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1.
J Sci Food Agric ; 2019 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-31487041

RESUMO

BACKGROUND: This study investigates the efficacy of short peptides secreted by Bacillus subtilis for fungi inhibition and shelf-life maintenance of fresh-cut pumpkin. RESULTS: Low-molecular-weight filtrate (LC< 1,000 Da) of B. subtilis culture (BC) significantly lowered the total number of moulds on fresh-cut pumpkin compared with the untreated control and BC group after storage. LC prevented the deterioration of sensory quality in pumpkin incision, and reduced pectinase activity. LC also inhibited the growth of Phytophthora capsici and Penicillium chrysogenum, and the activity of ß-1,3-glucan synthase (GS) secreted by both moulds. Fifty-seven GS-inhibiting peptides were screened from 95 LC peptides with 2-5 amino acid residues. The two most potent peptides, AWYW and HWWY, had highly suppressive effects on the growth of P. capsici and P. chrysogenum. CONCLUSION: Our study demonstrated that short peptides present in Bacillus subtilis culture can play an important role in the maintenance of fresh-cut pumpkin by suppressing fungal growth. This article is protected by copyright. All rights reserved.

2.
J Diabetes Complications ; : 107419, 2019 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-31473080

RESUMO

OBJECTIVE: Although diabetic kidney disease (DKD) has been considered as a glomerulocentric disease in the past few decades, growing evidence demonstrated that tubular damage was indispensable in its pathogenesis and progression. This study was designed to investigate the association of urinary acidification dysfunction with the progression of DKD in type 2 diabetic patients. METHODS: Here the urinary acidification functions were measured from 80 participants with renal biopsy-proven DKD. The different kinds of renal tubular transportation dysfunction were analyzed, including the dysfunction of bicarbonate reabsorption, titratable acid secretion, and ammonium secretion. In addition, patients were followed up for 17 (interquartile range, 11-32) months to evaluate the effect of urinary acidification dysfunction in the progression of DKD. RESULTS: The most common urinary acidification dysfunction was the disorder of ammonium secretion, accounting for 53.75%. The more proteinuria excretion and the lower glomerular filtration rate (GFR) were observed in the urinary titratable acid disorder group than the normal group, and the same results were obtained for ammonium secretion disorder. Urine titratable acid was positively correlated with eGFR whereas it was inversely correlated with proteinuria, serum creatinine, and BUN. Moreover, 24 h urine protein, serum creatinine, BUN and cystatin C increased from DKD stage II to stage IV, whereas the eGFR and urine titratable acid decreased in the same way. Furthermore, Kaplan-Meier analysis and Cox regression showed that the disorder of titratable acid was an independent risk factor for DKD progression. CONCLUSIONS: The dysfunction of urinary titratable acid is a potential biomarker for the severity of proteinuria, eGFR and glomerular lesions in patients with DKD. Moreover, the titratable acid disorder is an independent risk factor of the DKD progression.

3.
Artigo em Inglês | MEDLINE | ID: mdl-31491931

RESUMO

To explore the effects of different types of forest environments for forest therapy, this study focused on forest resting environments. Seven representative forest resting environments found in field research in Beijing were used as independent variables and were shown to subjects by a virtual reality (VR) video. Stress level was used as the dependent variable, and blood pressure, heart rate, salivary amylase, and the Brief Profile of Mood States (BPOMS) were used as physiological and psychological indicators. A between-subjects design was used in the experiment. A total of 96 subjects were randomly assigned to each environment type, and only one type of forest resting environment was observed. Through the relevant sample t-test and one-way analysis of variance, the pre- and post-test data of the indicators were analyzed. This study found that all the seven different types of forest resting environments can produce stress relief effects to some extent. Different types of forest resting environments have different effects on relieving stress. The most natural environment does not have the most significant effect on stress relief. A water landscape has a positive effect on the relief of stress. The conclusions of this study are conducive to the better use of the forest environment for forest therapy services.

