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1.
Food Chem ; 303: 125363, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31472383

RESUMO

Present in many plant foods, biogenic phenolic compounds are important bioactive phytonutrients with high anti-oxidant activity and thereby are praised for their health-promoting properties. However, current food nutrient improvement by high phenolic content in staples is limited by the shortage of genetic resources rich in phenolic compounds. To resolve this obstacle, we developed a non-destructive massive analytical approach to screen wheat phenolic mutants. In grains, multiple mutant lines showed significantly higher contents of flavonoids or cell wall-bound phenolic esters. Moreover, five mutants showed higher anti-oxidant potentials in wall-bound phenolic compounds ranging from 15% to 20%, with the maximal close to natural black wheat. In contrast to black wheat, two mutants accumulated higher phenolic compounds in the endosperm. lrf4 was mapped by BSR to a concentrated genomic region in the short arm of chromosome 1A. The present work represents an efficient high-throughput strategy to increase wheat anti-oxidant potential through traditional mutagenesis.

2.
Nature ; 2019 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-31597964

RESUMO

SF3B1 is the most commonly mutated RNA splicing factor in cancer1-4, but the mechanisms by which SF3B1 mutations promote malignancy are poorly understood. Here we integrated pan-cancer splicing analyses with a positive-enrichment CRISPR screen to prioritize splicing alterations that promote tumorigenesis. We report that diverse SF3B1 mutations converge on repression of BRD9, which is a core component of the recently described non-canonical BAF chromatin-remodelling complex that also contains GLTSCR1 and GLTSCR1L5-7. Mutant SF3B1 recognizes an aberrant, deep intronic branchpoint within BRD9 and thereby induces the inclusion of a poison exon that is derived from an endogenous retroviral element and subsequent degradation of BRD9 mRNA. Depletion of BRD9 causes the loss of non-canonical BAF at CTCF-associated loci and promotes melanomagenesis. BRD9 is a potent tumour suppressor in uveal melanoma, such that correcting mis-splicing of BRD9 in SF3B1-mutant cells using antisense oligonucleotides or CRISPR-directed mutagenesis suppresses tumour growth. Our results implicate the disruption of non-canonical BAF in the diverse cancer types that carry SF3B1 mutations and suggest a mechanism-based therapeutic approach for treating these malignancies.

3.
PLoS One ; 14(10): e0222835, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31574098

RESUMO

BACKGROUND: Guyana expanded its HIV response in 2005 but the epidemiology of hepatitis B virus (HBV) and hepatitis C virus (HCV) infections has not been characterized. METHODS: The 2011 Seroprevalence and Behavioral Epidemiology Risk Survey for HIV and STIs collected biologic specimens with demographic and behavioral data from a representative sample of Guyana military personnel. Diagnostics included commercial serum: HIV antibody; total antibody to hepatitis B core (anti-HBc); IgM anti-HBc; hepatitis B surface antigen (HBsAg); anti-HBs; antibody to HCV with confirmatory testing; and HBV DNA sequencing with S gene fragment phylogenetic analysis. Chi-square, p-values and prevalence ratios determined statistical significance. RESULTS: Among 480 participants providing serologic specimens, 176 (36.7%) tested anti-HBc-positive. Overall, 19 (4.0%) participants tested HBsAg-positive; 17 (89.5%) of the HBsAg-positive participants also had detectable anti-HBc, including 1 (5.3%) IgM anti-HBc-positive male. Four (6.8%) females with available HBV testing were HBsAg-positive, all aged 23-29 years. Sixteen (16, 84.2%) HBsAg-positive participants had sufficient specimen for DNA testing. All 16 had detectable HBV DNA, 4 with viral load >2x104IU/ml. Sequencing found: 12 genotype (gt) A1 with 99.9% genetic identity between 1 IgM anti-HBc-positive and 1 anti-HBc-negative; 2 gtD1; and 2 with insufficient specimen. No statistically significant associations between risk factors and HBV infection were identified. CONCLUSIONS: Integrated HIV surveillance identified likely recent adult HBV transmission, current HBV infection among females of reproductive age, moderate HBV infection prevalence (all gtA1 and D1), no HCV infections and low HIV frequency among Guyana military personnel. Integrated HIV surveillance helped characterize HBV and HCV epidemiology, including probable recent transmission, prompting targeted responses to control ongoing HBV transmission and examination of hepatitis B vaccine policies.

