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1.
Environ Pollut ; 259: 113918, 2020 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-32023794

RESUMO

Natural sources, such as soil and wind-erosion dust (SWD), biomass open burning (BOB), sea salt spray (SSAS) and biogenic source (BIO), are major contributors to atmospheric emissions of trace elements (TEs) globally. In this study, we used a comprehensive approach to account for area-, production- and biofuel consumption-based emission factor calculation methods, and thus developed an integrated high-resolution emission inventory for 15 types of TEs (As, B, Cd, Co, Cr, Cu, Hg, Mn, Mo, Ni, Pb, Sb, Se, V and Zn) originated from natural sources in China for the year 2015. The results show that national emissions of TEs in 2015 range from 7.45 tons (Hg) to 1, 400 tons (Zn) except for the extremely high emissions of Mn (10, 677 tons). SWD and BIO are identified as the top two source contributors, accounting for approximately 67.7% and 26.1% of the total emissions, respectively. Absolute emissions of TEs from natural sources are high in the Xinjiang, Inner Mongolia and Tibet autonomous regions with large areas of bare soil and desert. However, emission intensity of TEs per unit area in the Southern provinces of China is higher than those in Northern China and Southwestern China, with the Yunnan and Sichuan provinces displaying the highest emission intensity. Our results suggest that controlling SWD can play a significant role in reducing fugitive particulate matter and the associated emissions of TEs from natural sources in China; and desertification control is particularly critical in the Northwest provinces where the majority of deserts are located.

2.
Environ Sci Pollut Res Int ; 27(1): 469-481, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31797271

RESUMO

Sudden water pollution is a global environmental issue. On a large spatial scale, any pollution source may cause water pollution incidents. Dividing a large watershed into several units and giving each unit a different level would be favorable for managing sudden water pollution incidents. To scientifically divide an area into units and determine their risk grade of sudden water pollution, data of pollution sources were collected, and an area was divided into risk assessment units of sudden water pollution. The risk grade assessment was conducted following the analytic hierarchy process (AHP) and fuzzy comprehensive evaluation method. The technology combined with the AHP and fuzzy comprehensive evaluation (F-AHP) can generate the hydrology, pollution source, natural geography, and socioeconomic characteristics of each unit and provide a risk grade evaluation. A risk grade assessment was conducted using the Yongding River as a case study. The results show that the areas with high sudden water pollution risk were mainly distributed in Shanxi Datong and Hebei Zhangjiakou. Sufficient control of pollution sources in production processes and the establishment of necessary measures to strengthen inspections should reduce the risk of sudden water pollution.

3.
Neurobiol Dis ; 134: 104617, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31669733

RESUMO

As the most common cause of progressive cognitive decline in humans, Alzheimer's disease (AD) has been intensively studied, but the mechanisms underlying its profound synaptic dysfunction remain unclear. Here we confirm that exposing wild-type mice to an enriched environment (EE) facilitates signaling in the hippocampus that promotes long-term potentiation (LTP). Exposing the hippocampus of mice kept in standard housing to soluble Aß oligomers impairs LTP, but EE can fully prevent this. Mechanistically, the key molecular features of the EE benefit are an upregulation of miRNA-132 and an inhibition of histone deacetylase (HDAC) signaling. Specifically, soluble Aß oligomers decreased miR-132 expression and increased HDAC3 levels in cultured primary neurons. Further, we provide evidence that HDAC3 is a direct target of miR-132. Overexpressing miR-132 or injecting an HDAC3 inhibitor into mice in standard housing mimics the benefits of EE in enhancing hippocampal LTP and preventing hippocampal impairment by Aß oligomers in vivo. We conclude that EE enhances hippocampal synaptic plasticity by upregulating miRNA-132 and reducing HDAC3 signaling in a way that counteracts the synaptotoxicity of human Aß oligomers. Our findings provide a rationale for prolonged exposure to cognitive novelty and/or epigenetic modulation to lessen the progressive effects of Aß accumulation during human brain aging.

