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1.
Methods Mol Biol ; 2072: 129-139, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31541443

RESUMO

Upon fertilization, normal endosperm and embryo development require the contribution of both the maternal and paternal genomes. However, certain genes are expressed in a parent-of-origin-dependent manner, an epigenetic phenomenon known as genomic imprinting. Despite the blast of new technologies and the crucial advances of the past decades in the epigenetics field, novel imprinted genes are yet to be discovered and thus key regulators of early seed development. Using rice plant as a model, we describe a method for the identification of imprinted genes based on an RNA-Seq approach, which allows the identification of maternal and paternal gene expression in a parent-of-origin-specific manner.

2.
Food Chem ; 307: 125534, 2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-31644980

RESUMO

There has been increasing recent concern about the agricultural use of organophosphorus pesticides. A rapid and sensitive fluorescence assay for the detection of three organophosphorus pesticides has therefore been developed using 6-carboxy-fluorescein labeling aptamer as the probe and functionalized magnetic nanoparticles as the separation carrier. The aptamer hybridized with complementary DNA conjugated on the surface of the magnetic nanoparticles to form a magnetic aptamer-complementary DNA complex. Upon introducing the target organophosphorus pesticide, the aptamer departed from the complementary DNA, resulting in the fluorescence signal. Under optimized conditions, the limits of detection (LODs, S/N = 3) for trichlorfon, glyphosate, and malathion were 72.20 ng L-1, 88.80 ng L-1, and 195.37 ng L-1, respectively. The method was applied for the detection of trichlorfon, glyphosate, and malathion in spiked lettuce and carrot samples. The recoveries were in the range of 79.4%-118.7%, which were in good agreement with those obtained by gas chromatography, and the relative standard deviations were also acceptable. The method therefore has high sensitivity, so provides a means for the detection of multiple organophosphorus pesticides.

3.
IEEE Trans Vis Comput Graph ; 26(1): 216-226, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31443026

RESUMO

The density map is widely used for data sampling, time-varying detection, ensemble representation, etc. The visualization of dynamic evolution is a challenging task when exploring spatiotemporal data. Many approaches have been provided to explore the variation of data patterns over time, which commonly need multiple parameters and preprocessing works. Image generation is a well-known topic in deep learning, and a variety of generating models have been promoted in recent years. In this paper, we introduce a general pipeline called GenerativeMap to extract dynamics of density maps by generating interpolation information. First, a trained generative model comprises an important part of our approach, which can generate nonlinear and natural results by implementing a few parameters. Second, a visual presentation is proposed to show the density change, which is combined with the level of detail and blue noise sampling for a better visual effect. Third, for dynamic visualization of large-scale density maps, we extend this approach to show the evolution in regions of interest, which costs less to overcome the drawback of the learning-based generative model. We demonstrate our method on different types of cases, and we evaluate and compare the approach from multiple aspects. The results help identify the effectiveness of our approach and confirm its applicability in different scenarios.

4.
Food Microbiol ; 86: 103326, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31703871

RESUMO

This study focused on the microbial communities found in JIUYAO, the fermentation starter traditionally used in Shaoxing-jiu, and elucidated their relationship with the fermentation activities and volatile compounds involved in winemaking. The microbial communities found in all JIUYAO samples tested were dominated by Pediococcus and Weissella bacteria and Saccharomycopsis and Rhizopus fungi. Saccharifying power showed significant positive correlations with the presence of Pedioccoccus, Saccharomycopsis, and Rhizopus, whereas acid production capacity was strongly associated with Pedioccoccus, Weissella, and Rhizopus. Alcohol production capacity positively correlated with the presence of Pedioccoccus and Rhizopus. Fifteen important volatile compounds (odor-activity values ≥ 1) including esters, alcohols, acids, and aldehydes were identified in Huangjiu samples fermented with JIUYAO. Positive correlations were found between Saccharomycopsis and phenylethanol/ethyl butyrate, Rhizopus and ethyl propionate/ethyl laurate/ethyl butyrate, Pedioccoccus and ethyl laurate/acetic acid, and Weissella and decanoic acid/isopentanol. These results imply that these microorganisms significantly contribute to the fermentation activities and flavor of Shaoxing-jiu. Finally, the results showed that a combination of five core microbes with Saccharomyces cerevisiae could be used as a starter in winemaking. To conclude, this study provides a comprehensive overview of the core microbes found in JIUYAO and strategies for the selection of beneficial microorganisms to improve the quality and flavor of Shaoxing-jiu.