4.
Plant Sci ; 287: 110182, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31481196

RESUMO

Lesion mimic mutants are ideal genetic materials to study programmed cell death and defense signaling in plants. However, the molecular basis of lesion mimic formation remains largely unknown. Here, we first used a proteomic approach to identify differentially expressed proteins during dynamic lesion mimic formation in the rice oscul3a mutant, then electron microscope observation and physiological assays were used to analyze the mutant. The oscul3a mutant had disrupted cell metabolism balance, and the identified differentially expressed proteins were mainly located in the chloroplast and cytoplasm, which caused enhanced lipid metabolism, but suppressed carbon/nitrogen metabolism with reduced growth and grain quality. The oscul3a mutant had higher salicylic acid (SA) concentration in leaves, and H2O2 was shown to accumulate late in the formation of lesions. The secondary metabolite coumarin induced reactive oxygen species (ROS) and had rice blast resistance activity. Moreover, the cell death initiated lesion mimic formation of oscul3a mutant was light-sensitive, which might be associated with metabolite biosynthesis and accumulation. This study sheds light on the metabolic transition associated with cell death and defense response, which is under tight regulation by OsCUL3a and metabolism-related proteins, and the newly identified chemicals in the secondary metabolic pathway can potentially be used to control disease in crop plants.

5.
J Chem Phys ; 151(10): 104311, 2019 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-31521070

RESUMO

We have employed extended multiconfiguration quasidegenerate perturbation theory, fourfold-way diabatic molecular orbitals, and configurational uniformity to develop a global three-state diabatic representation of the potential energy surfaces and their couplings for the electronically nonadiabatic reaction OH* + H2 → H2O + H, where * denotes electronic excitation to the A 2Σ+ state. To achieve sign consistency of the computed diabatic couplings, we developed a graphics processing unit-accelerated algorithm called the cluster-growing algorithm. Having obtained consistent signs of the diabatic couplings, we fit the diabatic matrix elements (which consist of the diabatic potentials and the diabatic couplings) to analytic representations. Adiabatic potential energy surfaces are generated by diagonalizing the 3 × 3 diabatic potential energy matrix. The comparisons between the fitted and computed diabatic matrix elements and between the originally computed adiabatic potential energy surfaces and those generated from the fits indicate that the current fit is accurate enough for dynamical studies, and it may be used for quantal or semiclassical dynamics calculations.

6.
Sci Total Environ ; 697: 134047, 2019 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-31491641

RESUMO

In this study, simultaneous nitrification and denitrification (SND) process was successfully established in a hybrid sequencing batch biofilm reactor (HSBBR). High removal efficiency of NH4+-N (98.0±2.4% to 99.8±0.4%) and COD (86.6±4.0% to 91.6±1.8%) was observed in the salinity range of 0.0 to 2.4%. SND via nitrite, replacing SND via nitrate, became the main nitrogen removal pathway at 1.6% and 2.4% salinity. Suspended sludge and biofilm shared similar microbial composition. Dominant genera were substituted by salt-adaptable microbes as salinity increasing. Abundance of autotrophic ammonia-oxidizing bacteria (Nitrosomonas) increased with elevated salinity, while autotrophic nitrite-oxidizing bacteria (Nitrospira) exhibited extreme sensitivity to salinity. The presence of Gemmata demonstrated that heterotrophic nitrification co-existed with autotrophic nitrification in the SND process. Aerobic denitrifiers (Denitratisoma and Thauera) were also identified. Thiothrix, Sedimenticola, Sulfuritalea, Arcobacter (sulfide-based autotrophic denitrifier) and Hydrogenophaga (hydrogen-based autotrophic denitrifier) were detected in both S-sludge and biofilm. The occurrence of ANAMMOX bacteria Pirellula and Planctomyces indicated that ANAMMOX process was another pathway for nitrogen removal. Nitrogen removal in the HSBBR was accomplished via diverse pathways, including traditional autotrophic nitrification/heterotrophic denitrification, heterotrophic nitrification, aerobic and autotrophic denitrification, and ANAMMOX.

