RESUMO
Singlet molecular oxygen (1O2) has well-established roles in photosynthetic plants, bacteria and fungi1-3, but not in mammals. Chemically generated 1O2 oxidizes the amino acid tryptophan to precursors of a key metabolite called N-formylkynurenine4, whereas enzymatic oxidation of tryptophan to N-formylkynurenine is catalysed by a family of dioxygenases, including indoleamine 2,3-dioxygenase 15. Under inflammatory conditions, this haem-containing enzyme is expressed in arterial endothelial cells, where it contributes to the regulation of blood pressure6. However, whether indoleamine 2,3-dioxygenase 1 forms 1O2 and whether this contributes to blood pressure control have remained unknown. Here we show that arterial indoleamine 2,3-dioxygenase 1 regulates blood pressure via formation of 1O2. We observed that in the presence of hydrogen peroxide, the enzyme generates 1O2 and that this is associated with the stereoselective oxidation of L-tryptophan to a tricyclic hydroperoxide via a previously unrecognized oxidative activation of the dioxygenase activity. The tryptophan-derived hydroperoxide acts in vivo as a signalling molecule, inducing arterial relaxation and decreasing blood pressure; this activity is dependent on Cys42 of protein kinase G1α. Our findings demonstrate a pathophysiological role for 1O2 in mammals through formation of an amino acid-derived hydroperoxide that regulates vascular tone and blood pressure under inflammatory conditions.
Assuntos
Pressão Sanguínea/fisiologia , Inflamação/sangue , Inflamação/fisiopatologia , Oxigênio Singlete/metabolismo , Vasodilatadores/metabolismo , Animais , Linhagem Celular , Proteína Quinase Dependente de GMP Cíclico Tipo I/antagonistas & inibidores , Proteína Quinase Dependente de GMP Cíclico Tipo I/química , Proteína Quinase Dependente de GMP Cíclico Tipo I/metabolismo , Cisteína/metabolismo , Ativação Enzimática/efeitos dos fármacos , Feminino , Humanos , Peróxido de Hidrogênio/química , Peróxido de Hidrogênio/metabolismo , Peróxido de Hidrogênio/farmacologia , Indolamina-Pirrol 2,3,-Dioxigenase/química , Indolamina-Pirrol 2,3,-Dioxigenase/metabolismo , Inflamação/enzimologia , Masculino , Oxirredução/efeitos dos fármacos , Ratos , Transdução de Sinais , Oxigênio Singlete/química , Triptofano/química , Triptofano/metabolismoRESUMO
Cardiovascular diseases (CVDs) constitute a spectrum of disorders affecting the heart and blood vessels, which include coronary heart disease, cerebrovascular disease, and peripheral artery disease [...].
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Doenças Cardiovasculares , Transtornos Cerebrovasculares , Doença das Coronárias , Humanos , Coração/inervação , Sistema Nervoso SimpáticoRESUMO
Cardiovascular disease (CVD) encompasses a range of disorders affecting the heart and blood vessels, including coronary heart disease and cerebrovascular disease [...].
Assuntos
Doenças Cardiovasculares , Transtornos Cerebrovasculares , Doença das Coronárias , Diabetes Mellitus , Hipertensão , Humanos , Fatores de RiscoRESUMO
Thoracic aortic aneurysm (TAA) has a prevalence of 0.16-0.34% and an incidence of 7.6 per 100,000 person-years, accounting for 1-2% of all deaths in Western countries. Currently, no effective pharmacological therapies have been identified to slow TAA development and prevent TAA rupture. Large TAAs are treated with open surgical repair and less invasive thoracic endovascular aortic repair, both of which have high perioperative mortality risk. Therefore, there is an urgent medical need to identify the cellular and molecular mechanisms underlying TAA development and rupture to develop new therapies. In this review, we summarize animal TAA models including recent developments in porcine and zebrafish models: porcine models can assess new therapeutic devices or intervention strategies in a large mammal and zebrafish models can employ large-scale small-molecule suppressor screening in microwells. The second part of the review covers current views of TAA pathogenesis, derived from recent studies using these animal models, with a focus on the roles of the transforming growth factor-beta (TGFß) pathway and the vascular smooth muscle cell (VSMC)-elastin-contractile unit. The last part discusses TAA treatment options as they emerge from recent preclinical studies.
