Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 113
Filtrar
1.
Inorg Chem ; 60(20): 15118-15123, 2021 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-34597032

RESUMO

Treatment of PtMe3I in tetrahydrofuran with either in situ prepared [R-PNP]Li ([R-PNP]- = [(R2P-o-C6H4)2N]-; R = Ph, iPr) or H[R-PNP] in the presence of triethylamine at room temperature affords quantitatively fac-[R-PNP]PtMe3. Thermolysis of fac-[R-PNP]PtMe3 in benzene solutions generates mer-[R-PNP]PtMe3 and ultimately [R-PNP]PtMe and ethane. Complexes mer-[R-PNP]PtMe3 represent the first meridional trialkylplatinum(IV) derivatives to date.

2.
Luminescence ; 2021 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-34342392

RESUMO

Paper has become one of the most promising substrates for building low-cost and powerful sensing platforms due to its self-pumping ability and compatibility with multiple patterning methods. Paper-based sensors have been greatly developed in the field of environmental monitoring. In this review, we introduced the research and application of paper-based sensors in environmental monitoring, focusing on the deposition and patterning methods of building paper-based sensors, and summarized the applications of detecting environmental pollutants, including metal ions, anions, explosives, neurotoxins, volatile organic compounds, and small molecules. In addition, the development prospects and challenges of promoting paper-based sensors are also discussed. The current review will provide references for the construction of portable paper-based sensors, and has implications for the field of on-site real-time detection of the environment.

3.
ACS Appl Mater Interfaces ; 13(28): 33006-33014, 2021 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-34232630

RESUMO

Hindering the recombination of a photogenerated carrier is a crucial method to enhance the photoelectrochemical performance of ZnO due to its high exciton binding energy. Herein, the intramolecular donor-acceptor compensated semiconductor ZnO (I-D/A ZnO), introducing C dopants and oxygen vacancies, was prepared with the assistance of ascorbic acid (AA). According to the DFT calculations, the asymmetry DOS could lead to the longer carrier lifetime and the smaller electron transfer resistance. Then, the photoelectrochemical biosensor toward glucose was regarded as a model to discuss the application of ZnO in biosensors. As a result, the biosensor based on I-D/A ZnO showed good performance with high sensitivity, low limit of detection, and fine anti-interference, meaning that I-D/A ZnO is a promising semiconductor for photoelectrochemical biosensors.

4.
Am J Hum Genet ; 108(8): 1436-1449, 2021 08 05.
Artigo em Inglês | MEDLINE | ID: mdl-34216551

RESUMO

Despite widespread clinical genetic testing, many individuals with suspected genetic conditions lack a precise diagnosis, limiting their opportunity to take advantage of state-of-the-art treatments. In some cases, testing reveals difficult-to-evaluate structural differences, candidate variants that do not fully explain the phenotype, single pathogenic variants in recessive disorders, or no variants in genes of interest. Thus, there is a need for better tools to identify a precise genetic diagnosis in individuals when conventional testing approaches have been exhausted. We performed targeted long-read sequencing (T-LRS) using adaptive sampling on the Oxford Nanopore platform on 40 individuals, 10 of whom lacked a complete molecular diagnosis. We computationally targeted up to 151 Mbp of sequence per individual and searched for pathogenic substitutions, structural variants, and methylation differences using a single data source. We detected all genomic aberrations-including single-nucleotide variants, copy number changes, repeat expansions, and methylation differences-identified by prior clinical testing. In 8/8 individuals with complex structural rearrangements, T-LRS enabled more precise resolution of the mutation, leading to changes in clinical management in one case. In ten individuals with suspected Mendelian conditions lacking a precise genetic diagnosis, T-LRS identified pathogenic or likely pathogenic variants in six and variants of uncertain significance in two others. T-LRS accurately identifies pathogenic structural variants, resolves complex rearrangements, and identifies Mendelian variants not detected by other technologies. T-LRS represents an efficient and cost-effective strategy to evaluate high-priority genes and regions or complex clinical testing results.