5.
Nurse Educ Today ; 84: 104241, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31669965

RESUMO

BACKGROUND: Nursing students often find themselves in a highly competitive environment, and stress is a commonly acknowledged experience in nursing students. OBJECTIVES: The aim of this study was to explore factors, particularly an interest in nursing and in clinical practicum placement, associated with stress in Taiwanese nursing students. DESIGN: Cross-sectional survey study. SETTINGS: A nursing college in central Taiwan and a university in eastern Taiwan. PARTICIPANTS: 814 nursing students. METHODS: Level of stress of the participants was measured using the 43-items Stressors in Nursing Students (SINS) scale, which was translated into a traditional Chinese version (TC-SINS). Simple and multiple linear regression analyses were used to evaluate factors significantly associated with stress. RESULTS: A total of 814 nursing students completed the questionnaire with a return rate of 83.6%. The mean age of the participants was 18.9 years and 94.8% was female. Regarding the students' interest in nursing, 2.6% expressed that they strongly or somewhat disagree. In addition, regarding the students' interest in clinical practicum placement, 7.2% indicated that they strongly or somewhat disagree. Results from multiple regression analysis showed that students who expressed somewhat or strong disagreement to interest in clinical practicum placement were significantly associated with a higher level of stress. Of the various strategies for stress relief, listen to music (75.2%) was the most popular choice, followed by talk to a friend (72.3%), and catch up on sleep (61.3%). A third of the participants used three strategies for stress relief. CONCLUSIONS: Low interest in clinical practicum placement was associated with increased stress levels in nursing students in Taiwan. Future studies should explore the underlying reasons for stress induced by clinical practicum placement, and possible solutions for stress reduction in nursing students.

6.
Ecotoxicol Environ Saf ; 188: 109930, 2020 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-31727496

RESUMO

BACKGROUND: For the sake of children's health, iodized salt supply has been stopped in many areas with excessive iodine in the drinking water, but children's iodine nutrition status and thyroid function after terminating the iodized salt supply is unknown. Objective We assessed the iodine nutrition, thyroid function and influencing factors for thyroid abnormalities in children from areas with different concentrations of water iodine; the supply of iodized salt has been stopped in high water iodine areas. This study aimed to evaluate whether the strategy of stopping the supplies of iodized salt alone is enough to avoid thyroid dysfunction in all areas with excess water iodine while still meeting the iodine nutrition needs of children. METHODS: A cross-sectional study was conducted in children from four areas with different drinking water iodine concentrations in Tianjin, China. The drinking water samplings and spot urine samples were collected to estimate the external and internal iodine exposure levels. The thyroid volume was measured, and blood samples were collected to assess thyroid function. Logistic regression analysis was used to analyze risk factors for thyroid abnormalities. A dietary survey was conducted to determine the sources of iodine nutrition among the areas with different iodine concentrations in the drinking water. RESULTS: In the area with a drinking water iodine concentration ≥300 µg/L, the median urinary iodine concentration (UIC) in children was 476.30 (332.20-639.30) µg/L, which was higher than that in other groups (all P < 0.05), and the prevalence of thyroid nodules and the thyroid goiter rate were higher than those in the <100 µg/L, 100-150 µg/L and 150-300 µg/L areas (all P < 0.01). Binary logistic regression analysis indicated that the risk of thyroid abnormalities was significantly increased in the UIC 200-299 µg/L group (OR: 4.534; 95% CI: 1.565, 13.135; bootstrapped 95% CI: 1.689, 21.206, P = 0.004) and in the UIC ≥ 300 µg/L group (OR: 6.962; 95% CI: 2.490, 19.460; bootstrapped 95% CI: 2.838, 32.570, P = 0.001) compared to the 100-199 µg/L group. The iodine contribution rates from water in areas with water iodine concentrations ≥300 µg/L are up to 63.04%. CONCLUSIONS: After termination of the iodized salt supply, the level of iodine nutrition of children in the area with drinking water iodine concentrations ≥300 µg/L is still excessive. The water source needs to be replaced in this area. In the area with a water iodine concentration of 150-300 µg/L, it is proposed that stopping the supply of iodized salt is sufficient to achieve the proper iodine nutrition status in children.