Assuntos
Aneurisma da Aorta Torácica , Ruptura Aórtica , Humanos , Animais , Suínos , Peixe-Zebra , Aneurisma da Aorta Torácica/etiologia , Aneurisma da Aorta Torácica/terapia , Modelos Animais , Contração Muscular , MamíferosRESUMO
Traditional methodologies for assessing chemical toxicity are expensive and time-consuming. Computational modeling approaches have emerged as low-cost alternatives, especially those used to develop quantitative structure-activity relationship (QSAR) models. However, conventional QSAR models have limited training data, leading to low predictivity for new compounds. We developed a data-driven modeling approach for constructing carcinogenicity-related models and used these models to identify potential new human carcinogens. To this goal, we used a probe carcinogen dataset from the US Environmental Protection Agency's Integrated Risk Information System (IRIS) to identify relevant PubChem bioassays. Responses of 25 PubChem assays were significantly relevant to carcinogenicity. Eight assays inferred carcinogenicity predictivity and were selected for QSAR model training. Using 5 machine learning algorithms and 3 types of chemical fingerprints, 15 QSAR models were developed for each PubChem assay dataset. These models showed acceptable predictivity during 5-fold cross-validation (average CCR = 0.71). Using our QSAR models, we can correctly predict and rank 342 IRIS compounds' carcinogenic potentials (PPV = 0.72). The models predicted potential new carcinogens, which were validated by a literature search. This study portends an automated technique that can be applied to prioritize potential toxicants using validated QSAR models based on extensive training sets from public data resources.
Assuntos
Algoritmos , Relação Quantitativa Estrutura-Atividade , Humanos , Simulação por Computador , Carcinógenos/toxicidade , BioensaioRESUMO
BACKGROUND: Artial fibrosis has been recognized as a typical pathological change in atrial fibrillation. Although present evidence suggests that microRNA-499-5p (miR-499-5p) plays an important role in the development of atrial fibrosis, the specific mechanism is not fully understood. Therefore, this study attempted to assess the influence of miR-499-5p on atrial fibroblasts and explore the potential molecular mechanism. METHODS: Atrial fibroblasts from sprague dawley rat were respectively transfected with miR-499-5p mimic, miR-499-5p negative control and miR-499-5p inhibitor, atrial fibroblasts without any treatment were also established. Cell counting kit-8 assay and transwell assay were used to detect the proliferation and migration of atrial fibroblasts in each group. Expressions of miR-499-5p, TGF-ß1, smad2, α-SMA, collagen-I and TGFß-R1 in mRNA and protein level were subsequently detected via quantitative real-time polymerase chain reaction and western blot. Furthermore, the prediction of the binding sites of miR-499-5p and TGFß-R1 was performed via the bioinformatics online software TargetScan and verified by dual luciferase reporter. RESULTS: By utilizing miR-499-5p-transfected atrial fibroblasts model, expression of miR-499-5p in the miR-499-5p mimic group was upregulated, while it was downregulated in the miR-499-5p inhibitors group. Upregulated miR-499-5p expression led to to a significant decrease in the proliferative and migratory ability of cultured atrial fibroblasts, while downregulated miR-499-5p expression led to a significant increase in the proliferative and migratory ability of cultured atrial fibroblasts. Additionally, upregulated miR-499-5p expression made a significant rise in TGF-ß1-induced mRNA and protein expression of TGF-ß1, TGFß-R1, smad2, α-SMA and collagen-I in atrial fibroblasts. Furthermore, results from the dual luciferase reporter conformed that miR-499-5p may repress TGFß-R1 by binding the 3'UTR of TGFß-R1 directly. CONCLUSIONS: miR-499-5p is able to inhibit the activation of transforming growth factor ß-induced Smad2 signaling and eventually suppressed the proliferation, migration and invasion of atrial fibroblasts and collagen synthesis by targeting TGFß-R1.
