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The bacterial type II toxin-antitoxin (TA) system is a rich genetic element that participates in various physiological processes. Aeromonas veronii is the main bacterial pathogen threatening the freshwater aquaculture industry. However, the distribution of type II TA system in A. veronii was seldom documented and its roles in the life activities of A. veronii were still unexplored. In this study, a novel type II TA system AvtA-AvtT was predicted in a fish pathogen Aeromonas veronii biovar sobria with multi-drug resistance using TADB 2.0. Through an Escherichia coli host killing and rescue assay, we demonstrated that AvtA and AvtT worked as a genuine TA system, and the predicted toxin AvtT actually functioned as an antitoxin while the predicted antitoxin AvtA actually functioned as a toxin. The binding ability of AvtA with AvtT proteins were confirmed by dot blotting analysis and co-immunoprecipitation assay. Furthermore, we found that the toxin and antitoxin labelled with fluorescent proteins were co-localized. In addition, it was found that the transcription of AvtAT bicistronic operon was repressed by the AvtAT protein complex. Deletion of avtA gene and avtT gene had no obvious effect on the drug susceptibility. This study provides first characterization of type II TA system AvtA-AvtT in aquatic pathogen A. veronii.
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Aeromonas veronii , Proteínas Bacterianas , Sistemas Toxina-Antitoxina , Aeromonas veronii/genética , Aeromonas veronii/metabolismo , Sistemas Toxina-Antitoxina/genética , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , Toxinas Bacterianas/metabolismo , Toxinas Bacterianas/genética , Operón , Escherichia coli/genética , Escherichia coli/metabolismo , Escherichia coli/efectos de los fármacos , Antitoxinas/genética , Antitoxinas/metabolismo , Regulación Bacteriana de la Expresión GénicaRESUMEN
Cadmium (Cd) contamination poses a significant global threat to human health, primarily through dietary intake, with rice serving as a major source. While Cd predominantly resides in bound states in soil, the physiological processes by which rice facilitates Cd absorption in the rhizosphere remain largely elusive. This study delves into the mechanisms governing Cd uptake by rice plants in the rhizosphere, emphasizing the impact of daytime and nighttime fluctuations in microenvironmental conditions. Employing a microfluidic chip setup, the research reveals that radial oxygen loss from rice roots triggers dissolution of Cd in the rhizosphere. Notably, Cd mobility exhibits distinct diurnal fluctuations, peaking at 44.0 ± 4.1 nM during the daytime and dropping to 8.3 ± 1.3 nM during the nighttime. Further investigations reveal that variations in dissolved oxygen and hydroxyl radical concentrations influence Cd release, while pH changes and microbial reduction reactions play crucial roles in Cd immobilization. These findings provide insights into the intricate processes governing Cd mobilization in the rice rhizosphere, highlighting the importance of regulating these processes for effective Cd adsorption control in rice crops and safeguarding public health.
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BACKGROUND: Hypertension, sleep disorders, and depression represent notable public health issues, and their interconnected nature has long been acknowledged. The objective of this study is to explore the interplay between sleep disorders and depression in the context of hypertension. METHODS: This cross-sectional study involved 42,143 participants aged 18 and above from the NHANES database across seven survey cycles between 2005 and 2018. After excluding those with missing data on depression, sleep disorders, and hypertension, as well as incomplete main variables, 33,383 participants remained. We used weighted logistic regression to examine the relationship between sleep disorders, depression, and hypertension. Additionally, we assessed the interaction between sleep disorders and depression on hypertension using both multiplicative and additive approaches to quantify their combined effect. RESULTS: Compared to individuals without sleep disorders, those with sleep disorders have an increased risk of hypertension (OR = 1.51, 95% CI: 1.37-1.67). Furthermore, individuals with depression experience a significantly higher risk of hypertension compared to those with sleep disorders alone (OR = 2.34, 95% CI: 1.95-2.80). Our study reveals a positive interaction between sleep disorders and depression in relation to hypertension risk (OR = 1.07, 95% CI: 1.02-1.13). In addition, we observed the quantitative additive interaction indicators (RERI = 0.73, 95% CI: 0.56 ~ 0.92; API = 0.31, 95% CI: 0.11 ~ 0.46; SI = 2.19, 95% CI: 1.08-3.46) influencing hypertension risk. Furthermore, our research also identified that individuals with less than 7 h of sleep, a sleep latency period between 5 and 30 min, or a latency period exceeding 30 min experience a significantly increased risk of hypertension. CONCLUSIONS: Our research uncovered separate links between sleep disorders, depression, and hypertension prevalence. Moreover, we identified an interaction between depression and sleep disorders in hypertension prevalence. Enhancing mental well-being and tackling sleep disorders could help prevent and manage hypertension. Yet, more investigation is required to establish causation and clarify mechanisms.
