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1.
Anal Chim Acta ; 1106: 61-70, 2020 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-32145856

RESUMO

Analysis of C.elegans by droplet microfluidics has been widely used in study of locomotive behavior responses to neurotoxicity due to the capacity of high-throughput manipulating single cells. However, it has been difficult to manipulate droplets flexibly and actively on account of the limitation of the dimension of individual C. elegans droplets. In this study, a novel MiDMS (Micro-injection Droplet Microfluidic System) was proposed, which consisted of three parts: single C. elegans droplet generator, droplets drug micro-injection channels and drug-incubation observation array. Individual C.elegans droplets were produced initially by regulating the flow rates between oil and water phase as well as the concentration of C.elegans in suspension. Then, the drug solution was precisely injected into each C.elegans droplet, which by electricity induced surface tension of droplet changing. In addition, the effect of neurotoxic Cu2+ on locomotive behavior of C. elegans was evaluated at single cell resolution. The results showed that the neurotoxicity induced behavioral disorder of the C. elegans was more obvious with the increase of Cu2+ concentration or treatment time, and these dose-effect and time-effect relationship in MiDMS were similar as in petri dish. This study will provide a powerful platform for the study of the response of C. elegans to quantitative drug at single cell resolution.

2.
Clin Pediatr (Phila) ; : 9922820910821, 2020 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-32146830

RESUMO

Objectives. The available literature on pulmonary disease in pediatric inflammatory bowel disease is limited. We evaluated the prevalence of pulmonary manifestations in pediatric inflammatory bowel disease and their association with disease severity. Methods. Patients completed the St. George's Respiratory Questionnaire (SGRQ), a self-reported measure of quality of life in patients with pulmonary disease. Chart review provided demographic information and Pediatric Crohn's Disease Activity Index (PCDAI) and Pediatric Ulcerative Colitis Activity Index scores. Regression models were utilized to evaluate associations between SGRQ score and clinical risk factors. Results. The prevalence of pulmonary manifestations was 9.62% (95% confidence interval = 5.48% to -15.36%). PCDAI scores in Crohn's disease patients with pulmonary symptoms were significantly higher (SGRQ mean = 10.71 ± 10.94) than in patients without such symptoms. SGRQ score was also higher in patients with indeterminate colitis (8.64, 95% confidence interval = 0.72-16.57, P = .03), when compared with Crohn's disease. Conclusions. Additional investigations including pulmonary function tests and imaging could provide further insight into this issue.

3.
Sleep Health ; 2020 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-32147359

RESUMO

OBJECTIVES: Examine the associations of sleep problems with health-risk behaviors and psychological well-being in a representative sample of Canadian adults. DESIGN: Cross-sectional. SETTING: The 2011-2012 Canadian Community Health Survey (CCHS, conducted by Statistics Canada). PARTICIPANTS: Of all individuals taking part in the 2011-2012 CCHS, 42,600 participants aged ≥18 years from five provinces/territories (Nova Scotia, Quebec, Manitoba, Alberta, and Yukon) who participated in the sleep survey module were selected for this study. MEASUREMENTS: Health conditions were self-reported. Sleep problems referred to extreme sleep durations (either <5 or ≥10 hours) and insomnia symptom. Health-risk behaviors included physical inactivity, daily smoking, highly sedentary behavior, and insufficient fruit and vegetable consumption. Worse psychological well-being included having worse self-rated general health, worse self-rated mental health, and worse sense of belonging, and being dissatisfied with life. RESULTS: The participants represented 10,614,600 Canadian adults aged ≥18 years from the five abovementioned provinces/territories. A significantly higher prevalence of all health-risk behaviors and worse psychological well-being was found among participants with extreme sleep durations (than those with 7 to <8 hours) and insomnia symptom (than those without insomnia symptom). After multivariate adjustment, extreme sleep durations and insomnia symptom were still independently associated with increased odds of all health-risk behaviors and worse psychological well-being. CONCLUSIONS: Both extreme sleep durations and insomnia symptom were independently associated with health-risk behaviors and worse psychological well-being among Canadian adults.