Assuntos
Fibrilação Atrial , MicroRNAs , Receptores de Fatores de Crescimento Transformadores beta , Animais , Ratos , Fibrilação Atrial/genética , Fibrilação Atrial/patologia , Proliferação de Células/genética , Colágeno Tipo I/metabolismo , Fibroblastos/metabolismo , Fibrose , Luciferases/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Ratos Sprague-Dawley , RNA Mensageiro/genética , Transdução de Sinais/genética , Fator de Crescimento Transformador beta/metabolismo , Fator de Crescimento Transformador beta1/metabolismo , Proteína Smad2/metabolismo , Receptores de Fatores de Crescimento Transformadores beta/genética , Receptores de Fatores de Crescimento Transformadores beta/metabolismoRESUMO
Coconut cadang-cadang viroid (CCCVd) is an infectious single-stranded RNA (ssRNA) pathogen, which leads directly to the death of a large number of coconut palm trees and heavy economic loss to coconut farmers. Herein, a novel electrochemical impedance RNA genosensor is presented based on highly stable gold nanoparticles (AuNPs) decorated phosphorene (BP) nanohybrid with graphene (Gr) for highly sensitive, low-cost, and label-free detection of CCCVd. BP-AuNPs are environmentally friendly prepared by ultrasonic-assisted liquid-phase exfoliation of black phosphorus, accompanying direct reduction of chloroauric acid. Gr/BP-AuNPs are facilely prepared by the in situ growth of AuNPs onto the BP surface and its nanohybrid with Gr to improve environmental stability of BP. Gr/BP-AuNP-based RNA genosensor is fabricated by immobilizing the thiol-functionalized single-stranded DNA (ssDNA) oligonucleotide probe onto the surface of Gr/BP-AuNP-modified glassy carbon electrode via gold-thiol interactions, which served as an electrochemical genosensing platform for the label-free impedance detection of CCCVd by hybridization between the functionalized ssDNA probe and the complementary CCCVd ssRNA sequence in a wide linear range from 1.0 × 10-11 to 1.0 × 10-7 M with a low limit of detection of 2.8 × 10-12 M. This work supplies an experimental support and theoretical direction for the fabrication of RNA biosensors based on graphene-like materials and potential application for a specific diagnosis of plant RNA viral disease in Arecaceae planting industry.
Assuntos
Grafite , Nanopartículas Metálicas , Ouro , DNA de Cadeia Simples , Compostos de SulfidrilaRESUMO
This study aimed to investigate the effect of the sympatholytic drug moxonidine on atherosclerosis. The effects of moxonidine on oxidised low-density lipoprotein (LDL) uptake, inflammatory gene expression and cellular migration were investigated in vitro in cultured vascular smooth muscle cells (VSMCs). The effect of moxonidine on atherosclerosis was measured by examining aortic arch Sudan IV staining and quantifying the intima-to-media ratio of the left common carotid artery in apolipoprotein E-deficient (ApoE-/-) mice infused with angiotensin II. The levels of circulating lipid hydroperoxides in mouse plasma were measured by ferrous oxidation-xylenol orange assay. Moxonidine administration increased oxidised LDL uptake by VSMCs via activation of α2 adrenoceptors. Moxonidine increased the expression of LDL receptors and the lipid efflux transporter ABCG1. Moxonidine inhibited mRNA expression of inflammatory genes and increased VSMC migration. Moxonidine administration to ApoE-/- mice (18 mg/kg/day) decreased atherosclerosis formation in the aortic arch and left common carotid artery, associated with increased plasma lipid hydroperoxide levels. In conclusion, moxonidine inhibited atherosclerosis in ApoE-/- mice, which was accompanied by an increase in oxidised LDL uptake by VSMCs, VSMC migration, ABCG1 expression in VSMCs and lipid hydroperoxide levels in the plasma.
Assuntos
Aterosclerose , Imidazóis , Lipoproteínas LDL , Músculo Liso Vascular , Animais , Camundongos , Apolipoproteínas E/metabolismo , Aterosclerose/metabolismo , Proliferação de Células , Células Cultivadas , Peróxidos Lipídicos/metabolismo , Lipoproteínas LDL/metabolismo , Camundongos Endogâmicos C57BL , Músculo Liso Vascular/efeitos dos fármacos , Músculo Liso Vascular/metabolismo , Miócitos de Músculo Liso/metabolismo , Imidazóis/farmacologiaRESUMO
Atherosclerosis is characterized by the narrowing of the arterial lumen due to subendothelial lipid accumulation, with hypercholesterolemia being a major risk factor. Despite the recent advances in effective lipid-lowering therapies, atherosclerosis remains the leading cause of mortality globally, highlighting the need for additional therapeutic strategies. Accumulating evidence suggests that the sympathetic nervous system plays an important role in atherosclerosis. In this article, we reviewed the sympathetic innervation in the vasculature, norepinephrine synthesis and metabolism, sympathetic activity measurement, and common signaling pathways of sympathetic activation. The focus of this paper was to review the effectiveness of pharmacological antagonists or agonists of adrenoceptors (α1, α2, ß1, ß2, and ß3) and renal denervation on atherosclerosis. All five types of adrenoceptors are present in arterial blood vessels. α1 blockers inhibit atherosclerosis but increase the risk of heart failure while α2 agonism may protect against atherosclerosis and newer generations of ß blockers and ß3 agonists are promising therapies against atherosclerosis; however, new randomized controlled trials are warranted to investigate the effectiveness of these therapies in atherosclerosis inhibition and cardiovascular risk reduction in the future. The role of renal denervation in atherosclerosis inhibition in humans is yet to be established.