Assuntos
Aberrações Cromossômicas , Análise Citogenética/métodos , Doenças Genéticas Inatas/diagnóstico , Doenças Genéticas Inatas/genética , Predisposição Genética para Doença , Genoma Humano , Mutação , Variações do Número de Cópias de DNA , Feminino , Testes Genéticos , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Cariotipagem , Masculino , Análise de Sequência de DNA
5.
Luminescence ; 36(6): 1553-1560, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34089633

RESUMO

Tetracycline (TC) is a broad-spectrum antibiotic used to treat bacterial infections. In this study, a ratiometric fluorescence (FL) probe was developed to detect TC in water samples using waste printing paper extract as a FL indicator. For this ratiometric probe, the emission of printing paper extract at 436 nm gradually decreased and the emission of a mixed solution at 538 nm significantly increased with the sequential addition of TC upon excitation at 390 nm, coupled with a marked FL colour change from bright blue to faint yellow. Therefore, a ratiometric F538 /F436 FL probe was created for TC detection by simply mixing the printing paper extraction and TC. Under the optimized conditions, a linear range from 1 to 100 µM and a detection limit of 0.48 µM (S/N = 3) for TC were obtained. Importantly, the FL probe can be easily prepared with rapid response, high sensitivity, and good selectivity. The application of waste printing paper extract for detection of TC in environmental water samples was demonstrated.


Assuntos
Corantes Fluorescentes , Tetraciclina , Antibacterianos , Limite de Detecção , Espectrometria de Fluorescência
6.
Int J Mol Med ; 47(6)2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33846764

RESUMO

Mesenchymal stem cells (MSCs) have the ability of differentiating into osteoblasts. Elucidating the molecular mechanisms of MSC differentiation into osteoblasts may provide novel therapeutic strategies for bone­related diseases. Increasing evidence has confirmed that Wnt signaling plays the key role in osteoblast differentiation; however, the role of individual Wnt proteins in osteogenesis needs to be investigated. The present study thus aimed to explore the role of Wnt7a in bone formation. For this purpose, human bone­derived MSCs were identified by flow cytometry and the cell differentiation potential, including osteogenic and adipogenic differentiation was examined. In order to explore the role of Wnt7a in MSC osteogenic differentiation, Wnt7a expression was measured at the mRNA and protein level following treatment with the osteogenic inducer, bone morphogenetic protein (BMP)4/7, and following the induction of osteogenic or adipogenic differentiation. The ectopic expression of Wnt7a in MSCs was confirmed and its influence on MSC osteogenic differentiation was detected using osteocyte markers and by Alizarin Red S staining. Mechanistically, the influence of Wnt7a on Runt­related transcription factor 2 (RUNX2) expression was examined at the mRNA and protein level. The regulatory effects of Wnt7a on RUNX2 promoter activities were examined by promoter reporter assay, and by examining the binding of TCF1, a downstream target of Wnt, to the RUNX2 promoter by ChIP assay. The results revealed that the knockdown of Wnt7a in MSCs decreased the expression of osteocyte markers and inhibited osteogenic differentiation. In accordance, the overexpression of Wnt7a in MSCs increased the expression of osteocyte markers and promoted osteogenic differentiation. Mechanistically, the knockdown of Wnt7a in MSCs reduced RUNX2 expression and the overexpression of Wnt7a in MSCs promoted RUNX2 expression. Furthermore, it was confirmed that Wnt7a regulated RUNX2 promoter activities by promoter report assay, and by examining the binding of TCF1 to the RUNX2 promoter by ChIP assay. On the whole, the present study demonstrates that Wnt7a plays a key role in MSC differentiation into osteoblasts and the findings presented herein may provide a promising therapy target for bone­related diseases.

