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The association between high-density lipoprotein cholesterol (HDL-C) and cardiovascular disease (CVD) is controversial. HDL-C is one content type of high-density lipoprotein (HDL). HDL consists of diverse proteins and lipids and can be classified into different subclasses based on size, shape, charge, and density, and can change dynamically in disease states. Therefore, HDL-C levels alone cannot represent HDLs' cardioprotective role. In this review, we summarized the methods for separating HDL subclasses, the studies on the association between HDL subclasses and cardiovascular risk (CVR), and the impact of lipid-modifying medications and nonpharmacological approaches (exercise training, dietary omega fatty acids, and low-density lipoprotein apheresis) on HDL subclasses. As HDL is a natural nanoplatform, recombinant HDLs (rHDLs) have been used as a delivery system in vivo by loading small interfering RNA, drugs, contrast agents, etc. Therefore, we further reviewed the HDL subclasses used in rHDLs and their advantages and disadvantages. This review would provide recommendations and guidance for future studies on HDL subclasses' cardioprotective roles.
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Doenças Cardiovasculares , Lipoproteínas HDL , Humanos , Doenças Cardiovasculares/prevenção & controle , Lipoproteínas HDL/metabolismo , Lipoproteínas HDL/uso terapêutico , Lipoproteínas HDL/classificação , Animais , HDL-Colesterol/metabolismo , HDL-Colesterol/sangueRESUMO
BACKGROUND: Right heart failure (RHF) is a complication of pulmonary hypertension (PH) and increases the mortality independently of the underlying disease. However, the process of RHF development and progression is not fully understood. We aimed to develop effective approaches for early diagnosis and precise evaluation of RHF. METHODS: Right ventricle (RV) pressure overload was performed via pulmonary artery banding (PAB) surgery in Sprague-Dawley (SD) rats to induce RHF. Echocardiography, right heart catheterization, histological staining, fibroblast activation protein (FAP) immunofluorescence and 18 F-labelled FAP inhibitor-42 ([18 F] -FAPI-42) positron emission tomography/computed tomography (PET/CT) were performed at day 3, week 1, 2, 4 and 8 after PAB. RNA sequencing was performed to explore molecular alterations between PAB and sham group at week 2 and week 4 after PAB respectively. RESULTS: RV hemodynamic disorders were aggravated, and RV function was declined based on right heart catheterization and echocardiography at week 2, 4 and 8 after PAB. Progressive cardiac hypertrophy, fibrosis and capillary rarefaction could be observed in RV from 2 to 8 weeks after PAB. RNA sequencing indicated 80 upregulated genes and 43 downregulated genes in the RV at both week 2 and week 4 after PAB; Gene Ontology (GO) analysis revealed that fibrosis as the most significant biological process in the RV under pressure overload. Immunofluorescence indicated that FAP was upregulated in the RV from week 2 to week 8 after PAB; and [18 F] -FAPI-42 PET/CT revealed FAPI uptake was significantly higher in RV at week 2 and further increased at week 4 and 8 after PAB. CONCLUSION: RV function is progressively declined with fibrosis as the most prominent molecular change after pressure overload, and [18 F] -FAPI-42 PET/CT is as sensitive and accurate as histopathology in RV fibrosis evaluation.
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Insuficiência Cardíaca , Disfunção Ventricular Direita , Ratos , Animais , Ventrículos do Coração/patologia , Ratos Sprague-Dawley , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , FibroseRESUMO
BACKGROUND: The previous study investigated whether the functions of small, medium, and large high density lipoprotein (S/M/L-HDL) are correlated with protein changes in mice. Herein, the proteomic and functional analyses of high density lipoprotein (HDL) subclasses were performed in humans and rats. METHODS: After purifying S/M/L-HDL subclasses from healthy humans (n = 6) and rats (n = 3) using fast protein liquid chromatography (FPLC) with calcium silica hydrate (CSH) resin, the proteomic analysis by mass spectrometry was conducted, as well as the capacities of cholesterol efflux and antioxidation was measured. RESULTS: Of the 120 and 106 HDL proteins identified, 85 and 68 proteins were significantly changed in concentration among the S/M/L-HDL subclasses in humans and rats, respectively. Interestingly, it was found that the relatively abundant proteins in the small HDL (S-HDL) and large HDL (L-HDL) subclasses did not overlap, both in humans and in rats. Next, by searching for the biological functions of the relatively abundant proteins in the HDL subclasses via Gene Ontology, it was displayed that the relatively abundant proteins involved in lipid metabolism and antioxidation were enriched more in the medium HDL (M-HDL) subclass than in the S/L-HDL subclasses in humans, whereas in rats, the relatively abundant proteins associated with lipid metabolism and anti-oxidation were enriched in M/L-HDL and S/M-HDL, respectively. Finally, it was confirmed that M-HDL and L-HDL had the highest cholesterol efflux capacity among the three HDL subclasses in humans and rats, respectively; moreover, M-HDL exhibited higher antioxidative capacity than S-HDL in both humans and rats. CONCLUSIONS: The S-HDL and L-HDL subclasses are likely to have different proteomic components during HDL maturation, and results from the proteomics-based comparison of the HDL subclasses may explain the associated differences in function.