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Depresión , Hipertensión , Trastornos del Sueño-Vigilia , Humanos , Hipertensión/epidemiología , Estudios Transversales , Masculino , Femenino , Trastornos del Sueño-Vigilia/epidemiología , Trastornos del Sueño-Vigilia/complicaciones , Persona de Mediana Edad , Adulto , Depresión/epidemiología , Depresión/complicaciones , Adulto Joven , Anciano , Comorbilidad , Encuestas Nutricionales , Adolescente , Factores de RiesgoRESUMEN
Vardenafil hydrochloride tablet is an inhibitor of phosphodiesterase type 5, primarily for the treatment of erectile dysfunction. This postprandial study evaluated the pharmacokinetics and bioequivalence of the test and reference formulations of vardenafil hydrochloride tablets in healthy Chinese volunteers. An open, randomized, single-center, single-dose, 2-period, 2-sequence bioequivalence test was conducted on 66 healthy subjects under fed conditions. Subjects were randomly assigned to a 20-mg test or reference formulation with a 7-day washout period. Venous blood samples (4 mL) were collected from each subject 25 times spanning predose (0 hour) to 24 hours after dosing. The plasma concentration of vardenafil was determined by high-performance liquid chromatography-tandem mass spectrometry. Sixty-two volunteers completed the study. Under fed conditions, the maximum plasma concentration was 29.1 ng/mL, the area under the concentration-time curve (AUC) from time 0 to the time of the last measurable concentration was 85.3 ngâ¢h/mL, and AUC from time 0 to infinity was 87.1 ngâ¢h/mL. The 90% confidence intervals of the geometric mean ratio of AUC time 0 to the time of the last measurable concentration and AUC from time 0 to infinity were within the bioequivalence acceptance range of 0.80-1.25. The test formulation was a bioequivalent alternative to the reference formulation when taken under fed conditions in healthy Chinese subjects.
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Área Bajo la Curva , Pueblo Asiatico , Voluntarios Sanos , Inhibidores de Fosfodiesterasa 5 , Equivalencia Terapéutica , Diclorhidrato de Vardenafil , Humanos , Diclorhidrato de Vardenafil/farmacocinética , Diclorhidrato de Vardenafil/administración & dosificación , Masculino , Adulto , Adulto Joven , Inhibidores de Fosfodiesterasa 5/farmacocinética , Inhibidores de Fosfodiesterasa 5/administración & dosificación , Inhibidores de Fosfodiesterasa 5/sangre , Espectrometría de Masas en Tándem , Comprimidos , Cromatografía Líquida de Alta Presión , Estudios Cruzados , China , Periodo Posprandial , Pueblos del Este de AsiaRESUMEN
The effective iodine-131 (I-131) half-life (EHL) plays an important role in the evaluation of radioactive iodine therapy for Graves' disease (GD) patients. It has been observed that the EHL of GD patients varies after taking lithium carbonate. The purpose of this study is to investigate whether EHL can be extended and to identify the predictive factors associated with this outcome. The clinical data of 225 GD patients were retrospectively reviewed. Patients were divided into two groups based on whether the ΔEHL was ≥ 0.5 days. EHL tested after lithium carbonate was defined as Li-EHL. In the univariate analysis, age, sex, thyrotropin receptor antibody (TRAb), thyroglobulin antibody (TgAb), thyroid peroxidase antibody (TPOAb), and baseline-EHL exhibited significant differences between the two groups (P < 0.05). Cutoff values of age and baseline-EHL to predict significant EHL extension were 40.5 years and 4.85 days, respectively, as determined by receiver operating characteristic (ROC) curve analysis. Multiple linear regression analysis further revealed that the regression equation, which included age, sex, baseline-EHL, and the FT3, free triiodothyronine (FT4)/free thyroxine(FT3) ratio, was statistically significant (P < 0.05). Li-EHL positively correlated with baseline-EHL and the FT4/FT3 ratio, but negatively correlated with age. Li-EHL was also increased in female individuals. In conclusion, age, sex, baseline-EHL and the FT4/FT3 ratio were associated with Li-EHL in GD patients.