7.
Biomed Pharmacother ; 121: 109596, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31731193

RESUMO

Vasoactive intestinal peptide (VIP) is a neuropeptide that exerts anti-inflammatory functions. We have reported that VIP mediated by lentivirus attenuates acute lung injury (ALI) in lipopolysaccharide (LPS)-induced murine model. However, the exact role of VIP in uncontrolled inflammation during ALI is largely unknown. Accumulating evidence indicates that the NLRP3 inflammasome has a critical role during ALI. In this study, we investigated the effects of VIP on the activation of NLRP3 inflammasome during the development of ALI in mice. Seven days after the intratracheal injection of VIP-lentivirus, a murine ALI model was induced by intratracheal injection of LPS. VIP-lentivirus significantly reduced the expression of NLRP3 inflammasome components in lung tissue, including NLRP3, pro-caspase-1, pro-IL-1ß, and pro-IL-18. VIP-lentivirus also inhibited the formation of caspase-1 p10 and the maturation of IL-1ß and IL-18. In vitro, exogenous VIP pre-treatment inhibited the priming of NLRP3 inflammasome in murine primary peritoneal macrophages, indicated by down-regulation of expression of NLRP3 inflammasome components. VIP pre-treatment effectively prevented the LPS-induced degradation of I-κB and the synthesis of the downstream of NF-κB, including TNF-α and IL-17A. Furthermore, VIP pre-treatment pronouncedly suppressed the autoproteolysis of caspase-1 and the secretion of IL-1ß and IL-18 induced by LPS plus ATP in macrophages. In addition, VIP inhibited the generation of reactive oxygen species in macrophages by decreasing NOX1 and NOX2 expression. These findings illustrate one mechanism that VIP attenuates ALI induced by LPS through inhibiting the activation of the NLRP3 inflammasome and encourage further studies assessing the therapeutic potential of VIP to ALI.

8.
BMC Cancer ; 19(1): 1166, 2019 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-31791289

RESUMO

BACKGROUND: Lung cancer (LC) is one of the leading causes of death worldwide, which highlights the urgent need for better therapies. Peroxisome proliferator-activated nuclear receptor alpha (PPARα), known as a key nuclear transcription factor involved in glucose and lipid metabolism, has been also implicated in endothelial proliferation and angiogenesis. However, the effects and potential mechanisms of the novel PPARα ligand, AVE8134, on LC growth and progression remain unclear. METHODS: A subcutaneous tumour was established in mice by injecting TC-1 lung tumour cells (~ 1 × 106 cells) into their shaved left flank. These mice were treated with three different PPARα ligands: AVE8134 (0.025% in drinking water), Wyeth-14,643 (0.025%), or Bezafibrate (0.3%). Tumour sizes and metastasis between treated and untreated mice were then compared by morphology and histology, and the metabolites of arachidonic acid (AA) were detected by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Inhibition of either Cyp2c44 expression by genetic disruption or cyclooxygenase (COX) activity by indomethacin was used to test the mechanisms by which AVE8134 affects tumour growth. RESULTS: The pharmacodynamics effects of AVE8134, Wyeth-14,643, and Bezafibrate on lipids control were similar. However, their effects on tumour suppression were different. Eicosanoid profile analysis showed that all PPARα ligands reduced the production of AA-derived epoxyeicosatrienoic acids (EETs) and increased the hydroxyl product, 11-hydroxyeicosatetraenoic acids (11-HETE). Moreover, increased 11-HETE promoted endothelial proliferation, angiogenesis, and subsequent tumour deterioration in a dose-dependent manner possibly via activating the AKT/extracellular signal-regulated kinase (ERK) pathway. The increased 11-HETE partly neutralized the benefits provided by the Cyp2c44-EETs system inhibited by PPARα ligands in tumour-bearing mice. AVE8134 treatment worsened the tumour phenotype in Cyp2c44 knockout mice, indicating that AVE8134 has contradictory effects on tumour growth. The COX inhibitor indomethacin strengthened the inhibitory actions of AVE8134 on tumour growth and metastasis by inhibiting the 11-HETE production in vivo and in vitro. CONCLUSION: In this study, we found that the degrees of inhibition on LC growth and metastasis by PPARα ligands depended on their bidirectional regulation on EETs and 11-HETE. Considering their safety and efficacy, the novel PPARα ligand, AVE8134, is a potentially ideal anti-angiogenesis drug for cancer treatment when jointly applied with the COX inhibitor indomethacin.