7.
Appl Opt ; 60(10): 2886-2892, 2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33798168

RESUMO

An optic-fiber vibration sensor based on the reflected 81° tilted fiber grating (81° TFG) integrated with a symmetrical flexible hinge is proposed and experimentally demonstrated in this paper. The vibration sensor is composed of a symmetrical flexible hinge and a reflected 81° TFG, the ends of which are simply fixed on the upper surface of the mass. The theoretical model of the proposed vibration sensor is analyzed, by which the important parameters related to the resonant frequency of the sensor are simulated and discussed; then, the vibration sensing experiments are conducted. Experiment results show that TE/TM mode of the 81° TFG can provide the maximal acceleration sensitivity of 338.28 and 299.94 mV/g at 400 Hz in the flat area of the amplitude-frequency response (50-400 Hz), which is increased by 9.95 and 11.5 times as compared with the optical fiber cantilever beam structure, respectively. Further, the signal-to-noise ratio in the flat area (50-400 Hz) is about ∼66.275dB under the acceleration of 2 g, which is increased by ∼20dB. Furthermore, it can be used for detecting mechanical vibration of medium-high frequency ranging from 50 to 3500 Hz. The proposed 81° TFG vibration sensor has the characteristics of small volume, simple package, high acceleration sensitivity, and wide vibration signal response range, which will ensure it has broad application prospects in the field of mechanical vibration.

8.
J Hazard Mater ; 413: 125424, 2021 07 05.
Artigo em Inglês | MEDLINE | ID: mdl-33621771

RESUMO

Photocatalysis is an effective method to degrade ranitidine (RAN), which is a typical precursor of nitrosamine dimethylamine (NDMA), an extremely potent human carcinogen. Herein, MXene-Ti3C2/MoS2 composites were prepared by a hydrothermal treatment aiming to use them for the photocatalytic degradation of RAN and the reduction of NDMA formation potential (NDMA-FP) under visible light irradiation for the first time. The analysis of the morphology, chemical composition and structure of these composites as well as the results of electrochemical experiments showed that a heterojunction was formed between MoS2 and Ti3C2, which facilitated the separation of electron-hole pairs and charge transfer, and thereby the photocatalytic performance. The MXene-Ti3C2/MoS2 composite (MT-4) exhibited the best photocatalytic performance in 60 min, with the highest RAN degradation and mineralization efficiencies of 88.4% and 73.58%, and the lowest NDMA-FP of 2.01%. Active species, including •O2- radicals, h+ and •OH radicals, all contributed to the degradation of RAN, among which •OH radicals were the main active species involved in the photocatalytic activity. The mechanism of the photocatalytic degradation of RAN over MXene-Ti3C2/MoS2 photocatalyst under visible light irradiation was proposed. This work opens up a new perspective on the applications of MXene-based materials for photocatalytic degradation of challenging pollutants.


Assuntos
Nitrosaminas , Titânio , Catálise , Dimetilaminas , Humanos , Luz , Molibdênio , Ranitidina
9.
Clin Sci (Lond) ; 135(2): 409-427, 2021 01 29.
Artigo em Inglês | MEDLINE | ID: mdl-33458737

RESUMO

Hypertensive nephropathy (HN) is a common cause of end-stage renal disease with renal fibrosis; chronic kidney disease is associated with elevated serum gastrin. However, the relationship between gastrin and renal fibrosis in HN is still unknown. We, now, report that mice with angiotensin II (Ang II)-induced HN had increased renal cholecystokinin receptor B (CCKBR) expression. Knockout of CCKBR in mice aggravated, while long-term subcutaneous infusion of gastrin ameliorated the renal injury and interstitial fibrosis in HN and unilateral ureteral obstruction (UUO). The protective effects of gastrin on renal fibrosis can be independent of its regulation of blood pressure, because in UUO, gastrin decreased renal fibrosis without affecting blood pressure. Gastrin treatment decreased Ang II-induced renal tubule cell apoptosis, reversed Ang II-mediated inhibition of macrophage efferocytosis, and reduced renal inflammation. A screening of the regulatory factors of efferocytosis showed involvement of peroxisome proliferator-activated receptor α (PPAR-α). Knockdown of PPAR-α by shRNA blocked the anti-fibrotic effect of gastrin in vitro in mouse renal proximal tubule cells and macrophages. Immunofluorescence microscopy, Western blotting, luciferase reporter, and Cut&tag-qPCR analyses showed that CCKBR may be a transcription factor of PPAR-α, because gastrin treatment induced CCKBR translocation from cytosol to nucleus, binding to the PPAR-α promoter region, and increasing PPAR-α gene transcription. In conclusion, gastrin protects against HN by normalizing blood pressure, decreasing renal tubule cell apoptosis, and increasing macrophage efferocytosis. Gastrin-mediated CCKBR nuclear translocation may make it act as a transcription factor of PPAR-α, which is a novel signaling pathway. Gastrin may be a new potential drug for HN therapy.