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Antioxidantes , Proteômica , Humanos , Ratos , Camundongos , Animais , Estudo de Prova de Conceito , Lipoproteínas HDL , ColesterolRESUMO
Intrauterine exposure to flutamide not only causes abnormal development of the reproductive organs in male offspring, but also damages ovaries and uteri. The unfolded protein response (UPR) is believed to play an important role in embryo development and teratogenic processes. In the present study, pregnant mice were administered either flutamide (300mg kg-1 day-1, p.o.) on an equivalent volume of soybean oil (control) on Days 12-18 of gestation. Eight weeks after birth, female offspring in the flutamide-treated group had a lower bodyweight and lower ovarian and uterine weights, but there was no significant difference in uterine and ovarian weights normalised by bodyweight between the flutamide-treated and control groups. Furthermore, histopathological changes were observed in all uteri and ovaries in the flutamide-treated group, with fewer and less-developed follicles in the ovaries. In both the uteri and ovaries, flutamide increased the expression of UPR members, although the expression of cell cycle-related genes remained unchanged compared with the control group. Flutamide increased the expression of all autophagy- and apoptosis-related genes evaluated in the uterus, as well as some in the ovary. The results suggest that the in utero exposure of mice to flutamide may contribute to uterine and ovarian damage in the offspring, with endoplasmic reticulum stress possibly triggered by the UPR leading to the induction of excessive autophagy and apoptosis.
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Antagonistas de Androgênios/toxicidade , Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Flutamida/toxicidade , Ovário/efeitos dos fármacos , Resposta a Proteínas não Dobradas/efeitos dos fármacos , Útero/efeitos dos fármacos , Animais , Proteínas Reguladoras de Apoptose/genética , Proteínas Reguladoras de Apoptose/metabolismo , Proteínas Relacionadas à Autofagia/genética , Proteínas Relacionadas à Autofagia/metabolismo , Feminino , Regulação da Expressão Gênica , Idade Gestacional , Exposição Materna , Camundongos Endogâmicos ICR , Ovário/metabolismo , Ovário/patologia , Gravidez , Efeitos Tardios da Exposição Pré-Natal , Útero/metabolismo , Útero/patologiaRESUMO
OBJECTIVE: To study airway pathophysiology and the role of dendritic cells (DCs) and IL-17 receptor (IL-17R) signals in a mouse model for CBD. METHODS: Here, we present a CBD mouse model in which mice were exposed to beryllium during three weeks. We also exposed IL-17R-deficient mice and mice in which DCs were depleted. RESULTS: Eight weeks after the initial beryllium exposure, an inflammatory response was detected in the lungs. Mice displayed inflammation of the lower airways that included focal dense infiltrates, granuloma-like foci, and tertiary lymphoid structure (TLS) containing T cells, B cells, and germinal centers. Alveolar cell analysis showed significantly increased numbers of CD4+ T cells expressing IFNγ, IL-17, or both cytokines. The pathogenic role of IL-17R signals was demonstrated in IL-17R-deficient mice, which had strongly reduced lung inflammation and TLS development following beryllium exposure. In CBD mice, pulmonary DC subsets including CD103+ conventional DCs (cDCs), CD11b+ cDCs, and monocyte-derived DCs (moDCs) were also prominently increased. We used diphtheria toxin receptor-mediated targeted cell ablation to conditionally deplete DCs and found that DCs are essential for the maintenance of TLS in CBD. Furthermore, the presence of antinuclear autoantibodies in the serum of CBD mice showed that CBD had characteristics of autoimmune disease. CONCLUSIONS: We generated a translational model of sarcoidosis driven by beryllium and show that DCs and IL-17R signals play a pathophysiological role in CBD development as well as in established CBD in vivo.