Assuntos
Aterosclerose , Insuficiência Cardíaca , Hipercolesterolemia , Humanos , Sistema Nervoso Simpático , Receptores Adrenérgicos , LipídeosRESUMO
The rupture of an abdominal aortic aneurysm (AAA) causes about 200,000 deaths worldwide each year. However, there are currently no effective drug therapies to prevent AAA formation or, when present, to decrease progression and rupture, highlighting an urgent need for more research in this field. Increased vascular inflammation and enhanced apoptosis of vascular smooth muscle cells (VSMCs) are implicated in AAA formation. Here, we investigated whether hydralazine, which has anti-inflammatory and anti-apoptotic properties, inhibited AAA formation and pathological hallmarks. In cultured VSMCs, hydralazine (100 µM) inhibited the increase in inflammatory gene expression and apoptosis induced by acrolein and hydrogen peroxide, two oxidants that may play a role in AAA pathogenesis. The anti-apoptotic effect of hydralazine was associated with a decrease in caspase 8 gene expression. In a mouse model of AAA induced by subcutaneous angiotensin II infusion (1 µg/kg body weight/min) for 28 days in apolipoprotein E-deficient mice, hydralazine treatment (24 mg/kg/day) significantly decreased AAA incidence from 80% to 20% and suprarenal aortic diameter by 32% from 2.26 mm to 1.53 mm. Hydralazine treatment also significantly increased the survival rate from 60% to 100%. In conclusion, hydralazine inhibited AAA formation and rupture in a mouse model, which was associated with its anti-inflammatory and anti-apoptotic properties.
Assuntos
Angiotensina II , Aneurisma da Aorta Abdominal , Animais , Camundongos , Angiotensina II/farmacologia , Anti-Inflamatórios/farmacologia , Aorta Abdominal/metabolismo , Aneurisma da Aorta Abdominal/induzido quimicamente , Aneurisma da Aorta Abdominal/tratamento farmacológico , Aneurisma da Aorta Abdominal/metabolismo , Apolipoproteínas/farmacologia , Apolipoproteínas E , Apoptose , Modelos Animais de Doenças , Camundongos Endogâmicos C57BL , Camundongos KnockoutRESUMO
BACKGROUND: The 4S-AF scheme and the ABC pathway for integrated care have been proposed to better characterize and treat patients with atrial fibrillation (AF). We aimed to evaluate the assessment of the 4S-AF scheme and ABC pathway in Chinese AF patients. METHODS: The ChiOTEAF is a prospective, observational, multicentre registry. Consecutive AF patients from 44 centres across 20 Chinese provinces with available 1-year follow-up data were included. RESULTS: A total of 6419 patients were included, median age 76 years (interquartile range 67-83; 39.1% female). Of these, 3503 (59.8%) patients were not characterized using the 4S-AF scheme and not management according to the ABC pathway (group 1); 1795 (28.0%) were characterized according to the 4S-AF scheme but ABC pathway non-adherent or vice versa (group 2); and 1121 (17.4%) characterized according to the 4S-AF scheme and were ABC pathway adherent (group 3). As compared with group 1, group 2 and group 3 were independently associated with lower odds of the composite endpoint of all-cause death/any thromboembolic event, with the greatest benefit observed in group 3 (OR: 0.19; 95% CI 0.12-0.31) [for group 2: OR: 0.28; 95% CI 0.20-0.37]. Similar results were observed for all-cause death (group 2: OR: 0.18; 95% CI 0.12-0.27; group 3: OR: 0.14; 95% CI 0.07-0.25). CONCLUSIONS: In a contemporary real-word cohort of Chinese AF patients, it is feasible to characterize and manage AF patients using the novel 4S-AF scheme and ABC pathway for integrated care. The use of both these tools is associated with improved clinical outcomes.