Assuntos
Gastrinas/farmacologia , Hipertensão Renal/fisiopatologia , Nefrite/fisiopatologia , PPAR alfa/metabolismo , Receptores da Colecistocinina/metabolismo , Angiotensina II/administração & dosagem , Animais , Apoptose , Fibrose , Humanos , Hipertensão/complicações , Células Jurkat , Túbulos Renais Proximais/patologia , Camundongos , Camundongos Knockout , PPAR alfa/genética , Fagocitose , RNA Interferente Pequeno , Receptores da Colecistocinina/genética , Transdução de Sinais/efeitos dos fármacos , Obstrução Ureteral/fisiopatologia
10.
J Plant Physiol ; 258-259: 153361, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33429329

RESUMO

Abiotic stresses widely constrain the development and reproduction of plant, especially impaired the yield of crops greatly. Recent researches presented pentatricopeptide repeat (PPR) proteins play crucial role in response to abiotic stress. However, the underlying mechanism of PPR genes in regulation of abiotic stress is still obscures. In our recent study, we found that the knockout of rice PPS1 causes pleiotropic growth disorders, including growth retardation, dwarf and sterile pollen, and finally leads to impaired C-U RNA editing at five consecutive sites on the mitochondrial nad3. In this study, we further investigate the roles of PPS1 in abiotic stress tolerance, we confirmed that pss1-RNAi line exhibited enhanced sensitivity to salinity and ABA stress at vegetative stage, specifically. While reactive oxygen species (ROS) accumulate significantly only at reproductive stage, which further activated the expression of several ROS-scavenging system related genes. These results implied that PPS1 functioned on ROS signaling network to contribute for the flexibility to abiotic stresses. Our research emphasizes the stress adaptability mediated by the PPR protein, and also provides new insight into the understanding of the interaction between cytoplasm and nucleus and signal transduction involved in RNA editing.


Assuntos
Inativação Gênica/fisiologia , Oryza/fisiologia , Proteínas de Plantas/genética , Espécies Reativas de Oxigênio/metabolismo , Estresse Fisiológico/genética , Oryza/genética , Proteínas de Plantas/metabolismo
11.
Mol Ther ; 29(1): 176-190, 2021 01 06.
Artigo em Inglês | MEDLINE | ID: mdl-33002418

RESUMO

Zika virus (ZIKV) infection can lead to neurological complications and fetal defects, and it has attracted global public health concerns. Effective treatment for ZIKV infection remains elusive, and a preventative vaccine is not yet available. Therapeutics for fetuses need to overcome placenta barriers to reach the fetuses and require higher safety standards. In the present study, we engineered mammalian extracellular vesicles (EVs) to deliver a host restriction factor, interferon-induced transmembrane protein 3 (IFITM3), for the treatment of ZIKV infection. Our results demonstrated that the IFITM3-containing EVs (IFITM3-Exos) suppressed ZIKV viremia by a 2-log reduction in pregnant mice. Moreover, the engineered EVs effectively delivered IFITM3 protein across the placental barrier and suppressed ZIKV in the fetuses with significant reduction of viremia in key fetal organs as measured by quantitative real-time PCR. Mechanistic study showed that IFITM3 was delivered to late endosomes/lysosomes where it inhibited viral entry into the host cells. Our study demonstrated that EVs could act as a cross-placenta drug delivery vehicle to the fetus, and IFITM3, an endogenous restriction factor, is a potential treatment for ZIKV infection during pregnancy.