9.
Sci Total Environ ; : 135410, 2019 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-31791757

RESUMO

The proper disposal of copper (Cu) polluted plant residues after phytoremediation has attracted extensive attention. In this study, the Cu-polluted biogas residue produced through anaerobic digestion was applied directly. Wheat, soybean and pakchoi were grown in pots for four seasons over two years. The application dosage of Cu-polluted biogas residue was evaluated by measuring growth conditions of crops, Cu content in edible parts, and amelioration of saline-alkali soil. The results showed that the biomass of the crops, the content of soil organic matter, total N and available P and microbial diversity can be improved, and the Cu concentration of the edible parts was all lower than limit standard. Amendment with 2% biogas residue enhanced the growth of beneficial bacteria and fungi, and decreased the relative abundances of potentially pathogenic fungi in the saline-alkali soil. The results of this study provide a basis for the safe utilisation of copper-polluted plant residues.

10.
Curr Biol ; 2019 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-31786062

RESUMO

Certain vertebrates such as salamanders and zebrafish are able to regenerate complex tissues (e.g., limbs and fins) with remarkable fidelity. However, how positional information of the missing structure is recalled by appendage stump cells has puzzled researchers for centuries. Here, we report that sizing information for adult zebrafish tailfins is encoded within proliferating blastema cells during a critical period of regeneration. Using a chemical mutagenesis screen, we identified a temperature-sensitive allele of the gene encoding DNA polymerase alpha subunit 2 (pola2) that disrupts fin regeneration in zebrafish. Temperature shift assays revealed a 48-h window of regeneration, during which positional identities could be disrupted in pola2 mutants, leading to regeneration of miniaturized appendages. These fins retained memory of the new size in subsequent rounds of amputation and regeneration. Similar effects were observed upon transient genetic or pharmacological disruption of progenitor cell proliferation after plucking of zebrafish scales or head or tail amputation in amphioxus and annelids. Our results provide evidence that positional information in regenerating tissues is not hardwired but malleable, based on regulatory mechanisms that appear to be evolutionarily conserved across distantly related phyla.

11.
Artigo em Inglês | MEDLINE | ID: mdl-31786831

RESUMO

Recently, neutrophil-to-lymphocyte ratio (NLR) and monocyte-to-lymphocyte ratio (MLR) are frequently used to evaluate disease progression and outcome. Here, we aim to analyze the associations between NLR or MLR and kidney function in undiagnosed hypertensive individuals from general population during routine health checkup. Liver function was analyzed for comparison. From 2011 to 2016, 53 939 examiners have registered for health checkup in Yanbian University Hospital, Yanbian, China. Among 15 219 participants who have complete datasets, 4997 individuals were hypertensive (HTN, SBP/DBP: ≥ 140/90 mm Hg). NLR, glucose, lipids (Chol, TG, LDL), kidney (CREA, BUN), and liver (AST, ALT, GGT, ALB, TBIL) functional parameters were significantly higher in HTN. Pearman correlation analysis showed that NLR was positively correlated with SBP and CREA only in HTN. MLR was associated with CREA in both HTN and non-HTN. NLR or MLR was associated with liver functions similarly in HTN and non-HTN. The authors then divided NLR or MLR into tertiles (NLR: 0-1.7276, 1.7276-3, >3; MLR: 0-0.1845, 0.1845-0.3, >0.3). NLR was positively associated with BUN at NLR >1.7276 and with CREA at all tertiles in HTN. MLR was correlated with CREA and BUN at high MLR in non-HTN. Further analysis showed that age or gender did not affect the associations of NLR and MLR with kidney function in HTN, but strong association was observed in male or aged (>65 years old) non-HTN group. These results showed that NLR could be used as a cost-effective predictor of kidney abnormality in HTN patients even in a general population.