4.
J Am Coll Cardiol ; 75(8): 870-880, 2020 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-32130922

RESUMO

BACKGROUND: Arterial stiffening is central in the vascular aging process. Traditionally, vascular research has focused on atherosclerotic vascular disease, whereas arterial stiffness has not attracted similar attention. OBJECTIVES: The purpose of this study was to assess lifetime trajectories of arterial stiffening in Chinese populations facing a high burden of cardiovascular disease, with a particular focus on age-sex interactions and potential determinants. METHODS: This large-scale observational study comprised 2 independent cross-sectional population samples and 1 prospective cohort totaling 80,415 healthy subjects with brachial-ankle pulse wave velocity (baPWV) measurements available. Associations with potential risk conditions were analyzed using linear regression, linear random intercepts mixed models, and L1-regularized linear models. RESULTS: The dynamics of age-dependent arterial stiffening differed in sexes, with stiffer vessel observed in men from adolescence to age 58 years and in women thereafter. The steeper increase in baPWV in women after menopause is partly explained by the fact that vascular risk factors are more strongly associated with arterial stiffness in women than in men. Age and systolic blood pressures were the strongest determinants of baPWV, whereas other vascular and metabolic risk factors, except low-density lipoprotein cholesterol, showed consistent associations of moderate strength. CONCLUSIONS: The significant age-sex interaction in arterial stiffening provides an important clue of explanation for the heightened cardiovascular disease risk in postmenopausal women. Detailed knowledge on lifetime trajectories of arterial stiffening, and its potential risk factors is a prerequisite for the development of new prevention strategies counteracting vascular aging.

5.
Viruses ; 12(3)2020 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-32121117

RESUMO

The constant crosstalk between the large avian reservoir of influenza A viruses (IAV) and its mammalian hosts drives viral evolution and facilitates their host switching. Direct adaptation of an avian strain to human or reassortment between avian-origin gene segments with that of human strains are the two mechanisms for the emergence of pandemic viruses. While it was suggested that the 1918 pandemic virus is of avian origin, reassortment of 1918 human isolates and avian influenza viruses led to the generation of 1957 and 1968 pandemic viruses. Interestingly, the avian PB1 segment, which encodes the catalytic subunit of IAV polymerase, is present in the 1957 and 1968 pandemic viruses. The biological consequence and molecular basis of such gene exchange remain less well understood. Using the 2009 pandemic H1N1 virus as a model, whose polymerase contains a human-origin PB1 subunit, we demonstrate that the acquisition of an avian PB1 markedly enhances viral RNA synthesis. This enhancement is also effective in the absence of PB2 adaptive mutations, which are key determinants of host switching. Mechanistically, the avian-origin PB1 does not appear to affect polymerase assembly but imparts the reassorted pandemic polymerase-augmented viral primary transcription and replication. Moreover, compared to the parental pandemic polymerase, the reassorted polymerase displays comparable complementary RNA (cRNA)-stabilizing activity but is specifically enhanced in progeny viral RNA (vRNA) synthesis from cRNA in a trans-activating manner. Overall, our results provide the first insight into the mechanism via which avian-origin PB1 enhances viral RNA synthesis of the 2009 pandemic virus polymerase.

6.
Opt Express ; 28(4): 5000-5012, 2020 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-32121729

RESUMO

Detection of integrated circuit (IC) defects is vital in IC manufacturing. Traditional defect detection methods have relied on scanning electron microscopy and X-ray imaging techniques that are time consuming and destructive. Hence, in this paper we considered terahertz imaging as a label-free and nondestructive alternative. This study aimed to use a convolutional neural network model (CNN) to improve the performance of the terahertz imaging IC detection system. First, we constructed a terahertz imaging IC dataset and analyzed it. Subsequently, a new CNN structure was proposed based on the VGG16 network. Finally, it was optimized based on its structure and dropout rate. The method proposed above can improve IC defects detection accuracy of THz imaging. Most significantly, this work will promote the application of terahertz imaging in practice and provide a foundation to further research in relevant fields.