12.
Stem Cells Int ; 2020: 8852307, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33293963

RESUMO

The role and underlying mechanism of exosomes derived from human periodontal ligament stem cells (PDLSC) in osteogenesis are unclear. In the present study, we identified the exosomes derived from PDLSCs and found that osteogenic induction can enhance the osteogenic ability of PDLSC-derived exosomes in promoting the osteogenic differentiation of rat bone marrow stem cells (BMSCs). To investigate the underlying mechanism, we analyzed the exosomal miRNA expression profiles of undifferentiated and osteogenic differentiated PDLSCs by RNA sequencing. The results showed that seventy-two miRNAs were upregulated and thirty-five miRNAs were downregulated after osteogenic induction. The results of Gene Ontology analysis and pathway analysis demonstrated that the target genes of differentially expressed exosomal miRNAs participate in the regulation of a variety of biological processes, such as catalytic activity, protein binding, metabolic processes, cell development, and differentiation, and are enriched in osteogenic differentiation-related pathways, such as MAPK signaling, AMPK signaling, and insulin signaling pathways. Our results reveal for the first time that the exosomal miRNAs derived from osteogenic differentiated PDLSCs may promote the osteogenic differentiation of BMSCs, which provides a basis for further research on the regulatory function of exosomal miRNA of PDLSCs during osteogenesis.

13.
J Extracell Vesicles ; 9(1): 1809766, 2020 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-33144926

RESUMO

The utilization of extracellular vesicles (EVs) in clinical theranostics has rapidly advanced in the past decade. In November 2018, the International Society for Extracellular Vesicles (ISEV) held a workshop on "EVs in Clinical Theranostic". Here, we report the conclusions of roundtable discussions on the current advancement in the analysis technologies and we provide some guidelines to researchers in the field to consider the use of EVs in clinical application. The main challenges and the requirements for EV separation and characterization strategies, quality control and clinical investigation were discussed to promote the application of EVs in future clinical studies.

14.
J Exp Clin Cancer Res ; 39(1): 229, 2020 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-33121524

RESUMO

BACKGROUND: Dysregulation of long non-coding RNAs (lncRNAs) is responsible for cancer initiation and development, positioning lncRNAs as not only biomarkers but also promising therapeutic targets for cancer treatment. A growing number of lncRNAs have been reported in hepatocellular carcinoma (HCC), but their functional and mechanistic roles remain unclear. METHODS: Gene Set Enrichment Analysis was used to investigate the molecular mechanism of UPK1A antisense RNA 1 (UPK1A-AS1). Cell Counting Kit-8 assays, EdU assays, flow cytometry, western blotting, and xenograft assays were used to confirm the role of UPK1A-AS1 in the proliferation of HCC cells in vitro and in vivo. Bioinformatics analyses and quantitative polymerase chain reaction (qRT-PCR) were performed to explore the interplay between UPK1A-AS1 and enhancer of zeste homologue 2 (EZH2). RNA immunoprecipitation (RIP), RNA pull-down assays, western blotting, and qRT-PCR were conducted to confirm the interaction between UPK1A-AS1 and EZH2. The interaction between UPK1A-AS1 and miR-138-5p was examined by luciferase reporter and RIP assays. Finally, the expression level and prognosis value of UPK1A-AS1 in HCC were analyzed using RNA sequencing data from The Cancer Genome Atlas datasets. RESULTS: We showed that UPK1A-AS1, a newly identified lncRNA, promoted cellular proliferation and tumor growth by accelerating cell cycle progression. Cell cycle-related genes, including CCND1, CDK2, CDK4, CCNB1, and CCNB2, were significantly upregulated in HCC cells overexpressing UPK1A-AS1. Furthermore, overexpression of UPK1A-AS1 could protect HCC cells from cis-platinum toxicity. Mechanistically, UPK1A-AS1 interacted with EZH2 to mediate its nuclear translocation and reinforce its binding to SUZ12, leading to increased H27K3 trimethylation. Targeting EZH2 with specific small interfering RNA impaired the UPK1A-AS1-mediated upregulation of proliferation and cell cycle progression-related genes. Moreover, miR-138-5p was identified as a direct target of UPK1A-AS1. Additionally, UPK1A-AS1 was significantly upregulated in HCC, and the upregulation of UPK1A-AS1 predicted poor prognosis for patients with HCC. CONCLUSIONS: Our study revealed that UPK1A-AS1 promotes HCC development by accelerating cell cycle progression through interaction with EZH2 and sponging of miR-138-5p, suggesting that UPK1A-AS1 possesses substantial potential as a novel biomarker for HCC prognosis and therapy.

