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1.
Food Chem ; 302: 125337, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31419770

RESUMO

The composition of volatile compounds in Korla fragrant pears was determined using headspace solid-phase microextraction followed by a gas chromatography-mass spectrometry analysis using fruits at 30, 90, and 150 days after bloom. Hexanal, (E)-2-hexenal, 1-hexanol, (E)-2-hexen-1-ol, (Z)-3-hexen-1-ol, and hexyl acetate were identified as the major compounds. The composition of volatile compounds was associated with fatty acid concentrations and key enzyme activity in the lipoxygenase pathway. In vitro linoleic and linolenic acid feeding experiments conducted using cubes of fruit flesh demonstrated that the concentrations of volatile esters, such as hexyl acetate, in the treated fruits increased significantly after incubation for 12 h compared with those in the control fruits, which was accompanied by a reduction in aldehyde and alcohol concentrations (p < 0.05 or p < 0.01). However, the treatments did not significantly influence the enzyme activity and expression of genes encoding the enzymes.


Assuntos
Frutas/química , Odorantes/análise , Pyrus/química , Pyrus/fisiologia , Compostos Orgânicos Voláteis/análise , Aldeídos/análise , Ésteres/análise , Ácidos Graxos/análise , Ácidos Graxos/metabolismo , Análise de Alimentos/métodos , Frutas/efeitos dos fármacos , Frutas/fisiologia , Cromatografia Gasosa-Espectrometria de Massas/métodos , Regulação da Expressão Gênica de Plantas , Hexanóis/análise , Ácido Linoleico/farmacologia , Pyrus/efeitos dos fármacos , Microextração em Fase Sólida/métodos , Compostos Orgânicos Voláteis/metabolismo , Ácido alfa-Linoleico/farmacologia
2.
Water Res ; 168: 115121, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31605833

RESUMO

Plastic debris and marine microplastics are being discharged into the ocean at an alarming scale and have been observed throughout the marine environment. Here we report microplastic in sediments of the Challenger Deep, the deepest known region on the planet, abyssal plains and hadal trenches located in the Pacific Ocean (4900 m-10,890 m). Microplastic abundance reached 71.1 items per kg dry weight sediment. That high concentrations are found at such remote depths, knowing the very slow sinking speed of microplastics, suggests that supporting mechanisms must be at-play. We discuss cascading processes that transport microplastics on their journey from land and oceanic gyres through intermediate waters to the deepest corners of the ocean. We propose that hadal trenches will be the ultimate sink for a significant proportion of the microplastics disposed in the ocean. The build-up of microplastics in hadal trenches could have large consequences for fragile deep-sea ecosystems.


Assuntos
Plásticos , Poluentes Químicos da Água , Ecossistema , Monitoramento Ambiental , Poluição Ambiental , Oceanos e Mares
3.
J Nanosci Nanotechnol ; 20(5): 2728-2735, 2020 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-31635608

RESUMO

Biomass-derived porous carbons are considered as one of the most promising electrode materials for supercapacitors due to their low-cost and natural abundance. In this work, pinecone is used to fabricate biomass N, S, O-doped porous carbon via one-step carbonization process with KOH activation. By optimizing the additive amount of KOH and calcination temperature, the asprepared product shows a high specific surface area and pore volume up to 1593.8 m² g-1 and 0.8582 cm³ g-1, respectively. As an electric double-layer capacitor (EDLC) electrode, the N, S, O-doped porous carbon exhibits a high specific capacitance of 285 F g-1 at 0.5 A g-1 and good rate performance with a capacitance retention of 78.6% from 0.5 to 20 A g-1. Furthermore, the as-assembled symmetric supercapacitor with 6 mol L-1 KOH as electrolyte possesses a promising energy density of 6.34 Wh kg-1 and a power density of 250 W kg-1. Outstanding cycling stability was also demonstrated with 94.4% capacitance retention after 10,000 charge/discharge cycles at 1 A g-1.

4.
Methods Mol Biol ; 2085: 133-144, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31734922

RESUMO

In the jasmonate signaling pathway, a region of 17 amino acids within the Jas motif of JAZ proteins and a conserved region within the N-terminus of MYC proteins are sufficient for JAZ-MYC interactions. Crystal structures of Jas-MYC complexes have revealed the structural basis of this important interaction. Here, we describe methods of cloning, expression, and purification of MYC N-terminal proteins and their co-crystallization with Jas motif peptides.

