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BACKGROUND: The hypoxic tumor microenvironment is a key factor that promotes metabolic reprogramming and vascular mimicry (VM) in ovarian cancer (OC) patients. ESM1, a secreted protein, plays an important role in promoting proliferation and angiogenesis in OC. However, the role of ESM1 in metabolic reprogramming and VM in the hypoxic microenvironment in OC patients has not been determined. METHODS: Liquid chromatography coupled with tandem MS was used to analyze CAOV3 and OV90 cells. Interactions between ESM1, PKM2, UBA2, and SUMO1 were detected by GST pull-down, Co-IP, and molecular docking. The effects of the ESM1-PKM2 axis on cell glucose metabolism were analyzed based on an ECAR experiment. The biological effects of the signaling axis on OC cells were detected by tubule formation, transwell assay, RTâPCR, Western blot, immunofluorescence, and in vivo xenograft tumor experiments. RESULTS: Our findings demonstrated that hypoxia induces the upregulation of ESM1 expression through the transcription of HIF-1α. ESM1 serves as a crucial mediator of the interaction between PKM2 and UBA2, facilitating the SUMOylation of PKM2 and the subsequent formation of PKM2 dimers. This process promotes the Warburg effect and facilitates the nuclear translocation of PKM2, ultimately leading to the phosphorylation of STAT3. These molecular events contribute to the promotion of ovarian cancer glycolysis and vasculogenic mimicry. Furthermore, our study revealed that Shikonin effectively inhibits the molecular interaction between ESM1 and PKM2, consequently preventing the formation of PKM2 dimers and thereby inhibiting ovarian cancer glycolysis, fatty acid synthesis and vasculogenic mimicry. CONCLUSION: Our findings demonstrated that hypoxia increases ESM1 expression through the transcriptional regulation of HIF-1α to induce dimerization via PKM2 SUMOylation, which promotes the OC Warburg effect and VM.
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Proteínas Portadoras , Ácidos Grasos , Proteínas de la Membrana , Proteínas de Neoplasias , Neoplasias Ováricas , Proteínas de Unión a Hormona Tiroide , Hormonas Tiroideas , Microambiente Tumoral , Femenino , Humanos , Neoplasias Ováricas/metabolismo , Neoplasias Ováricas/patología , Neoplasias Ováricas/genética , Animales , Hormonas Tiroideas/metabolismo , Ratones , Proteínas de la Membrana/metabolismo , Proteínas de la Membrana/genética , Línea Celular Tumoral , Ácidos Grasos/metabolismo , Proteínas de Neoplasias/metabolismo , Proteínas de Neoplasias/genética , Proteínas Portadoras/metabolismo , Proteínas Portadoras/genética , Efecto Warburg en Oncología , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Subunidad alfa del Factor 1 Inducible por Hipoxia/genética , Regulación Neoplásica de la Expresión Génica , Neovascularización Patológica/metabolismo , Neovascularización Patológica/genética , Neovascularización Patológica/patología , Ensayos Antitumor por Modelo de Xenoinjerto , Proliferación Celular , ProteoglicanosRESUMEN
Objective: To examine the impact of moderate alcohol consumption on the progression of chronic kidney disease (CKD) in individuals diagnosed with non-alcoholic fatty liver disease (NAFLD), as NAFLD has been identified as an autonomous risk factor for CKD and previous research has demonstrated a reduction in overall mortality in NAFLD patients who consume alcohol in moderation.Methods: This study included participants from ten consecutive rounds of the National Health and Nutrition Examination Survey (NHANES:1998-2018). Multivariate logistic regression models were employed to assess the impact of moderate alcohol consumption on chronic kidney disease (CKD) in both male and female populations. Subgroup analysis was conducted by categorizing patients with non-alcoholic fatty liver disease (NAFLD) based on the Fibrosis-4 (FIB-4) index.Results: 17040 participants were eligible to be included in the study. The logistic regression analysis model showed that moderate alcohol consumption was a protective factor for CKD in male NAFLD patients, with an unadjusted OR: 0.37 (0.22,0.65), and p < 0.001. After further adjustment, the association persisted. However, the association was not significant in female patients with NAFLD. Among men with low risk of liver fibrosis group, moderate alcohol consumption remained a protective factor for CKD (OR = 0.32, 95% CI 0.12-0.84, p = 0.02), but the association was not significant in the high risk of liver fibrosis group. In female patients, both moderate alcohol consumption and excessive alcohol consumption were not significantly associated with CKD in either the low-risk group or the high-risk group.Conclusion: Moderate alcohol consumption is associated with a lower prevalence of CKD in men with NAFLD.