4.
Oncogene ; 39(1): 50-63, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31462705

RESUMO

Resistance of breast cancer to human epidermal growth factor receptor 2 (HER2) inhibitors involves reprogramming of the kinome through HER2/HER3 signaling via the activation of multiple tyrosine kinases and transcriptional upregulation. The heterogeneity of induced kinases prevents kinase targeting by a single kinase inhibitor and presents a major challenge to the treatment of therapeutically recalcitrant HER2-positive breast cancers (HER2+ BCs). As a result, there is a critical need for effective treatment that attacks the aberrant kinome activation associated with resistance to HER2-targeted therapy. Here, we describe a novel treatment strategy that targets cyclin-dependent kinase 7 (CDK7) in HER2 inhibitor-resistant (HER2iR) breast cancer. We show that both HER2 inhibitor-sensitive (HER2iS) and HER2iR breast cancer cell lines exhibit high sensitivity to THZ1, a newly identified covalent inhibitor of the transcription regulatory kinase CDK7. CDK7 promotes cell cycle progression through inhibition of transcription, rather than via direct phosphorylation of classical CDK targets. The transcriptional kinase activity of CDK7 is regulated by HER2, and by the receptor tyrosine kinases activated in response to HER2 inhibition, as well as by the downstream SHP2 and PI3K/AKT pathways. A low dose of THZ1 displayed potent synergy with the HER2 inhibitor lapatinib in HER2iR BC cells in vitro. Dual HER2 and CDK7 inhibition induced tumor regression in two HER2iR BC xenograft models in vivo. Our data support the utilization of CDK7 inhibition as an additional therapeutic avenue that blocks the activation of genes engaged by multiple HER2iR kinases.

5.
Biomed Pharmacother ; 123: 109749, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31846840

RESUMO

OBJECTIVE: Intestinal mucosal barrier damage is an important mechanism for the development of sepsis and multiple organ dysfunction syndrome. At present, there are no satisfactory and effective methods for the protection of the intestinal mucosal barrier. Jinzhi, the first fecal microbiota transplantation worldwide, is often used to treat critically ill patients; however, the specific mechanism involved in this process remains unclear. The aim of this study was to investigate the therapeutic effect and mechanism of Jinzhi intervention on mice with sepsis induced through treatment with lipopolysaccharide (LPS). METHODS: Mice were intraperitoneally injected with LPS to simulate intestinal mucosal barrier function damage in sepsis; intervention was performed through the oral administration of Jinzhi. The effect of Jinzhi on LPS-induced sepsis was analyzed by comparing the vital signs and survival rate of mice under different treatments. Pathological staining and enzyme-linked immunosorbent assay were used to identify the effects of LPS or treatment with Jinzhi on the intestinal mucosal barrier in mice. The effect of LPS or treatment with Jinzhi on the intestinal flora was analyzed via 16S rRNA gene sequencing of ileal contents. RESULTS: Immunohistochemistry and enzyme-linked immunosorbent assay showed that treatment with LPS increased levels of inflammatory factors (interleukin-1α, interleukin-6, tumor necrosis factor-α), caspase-3, and caspase-8 in the serum and ileum, and destroyed the tight junction between epithelial cells. Intervention with Jinzhi reduced levels of serum LPS and tumor necrosis factor-α, and repaired the tight junction between epithelial cells. Furthermore, 16S rRNA gene sequencing analysis showed that treatment with Jinzhi improved the diversity and physiological function of the intestinal flora. CONCLUSIONS: These results suggest that Jinzhi may be a promising option for the treatment of sepsis caused by LPS, and emphasize that Jinzhi exerts a recovery effect on the imbalance of intestinal flora.

