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1.
Drug Discov Today ; 2019 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-31669330

RESUMO

Drug-induced liver injury (DILI) is of significant concern to drug development and review because of the limited success with existing preclinical models. For developing alternative methods, a large drug list is needed with known DILI severity and toxicity. We augmented the DILIrank data set [annotated using US Food and Drug Administration (FDA) drug labeling)] with four literature datasets (N >350 drugs) to generate the largest drug list with DILI classification, called DILIst (DILI severity and toxicity). DILIst comprises 1303 drugs, of which 789 a DILI positives (increase of 69% from DILIrank), whereas 514 were DILI negatives (increase of 66%). The investigation of DILI positive-negative distribution across various therapeutic categories revealed the most and least frequent DILI categories. Thus, we consider DILIst to be an invaluable resource for the community to improve DILI research.

2.
Artigo em Inglês | MEDLINE | ID: mdl-31670499

RESUMO

In this work, photothermal-responsive graphene oxide (GO) based membranes intercalated by multiwalled carbon nanotubes (MWCNTs) were prepared by polydopamine (PDA) modification and 2-ureido-4[1H]-pyrimidinone (UPy) assembly process. Benefited from the high photothermal conversion ability of PDA and reversible UPy dimer, the permeation flux of GO-based membrane can be easily modulated with a high gating ratio under near-infrared (NIR) light switched off and on. Nanochannels created by the intercalation of MWCNTs into GO layers greatly increase water permeation without sacrificing the rejection of dye molecules in water (96.2% for methyl orange, 98.9% for rhodamine B, and 99.7% for coomassie brilliant blue). The composite membranes also exhibit trade-off between rejection of heavy metal ions (Cu2+ and Fe3+). Moreover, such GO-based membranes show high pH-stabilities, which shows great potential in the water purification applications.

3.
Genome ; 2019 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-31580743

RESUMO

A completely developed and vigorous root system can provide a stable platform for above-ground plant organs. To identify loci controlling root traits that could be used in wheat (Triticum aestivum L.) breeding, 199 recombinant inbred lines were used to measure and analyze eight root traits. A total of 18 quantitative trait loci (QTL) located on chromosomes 1A, 2A, 2B, 2D, 4B, 4D, 6A, 7A, and 7B were identified. The phenotypic variation explained by these 18 QTL ranged from 3.27% to 11.75%, and the logarithm of odds scores ranged from 2.50 to 6.58. A comparison of physical intervals indicated several new QTL for root traits were identified. In addition, significant correlations between root and agronomic traits were detected and discussed. The results presented in this study, along with those of previous reports, suggest that chromosomes 2 and 7 likely play important roles in the growth and development of wheat roots.

4.
Brain Stimul ; 2019 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-31606448

RESUMO

BACKGROUND: Transcranial direct current stimulation (tDCS) has been explored in epilepsy with limited samples, varied parameters, and inconclusive results. We aimed to study the efficacy of tDCS for patients with refractory focal epilepsy. METHOD: We conducted a randomized, double-blind, sham-controlled, and three-arm (Group 1 (sham), Group 2 (20-min), and Group 3 (2 × 20-min)) tDCS parallel multicenter study. The primary outcome measurement was seizure frequencies (SFs). The study consisted of 28-days baseline, 14-days treatment, and 56-days follow-up. The cathode was placed over the epileptogenic focus, and the current intensity was 2 mA. The generalized estimating equations model, one-way analysis of variance, chi-square and Kruskal-Wallis test were used for analysis. RESULTS: Of the 82 enrolled patients, 70 patients were included for final analysis (Group 1, n = 21; Group 2, n = 24; and Group 3, n = 25). There was a significant reduction in SFs for both active tDCS groups compared with the sham group. Patients in Group 2 showed a significantly 50.73-21.91% greater reduction in SFs that lasted for 4 weeks (p = 0.008-0.060). Patients in Group 3 showed a significantly 63.19-49.79% greater reduction in SFs compared with the sham group that lasted for 5 weeks (p = 0.011-0.045). Patients in Group 3 had a 64.98-66.32% greater reduction in SFs at W9-W10, when compared with Group 2 (p = 0.021-0.022). CONCLUSION: Fourteen consecutive days tDCS significantly decreased SFs in patients with refractory focal epilepsy, with 2 × 20-min daily stimulation protocol being superior to 20-min daily stimulation protocol.