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Beriliose , Estruturas Linfoides Terciárias , Animais , Células Dendríticas , Granuloma , Camundongos , Células Th17RESUMO
OBJECTIVE: To investigate the association of migraine genetic variants with cerebral blood flow (CBF). BACKGROUND: Migraine is a common disorder with many genetic and non-genetic factors affecting its occurrence. The exact pathophysiological mechanisms underlying the disease remain unclear, but are known to involve hemodynamic and vascular disruptions. Recent genome-wide association studies have identified 44 genetic variants in 38 genetic loci that affect the risk of migraine, which provide the opportunity to further disentangle these mechanisms. METHODS: We included 4665 participants of the population-based Rotterdam Study (mean age 65.0 ± 10.9 years, 55.6% women). Cross-sectional area (mm2 ), flow velocity (mm/s), and blood flow (mL/min) were measured in both carotids and the basilar artery using 2-dimensional phase-contrast magnetic resonance imaging. We analyzed 43 previously identified migraine variants separately and calculated a genetic risk score (GRS). To assess the association with CBF, we used linear regression models adjusted for age, sex, and total brain volume. Hierarchical clustering was performed based on the associations with CBF measures and tissue enrichment. RESULTS: The rs67338227 risk allele was associated with higher flow velocity and smaller cross-sectional area in the carotids (Pminimum = 3.7 × 10-8 ). Other variants were related to CBF with opposite directions of effect, but not significantly after multiple testing adjustments (P < 1.4 × 10-4 ). The migraine GRS was not associated with CBF after multiple testing corrections. Migraine risk variants were found to be enriched for flow in the basilar artery (λ = 2.39). CONCLUSIONS: These findings show that genetic migraine risk is complexly associated with alterations in cerebral hemodynamics.
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Circulação Cerebrovascular/genética , Predisposição Genética para Doença/genética , Transtornos de Enxaqueca/genética , Idoso , Artéria Basilar/diagnóstico por imagem , Artéria Basilar/fisiopatologia , Artérias Carótidas/efeitos dos fármacos , Artérias Carótidas/fisiopatologia , Circulação Cerebrovascular/fisiologia , Estudos de Coortes , Feminino , Estudos de Associação Genética , Variação Genética , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Transtornos de Enxaqueca/diagnóstico por imagem , Transtornos de Enxaqueca/fisiopatologia , Países BaixosRESUMO
BACKGROUND: To explore the role of large-artery atherosclerosis in migraine, we investigated the association between migraine and arterial calcification in different intracranial and extracranial vessels. METHODS: 1856 participants were included, mean age (standard deviation) 67.4 (5.8) years, from the population-based Rotterdam Study cohort. Migraine was assessed by validated questionnaire and vascular calcification was assessed by computed tomography (expressed in Agatston score for the coronary arteries and volume in mm3 for the aortic arch, intracranial, and extracranial carotid arteries). Per vessel, the association of migraine with calcification was investigated by linear regression, adjusted for age, sex, cardiovascular risk factors, and calcification in other vessels. RESULTS: Of the participants, 279 (15%) were identified as persons with lifetime migraine. In multivariable adjusted models, migraine was associated with smaller intracranial carotid artery calcification volume (difference in log-transformed calcification volume in persons with migraine compared to persons without migraine: -0.19[-0.29, -0.08]). While subjects with migraine also showed a lower calcification burden in the remaining arterial beds, those associations did not reach statistical significance. CONCLUSIONS: Persons with migraine, compared to those without, had less arterial calcification in the intracranial carotid artery, but not in other arterial beds. Future studies are needed to confirm these findings.
