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1.
Artigo em Inglês | MEDLINE | ID: mdl-32403253

RESUMO

(1) Background: Many studies have shown that increasing taxation on cigarettes does play a role in tobacco control, but few studies have focused on whether increasing cigarette excise taxes significantly affects alcohol consumption. In this article, we aim to examine the effects of China's 2015 increase in the cigarette excise tax on residents' regular drinking behavior. (2) Methods: Using survey data from China Family Panel Studies (CFPS), we performed a panel logit regression analysis to model the relationship between the cigarette excise tax and regular drinking behavior. The Propensity Score Matching with Difference-in-Differences (PSM-DID) approach was adopted to determine the extent to which the cigarette excise tax affected residents' drinking behavior. To test whether the cigarette excise tax could change regular drinking behavior by decreasing daily smoking quantity, we used an interaction term model. (3) Results: China's 2015 increase in the cigarette excise tax had a significant negative effect on the probability of regular alcohol consumption among smokers, and the cigarette excise tax worked by reducing the average daily smoking of smokers. We also found that the regular drinking behavior of male smokers was more deeply affected by the increased cigarette excise tax than females. (4) Conclusions: Our research results not only give a deeper understanding of the impact of the cigarette excise tax, but also provide an important reference with which to guide future decisions concerning excise taxes imposed on cigarettes.

2.
Free Radic Biol Med ; 153: 89-102, 2020 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-32289481

RESUMO

BACKGROUND: It is well acknowledged that alcoholic liver disease (ALD) is widely prevalent all over the world, characterized by aberrant lipid deposition and excessive oxidative stress in hepatocytes. Recently, pyroptosis, a new type of programmed cell death, has been found in ALD, which provides new ideas for the treatment of ALD. METHODS: Male ICR mice were treated with the Lieber-De-Carli diet (Dyets) or isocaloric liquid diet for 8 weeks, and binge alcohol model was also used for ALD. Blood and livers were taken to evaluate the efficacy of oroxylin A. The levels of factors related to hepatocyte pyroptosis were measured via western blot analyses, immunofluorescence analyses and quantitative reverse transcriptase in vitro. RESULT: Our study found that oroxylin A suppressed hepatocyte pyroptosis through a NLRP3 inflammasome dependent-canonical caspase-1 pathway. Results illuminated that oroxylin A inhibited NLRP3 inflammasome activation by reducing ROS accumulation. Furthermore, oroxylin A upregulated mitofusin 2 (Mfn2) to resist lipid deposition and mitochondria-derived ROS overproduction. As an upstream mediator of Mfn2, peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1α), a major regulator of mitochondria, was found to promote transcription of Mfn2 under oroxylin A treatment. CONCLUSION: Our research revealed that oroxylin A could alleviate ALD via PGC-1α/Mfn2 signaling mediated canonical pyroptosis pathway resistance.

3.
Int Immunopharmacol ; 84: 106470, 2020 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-32304991

RESUMO

Activation of hepatic stellate cells (HSCs) is a pivotal event in liver fibrosis, characterized by enhanced retinoic acid signals. Although up-regulated retinoic acid signal responds further to maintain HSC activation, the underlying molecular mechanisms are largely unknown. In this study, we sought to investigate the role of lncRNA-H19 in regulation of retinoic acid signals, and to further examine the underlying mechanism in this molecular context. We found that lncRNA-H19 upregulation could enhance retinoic acid signals to induce HSC activation, whereas lncRNA-H19 knockdown completely disturbed retinoic acid signals. Moreover, the activation of retinoic acid signals impaired the lncRNA-H19 knockdown mediated HSC inactivation. Interestingly, we also found that enhanced retinoic acid signals by lncRNA-H19 was associated with a coordinate increase in retinol metabolism during HSC activation. Increased retinol metabolism contributed to obvious lipid droplet consumption. Importantly, we identified that alcohol dehydrogenase III (ADH3) was essential for lncRNA-H19 to enhance retinoic acid signals. The inhibition of ADH3 completely abrogated the lncRNA-H19 mediated retinoic acid signals and HSC activation. Of note, we identified dihydroartemisinin (DHA) as a natural inhibitor for lncRNA-H19. Treatment with DHA significantly decreased the expression of lncRNA-H19, reduced the expression of ADH3, blocked retinoic acid signals, and in turn, inhibited HSC activation. Overall, these results provided novel implications to reveal the molecular mechanism of increased retinoic acid signals during HSC activation, and identify lncRNA-H19/ADH3 pathway as a potential target for the treatment of liver fibrosis.