4.
Sci Rep ; 9(1): 12824, 2019 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-31492890

RESUMO

The search for green and sustainable modification method to produce durable bamboo materials remains a challenge in industry. Here, heat treatment in tung oil at 100-200 °C was employed to modify bamboo materials. Oil permeation and distribution in the structure of bamboo samples during heat treatment were explored. The synergistic effects of tung oil and heat treatment on the chemical, physical and mechanical properties of bamboo materials, and their mutual relationships were also investigated in detail. Results showed that the tung oil heat treated bamboo not only had an enhanced hydrophobic property and dimensional stability, improved fungi resistance, but also displayed good mechanical performance. Compared with the untreated sample, the water-saturated swelling reduced from 3.17% to 2.42% for the sample after oil heat treatment at 200 °C, and the contact angles of the sample after oil heat treatment at 200 °C can keep >100° after 300 s in radial direction. Such improvement can be attributed to changes of chemical components, increased crystallinity structure, and the formation of oily films inside or over the bamboo surface. Therefore, tung oil heat treatment can be a highly promising technology for bamboo modification in the industry.

5.
J Am Chem Soc ; 2019 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-31487162

RESUMO

The iron-dependent oxidase UndA cleaves one C3-H bond and the C1-C2 bond of dodecanoic acid to produce 1-undecene and CO2. A published x-ray crystal structure showed that UndA has a heme-oxygenase-like fold, thus associating it with a structural superfamily that includes known and postulated nonheme diiron proteins, but revealed only a single iron ion in the active site. Mechanisms proposed for initiation of decarboxylation by cleavage of the C3-H bond using a mono-iron cofactor to activate O2 necessarily invoked unusual or potentially unfeasible steps. Here we present spectroscopic, crystallographic, and biochemical evidence that the cofactor of Pseudomonas fluorescens Pf-5 UndA is, in fact, a diiron cluster and show that binding of the substrate triggers rapid addition of O2 to the Fe2(II/II) cofactor to produce a transient peroxo-Fe2(III/III) intermediate. The observations of a diiron cofactor and substrate-triggered formation of a peroxo-Fe2(III/III) intermediate suggest a small set of possible mechanisms for O2, C3-H and C1-C2 activation by UndA; these routes obviate the problematic steps of the earlier hypotheses that invoked a single iron.

6.
Infect Genet Evol ; : 104035, 2019 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-31505276

RESUMO

The human mastadenovirus C (HAdV-C) cause respiratory infections in children. Homologous recombination was clearly involved in the molecular evolution of HAdV-A, B, and D, but little is known about the molecular evolution of HAdV-C. From 2000 to 2016, 201 HAdV-C strains were collected from nine provinces covering six administrative regions of mainland of China via 3 existing surveillance programs, namely the febrile respiratory syndrome surveillance, the acute flaccid paralysis surveillance, and the hand, foot, and mouth disease surveillance system. The genes coding for the capsid protein (penton base, hexon, and fiber) of 201 HAdV-C strains were sequenced and compared with representative sequences publicly available. In addition, the whole genome sequence of 24 representative strains of HAdV-C was generated for further recombination analysis. Phylogenetic analysis of the penton base sequences of HAdV-C revealed six genetic groups (labelled as Px1-6), which showed that the penton base had more variation than previously thought. Based on the penton base, hexon, and fiber gene sequences, 16 new genetic patterns of HAdV-C circulating in mainland of China were identified in this study. Whole genome sequence analysis revealed frequent recombination events among HAdV-C genomes. This study is highly beneficial for case classification, tracking the transmission chain, and further epidemiological exploration of HAdV-C-related severe clinical diseases in the near future. Our data demonstrated that multiple newly divergent HAdV-C co-circulated across mainland China during the research period.