5.
Artigo em Inglês | MEDLINE | ID: mdl-31425724

RESUMO

BACKGROUND: Schizophrenia (SCZ) is a severe mental disorder. Both environmental and genetic factors contribute to the development of SCZ. The estimated heritability of SCZ is about 80%. Previous genetic studies of SCZ mainly focused on the genetic variations associated the risk of SCZ. Limited efforts are paid to explore the roles and biological mechanism of nuclear acid methylation implicated in the pathogenesis of SCZ. METHODS: A two-stage integrative analysis of SCZ GWAS and nuclear acid methylation functional annotation data (including meQTLs and m6A) was performed in this study. First, the discovery GWAS of SCZ was aligned with genomic meQTLs and m6A annotation data to identify the candidate genes associated with SCZ. Second, another independent replication GWAS dataset of SCZ was applied to validate the discovery results. Furthermore, the functional relevance of identified candidate genes with SCZ were validated by the mRNA expression profiling of SCZ brain tissues. Gene ontology (GO) and pathway enrichment analysis of identified candidate genes was performed by the DAVID tool. RESULTS: The two-stage integrative analysis detected 106 meQTLs related candidate genes for SCZ. After comparing with the differentially expressed genes in SCZ brain tissues, 49 overlapped genes were identified for meQTLs, such as ZSCAN12, BTN3A2 and HLA-DQA1. Besides, for meQTLs, 29 SCZ associated pathways and 56 SCZ associated GO terms were detected, such as cell adhesion molecules and asthma. For m6A, 25 candidate genes were detected by the two-stage integrative analysis for SCZ, such as ZSCAN12, HLA-DQA1 and SNX19. Furthermore, 17 of the 25 genes were detected in the mRNA expression profiling of SCZ brain tissues. CONCLUSION: This study identified multiple SCZ associated genes and pathways, supporting the implication of nuclear acid methylation in the pathogenesis of SCZ.

6.
J Ethnopharmacol ; 247: 112299, 2020 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-31606537

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Hua-Feng-Dan (HFD) is a traditional Chinese medicine used for neurological disorders. HFD contains cinnabar (HgS) and realgar (As4S4). The ethnopharmacological basis of cinnabar and realgar in HFD is not known. AIM OF THE STUDY: To address the role of cinnabar and realgar in HFD-produced neuroprotection against neurodegenerative diseases and disturbance of gut microbiota. MATERIALS AND METHODS: Lipopolysaccharide (LPS) plus rotenone (ROT)-elicited rat dopaminergic (DA) neuronal damage loss was performed as a Parkinson's disease animal model. Rats were given a single injection of LPS. Four months later, rats were challenged with the threshold dose of ROT. The clinical dose of HFD was administered via feed, starting from ROT administration for 46 days. Behavioral dysfunction was detected by rotarod and Y-maze tests. DA neuron loss and microglial activation were assessed via immunohistochemical staining and western bolt analysis. The colon content was collected to extract bacterial DNA followed by real-time PCR analysis with 16S rRNA primers. RESULTS: LPS plus ROT induced neurotoxicity, as evidenced by DA neuron loss in substantia nigra, impaired behavioral functions and increased microglial activation. HFD-original (containing 10% cinnabar and 10% realgar) rescued loss of DA neurons, improved behavioral dysfunction and attenuated microglial activation. Compared with HFD-original, HFD-reduced (3% cinnabar and 3% realgar) was also effective, but to be a less extent, while HFD-removed (without cinnabar and realgar) was ineffective. In analysis of gut microbiome, the increased Verrucomicrobiaceae and Lactobacteriaceae, and the decreased Enterobacteeriaceae by LPS plus ROT were ameliorated by HFD-original, and to be the less extent by HFD-reduced. CONCLUSION: Cinnabar and realgar are active ingredients in HFD to exert beneficial effects in a neurodegenerative model and gut microbiota.