7.
Phys Med Biol ; 2020 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-32155611

RESUMO

Fibroglandular tissue (FGT) segmentation is a crucial step for quantitative analysis of background parenchymal enhancement (BPE) in MRI, which is useful for breast cancer risk assessment. In this study, we develop an automated deep learning method based on a generative adversarial network (GAN) to identify the FGT region in MRI volumes and evaluate its impact on a specific clinical application. The GAN consists of an improved U-Net as a generator to generate FGT candidate areas and a patch deep convolutional neural network (DCNN) as discriminator to evaluate the authenticity of the synthetic FGT region. The proposed method has two improvements compared to the classical U-Net: 1) the improved U-Net is designed to extract more features of the FGT region for a more accurate description of the FGT region; 2) a patch DCNN is designed for discriminating the authenticity of the FGT region generated by the improved U-Net, which makes the segmentation result more stable and accurate. A dataset of 100 three-dimensional bilateral breast MRI scans from 100 patients (aged 22-78 years) was used in this study with the Institutional Review Board (IRB) approval. Three-dimensional hand segmented FGT areas for all breasts were provided as a reference standard. Five-fold cross-validation was used in training and testing of the models. The Dice similarity coefficient (DSC) and Jaccard index (JI) values were evaluated to measure the segmentation accuracy. Previous method using classical U-Net was used as a baseline in this study. In the five partitions of the cross-validation set, the GAN achieved DSC and JI values of 87.0±7.0% and 77.6±10.1% respectively, while the corresponding values obtained through by the baseline method were 81.1±8.7% and 69.0±11.3% respectively. The proposed method is significantly superior to the previous method using U-Net. The FGT segmentation impacted the BPE quantification application in the following manner: the correlation coefficients between quantified BPE value and BI-RADS BPE categories provided by the radiologist were 0.46±0.15 (best: 0.63) based on GAN segmented FGT areas, while the corresponding correlation coefficients were 0.41±0.16 (best: 0.60) based on baseline U-Net segmented FGT areas. BPE can be quantified better using the FGT areas segmented by the proposed GAN model than using the FGT areas segmented by the baseline U-Net.

8.
AJR Am J Roentgenol ; : 1-7, 2020 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-32160054

RESUMO

OBJECTIVE. The purpose of this study was to evaluate the feasibility of ultrasound (US)-guided percutaneous transhepatic cholangial drainage (PTCD) and consequent percutaneous US cholangiography in managing the dilated biliary tracts of children who have undergone hepatobiliary surgery. SUBJECTS AND METHODS. Sixteen children (11 boys, five girls; age range, 3-144 months) who underwent hepatobiliary surgery from December 2016 to October 2018 and had US evidence of biliary dilatation were included. All patients had undergone US-guided PTCD because of elevated postoperative serum bilirubin levels or bile duct infection. Immediately after the PTCD procedure, diluted sulphur hexafluoride microbubbles dispersion was injected through the PTCD tube to evaluate the anastomosis and the intrahepatic bile duct tree. Laboratory results, including those of serum bilirubin measurement, liver function tests, and routine blood tests, were evaluated before and after PTCD. Nine of 16 patients also underwent percutaneous transhepatic cholangiography (PTC). The percutaneous US cholangiography findings were evaluated and compared with the PTC findings. RESULTS. Liver enzyme levels decreased after PTCD with a statistically significant difference from the values before PTCD. Percutaneous US cholangiography showed that the anastomosis in 6 of the 16 patients (37.5%) was patent and depicted the morphologic featuresof intrahepatic bile duct tree in five of these patients. In the other 10 patients, the anastomosis was completely obstructed, and percutaneous US cholangiography depicted the morphologic features of intrahepatic bile duct tree in eight patients. In the nine patients who underwent PTC, the percutaneous US cholangiographic findings were the same as the PTC findings. CONCLUSION. US-guided PTCD is helpful in relieving jaundice and inflammation in children who have undergone hepatobiliary surgery and have biliary dilatation. Findings at consequent percutaneous US cholangiography are comparable to those of PTC in depicting the anastomosis in these patients.