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Addictive properties of propofol have been demonstrated in both humans and animals. The nucleus accumbens (NAc) shell (NAsh) in the brain, along with the interactions between N-methyl-D-aspartate receptor (NMDAR) and the dopamine D1 receptor (D1R), as well as their downstream ERK/CREB signalling pathway in the NAc, are integral in regulating reward-seeking behaviour. Nevertheless, it remains unclear whether NMDARs and the NMDAR-D1R/ERK/CREB signalling pathway in the NAsh are involved in mediating propofol addiction. To investigate it, we conducted experiments with adult male Sprague-Dawley rats to establish a model of propofol self-administration behaviour. Subsequently, we microinjected D-AP5 (a competitive antagonist of NMDARs, 1.0-4.0 µg/0.3 µL/site) or vehicle into bilateral NAsh in rats that had previously self-administered propofol to examine the impact of NMDARs within the NAsh on propofol self-administration behaviour. Additionally, we examined the protein expressions of NR2A and NR2B subunits, and the D1R/ERK/CREB signalling pathways within the NAc. The results revealed that propofol administration behaviour was enhanced by D-AP5 pretreatment in NAsh, accompanied by elevated expressions of phosphorylation of NR2A (Tyr1246) and NR2B (Tyr1472) subunits. There were statistically significant increases in the expressions of D1Rs, as well as in the phosphorylated ERK1/2 (p-ERK1/2) and CREB (p-CREB). This evidence substantiates a pivotal role of NMDARs in the NAsh, with a particular emphasis on the NR2A and NR2B subunits, in mediating propofol self-administration behaviour. Furthermore, it suggests that this central reward processing mechanism may operate through the NMDAR-D1R/ERK/CREB signal transduction pathway.
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Proteína de Unión a Elemento de Respuesta al AMP Cíclico , Núcleo Accumbens , Propofol , Ratas Sprague-Dawley , Receptores de Dopamina D1 , Receptores de N-Metil-D-Aspartato , Autoadministración , Transducción de Señal , Animales , Núcleo Accumbens/efectos de los fármacos , Núcleo Accumbens/metabolismo , Propofol/farmacología , Receptores de N-Metil-D-Aspartato/metabolismo , Receptores de N-Metil-D-Aspartato/efectos de los fármacos , Masculino , Receptores de Dopamina D1/metabolismo , Receptores de Dopamina D1/efectos de los fármacos , Ratas , Transducción de Señal/efectos de los fármacos , Proteína de Unión a Elemento de Respuesta al AMP Cíclico/metabolismo , Sistema de Señalización de MAP Quinasas/efectos de los fármacosRESUMEN
BACKGROUND: The incidence of male breast cancer has been increasing in recent years; however, the long-term survival outcomes of diagnosed patients remain uncertain. This study was designed to evaluate the conditional survival of male breast cancer patients and to predict the future survival of patients through the conditional nomogram, to provide important suggestions for clinical decision-making. METHODS: Retrospective data from the SEER database included 3600 male breast cancer patients, divided into training and validation groups (7â :â 3 ratio). Overall survival rates were calculated using Kaplan-Meier analysis. Conditional survival analysis described survival at specific years. Time-dependent multivariate Cox analysis identified prognostic factors' impact. The conditional survival nomogram model predicted real-time survival rates. RESULTS: Over time, the 5-year real-time survival rate of patients gradually improved, increasing from 70.5 to 74.8, 79.4, 85.8, and 92.9% (respectively, representing 5-year survival rates of 1-4â years after diagnosis). In addition, the improvement in conditional survival rate CS5 showed a nonlinear trend. After 5â years of diagnosis, age, tumor size, and tumor stage had a sustained impact on patient prognosis. Finally, a conditional survival nomogram was constructed to predict the 10-year survival rate in real time. CONCLUSION: Five years after diagnosis, the conditional survival rate of male patients with breast cancer has improved, but it is not nonlinear. In the first 5â years after diagnosis, patients with older age, larger tumor size, poorer tumor stage, and distant metastasis should be actively followed up and treated to improve their long-term survival.