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Transtornos de Enxaqueca/diagnóstico por imagem , Transtornos de Enxaqueca/epidemiologia , Calcificação Vascular/diagnóstico por imagem , Calcificação Vascular/epidemiologia , Idoso , Aorta Torácica/diagnóstico por imagem , Artérias Carótidas/diagnóstico por imagem , Doenças das Artérias Carótidas/sangue , Doenças das Artérias Carótidas/diagnóstico por imagem , Doenças das Artérias Carótidas/epidemiologia , Artérias Cerebrais/diagnóstico por imagem , Estudos de Coortes , Vasos Coronários/diagnóstico por imagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Transtornos de Enxaqueca/sangue , Países Baixos/epidemiologia , Estudos Prospectivos , Fatores de Risco , Calcificação Vascular/sangueRESUMO
Background To explore the role of microvascular pathology in migraine, we investigated the association between migraine and retinal microvascular damage. Methods We included 3270 participants (age ≥ 45 years, 63% women) from the population-based Rotterdam Study (2006-2009). Participants with migraine were identified using a validated questionnaire based on ICHD-II criteria (n = 562). Retinopathy signs were graded on fundus photographs. Retinal arteriolar and venular caliber were measured by semi-automatic assessment of fundus photographs. Associations of migraine with retinopathy and retinal microvascular calibers were examined using logistic and linear regression models, respectively, adjusting for age, sex, and cardiovascular risk factors. Results Migraine was not associated with the presence of retinopathy (odds ratio (OR): 1.09, 95% confidence interval (CI) 0.62; 1.92). In the fully adjusted model, adjusting for the companion vessel, persons with migraine did not differ in retinal arteriolar or venular caliber compared to persons without migraine (mean difference in standardized arteriolar caliber -0.05 (95%CI -0.13; 0.03); in standardized venular caliber -0.00 (95%CI -0.09; 0.08)). Migraine subtypes, including migraine with aura, were also not associated with retinal microvascular damage. Conclusions Our findings suggest that migraine is not associated with retinopathy or difference in retinal microvascular caliber. Further studies are needed to confirm these results.
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Microvasos/patologia , Transtornos de Enxaqueca/patologia , Vasos Retinianos/patologia , Adulto , Idoso , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doenças Retinianas/epidemiologiaRESUMO
OBJECTIVE: To investigate the effects of flutamide on the reproductive organs development and oxidative stress response of male offspring after exposure to pregnant mice, and to provide further evidence for the application of the model and mechanism research. METHODS: Choose 7-week-old ICR mice, female mice were randomly divided into experimental group and control group after pregnancy, thenflutamide was orally administered to pregnant mice with dose 300 mg/( kg·d) during gestation days 12-18, while the control group was treated with equal volume of soybean oil. More than 7 weeks after birth, 40 male mice were randomly chosen to observe the urethral development and test the anogenital distance( AGD), testicular volume and penile length, and then some of these mice's reproductive organs were took for histopathological examination. After grind and centrifuge to obtain the supernatant, twelve penis and testes were randomly selected for examining the level of malondialdehyde( MDA), superoxide dismutase( SOD), and glutathioneperoxidase( GSH-Px) use corresponding kit and microplate reader. The abundance of oxidative stress related genes Noxo1, Sod1 and Gpx1 were detected by qPCR. RESULTS: The incidence of hypospadias in male mice in the treatment group was 100%( 91/91). AGD in the treatment group was( 10. 22 ± 1. 53) mm, which was significantly lower than the control( 17. 46 ± 1. 25) mm( P < 0. 05). The volume of testicles in the treatment group was( 166. 34 ± 26. 59) vs. ( 178. 25 ± 25. 77) mm~3 in the control group( P < 0. 05). The length of the penis in the treatment group was( 7. 46 ± 0. 76) vs. ( 12. 60 ± 0. 80) mm in the control group( P <0. 05). In the testicles, the level of SOD was( 171. 08 ± 57. 24) vs. ( 102. 79 ± 15. 31) U/mg pro, MDA was( 4. 45 ± 1. 67) vs. ( 2. 93 ± 1. 00) nmol/mg pro, GSH-Px was( 41. 55± 12. 15) vs. ( 78. 27 ± 7. 60) U/mg pro( P < 0. 05). The abundance of Noxo1 in the testis from the treatment group was higher than that in the control group, while the expressions of Sod1 and Gpx1 in testis from the treatment group were lower than those in the control group( P < 0. 05). There is no significant difference in SOD, MDA, GSH-Px levels and Sod1, Noxo1, and Gpx1 expressions were found in the penises of both groups. CONCLUSION: Prenatal exposure of flutamide may cause developmental abnormalities such as hypospadias and shortening of the penis in male offspring, and abnormal testicular function of oxidation and anti-oxidation. However, there is no significant effect on penis oxidative/anti-oxidant function.