7.
Dev Comp Immunol ; 102: 103486, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31473265

RESUMO

The complement system is a crucial component of the innate immune system that links innate and adaptive immunity. CL-11, a protein similar to Mannose-binding lectin (MBL), plays significant role in the innate immune system in mammals and fish, serving as an initiator of the lectin pathway of complement activation. In this study, a CL-11 homolog (TfCol-11) was identified in roughskin sculpin (Trachidermus fasciatus), and its expression and role in immune responses were characterized. The open reading frame of TfCol-11 is 795 bp long, encoding a 264 amino acid polypeptide. The deduced amino acid sequence of this protein is highly homologous to sequences in other teleosts, and is similar to vertebrate CL-11, containing a canonical collagen-like region, a carbohydrate recognition domain, and a neck region. Recombinant TfCol-11 purified from Escherichia coli(E.coli) was able to bind to different microbes in a Ca2+-independent manner. Meanwhile, a 993 bp-long of partial MASP cDNA with a 96 bp 5' untranslated region (UTR) was also cloned from roughskin sculpin, containing 299 amino acids and consisting of three domains (CUB-EGF-CUB). qRT-PCR indicated that TfCol-11 and MASP mRNAs were predominately co-expressed in the liver. The temporal expression of TfCol-11 and MASP were both drastically up-regulated in the liver, skin, and blood by LPS challenge. Recombinant TfCol-11 purified from E.coli BL21(DE3) was able to agglutinate some bacteria in a Ca2+-dependent manner. In addition, an in vitro pull-down experiment demonstrated that TfCol-11 was able to bind to MASP, and in vivo experiments showed that TfCol-11 was associated with increased membrane attack complex (MAC) levels. It is therefore possible that TfCol-11 may plays a role in activating the complement system and in the defense against invading microorganisms in roughskin sculpin.

8.
Opt Express ; 27(21): 29803-29816, 2019 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-31684237

RESUMO

Traditional methods for distortion measurement of large-aperture optical systems are time-consuming and ineffective because they require each field of view to be individually measured using a high-precision rotating platform. In this study, a new method that uses a phase diffractive beam splitter (DBS) is proposed to measure the distortion of optical systems, which has great potential application for the large-aperture optical system. The proposed method has a very high degree of accuracy and is extremely economical. A high-precision calibration method is proposed to measure the angular distribution of the DBS. The uncertainty analysis of the factors involved in the measurement process has been performed to highlight the low level of errors in the measurement methodology. Results show that high-precision measurements of the focal length and distortion were successfully achieved with high efficiency. The proposed method can be used for large-aperture wide-angle optical systems such as those used for aerial mapping applications.

9.
Opt Express ; 27(20): A1569-A1590, 2019 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-31684562

RESUMO

A multi-layer solar radiative transfer (RT) scheme is proposed to deal with the vertical variation of inherent microphysical properties of clouds in this study. The exponential expressions are used to represent the vertical variation of optical properties caused by inhomogeneous microphysical properties. A perturbation method, coupled with the Eddington approximation, is used to solve the RT equation. In order to have a more accurate estimation of reflectance/transmittance for every single layer, the optical properties are adjusted following the theory of delta scaling in the proposed scheme. In addition, a modified adding method based on Chandrasekhar's invariance principle is introduced to solve the multi-layer RT. The accuracy of the proposed scheme is investigated by comparing the reflectance/absorptance to the benchmark for two double-layer cases, and each layer with vertically inhomogeneous optical properties. Results show that the bias related to vertically inhomogeneous optical properties reaches 13.8 % for reflectance and 29.2 % for absorptance while the bias of the proposed scheme is only -0.8 % for reflectance and 1.7 % for absorptance. We also apply the proposed scheme as well as the conventional Eddington approximation to the CanadianClimate Center RT model which handle RT in CanAM4. The calculations are performed in the following four solar wavenumber bands 2500-4200, 4200-8400, 8400-14500 and 14500-50000 cm -1. The result also shows that the proposed scheme also improved the accuracy in both flux and heating rate calculation by taking the vertical variation of inherent microphysical properties into account. The proposed scheme is approximately three times more computationally expensive compared to the Eddington approximation when we only consider the algorithm itself. The computational time is doubled compared to the Eddington approximation when we take the complete radiative transfer process into account. Due to its accuracy and efficiency, the proposed scheme is suitable to improve the RT calculations regarding the vertical variation of inherent microphysical properties in climate models.