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Iron minerals are widespread in earth's surface water and soil. Recent studies have revealed that under sunlight irradiation, iron minerals are photoactive on producing reactive oxygen species (ROS), a group of key species in regulating elemental cycling, microbe inactivation, and pollutant degradation. In nature, iron minerals exhibit varying crystallinity under different hydrogeological conditions. While crystallinity is a known key parameter determining the overall activity of iron minerals, the impact of iron mineral crystallinity on photochemical ROS production remains unknown. Here, we assessed the photochemical ROS production from ferrihydrites with different degrees of crystallinity. All examined ferrihydrites demonstrated photoactivity under irradiation, resulting in the generation of hydrogen peroxide (H2O2) and hydroxyl radical (â¢OH). The photochemical ROS production from ferrihydrites increased with decreasing ferrihydrite crystallinity. The crystallinity-dependent photochemical â¢OH production was primarily attributed to conduction band reduction reactions, with the reduction of O2 by conduction band electrons being the rate-limiting key process. Conversely, the crystallinity of iron minerals had a negligible influence on photon-to-electron conversion efficiency or surface Fenton-like activity. The difference in ROS productions led to a discrepant degradation efficiency of organic pollutants on iron mineral surfaces. Our study provides valuable insights into the crystallinity-dependent ROS productions from iron minerals in natural systems, emphasizing the significance of iron mineral photochemistry in natural sites with abundant lower-crystallinity iron minerals such as wetland water and surface soils.
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Hierro , Minerales , Especies Reactivas de Oxígeno , Hierro/química , Especies Reactivas de Oxígeno/química , Minerales/química , Radical Hidroxilo/química , Peróxido de Hidrógeno/químicaRESUMEN
The successful implementation of neural network-based EEG signal compression has led to significant cost reductions in data transmission. However, a major obstacle in this process arises from the decline in performance when compressing EEG signals from multiple subjects. This challenge arises due to the notable feature shift of EEG signals between subjects, which poses an impediment to the neural network's efficient concurrent acquisition of information from multiple subjects. To address this limitation and enable more effective utilization of data for improving the performance on target domain, we propose a Domain Adaptation (DA) framework based on LSTM-autoencoder. Our experiments encompassed the following: (1) A comparison between LSTM-autoencoder, GRU-autoencoder, and the commonly used convolutional autoencoder (CAE) in EEG compression. (2) A comparison between our proposed DA method and the MMD-based DA method, as well as Fine-tuning transfer learning. The results demonstrate the following: (1) LSTM-autoencoder outperforms other models in both subject-specific and cross-subject scenarios. (2) Using transfer learning improves the performance of LSTM-autoencoder on the target subject. (3) Our proposed method outperforms maximum mean discrepancy (MMD)-based domain adaptation and fine-tuning approaches, resulting in a more significant enhancement.