5.
J Formos Med Assoc ; 2019 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-31594668

RESUMO

BACKGROUND/PURPOSE: Understanding the root canal systems of molars and the association of root canal system in adjacent or contralateral molars is important for dental practice. This study aimed to use cone-beam computed tomography (CBCT) to analyze the morphology similarity of root canal systems in the maxillary first and second molars. METHODS: CBCT images of 1741 maxillary molars in a total of 519 patients were blindly examined to analyze the correlation of root canal systems between maxillary first and second molars as well as the bilateral first and second molars. RESULTS: The most common type in maxillary first molars is 3R4C (3 roots/4 canals), whereas in maxillary second molars is 3R3C.The symmetry in type of root canals in bilateral maxillary first and second molars were 87.36% and 79.85%, respectively. The similarities of root canal system in adjacent maxillary first and second molars were 53.07% (right side) and 52.58% (left side). The concurrence of MB2 canal in bilateral maxillary first molars is 77.8%, and 35.97% in maxillary second molars. In the 110 patients with MB2 canal in bilateral maxillary second molars, the chance of bilateral MB2 canals in their maxillary first molar is almost 100%. CONCLUSION: Maxillary first molars have higher prevalence of 3R4C than second molars. The symmetry in bilateral maxillary molars is higher than the similarity in adjacent maxillary first and second molars. Application of CBCT analysis of root canal system can improve endodontic treatment outcomes. The correlation of root canal system between teeth is useful for genetic linkage.

6.
Nat Microbiol ; 2019 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-31591554

RESUMO

Phototrophic communities of photosynthetic algae or cyanobacteria and heterotrophic bacteria or fungi are pervasive throughout the environment1. How interactions between members contribute to the resilience and affect the fitness of phototrophic communities is not fully understood2,3. Here, we integrated metatranscriptomics, metabolomics and phenotyping with computational modelling to reveal condition-dependent secretion and cross-feeding of metabolites in a synthetic community. We discovered that interactions between members are highly dynamic and are driven by the availability of organic and inorganic nutrients. Environmental factors, such as ammonia concentration, influenced community stability by shifting members from collaborating to competing. Furthermore, overall fitness was dependent on genotype and streamlined genomes improved growth of the entire community. Our mechanistic framework provides insights into the physiology and metabolic response to environmental and genetic perturbation of these ubiquitous microbial associations.

7.
Plant Sci ; 289: 110277, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31623780

RESUMO

Along with the species evolution, plants have evolved ways to produce a different collection of terpenoids to accommodate its biotic and abiotic environment, and terpene synthase (TPS) is one of the major contributors to various terpene compounds. The timber of a monotypic and relictual conifer species of Cupressace, Taiwania cryptomerioides, has excellent durability, and one of the essential factors for Taiwania to resist decay and insect pests is sesquiterpene. Compared to other conifers, Taiwania has much higher abundance of cadinene-type sesquiterpenes, and the presence of cedrene-type sesquiterpenes. To understand sesquiterpene biosynthesis in Taiwania, we functionally characterized 10 T. cryptomerioides TPSs (TcTPSs) in vivo or in planta, which could catalyze sesquiterpene formation and potentially are involved in biosynthesis of diverse sesquiterpenoids in Taiwania. The distant phylogenetic relationship and the intron loss event of TcTPSs correlate to the differentiation of chemical profile Taiwania compared to other conifers. Furthermore, we identified TcTPS3 and TcTPS12 as δ-cadinene synthase, and TcTPS6 as cedrol synthase, which demonstrates the important contributions of dynamic evolution in TPSs to the chemical diversity in plants. Combining with functional characterization and comparison of catalytic residues, we conclude at least three catalytic routes for sesquiterpene biosynthesis in this species, and the skeleton diversity has been expended in T. cryptomeriodes.