12.
Am J Chin Med ; : 1-17, 2019 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-31786947

RESUMO

Acute liver injury (ALI) induced by acetaminophen (APAP) is the main cause of drug-induced liver injury. Previous reports indicated liver failure could be alleviated by saponins (ginsenosides) from Panax ginseng against APAP-induced inflammatory responses in vivo. However, validation towards ginsenoside Rb1 as a major and marker saponin may protect liver from APAP-induced ALI and its mechanisms are poorly elucidated. In this study, the protective effects and the latent mechanisms of Rb1 action against APAP-induced hepatotoxicity were investigated. Rb1 was administered orally with 10mg/kg and 20mg/kg daily for 1 week before a single injection of APAP (250mg/kg, i.p.) 1h after the last treatment of Rb1. Serum alanine/aspartate aminotransferases (ALT/AST), liver glutathione (GSH) depletion, as well as the inflammatory cytokines, such as tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2), were analyzed to indicate the underlying protective effects of Rb1 against APAP-induced hepatotoxicity with significant inflammatory responses. Histological examination further proved Rb1's protective effects. Importantly, Rb1 mitigated the changes in the phosphorylation of MAPK and PI3K/Akt, as well as its downstream factor NF-κB. In conclusion, experimental data clearly demonstrated that Rb1 exhibited a remarkable liver protective effect against APAP-induced ALI, partly through regulating MAPK and PI3K/Akt signaling pathways-mediated inflammatory responses.

13.
Hypertension ; : HYPERTENSIONAHA11913709, 2019 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-31786982

RESUMO

The A2AR (adenosine 2A receptor) plays a crucial role in the pathophysiological process of cardiovascular diseases, yet its effect on aortic remodeling remains unclear. We observed elevated adenosine and A2AR levels following infusion of mice with Ang II (angiotensin II), suggesting a potential role for the adenosine-A2AR system in macrophage accumulation and subsequent aortic remodeling. The effects and mechanisms of A2AR on macrophage dynamics during aortic remodeling were further investigated using mice with macrophage knockout of A2AR and by transplantation of A2AR-/- bone marrow. We demonstrated that macrophage knockout of A2AR inhibited macrophage accumulation and subsequent aortic remodeling by inhibiting macrophage retention. This was shown to occur via promotion of macrophage emigration to the draining lymph node. These effects correlated with restoration of the expression and surface content of CCR7 (CC chemokine receptor 7). Consistently, A2AR-/- bone marrow transplantation relieved Ang II-induced aortic remodeling, macrophage retention, and CCR7 downregulation and internalization, all of which were rescued by A2AR+/+ bone marrow transplantation. In addition, CCR7 antibody treatment blocked all the protective effects observed in A2AR-cKO mice, including attenuation of aortic remodeling and decreased macrophage retention. In in vitro studies, A2AR activation induced by Ang II suppressed macrophage migration to CCL19 (CC-chemokine ligand) 19 through downregulation and internalization of CCR7. In summary, A2AR activation contributes to Ang II-induced macrophage retention and subsequent aortic remodeling by inhibiting migration of macrophages to the draining lymph node through regulating CCR7 expression and internalization.

15.
J Transl Med ; 17(1): 403, 2019 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-31801571

RESUMO

BACKGROUND: Although there is abundant evidence indicating the connection between triglyceride and type 2 diabetes mellitus (T2DM), few reports or cohort studies confirm that high TG concentration may predict the incidence of T2DM independently. Thus, we studied the association between triglyceride (TG) and T2DM in a male-dominated, middle and older aged cohort, Tianjin General Hospital Cohort. And we further verified our results in the China Health and Retirement Longitudinal Study (CHARLS). METHODS: We conducted an 8-year retrospective cohort study (2009-2017) with 7241 participants who were free from T2DM at baseline. Three groups were constructed based on baseline TG levels (normal, borderline-high, and high). We used a Cox proportional hazards model to evaluate the relationship between TG and T2DM after adjusting for possible risk factors. A Kaplan-Meier survival analysis was performed to compare the incidence of T2DM among subjects in each TG group. We also tested the association between TG and T2DM in the CHARLS cohort. RESULTS: In Tianjin General Hospital Cohort, 7241 participants (male 75.8%, female 24.2%) were included, mean age was 61.49 ± 13.85 years at baseline. The cumulative incidence of T2DM in our cohort study was 8.6% (9.2% in men and 6.6% in women). Compared with the normal TG group, the hazard ratios in the borderline and high group were 1.30 (95% CI 1.04-1.62) and 1.54 (95% CI 1.24-1.90). The Kaplan-Meier survival analysis indicated that higher TG levels may predict higher onset of T2DM. These results were verified in the CHARLS cohort, the hazard ratio with T2DM (95% CI) for logTG was 3.94 (2.64-5.87). CONCLUSIONS: Our findings suggest that the TG level may be an independent risk factor and predictor for T2DM.