7.
Pharmacology ; : 1-10, 2019 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-31514188

RESUMO

The present study evaluated the protective effects of pseurotin A against inflammation and the destruction of cartilage in a rat model of rheumatoid arthritis (RA). RA was induced by intradermal injections of Freund's complete adjuvant (1 mg/mL), and the treatment with pseurotin A (50 and 100 mg/kg, p.o.) was administered over 1 week. The effects of pseurotin A were assessed by estimating hind paw volume (HPV) and determining the levels of inflammatory mediators in the serum and synovial fluid of collagen-induced arthritis (CIA)-induced RA rats. Western blot and histopathological assays were performed to assess changes in synovial tissues. Additionally, in vitro analyses of receptor activator of nuclear factor-kappa-Β ligand (RANKL)-stimulated RAW264.7 cells treated with pseurotin A at different concentrations (1, 10, and 100 µg/mL) were conducted to assess the effects of pseurotin A on apoptosis ratio, real-time polymerase chain reaction data, and tartrate-resistant acid phosphatase staining. Compared to the RA group, treatment with pseurotin A significantly decreased HPV and reduced the levels of inflammatory mediators in the synovial fluid and blood. Additionally, pseurotin A ameliorated the protein expressions of osteoprotegerin, nuclear factor of activated T-cells, nuclear factor-kappa beta (NF-κB), IκBα, extracellular signal regulated kinase, and P38 as well as histopathological changes in the synovial tissue of CIA-induced RA rats. The in vitro findings revealed that pseurotin A treatment did not alter the apoptosis ratio in RANKL-stimulated RAW264.7 cells but significantly reduced the mRNA expressions of calcitonin receptor, NF-κB, and matrix metallopeptidase-9. The present findings suggest that pseurotin A ameliorated the differentiation of osteoclasts and the destruction of cartilage in RA rats via regulation of the mitogen-activated protein kinase/RANKL/NF-kB pathway.

8.
J Food Biochem ; : e13032, 2019 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-31502279

RESUMO

This animal experiment was framed to evaluate the beneficial effect of ginsenoside Rg1 (GRg1) against imiquimod (IMQ)-induced psoriasis-like dermatitis model to reveal the underpinning mechanism. Fifty healthy BALB/c mice were divided into five groups as control, GRg1, IMQ induced, oral treatment of GRg1 (50 mg/kg), or dexamethasone (DXM; 10 mg/kg) in IMQ-induced mice. Treatment with GRg1 or DXM significantly mitigates (p < .01) psoriasis area severity index (PASI) score, skin thickness, lipid peroxidation, and inflammatory markers (IL-23, 22, 17A, 1ß, and TNF-α). Moreover, administration of GRg1 or DXM considerably reversed the morphological changes induced by IMQ with improved (p < .01) antioxidant activity (SOD, CAT). In addition, a marked downregulation (p < .01) of protein expressions of pIκB and NF-κB p65 (NF-κB signaling pathway) were noted in GRg1 group. Collectively, GRg1 or DXM treatment significantly abolishes IMQ-induced psoriasis-like dermatitis by lowering PASI score, inflammation through downregulating NF-κB signaling pathway. PRACTICAL APPLICATIONS: This is the very first study to explore the efficacy of ginsenoside Rg1 (GRg1) against IMQ-induced psoriasis in the mice model to reveal the underpinning mechanism. The results clearly showed that GRg1 potent anti-psoriasis activity by lowering PASI score, inflammation through downregulating NF-κB signaling pathway. Hence, this study helps in the development of novel nutraceutical/functional food against psoriasis and thus could improve the quality of life in psoriasis patients. However, further clinical trials are needed to justify the above results before developing a commercial functional food using GRg1 against psoriasis.

9.
Cell Death Dis ; 10(9): 648, 2019 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-31501415

RESUMO

Pulmonary fibrosis is characterized by the remodeling of fibrotic tissue and collagen deposition, which mainly results from aberrant fibroblasts proliferation and trans-differentiation to myofibroblasts. Patients with chronic myelogenous leukemia, myeloproliferative disorder, and scleroderma with pulmonary fibrosis complications show megakaryocyte infiltration in the lung. In this study, we demonstrated that the number of CD41+ megakaryocytes increased in bleomycin (BLM)-induced lung fibrosis tissues through the Chemokine (CXCmotif) ligand 12/Chemokine receptor 4 (CXCL12/CXCR4) axis. Pharmacological inhibition of the CXCL12/CXCR4 axis with WZ811 prevented migration of CD41+ megakaryocytes induced by BLM-injured lung tissue ex vivo and in vivo. In addition, WZ811 significantly attenuated lung fibrosis after BLM challenge. Moreover, megakaryocytes directly promoted fibroblast proliferation and trans-differentiation to myofibroblasts. We conclude that thrombopoietin (TPO) activated megakaryocytes through transforming growth factor ß (TGF-ß) pathway to promote fibroblast proliferation and trans-differentiation to myofibroblasts, which is abolished by treatment with selective TGF-ßR-1/ALK5 inhibitors. Therefore, CD41+ megakaryocytes migrate to injured lung tissue partially through the CXCL12/CXCR4 axis to promote the proliferation and trans-differentiation of fibroblasts through direct contact and the TGF-ß1 pathway.