6.
J Diabetes Res ; 2019: 4251829, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31871946

RESUMO

The correlation between serum 25-hydroxy vitamin D (25(OH)D) levels and lower extremity atherosclerotic disease and the predictive value of 25(OH)D for early-stage lower extremity atherosclerotic disease in patients with type 2 diabetes mellitus (T2DM) were explored. In total, 620 subjects (590 T2DM patients and 30 healthy subjects) completed a questionnaire. All subjects were divided into four groups according to serum 25(OH)D concentration quartile: Q1 (<12.18 ng/ml), Q2 (12.18~20.65 ng/ml), Q3 (20.65~31.97 ng/ml), and Q4 (>31.97 ng/ml). Participants were also divided into four groups based on the degree of lower extremity arteriostenosis: A1 (T2DM), A2 (T2DM with mild lower extremity vascular lesions (LEVL)), A3 (T2DM with moderate LEVL), and A4 (T2DM with severe LEVL). The incidence of lower extremity artery plaque was significantly higher in groups Q1 and Q2 than in group Q4 (both P < 0.05). The concentration of 25(OH)D was significantly lower in group A4 than in groups A1 and A2. Pearson correlation analysis revealed that the degree of lower extremity vascular stenosis was positively correlated with age, smoking, and HbA1c, CRP, and LDL-C levels and negatively correlated with 25(OH)D concentrations. Logistic regression analysis demonstrated that 25(OH)D concentrations exerted a protective effect against LEVL in T2DM patients. Serum 25(OH)D concentrations may be correlated with the incidence of macrovascular disease in T2DM patients. A low serum 25(OH)D concentration is an independent risk factor for lower extremity vascular pathological changes and acts as a prognostic index for lower extremity atherosclerotic disease.

7.
Adv Mater ; 31(46): e1904589, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31566277

RESUMO

Insertion-type anode materials with beneficial micro- and nanostructures are proved to be promising for high-performance electrochemical metal ion storage. In this work, heterostructured TiO2 shperes with tunable interiors and shells are controllably fabricated through newly proposed programs, resulting in enhanced pseudocapacitive response as well as favorable Na+ storage kinetics and performances. In addition, reasonably designed nanosheets in the extrinsic shells are also able to reduce the excess space generated by hierarchical structure, thus improving the packing density of TiO2 shperes. Lastly, detailed density functional theory calculations with regard to sodium intercalation and diffusion in TiO2 crystal units are also employed, further proving the significance of the surface-controlled pseudocapacitive Na+ storage mechanism. The structure design strategies and experimental results demonstrated in this work are meaningful for electrode material preparation with high rate performance and volume energy density.

8.
Sci Total Environ ; 694: 133633, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31386953

RESUMO

Modelling is a useful tool for comprehensively describing the processes occurring in floating treatment wetlands (FTWs). However, temperature effects and phosphorus dynamics are not considered in the current FTW models. Therefore, a process-based model comprised of a plant growth submodel, a nitrogen dynamic submodel and a phosphorus dynamic submodel was developed to understand the complicated processes occurring in FTWs. The model was fully calibrated using a mesocosm FTW system operated for 168 days. Global sensitivity analysis revealed that nitrogen removal performance was predominantly sensitive to parameters representing plant characteristics and microbial activity. Because of the high concentration of organic matter, mineralization and sedimentation played important roles in nitrogen and phosphorus removal. In addition, the coprecipitation rate of phosphate also had a significant influence on phosphorus removal performance. When further investigation was applied to understand the behavior of the model, the ratio of nitrogen to phosphorus in plant tissue was found to be an indicator of the nutrient limitation in the water column. Furthermore, the model illustrated that both FTW operating conditions and plant characteristic parameters exerted an important influence on nitrogen removal and plant uptake contribution. Therefore, the selection of appropriate operating conditions and plant species can achieve high nutrients removal and make effective use of plants in FTWs. The model provides a useful tool for assessing the nutrients removal performance of FTWs and for evaluating strategies for them in design and operation.


Assuntos
Monitoramento Ambiental , Poluentes Químicos da Água/análise , Áreas Alagadas , Biodegradação Ambiental , Nitrogênio/análise , Fosfatos/análise , Fósforo/análise , Plantas
9.
Sensors (Basel) ; 19(9)2019 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-31071991