15.
J Cancer ; 11(22): 6737-6747, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33046996

RESUMO

Uroplakin 1A (UPK1A) has recently been found dysregulation in many cancers. However, the functions of UPK1A and its underlying mechanisms in hepatocellular carcinoma (HCC) remain poorly understand. In the present study, we found that UPK1A was highly expressed in HCC tumor tissues compared with adjacent non-tumor tissues. Datasets from the Cancer Genome Atlas project (TCGA) and Gene expression Omnibus confirmed that UPK1A was highly expressed in HCC. High expression of UPK1A predicted poor overall survival (OS) in patients with HCC. Univariate and multivariate analysis showed that UPK1A was a significant and independent prognostic predictor for OS of patients with HCC. Functionally, silencing UPK1A suppressed HCC cell glycolysis and proliferation. Mechanistically, hypoxia-inducible factor 1α (HIF-1α) directly bound to the hypoxia response elements (HRE) of UPK1A promoter region, which led to the up-regulation of UPK1A under hypoxia. Furthermore, downregulation of UPK1A reduced key enzyme of glycolysis via regulating HIF-1α. Taken together, these data indicates the existence of a positive feedback loop between HIF-1α and UPK1A that modulates glycolysis and proliferation under hypoxia in HCC cells.

16.
Anesth Analg ; 131(4): 1083-1089, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32925328

RESUMO

BACKGROUND: The objective of this study is to estimate the surgical risk of noncardiac procedures on the incidence of 30-day mortality in children with congenital heart disease. METHODS: Children with congenital heart disease undergoing noncardiac surgery from 2012 to 2016 and included in the American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) Pediatric database were included in the derivation cohort, while the 2017 database was used as a validation cohort. Intrinsic surgical risk quartiles were built utilizing 30-day mortality rates for each Current Procedural Terminology code and relative value units to create 2 groups defined as low surgical risk (quartiles 1-3) and high surgical risk procedures (quartile 4). We used multivariable logistic regression to determine the predictors for 30-day mortality including patient comorbidities and intrinsic surgical risk. A partially external validation of the model was performed using the 2017 version of the database. RESULTS: We included 37,658 children with congenital heart disease undergoing noncardiac surgery with an incidence of overall 30-day mortality of 1.7% in the derivation cohort and 1.5% in the validation cohort (n = 13,129). Intrinsic surgical risk of procedures represented by Current Procedural Terminology procedural codes and relative value units risk quartiles was significantly associated with 30-day mortality (unadjusted P < .001). Predicted probability of 30-day mortality ranges from 0.2% (95% confidence interval [CI], 0.2-0.2) with no comorbidities to 39.6% (95% CI, 23.2-56.0) when all comorbidities were present among high surgical risk procedures and from 0.3% (95% CI, 0.3-0.3) to 54.8% (95% CI, 39.4-70.1) among low surgical risk procedures. An excellent discrimination was reported for the multivariable model with area under the curve (AUC) of 0.86 (95% CI, 0.85-0.88). High surgical risk was not associated with increased odds of 30-day mortality after adjustment for all other predictors (adjusted odds ratio [OR]: 0.75, 95% CI, 0.62-0.91). We also estimated the discriminative ability of a model that does not include the surgical risk (0.86 [95% CI, 0.84-0.88], with P value for the direct comparison of the AUC of the 2 models = 0.831). The multivariable model obtained from an external validation cohort reported an optimism corrected AUC of 0.88 (95% CI, 0.85-0.91). CONCLUSIONS: Our study demonstrates that integration of intrinsic surgical risk to comorbidities and severity of cardiac disease does not improve prediction of 30-day mortality in children undergoing noncardiac surgery. In children with congenital heart disease, patient comorbidities, and severity of the cardiac lesion are the predominant predictors of 30-day mortality.