10.
Opt Express ; 27(15): 21546-21564, 2019 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-31510230

RESUMO

Recently, silicon optical in-phase quadrature (IQ) modulators have played an increasingly important role in coherent optical transmission networks because of their small package size and low cost. To stabilize the modulation performance of the silicon IQ optical modulator (SIQOM), the bias voltages of the SIQOM must be maintained at optimum points. Because of the nonlinear modulation characteristic of the silicon material, it is difficult to achieve high-precision closed-loop control of the bias voltage for the SIQOM. In this paper, a novel automatic bias-control scheme for the SIQOM is proposed and investigated theoretically and experimentally. First, two sinusoidal power dithers with different low frequencies are applied to the channels I and Q biases of the SIQOM. Next, a pair of orthogonal trigonometric functions with the same frequency as the power dither signal is constructed. We find that the optimum point of the bias voltage is the intersection of the orthogonal-integral curves via cross-correlation integral operations between the output signal of the SIQOM and the aforementioned trigonometric functions. The results indicate that the bias errors of the channels I/Q/P relative to the optimum point can be corrected precisely by the proposed scheme, and the jitters of the vector amplitude error caused by this scheme are <1% in 128-Gb/s dual-polarization quadrature phase-shift keying and single-polarization 16-quadrature amplitude modulation formats.

11.
Autism Res ; 2019 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-31389199

RESUMO

The cognitive phenotypes of Rett syndrome (RTT) remain unclarified compared with the well-defined genetic etiology. Recent clinical studies suggest the eye-tracking method as a promising avenue to quantify the visual phenotypes of the syndrome. The present study explored various aspects of visual attention of the methyl-CpG-binding protein 2 gene mutant RTT monkeys with the eye-tracking procedure. Comprehensive testing paradigms, including social valence comparison (SVC), visual paired comparison (VPC), and social recognition memory (SRM), were utilized to investigate their attentional features to social stimuli with differential valence, the novelty preferences, and short-term recognition memory, respectively. To explore the neurobiological mechanisms underlying the eye-tracking findings, we assessed changes of the brain subregion volumes and neurotransmitter concentrations. Compared with control monkeys, RTT monkeys demonstrated increased viewing on the more salient stare faces than profile faces in the SVC test, and increased viewing on the whole presented images composed of monkey faces in the VPC and SRM tests. Brain imaging revealed reduced bilateral occipital gyrus in RTT monkeys. The exploratory neurotransmitter analyses revealed no significant changes of various neurotransmitter concentrations in the cerebrospinal fluid and blood of RTT monkeys. The eye-tracking results suggested social-valence-related increased attention in RTT monkeys, supplementing the cognitive phenotypes associated with the syndrome. Further investigations from broader perspectives are required to uncover the underlying neurobiological mechanisms. Autism Res 2019, 00: 1-13. © 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: Altered expressions of the methyl-CpG-binding protein 2 (MECP2) gene are usually associated with neurodevelopmental disorders, such as autism spectrum disorders, Rett syndrome (RTT), and so forth. The present eye-tracking study found social-valence-related increased attention in our firstly established MECP2 mutant RTT monkeys. The novel findings supplement the cognitive phenotypes and potentially benefit the behavioral interventions of the RTT syndrome.