9.
Zhen Ci Yan Jiu ; 45(2): 122-7, 2020 Feb 25.
Artigo em Chinês | MEDLINE | ID: mdl-32144922

RESUMO

OBJECTIVE: To investigate the effect of Tongli Shuji acupuncture on the behavioristics, the percentage of cerebral infarct volume, and the expression of Jagged2 and Notch2 proteins in the hippocampus of the ischemic hemisphere in rats with permanent ischemia of the right middle cerebral artery, as well as the mechanism of Tongli Shuji acupuncture in improving ischemic cerebrovascular disease. METHODS: Sprague-Dawley rats were randomly divided into sham-operation group, model control group, medication group, routine acupuncture group, and Tongli Shuji group, with 10 rats in each group. The suture method was used to establish a model of permanent ischemia of the right middle cerebral artery. The rats in the medication group were given Citicoline (0.4 mg/kg) by gavage, those in the routine acupuncture group were given acupuncture at"Baihui"(GV20) and"Dazhui" (GV14) 15 minutes per day, and those in the Tongli Shuji group were given acupuncture at "Zhengying "(GB17), "Tianjing"(SJ10), and"Huantiao"(GB30) at the left side. The neurological deficit score was determined on days 1, 7, 14, 21 and 28 after surgery, the percentage of cerebral infarct volume was measured after treatment, and Western blot was used to measure the protein expression of Jagged2 and Notch2 in the right hippocampal tissue. RESULTS: Compared with the sham-operation group, the model control group had significant increases in the neurological deficit score on day 1 after surgery (P<0.001). Compared with the model control, medication and routine acupuncture groups, the Tongli Shuji group had significant reductions in the neurological deficit score on day 21 after surgery (P<0.01). Compared with the sham-operation group, the model control group had a significant increase in the percentage of cerebral infarct volume(P<0.05).The Tongli Shuji group had a significant reduction in the percentage of cerebral infarct volume compared with the medication groups (P<0.05). Compared with the model control group, the routine acupuncture group had a significant increase in the expression of hippocapmal Jagged2(P<0.01).Compared with the model control, medication and routine acupuncture groups, the Tongli Shuji group had significant increases in the expression of hippocampal Jagged2 and Notch2 (P<0.01). CONCLUSION: Acupuncture can improve the behavioral manifestations of neurological deficit in rats with permanent ischemia of the right middle cerebral artery. Tongli Shuji acupuncture can significantly up-regulate the protein expression of Jagged2 and Notch2 in the hippocampal tissue of the ischemic region, possibly by activating the Notch signaling pathway to exert a neuroprotective effect.


Assuntos
Terapia por Acupuntura , Isquemia Encefálica , Animais , Infarto da Artéria Cerebral Média , Artéria Cerebral Média , Ratos , Ratos Sprague-Dawley , Receptor Notch2
10.
Theranostics ; 10(7): 2918-2929, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32194844

RESUMO

Nanoparticle formulations have proven effective for cisplatin delivery. However, the development of a versatile nanoplatform for cisplatin-based combination cancer therapies still remains a great challenge. Methods: In this study, we developed a one-pot synthesis method for a microporous organosilica shell-coated cisplatin nanoplatform using a reverse microemulsion method, and explored its application in co-delivering acriflavine (ACF) for inhibiting hypoxia-inducible factor-1 (HIF-1). Results: The resulting nanoparticles were tunable, and they could be optimized to a monodisperse population of particles in the desired size range (40-50 nm). In addition, organic mPEG2000-silane and tetrasulfide bond-bridged organosilica were integrated into the surface and silica matrix of nanoparticles for prolonged blood circulation and tumor-selective glutathione-responsive degradation, respectively. After reaching the tumor sites, cisplatin induced cancer cell death and activated HIF-1 pathways, resulting in acquired drug resistance and tumor metastasis. To address this issue, ACF was co-loaded with cisplatin to prevent the formation of HIF-1α/ß dimers and suppress HIF-1 function. Hence, the efficacy of cisplatin was improved, and cancer metastasis was inhibited. Conclusion: Both in vitro and in vivo results suggested that this core-shell nanostructured cisplatin delivery system represented a highly efficacious and promising nanoplatform for the synergistic delivery of combination therapies involving cisplatin.