8.
Inorg Chem ; 2019 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-31625384

RESUMO

An unprecedented cyclic TbIII-radical cluster, [Tb3(hfac)6(4-Me-3-NITtrz)2(OH)3] (1), has been self-assembled from Tb(hfac)3·2H2O and 4-Me-3-NITtrz in the presence of Cu(hfac)2·2H2O. Alternating-current magnetic studies show that the Tb3 cluster displays a dual slow relaxation of magnetization behavior under a zero direct-current (dc) field and a single relaxation process under an induced dc field with an effective energy barrier of 14 K, representing the first triangle 2p-4f cluster with a slow magnetic relaxation property.

9.
Zhongguo Zhong Yao Za Zhi ; 44(14): 3070-3077, 2019 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-31602855

RESUMO

In order to evaluate the quality of Styrax more comprehensively,this study attempted to establish an HPLC wavelength switching method to simultaneously determine the content of seven compounds in Styrax,and chemometrics were used to analyze the quality difference between different sources of Styrax,and finally establish a characteristic chromatogram of Styrax. The column was Agilent ZORBAX Extend C18( 4. 6 mm×250 mm,5 µm) with phase a mixture of acetonitrile-0. 1% phosphoric acid aqueous solution as the mobile phase in a gradient elution procedure; the detection wavelength was set as follows: 0-13. 5 min,194 nm( benzoic acid);13. 5-20. 5 min,278 nm( cinnamic acid); 20. 5-32 min,194 nm( benzyl benzoate,benzyl cinnamate,cinnamyl cinnamate,dehydroabietic acid); 32-55 min,241 nm( abietic acid). The methodological verification results showed that when the injection masses of benzoic acid,cinnamic acid,benzyl benzoate,benzyl cinnamate,cinnamyl cinnamate,dehydroabietic acid and abietic acid were0. 006 948-0. 694 8,0. 001 426-0. 142 6,0. 013 16-0. 658 0,0. 006 148-0. 614 8,0. 008 035-0. 803 5,0. 002 121-0. 212 1,and0. 010 172-1. 017 2 µg,respectively,there were good linear relationship between injection mass and peak area. The average recovery rates of seven compounds were in the range from 94. 34% to 105. 8%,and all RSD were less than 3. 0%( n = 6). The methodological verification results showed that the developed HPLC wavelength switching method has good accuracy and repeatability. The results of the sample analysis showed that the quality of Styrax from different sources was quite different. The chromatogram of Styrax reference material( S1) was used as the reference chromatogram to calculate the fingerprint similarity of each batch of samples. The results showed that the similarities of samples S2-S10 were 0. 952,0. 949,0. 981,0. 351,0. 751,0. 969,0. 979,0. 992 and 0. 971,respectively.The similarity values of other batches samples were satisfactory,except for sample S5 and S6,indicating that the quality difference among these samples is small. The similarity values of S11-S20 were 0. 060,0. 055,0. 054,0. 285,0. 092,0. 002,0. 044,0. 044,0. 044,and 0. 040,respectively. The results showed that compared with the sample S1,there was a large quality difference among S11-S20. Based on the chromatograms of S1-S10,the HPLC characteristic chromatograms of Styrax was established and the purpose is to give reference to other pharmaceutical researchers. The newly developed HPLC wavelength switching method have the advantages of simplicity,reproducibility and specificity,and the developed HPLC characteristic chromatograms provided a reference method for the overall quality evaluation of Styrax.