12.
PLoS Genet ; 15(8): e1008328, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31404065

RESUMO

TRAM is a conserved domain among RNA modification proteins that are widely distributed in various organisms. In Archaea, TRAM occurs frequently as a standalone protein with in vitro RNA chaperone activity; however, its biological significance and functional mechanism remain unknown. This work demonstrated that TRAM0076 is an abundant standalone TRAM protein in the genetically tractable methanoarcheaon Methanococcus maripaludis. Deletion of MMP0076, the gene encoding TRAM0076, markedly reduced the growth and altered transcription of 55% of the genome. Substitution mutations of Phe39, Phe42, Phe63, Phe65 and Arg35 in the recombinant TRAM0076 decreased the in vitro duplex RNA unfolding activity. These mutations also prevented complementation of the growth defect of the MMP0076 deletion mutant, indicating that the duplex RNA unfolding activity was essential for its physiological function. A genome-wide mapping of transcription start sites identified many 5' untranslated regions (5'UTRs) of 20-60 nt which could be potential targets of a RNA chaperone. TRAM0076 unfolded three representative 5'UTR structures in vitro and facilitated the in vivo expression of a mCherry reporter system fused to the 5'UTRs, thus behaving like a transcription anti-terminator. Flag-tagged-TRAM0076 co-immunoprecipitated a large number of cellular RNAs, suggesting that TRAM0076 plays multiple roles in addition to unfolding incorrect RNA structures. This work demonstrates that the conserved archaeal RNA chaperone TRAM globally affects gene expression and may represent a transcriptional element in ancient life of the RNA world.

13.
J Immunother Cancer ; 7(1): 233, 2019 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-31464648

RESUMO

BACKGROUND: Programmed cell death protein 1 (PD-1) is a key immune checkpoint that regulates peripheral tolerance and protects against autoimmunity. Programmed death ligand-2 (PD-L2) is a less studied ligand to PD-1 and has yet to be fully explored, especially in pancreatic ductal adenocarcinoma (PDAC). METHODS: In this study, we performed immunohistochemistry to detect the PD-L2, CD3, CD8, transforming growth factor-ß2 (TGF-ß2) and FOXP3 levels in paraffin sections from 305 patients with resected PDAC as a training set. Expression levels of intratumoral and stromal immune markers were compared in relation to survival using Kaplan-Meier curves, random survival forest model and survival tree analysis. A multivariable Cox proportional-hazards model of associated markers was used to calculate the risk scores. RESULTS: PD-L2 was expressed in 71.5% of PDAC samples and showed strong correlations with CD3+, CD8+ T cells and FOXP3+ regulatory T cell densities. High levels of intratumoral PD-L2 and FOXP3 were related to poor survival; only stromal FOXP3 overexpression was associated with worse prognosis. Four patterns generated from survival tree analysis demonstrated that PD-L2lowstromalFOXP3low patients had the longest survival, while PD-L2highintratumoralCD3low patients had the shortest survival (P <  0.001). The area under the curve was 0.631(95% confidence interval (CI): 0.447-0.826) for the immune marker-based signature and 0.549 (95% CI: 0.323-0.829; P <  0.001) for the clinical parameter-based signature, which was consistent with the results in the validation set including 150 patients (P <  0.001). A higher risk score indicated shorter survival and could serve as an independent prognostic factor. PD-L2 was also showed associated with TGF-ß2 and other immune molecules based on bioinformatics analysis. CONCLUSIONS: Our work highlighted PD-L2 as a promising immunotherapeutic target with prognostic value combined with complex tumor infiltrating cells in PDAC.

14.
Inflammopharmacology ; 2019 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-31463666

RESUMO

This study aimed to explore the predictive value of 10 serum cytokines for clinical response to etanercept (ETN) in rheumatoid arthritis (RA) patients. Totally 128 active RA patients were enrolled, and their serum cytokines levels were detected by enzyme-linked immune sorbent assay at baseline. All patients received ETN treatment for 24 weeks, and clinical response to ETN was assessed at week 4 (W4), week 12 (W12) and week 24 (W24). There were 40 (31.3%), 74 (57.8%) and 94 (73.4%) patients who achieved clinical response at W4, W12 and W24, respectively. Based on the clinical response status at W24, patients were divided into responders and non-responders. Baseline levels of interleukin (IL)-1ß and IL-17A were higher in responders, while baseline levels of tumor necrosis factor (TNF)-α, IL-6, 1L-8, IL-21, IL-23, intercellular cell adhesion molecule-1 (ICAM-1) and vascular endothelial growth factor (VEGF) were similar in responders compared with non-responders. Responders had less of a history of biologics, and higher baseline level of C-reactive protein (CRP) compared with non-responders. Further analysis revealed that CRP and IL-1ß were independent factors predicting increased clinical response. Subsequent receiver operating characteristics (ROC) curve analysis illustrated that the combination of CRP and IL-1ß (AUC: 0.730, 95% CI 0.636-0.824) well distinguished responders from non-responders. In conclusion, IL-1ß, IL-17A, CRP and biologics history would serve as potential markers for clinical response to ETN in RA patients.