RESUMO

Fault identification for closed-loop control systems is a future trend in the field of fault diagnosis. Due to the inherent feedback adjustment mechanism, a closed-loop control system is generally very robust to external disturbances and internal noises. Closed-loop control systems often encourage faults to propagate inside the systems, which may lead to the consequence that faults amplitude becomes smaller and fault characteristics difference becomes more inapparent. Hence, it has been challenging to achieve fault identification for such systems. Traditional fault identification methods are not particularly designed for closed-loop control systems and thus cannot be applied directly. In this work, a new fault identification method is proposed, which is based on the deep neural network for closed-loop control systems. Firstly, the fault propagation mechanism in closed-loop control systems is theoretically derived, and the influence of fault propagation on system variables is analyzed. Then deep neural network is applied to find fault characteristics difference between different data modes, and a sliding window is used to amplify the fault-to-noise ratio and characteristics difference, with an aim to increase the identification performance. To verify this method, the simulations that are based on a numerical simulation model, the Tennessee industrial system and the satellite attitude control system are conducted. The results show that the proposed method is more feasible and more effective in fault identification for closed-loop control systems compared with traditional data-driven identification methods, including distance-based and angle-based identification methods.

10.
Environ Sci Pollut Res Int ; 26(21): 21161-21171, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31119534

RESUMO

Artificial substrates (ASs) and floating treatment wetlands (FTWs) have been widely used in the treatment of polluted surface water. In fact, periphyton on ASs functions in nutrient removal, while the plant-periphyton complex functions in FTWs. However, the nutrient removal performance of the periphyton on ASs and the plant-periphyton complex in FTWs has not been systematically compared. Thus, ASs and FTWs were established in a mesocosm experiment to compare nitrogen and phosphorus removal between the two ecological treatment techniques. The results showed that the total nitrogen removal efficiency was 60.4% in the AS treatments and 65.3% in the FTWs, while the total phosphorus removal efficiency was 83.7% in the AS treatments and 39.45% in the FTWs. Periphyton on the ASs absorbed 2.5 g N m-2 and 0.85 g P m-2, accounting for 20.8% of the N removal and 18.7% of the P removal. Sedimentation contributed to 71.3% of the N removal and 56.1% of the P removal in the AS treatments. For the plant-periphyton complex in the FTWs, 25.1% of the N and 53.0% of the P accumulated in plant tissue. Most of the reduced N (47.1%) was removed by other pathways, which was likely the effect of periphyton attached on plant roots and floating rafts. The nutrient removal efficiencies and pathways of AS and FTW treatments showed different characteristics, providing a reference for the selection of treatment measures for polluted surface water remediation.


Assuntos
Perifíton , Eliminação de Resíduos Líquidos/métodos , Poluentes Químicos da Água/análise , Áreas Alagadas , Nitrogênio/análise , Fósforo/análise , Plantas/metabolismo , Poluição da Água
11.
Endocr Connect ; 2019 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-31137015

RESUMO

OBJECTIVES: The pathogenesis of Graves' disease (GD) remains unclear. In terms of environmental factors, GD development may be associated with chronic inflammation caused by alteration of the intestinal flora. This study explored the association of intestinal flora alteration with the development of GD among the Han population in southwest China. DESIGN AND METHODS: Fifteen GD patients at the Affiliated Hospital of Zunyi Medical College between March 2016 and March 2017 were randomly enrolled. Additionally, 15 sex- and age-matched healthy volunteers were selected as the control group during the same period. Fresh stool samples were collected, and bacterial 16S RNA was extracted and amplified for gene sequencing with the Illumina MiSeq platform. The sequencing results were subjected to operational taxonomic unit-based classification, classification verification, alpha diversity analysis, taxonomic composition analysis, and partial least squares-discriminant analysis (PLS-DA). RESULTS: The diversity indices for the GD group were lower than those for the control group. The GD group showed significantly higher abundances of Firmicutes, Proteobacteria and Actinobacillus and a higher Firmicutes/Bacteroidetes ratio than the control group. PLS-DA suggested the satisfactory classification of the flora between the GD group and the control group. The abundances of the genera Oribacterium, Mogibacterium, Lactobacillus, Aggregatibacter and Mogibacterium were significantly higher in the GD group than in the control group (P<0.05). CONCLUSIONS: The intestinal flora of GD patients was significantly different from that of the healthy population. Thus, alteration of intestinal flora may be associated with the development of GD.

