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1.
Molecules ; 25(3)2020 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-32028657

RESUMO

A highly efficient quinine-derived primary-amine-catalyzed asymmetric aldol addition of hydroxyacetone to arylglyoxals is described. Structurally diverse anti-2,3-dihydroxy-1,4-diones were generated in high yields, with good diastereoselectivities and enantioselectivities.

2.
Bioresour Technol ; 302: 122865, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32004814

RESUMO

Fermentative caproate production from wastewater is attractive but is currently limited by the low product purity and concentration. In this work, continuous, selective production of caproate from acetate and ethanol, the common products of wastewater anaerobic fermentation, was achieved in an anaerobic membrane bioreactor (AnMBR). The reactor was continuously operated for over 522 days without need for chemical cleaning. With an ethanol-to-acetate ratio of 3.0, the effluent caproate concentration was 2.62 g/L on average and the caproate ratio in liquid products reached 74%. Further raising the influent ethanol content slightly increased the effluent caproate level but lowered the product selectivity and resulted in microbial inhibition. The Clostridia (the major caproate-producing bacteria) and Methanobacterium species (which consume hydrogen to alleviate microbial inhibition) was significantly enriched in the acclimated sludge. Our results imply a great potential of utilizing AnMBR to recover caproate from the effluent of wastewater acidogenic fermentation process.

3.
Int J Infect Dis ; 2020 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-32061862

RESUMO

BACKGROUND: The clinical utilisation of deep sequencing in HIV treatment has been hindered due to its unknown correlation with standard Sanger genotyping and the undetermined value of minority drug resistance mutation (DRM) detection. OBJECTIVES: To compare deep sequencing performance to standard Sanger genotyping with clinical samples, in an effort to delineate the correlation between the results from the two methods and to find the optimal deep sequencing threshold for clinical utilisation. METHODS: We conducted a retrospective study using stored plasma collected from August 2014 to March 2018 for HIV genotyping with the commercial Sanger genotyping kit. Samples with available Sanger genotyping reports were further deep sequenced. Drug resistance was interpreted according to the Stanford HIV drug resistance database algorithm. RESULTS: At 15-25% minority detection thresholds, 9-15% cases were underestimated of DRMs by Sanger sequencing. The concordance between the Sanger and deep sequencing reports was 68-82% in protease-reverse transcriptase region and 88-97% in integrase region at 5-25% thresholds. The undetected drug resistant minority variants by Sanger sequencing contributed to the lower negative predictive value of Sanger genotyping in cases harbouring DRMs. CONCLUSIONS: Use of deep sequencing improved detection of antiretroviral resistance mutations especially in cases with virological failure or previous treatment interruption. Deep sequencing with 10-15% detection thresholds may be considered a suitable substitute for Sanger sequencing on antiretroviral DRM detection.

4.
Environ Sci Technol ; 2020 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-32062962

RESUMO

Pursuing efficient approaches to promote the extracellular electron transfer (EET) of extracellular respiratory bacteria is essential to their applications in environmental remediation and waste treatment. Here, we report a new strategy of tuning electron flux by clustered regularly interspaced short palindromic repeats (CRISPR)-ddAsCpf1 based rediverting (namely STAR) to enhance the EET capacity of Shewanella oneidensis MR-1, one model extracellular respiratory bacterium widely present in environments. The developed CRISPR-ddAsCpf1 system enabled approximately 100% gene repression with the green fluorescent protein (GFP) as reporter. By using WO3 probe, 10 representative genes encoding for putative competitive electron transfer proteins were screened, among which 7 genes were identified as the valid targets for the EET enhancement. Repressing the valid genes not only increased the transcription level of the L-lactate metabolism genes, but also affected the genes involved in the direct and indirect EET. A raised riboflavin production was also observed. The feasibility of this strategy to enhance the bio-reductions of methyl orange, an organic pollutant, and chromium, a typical heavy metal, was demonstrated. This work implies a great potential of the STAR strategy with the CIRPSR-ddAsCpf1 system for enhancing bacterial EET to favor more efficient environmental remediation applications.