Assuntos
Medicamentos de Ervas Chinesas/análise , Compostos Fitoquímicos/análise , Styrax/química , Cromatografia Líquida de Alta Pressão , Controle de Qualidade , Reprodutibilidade dos Testes
10.
J Org Chem ; 2019 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-31645096

RESUMO

A facile and practical approach for the difluoromethylation of phenols and thiophenols was described. Making use of the recently developed bench-stable S-(difluoromethyl)sulfonium salt as the difluorocarbene precursor, a wide variety of diversely functionalized phenols and thiophenols were readily converted to their corresponding aryl difluoromethyl ethers in good to excellent yields in the presence of lithium hydroxide. Chemoselectivity of various O, S-nucleophiles toward difluorocarbene was systematically studied, suggesting the reactivity order ArS- > RS-, ArO- > ROH > RO- , ArSH, ArOH, RSH.

11.
Sci Rep ; 9(1): 14276, 2019 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-31582790

RESUMO

We wanted to determine whether subjective sleep disturbance was associated with serum glycated hemoglobin (HbA1c) in people with type 2 diabetes mellitus. In total, 944 randomly-selected people with diabetes completed the Chinese version of the Pittsburgh Sleep Quality Index (PSQI). Participants' glycaemia was assessed using HbA1c in March 2016 and September 2017. The PSQI score and the change in score(△PSQI), and the HbA1c and its change (△HbAlc) were analysed by sex and age (30-45, 46-60, 61-75, and 76-89 years). Associations between time point PSQI and △PSQI with static HbA1c and △HbA1c were analysed using multiple linear regression. The results showed subjective sleep disturbance among people with diabetes was not correlated with serum HbAlc (ß coefficient = 0.032, P = 0.103). However, cross-sectional multiple linear regression showed the relationship was present in women (ß coefficient = 0.163, P < 0.01). In multiple linear regression, △PSQI score was correlated with △HbAlc value (ß coefficient = 0.142, P < 0.01). The regression coefficient (ß) for the relationship between △PSQI score and △HbA1c in men was greater than that in women, and for age was ß61-75years < ß46-60years < ß30-45years. The strongest relationship between △PSQI and △HbA1c was in men aged 30-45 years (ß = 0.452, P < 0.01). Subjective sleep disturbance among people with diabetes was not related to glycaemic status in the whole sample, but there was a correlation in women. The change in subjective sleep disturbance correlated with the change in glycaemia, most strongly in younger participants, especially men aged 30-45 years.

12.
Mediators Inflamm ; 2019: 6750861, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31582901

RESUMO

Background: Pneumocystis pneumonia (PCP) remains a common opportunistic infection in immunosuppressed individuals. Current studies showed that multiple immune cells and cytokines took part in the host defense against Pneumocystis (PC). However, the roles of IL-17 and IL-10 in the development of PCP have not been elucidated. Methods: IL-10 and IL-17 levels in serum from PCP mice were detected via ELISA. The percentages of B10 cells, IL-10+ macrophages, and IL-10+ T cells in the lung from IL-17-/- PCP mice and Th17 cells and IL-17+ γδT cells in IL-10-/- PCP mice were examined via flow cytometry. Also, antibody neutralization examination was also performed to elucidate the relationship of IL-17 and IL-10 in the PCP model. Results: We noted the increase of IL-17 and IL-10 levels in serum from mice infected with Pneumocystis. Furthermore, deficiency of IL-17 or IL-10 could lead to the delayed clearance of Pneumocystis and more severed lung damage. Our data also demonstrated that IL-17 deficiency enhanced the serum IL-10 level and the percentages of B10 cells, IL-10+ macrophages, and IL-10+ T cells in the lung from PCP mice. Interestingly, we also noted an increase of the IL-17 level in serum and Th17 cell and IL-17+ γδT cell percentages in the lung from IL-10-/- PCP mice. Using antibody neutralization experiments, we found that the STAT3 gene might play a critical role in the interplay of IL-17 and IL-10 in PCP. Conclusion: Taken together, our results demonstrated that IL-17 and IL-10 could play the protective roles in the progression of PCP and the inverse correlation of them might be mediated by STAT3.