4.
Diabetes Metab Res Rev ; : e3319, 2020 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-32233013

RESUMO

BACKGOUND: To figure out whether diabetes is a risk factor influencing the progression and prognosis of 2019 novel coronavirus disease (COVID-19). METHODS: A total of 174 consecutive patients confirmed with COVID-19 were studied. Demographic data, medical history, symptoms and signs, laboratory findings, chest computed tomography (CT) as well the treatment measures were collected and analysed. RESULTS: We found that COVID-19 patients without other comorbidities but with diabetes (n = 24) were at higher risk of severe pneumonia, release of tissue injury-related enzymes, excessive uncontrolled inflammation responses and hypercoagulable state associated with dysregulation of glucose metabolism. Furthermore, serum levels of inflammation-related biomarkers such as IL-6, C-reactive protein, serum ferritin and coagulation index, D-dimer, were significantly higher (P < .01) in diabetic patients compared with those without, suggesting that patients with diabetes are more susceptible to an inflammatory storm eventually leading to rapid deterioration of COVID-19. CONCLUSIONS: Our data support the notion that diabetes should be considered as a risk factor for a rapid progression and bad prognosis of COVID-19. More intensive attention should be paid to patients with diabetes, in case of rapid deterioration.

5.
Microsc Microanal ; : 1-8, 2020 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-32321618

RESUMO

Advanced Ni8W/Ni12W/Ni8W alloy composite substrates used in YBCO-coated conductors with a strong cube texture and high yield strength have been fabricated, and a CeO2 buffer layer film was successfully deposited on the composite substrates. Through in situ tensile testing coupled with electron backscattered diffraction (EBSD) analysis, the stability of the cube texture of Ni8W/Ni12W/Ni8W alloy composite substrates has been investigated. The stress-strain curve shows that the yield strength (at 0.2% strain) of the composite substrates exceeds 250 Mpa. The orientation of grains and boundaries on the surface of the substrates was almost unchanged, while the strain exceeds 0.2%, which indicated that the composite substrates are adequate for depositing buffer layers and YBCO layers by the reel-to-reel process.

7.
Cell Prolif ; 53(3): e12762, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32119185

RESUMO

OBJECTIVE: Hepatic sinusoidal angiogenesis owing to dysfunctional liver sinusoidal endothelial cells (LSECs) accompanied by an abnormal angioarchitecture is a symbol related to liver fibrogenesis, which indicates a potential target for therapeutic interventions. However, there are few researches connecting angiogenesis with liver fibrosis, and the deeper mechanism remains to be explored. MATERIALS AND METHODS: Cell angiogenesis and angiogenic protein were examined in primary LSECs of rats, and multifarious cellular and molecular assays revealed the efficiency of curcumol intervention in fibrotic mice. RESULTS: We found that curcumol inhibited angiogenic properties through regulating their upstream mediator hypoxia-inducible factor-1α (HIF-1α). The transcription activation of HIF-1α was regulated by hedgehog signalling on the one hand, and the protein stabilization of HIF-1α was under the control of Prospero-related homeobox 1 (PROX1) on the other. A deubiquitinase called USP19 could be recruited by PROX1 and involved in ubiquitin-dependent degradation of HIF-1α. Furthermore, our researches revealed that hedgehog signalling participated in the activation of PROX1 transcription probably in vitro. Besides, curcumol was found to ameliorate liver fibrosis and sinusoid angiogenesis via hedgehog pathway in carbon tetrachloride (CCl4 ) induced liver fibrotic mice. The protein expression of key regulatory factors, PROX1 and HIF-1α, was consistent with the Smo, the marker protein of Hh signalling pathway. CONCLUSIONS: In this article, we evidenced that curcumol controlling LSEC-mediated angiogenesis could be a promising therapeutic approach for liver fibrosis.