5.
Bioorg Med Chem Lett ; : 127025, 2020 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-32063430

RESUMO

Twenty-six novel pyrazolo[3,4-b]pyridine-bridged analogues of combretastatin A-4 possessing 3,4,5-trimethoxylphenyl groups, were synthesized and evaluated for their antiproliferative and tubulin polymerization inhibitory activities. Preliminary biological evaluation demonstrated that some of the target compounds displayed significant antiproliferative effectagainst four different cell lines including MCF-7, MDA-MB-231, HeLa and Kyse150. The most active analogue 6n was found to induce HeLa cells arrest in the G2/M phase in a dose-dependent manner. Molecular modeling studies indicated that derivative 6n most likely occupies the colchicine site of tubulin. The initial results suggest that the 3,4,5-trimethoxyphenyl substituted pyrazolo[3,4-b]pyridine could serve as a promising scaffold for development of potent tubulin inhibitors as anticancer agents.

6.
Anal Chem ; 2020 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-32020800

RESUMO

Mercury (Hg), as a highly harmful environmental pollutant, poses severe ecological and health risks even at low concentrations. Accurate and sensitive methods for detecting Hg2+ ions in aquatic environments are highly needed. In this work, we developed a highly sensitive fluorescence sensor for Hg2+ detection with an integrated use of biosynthetic CdSe/CdS quantum dots (QDs) and liposome carrier signal amplification. To construct such a sensor, three single-stranded DNA probes were rationally designed based on the thymine-Hg2+-thymine (T-Hg2+-T) coordination chemical principles and by taking advantage of the biocompatibility and facile-modification properties of the biosynthetic QDs. Hg2+ could be determined in a range from 0.25 to 100 nM with a detection limit of 0.01 nM, which met the requirements of environmental sample detection. The sensor also exhibited a high selectivity for Hg2+ detection in the presence of other high-level metal ions. A satisfactory capacity of the sensor for detecting environmental samples including tap water, river water, and landfill leachate was also demonstrated. This work opens up a new application scenario for biosynthetic QDs and holds a great potential for environmental monitoring applications.

7.
Biotechnol Bioeng ; 2020 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-32048726

RESUMO

The bioreduction capacity of Cr(VI) by Shewanella is mainly governed by its bidirectional extracellular electron transfer (EET). However, the low bidirectional EET efficiency restricts its wider applications in remediation of the environments contaminated by Cr(VI). Cyclic adenosine 3',5'-monophosphate (cAMP) commonly exists in Shewanella strains and cAMP-cyclic adenosine 3',5'-monophosphate receptor protein (CRP) system regulates multiple bidirectional EET-related pathways. This inspires us to strengthen the bidirectional EET through elevating the intracellular cAMP level in Shewanella strains. In this study, an exogenous gene encoding adenylate cyclase from the soil bacterium Beggiatoa sp. PS is functionally expressed in Shewanella oneidensis MR-1 (the strain MR-1/pbPAC) and a MR-1 mutant lacking all endogenous adenylate cyclase encoding genes (the strain Δca/pbPAC). The engineered strains exhibit the enhanced bidirectional EET capacities in microbial electrochemical systems compared with their counterparts. Meanwhile, a three times more rapid reduction rate of Cr(VI) is achieved by the strain MR-1/pbPAC than the control in batch experiments. Furthermore, a higher Cr(VI) reduction efficiency is also achieved by the strain MR-1/pbPAC in the Cr(VI)-reducing biocathode experiments. Such a bidirectional enhancement is attributed to the improved production of cAMP-CRP complex, which upregulates the expression levels of the genes encoding the c-type cytochromes and flavins synthetic pathways. Specially, this strategy could be used as a broad-spectrum approach for the other Shewanella strains. Our results demonstrate that elevating the intracellular cAMP levels could be an efficient strategy to enhance the bidirectional EET of Shewanella strains and improve their pollutant transformation capacity.

8.
Steroids ; : 108600, 2020 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-32068080

RESUMO

A novel synthetic route of producing ursodeoxycholic acid (UDCA) was developed through multiple reactions from cheap and commercially available bisnoralcohol (BA). The key reaction conditions, including solvents, bases and reaction temperatures of the route were investigated and optimized. In the straightforward route for preparation of UDCA, most of the reaction steps have high conversions with average yields of 91%, and overall yield up to 59% (6 steps) from the plant-source BA. Especially in the last step of reduction and hydrolysis, there are five functional groups converted with calcd 97% per conversion in one-pot reaction. This promising route offers economical and efficient strategies for potential large-scale production of UDCA.