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In this work, we report a novel high-pressure solid-state metathesis (HSM) reaction to produce spherical bulk (diameters 2-4 mm) Co-C alloys (Co3C and Co1-xCx). At 2-5 GPa and 1300 °C, C atoms preferentially occupy the interstitial sites of the face-centered cubic (fcc) Co lattice, leading to the formation of metastable Pnma Co3C. The Co3C decomposes above 1400 °C at 2-5 GPa, C atoms infiltrate the interstitial sites of the fcc Co lattice, saturating the C content in Co, forming an fcc Co1-xCx solid solution while the C atoms in excess are found to precipitate in the form of graphite. The Vickers hardness of the Co-C alloys is approximately 6.1 GPa, representing a 19.6% increase compared to hexagonal close-packed (hcp) Co. First-principles calculations indicate that the presence of C atoms in the Pnma Co3C structure leads to a relative decrease in the magnetic moments of the two distinct Co atom occupancies. The Co-C alloys exhibited a soft magnetic behavior with saturation magnetization up to 93.71 emu g-1 and coercivity of 74.8 Oe; coercivity increased as the synthesis pressure rises.
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OBJECTIVES: The aim of this study was to investigate the dynamic longitudinal relationship between grip strength and cognitive function. METHODS: 6175 participants aged ≥50 years were included in the study using three waves of follow-up data from the Survey of Health, Ageing, and Retirement in Europe in 2015 (T1), 2017 (T2) and 2019 (T3). Cognitive function was assessed using numeracy, verbal fluency, immediate recall, delayed recall and total. The cross-lagged panel model was used for analysis. RESULTS: There was a correlation between grip strength and cognitive function. Standardized path coefficient from numeracy T1 to grip strength T2 was 0.017 (p = 0.003), and from numeracy T2 to grip strength T3 was 0.014 (p = 0.012). Standardized path coefficient from grip strength T1 to numeracy T2 was 0.096 (p < 0.001), and from grip strength T2 to numeracy T3 was 0.113 (p < 0.001). Other indicators of cognitive function had similar relationships with grip strength. CONCLUSIONS: The study found a statistically significant longitudinal and bidirectional relationship between grip strength and cognitive function in a sample of people aged ≥50 years from several European countries.
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Cognición , Fuerza de la Mano , Humanos , Fuerza de la Mano/fisiología , Masculino , Femenino , Persona de Mediana Edad , Europa (Continente) , Anciano , Cognición/fisiología , Estudios Longitudinales , Envejecimiento/fisiología , Envejecimiento/psicologíaRESUMEN
Aqueous electrochemical coupling reactions, which enable the green synthesis of complex organic compounds, will be a crucial tool in synthetic chemistry. However, a lack of informed approaches for screening suitable catalysts is a major obstacle to its development. Here, we propose a pioneering electrochemical reductive coupling reaction toward direct electrosynthesis of oxime from NOx and aldehyde. Through integrating experimental and theoretical methods, we screen out the optimal catalyst, i.e., metal Fe catalyst, that facilitates the enrichment and C-N coupling of key reaction intermediates, all leading to high yields (e.g., â¼99% yield of benzaldoxime) for the direct electrosynthesis of oxime over Fe. With a divided flow reactor, we achieve a high benzaldoxime production of 22.8 g h-1 gcat-1 in â¼94% isolated yield. This work not only paves the way to the industrial mass production of oxime via electrosynthesis but also offers references for the catalyst selection of other electrochemical coupling reactions.
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Hydroxyl radical (â¢OH) is a powerful oxidant abundantly found in nature and plays a central role in numerous environmental processes. On-site detection of â¢OH is highly desirable for real-time assessments of â¢OH-centered processes and yet is restrained by a lack of an analysis system suitable for field applications. Here, we report the development of a flow-injection chemiluminescence analysis (FIA-CL) system for the continuous field detection of â¢OH. The system is based on the reaction of â¢OH with phthalhydrazide to generate 5-hydroxy-2,3-dihydro-1,4-phthalazinedione, which emits chemiluminescence (CL) when oxidatively activated by H2O2 and Cu3+. The FIA-CL system was successfully validated using the Fenton reaction as a standard â¢OH source. Unlike traditional absorbance- or fluorescence-based methods, CL detection could minimize interference from an environmental medium (e.g., organic matter), therefore attaining highly sensitive â¢OH detection (limits of detection and quantification = 0.035 and 0.12 nM, respectively). The broad applications of FIA-CL were illustrated for on-site 24 h detection of â¢OH produced from photochemical processes in lake water and air, where the temporal variations on â¢OH productions (1.0-12.2 nM in water and 1.5-37.1 × 107 cm-3 in air) agreed well with sunlight photon flux. Further, the FIA-CL system enabled field 24 h field analysis of â¢OH productions from the oxidation of reduced substances triggered by tidal fluctuations in coastal soils. The superior analytical capability of the FIA-CL system opens new opportunities for monitoring â¢OH dynamics under field conditions.