16.
J Am Chem Soc ; 2019 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-31804069

RESUMO

Designing atomically dispersed metal catalysts for oxygen reduction reaction (ORR) is a promising approach to achieve efficient energy conversion. Herein, we develop a template-assisted method to synthesize a series of single metal atoms anchored on porous N, S co-doped carbon (NSC) matrix as highly efficient ORR catalysts to investigate the correlation between the structure and their catalytic performance. The structure analysis indicates that identical synthesis method results in distinguished structural differences between Fe-centred single-atom catalyst (Fe-SAs/NSC) and Co-centred/Ni-centred single-atom catalysts (Co-SAs/NSC and Ni-SAs/NSC) because of the different trends of each metal ion in forming a complex with the N, S-containing precursor during the initial synthesis process. The Fe-SAs/NSC mainly consists of well-dispersed FeN4S2 centre site where S atoms form bonds with the N atoms. The S atoms in Co-SAs/NSC and Ni-SAs/NSC, on the other hand, form metal-S bonds, resulting in CoN3S1 and NiN3S1 centre sites. Density functional theory (DFT) reveal that the FeN4S2 centre site is more active than the CoN3S1 and NiN3S1 sites, owing to the higher charge density, lower energy barriers of the intermediates and products involved. The experimental results indicate that all three single-atom catalysts could contribute high ORR electrochemical performances while Fe-SAs/NSC exhibits the highest of all, which is even better than commercial Pt/C. Furthermore, Fe-SAs/NSC also displays high methanol tolerance compared with commercial Pt/C and high stability up to 5000 cycles. This work provides insights into the rational design of the definitive structure of single-atom catalysts with tunable electrocatalytic activities for efficient energy conversion.

17.
Int J Nanomedicine ; 14: 6735-6748, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31686806

RESUMO

Background: Graphene-like material such as functionalized carboxyl-graphene oxide (carboxyl-GO) can be intelligently tuned to achieve particular properties for biological and chemical sensing applications. Methods: In this study, we propose a method to improve interference of non-specific proteins for use in human plasma assays. The highly specific interactions between molecules are an advantage of carboxyl-GO-based surface plasmon resonance (SPR) immunoassays, and this can be applied to spiked plasma samples with pregnancy-associated plasma protein A2 (PAPPA2). Results: The experiment results showed that carboxyl-GO could be used to modulate the plasmon resonance energy, work function and conductivity properties. In addition, carboxyl groups could be used to enhance the conduction of electrons between carboxyl-GO and Au electrodes due to the excellent conductivity and electron transfer rate. The carboxyl-GO-based SPR chip exhibited high sensitivity based on the electric field amplification effects of the composite dielectric material. Therefore, the surface electric field could be enhanced by electron transfer, thereby greatly improving the sensitivity of the sensing system. Enhanced electric field intensity was generated around the carboxyl-GO of 63.58 V/m, and the measured work function was 4.95 eV. The results showed that the carboxyl-GO-based SPR biosensor had high sensitivity, affinity and selective ability for PAPPA2 protein with a high association rate constant (ka) of 3.1 ×109 M-1 S-1 and a limit of detection of 0.01 pg/mL in spiked human plasma. Conclusion: The results showed a detection accuracy of protein in spiked plasma of >90% compared to PBS buffer, suggesting that the carboxyl-GO-based SPR biosensor could be used in assays of human plasma for early and late gynecological diseases. The future of this technology will be useful for the diagnosis and evaluation of the risk of early maternal preeclampsia and potentially in clinical applications for gestational diseases.