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Flutamida , Genitália Masculina , Estresse Oxidativo , Testículo , Animais , Feminino , Flutamida/toxicidade , Masculino , Malondialdeído , Camundongos , Camundongos Endogâmicos ICR , Estresse Oxidativo/efeitos dos fármacos , Gravidez , Efeitos Tardios da Exposição Pré-Natal , Distribuição Aleatória , Testículo/efeitos dos fármacos , Testículo/crescimento & desenvolvimentoRESUMO
This study investigated the effects of ultrasound-assisted immersion freezing (UIF) at different power rates (0, 200, 400, and 600 W) on the changes in beef quality and flavor after braising. The results demonstrated that UIF treatment at 400 W significantly reduced the juice loss (cooking loss decreased from 49.04% to 39.74%) and fat oxidation (TBARS value decreased from 0.32 mg/kg to 0.20 mg/kg) of braised beef. In addition, the tenderness (hardness value decreased from 5601.50 g to 2849.46 g) and color stability of braised beef were improved after UIF treatment. The flavor characteristics of braised beef were characterized using an electronic nose and an electronic tongue. The PCA analysis data showed that the cumulative contribution rates of the first and second principal components were 85% and 93.2%, respectively, with the first principal component accounting for a higher proportion. The UIF-400 W group had the highest concentration for the first principal component, and the differentiation was not significant compared to the control group. The total amino acid values of different power UIF treatment groups were improved compared to the AF treatment group, indicating that UIF can effectively reduce the losses caused by freezing. The results demonstrate that ultrasound-assisted freezing treatment is beneficial in enhancing the tenderness and flavor attributes of beef after braising, providing new insights into the processing of meat products with desirable quality characteristics.
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Background: Previous studies have not consistently found significant improvements in left ventricular ejection fraction or global longitudinal strain (GLS) after radiofrequency catheter ablation (RFCA) in patients with ventricular pre-excitation. The aim of this study was thus to explore the effects of RFCA on left ventricular function in patients with ventricular pre-excitation using a new noninvasive echocardiographic method of myocardial work. Methods: A total of 34 patients with ventricular pre-excitation who underwent RFCA and 18 healthy controls were prospectively included in this study. Before and after participants underwent RFCA, electrocardiographic and echocardiographic data of the patients were collected at resting and pacing heart rates (HRs) of 100 beats per minute (bpm) and 120 bpm (controlled by high right atrial pacing during the procedure). Clinical data of the healthy controls at resting HR were also collected. A self-controlled paired sample t test was used to compare the differences before and after participants underwent RFCA. Results: After participants underwent RFCA, the global wasted work (GWW) of the included patients decreased (resting HR: 165.3±68.8 vs. 92.6±42.5 mmHg%, P<0.001; HR of 100 bpm: 276.3±121.2 vs. 187.9±96.0 mmHg%, P<0.001; HR of 120 bpm: 323.9±126.7 vs. 181.0%±74.3 mmHg%. P<0.001), while the global work efficiency (GWE) increased (resting HR: 91.5%±3.8% vs. 94.9%±1.6%; P<0.001; HR of 100 bpm: 87.0%±5.2% vs. 91.0%±3.3%, P<0.001; HR of 120 bpm: 85.0%±5.1% vs. 90.3%±3.7%, P<0.001). Conclusions: In patients with ventricular pre-excitation, impaired GWW and GWE can be improved with RFCA. In clinical practice, noninvasive myocardial work assessment can be used in patients with ventricular pre-excitation.
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The toxicity of insecticides used in the field decreases gradually to sublethal concentrations over time. Therefore, it is necessary to study sublethal effects of pesticides for controlling population explosion. Panonychus citri is a global pest which control is based on insecticides. This study explores the stress responses of spirobudiclofen on the P. citri. Spirobudiclofen significantly inhibited survival and reproduction of P. citri, and the effects aggravated as concentration increased. The transcriptomes and metabolomes of spirobudiclofen-treated and control were compared to characterize spirobudiclofen molecular mechanism. Transcriptomics indicated stress induced by spirobudiclofen stimulated immune defense, antioxidative system, cuticle formation, and lipid metabolism, as deduced from RNA-seq analysis. Meanwhile, our study found that tolerance metabolism in P. citri was regulated by promoting the metabolism of glycerophospholipids, glycine, serine, and threonine. The results of this study can provide a basis for exploring the adaptation strategies of P. citri to spirobudiclofen stress.