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Radical Hidroxilo , Luminiscencia , Radical Hidroxilo/análisis , Radical Hidroxilo/química , Peróxido de Hidrógeno , Oxidación-Reducción , AguaRESUMEN
Cysteine (Cys) and homocysteine (Hcy) are important biothiols in living organisms. They play important roles in a variety of physiological and pathological processes. Therefore, it is very important to design an optical probe for the selective detection of Cys/Hcy. Herein, we report the design and synthesis of a fluorescent probe NBD-B-T based on a boron-dipyrromethene (BODIPY) structure, which showed an excellent lysosome targeting ability and an outstanding Cys/Hcy detection capacity. For NBD-B-T, the sensing group 7-nitro-2,1,3-benzoxadiazole (NBD) and the lysosomal targeting group morpholine were introduced. The results show that the NBD-B-T probe can detect Cys/Hcy with fluorescence emission turn-on performance. The low detection limits of this probe are about 76.0 nM for Hcy and 97.6 nM for Cys, respectively. The NBD-B-T probe has a low detection limit, high stability, and excellent selectivity and sensitivity. More importantly, the NBD-B-T can target lysosome, and simultaneously detect the Cys/Hcy in living cells.
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Compuestos de Boro , Cisteína , Colorantes Fluorescentes , Humanos , Colorantes Fluorescentes/química , Células HeLa , LisosomasRESUMEN
Sunlight-induced photochemical transformations greatly affect the persistence of organic pollutants in natural environment. Whereas sunlight intensity is well-known to affect pollutant phototransformation rates, the reliance of pollutant phototransformation kinetics on sunlight spectrum remains poorly understood, which may greatly vary under different spatial-temporal, water matrix, and climatic conditions. Here, we systematically assessed the wavelength-dependent direct and indirect phototransformations of 12 organic pollutants. Their phototransformation rates dramatically decreased with light wavelength increasing from 375 to 632 nm, with direct photolysis displaying higher wavelength-dependence than indirect photolysis. Remarkably, UV light dominated both direct (90.4-99.5 %) and indirect (64.6-98.7 %) photochemical transformations of all investigated organic pollutants, despite its minor portion in sunlight spectrum (e.g., 6.5 % on March 20 at the equator). Based on wavelength-dependent rate constant spectrum, the predicted phototransformation rate of chloramphenicol (4.5 ± 0.7 × 10-4 s-1) agreed well with the observed rate under outdoor sunlight irradiation (4.3 ± 0.0 × 10-4 s-1), and there is no significant difference between the predicted rate and the observed rate (p-value = 0.132). Moreover, rate constant and quantum yield coefficient (QYC) spectrum could be applied for facilely investigate the influence of spectral changes on the phototransformation of pollutants under varying spatial-temporal (e.g., season, latitude) and climatic conditions (e.g., cloud cover). Our study highlights the wavelength-dependence of both direct and indirect phototransformation of pollutants, and the UV part of natural sunlight plays a decisive role in the phototransformation of pollutants.