9.
Nat Prod Bioprospect ; 2020 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-32016770

RESUMO

A series of dearomatized isoprenylated acylphloroglucinols derivatives, hyperhenols A-E (1-5), as well as seven known analogues (6-12), were characterized from Hypericum henryi. Their structures were determined by combination of NMR, ECD spectroscopy, and X-ray diffraction analysis. Compounds 1 and 6-8 were tested to exhibit potential antitumor properties, of which 6 and 7 inhibited cell growth through inducing apoptosis and cell cycle arrest. In addition, these compounds could induce autophagy and PINK1/Parkin-mediated mitophagy in cancer cell lines, as well as suppress lung cancer A549 cells metastasis in vitro.

10.
Medicina (Kaunas) ; 56(2)2020 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-32019121

RESUMO

BACKGROUND AND OBJECTIVES: Patients with oral squamous cell carcinoma (OSCC), a common malignancy in Asian countries, have a poor prognosis. We investigated the role of Krüppel-like factor 17 (KLF17) and its prognostic significance in OSCC. MATERIALS AND METHODS: KLF17 expression was measured by immunohistochemical staining of specimens from 283 patients with OSCC. We analyzed correlations between KLF17 expression and clinicopathologic features and between KLF17 expression and overall survival. The prognostic value of KLF17 was tested using Kaplan-Meier analysis and Cox proportional hazard models. RESULTS: Among the 283 patients, high KLF17 expression was significantly associated with an early OSCC stage and low T-value (p = 0.033 and p = 0.036, respectively). The five-year survival rates were better in patients with high KLF17 expression than with low expression (66.5% and 49.6%, respectively). The prognostic role of KLF17 was further confirmed through multivariate analysis (hazard ratio 1.506, 95% confidence interval 1.034-2.191, p = 0.033). The prognostic value was more significant in patients with a history of betel quid chewing or with a low T-value. CONCLUSIONS: High KLF17 expression can serve as a marker for a favorable prognosis in patients with OSCC. The prognostic role of KLF17 is more significant in patients with a history of betel quid chewing or a low T-value.

11.
J Cell Physiol ; 2020 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-32026462

RESUMO

Increasing evidence confirms that exosome-mediated transfer of microRNAs can influence cancer progression including tumor cell invasion, cell proliferation, and drug resistance via cell-cell communication. However, the potential role of exosomal-miR-1260b in lung adenocarcinoma (LAC) remains poorly understood. Thus, this study focused on investigating the function of exosomal-miR-1260b on cell invasion. Exosomal-miR-1260b was found to be higher in plasma of patients with LAC than that of healthy persons via quantitative real-time polymerase chain reaction assay. The sensitivity and specificity of exosomal-miR-1260b (cutoff point: 2.027) were 72% and 86%, and area under the curve of 0.845 (95% CI = 0.772-0.922). Elevated expression of miR-1260b in LAC tissues was positively correlated with exosomal-miR-1260b in plasma (r = .642, p < .05). Furthermore, ceramide biosynthesis regulated exosomal-miR-1260b secretion. Exosome-mediated transfer of miR-1260b promoted A549 cell invasion and was still functional inside A549 cells. Moreover, exosomal-miR-1260b regulated Wnt/ß-catenin signaling pathway by inhibiting sFRP1 and Smad4. This study identified a new regulation mechanism involving in cell invasion by exosome-mediated tumor-cell-to-tumor-cell communication. Targeting exosome-microRNAs may provide new insights into the diagnosis and treatment of LAC.

12.
Cell Biol Toxicol ; 2020 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-32002708

RESUMO

Androgen deprivation therapy (ADT) via surgical or chemical castration frequently fails to halt lethal castration-resistant prostate cancer (CRPC), which is induced by multiple mechanisms involving constitutive androgen receptor (AR) splice variants, AR mutation, and/or de novo androgen synthesis. The AR N-terminal domain (NTD) possesses most transcriptional activity and is proposed as a potential target for CRPC drug development. We constructed a screening system targeting AR-NTD transcription activity to screening a compound library and identified a novel small molecule compound named QW07. The function evaluation and mechanism investigation of QW07 were carried out in vitro and in vivo. QW07 bound to AR-NTD directly, blocked the transactivation of AR-NTD, blocked interactions between co-regulatory proteins and androgen response elements (AREs), inhibited the expression of genes downstream of AR, and inhibited prostate cancer growth in vitro and in vivo. QW07 was demonstrated as an AR-NTD-specific antagonist with the potential to inhibit both canonical and variant-mediated AR signaling to regress the CRPC xenografts and is proposed as a lead compound for a specific antagonist targeting AR-NTD.