13.
J Agric Food Chem ; 67(42): 11665-11674, 2019 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-31588753

RESUMO

A long-term high-fat diet (HFD) can cause a range of health problems. Gut microbiota plays a decisive role in the development of HFD-associated inflammation, involved in function of T cells. This study was designed to probe the regulative effects of dietary stachyose, a functional oligosaccharide, on HFD-induced weight gain, inflammation, gut microbiota dysbiosis, and T cell abnormality in C57Bl/6 mice. Mice were divided into three groups which received normal chow, HFD and HFD plus stachyose (400 mg/kg), respectively. Results showed that administration of stachyose diminished the HFD-induced upregulation of serum TNF-α level and elevation of peripheral blood leukocyte populations to alleviate the HFD-caused colonic and hepatic inflammation in mice. Analysis of gut microbiota revealed that stachyose improved the intestinal homeostasis of HFD-fed mice by improving the bacterial diversity with the increases in the relative abundances of the Prevotellaceae_NK3B31_group, Parasutterella, Christensenellaceae_R-7_group, and Anaerovorax, as well as the fecal level of butanoic acid, while decreasing the ratio of Firmicutes-to-Bacteroidetes and the abundances of the Lachnospiraceae_NK4A136_group, Desulfovibrio, Anaerotruncus, Mucispirillum, Roseburia, and Odoribacter. Flow cytometric analysis showed that stachyose antagonized the HFD-induced decrease of peripheral CD4+ T cell population in mice. Conclusively, these findings suggest that long-term consumption of stachyose can ameliorate the HFD-associated colonic and hepatic inflammation and its complications by modulating gut microbiota.

14.
Nat Biotechnol ; 2019 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-31659337

RESUMO

Bacterial blight of rice is an important disease in Asia and Africa. The pathogen, Xanthomonas oryzae pv. oryzae (Xoo), secretes one or more of six known transcription-activator-like effectors (TALes) that bind specific promoter sequences and induce, at minimum, one of the three host sucrose transporter genes SWEET11, SWEET13 and SWEET14, the expression of which is required for disease susceptibility. We used CRISPR-Cas9-mediated genome editing to introduce mutations in all three SWEET gene promoters. Editing was further informed by sequence analyses of TALe genes in 63 Xoo strains, which revealed multiple TALe variants for SWEET13 alleles. Mutations were also created in SWEET14, which is also targeted by two TALes from an African Xoo lineage. A total of five promoter mutations were simultaneously introduced into the rice line Kitaake and the elite mega varieties IR64 and Ciherang-Sub1. Paddy trials showed that genome-edited SWEET promoters endow rice lines with robust, broad-spectrum resistance.

15.
Artigo em Inglês | MEDLINE | ID: mdl-31660716

RESUMO

High magnetization materials are in great demand for the fabrication of advanced multifunctional magnetic devices. Notwithstanding this demand, the development of new materials with these attributes has been relatively slow. In this work, we propose a new strategy to achieve high magnetic moments above room temperature. Our materials engineering approach invoked the embedding of magnetic nanoclusters in an oxide matrix. By precisely controlling pulsed laser deposition parameters, Co nanoclusters are formed in a 5 at.% Co-TiO2 film. The presence of these nanoclusters was confirmed using transmission electron microscopy, energy dispersive X-ray spectroscopy and X-ray absorption fine structure. The film exhibits a very high saturation magnetization of 99 emu/cm3. Detailed studies using X-ray magnetic circular dichroism confirm that Co has an enhanced magnetic moment of 3.5 B/atom, whilst the Ti and O also contribute to the magnetic moments. First principles calculations supported our hypothesis that the metallic Co nanoclusters surrounded by a TiO2 matrix can exhibit both large spin and orbital moments. Moreover, a quantum confinement effect results in a high Curie temperature for the embedded Co nanoclusters. These findings reveal that 1-2 nm nanoclusters that are quantum confined can exhibit very large magnetic moments above room temperature, representing a promising advance for the design of new high magnetization materials.