7.
Toxicol Sci ; 2019 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-31504961

RESUMO

Carbon nanomaterials (CNMs) are widely used in industrial and medical sectors. The increasing exposure of CNMs necessitates the studies of their potential environmental and health effects. High mobility group box-1 (HMGB1) is a nuclear DNA-binding protein, but when released from cells, may cause sustained inflammatory response and promote cell migration and invasion. In this work, we found that 7-day exposure of 2.5 mg/kg/day CNMs, including C60, single-walled carbon nanotubes (SWCNTs), and Graphene oxides (GOs) significantly elevated the level of HMGB1 in blood and lung lavage fluids in C57BL/6 mice. Subsequently, cellular effects and underlying mechanism was explored by using Raw264.7. The results showed that non-cytotoxic CNMs enhanced HMGB1 intracellular translocation and release via activating P2X7 receptor. Released HMGB1 further activated receptor for advanced glycation end products (RAGE) and downstream signaling pathway by up-regulating RAGE and Rac1 expression. Simultaneously, CNMs prepared the cells for migration and invasion by modulating MMP2 and TIMP2 gene expression as well as cytoskeleton reorganization. Intriguingly, released HMGB1 from macrophages promoted the migration of nearby lung cancer cell, which can be efficiently inhibited by neutralizing antibodies against HMGB1 and RAGE. Taken together, our work demonstrated that CNMs stimulated HMGB1 release and cell migration/invasion through P2X7R-HMGB1-RAGE pathway. The revealed mechanisms might facilitate a better understanding on the inflammatory property and subsequent cell functional alteration of CNMs.

8.
New Phytol ; 2019 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-31478201

RESUMO

Protein arginine methyltransferases (PRMTs) regulate many physiological processes, including autophagy. However, the direct roles of the various PRMTs during autophagosome formation remain unclear. Here, we characterised the function of MoHMT1 in the rice blast fungus, Magnaporthe oryzae. Knockout of MoHMT1 results in inhibited growth and a decreased ability to cause disease lesions on rice seedlings. MoHMT1 catalyses the di-methylation of arginine 247, 251, 261 and 271 residues of MoSNP1, a U1 small nuclear ribonucleoprotein (snRNP) component, likely in a manner dependent on direct interaction. RNA-seq analysis revealed that alternative splicing of pre-mRNAs of 558 genes, including the autophagy-related (ATG) gene MoATG4, was altered in MoHMT1 deletion mutants, compared with wild-type strains under normal growth conditions. During light exposure or nitrogen starvation, MoHMT1 localises to autophagosomes and MoHMT1 mutants display defects in autophagy induction. Under nitrogen starvation, six additional MoATG genes were identified with retained introns in their mRNA transcripts, corresponding with a significant reduction in transcripts of intron-spliced isoforms in the MoHMT1 mutant strain. Our study shows that arginine methylation plays an essential role in accurate pre-mRNA splicing necessary for a range of developmental processes, including autophagosome formation.

9.
Nano Lett ; 19(10): 7526-7533, 2019 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-31487192

RESUMO

Amplitude, duration, and frequency of activation of the extracellular-signal-regulated kinase (ERK) pathway code distinct information to instruct cells to migrate, proliferate, or differentiate. Synchronized frequency control of ERK activation would provide a powerful approach to regulate cell behaviors. Here we demonstrated modulation of ERK activities using alternative current (AC) electric fields (EFs) applied through high-k dielectric passivated microelectrodes. Both the amplitude and frequency of ERK activation can be precisely synchronized and modulated. ERK activation in our system is independent of Faradaic currents and electroporation, thus excluding mechanisms of changes in pH, reactive oxygen species, and other electrochemical reaction. Further experiments pinpointed a mechanism of phosphorylation site of epidermal growth factor (EGF) receptor to activate the EGFR-ERK pathway, and independent of EGF. AC EFs thus provide a powerful platform for practical and precise control of EGFR-ERK pathway.