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The left atrial appendage (LAA) is a major site of thrombosis in patients with non-valvular atrial fibrillation. The myocardial trabeculae within the LAA have a peculiar tendency to protrude but its relationship to thrombosis remains unknown. This study aimed to investigate the relationship between the condition of trabeculae protrusion and LAA thrombosis. This retrospective study consecutively selected patients diagnosed with non-valvular atrial fibrillation and prepared for radiofrequency ablation from January 2011 to May 2020. Patients were divided into the thrombus group (n = 43), the sludge group (n = 35), and the normal group (n = 407) according to whether the thrombus or sludge was present. The trabeculae protruding angle (TPA), which was measured by the CT scans, was used to quantify the trabeculae protrusion condition. Patients' clinical data, TPA, LAA emptying velocity, and other factors were collected and compared among the three groups. A total of 485 patients were enrolled. The range of TPA was between 0 and 158 degrees, with an average of 89.3 ± 35.6 degrees. The TPA was significantly greater in the thrombus (109.3 ± 14.8 degrees) and sludge groups (110.8 ± 12.8 degrees) than in the normal group (85.3 ± 37.1). The incidence of LAA thrombus and sludge increased with increasing TPA. Multivariate regression analysis showed that the TPA was an independent risk factor for LAA thrombus (OR = 1.046, 95%CI: 1.020-1.073, p < 0.001) and sludge (OR = 1.035, 95%CI: 1.017-1.053, p < 0.001). Further analysis revealed that the TPA was negatively correlated with LAA emptying velocity but its effect on promoting thrombosis was not only mediated by slowing down the flow velocity. The TPA can well reflect the condition of trabeculae protrusion. This study revealed that the TPA was an independent risk factor for LAA thrombus or sludge, providing a potential indicator for future thrombosis risk assessment.
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Apêndice Atrial , Fibrilação Atrial , Cardiopatias , Trombose , Humanos , Fibrilação Atrial/complicações , Fibrilação Atrial/diagnóstico por imagem , Apêndice Atrial/diagnóstico por imagem , Estudos Retrospectivos , Esgotos , Valor Preditivo dos Testes , Trombose/etiologia , Trombose/complicações , Cardiopatias/etiologia , Ecocardiografia TransesofagianaRESUMO
Background: Acute kidney injury (AKI) is a common complication in critically ill patients. Some predictive models have been reported, but the conclusions are controversial. The aim of this study was the formation of nomograms to predict risk factors for AKI in critically ill patients within the first 7 days after admission to the intensive care unit (ICU). Methods: Data were extracted from the Medical Information Mart for Intensive Care- (MIMIC-) III database. The random forest method was used to fill in the missing values, and least absolute shrinkage and selection operator (Lasso) regression analysis was performed to screen for possible risk factors. Results: A total of 561 patients were enrolled. Complication with AKI is significantly associated with a longer length of stay (LOS). For all patients, the predictors contained in the prediction nomogram included hypertension, coronary artery disease (CAD), cardiopulmonary bypass (CPB), coronary artery bypass grafting (CABG), Simplified Acute Physiology Score II (SAPS II), central venous pressure (CVP) measured for the first time after admission, and maximum and minimum mean artery pressure (MAP). The model showed good discrimination (C - index = 0.818, 95% CI: 0.779-0.857). In the subgroup of patients with well-controlled blood glucose levels, the significant predictors included hypertension, CABG, CPB, SAPS II, and maximum and minimum MAP. Good discrimination was also present before (C - index = 0.785, 95% CI: 0.736-0.834) and after adjustment (adjusted C - index = 0.770). Conclusion: Hypertension, CAD, CPB, CABG, SAPS II, CVP measured for the first time after admission, and maximum and minimum MAP were independent risk factors for AKI in critically ill patients.