11.
Theranostics ; 10(7): 2965-2981, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32194849

RESUMO

Magnetic fluid hyperthermia (MFH) treatment makes use of a suspension of superparamagnetic iron oxide nanoparticles, administered systemically or locally, in combination with an externally applied alternating magnetic field, to ablate target tissue by generating heat through a process called induction. The heat generated above the mammalian euthermic temperature of 37°C induces apoptotic cell death and/or enhances the susceptibility of the target tissue to other therapies such as radiation and chemotherapy. While most hyperthermia techniques currently in development are targeted towards cancer treatment, hyperthermia is also used to treat restenosis, to remove plaques, to ablate nerves and to alleviate pain by increasing regional blood flow. While RF hyperthermia can be directed invasively towards the site of treatment, non-invasive localization of heat through induction is challenging. In this review, we discuss recent progress in the field of RF magnetic fluid hyperthermia and introduce a new diagnostic imaging modality called magnetic particle imaging that allows for a focused theranostic approach encompassing treatment planning, treatment monitoring and spatially localized inductive heating.

12.
J Geriatr Oncol ; 2020 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-32199776

RESUMO

OBJECTIVES: Polypharmacy (≥5 concurrent medications) is common among older patients with cancer (48%-80%) and associated with increased frailty, morbidity, and mortality. This study examined the relationship between polypharmacy and inpatient hospitalization among older adults with cancer treated with intravenous (IV) chemotherapy. MATERIALS AND METHODS: The main data source was the Surveillance, Epidemiology, and End Results-Medicare linked files. Patients (≥65 years) were included if they were diagnosed with prostate (n = 1430), breast (n = 5490), or lung cancer (n = 7309) in 1991-2013 and received IV chemotherapy in 2011-2014. The number of medications during the six-month window pre-IV chemotherapy initiation determined polypharmacy status. Negative binomial models were used to assess the association between polypharmacy and post-chemotherapy inpatient hospitalization. The results were presented as incidence rate ratios. RESULTS: We identified 13,959 patients with prostate, breast, or lung cancer treated with IV chemotherapy. The median number of prescription medications during the six-month window pre-IV chemotherapy initiation was high: ten among patients with prostate cancer, nine among patients with breast cancer, and eleven among patients with lung cancer. Compared to patients taking <5 prescriptions, post-chemotherapy hospitalization rate for patients with prostate cancer was 42%, 75%, and 114% higher among those taking 5-9, 10-14, and 15+ medications, respectively. Patients with breast and lung cancer demonstrated similar patterns. CONCLUSION: This large population-based study found that polypharmacy during the six-month window pre-IV chemotherapy is highly predictive of post-chemotherapy inpatient hospitalization. Further studies are needed to evaluate whether medication management interventions can reduce post-chemotherapy inpatient hospitalization among older patients with cancer.