10.
J Phys Chem B ; 123(40): 8580-8589, 2019 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-31532678

RESUMO

Broad applications of electropolymerized conducting polymers (CPs) often prefer thinner soft electrodes to comply with downscaling of the fabrication resolution. However, high conductivity of existing CP films vanishes as thickness decreases to the nanoscale (i.e., below 100 nm), with an unclear mechanism so far. In this study, with an unprecedented family of polypyrrole (PPy) nanofilms that can be easily transferred in a fast and contamination-free manner, we are able to trace the initial development of electrical conductance along with chains' arrangement starting from the very early electrochemical deposition. Our results evidence that the classical nodular polymeric aggregation fundamentally accounts for the persistent losses of interchain connectivity and macroscopic conductivity at a limited thickness. Surprisingly, this seemingly disadvantageous structure can be altered into a large conjugated network to robustly restore the conductivity back to over 80 S cm-1 even below 100 nm, while the controllable formation, growth, and collapse of such networks radically vary the conductivity over a range of 3 orders of magnitude (0.8-129 S cm-1). These observations depict the first physical picture detailing how the long-range conductivity builds up in a growing conjugated network, which opens a route to fast synthesis and diverse applications of such highly conductive CP nanofilms.

11.
BMC Ecol ; 19(1): 41, 2019 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-31533695

RESUMO

BACKGROUND: Understanding how traditional agriculture systems have been maintained would help design sustainable agriculture. In this study, we examined how farmers have used two types of local trees (Torreya grandis) for stable yield and maintaining genetic diversity in the "globally important agricultural heritage torreya tree system". The two type of torreya trees are grafted torreya (GT) tree and non-grafted-torreya (NGT) tree. The GT tree has only female and was used to produced seed yields. The NGT tree has both male and female and was used to support GT tree by providing pollens and rootstocks. We first tested the ratio of GT tree to NGT tree, their age groups, ratio of female trees (including GT and NGT trees) to male, and the flowering period of GT and NGT trees. We then tested seed yields and genetic diversity of GT and NGT trees. We further tested gene flow among NGT trees, and the relationship of gene flow with exchange rates of pollens and seeds. RESULTS: GT and NGT trees (male and female) were planted in a mosaic pattern with a ratio of 4:1 (GT:NGT). In this planting pattern, one NGT male trees provided pollen for 20 female trees of GT and NGT. The trees were classified into four age groups (I = 100-400 years old; II = 400-700 years old; III = 700-1000 years old; and IV = 1000-1300 years old) based on basal diameter. The entire flowering period was longer for NGT trees than for GT trees that ensured GT trees (which lack of males) being exposed to pollens. GT tree had high and stable seed yield that increased with age groups. High genetic diversity has been maintained in both rootstocks of the GT trees and NGT trees. There was a strong gene flow among NGT trees, which positive correlated with the exchange rates of pollens and seeds. CONCLUSIONS: Our results suggest that farmers obtain stable seed yields, and maintain high genetic diversity by ingeniously using the local GT tree as yield producer and NGT tree as supporter. These GT and NGT trees together ensure sustainable torreya production.

12.
Environ Pollut ; 254(Pt B): 113118, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31476674

RESUMO

Carbon nanotubes (CNTs) inevitably enter domestic sewage and industrial wastewater with the continuous increase of their production and application field. The potential effect of CNTs on biological wastewater treatment processes has raised wide concerns due to their biotoxicity. In the present study, the performance, microbial community and enzymatic activity of sequencing batch reactors (SBRs) were evaluated under 148-day exposure of amino-functionalized multi-walled CNTs (MWCNTs-NH2) at 10 and 30 mg/L. The COD removal efficiency at 10 and 30 mg/L MWCNTs-NH2 gradually reduced from 91.03% and 90.43% on day to 89.11% and 86.70% on day 148, respectively. The NH4+-N removal efficiency at 10 and 30 mg/L MWCNTs-NH2 gradually reduced from 98.98% and 98.46% on day 1 to 96.65% and 63.39% on day 148, respectively. Compared to 0 mg/L MWCNTs-NH2, the oxygen-utilizing rate, ammonia-oxidizing rate, nitrite-oxidizing rate, nitrite-reducing rate and nitrate-reducing rate at 30 mg/L MWCNTs-NH2 were decreased by 52.35%, 60.58%, 55.12%, 56.56% and 57.42% on day 148, respectively. The microbial reactive oxygen species and lactate dehydrogenase release on day 148 was increased by 59.71% and 55.28% at 30 mg/L MWCNTs-NH2, respectively. The key microbial enzymatic activity related to nitrogen removal decreased with the increase of operation time under MWCNTs-NH2 stress. The relative abundances of Nitrosomonas, Nitrosospira, Nitrospira and some denitrifying bacteria at 10 mg/L MWCNTs-NH2 gradually reduced with an increment in operation time. The changes of nitrogen removal rate, microbial community and enzymatic activity of SBR were related to the time-cumulative nonlinear inhibition effect under long-term exposure.