12.
Am J Cancer Res ; 9(1): 145-159, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30755818

RESUMO

The scaffold/adaptor growth factor receptor bound 2 (GRB2)-associated binding protein 2 (GAB2) is frequently amplified and/or overexpressed in primary high-grade serous ovarian cancers (HGSOCs). Here we investigate a novel treatment strategy by targeting SHP2 and PI3K signaling in HGSOCs with GAB2 amplification/overexpression (GAB2High). The expression of GAB2 was analyzed in primary HGSOCs and ovarian cancer cell lines. In vitro and in vivo assays were performed to demonstrate the effect of SHP2 and PI3K-mediated GAB2High HGSOC progression. Analysis of gene expression data reveals that primary GAB2High HGSOCs are associated with increased ERBB, RAS, and MAPK activity signatures. Inhibition of SHP2 by an allosteric inhibitor SHP099 selectively inhibits ERK1/2 activity, proliferation, and survival of GAB2High ovarian cancer cell lines. Treatment with SHP099 has a synergistic effect with BKM120, a pan-class I PI3K inhibitor, at suppressing proliferation and survival of GAB2High ovarian cancer cells in vitro and in vivo by more effectively activating both BIM and BAD and inhibiting c-MYC compared with individual inhibitor. Our findings identify an important role of SHP2 in promoting proliferation and survival of GAB2High ovarian cancer cells, and combinatorial SHP2 and PI3K inhibition may be a promising therapeutic approach for such cancer.

13.
Sci Rep ; 9(1): 1345, 2019 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-30718895

RESUMO

Proportion and pathways of the eddy-induced heat transport are critical in maintaining world's ocean and climate states. However, an observation-based three-dimensional picture of how oceanic eddies contribute to the global heat transport is yet not quantitatively specified, particularly due to insufficiency of data. Here, using refined methods, we have achieved this goal by analyzing millions of high-quality Argo hydrographic profiles and high-resolution satellite altimetric data. We first presented the spatial differences of individual eddies by reconstructing 254 representative eddies all over the ocean, and then calculated heat fluxes associated with eddies in 5° × 5° boxes. It is revealed that all parameters of eddies vary significantly with both latitudes and longitudes, which is crucial in yielding spatially varying heat fluxes and transports. The eddies not only transport heat towards high latitudes (down-gradient), but also towards low latitudes (up-gradient), particularly at subsurface layers of mid-latitude northern Pacific Ocean and low-latitude Atlantic Ocean. The eddy heat transport is mainly confined in the upper 1000 m of the western part and mid-latitudes of the world's ocean basins, coinciding with maximum meridional temperature gradients. It peaks at 0.8 PW and 0.3 PW (1 PW = 1015 W) at 45°S and 35°N, respectively, stronger than previous estimates based on model results, and accounts for about one half and one third of the estimated total oceanic heat transport at the same latitudes, respectively. In any location except for the areas associated with the Antarctic Circumpolar Current, the eddy stirring component is distinctly (1-10 times) larger than the eddy trapping component.

14.
Small ; 15(29): e1804115, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30645027

RESUMO

Development of noble-metal-free photocatalysts for highly efficient sunlight-driven water splitting is of great interest. Nevertheless, for the photocatalytic H2 evolution reaction (HER), the integrated regulation study on morphology, electronic band structures, and surface active sites of catalyst is still minimal up to now. Herein, well-defined 1D Cd1- x Znx S@O-MoS2 /NiOx hybrid nanostructures with enhanced activity and stability for photocatalytic HER are prepared. Interestingly, the band alignments, exposure of active sites, and interfacial charge separation of Cd1- x Znx S@O-MoS2 /NiOx are optimized by tuning the Zn-doping content as well as the growth of defect-rich O-MoS2 layer and NiOx nanoparticles, which endow the hybrids with excellent HER performances. Specifically, the visible-light-driven (>420 nm) HER activity of Cd1- x Znx S@O-MoS2 /NiOx with 15% Zn-doping and 0.2 wt% O-MoS2 (CZ0.15 S-0.2M-NiOx ) in lactic acid solution (66.08 mmol h-1 g-1 ) is about 25 times that of Pt loaded CZ0.15 S, which is further increased to 223.17 mmol h-1 g-1 when using Na2 S/Na2 SO3 as the sacrificial agent. Meanwhile, in Na2 S/Na2 SO3 solution, the CZ0.15 S-0.2M-NiOx sample demonstrates an apparent quantum yield of 64.1% at 420 nm and a good stability for HER under long-time illumination. The results presented in this work can be valuable inspirations for the exploitation of advanced materials for energy-related applications.