10.
Int J Cardiol ; 2019 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-31685245

RESUMO

BACKGROUND: Obesity is often considered as a risk factor of cardiovascular events, but recent researches showed conflicting results regarding to the effect of body weight on prognosis of coronary artery disease (CAD). This study aimed to evaluate the relationship between body mass index (BMI) and clinical outcomes of CAD in Asian population. METHODS: A total of 4315 patients from the FOCUS registry were enrolled into this analysis. Patients were divided into 4 groups according to BMI: lean group (BMI<18.5 kg/m2), normal group (BMI 18.5-24.9 kg/m2), overweight group (BMI 25-30 kg/m2) and obesity group (BMI>30 kg/m2). Follow-up was continued to 3 years to evaluate clinical outcomes, and the primary endpoint was a composite of all-cause death and myocardial infarction (MI). RESULTS: Patients with higher BMI were more likely to be associated with cardiovascular risk factors like hypertension, hypercholesterolemia and diabetes, but not smoking. At the end of the follow-up period, however, the incidence of a composite endpoint of all-cause death and MI was significantly lower in the higher BMI (overweight and obese) subsets, as compared with the lower BMI group (5.2% vs. 8.0%, p < 0.001). So did the cumulative rates of all-cause death (p < 0.001), cardiovascular death (p < 0.001), and a combined endpoint of cardiovascular death and MI (p = 0.001). CONCLUSIONS: In Asian patients with CAD, an inverse association between BMI and long-term prognosis was observed. Although overweight or obese patients were associated with more metabolism-associated comorbidities, they had significantly lower adverse events at 3-year follow up after percutaneous coronary intervention.

11.
Psychiatry Res ; : 112639, 2019 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-31685286

RESUMO

BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) is a common neurodevelopmental disorder, but the genetic mechanism of ADHD remains elusive now. METHODS: Tissue specific transcriptome-wide association study (TWAS) of ADHD was performed by FUSION utilizing a genome-wide association study (GWAS) dataset of ADHD (including 20,183 ADHD cases and 35,191 healthy controls) and gene expression reference from brain and blood. Furthermore, the genes identified by TWAS were compared with the differently expressed genes detected by mRNA expression profiles of ADHD rat model and autism spectrum disorders (ASD) patients. Functional enrichment and annotation analysis of the identified genes were performed by DAVID and FUMAGWAS tool. RESULTS: For brain tissue, TWAS identified 148 genes with P value < 0.05, such as TDO2 (PTWAS=4.01×10-2), CHD1L (PTWAS=9.64×10-3) and KIAA0319L (PTWAS=4.05×10-4). Further 11 common genes were examined in the mRNA expression datasets, such as ACSM5 (PTWAS=3.62×10-2, PmRNA=0.005), CCDC24 (PTWAS=1.49×10-2, PmRNA=2.35×10-3) and MVP (PTWAS=5.55×10-3, PmRNA=5.40×10-3). Pathway enrichment analysis of the genes identified by TWAS detected 3 pathways for ADHD, including Other glycan degradation (P value=0.021), Viral myocarditis (P value=0.034) and Endocytosis (P value=0.041). CONCLUSIONS: Through integrating GWAS and mRNA expression data, we identified a group of ADHD-associated genes and pathways, providing novel clues for understanding the genetic mechanism of ADHD.