13.
Orthop Surg ; 2020 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-32202051

RESUMO

OBJECTIVE: To analyze the relationship between the length from injury to first debridement (LFITFD) of open tibial fractures and perioperative infection, and explore independent risk factors related to infection. METHODS: This retrospective study focused on 215 clinical patients with open tibial fractures who were admitted from January 2012 to January 2017. According to the time from injury to the operation, the patients were categorized into four groups: LFITFD ≤ 6 h, 6 < LFITFD ≤ 12 h, 12 < LFITFD≤24 h, and (LFITFD > 24 h). Infection risk factors were screened by univariate analysis, and multivariate logistic regression analysis was used to determine independent risk factors. RESULTS: The infection rates of four groups were 9.2%, 9.5%, 11.1%, and 10.5% with six of 65, nine of 95, four of 36, and two of 19 patients being infected, respectively. There was no statistical significance between the four groups. The infection rates among fractures of different Gustilo-Anderson classifications were as follows. Of 62 cases of type I fractures, two were infected, and the infection rate was 3.2%. Among those with type II fractures, eight were infected, and the infection rate was 8.2%. Three of 26 cases of type IIIA fracture were infected, yielding an infection rate of 11.5%, seven of 25 cases of type III B fracture were infected (28% infection rate), and one of four cases of type III C fracture was infected (25% infection rate). There was a statistically significant difference between the five groups. Multivariate regression analysis showed that smoking, combined diabetes, surgical time, and fracture Gustilo-Anderson classification were independent risk factors for perioperative infection of open tibial fractures, and the difference in time from injury to first debridement was not related to infection. CONCLUSION: The incidence of perioperative infection in patients with open tibial fractures has little to do with the time of the first debridement, which is mainly related to the level of the fracture's Gustilo-Anderson classification. At the same time, smoking is prohibited before the operation, the patient's blood glucose is managed, and the debridement operation time is minimized conducive to reducing the incidence of infection.

14.
Colloids Surf B Biointerfaces ; 190: 110903, 2020 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-32120128

RESUMO

Small intestinal submucosa extracellular matrix (SIS-ECM) composite materials are catching eyes in tissue engineering but have been rarely studied in bone repair. In this study, we developed the unique bilayer bone scaffolds by assembling decellularized SIS-ECM and poly(lactic-co-glycolic acid) (PLGA) nanofibers through the electrospinning technique. To strengthen the bioactivity of the scaffolds, pifithrin-α (PFTα), a p53 inhibitor that can reduce the repressive function of p53 in osteogenesis, was preloaded in the PLGA electrospinning solution. We found that the resultant SIS-ECM/PLGA/PFTα scaffolds exhibited porous morphology, good biocompatibility, and enhanced osteoinductivity. Specifically, the SIS-ECM/PLGA/PFTα scaffolds could promote the osteogenic differentiation and mineralization of the preosteoblasts MC3T3-E1 in a PFTα does dependent manner in vitro. Furthermore, the SIS-ECM/PLGA/PFTα scaffolds were better than the pure SIS-ECM and SIS-ECM/PLGA scaffolds in terms of vessel and new bone tissue formation after 4 weeks post-implantation in vivo. These overall findings indicated that the bilayer PFTα loaded SIS-ECM/PLGA scaffolds facilitated vascularized bone regeneration, showing promising potential for bone tissue engineering.

15.
J Food Prot ; 83(4): 677-685, 2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-32221573

RESUMO

ABSTRACT: Restaurants are a place where food is prepared and cooked directly for customers. Food safety in restaurants is a public health concern and a multidisciplinary issue that needs to be explored. To protect the health of consumers and identify external factors that may affect food safety risk, this study explores how economic development and population density at the local level relate to food safety inspection outcomes in restaurants of different sizes. Using food safety violation data from 2017 and 2018, we categorized restaurants in Gansu Province, China, into small and large ventures to examine the relationships among regional character, restaurant size, and food safety risk. Data were analyzed using Mann-Whitney U tests and negative binomial regression models. Our results show that large restaurants have a higher food safety risk than small restaurants. Moreover, the region with the lowest level of economic development had the highest food safety risk, while the region with the lowest population density had insufficient local inspections. By providing insight into which establishments demonstrate the highest food safety risks, our findings contribute to the development of processes that seek to effectively identifying food safety risks.