15.
Food Funct ; 9(8): 4135-4142, 2018 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-30019729

RESUMO

In this study, with grass fish bones as the substrate, after flavourzyme treatment, and fermentation with Leuconostoc mesenteroides, a fermentation solution with a high content of soluble calcium was obtained. High performance liquid chromatography and GC-MS analysis indicated that free calcium (11.29 mmol L-1) in the fermentation solution was composed of calcium lactate (3.89 mmol L-1), calcium acetate (6.21 mmol L-1), calcium amino acids and small peptide calcium. Animal experiments show that the fermentation solution of grass fish bones could promote the growth and development of calcium-deficient rats. Complex organic calcium could be well absorbed and utilized by rats so that serum calcium, alkaline phosphatase levels, femur weight and other indicators in calcium-deficient rats could be returned to normal levels. The fermentation solution of grass fish bones can avoid the waste of aquatic proteins and fish bone calcium, and it exhibited high calcium bioavailability. Therefore, the fermentation solution of grass fish bones might be used as a new efficient calcium supplement.


Assuntos
Osso e Ossos/química , Cálcio/farmacocinética , Carpas , Fosfatase Alcalina , Ração Animal/análise , Animais , Densidade Óssea , Cálcio/administração & dosagem , Cálcio/sangue , Cálcio/química , Dieta/veterinária , Fermentação , Manipulação de Alimentos , Leuconostoc mesenteroides/fisiologia , Masculino , Fósforo/sangue , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley
16.
Med Sci Monit ; 24: 4573-4582, 2018 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-29967316

RESUMO

BACKGROUND The weak antitumor efficacy and limited lifespan are the main obstacles that hinder the therapeutic effect of cytokine-induced killer (CIK) cell immunotherapy. In the study, we enhanced the persistence and the antitumor efficacy of CIK cell through PD-1 knockout and hTERT transduction. MATERIAL AND METHODS CIK cells were cultured from patients with hepatocellular carcinoma and PD-1 gene was knocked out through the Cas9 ribonucleoproteins (Cas9 RNPs) electroporation. TIDE assay, T7E1 mismatch cleavage assay, and clone Sanger sequencing were used to detect PD-1 knockout efficiency. The immunophenotype was analyzed by flow cytometry. After PD-1 knockout, the hTERT gene was transduced into PD-1 KO/CIK cells with lentiviral transduction. The hTERT expression and persistence of hTERT/PD-1 KO/CIK cells were evaluated by Western blotting and proliferation curve. The antitumor efficacy was detected by ELISPOT and cytotoxicity assay. The telomere length was measured by the Q-FISH and qPCR method. The karyotype assay was used to analyze the chromosome structural stability. RESULTS The optimal knockout efficiency of PD-1 gene in CIK cells could reach 41.23±0.52%. PD-1 knockout did not affect the immunophenotype of CIK cells. The hTERT transduction enhanced persistence and increased the telomere length. ELISPOT and cytotoxicity assay showed hTERT/PD-1 KO/CIK cells had an enhanced antitumor efficacy. Meanwhile, PD-1 KO/CIK cells transduced with hTERT showed a normal karyotype. CONCLUSIONS PD-1 knockout combined with hTERT transduction could prolong the lifespan and enhance antitumor efficacy of CIK cells against hepatocellular carcinoma cell line.