13.
J Mater Chem B ; 2019 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-31720683

RESUMO

Transplantation of tissue-engineered neural scaffolds bears great potential for reconstructing neural circuits after spinal cord injury (SCI). In this study, a 3D porous silk fibrous scaffold (3D-SF) with biomimetic interconnected micro- to nanofibrous structure and good biocompatibility is fabricated. Then, a small-molecule combination CFLSSVY (CHIR99021, Forskolin, LDN193189, SB431542, SP600125, VPA, and Y27632) that efficiently reprograms rat dermal fibroblasts into neurons is screened, and these chemically induced neurons (CiNs) are shown to readily communicate on the 3D-SF and form neural scaffolds. After transplantation of these silk-based neural scaffolds into the stumps of transected spinal cords in rats, the damaged tissue is repaired significantly, as indicated by the reduced cavity areas, decreased GFAP expression, and improved axonal regeneration and myelination in the injury site. Moreover, the hindlimb movement and motor-nerve conductivity are greatly improved as indicated by the elevated BBB score, the alternate movement of two hindlimbs during the 45° inclined grid test, and the shortened latency and enhanced amplitude in cMEP detection. Together, these results demonstrate that transplantation of neural scaffolds consisting of 3D-SF and dermal fibroblast-reprogrammed neurons leads to significant nerve regeneration and functional recovery, providing a promising therapeutic strategy for SCI.

14.
Autophagy ; : 1-24, 2019 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-31679460

RESUMO

Ferroptosis is a recently discovered form of programmed cell death, but its regulatory mechanisms remain poorly understood. Here, we show that the RNA-binding protein ZFP36/TTP (ZFP36 ring finger protein) plays a crucial role in regulating ferroptosis in hepatic stellate cells (HSCs). Upon exposure to ferroptosis-inducing compounds, the ubiquitin ligase FBXW7/CDC4 (F-box and WD repeat domain containing 7) decreased ZFP36 protein expression by recognizing SFSGLPS motif. FBXW7 plasmid contributed to classical ferroptotic events, whereas ZFP36 plasmid impaired FBXW7 plasmid-induced HSC ferroptosis. Interestingly, ZFP36 plasmid inhibited macroautophagy/autophagy activation by destabilizing ATG16L1 (autophagy related 16 like 1) mRNA. ATG16L1 plasmid eliminated the inhibitory action of ZFP36 plasmid on ferroptosis, and FBXW7 plasmid enhanced the effect of ATG16L1 plasmid on autophagy. Importantly, ZFP36 plasmid promoted ATG16L1 mRNA decay via binding to the AU-rich elements (AREs) within the 3'-untranslated region. The internal mutation of the ARE region abrogated the ZFP36-mediated ATG16L1 mRNA instability, and prevented ZFP36 plasmid-mediated ferroptosis resistance. In mice, treatment with erastin and sorafenib alleviated murine liver fibrosis by inducing HSC ferroptosis. HSC-specific overexpression of Zfp36 impaired erastin- or sorafenib-induced HSC ferroptosis. Noteworthy, we analyzed the effect of sorafenib on HSC ferroptosis in fibrotic patients with hepatocellular carcinoma receiving sorafenib monotherapy. Attractively, sorafenib monotherapy led to ZFP36 downregulation, ferritinophagy activation, and ferroptosis induction in human HSCs. Overall, these results revealed novel molecular mechanisms and signaling pathways of ferroptosis, and also identified ZFP36-autophagy-dependent ferroptosis as a potential target for the treatment of liver fibrosis.Abbreviations: ARE: AU-rich elements; ATG: autophagy related; BECN1: beclin 1; CHX: cycloheximide; COL1A1: collagen type I alpha 1 chain; ELAVL1/HuR: ELAV like RNA binding protein 1; FBXW7/CDC4: F-box and WD repeat domain containing 7; FN1: fibronectin 1; FTH1: ferritin heavy chain 1; GPX4/PHGPx: glutathione peroxidase 4; GSH: glutathione; HCC: hepatocellular carcinoma; HSC: hepatic stellate cell; LSEC: liver sinusoidal endothelial cell; MAP1LC3A: microtubule associated protein 1 light chain 3 alpha; MDA: malondialdehyde; NCOA4: nuclear receptor coactivator 4; PTGS2/COX2: prostaglandin-endoperoxide synthase 2; RBP: RNA-binding protein; ROS: reactive oxygen species; SLC7A11/xCT: solute carrier family 7 member 11; SQSTM1/p62: sequestosome 1; TNF: tumor necrosis factor; TP53/p53: tumor protein p53; UTR: untranslated region; ZFP36/TTP: ZFP36 ring finger protein.