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The present study elucidated cuproptosis-related molecular clusters involved in ischemic stroke and developed predictive models. Transcriptomic and immunological profiles of ischemic stroke-related datasets were extracted from the Gene Expression Omnibus database. Next, we conducted weighted gene co-expression network analysis to determine cluster-specific differentially expressed genes (DEGs). Models such as random forest and eXtreme gradient boosting (XGB) were evaluated to select the best prediction performance model. Subsequently, we validated the model's predictive efficiency by using nomograms, decision curve analysis, calibration curves, and receiver operating characteristic curve analysis with an external dataset. We identified two cuproptosis-related clusters involved in ischemic stroke. The DEGs in Cluster 2 were closely associated with amino acid metabolism, various immune responses, and cell proliferation pathways. The XGB model showed lower residuals, a smaller root mean square error, and a greater area under the curve value (AUCâ =â 0.923), thus exhibiting the best discriminative performance. The AUC value for the external validation dataset was 0.921, thus confirming the high performance of the model. NFE2L2, NLRP3, GLS, LIPT1, and MTF1 were identified as potential cuproptosis predictors, thus shedding new light on ischemic stroke pathogenesis and heterogeneity.
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Accidente Cerebrovascular Isquémico , Humanos , Accidente Cerebrovascular Isquémico/genética , Proliferación Celular , Bases de Datos Factuales , Perfilación de la Expresión Génica , Curva ROCRESUMEN
The effect of fenugreek (Trigonella foenum-graecum L.) seed extracts (FSEs) on the structure of duck myofibrillar protein (MP) oxidation was researched via particle size, zeta potential, Fourier transform infrared (FTIR), fluorescence spectroscopy, SDS-PAGE, and scanning electron microscopy (SEM) in the Fenton oxidation system. FSE (0.3 mg/mL) could scavenge 58.79% of the hydroxyl radical and possessed good antioxidation. FSE could retard the oxidation of MP, and the carbonyl formation and total sulfhydryl loss of MP decreased by 42.00% and 105.94%, respectively, after 4.67% of FSE treatment. SDS-PAGE results showed that 0.67% and 2.67% of FSE decreased the strength of the myosin heavy chain (MHC) and actin bands of the oxidized MP, respectively. The FSE changed the secondary structures of the MP and promoted the unfolding of the MP structure and the transformation from α-helix to ß-turn. When treated with 0.67% of FSE, the hydrophobicity of the MP declined by 26.14%, and solubility was improved by 37.21% compared with the oxidation group. After 0.67% of FSE treatment, the particle size and zeta potential of the MP returned to the level of the blank group. Scanning electron microscopy revealed that FSE improved the apparent morphology of the MP. Overall, FSE had positive effects on the antioxidation of the duck MP, and it could improve the structure and characteristics of the MP. It is hoped that FSE could be considered as a natural antioxidant to retard the oxidation of the MP in meat products.
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Two new compounds, named rhizoaspergillin A (1) and rhizoaspergillinol A (2), were isolated from the mangrove endophytic fungus Aspergillus sp. A1E3, associated with the fruit of Rhizophora mucronata, together with averufanin (3). The planar structures and absolute configurations of rhizoaspergillinol A (2) and averufanin (3) were established by extensive NMR investigations and quantum-chemical electronic circular dichroism (ECD) calculations. Most notably, the constitution and absolute configuration of rhizoaspergillin A (1) were unambiguously determined by single-crystal X-ray diffraction analysis of its tri-pivaloyl derivative 4, conducted with Cu Kα radiation, whereas those of averufanin (3) were first clarified by quantum-chemical ECD calculations. Rhizoaspergillin A is the first orsellinic acid-ribose-pyridazinone-N-oxide hybrid containing a unique ß-oxo-2,3-dihydropyridazine 1-oxide moiety, whereas rhizoaspergillinol A (2) and averufanin (3) are sterigmatocystin and anthraquinone derivatives, respectively. From the perspective of biosynthesis, rhizoaspergillin A (1) could be originated from the combined assembly of three building blocks, viz., orsellinic acid, ß-D-ribofuranose, and L-glutamine. It is an unprecedented alkaloid-N-oxide involving biosynthetic pathways of polyketides, pentose, and amino acids. In addition, rhizoaspergillinol A (2) exhibited potent antiproliferative activity against four cancer cell lines. It could dose-dependently induce G2/M phase arrest in HepG2 cells.