15.
BMC Plant Biol ; 19(1): 375, 2019 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-31455268

RESUMO

BACKGROUND: Gynodioecy, a sexual system with hermaphrodite and female individuals in a population, raises the question how the two sexual morphs are maintained. Salvia pratensis is a gynodioecious species featured by its modified stamens that act as a lever mechanism in pollination. Given sexual dimorphism in floral traits of the species, it is predictable that two sexual morphs differ in their interplay with pollinators and thus in their fitness. In this study, we investigated sex-specific reproduction success and floral adaptation in a population of S. pratensis. RESULTS: We found that two sexual morphs in S. pratensis distinctly differed in their floral proportions. Female flowers fitted better to the pollinators than hermaphrodites in terms of touching the stigmas when being probed, and hence were more efficient in pollen deposition. Floral traits overall underwent stronger selection in the population, with stigma position and corolla length subject to disruptive selection mediated by different body-sized bumble bees; some selections on floral traits were significantly different in the strength, even opposite in the direction between two morphs. Flower production tended to be under correlational selection with floral structural traits, implying that a large plant with many flowers did not show an advantage in fitness unless its flower construction mechanically matched the pollinators well. CONCLUSIONS: In conclusion, the pollinator-mediated selection likely played an important role in the evolution and maintenance of sexual dimorphism in the gynodioecious S. pratensis; and sex-divergent mechanical interaction with pollinators served as a critical mechanism by which female individuals were maintained in the population with a female advantage in pollen deposition efficiency (i.e. receiving pollen).

16.
Inorg Chem ; 58(17): 11622-11629, 2019 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-31411464

RESUMO

For the nuclear industry, uranium is not only an important strategic resource but also a serious global contaminant with radiotoxicity and high chemotoxicity. It is very important to efficiently capture uranium from complex aqueous solutions for further treatment and disposal of nuclear wastes. Herein, we first demonstrate the suitability of a three-dimensional (3D) water-stable K+-exchanged zeolitic sulfide, namely K@GaSnS-1, for the remediation of radioactive and toxic uranium by ion exchange. In comparison to the pristine compound GaSnS-1, the K+-activated porous sulfide K@GaSnS-1 exhibits faster [UO2]2+ ion uptake kinetics, following the pseudo-second-order adsorption model. Further studies indicate that K@GaSnS-1 shows high exchange capacity (qmU = 147.6 mg/g) and wide pH resistance (pH 2.75-10.87). In particular, it can efficiently capture [UO2]2+ ion even when excessive amounts of Na+, K+, Mg2+, and Ca2+ ions are present. The highest distribution coefficient value Kd, signifying the affinity and selectivity for [UO2]2+ ion, reaches as high as 1.24 × 104 mL/g. More importantly, the uranium in corresponding exchanged samples can be facilely and effectively eluted by a low-cost and eco-friendly method. These merits of K@GaSnS-1 make it promising for the effective and selective removal of uranium from complex contaminated water.

17.
J Eval Clin Pract ; 2019 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-31429175

RESUMO

OBJECTIVE: To discuss the study design and data analysis for three-phase interrupted time series (ITS) studies to evaluate the impact of health policy, systems, or environmental interventions. Simulation methods are used to conduct power and sample size calculation for these studies. METHODS: We consider the design and analysis of three-phase ITS studies using a study funded by National Institutes of Health as an exemplar. The design and analysis of both one-arm and two-arm three-phase ITS studies are introduced. RESULTS: A simulation-based approach, with ready-to-use computer programs, was developed to determine the power for two types of three-phase ITS studies. Simulations were conducted to estimate the power of segmented autoregressive (AR) error models when autocorrelation ranged from -0.9 to 0.9 with various effect sizes. The power increased as the sample size or the effect size increased. The power to detect the same effect sizes varied largely, depending on testing level change, trend changes, or both. CONCLUSION: This article provides a convenient tool for investigators to generate sample sizes to ensure sufficient statistical power when three-phase ITS study design is implemented.