Assuntos
Carcinoma Hepatocelular/terapia , Células Matadoras Induzidas por Citocinas/imunologia , Neoplasias Hepáticas/terapia , Receptor de Morte Celular Programada 1/imunologia , Telomerase/imunologia , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/imunologia , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Técnicas de Inativação de Genes/métodos , Humanos , Células Matadoras Naturais/imunologia , Células Matadoras Naturais/metabolismo , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/imunologia , Neoplasias Hepáticas/metabolismo , Receptor de Morte Celular Programada 1/genética , Receptor de Morte Celular Programada 1/metabolismo , Telomerase/genética , Telomerase/metabolismo
17.
Environ Sci Pollut Res Int ; 25(23): 23328-23341, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29872980

RESUMO

The risk of water shortage caused by uncertainties, such as frequent drought, varied precipitation, multiple water resources, and different water demands, brings new challenges to the water transfer projects. Uncertainties exist for transferring water and local surface water; therefore, the relationship between them should be thoroughly studied to prevent water shortage. For more effective water management, an uncertainty-based water shortage risk assessment model (UWSRAM) is developed to study the combined effect of multiple water resources and analyze the shortage degree under uncertainty. The UWSRAM combines copula-based Monte Carlo stochastic simulation and the chance-constrained programming-stochastic multiobjective optimization model, using the Lunan water-receiving area in China as an example. Statistical copula functions are employed to estimate the joint probability of available transferring water and local surface water and sampling from the multivariate probability distribution, which are used as inputs for the optimization model. The approach reveals the distribution of water shortage and is able to emphasize the importance of improving and updating transferring water and local surface water management, and examine their combined influence on water shortage risk assessment. The possible available water and shortages can be calculated applying the UWSRAM, also with the corresponding allocation measures under different water availability levels and violating probabilities. The UWSRAM is valuable for mastering the overall multi-water resource and water shortage degree, adapting to the uncertainty surrounding water resources, establishing effective water resource planning policies for managers and achieving sustainable development.


Assuntos
Conservação dos Recursos Naturais/métodos , Recursos Hídricos , Abastecimento de Água , Estudos de Casos e Controles , China , Humanos , Modelos Teóricos , Método de Monte Carlo , Probabilidade , Medição de Risco , Incerteza
18.
Oncotarget ; 9(35): 23878-23889, 2018 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-29844859

RESUMO

Aberrant activation of phosphatidylinosito-4,5-bisphosphate 3-kinase/protein kinase B (PI3K/AKT) signaling in cancer has led to pursuit of inhibitors for targeting this pathway. However, inhibitors of PI3K and AKT have failed to yield efficacious results without adverse effects. Here, we screened a library containing 441 authenticated traditional chinese medicine (TCM) plant extracts by examining their effect on cell viability of a human mammary epithelial cell line HMEC-PIK3CAH1047R, which expresses mutant PIK3CAH1047R and has constitutively active AKT signaling. We found that Oridonin, an extract from Rabdosia rubescens, reduced cell viability to the greatest extent. Oridonin binds to AKT1 and potentially functions as an ATP-competitive AKT inhibitor. Importantly, Oridonin selectively impaired tumor growth of human breast cancer cells with hyperactivation of PI3K/AKT signaling. Moreover, Oridonin prevented the initiation of mouse mammary tumors driven by PIK3CAH1047R. Our results suggest that Oridonin may serve as a potent and durable therapeutic agent for the treatment of breast cancers with hyperactivation of PI3K/AKT signaling.