Assuntos
Comorbidade , Cardiopatias Congênitas/mortalidade , Medição de Risco/métodos , Procedimentos Cirúrgicos Operatórios/mortalidade , Área Sob a Curva , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Cardiopatias Congênitas/complicações , Mortalidade Hospitalar , Humanos , Incidência , Lactente , Recém-Nascido , Masculino , Modelos Estatísticos , Resultados Negativos , Valor Preditivo dos Testes , Análise de Sobrevida
17.
Environ Pollut ; 265(Pt B): 114628, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32806440

RESUMO

Volatile organic compounds (VOCs) are important precursors of ozone (O3) and secondary organic aerosols (SOAs). Tracing VOC pollution sources is important for controlling VOC emissions and reducing O3 and SOAs. We built a novel mobile proton transfer reaction mass spectrometry (M-PTR-MS) instrument to image the distribution of VOCs and trace their emission sources in cities and industrial parks. The M-PTR-MS is composed of a vibration-resistant proton transfer reaction mass spectrometry (PTR-MS) with a global positioning system receiver, modified box vehicle, and geographic information system (GIS) software. The PTR-MS, mounted on a vehicle, sends VOC data and vehicle position information to the GIS software. These data are used to image the space distribution of VOCs in real time while the vehicle platform is in motion and the VOC sources are precisely traced using the GIS. The spatial data resolution of the M-PTR-MS is typically 0.8 m. The limits of detection, sensitivity, and repeatability of the M-PTR-MS are 43.5 ppt, 347 counts ppb-1, and 2.4% (RSD, n = 5), respectively. The intensity of reagent ions is stable over 8 h (RSD = 0.45%). Compared with commercial PTR-MS equipment, the M-PTR-MS demonstrated high consistency, with a correlation coefficient of 92.665%. Several field experiments were conducted in China using the M-PTR-MS. In one field experiment, the VOC distribution along three different routes was surveyed; the navigation monitoring lasted 1.8 h over a distance of 26.7 km at an average speed of 15 km h-1. The VOC sources in an industrial park were identified by analyzing the components near different factories. The main species from a VOC source in an underground garage was related to paint. The M-PTR-MS instrument can be used by environmental protection agencies to trace VOC pollution sources in real time, and by researchers to survey VOC emissions in regions of concern.


Assuntos
Compostos Orgânicos Voláteis , China , Cidades , Espectrometria de Massas , Prótons
18.
J Mol Model ; 26(9): 237, 2020 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-32812072

RESUMO

Cu-based catalysts have been widely used for water-gas shift reaction (WGS, CO + H2O → CO2 + H2), and α-MoC support also shows the good performance for the reaction. Therefore, WGS reaction is systematically studied over Cu/α-MoC by using density functional theory (DFT). DFT result shows the strong metal-support interaction between Cu and α-MoC(111) support. As a result, an extensive tensile strain is introduced in the Cu lattice due to α-MoC support, and Cu 3d band center shifts to Fermi level. However, the strong metal-support interaction does not lead to significant polarization of the Cu/α-MoC surface due to the less charge transfer from Mo to Cu. For the WGS reaction, small Cu particles on α-MoC(111) are likely to facilitate the reaction. At the interface of Cu-α-MoC(111), oxygen stabilizes the dissociated *H, which is benefit of H2O scission. Then, the activity increases compared with Cu(111) surface. In general, small Cu particles on α-MoC support also have good activity for WGS reaction compared with Au deposition on α-MoC. Graphical abstract.