13.
Environ Pollut ; 254(Pt B): 113088, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31491697

RESUMO

Airborne lower-chlorinated PCBs are vulnerable to metabolization to PCB sulfates through further sulfation of the hydroxylated metabolites (OH-PCBs). However, studies on the toxic effects and mechanisms of PCB sulfates are still very limited. Here, we investigated for the first time the potential endocrine disruption effects of PCB sulfates through estrogen-related receptor γ (ERRγ) in comparison with their OH-PCBs precursors and PCB parent compounds. The binding affinity of thirteen PCBs/OH-PCBs/PCB sulfates was measured by using fluorescence competitive binding assays based on fluorescence polarization (FP). All of the tested chemicals could bind to ERRγ with the Kd (dissociation constant) values ranging from not available (NA) to 3.2 µM 4'-OH-PCB 12 showed the highest binding affinity with Kd value of 3.2 µM, which was comparable to that of a synthetic ERRγ agonist GSK4716. The effects of the thirteen chemicals on the ERRγ transcriptional activity were determined by using the luciferase reporter gene assay. We found the PCBs/OH-PCBs/PCB sulfates acted as agonists for ERRγ, with the lowest observed effective concentration reaching 3 µM. The binding affinity and agonistic activity of PCBs towards ERRγ were both enhanced after hydroxylation, while further sulfation of OH-PCBs decreased the activity instead. Molecular docking simulation showed that OH-PCBs had lower binding energy than the corresponding PCBs and PCB sulfates, indicating that OH-PCBs had higher binding affinity theoretically. In addition, OH-PCBs could form hydrogen bonds with amino acids Glu316 and Arg247 while PCBs and PCB sulfates could not, which might be the main factor impacting the binding affinity and agonistic activity. Overall, ERRγ is a novel target for lower-chlorinated PCBs and their metabolites.

14.
Artigo em Inglês | MEDLINE | ID: mdl-31550180

RESUMO

Although many studies have shown that histamine and its signaling regulate energy homeostasis through the CNS (central nervous system), its role in adipose tissues remains poorly understood. Here, we identified the HrH4 (histamine H4 receptor) was highly expressed in adipocytes, at a level higher than that of the other three receptors (i.e., HrH1, HrH2, and HrH3). The HrH4 expression in adipocytes responded to cold through thermogenesis and lipolysis, supported by results from both mouse and cell models. When HrH4 expression was knocked down in the scWAT (subcutaneous white adipose tissue), browning and lipolysis effects triggered by cold were ablated, and the oxygen consumption was also lowered both at the normal and cold conditions. Moreover, mice exhibited browned scWAT, accelerated metabolic rates, and tolerance to hypothermia when 4MH (4-methylhistamine), a selective HrH4 agonist, was adjacently injected to the scWAT. Consistent with these findings, 4MH also triggered the browning and lipolytic effects in cultured C3H10T1/2 adipocytes. Mechanically, we demonstrated that p38/MAPK and ERK/MAPK pathways were involved in these processes. In conclusion, our findings have uncovered an effective role of HrH4 in adipose tissue browning.

15.
Kidney Blood Press Res ; : 1-8, 2019 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-31550724

RESUMO

BACKGROUND: Although reduced red blood cell (RBC) lifespan has been reported to be a contributory factor to anemia in patients with end-stage chronic kidney disease (CKD), there are limited data regarding RBC lifespan in early-stage CKD. Serum erythropoietin (EPO) is considered a primary causative factor of renal anemia. The aims of this study were to compare the RBC lifespan, serum EPO levels, and other renal anemia indicators across CKD-stage groups of patients and to analyze the impacts of etiological factors on renal anemia. METHODS: A cohort of 74 non-smoking patients with CKD were enrolled, including 15 in stage 1, 18 in stage 2, 15 in stage 3, 15 in stage 4, and 11 in stage 5. RBC lifespan was determined by CO breath tests. Potential correlations of hemoglobin (Hb) concentration with RBC lifespan, reticulocyte count (Ret), and levels of EPO, ferritin, folic acid, and vitamin B12 were analyzed. RESULTS: CKD progression was associated with decreases in (Hb) and RBC lifespan. RBC lifespan durations in CKD stages 1-5 were 122 ± 50, 112 ± 26, 90 ± 32, 88 ± 28, and 60 ± 24 days, respectively. RBC lifespan means for the stage 3, 4 and 5 groups were significantly shorter than those for the stage 1 and 2 groups. Serum EPO did not differ significantly between the CKD stage groups. (Hb) correlated directly with RBC lifespan (r = 0.372, p = 0.002) and Ret (r = 0.308, p = 0.011), but did not correlate with serum EPO, ferritin, folic acid, or vitamin B12 levels. CONCLUSIONS: Reduced RBC lifespan in early-stage CKD, demonstrated in this study, suggests that increased RBC destruction may play a more important etiological role in renal anemia than other indicators in patients with CKD.