Assuntos
Inibidores da Angiogênese/uso terapêutico , Cirrose Hepática/tratamento farmacológico , Neovascularização Patológica/tratamento farmacológico , Sesquiterpenos/uso terapêutico , Transdução de Sinais/efeitos dos fármacos , Animais , Células Cultivadas , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/metabolismo , Células Endoteliais/patologia , Proteínas Hedgehog/metabolismo , Proteínas de Homeodomínio/metabolismo , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Cirrose Hepática/metabolismo , Cirrose Hepática/patologia , Masculino , Camundongos Endogâmicos ICR , Neovascularização Patológica/metabolismo , Neovascularização Patológica/patologia , Ratos Sprague-Dawley , Proteínas Supressoras de Tumor/metabolismo , Proteína GLI1 em Dedos de Zinco/metabolismo
8.
Hum Mutat ; 2020 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-32196811

RESUMO

The aberrant expression of matrix metalloproteinases (MMPs) is known to contribute to the pathogenesis of airway remodeling and alveolar disruption in chronic obstructive pulmonary disease (COPD). In the discovery stage, 11 COPD from five families were subjected to whole-genome sequencing, and 21 common polymorphisms in MMPs and TIMPs were identified. These polymorphisms were genotyped in two subsequent verification studies. Of these polymorphisms, c.2392G>A (rs2664370T>C) and c.4158C>A (rs2664369T>G) in MMP16 remained significantly different. Functionally, we found that MMP16 expression was significantly increased in peripheral blood monocytes (PBMCs) from COPD and in cigarette smoke extract-treated 16HBE cells compared with controls. This was also shown by bioinformatics analysis. COPD carrying rs2664370CC showed decreased levels of MMP16 in the plasma and in PBMCs compared with those carrying CT and TT. Treatment with hsa-miR-576-5p mimics led to a greater reduction in luciferase reporter activity in cells transfected with rs2664370CC. Moreover, blood levels of base excess, PCO2 , and PO2 in COPD with rs2664370CC were significantly lower than those with rs2664370CT+TT. Taken together, these results demonstrate that the rs2664370T>C polymorphism in MMP16 protects against the risk of COPD, likely by favoring interaction with hsa-miR-576-5p, leading to reduced MMP16 expression and improved blood gas levels.

9.
Expert Rev Gastroenterol Hepatol ; 14(4): 259-270, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32124651

RESUMO

Introduction: Epigenetic modification is a type of gene expression and regulation that does not involve changes in DNA sequences. An increasing number of studies have proven that epigenetic modifications play an important role in the occurrence and progression of liver diseases through the gene regulation and protein expressions of hepatocellular lipid metabolism, inflammatory reaction, cell proliferation, and activation, etc.Areas covered: In this study, we elaborated and analyzed the underlying functional mechanism of epigenetic modification in alcoholic liver disease (ALD), nonalcoholic fatty liver disease (NAFLD), liver fibrosis (LF), viral hepatitis, hepatocellular carcinoma (HCC), and research progress of recent years.Expert opinion: The further understanding of epigenetic mechanisms that can regulate gene expression and cell phenotype leads to new insights in epigenetic control of chronic liver disease. Currently, hepatologists are exploring the role of DNA methylation, histone/chromatin modification, and non-coding RNA in specific liver pathology. These findings have led to advances in direct epigenetic biomarker testing of patient tissue or body fluid specimens, as well as quantitative analysis. Based on these findings, drug validation of some targets involved in the epigenetic mechanism of liver disease is gradually being carried out clinically.