15.
Keio J Med ; 2019 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-31723075

RESUMO

The class 2 CRISPR-Cas endonuclease Cas12a (previously known as Cpf1) offers several advantages over Cas9, including the ability to process its own array and the requirement for just a single RNA guide. These attributes make Cas12a promising for many genome engineering applications. To further expand the suite of Cas12a tools available, we tested 16 Cas12a orthologs for activity in eukaryotic cells. Four of these new enzymes demonstrated targeted activity, one of which, from Moraxella bovoculi AAX11_00205 (Mb3Cas12a), exhibited robust indel formation. We also showed that Mb3Cas12a displays some tolerance for a shortened PAM (TTN versus the canonical Cas12a PAM TTTV). The addition of these enzymes to the genome editing toolbox will further expand the utility of this powerful technology.

16.
Am J Hum Genet ; 2019 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-31735294

RESUMO

As a type of severe asthenoteratospermia, multiple morphological abnormalities of the flagella (MMAF) are characterized by the presence of immotile spermatozoa with severe flagellar malformations. MMAF is a genetically heterogeneous disorder, and the known MMAF-associated genes can only account for approximately 60% of human MMAF cases. Here we conducted whole-exome sequencing and identified bi-allelic truncating mutations of the TTC29 (tetratricopeptide repeat domain 29) gene in three (3.8%) unrelated cases from a cohort of 80 MMAF-affected Han Chinese men. TTC29 is preferentially expressed in the testis, and TTC29 protein contains the tetratricopeptide repeat domains that play an important role in cilia- and flagella-associated functions. All of the men harboring TTC29 mutations presented a typical MMAF phenotype and dramatic disorganization in axonemal and/or other peri-axonemal structures. Immunofluorescence assays of spermatozoa from men harboring TTC29 mutations showed deficiency of TTC29 and remarkably reduced staining of intraflagellar-transport-complex-B-associated proteins (TTC30A and IFT52). We also generated a Ttc29-mutated mouse model through the use of CRISPR-Cas9 technology. Remarkably, Ttc29-mutated male mice also presented reduced sperm motility, abnormal flagellar ultrastructure, and male subfertility. Furthermore, intracytoplasmic sperm injections performed for Ttc29-mutated mice and men harboring TTC29 mutations consistently acquired satisfactory outcomes. Collectively, our experimental observations in humans and mice suggest that bi-allelic mutations in TTC29, as an important genetic pathogeny, can induce MMAF-related asthenoteratospermia. Our study also provided effective guidance for clinical diagnosis and assisted reproduction treatments.

17.
Neurotoxicology ; 76: 93-98, 2019 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-31704102

RESUMO

OBJECTIVE: The compositions of the gut microbiota and its metabolites were altered in individuals with Autism Spectrum Disorder (ASD). The aim of this study was to assess whether plasma levels of gut-derived metabolite trimethylamine N-oxide (TMAO) were associated with ASD and the degree of symptom severity. METHODS: From September 2017 to January 2019, a total of three hundred and twenty-eight Chinese children (164 with ASD and 164 their age-sex matched control subjects) aged 3-8 years were included. TMAO levels in plasma were determined using high-performance liquid chromatography tandem mass spectrometry (LC/MS/MS). Logistic regression analysis was used to examine the TMAO-ASD association. RESULTS: In the study, the median age of the ASD group was 5 years (interquartile range [IQR], 4-6 years) and 129 (78.7%) were boys. The median plasma levels of TMAO in children with ASD and typically-developing (TD) children at admission were 4.2 (IQR, 3.0-5.6) µmol/l and 3.0 (2.0-4.4) µmol/l, respectively (P < 0.001). For each 1 µmol/l increase of plasma TMAO, the unadjusted and adjusted risk of ASD would be increased by 54% (with the odds ratios [OR] of 1.54; 95% confidence intervals [CI]: 1.32-1.78; P < 0.001) and 27% (1.27 [1.10-1.45], P < 0.001), respectively. Symptom severity was classified as mild-to-moderate (CARS < 37) for 66 children with ASD (40.2%). In these children, the plasma levels of TMAO were lower than in the 98 children with ASD (59.8%) whose symptoms were classified as severe (CARS > 36) (3.5[2.5-4.9] µmol/l vs. 4.5(3.7-6.0) µmol/l; P < 0.001). For each 1 µmol/l increase of plasma TMAO, the unadjusted and adjusted risk of severe autism would be increased by 61% (with the OR of 1.61 [95% CI 1.28-2.01], P < 0.001) and 31% (1.31 [1.08-1.49], P < 0.001), respectively. CONCLUSIONS: Elevated plasma levels of TMAO were associated with ASD and symptom severity.