Assuntos
Fibrilação Atrial , Acidente Vascular Cerebral , Tromboembolia , Idoso , Anticoagulantes/uso terapêutico , Fibrilação Atrial/complicações , Feminino , Humanos , Masculino , Estudos Prospectivos , Sistema de Registros , Fatores de Risco , Acidente Vascular Cerebral/etiologiaRESUMO
AIMS: Prior studies have reported conflicting results on digoxin's impact on clinical outcomes and quality of life, and there are limited data from Asia. The aim of this study is to evaluate the use of digoxin and its impact on clinical outcomes and quality of life in a high-risk cohort of elderly Chinese atrial fibrillation (AF) patients. METHODS AND RESULTS: The Optimal Thromboprophylaxis in Elderly Chinese Patients with Atrial Fibrillation (ChiOTEAF) registry is a prospective, multicentre nationwide study conducted from October 2014 to December 2018. Endpoints of interest were the composite outcome of all-cause death/any thromboembolism (TE), all-cause death, cardiovascular death, sudden cardiac death, and TE events, as well as the quality of life. The eligible cohort for this analysis included 6391 individuals, of whom 751 (11.8%) patients were treated with digoxin. On multivariate analysis, the use of digoxin was associated with a higher odds ratio (OR) of composite outcome [OR: 1.71; 95% confidence interval (CI): 1.32-2.22], all-cause death (OR: 1.62; 95% CI: 1.23-2.14), and any TE (OR: 1.78; 95% CI: 1.08-2.95). Results were consistent in a subgroup of patients with diagnosed heart failure (HF) and patients with permanent AF. The use of digoxin was associated with worse health-related quality of life (mean EQ index: 0.76 ± 0.19 vs. 0.84 ± 0.18; P < 0.001). CONCLUSIONS: In this nationwide cohort study, digoxin use was associated with an overall higher risk of the composite outcome of all-cause death/any TE, all-cause death, and any TE, regardless of HF diagnosis. Patients treated with digoxin had a worse health-related quality of life.
Assuntos
Fibrilação Atrial , Insuficiência Cardíaca , Tromboembolia Venosa , Idoso , Antiarrítmicos/efeitos adversos , Anticoagulantes/uso terapêutico , Fibrilação Atrial/complicações , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/tratamento farmacológico , China/epidemiologia , Estudos de Coortes , Digoxina/efeitos adversos , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/epidemiologia , Insuficiência Cardíaca/prevenção & controle , Humanos , Estudos Prospectivos , Qualidade de Vida , Sistema de RegistrosRESUMO
Shigella sonnei is a species of Shigella, and the infection rate of S. sonnei is increasing year by year. Eugenol is an active ingredient in clove essential oil and is a generally recognized as safe (GRAS)-certified food ingredient. The mechanism of inhibition of S. sonnei by eugenol has been investigated in this study. The minimum inhibitory concentration of eugenol against both S. sonnei ATCC 25931 and S. sonnei CMCC 51592 was 0.5 mg/mL and minimum bactericidal concentration (MBC) for both strains was 0.8 mg/mL. The inhibition effect of eugenol against S. sonnei was due to increased levels of reactive oxygen species in cells, changed cell membrane permeability, and induced cell membrane dysfunction, for instance, cell membrane hyperpolarization and intracellular ATP concentration drops. The results of confocal laser scanning microscope and field emission scanning electron microscopy showed that eugenol leads to decreased cell membrane integrity, resulting in changed cell morphology. Moreover, eugenol inactivated S. sonnei in Luria-Bertani (LB) broth and lettuce juice. These results indicated that eugenol could inactivate S. sonnei and has the potential to control S. sonnei in the food industry.