16.
Mol Biol Rep ; 2019 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-31535324

RESUMO

Norisoprenoids are produced from carotenoids under oxidative degradation mediated by carotenoid cleavage dioxygenases (CCDs) and contribute to floral and fruity notes in grape berries and wine. The diversity of CCD substrates and products has been demonstrated by in vitro recombinant proteins extracted from Escherichia coli expressing CCD genes and of in vivo proteins in an E. coli system co-expressing genes for carotenoid synthesis and cleavage. In the current study, VvCCD1 and VvCCD4b were isolated from the cDNA library of Vitis vinifera L. cv. Cabernet Sauvignon and then transformed into carotenoid-accumulating recombinant Saccharomyces cerevisiae strains. The expression of the target genes was monitored during the yeast growth period, and the accumulation of carotenoids and norisoprenoids in the recombinant strains was measured. The results indicated that both of the VvCCDs cleaved ß-carotene at the 7, 8 (7', 8') position into ß-cyclocitral for the first time. Additionally, the two enzymes also degraded ß-carotene at the 9, 10 (9', 10') position to generate ß-ionone and cleaved lycopene at the 5, 6 (5', 6') position into 6-methyl-5-hepten-2-one. These findings suggested that the VvCCDs may possess more cleavage characteristics under the eukaryotic expression system in S. cerevisiae than the prokaryotic system in E. coli, which could better explain the biochemical functions of VvCCDs in grape berries.

17.
Environ Pollut ; 255(Pt 1): 113216, 2019 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-31541835

RESUMO

The performance, microbial community and enzymatic activity of sequencing batch reactors (SBRs) were investigated under 75-day exposure of different Cu(II) concentrations. Cu(II) at 0-5 mg/L had no distinct impact on the chemical oxygen demand (COD) and nitrogen removal, oxygen-uptake rate (OUR), nitrification and denitrification rate, and microbial enzymatic activity. The inhibitory effects of Cu(II) at 10 and 30 mg/L on the nitrogen removal rate, OUR, and microbial enzymatic activity of SBR increased with an increment in operation time due to the Cu(II) biotoxicity and the Cu(II) accumulation in activated sludge. The changes of microbial reactive oxygen species production, lactate dehydrogenase release, catalase activity and superoxide dismutase activity demonstrated that Cu(II) at 10 and 30 mg/L broke the equilibrium between the oxidation and antioxidation processes in microbial cells and also damaged the cytomembrance integrity, which could affect the COD and nitrogen removal performance and change normal microbial cell morphology. The Cu(II) in the influent could be removed by the microbial absorption and accumulated in the activated sludge under long-term exposure. The microbial community displayed some distinct changes from 0 to 30 mg/L Cu(II). In contrast with 0 mg/L Cu(II), Nitrosomonas, Nitrospira and some denitrifying bacteria obviously decreased in relative abundance under long-term exposure of 10 and 30 mg/L Cu(II).