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Injúria Renal Aguda , Doença da Artéria Coronariana , Hipertensão , Humanos , Estado Terminal , Unidades de Terapia Intensiva , Injúria Renal Aguda/diagnóstico , Injúria Renal Aguda/epidemiologia , Injúria Renal Aguda/etiologia , Doença da Artéria Coronariana/complicações , Fatores de Risco , Hipertensão/complicações , Estudos RetrospectivosRESUMO
Balancing the supply and demand for ride-sourcing companies is a challenging issue, especially with real-time requests and stochastic traffic conditions of large-scale congested road networks. To tackle this challenge, this article proposes a robust and scalable approach that integrates reinforcement learning (RL) and a centralized programming (CP) structure to promote real-time taxi operations. Both real-time order matching decisions and vehicle relocation decisions at the microscopic network scale are integrated within a Markov decision process framework. The RL component learns the decomposed state-value function, which represents the taxi drivers' experience, the off-line historical demand pattern, and the traffic network congestion. The CP component plans nonmyopic decisions for drivers collectively under the prescribed system constraints to explicitly realize cooperation. Furthermore, to circumvent sparse reward and sample imbalance problems over the microscopic road network, this article proposed a temporal-difference learning algorithm with prioritized gradient descent and adaptive exploration techniques. A simulator is built and trained with the Manhattan road network and New York City yellow taxi data to simulate the real-time vehicle dispatching environment. Both centralized and decentralized taxi dispatching policies are examined with the simulator. This case study shows that the proposed approach can further improve taxi drivers' profits while reducing customers' waiting times compared to several existing vehicle dispatching algorithms.
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Amblyseius orientalis Ehara is a predatory mite that belongs to the family Phytoseiidae. It is mainly found in Jiangxi, Shanghai, Guangdong, and other areas of China. Although A. orientalis is a dominant predatory mite species in China and is also important for agriculture and biological control, not many studies have investigated it. Thus, research on A. orientalis is necessary. However, its application in biological control is hindered by the absence of techniques for the mass rearing of A. orientalis in captivity. We conducted experiments to determine the growth, development, reproduction, and functional response of A. orientalis in this study by indoor single-head rearing at 25 ± 1 °C, 65 ± 5% relative humidity, and a photoperiod of a 16 h:8 h light/dark cycle under laboratory conditions. The results of the age stage, two-sex life table showed that the individuals in the pollen + yeast and pollen + yeast + sucrose groups had significantly higher oviposition period, fecundity, net reproductive rate (R0), and gross reproduction rate (GRR) than those in the pollen group. The results of the function response showed that the pollen + yeast + sucrose group was the most favorable for captive breeding of A. orientalis and had the best predatory ability along with rejuvenation and recovery ability. The results of the study provided a theoretical basis for indoor rearing, propagation, and utilization of A. orientalis.
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In flowering plants, pollen development is a critical step for reproductive success and necessarily involves complex genetic regulatory networks. Calcium-dependent protein kinases (CPKs) are plant-specific calcium sensors involved in the regulation of plant development and adaption to the environment; however, whether they play a role in regulating male reproduction remains elusive. Here, we found that the knockdown of spikelet-specific OsCPK21 causes pollen abortion in OsCPK21-RNAi transgenic plants. Severe defects in pollen development initiated at stage 10 of anther development and simultaneous cell death occurred in the pollen cells of OsCPK21-RNAi plants. Microarray analysis and qRT-PCR revealed that the transcription of OsCPK21 is coordinated with that of MIKC*-type MADS box transcription factors OsMADS62, OsMADS63, and OsMADS68 during rice anther development. We further showed that OsCPK21 indirectly up-regulates the transcription of OsMADS62, OsMADS63, and OsMADS68 through the potential MYB binding site, DRE/CRT element, and/or new ERF binding motif localised in the promoter region of these three MADS genes. These findings suggest that OsCPK21 plays an essential role in pollengenesis, possibly via indirectly regulating the transcription of MIKC*-type MADS box proteins.
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Regulação da Expressão Gênica de Plantas , Oryza/genética , Proteínas de Plantas/genética , Proteínas Quinases/genética , Oryza/crescimento & desenvolvimento , Oryza/metabolismo , Proteínas de Plantas/metabolismo , Plantas Geneticamente Modificadas/genética , Plantas Geneticamente Modificadas/crescimento & desenvolvimento , Plantas Geneticamente Modificadas/metabolismo , Pólen/genética , Pólen/crescimento & desenvolvimento , Proteínas Quinases/metabolismo , Interferência de RNARESUMO
OBJECTIVE: To identify a plasma metabolomic biomarker signature for migraine. METHODS: Plasma samples from 8 Dutch cohorts (n = 10,153: 2,800 migraine patients and 7,353 controls) were profiled on a 1H-NMR-based metabolomics platform, to quantify 146 individual metabolites (e.g., lipids, fatty acids, and lipoproteins) and 79 metabolite ratios. Metabolite measures associated with migraine were obtained after single-metabolite logistic regression combined with a random-effects meta-analysis performed in a nonstratified and sex-stratified manner. Next, a global test analysis was performed to identify sets of related metabolites associated with migraine. The Holm procedure was applied to control the family-wise error rate at 5% in single-metabolite and global test analyses. RESULTS: Decreases in the level of apolipoprotein A1 (ß -0.10; 95% confidence interval [CI] -0.16, -0.05; adjusted p = 0.029) and free cholesterol to total lipid ratio present in small high-density lipoprotein subspecies (HDL) (ß -0.10; 95% CI -0.15, -0.05; adjusted p = 0.029) were associated with migraine status. In addition, only in male participants, a decreased level of omega-3 fatty acids (ß -0.24; 95% CI -0.36, -0.12; adjusted p = 0.033) was associated with migraine. Global test analysis further supported that HDL traits (but not other lipoproteins) were associated with migraine status. CONCLUSIONS: Metabolic profiling of plasma yielded alterations in HDL metabolism in migraine patients and decreased omega-3 fatty acids only in male migraineurs.