16.
Ann Rheum Dis ; 2019 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-31662318

RESUMO

OBJECTIVES: Diverse evidence including clinical, genetic and microbiome studies support a major role of the gut microbiome in the common immune-mediated arthropathy, ankylosing spondylitis (AS). We set out to (1) further define the key microbial characteristics driving disease, and (2) examine the effects of tumour necrosis factor-inhibitor (TNFi) therapy upon the microbiome. METHODS: The stools from a case-control cohort of 250 Han-Chinese subjects underwent shotgun metagenomic sequencing. All subjects were genotyped using the Illumina CoreExome SNP microarray. RESULTS: Previous reports of gut dysbiosis in AS were reconfirmed and several notable bacterial species and functional categories were differentially abundant. TNFi therapy was correlated with a restoration the perturbed microbiome observed in untreated AS cases to that of healthy controls, including several important bacterial species that have been previously associated with AS and other related diseases. Enrichment of bacterial peptides homologous to HLA-B27-presented epitopes was observed in the stools of patients with AS, suggesting that either HLA-B27 fails to clear these or that they are involved in driving HLA-B27-associated immune reactions. TNFi therapy largely restored the perturbed microbiome observed in untreated AS cases to that of healthy controls, including several important bacterial species that have been previously associated with AS and other related diseases. TNFi therapy of patients with AS was also associated with a reduction of potentially arthritogenic bacterial peptides, relative to untreated patients. CONCLUSION: These findings emphasise the key role that the gut microbiome plays in driving the pathogenesis of AS and highlight potential therapeutic and/or preventative targets.

17.
Environ Sci Technol ; 2019 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-31603658

RESUMO

The production and usage of non-polybrominated diphenyl ether (PBDE) halogenated flame retardants (HFRs) have substantially increased after the ban of several PBDEs. This has resulted in widespread environmental occurrence of non-PBDE HFRs, further amplified by emissions from primitive recycling of obsolete electronics (e-waste). The present study conducted chamber experiments to characterize 15 HFRs (∑15HFR) from thermal treatment and open burning of typical e-waste. Emission factors of ∑15HFR from thermal treatment were 2.6 × 104-3.9 × 105 ng g-1, slightly higher than those from open burning (8.8 × 103-1.0 × 105 ng g-1). Greater output over input mass ratios of ∑15HFR were obtained in thermal treatment than in open burning. Particulate and gaseous HFRs dominated the emissions in thermal treatment and open burning, respectively, largely because of the different temperatures used in the two processes. Particulate HFRs were primarily affiliated with fine particles (Dp < 1.8 µm) peaking at 0.56-1.0 or 0.32-0.56 µm in both thermal treatment and open burning. Occupational exposure to most FRs was relatively low, but several PBDEs may pose potential health risk to workers in e-waste home-workshops. Potentially accruing emissions and health risks of non-PBDE HFRs from primitive recycling of e-waste remain a great concern.

19.
Ecotoxicol Environ Saf ; 187: 109829, 2019 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-31654869

RESUMO

Screening appropriate washing agents to remediate soils contaminated with heavy metals is crucial for decreasing metal hazards posing to environment and human health. In this study, two plant washing agents-water-extracted from Fagopyrum esculentum and Fordiophyton faberi, were applied to remove soil Pb, Zn, and Cd by washing. Results indicated that metal removals augmented with increase of washing solution concentrations, decreased with increasing pH values of the solution and followed the pseudo-second-order model depending on contact duration. At concentration of 50 g/L, pH 3 and contact duration of 120 min, F. esculentum had higher removals of Pb (5.98-6.83%), Zn (21.82-27.94%), and Cd (39.90-40.74%) than those of F. faberi. And metal ions could be removed by binding with carboxyl, hydroxyl, amide, amine and aromatic groups in washing solutions. The potential risks of residual metals declined by 51.35-52.12% for mine soil and 48.51-49.96% for farmland soil with exchangeable and carbonate-bound fractions obviously extracted after a single washing (P < 0.05). And soil organic carbon and nutrients increased to some extent except for total phosphorus and available potassium. Moreover, soil phytotoxicity lowered except that some adverse effects on seed germination existed. Therefore, the water extract from F. esculentum is a promising washing agent for heavy metal removal.

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