Assuntos
Disenteria Bacilar , Shigella sonnei , Eugenol/farmacologia , Lactuca/microbiologia , Testes de Sensibilidade Microbiana , Antibacterianos/farmacologiaRESUMO
Shigella flexneri, a common Gram-negative foodborne pathogen, is widely distributed in fresh-cut fruits and vegetables, unpasteurized milk, and food processing environments. The aims of this study were to evaluate the antibacterial effects of 405-nm light-emitting diode (LED) treatment on S. flexneri and to investigate the possible mechanism. The results showed that LED irradiation (360 min) reduced the number of S. flexneri in phosphate-buffered saline by 3.29 log colony-forming unit (CFU)/mL (initial bacterial count: 6.81 log CFU/mL). The cells in reconstituted infant formula, cells on fresh-cut carrot slices, and biofilm-associated cells on stainless steel surfaces were reduced by 1.83 log CFU/mL, 7.00 log CFU/cm2, and 4.35 log CFU/cm2 following LED treatment for 360, 120, and 120 min, respectively. LED treatment damaged both DNA and cell wall of S. flexneri and changed cell morphology and cell membrane permeability. In addition, LED treatment decreased total cell protein concentration of S. flexneri. These results indicated that 405-nm LED treatment effectively controlled S. flexneri contamination of foods and food contact surfaces and that the bacterial inactivation may be the result of damage to multiple cellular components. These findings highlight the potential of LED technology in controlling S. flexneri during food processing, storage, and preparation.
Assuntos
Microbiologia de Alimentos , Shigella flexneri , Contagem de Colônia Microbiana , Manipulação de Alimentos , Humanos , Aço InoxidávelRESUMO
BACKGROUND: It is unknown whether higher triglyceride results in higher mortality from diabetes, i.e., diabetes mortality. This study aimed to investigate the association of fasting triglyceride with diabetes mortality. METHODS: This study included 26,582 US adults from the National Health and Nutrition Examination Surveys from 1988 to 2014. Diabetes mortality outcomes were ascertained by linkage to the National Death Index records. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) of triglyceride for diabetes mortality. RESULTS: Higher levels of fasting triglyceride were associated with higher levels of glucose, glycated hemoglobin, insulin, and homeostatic model assessment for insulin resistance at baseline. A 1-natural-log-unit increase in triglyceride (e.g., from 70 to 190 mg/dL) was associated with a 115% higher multivariate-adjusted risk of diabetes diagnosis (odds ratio, 2.15; 95% CI, 2.00-2.33). During 319,758 person-years of follow-up with a mean follow-up of 12.0 years, 582 diabetes deaths were documented. Compared with people with triglyceride in the lowest quintile, people with triglyceride in the highest quintile had an 85% higher risk of diabetes mortality (HR, 1.85; 95% CI, 1.25-2.73). A 1-natural-log-unit increase in triglyceride was associated with a 40% higher multivariate-adjusted risk of diabetes mortality. The positive association between triglyceride and diabetes mortality was also presented in sub-cohorts of participants with or without diabetes. CONCLUSIONS: This study demonstrated that higher fasting triglyceride was associated with a higher diabetes mortality risk.
Assuntos
Diabetes Mellitus/mortalidade , Hipertrigliceridemia/mortalidade , Triglicerídeos/sangue , Glicemia/análise , Diabetes Mellitus/sangue , Hemoglobinas Glicadas/análise , Humanos , Hipertrigliceridemia/sangue , Insulina/sangue , Masculino , Pessoa de Meia-Idade , Inquéritos Nutricionais , Fatores de Risco , Estados Unidos/epidemiologiaRESUMO
Coenzyme Q0 (CoQ0) is a natural compound found in Antrodia cinnamomea, which has a variety of biological activities. Here, the antibacterial activity and possible antibacterial mechanism of CoQ0 against Escherichia coli were investigated. The antibacterial effect was evaluated by determining minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values, and by assessing bacterial survival and the effect on the growth of E. coli after CoQ0 treatment in Luria-Bertani (LB) broth. To reveal the antibacterial mechanism of CoQ0, changes in intracellular adenosine triphosphate (ATP) concentration, membrane potential, and bacterial protein content, as well as effects on cell morphology and membrane integrity, were investigated. Both the MICs and MBCs of CoQ0 against E. coli were 0.1 mg/mL. After treatment of E. coli (6.5 log colony-forming units/mL) with 0.1 mg/mL of CoQ0 in LB broth for 3 h, the number of viable cells dropped below the detection limit. In addition, CoQ0 treatment resulted in the reduction in intracellular ATP concentration, cell membrane hyperpolarization, decreased bacterial protein concentrations, and damage to cell membrane integrity and cellular morphology. These results indicated that CoQ0 has effective antibacterial activity against E. coli, suggesting potential applications in food industry safety.