10.
FASEB J ; 34(3): 4527-4539, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32003501

RESUMO

Obesity has become an epidemic concern in modern society. The chronic obesity is associated with metabolic disorders, such as hyperglycemia, hyperlipidemia, fatty liver, and cadiovascular disease, which cause high risk for mortality. The novel potential strategy to overcome obesity is to "burn out" the extra fat via "browning" of the white adipose tissues. The phytochemical resveratrol (Res) has attracted substantial attention due to its powerful amelioratory effects in metabolic diseases. However, how Res regulates the browning of adipose tissues remains largely elusive. Our data show that the NAD+ -dependent deacetylase silent information regulator 1 (Sirt1) mediates Res-induced browning and fat reduction of adipocytes, as well as other Res-improved metabolic phenotypes including hyperglycemina and hyperlipidemia in mice. Interestingly, we found that the major metabolites of Res in vivo (Res-3-O-glucuronide, Res-4'-O-glucuronide, and Res-3-O-sulfate) were much less potent in promoting browning gene expressions and reducing fat content in comparison to Res itself in mouse and human adipocytes in vitro, suggesting the importance and necessarity to enhance the bioavailability of Res in vivo in consideration of therapeutic application. Taken together, our findings clarify the beneficial effects of Res on excess fat utilization via promotion of browning in a Sirt1-dependent manner, suggesting the potential therapeutic application of Res in the treatment of obesity and related metabolic disorders.

11.
IEEE Trans Cybern ; 2019 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-31751260

RESUMO

Clustering is a fundamental data exploration task which aims at discovering the hidden grouping structure in the data. The traditional clustering methods typically compute a single partition. However, there often exist different and equally meaningful clusterings in complex data. To solve this issue, multiple clustering approaches have emerged with the goal of exploring alternative clusterings from different perspectives. Existing solutions to this problem mainly focus on one-way clustering, that is, they cluster either the samples or the features. However, for many practical tasks, it is meaningful and desirable to explore alternative two-way clusterings (or co-clusterings), which capture not only the sample cluster structure but also the feature cluster structure. To tackle this interesting and unresolved task, we introduce an approach, called multiple co-clusterings (MultiCCs), to generate multiple alternative co-clusterings at the same time. MultiCC takes advantage of matrix tri-factorization to seek the co-clustering indicator matrices for samples and features and defines the row and column redundancy quantification terms to enforce diversity among co-clusterings based on these indicator matrices. After that, it integrates matrix tri-factorization and two nonredundancy terms into a unified objective function and gives an alternative optimization procedure to optimize the objective function. Extensive experimental results demonstrate that MultiCC performs significantly better than the existing multiple clustering methods. In addition, MultiCC can find out interesting co-clusters, which cannot be made by those comparing methods.

12.
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.

13.
Life Sci ; 238: 116934, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31610205

RESUMO

Proliferation and differentiation of hepatic stellate cells (HSCs) are the most noticeable events in hepatic fibrosis, in which the loss of lipid droplets (LDs) is the most important feature. However, the complex mechanisms of LD disappearance have not been fully elucidated. In the current study, we investigated whether oroxylin A has the pharmacological activity of reversing LDs in activated HSCs, and further examined its potential molecular mechanisms. Using genetic, pharmacological, and molecular biological measure, we found that LD content significantly decreased during HSC activation, whereas oroxylin A markedly reversed LD content in activated HSCs. Interestingly, oroxylin A treatment observably decreased the expression of adipose triglyceride lipase (ATGL) without large differences in classical LD synthesis pathway, LD-related transcription factors, and autophagy pathway. ATGL overexpression could completely impair the effect of oroxylin A on reversing LD content. Importantly, reactive oxygen species (ROS) signaling pathway mediated oroxylin A-induced ATGL downregulation and LD revision in activated HSCs. ROS specific stimulant buthionine sulfoximine (BSO) could dramatically diminish the antioxidant effect of oroxylin A, and in turn, abolish reversal effect of oroxylin A on LD content. Conversely, ROS specific scavenger N-acetyl cystenine (NAC) can significantly enhance the pharmacological effect of oroxylin A on LD revision. Taken together, our study reveals the important molecular mechanism of anti-fibrosis effect of oroxylin A, and also suggests that ROS-ATGL pathway is a potential target for reversing LDs.