13.
J Ultrasound Med ; 2020 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-32003904

RESUMO

OBJECTIVES: The primary purpose of this study was to determine whether elasticity quantification of the levator ani muscle (LAM) using shear wave elastography (SWE) is different between women with and without pelvic organ prolapse (POP) and to determine whether LAM elasticity is associated with the prolapse stage or the dimensions of the levator hiatus. The secondary aim was to evaluate the intraobserver and interobserver reliability of LAM elasticity measurements using SWE. METHODS: The study participants included 20 women with normal pelvic support and 38 women with prolapse (stages I-III). The levator hiatus was imaged by transperineal 3-dimensional ultrasound, and LAM elasticity and the elastic modulus were measured by SWE at rest and while performing the Valsalva maneuver. RESULTS: The elastic modulus increased significantly from rest to during to maximal Valsalva maneuver (29.2 versus 54.1 kPa; P < .05) in all women. Levator ani muscle elasticity was significantly higher under prolapse conditions than under normal conditions at rest (27.9 versus 31 kPa; P < .001) but was lower during the maximal Valsalva maneuver than under normal conditions (57.3 versus 53.1 kPa; P < .05). Levator ani muscle elasticity at rest was associated with the hiatus area during the Valsalva maneuver (Spearman r = 0.608; P < .001) and distensibility of the levator hiatus (r = 0.594; P < .001), and the hiatus area decreased as the LAM elastic modulus increased during the maximal Valsalva maneuver (r = -0.414; P < .05). Moreover, LAM elasticity was associated with the severity of prolapse (P < .001). CONCLUSIONS: As a noninvasive quantitative method, SWE, may be used to assess the biomechanical properties of the pelvic floor muscle, providing some research basis for a thorough understanding of POP and its treatment and prevention.

14.
Invest Ophthalmol Vis Sci ; 61(2): 12, 2020 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-32049343

RESUMO

Purpose: This study aims at exploring alterations of major metabolites and metabolic pathways in retinopathy of prematurity (ROP) infants and identifying biomarkers that may merit early diagnosis of ROP. Methods: We analyzed targeted metabolites from 81 premature infants (<34 weeks of gestational age), including 40 ROP cases (15 males and 25 females, birth weight 1.263 ± 0. 345 kg, gestational age 31.20 ± 4.62 weeks) and 41 cases (30 males, 11 females, birth weight 1.220 ± 0.293 kg, gestational age 30.96 ± 4.17 weeks) of well-matched non-ROP controls. Metabolites were measured by ultra-performance liquid chromatography-tandem mass spectrometry. Standard multivariate and univariate analysis was performed to interpret metabolomic results. Results: Glycine, glutamate, leucine, serine, piperidine, valine, tryptophan, citrulline, malonyl carnitine (C3DC), and homocysteine were identified as the top discriminant metabolites. In particular, discriminant concentrations of C3DC and glycine were also confirmed by univariate analysis as statistically significant different between ROP and non-ROP infants. Conclusions: This study gained an insight into the metabolomic aspects of ROP development. We suggest that higher blood levels of C3DC and glycine can be promising biomarkers to predict the occurrence, but not the severity of ROP.

15.
Jpn J Clin Oncol ; 2020 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-31894237

RESUMO

BACKGROUND: Cadherin-11 (CDH11) is a type II cadherin and reported to function as an oncogene in various cancers. Our present study aims to investigate the role of CDH11 in bladder cancer (BCA). METHODS: Bioinformatics analysis was performed in four independent microarray data including 56 non-muscle-invasive bladder cancer (NMIBC) and 132 muscle-invasive bladder cancer (MIBC) tissues from Gene Expression Omnibus to screen out differentially expressed genes. Next, we detected CDH11 expression in BCA specimens and cell lines by qPCR and western blotting assays. Immunohistochemical analyses were performed in 209 paraffin-embedded BCA samples and 30 adjacent normal bladder tissues. RESULTS: Bioinformatics analysis revealed that CDH11 had a higher expression level in MIBC tissues than in NMIBC, which was consistent with our clinical BCA specimens and cell lines at both mRNA and protein levels. Immunohistochemical analysis demonstrated that over-expression of CDH11 was closely related to the histological grade, pT status, tumour size and poor outcomes of BCA patients. What's more, CDH11 (area under curve (AUC) = 0.673 and 0.735) had a better predictive value than E-cadherin (AUC = 0.629 and 0.629) and a similar discrimination with the European Organization for Research and Treatment of Cancer (EORTC) score system (AUC = 0.719 and 0.667) in evaluating potential recurrence and progression of NMIBC. Moreover, combination of CDH11 and EORTC score system was the best predictive model in predicting recurrence of NMIBC (AUC = 0.779) among the three models. CONCLUSIONS: CDH11 was a reliable therapeutic target in BCA and a useful index to predict the possibilities of recurrence and progression in NMIBC patients.