18.
Theranostics ; 9(24): 7268-7281, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31695767

RESUMO

Rationale: An imbalance between protein synthesis and degradation is one of the mechanisms of cardiac hypertrophy. Increased transcription in cardiomyocytes can lead to excessive protein synthesis and cardiac hypertrophy. Maf1 is an RNA polymerase III (RNA pol III) inhibitor that plays a pivotal role in regulating transcription. However, whether Maf1 regulates of cardiac hypertrophy remains unclear. Methods: Cardiac hypertrophy was induced in vivo by thoracic aortic banding (AB) surgery. Both the in vivo and in vitro gain- and loss-of-function experiments by Maf1 knockout (KO) mice and adenoviral transfection were used to verify the role of Maf1 in cardiac hypertrophy. RNA pol III and ERK1/2 inhibitor were utilized to identify the effects of RNA pol III and ERK1/2. The possible interaction between Maf1 and ERK1/2 was clarified by immunoprecipitation (IP) analysis. Results: Four weeks after surgery, Maf1 KO mice exhibited significantly exacerbated AB-induced cardiac hypertrophy characterized by increased heart size, cardiomyocyte surface area, and atrial natriuretic peptide (ANP) expression and by exacerbated pulmonary edema. Also, the deficiency of Maf1 causes more severe cardiac dilation and dysfunction than wild type (WT) mice after pressure overload. In contrast, compared with adenoviral-GFP injected mice, mice injected with adenoviral-Maf1 showed significantly ameliorated AB-induced cardiac hypertrophy. In vitro study has demonstrated that Maf1 could significantly block phenylephrine (PE)-induced cardiomyocyte hypertrophy by inhibiting RNA pol III transcription. However, application of an RNA pol III inhibitor markedly improved Maf1 knockdown-promoted cardiac hypertrophy. Moreover, ERK1/2 was identified as a regulator of RNA pol III, and ERK1/2 inhibition by U0126 significantly repressed Maf1 knockdown-promoted cardiac hypertrophy accompanied by suppressed RNA pol III transcription. Additionally, IP analysis demonstrated that Maf1 could directly bind ERK1/2, suggesting Maf1 could interact with ERK1/2 and then inhibit RNA pol III transcription so as to attenuate the development of cardiac hypertrophy. Conclusions: Maf1 ameliorates PE- and AB-induced cardiac hypertrophy by inhibiting RNA pol III transcription via ERK1/2 signaling suppression.

19.
Hypertens Res ; 2019 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-31700166

RESUMO

Atrial fibrillation (AF) is the most common human arrhythmia in clinical practice and may be promoted by atrial inflammation and fibrosis. Ubiquitination is an important posttranslational modification process that is reversed by deubiquitinating enzymes (DUBs). DUBs play critical roles in modulating the degradation, activity, trafficking, and recycling of substrates. However, less research has focused on the role of DUBs in AF. Here, we investigated the effect of ubiquitin C-terminal hydrolase 1 (UCHL1), an important DUB, on the development of AF induced by angiotensin II (Ang II). Male wild-type mice were treated with the UCHL1 inhibitor LDN57444 (LDN) at a dose of 40 µg/kg and infused with Ang II (2000 ng/kg/min) for 3 weeks. Our results showed that Ang II-infused wild-type (WT) mice had higher systolic blood pressure and an increased incidence and duration of AF. Conversely, this effect was attenuated in LDN-treated mice. Moreover, the administration of LDN significantly reduced Ang II-induced left atrial dilation, fibrosis, inflammatory cell infiltration, and reactive oxygen species (ROS) production. Mechanistically, LDN treatment inhibited the activation of multiple signaling pathways (the AKT, ERK1/2, HIF-1α, and TGF-ß/smad2/3 pathways) and the expression of CX43 protein in atrial tissues compared with that in vehicle-treated control mice. Overall, our study identified UCHL1 as a novel regulator that contributes to Ang II-induced AF and suggests that the administration of LDN may represent a potential therapeutic approach for treating hypertensive AF.

20.
Nucleic Acids Res ; 2019 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-31701128

RESUMO

An integrative multi-omics database is needed urgently, because focusing only on analysis of one-dimensional data falls far short of providing an understanding of cancer. Previously, we presented DriverDB, a cancer driver gene database that applies published bioinformatics algorithms to identify driver genes/mutations. The updated DriverDBv3 database (http://ngs.ym.edu.tw/driverdb) is designed to interpret cancer omics' sophisticated information with concise data visualization. To offer diverse insights into molecular dysregulation/dysfunction events, we incorporated computational tools to define CNV and methylation drivers. Further, four new features, CNV, Methylation, Survival, and miRNA, allow users to explore the relations from two perspectives in the 'Cancer' and 'Gene' sections. The 'Survival' panel offers not only significant survival genes, but gene pairs synergistic effects determine. A fresh function, 'Survival Analysis' in 'Customized-analysis,' allows users to investigate the co-occurring events in user-defined gene(s) by mutation status or by expression in a specific patient group. Moreover, we redesigned the web interface and provided interactive figures to interpret cancer omics' sophisticated information, and also constructed a Summary panel in the 'Cancer' and 'Gene' sections to visualize the features on multi-omics levels concisely. DriverDBv3 seeks to improve the study of integrative cancer omics data by identifying driver genes and contributes to cancer biology.

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