Assuntos
Flavonoides/farmacologia , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Células Estreladas do Fígado/efeitos dos fármacos , Lipase/antagonistas & inibidores , Gotículas Lipídicas/metabolismo , Cirrose Hepática/tratamento farmacológico , Animais , Autofagia , Células Cultivadas , Regulação para Baixo , Células Estreladas do Fígado/metabolismo , Células Estreladas do Fígado/patologia , Gotículas Lipídicas/efeitos dos fármacos , Cirrose Hepática/etiologia , Cirrose Hepática/metabolismo , Cirrose Hepática/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Transdução de Sinais
14.
ACS Nano ; 13(10): 11363-11371, 2019 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-31525956

RESUMO

Potassium-ion batteries are potential alternatives to lithium-ion batteries for large-scale energy storage considering the low cost and high abundance of potassium. However, it is challenging to obtain stable electrode materials capable of undergoing long-term potassiation/depotassiation due to the high accumulated stress associated with the huge volume variation of the electrode. Here, we simulate the von Mises stress distributions of four different carbon three-dimensional models under an isotropic initial stress by the finite element method and reveal the critical role of the structure of a hollow multihole bowl on the strain-relaxation behavior. In this regard, nitrogen/oxygen codoped carbon hollow multihole bowls (CHMBs) are synthesized via hydrothermal carbonization coupled with an emulsion-templating strategy using biomass as the carbon source. Consistent with our simulation results, the CHMB anode remains stable for over 1000 cycles and delivers a high reversible capacity of 304 mAh g-1 at 0.1 A g-1. In addition to the reduced stress accumulation, the good electrochemical performances are also attributed to the surface capacitive mechanism and the shortened electron/ion transport distance in CHMBs. In particular, the CHMB composite electrode has a volumetric specific capacity 56% higher than that of hollow spheres due to the high tapped density of the bowl-shaped particles.

15.
Phys Life Rev ; 29: 51-54, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31307950

RESUMO

We look at a recent expansion of Physarum research from inspiring biomimetic algorithms to serving as a model organism in the evolutionary study of perception, memory, learning, and decision making.


Assuntos
Physarum , Algoritmos , Biomimética , Resolução de Problemas , Inquéritos e Questionários
16.
Life Sci ; 232: 116650, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31302196

RESUMO

BACKGROUND: Inhalation of NO2 leads to a progressive airflow limitation and the development of emphysema-like lesions. We report on the efficacy of hydrogen sulfide (NaHS) for alleviating NO2-induced pulmonary impairment. METHODS: Sprague Dawley rats were exposed to 20 ppm NO2 for 6 h over six consecutive days for 75 days. At day 75, rats who had developed NO2-induced emphysema were then divided into sodium hydrosulfide (NaHS) administrated group, placebo (NaCl) group and spontaneous recovery group for about one month (days 76-105); Pulmonary function (PF) and hematological and biochemical indices were measured at days 14, 45, 75, and 105. RESULTS: NO2 exposure for 75 days was associated with a significant decrease in FEV100/FVC%, an increased in functional residual capacity (FRC), and histologic evidence of emphysema, moreover; NO2 exposure led to elevated triglyceride (TG), red blood cell (RBC), hemoglobin (HGB), and hematocrit (HCT) levels. Impaired rats treated with NaHS showed no further deterioration in PF compared to rats exposed to ambient air and elevated WBC, granulocyte and lymphocyte counts and HDL-C levels to rats given NaCl. CONCLUSIONS: NO2 exposure causes emphysema and a decline in PF in rats. NaHS could alleviate the PF decline as possible indicated by an elevation of HDL-C levels and leukocyte. NaHS has therapeutic potential for emphysema caused by air pollutant NO2.


Assuntos
Testes Hematológicos , Pulmão/efeitos dos fármacos , Dióxido de Nitrogênio/toxicidade , Sulfetos/administração & dosagem , Sulfetos/farmacologia , Administração por Inalação , Animais , Pulmão/fisiopatologia , Masculino , Ratos , Ratos Sprague-Dawley , Testes de Função Respiratória
17.
Sci Rep ; 9(1): 9265, 2019 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-31239526

RESUMO

The determinations of water status incorporated in hydrous minerals are of considerable significances in geoscience fields. Coincidentally, the aqueous sensitivity of terahertz radiation has motivated numerous explorations in several cross-domain applications. Terahertz time-domain spectroscopy is employed as a major probing technique coupling of traditional detecting methods to uncover the mask of water status in copper sulfate pentahydrate as well as mineral quartz in this article. Based on the quantitative identification of water status in copper sulfate pentahydrate, the water incorporated in mineral quartz is verified qualitatively. Notable differences of optical constants originating from the water content are obtained for copper sulfate pentahydrate and mineral quartz. These present works indicate that terahertz technology can be considered as a promising method to satisfy the ever-increasing requirements in hydrous mineral analyses.