16.
Neuroimage Clin ; 25: 102182, 2020 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-31978826

RESUMO

Dementia affects 47 million individuals worldwide, and assuming the status quo is projected to rise to 150 million by 2050. Prevention of age-related cognitive impairment in older persons with lifestyle interventions continues to garner evidence but whether this can combat underlying neurodegeneration is unknown. The Study of Mental Activity and Resistance Training (SMART) trial has previously reported within-training findings; the aim of this study was to investigate the long-term neurostructural and cognitive impact of resistance exercise in Mild Cognitive Impairment (MCI). For the first time we show that hippocampal subareas particularly susceptible to volume loss in Alzheimer's disease (AD) are protected by resistance exercise for up to one year after training. One hundred MCI participants were randomised to one of four training groups: (1) Combined high intensity progressive resistance and computerised cognitive training (PRT+CCT), (2) PRT+Sham CCT, (3) CCT+Sham PRT, (4) Sham physical+sham cognitive training (SHAM+SHAM). Physical, neuropsychological and MRI assessments were carried out at baseline, 6 months (directly after training) and 18 months from baseline (12 months after intervention cessation). Here we report neuro-structural and functional changes over the 18-month trial period and the association with global cognitive and executive function measures. PRT but not CCT or PRT+CCT led to global long-term cognitive improvements above SHAM intervention at 18-month follow-up. Furthermore, hippocampal subfields susceptible to atrophy in AD were protected by PRT revealing an elimination of long-term atrophy in the left subiculum, and attenuation of atrophy in left CA1 and dentate gyrus when compared to SHAM+SHAM (p = 0.023, p = 0.020 and p = 0.027). These neuroprotective effects mediated a significant portion of long-term cognitive benefits. By contrast, within-training posterior cingulate plasticity decayed after training cessation and was unrelated to long term cognitive benefits. Neither general physical activity levels nor fitness change over the 18-month period mediated hippocampal trajectory, demonstrating that enduring hippocampal subfield plasticity is not a simple reflection of post-training changes in fitness or physical activity participation. Notably, resting-state fMRI analysis revealed that both the hippocampus and posterior cingulate participate in a functional network that continued to be upregulated following intervention cessation. Multiple structural mechanisms may contribute to the long-term global cognitive benefit of resistance exercise, developing along different time courses but functionally linked. For the first time we show that 6 months of high intensity resistance exercise is capable of not only promoting better cognition in those with MCI, but also protecting AD-vulnerable hippocampal subfields from degeneration for at least 12 months post-intervention. These findings emphasise the therapeutic potential of resistance exercise; however, future work will need to establish just how long-lived these outcomes are and whether they are sufficient to delay dementia.

17.
Nanotechnology ; 2020 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-31978931

RESUMO

Both p-type ZrO2and n-type ZnO are widely adopted oxides towards trace gas detections; however, their combinations to achieve an enhanced gas sensing performance are rarely reported. Herein, we adopted a simple solution combustion technique to synthesize ZnO-ZrO2composites for isopropanol sensing. The one-step combustion achieved coral-like macro/mesoporous hierarchical architectures. It is found that, when the Zr/Zn molar ratio is less than 0.02, all Zr atoms were doped into ZnO crystallites; whilst ZrO2appeared when the ratio is beyond 0.03. When utilized to detect trace isopropanol in air, the response increases linearly with the increasing concentration of the target gas in the range of 10~1000 ppm. At the optimal operation temperature of 350°C, the largest slope (0.18 ppm-1) is recorded for the ZnO-ZrO2 composite with a Zr/Zn molar ratio of 0.04 and the slope is 23 times that of pure ZnO (0.0078 ppm-1). It exhibits also a fast response time and recovery time of 19 s and 8 s, respectively, under 100 ppm isopropanol. The impressive gas sensing property can be contributed to both the macro-/mesoporous structure, which facilitates an intimate contact between the target gas and the sensing site, and the p-n junction induced built-in electric field, which favors the charge separation.