18.
Eur J Pharmacol ; : 172671, 2019 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-31542477

RESUMO

Methamphetamine addiction has been widely spread and caused serious problems both in society and public health in recent years, but there is a shortage of medication available. The naltrexone as a non-selective opioid receptor antagonist has been widely used to treat alcohol addiction and the relapse to opioid addiction after detoxification. In the present study, we investigated the potent pharmacotherapeutic effect of naltrexone in attenuating relapse to drug-seeking behavior in the methamphetamine self-administration and conditioned place preference (CPP) in rats. The results showed that acute intragastrical administration of naltrexone (40 mg/kg) significantly reduced cue-induced drug-seeking behavior after extinction training. The similar inhibition effect was observed in the CPP model, that the intragastrical administration of naltrexone (30 mg/kg) significantly disrupted the reactivation by intraperitoneal injection of methamphetamine (0.5 mg/kg) after extinction training process. However, respective intragastrical administration of naltrexone (20 or 40 mg/kg) failed to alter the dose-response curve of methamphetamine under fixed ratio 2 program and intraperitoneal injection of methamphetamine (1.0 mg/kg)-induced reinstatement in rat self-administration. Overall, our findings suggest that naltrexone have the pharmacotherapeutic potential in reducing the relapse of methamphetamine addiction, which deserves further investigation as a promising medication for the treatment of methamphetamine addiction.

19.
Neurol Res ; : 1-9, 2019 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-31559927

RESUMO

Objectives Cerebral vasospasm after subarachnoid haemorrhage (SAH) is associated with cerebrovascular contractile receptor upregulation resulted from haemolysis in the subarachnoid space. This study developed a new magnesium-rich artificial cerebrospinal fluid (MACSF) formula and investigated its effects on receptor-mediated contraction in rat basilar arteries. Methods Clear and haemorrhagic cerebrospinal fluid (CSF) were collected from patients with hydrocephalus or SAH. MACSF was freshly prepared using clinical intravenous injections. Rat basilar arteries were segmented and incubated with clear CSF, haemorrhagic CSF or MACSF. The contractile responses were studied by myograph. The messenger ribonucleic acid (mRNA) and protein expression of 5-hydroxytryptamine 1B (5-HT1B), endothelin subtype B (ETB) and endothelin subtype A (ETA) receptors were evaluated by real-time polymerase chain reaction (PCR) and Western blot analyses. Results Haemorrhagic CSF exposure shifted the contractile curves induced by 5-hydroxytryptamine (5-HT), sarafotoxins 6c (S6c) and endothelin-1 (ET-1) leftward with increased maximal contraction values. Furthermore, mRNA and protein expression were markedly elevated for 5-HT1B, ETB and ETA receptors on arteries exposed to haemorrhagic CSF. However, the contractile responses to 5-HT, S6c or ET-1 and expression of 5-HT1B, ETB and ETA receptors in rat cerebral arteries exposed to MACSF remained unaffected compared to those exposed to clear CSF. Besides, unlike normal saline which can inactive in-vitro vessels, MACSF can maintain their physiological activity. Conclusion Haemorrhagic CSF induces upregulation of 5-HT1B, ETB and ETA receptors in rat cerebral arteries. However, MACSF can maintain in-vitro rat basilar arteries in good physiological activity and normal expression of contractile 5-HT and ET receptors.

20.
Mol Aspects Med ; 2019 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-31558294

RESUMO

The role of microRNAs (miRNAs) in cancer development was implicated as oncogene or tumor suppressor. One of the miRNA family, the miR-200 family, was mainly characterized as tumor suppressor. However, controversial results were reported. The associations between miR-200 family (consisting of five miRNAs: miR-141/200a/200b/200c/429) and cancer prognosis were inconsistent. Therefore, we conducted a meta-analysis by searching PubMed and Embase databases for studies assessing the association between the expression of miR-200 family and patients' survival of cancers. Hazard ratios (HRs) with 95% confidence intervals (CIs) were extracted from the studies and pooled HRs was determined to evaluate the association. This meta-analysis comprised 58 articles with 8107 cancer patients. The overall analysis showed that patients with higher expression of miR-200 family were associated with worse survival (HR = 1.206, 95% CI: 1.115-1.305, p < 0.001). In the stratified analysis, high level of miR-200b and miR-200c was associated with poor patients' survival. In the subgroup analysis, expression of miR-200a and miR-429 was associated with survival of breast cancer and liver cancer, respectively. Expression of miR-141 was found to be associated with favorable patients' survival in pancreatic cancer (HR = 0.275, 95% CI: 0.104-0.727, p = 0.009). In the subgroup analysis of sample type of miR-141, reverse associations with patients' survival were found from tissue (HR = 0.769, 95% CI: 0.597-0.990, p = 0.042) and blood (HR = 1.496, 95% CI: 1.183-1.893, p = 0.001). Our findings revealed that association between miR-200 family and prognosis of various cancer types was significant and the results needed specific interpretation.

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