Assuntos
Lipoproteínas HDL/metabolismo , Transtornos de Enxaqueca/sangue , Adulto , Idoso , Biomarcadores/sangue , Estudos de Coortes , Ácidos Graxos Ômega-3/sangue , Feminino , Humanos , Masculino , Metaboloma , Metabolômica , Pessoa de Meia-Idade , Ressonância Magnética Nuclear Biomolecular , Espectroscopia de Prótons por Ressonância Magnética , Fatores SexuaisRESUMO
BACKGROUND: Limited evidence is available about the association between serum uric acid and sub-stages of the spectrum from normoglycaemia to type 2 diabetes mellitus. We aimed to investigate the association between serum uric acid and risk of prediabetes and type 2 diabetes mellitus. METHODS: Eligible participants of the Rotterdam Study (n = 8,367) were classified into mutually exclusive subgroups of normoglycaemia (n = 7,030) and prediabetes (n = 1,337) at baseline. These subgroups were followed up for incident prediabetes (n = 1,071) and incident type 2 diabetes mellitus (n = 407), respectively. We used Cox proportional hazard models to determine hazard ratios (HRs) for incident prediabetes among individuals with normoglycaemia and incident type 2 diabetes mellitus among individuals with prediabetes. RESULTS: The mean duration of follow-up was 7.5 years for incident prediabetes and 7.2 years for incident type 2 diabetes mellitus. A standard deviation increment in serum uric acid was significantly associated with incident prediabetes among individuals with normoglycaemia (HR 1.10, 95% confidence interval (CI) 1.01; 1.18), but not with incident type 2 diabetes mellitus among individuals with prediabetes (HR 1.07, 95% CI 0.94; 1.21). Exclusion of individuals who used diuretics or individuals with hypertension did not change our results. Serum uric acid was significantly associated with incident prediabetes among normoglycaemic women (HR 1.13, 95% CI 1.02; 1.25) but not among normoglycaemic men (HR 1.08, 95% CI 0.96; 1.21). In contrast, serum uric acid was significantly associated with incident type 2 diabetes mellitus among prediabetic men (HR 1.23, 95% CI 1.01; 1.48) but not among prediabetic women (HR 1.00, 95% CI 0.84; 1.19). CONCLUSIONS: Our findings agree with the notion that serum uric acid is more closely related to early-phase mechanisms in the development of type 2 diabetes mellitus than late-phase mechanisms.
Assuntos
Diabetes Mellitus Tipo 2/diagnóstico , Estado Pré-Diabético/diagnóstico , Ácido Úrico/sangue , Glicemia/análise , Diabetes Mellitus Tipo 2/epidemiologia , Feminino , Seguimentos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Estado Pré-Diabético/epidemiologia , Modelos de Riscos Proporcionais , Fatores de Risco , Fatores SexuaisRESUMO
The association of smoking with preclinical cognitive decline remains unclear and may be modified by the APOEÉ4 genotype. In 5,705 participants (mean age: 63.9±9.1 years; 57.4% women) from the population-based Rotterdam Study, we investigated the relationship between smoking and cognitive decline over a 5.5-year period and examined potential effect modification by APOEÉ4 genotype. We found that current smoking was related to decline in global cognition [difference compared to never smoking: -0.06 (95% C.I.-0.10;-0.01)], as well as decline on specific cognitive tests including the Letter Digit Substitution Task, the 15-Word Learning Test, and the Purdue Pegboard. We found no evidence for effect modification by APOEÉ4 genotype on this relation.