardmetals, geometry and the preferential orientation of plate-like WC were investigated by X-ray diffraction （XRD） and scanning electron microscopy （SEM） analysis. The results demon- strate that the microstructure and mechanical properties of the sintered hardmetals are related to the morphology of W grain which is dependent on DBDP-milling time. The DBDP for 1 h （DBDP-1 h）-milled W-C-Co powder contains granular W particles that tend to form prismatic WC grains, while the DBDP for 3 h （DBDP-3 h）-milled powder contains lamellar W particles that generate plate-like WC grains. By adjusting the weight ratio of DBDP-1 h powder and DBDP-3 h powder in W-C-8Co mixture, the proportion of plate-like WC in the hardmetals can be controlled, and relatively high transverse rupture strength （TRS） is obtained as the proportion of plate-like WC grain in the hardmetals is about 35 % in present experimental condition.
t To investigate the effect of Nb on the dehydro- genation properties of Mg-Nb composite films, Mg/Nb eight- layer film and Mg- 10 at% Nb alloy film with the similar Mg- to-Nb atomic ratio were ...prepared by magnetron sputtering. Results show that both Mg/Nb eight-layer film and Mg- 10 at% Nb alloy film exhibit excellent de/hydrogenation properties. Mg- 10 at% Nb alloy film starts to release hydrogen at 108 ℃, and its desorption peak temperature is lower to 146 ℃, which is much better than that of pure MgH2 under the same condi- tion. Scanning electron microscopy （SEM） results demon- strate that the dispersive Nb nanoparticles in Mg/Nb eight- layer film may serve as nucleation sites for Mg ←→ MgH2 reactions, which can provide channels for H diffusion. For Mg- 10 at% Nb alloy film, the uniform distributions of Nb can accelerate the hydrogen diffusion and effectively improve the dehydrogenation kinetics for MgH2. This study provides an enlightening way for designing and preparing Mg-based composite films with excellent dehydrogenation properties.
Colla corii asini (Ejiao), a gelatin-like food and drug obtained from Equus asinus Linnaeus, has been widely used in clinical hematic antianemic therapy for more than 2000 years. The elucidation of ...the characteristic metabolic alterations achieved during its treatment of anemia is critical to the screening of the biomarkers involved in anemia and improving the understanding of the hematinic effects of Ejiao. This work presents the first 1H-NMR-based metabolomics coupled with a correlation analysis study of the characteristic metabolic profiles of APH-induced anemic rats subjected to Ejiao treatment. Significant differences in the metabolic profiles of the rats in the control, blood deficiency and treatment groups were observed, and the identified serum biomarkers including arginine, aspartate, choline and dimethylglycine, could be used for the diagnosis of anemia. The results also showed that Ejiao may play a hematinic role through regulating the lipid and lipoprotein metabolism, energy metabolism, gut microflora and amino acid metabolism, reflecting the multi-target therapeutic effect of traditional Chinese medicine, which may be helpful for understanding the hematinic mechanism of Ejiao.
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