16.
J Hazard Mater ; 392: 122475, 2020 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-32208312

RESUMO

Humans are frequently exposed to the antimicrobial triclocarban (TCC) due to its widespread use in consumer and personal care products. However, there is a paucity of research on potential hepatotoxic risks of TCC exposure. In this study, nontargeted metabolomics approach was applied to simultaneously investigate TCC-induced perturbation of endogenous metabolites and generation of xenobiotic metabolites in human hepatic cells. In normal hepatocytes, TCC exposure induced cellular redox imbalance as evidenced by the decrease of glutathione metabolism and overproduction of reactive oxygen species (ROS), resulting in DNA damage and lipid peroxidation. Defective oxidative phosphorylation and increased purine metabolism were two potential sources of elevated ROS. However, in cancerous hepatocytes, TCC exposure enhanced glutathione metabolism, glycolysis, and glutaminolysis, which contributed to the cellular homeostasis of redox and energy status, as well as the progression of liver cancer. As a xenobiotic, metabolic activation of TCC through phase I hydroxylation was observed. The hepatic cytotoxicity follows the order of 6-OH-TCC > 2'-OH-TCC > 3'-OH-TCC > DHC, with EC50 values of 2.42, 3.38, 7.38, and 24.8 µM, respectively, in 48 h-treated normal cells. This study improves current understanding of TCC-triggered hepatotoxicity, and provides novel perspectives for evaluating the interaction of environmental pollutants with biological systems.

17.
Artigo em Inglês | MEDLINE | ID: mdl-32009375

RESUMO

Due to the limited thermoelectric (TE) performance of conducting polymers and rigidity of inorganic materials, it is still a huge challenge to prepare low-cost, highly flexible, and high-performance TE materials. Herein, we fabricated n-type Ag2Se films using a porous nylon membrane as a flexible substrate by vacuum-assisted filtration, followed by hot pressing. A very high power factor of ∼1882 µW m-1 K-2 at room temperature is obtained. The high power factor is mainly the result of the high density of the Ag2Se film and the tuned grain orientation, which is realized by the synthesis of multisized Ag2Se nanostructures. The film also exhibits excellent flexibility with 90.7% retention of the power factor after bending around a rod of 4 mm radius for 1000 times. A four-leg TE generator is assembled with the Ag2Se film, and its maximum output power is up to 3.2 µW at a temperature difference of 30 K, corresponding to the maximum power density of 22.0 W m-2 and a normalized maximum power density of 408 µW m-1 K-2. This work provides an effective route to achieve high-power-factor, high-flexibility, and low-cost TE films.

18.
Artigo em Inglês | MEDLINE | ID: mdl-32065624

RESUMO

AIMS: In patients without obstructive coronary artery disease (CAD), we examined the prognostic value of risk factors and atherosclerotic extent. METHODS AND RESULTS: Patients from the long-term CONFIRM registry without prior CAD and without obstructive (≥50%) stenosis were included. Within the groups of normal coronary computed tomography angiography (CCTA) (N = 1849) and non-obstructive CAD (N = 1698), the prognostic value of traditional clinical risk factors and atherosclerotic extent (segment involvement score, SIS) was assessed with Cox models. Major adverse cardiac events (MACE) were defined as all-cause mortality, non-fatal myocardial infarction, or late revascularization. In total, 3547 patients were included (age 57.9 ± 12.1 years, 57.8% male), experiencing 460 MACE during 5.4 years of follow-up. Age, body mass index, hypertension, and diabetes were the clinical variables associated with increased MACE risk, but the magnitude of risk was higher for CCTA defined atherosclerotic extent; adjusted hazard ratio (HR) for SIS >5 was 3.4 (95% confidence interval [CI] 2.3-4.9) while HR for diabetes and hypertension were 1.7 (95% CI 1.3-2.2) and 1.4 (95% CI 1.1-1.7), respectively. Exclusion of revascularization as endpoint did not modify the results. In normal CCTA, presence of ≥1 traditional risk factors did not worsen prognosis (log-rank P = 0.248), while it did in non-obstructive CAD (log-rank P = 0.025). Adjusted for SIS, hypertension and diabetes predicted MACE risk in non-obstructive CAD, while diabetes did not increase risk in absence of CAD (P-interaction = 0.004). CONCLUSION: Among patients without obstructive CAD, the extent of CAD provides more prognostic information for MACE than traditional cardiovascular risk factors. An interaction was observed between risk factors and CAD burden, suggesting synergistic effects of both.