19.
World Neurosurg ; 113: e213-e221, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29432944

RESUMO

OBJECTIVE: Matrix metalloproteinase-9 (MMP-9), pituitary tumor transforming gene (PTTG), and high mobility group A 2 (HMGA2) play important roles in the tumorigenesis of adrenocorticotrophic hormone (ACTH)-secreting pituitary tumors, but their associations with tumor recurrence after transsphenoidal adenomectomy remain unclear. The aim of the study was to investigate the immunohistochemical expression profiles of MMP-9, PTTG, HMGA2, and Ki-67 in recurrent and nonrecurrent ACTH-secreting pituitary tumors and to identify their associations with tumor behavior and recurrence status. METHODS: A retrospective study was performed including 55 patients with sporadic Cushing's disease with long-term remission after transsphenoidal adenomectomy. Fifty-five ACTH-secreting pituitary tumor specimens and 2 normal pituitary glands were collected. After an intensive follow-up (33-59 months, mean 41.8 months), patients were divided into 2 groups based on their recurrence status: the nonrecurrent group (n = 28) and the recurrent group (n = 27). The expression of MMP-9, PTTG, HMGA2, and Ki-67 in each sample was examined and quantified by immunohistochemistry. The association between MMP-9, PTTG, HMGA2, and Ki-67 expression and clinicopathologic characteristics and tumor recurrence were evaluated. RESULTS: There was a significantly increased expression of MMP-9 in the recurrent group compared with the nonrecurrent group (P = 0.022), and this was strongly associated with the recurrence-free interval (P = 0.007, correlation coefficient. = -0.354). PTTG, HMGA2, and Ki-67 expression were not significantly different between the recurrent group and the nonrecurrent group. No expression of MMP-9, PTTG, HMGA2, or Ki-67 was detected in the 2normal pituitary glands. CONCLUSIONS: ACTH-secreting pituitary tumors with greater levels of MMP-9 were associated with a greater recurrence rate and a shorter recurrence-free interval. MMP-9 could be a valuable tool for predicting recurrence of ACTH-secreting pituitary tumors.


Assuntos
Adenoma Hipofisário Secretor de ACT/química , Adenoma/química , Proteína HMGA2/análise , Hipofisectomia , Antígeno Ki-67/análise , Metaloproteinase 9 da Matriz/análise , Proteínas de Neoplasias/análise , Securina/análise , Adenoma Hipofisário Secretor de ACT/complicações , Adenoma Hipofisário Secretor de ACT/cirurgia , Adenoma/complicações , Adenoma/cirurgia , Adolescente , Adulto , Idoso , Núcleo Celular/química , Síndrome de Cushing/etiologia , Citoplasma/química , Feminino , Perfilação da Expressão Gênica , Humanos , Hidrocortisona/sangue , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/metabolismo , Estudos Retrospectivos , Adulto Jovem
20.
Zhen Ci Yan Jiu ; 42(2): 178-82, 2017 Apr 25.
Artigo em Chinês | MEDLINE | ID: mdl-29071970

RESUMO

OBJECTIVE: To review systematically the clinical effects of spastic paralysis after stroke treated with acupuncture at meridian sinew ("Jingjin", musculotendon). METHODS: "Meridian sinew" "stroke" and "spasm" were taken as the key words to retrieve from the Chinese National Knowledge Infrastracture Database (CNKI), Chongqing VIP Chinese Science and Technology Periodical Database (VIP), Chinese Biomedical Library (CBM), Wanfang Data, PubMed and the Cochrane Library. The Cochrane"risk of bias" tool was used to conduct the methodological quality evaluation to the literature. RevMan 5.3 software was adopted for Meta-analysis. RESULTS: Totally, 13 papers were included, with 820 patients involved. In reference to Cochrane Reviewers' Handbook 5.0.2, the randomized controlled trial (RCT) risk of bias was assessed and it was unclear for all of the 13 papers. The results of Meta-analysis showed that the clinical effect was improved with acupuncture at meridian sinew as compared with normal acupuncture technique[①total effective rate:OR=3.86, 95% CI (2.67,5.57), Z=7.20, P<0.00001; ②modified Ashworth spasm scale:OR=4.54, 95% CI (2.91,7.10), Z=6.64, P<0.00001; ③evaluation of limb motor function with Fugl-Meyer score:MD=4.18, 95% CI (-0.59,8.94), Z=1.72, P=0.09>0.05]. The publication bias of included papers was not obvious and therefore it could be neglected in the impact on the combined effect size. CONCLUSIONS: Acupuncture at meridian sinew is effective in the treatment of spastic paralysis after stroke. The total clinical effect and the improvement in muscular tone with acupuncture at meridian sinew are better than those with normal acupuncture technique. The quality of the included literature is not high generally. Hence, it is necessary to have more clinical studies with high-quality and strict design.


Assuntos
Terapia por Acupuntura , Meridianos , Espasticidade Muscular/terapia , Acidente Vascular Cerebral/complicações , Humanos , Espasticidade Muscular/etiologia , Resultado do Tratamento
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