18.
Cell Death Dis ; 10(7): 493, 2019 06 24.
Artigo em Inglês | MEDLINE | ID: mdl-31235688

RESUMO

Necroptosis is a form of regulated necrosis controlled by receptor-interacting kinase 1 (RIPK1 or RIP1), RIPK3 (RIP3), and pseudokinase mixed lineage kinase domain-like protein (MLKL). Increasing evidence suggests that necroptosis is closely associated with pathologies including inflammatory diseases, neurodegenerative diseases, and cancer metastasis. Herein, we discovered the small-molecule PK6 and its derivatives as a novel class of necroptosis inhibitors that directly block the kinase activity of RIPK1. Optimization of PK6 led to PK68, which has improved efficacy for the inhibition of RIPK1-dependent necroptosis, with an EC50 of around 14-22 nM in human and mouse cells. PK68 efficiently blocks cellular activation of RIPK1, RIPK3, and MLKL upon necroptosis stimuli. PK68 displays reasonable selectivity for inhibition of RIPK1 kinase activity and favorable pharmacokinetic properties. Importantly, PK68 provides strong protection against TNF-α-induced systemic inflammatory response syndrome in vivo. Moreover, pre-treatment of PK68 significantly represses metastasis of both melanoma cells and lung carcinoma cells in mice. Together, our study demonstrates that PK68 is a potent and selective inhibitor of RIPK1 and also highlights its great potential for use in the treatment of inflammatory disorders and cancer metastasis.

19.
Evol Comput ; : 1-28, 2019 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-31012736

RESUMO

The uncertain capacitated arc routing problem is of great significance for its wide applications in the real world. In the uncertain capacitated arc routing problem, variables such as task demands and travel costs are realised in real time. This may cause the predefined solution to become ineffective and/or infeasible. There are two main challenges in solving this problem. One is to obtain a high-quality and robust baseline task sequence, and the other is to design an effective recourse policy to adjust the baseline task sequence when it becomes infeasible and/or ineffective during the execution. Existing studies typically only tackle one challenge (the other being addressed using a naive strategy). No existing work optimises the baseline task sequence and recourse policy simultaneously. To fill this gap, we propose a novel proactive-reactive approach, which represents a solution as a baseline task sequence and a recourse policy. The two components are optimised under a cooperative coevolution framework, in which the baseline task sequence is evolved by an estimation of distribution algorithm, and the recourse policy is evolved by genetic programming. The experimental results show that the proposed algorithm, called Solution-Policy Coevolver, significantly outperforms the state-of-the-art algorithms to the uncertain capacitated arc routing problem for the ugdb and uval benchmark instances. Through further analysis, we discovered that route failure is not always detrimental. Instead, in certain cases (e.g., when the vehicle is on the way back to the depot) allowing route failure can lead to better solutions.

20.
Medicine (Baltimore) ; 98(17): e15260, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31027076

RESUMO

INTRODUCTION: Ectopic liver (EL) is a rare entity, which is reported to develop at various sites, such as the abdominal cavity, the retroperitoneal cavity, the pleural cavity, and the mediastinum. PATIENT CONCERNS: A 27-year-old previously healthy Chinese man suffered from a discontinuous abdominal pain in the upper abdomen for 2 months. DIAGNOSIS: The upper gastrointestinal endoscopy revealed there was a polypoid mucosal uplift on the distal region of the esophagus near the cardia. INTERVENTIONS: Endoscopic polypectomy was performed. OUTCOMES: Pathology examination showed the liver tissue. CONCLUSION: EL should be excised as it may possibly lead to the development of a malignancy. Endoscopic resection was found to be safe and reliable in this case.


Assuntos
Coristoma/patologia , Coristoma/cirurgia , Esôfago/patologia , Fígado/patologia , Dor Abdominal/etiologia , Adulto , China , Coristoma/complicações , Endoscopia Gastrointestinal , Humanos , Masculino
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