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Aspergillus , Ribosa , Ribosa/metabolismo , Aspergillus/química , Antraquinonas/metabolismo , Estructura MolecularRESUMEN
AIMS: Dissecting complex interactions among transcription factors (TFs), microRNAs (miRNAs) and long noncoding RNAs (lncRNAs) are central for understanding heart development and function. Although computational approaches and platforms have been described to infer relationships among regulatory factors and genes, current approaches do not adequately account for how highly diverse, interacting regulators that include noncoding RNAs (ncRNAs) control cardiac gene expression dynamics over time. METHODS: To overcome this limitation, we devised an integrated framework, cardiac gene regulatory modeling (CGRM) that integrates LogicTRN and regulatory component analysis bioinformatics modeling platforms to infer complex regulatory mechanisms. We then used CGRM to identify and compare the TF-ncRNA gene regulatory networks that govern early- and late-stage cardiomyocytes (CMs) generated by in vitro differentiation of human pluripotent stem cells (hPSC) and ventricular and atrial CMs isolated during in vivo human cardiac development. RESULTS: Comparisons of in vitro versus in vivo derived CMs revealed conserved regulatory networks among TFs and ncRNAs in early cells that significantly diverged in late staged cells. We report that cardiac genes ("heart targets") expressed in early-stage hPSC-CMs are primarily regulated by MESP1, miR-1, miR-23, lncRNAs NEAT1 and MALAT1, while GATA6, HAND2, miR-200c, NEAT1 and MALAT1 are critical for late hPSC-CMs. The inferred TF-miRNA-lncRNA networks regulating heart development and contraction were similar among early-stage CMs, among individual hPSC-CM datasets and between in vitro and in vivo samples. However, genes related to apoptosis, cell cycle and proliferation, and transmembrane transport showed a high degree of divergence between in vitro and in vivo derived late-stage CMs. Overall, late-, but not early-stage CMs diverged greatly in the expression of "heart target" transcripts and their regulatory mechanisms. CONCLUSIONS: In conclusion, we find that hPSC-CMs are regulated in a cell autonomous manner during early development that diverges significantly as a function of time when compared to in vivo derived CMs. These findings demonstrate the feasibility of using CGRM to reveal dynamic and complex transcriptional and posttranscriptional regulatory interactions that underlie cell directed versus environment-dependent CM development. These results with in vitro versus in vivo derived CMs thus establish this approach for detailed analyses of heart disease and for the analysis of cell regulatory systems in other biomedical fields.
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MicroARNs , ARN Largo no Codificante , Humanos , ARN Largo no Codificante/genética , Factores de Transcripción/genética , MicroARNs/genética , Miocitos Cardíacos , Ventrículos CardíacosRESUMEN
Purpose: This study aimed to characterize the gut microbiota in obese adolescents from Shenzhen (China), and evaluate influence of gender on BMI-related differences in the gut microbiome. Methods: Evaluation of physical examination, blood pressure measurement, serological assay and body composition were conducted in 205 adolescent subjects at Shenzhen. Fecal microbiome composition was profiled via high-throughput sequencing of the V3-V4 regions of the 16S rRNA gene. A Random Forest (RF) classifier model was built to distinguish the BMI categories based on the gut bacterial composition. Results: Fifty-six taxa consisting mainly of Firmicutes were identified that having significant associations with BMI; 2 OTUs belonging to Ruminococcaceae and 1 belonging to Lachnospiraceae had relatively strong positive correlations with body fate rate, waistline and most of serum biochemical properties. Based on the 56 BMI-associated OTUs, the RF model showed a robust classification accuracy (AUC 0.96) for predicting the obese phenotype. Gender-specific differences in the gut microbiome composition was obtained, and a lower relative abundance of Odoribacter genus was particularly found in obese boys. Functional analysis revealed a deficiency in bacterial gene contents related to peroxisome and PPAR signaling pathway in the obese subjects for both genders. Conclusions: This study reveals unique features of gut microbiome in terms of microbial composition and metabolic functions in obese adolescents, and provides a baseline for reference and comparison studies. Supplementary Information: The online version contains supplementary material available at 10.1007/s13755-023-00236-9.