Assuntos
Antibacterianos/farmacologia , Benzoquinonas/farmacologia , Escherichia coli/efeitos dos fármacos , Trifosfato de Adenosina/metabolismo , Membrana Celular/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Polyporales/químicaRESUMO
OBJECTIVE: Circumferential pulmonary vein isolation (CPVI) is a common procedure that is performed on patients with atrial fibrillation (AF). However, AF may recur in some patients after treatment. This study assesses the association between autonomic modulation and late recurrence after CPVI and between autonomic modulation and ablation lesion quality. METHODS: We prospectively enrolled 72 patients with paroxysmal AF who underwent CPVI from January 2017 to January 2018. Pre- and post-ablation 24 h electrocardiograms were performed to document heart rate variability (HRV), which represents cardiac autonomic function. The intraablation force-time integral (FTI) was used to indicate the extent of ablation injury. Patients were followed up for 12 months after the procedure and cases of AF recurrence were recorded. RESULTS: Changes in HRV decreased after the procedure, which was correlated with FTI (ΔSDNN: r = -0.26, P = 0.03; ΔrMMSD: r = -0.28, P = 0.02; ΔlnHF: r = -0.22, P = 0.04; ΔLnLF: r = -0.29, P = 0.01). Patients without AF recurrence had more pronounced ΔLF (-21.84 ± 33.21% vs. -8.68 ± 34.59%, P = 0.01) and ΔHF (-17.26 ± 16.61% vs. -1.28 ± 9.81%, P = 0.01) than patients with recurrence. Multivariate regression analysis showed that both ΔLF (HR: 1.07, P = 0.04) and ΔHF (HR: 1.11, P = 0.01) were associated with AF recurrence. After adjusting for FTI, ΔLF was no longer associated with AF recurrence (HR: 1.05, P = 0.10). ΔHF remained associated with AF recurrence (HR: 1.08, P = 0.03), but the correlation coefficient was decreased (HR: 1.08, P = 0.03). CONCLUSION: Decreased autonomic nerve function is a valid predictor of AF recurrence and is indicated by the extent of ablation injury, which is independently associated with AF recurrence after CPVI.
Assuntos
Fibrilação Atrial , Ablação por Cateter , Veias Pulmonares , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/cirurgia , Vias Autônomas , Eletrocardiografia , Humanos , Veias Pulmonares/cirurgia , Recidiva , Resultado do TratamentoRESUMO
Sensor differential signals are widely used in many systems. The tracking differentiator (TD) is an effective method to obtain signal differentials. Differential calculation is noise-sensitive. There is the characteristics of low-pass filter (LPF) in the TD to suppress the noise, but phase lag is introduced. For LPF, fixed filtering parameters cannot achieve both noise suppression and phase compensation lag compensation. We propose a fuzzy self-tuning tracking differentiator (FSTD) capable of adaptively adjusting parameters, which uses the frequency information of the signal to achieve a trade-off between the phase lag and noise suppression capabilities. Based on the frequency information, the parameters of TD are self-tuning by a fuzzy method, which makes self-tuning designs more flexible. Simulations and experiments using motion measurement sensors show that the proposed method has good filtering performance for low-frequency signals and improves tracking ability for high-frequency signals compared to fixed-parameter differentiator.
RESUMO
Electrochemical synthesis based on electrons as reagents provides a broad prospect for commodity chemical manufacturing. A direct one-step route for the electrooxidation of amino C-N bonds to nitrile C≡N bonds offers an alternative pathway for nitrile production. However, this route has not been fully explored with respect to either the chemical bond reforming process or the performance optimization. Proposed here is a model of vacancy-rich Ni(OH)2 atomic layers for studying the performance relationship with respect to structure. Theoretical calculations show the vacancy-induced local electropositive sites chemisorb the N atom with a lone pair of electrons and then attack the corresponding N(sp3 )-H, thus accelerating amino C-N bond activation for dehydrogenation directly into the C≡N bond. Vacancy-rich nanosheets exhibit up to 96.5 % propionitrile selectivity at a moderate potential of 1.38â V. These findings can lead to a new pathway for facilitating catalytic reactions in the chemicals industry.