18.
J Am Chem Soc ; 141(35): 13914-13922, 2019 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-31394035

RESUMO

Multicomponent reactions are fundamentally different from two-component reactions, as multicomponent reactions can enable the efficient and step-economical construction of complex molecular scaffolds from simple precursors. Here, an unprecedented three-component direct C-H addition was achieved in the challenging meta-selective fashion. Fluoroalkyl halides and a wide range of alkenes, including vinylarenes, unactivated alkenes, and internal alkenes, were employed as the coupling partners of arenes in this strategy. The detailed mechanism presented is supported by kinetic isotope studies, radical clock experiments, and density functional theory calculations. Moreover, this strategy provided access to various fluoride-containing bioactive 1,1-diarylalkanes and other challenging synthetically potential products.

19.
Artigo em Inglês | MEDLINE | ID: mdl-31422138

RESUMO

OBJECTIVES: The aim of this study was to validate the feasibility of a novel structural and computational fluid dynamics-based fractional flow reserve (FFR) algorithm for coronary computed tomography angiography (CTA), using alternative boundary conditions to detect lesion-specific ischemia. BACKGROUND: A new model of computed tomographic (CT) FFR relying on boundary conditions derived from structural deformation of the coronary lumen and aorta with transluminal attenuation gradient and assumptions regarding microvascular resistance has been developed, but its accuracy has not yet been validated. METHODS: A total of 338 consecutive patients with 422 vessels from 9 Chinese medical centers undergoing CTA and invasive FFR were retrospectively analyzed. CT FFR values were obtained on a novel on-site computational fluid dynamics-based CT FFR (uCT-FFR [version 1.5, United-Imaging Healthcare, Shanghai, China]). Performance characteristics of uCT-FFR and CTA in detecting lesion-specific ischemia in all lesions, intermediate lesions (luminal stenosis 30% to 70%), and "gray zone" lesions (FFR 0.75 to 0.80) were calculated with invasive FFR as the reference standard. The effect of coronary calcification on uCT-FFR measurements was also assessed. RESULTS: Per vessel sensitivities, specificities, and accuracies of 0.89, 0.91, and 0.91 with uCT-FFR, 0.92, 0.34, and 0.55 with CTA, and 0.94, 0.37, and 0.58 with invasive coronary angiography, respectively, were found. There was higher specificity, accuracy, and AUC for uCT-FFR compared with CTA and qualitative invasive coronary angiography in all lesions, including intermediate lesions (p < 0.001 for all). No significant difference in diagnostic accuracy was observed in the "gray zone" range versus the other 2 lesion groups (FFR ≤0.75 and >0.80; p = 0.397) and in patients with "gray zone" versus FFR ≤0.75 (p = 0.633) and versus FFR >0.80 (p = 0.364), respectively. No significant difference in the diagnostic performance of uCT-FFR was found between patients with calcium scores ≥400 and <400 (p = 0.393). CONCLUSIONS: This novel computational fluid dynamics-based CT FFR approach demonstrates good performance in detecting lesion-specific ischemia. Additionally, it outperforms CTA and qualitative invasive coronary angiography, most notably in intermediate lesions, and may potentially have diagnostic power in gray zone and highly calcified lesions.

20.
Chem Commun (Camb) ; 55(73): 10980-10983, 2019 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-31453610

RESUMO

Photoredox-catalyzed direct keto-difluoroacetylation of styrenes with (fluorosulfonyl)difluoroacetate and dimethyl sulfoxide as an oxidant is disclosed. A variety of α-difluoroacetylated ketones bearing functional groups with good yields are obtained using fac-Ir(ppy)3 as a photocatalyst under visible light irradiation.

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