19.
Artigo em Inglês | MEDLINE | ID: mdl-32093892

RESUMO

BACKGROUND: ß-cell dysfunction is one of the core pathogenetic mechanisms of type 2 diabetes mellitus (T2DM). However, there are currently no effective therapeutic strategies to preserve ß-cell mass and function. The role of islet macrophage phenotype reprogramming in ß-cell dysfunction has attracted great attention. Given that advanced glycation end products (AGEs) are major pathogenic factors in T2DM, we investigated the effect of AGEs on macrophage activation and their role in ß-cell dysfunction. METHODS: We examined cytokine secretion, M1 and M2 macrophage-associated marker expression and MAPK phosphorylation levels in AGEs-stimulated macrophages. MIN6 cells were cocultured with AGEs-pretreated macrophages to study the effect of AGEs-induced macrophage activation on ß-cell dysfunction. RESULTS: We found that AGEs treatment significantly enhanced macrophage secretion of proinflammatory cytokines. The expression of M1 macrophage markers, such as iNOS and the surface marker CD11c, was significantly upregulated, whereas the expression of M2 macrophage markers, such as Arg1 and CD206, was reciprocally downregulated upon AGEs stimulation. AGEs treatment predominantly activated the MAPK pathway, and the inhibition of the MAPK pathway partially attenuated the AGEs-induced polarization of macrophages. In addition, coculture with AGEs-pretreated macrophages significantly inhibited the expression of molecules involved in ß-cell function and was accompanied by the impairment of glucose-stimulated insulin secretion (GSIS) in MIN6 cells. CONCLUSION: AGEs enhance the expression of proinflammatory molecules by activating the MAPK pathway. Moreover, these data imply that AGEs induce macrophage M1 phenotype polarization but restrain M2 polarization, which might contribute to ß-cell dysfunction in the pathogenesis of T2DM.

20.
Inflamm Res ; 69(4): 331-345, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32088731

RESUMO

BACKGROUND AND AIMS: The relationship between serum amyloid A (SAA) and coronary heart disease (CHD) remains inconsistent, and the correlation of SAA levels and some factors have not been thoroughly evaluated in CHD. The present study assessed the associations of SAA levels and CHD, and the correlation of SAA levels and CRP, fibrinogen, interleukin-6 (IL-6), and HDL-C levels in CHD patient. METHODS: We systematically searched databases of Cochrane Library, PubMed, Embase, and ScienceDirect from their inception to 2018. Pooled standardized mean difference (SMD), correlation coefficient (r), and 95% confidence intervals (CI) were computed using random-effect model. RESULT: A total of 26 studies were identified for analysis, involving a total of 6466 CHD cases and 16,184 participants. Compared with the control group, the case group had markedly higher SAA levels (SMD = 0.38, 95% CI 0.21, 0.56). Subgroup analysis manifested that SAA level difference between case group and control group were associated with age, continent, and study type. Moreover, meta-regression model suggested that different continent, sex, and publication year can explain the origin of 52.05%, 50.17%, 28.07% heterogeneity, respectively. By stratified analyses, we further found that the concentration of SAA increased gradually with the aggravation of CHD. Additionally, the meta-analysis of correlation showed that SAA levels were positively related with CRP (r = 0.45, 95% CI 0.19, 0.71), fibrinogen (r = 0.41, 95% CI 0.35, 0.47), and IL-6 (r = 0.48, 95% CI 0.41, 0.54) levels, but negatively linked with HDL-C levels (r = - 0.28, 95% CI - 0.38, - 0.18) in CHD patients. CONCLUSION: High levels of SAA are significantly associated with increased risk of CHD, especially for participants aged more than 55 years, subjects from Europe and Asia, or case-control study. Furthermore, we find that SAA concentrations increased with the severity of CHD. Importantly, our study suggests that high levels of SAA might play a role in CHD by increasing CRP, fibrinogen, IL-6 levels, or attenuating HDL-C levels.

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