18.
J Hematol Oncol ; 13(1): 3, 2020 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-31907001

RESUMO

BACKGROUND: The propensity of the activated neutrophils to form extracellular traps (NETs) is demonstrated in multiple inflammatory conditions. In this study, we investigated the roles of NETs in metastasis of hepatocellular carcinoma (HCC) and further explored the underlying mechanism of how NETs affect metastasis as well as the therapeutic value. METHODS: The neutrophils were isolated from the blood of human HCC patients and used to evaluate the formation of NETs. The expression of NET markers was detected in tumor specimens. A LPS-induced NET model was used to investigate the role of NETs on HCC metastasis. RNA-seq was performed to identify the key molecular event triggered by NETs, and their underlying mechanism and therapeutic significance were explored using both in vitro and in vivo assays. RESULTS: NET formation was enhanced in neutrophils derived from HCC patients, especially those with metastatic HCCs. NETs trapped HCC cells and subsequently induced cell-death resistance and enhanced invasiveness to trigger their metastatic potential, which was mediated by internalization of NETs into trapped HCC cells and activation of Toll-like receptors TLR4/9-COX2 signaling. Inhibition of TLR4/9-COX2 signaling abrogated the NET-aroused metastatic potential. A combination of DNase 1 directly wrecking NETs with anti-inflammation drugs aspirin/hydroxychloroquine effectively reduced HCC metastasis in mice model. CONCLUSIONS: NETs trigger tumorous inflammatory response and fuel HCC metastasis. Targeting NETs rather than neutrophils themselves can be a practice strategy against HCC metastasis.

19.
J Neurol Sci ; 409: 116621, 2020 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-31945583

RESUMO

BACKGROUND AND PURPOSE: To develop and validate a novel perivascular space rating scale, based on single axial slices in the basal ganglia and the centrum semiovale on T1-weighted and FLAIR images obtained on a 3T MRI scanner. METHODS: 414 community dwelling older adults age 70-90 were assessed. The number of perivascular spaces in the slices 2 mm (basal ganglia) and 37 mm (centrum semiovale) above the anterior commissure were counted. The construct validity of the scale was tested by examining associations with age, sex, vascular risk factors and neuroimaging markers of small vessel disease; white matter hyperintensities, lacunes and cerebral microbleeds. Associations with cross sectional global and domain specific cognition were also examined. RESULTS: The rating scale had excellent inter-rater reliability (intraclass correlation coefficient in basal ganglia 0.82 and centrum semiovale 0.96), good intra-rater reliability (ICC in basal ganglia 0.72 and centrum semiovale 0.87) and reasonable concurrent validity with an existing perivascular spaces scale (Spearman rho = 0.49, p < .001). There was a median of four basal ganglia and zero centrum semiovale perivascular spaces. Basal ganglia perivascular spaces were more common in men and associated with the other neuroimaging markers. Perivascular spaces in either location were not independently associated with global or domain specific cognitive impairment. CONCLUSION: The new rating scale is easy to use, quick, has good psychometric properties and performs better than existing scales in a community dwelling older cohort. Further studies are needed to validate the scale in more diverse cohorts with greater cerebrovascular burden.

20.
Artigo em Inglês | MEDLINE | ID: mdl-31989496

RESUMO

Itol A, an isoryanodane diterpene derived from Itoa orientalis Hemsl. (Flacourtiaceae), is a potential plant-based insecticide. However, the effect of itol A on the tobacco cutworm [Spodoptera litura (Fab.) (Lepidoptera: Noctuidae)], an important and widely distributed insect pest, remains unclear. In this study, the toxicity and inhibitory potency of itol A on S. litura were evaluated. The results indicated that itol A exhibited larvicidal activity against the third instar larvae in a concentration-dependent manner (LC50 875.48 mg/L at 96 h). Antifeedant activity also was observed, and the 24-h AFC50 values were 562.05 and 81.47 mg/L in the no-choice and choice experiments, respectively. The insect growth was inhibited after treatment of itol A, as reflected by long developmental periods, low-quality pupae, and various abnormalities. Itol A exerted ovicidal effect on S. litura, with an estimated LC50 of 759.30 mg/L. Itol A deterred oviposition in the choice experiment (ODI50 909.60 mg/L). Besides, the activities of α-amylase, general protease, superoxide dismutase (SOD), catalase (CAT), and peroxidase (POD) were inhibited after itol A treatment over time compared to controls, which may be a relevant mechanism underlying the toxicity of itol A toward S. litura. However, the activities of lipase, carboxylesterase (CarE), glutathione S-transferase (GST), and cytochrome P450 monooxygenase (P450) were increased. Taken together, these results suggest that itol A could be a good botanical pesticide to reduce the population of S. litura in integrated pest management programs.

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