18.
Cephalalgia ; : 333102419888222, 2019 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-31707815

RESUMO

BACKGROUND: Efficacy and safety of erenumab have been evaluated in a comprehensive clinical development program resulting in approval for migraine prevention in over 40 countries to date. METHODS: This integrated safety analysis included four double-blind randomized trials and their extensions (up to three-plus years). Safety endpoints included exposure-adjusted patient incidences of adverse events, serious adverse events, and anti-erenumab antibodies. RESULTS: In all, 2375 of the patients randomized across the four studies received at least one dose of erenumab (70 mg or 140 mg), with cumulative exposure of 2641.2 patient-years. Exposure-adjusted adverse event rates during the double-blind treatment phase were similar to placebo, with the exception of injection-site reactions (17.1 vs. 10.8 per 100 patient-years), constipation (7.0 vs. 3.8 per 100 patient-years), and muscle spasm (2.3 vs. 1.2 per 100 patient-years). During the long-term extensions, adverse events reported were similar to those observed during the double-blind treatment phase, and rates of injection site reactions, constipation, and muscle spasm were reported at lower rates than in the double-blind treatment phase. There were two deaths reported, both confounded by pre-existing conditions. CONCLUSIONS: This pooled safety analysis revealed a favorable and stable adverse event profile over time for erenumab with more than three years of exposure. TRIAL REGISTRATION: ClinicalTrials.gov NCT01952574, NCT02483585, NCT02456740, NCT02066415, and NCT02174861.

19.
Artigo em Inglês | MEDLINE | ID: mdl-31702123

RESUMO

Rational construction of mixed metal-organic frameworks (MOFs) has been proved to be an effective way to heighten the electrocatalytic performance for MOFs, while the function of mixed metal clusters in MOFs to the electrocatalytic activity has not been known. For the first time, we present a mixed-metal-cluster strategy to boost electrocatalytic oxygen evolution reaction (OER) performance for MOFs. Heterometal clusters (Fe2M(µ3-O) (CH3COO)6(H2O)3, denoted as Fe2M (M: Co or Ni)), were chosen as the metal source to construct two bimetal PCN-250-Fe2M. Then, we further mixed Fe2Co and Fe2Ni clusters to construct mixed-metal-cluster PCN-Fe2Co-Fe2Ni by the in situ solvothermal reaction. Consequently, the OER activity of PCN-Fe2Co-Fe2Ni shows a dramatic enhancement compared with that of the parent bimetal MOFs. The PCN-Fe2Co-Fe2Ni displays a lower overpotential of 271 mV (η10), small Tafel slope (67.7 mV dec-1), and good linear sweep voltammetry cycle stability for the OER. Combination of DFT calculation and experiment results show that the improved electrocatalytic activity of PCN-Fe2Co-Fe2Ni is ascribed to the increased electron density of Co and Ni active centers and electrochemically active areas.

20.
Anal Chem ; 2019 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-31718158

RESUMO

Simultaneous detection of large viruses has been a great obstacle in the field of molecular imprinting. In this work, for the first time, a multifunctional molecularly imprinted sensor for single or simultaneous determination of hepatitis A virus (HAV) and hepatitis B virus (HBV) is provided. Visual detection was realized due to the color of green and red quantum dots that varied with the concentration of the target substance. The combination of hydrophilic monomers and metal chelation reduced the nonspecific binding and enhanced the specificity of adsorption. As a result, satisfactory selectivity and sensitivity were obtained for the detection of the two viruses, with imprinting factors of 3.70 and 3.35 for HAV and HBV, and limits of detection of 3.4 and 5.3 pmol/L, respectively, that were achieved within 20 min. The excellent recoveries during simultaneous detection and single detection modes indicate the prominent ability of the proposed sensor to detect HAV and HBV in human serum and the potential ability to simultaneously detect multiple viruses in real applications.

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