19.
FASEB J ; 34(9): 11594-11604, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32687659

RESUMO

The endothelin receptor type B (ETBR) regulates water and electrolyte balance and blood pressure, in part, by inhibiting renal sodium transport. Our preliminary study found that the ETBR-mediated diuresis and natriuresis are impaired in hypertension with unknown mechanism. Persistently increased activity of G protein-coupled receptor kinase 4 (GRK4), caused by increased expression or genetic variants (eg, GRKγ142V), impairs the ability of the kidney to excrete a sodium load, in part, by impairing renal dopamine D1 receptor function through persistent phosphorylation. Our present study found that although renal ETBR expression was not different between Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHRs), renal ETBR phosphorylation was higher in SHRs. The role of hyper-phosphorylation in impaired ETBR-function was supported by results in human (h) GRK4γ transgenic mice. Stimulation of ETBR by BQ3020-induced natriuresis in human (h) GRK4γ wild-type (WT) mice. However, in hGRK4γ 142V transgenic mice, the renal ETBR was hyperphosphorylated and ETBR-mediated natriuresis and diuresis were not evident. There were co-localization and co-immunoprecipitation of ETBR and GRK4 in renal proximal tubule (RPT) cells from both WKY and SHRs but was greater in the latter than the former group. SiRNA-mediated downregulation of GRK4 expression, recovered the impaired inhibitory effect of ETBR on Na+ -K+ -ATPase activity in RPT cells from SHR. In vivo downregulation of renal GRK4 expression, via ultrasound-targeted microbubble destruction, decreased ETBR phosphorylation and restored ETBR-mediated natriuresis and diuresis in SHRs. This study provides a mechanism by which GRK4, via regulation of renal ETBR function, participates in the pathogenesis of hypertension.


Assuntos
Quinase 4 de Receptor Acoplado a Proteína G/metabolismo , Hipertensão/metabolismo , Rim/metabolismo , Receptor de Endotelina B/metabolismo , Animais , Células Cultivadas , Feminino , Quinase 4 de Receptor Acoplado a Proteína G/genética , Hipertensão/genética , Túbulos Renais Proximais/metabolismo , Masculino , Camundongos Transgênicos , Fosforilação , Ratos , Ratos Endogâmicos SHR , Ratos Endogâmicos WKY , Receptor de Endotelina B/genética , Sódio/metabolismo , Especificidade da Espécie
20.
Ther Adv Med Oncol ; 12: 1758835920929583, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32595775

RESUMO

Background: We assessed the surrogacy of objective response rate (ORR), disease control rate (DCR) and progression-free survival (PFS) for overall survival (OS) in anti-PD-1/PD-L1 trials of metastatic melanoma through a meta-analysis of randomized controlled trials (RCTs). Methods: PubMed and EMBASE were searched for phase II/III RCTs till June 2019 investigating anti-PD-1/PD-L1 agents. Treatment effect (hazard ratio or odds ratio) on potential surrogates (ORR/DCR/PFS) and OS were collected. At trial level, we assessed the correlation between treatment effect on potential surrogates and OS, weighted by sample size, fixed and random effect models, and calculated the surrogate threshold effect (STE). Sensitivity analyses and leave-one-out cross-validation approach were performed to evaluate the robustness of our findings. Results: We included 8 RCTs (4110 patients; 11 comparisons). We did not identify strong correlations between ORR [coefficient of determination (R 2): 0.09-0.25], DCR (0.41-0.57) and OS. However, we noted a strong correlation between PFS and OS, with R 2 of 0.82 in sample size, 0.75 in fixed effect and 0.72 in random effect model weighting, the robustness of which was further verified by leave-one-out cross-validation approach. Sensitivity analyses with restriction to trials with less than 50% crossover, phase III trials, large trials and first-line trials strengthened the correlation (0.78-0.94). The STE for PFS was 0.78. Conclusions: PFS may be the appropriate surrogate for OS in anti-PD-1/PD-L1 trials of metastatic melanoma. A future anti-PD-1/PD-L1 trial would need less than 0.78 for PFS of the upper limit of confidence interval to predict an OS benefit.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...