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Enfermedad del Hígado Graso no Alcohólico , Insuficiencia Renal Crónica , Humanos , Masculino , Femenino , Enfermedad del Hígado Graso no Alcohólico/complicaciones , Enfermedad del Hígado Graso no Alcohólico/epidemiología , Encuestas Nutricionales , Insuficiencia Renal Crónica/epidemiología , Insuficiencia Renal Crónica/etiología , Consumo de Bebidas Alcohólicas/efectos adversos , Consumo de Bebidas Alcohólicas/epidemiología , Cirrosis Hepática/complicacionesRESUMEN
This study aimed to investigate the role of Sirt6 and inflammatory cytokines in blood samples of patients with ACS. This is a retrospective randomized controlled clinical trial, a total of 30 patients from our hospital are included and divided into following two groups: control group and experimental group, and experimental group consists of 15 patients with ACS and control group consists of 15 patients with non-acute coronary syndrome. Sirt6 protein is detected by western blotting and Sirt6 mRNA is detected by real-time PCR, then inflammatory cytokines such as IL-1ß, IL-18, TnI, and CK-MB are measured by ELISA and cytokines NT-proBNP are monitored by immunofluorescence. Our outcomes show that Sirt6 protein and Sirt6 mRNA in experimental group are remarkably lower than those in control group, and IL-1ß, IL-18, TnI, CK-MB, and NT-proBNP in the experimental group are remarkably higher than those in control group. We can conclude that Sirt6 can prevent or inhibit the development of ACS and IL-1ß, IL-18, TnI, CK-MB, and NT-proBNP can accelerate the development of ACS.
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Síndrome Coronario Agudo , Sirtuinas , Humanos , Biomarcadores , Citocinas , Interleucina-18/genética , Estudios Retrospectivos , ARN Mensajero , Sirtuinas/sangre , Sirtuinas/metabolismoRESUMEN
Alzheimer's disease (AD) is a serious brain disorder characterized by the presence of beta-amyloid plaques, tau pathology, inflammation, neurodegeneration, and cerebrovascular dysfunction. The presence of chronic neuroinflammation, breaches in the blood-brain barrier (BBB), and increased levels of inflammatory mediators are central to the pathogenesis of AD. These factors promote the penetration of immune cells into the brain, potentially exacerbating clinical symptoms and neuronal death in AD patients. While microglia, the resident immune cells of the central nervous system (CNS), play a crucial role in AD, recent evidence suggests the infiltration of cerebral vessels and parenchyma by peripheral immune cells, including neutrophils, T lymphocytes, B lymphocytes, NK cells, and monocytes in AD. These cells participate in the regulation of immunity and inflammation, which is expected to play a huge role in future immunotherapy. Given the crucial role of peripheral immune cells in AD, this article seeks to offer a comprehensive overview of their contributions to neuroinflammation in the disease. Understanding the role of these cells in the neuroinflammatory response is vital for developing new diagnostic markers and therapeutic targets to enhance the diagnosis and treatment of AD patients.
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OBJECTIVE: Current guidelines are debated when it comes to starting anticoagulant therapy in patients with non-valvular atrial fibrillation (NVAF) and low CHA2DS2-VASc scores (1-2 in women and 0-1 in men). However, these individuals still have a high likelihood of developing left atrial thrombus/spontaneous echo contrast (LAT/SEC) and experiencing subsequent thromboembolism. Recent research has demonstrated that lipoprotein(a) [Lp(a)] may increase the risk of thrombosis, but the relationship between Lp(a) and LAT/SEC in NVAF patients is not clearly established. Therefore, this study sought to evaluate the predictive ability of Lp(a) for LAT/SEC among NVAF patients with low CHA2DS2-VASc scores. METHODS: NVAF patients with available transesophageal echocardiography (TEE) data were evaluated. Based on the TEE results, the subjects were classified into non-LAT/SEC and LAT/SEC groups. The risk factors for LAT/SEC were examined using binary logistic regression analyses and were validated by using 1:1 propensity score matching (PSM). Subsequently, novel predictive models for LAT/SEC were developed by integrating the CHA2DS2-VASc score with the identified factors, and the accuracy of these models was tested using receiver operating characteristic (ROC) analysis. RESULTS: In total, 481 NVAF patients were enrolled. The LAT/SEC group displayed higher Lp(a) concentrations. It was found that enlarged left atrial diameter (LAD), high concentrations of Lp(a), and a history of coronary heart disease (CHD) were independent predictors of LAT/SEC. Lp(a) and LAD still had predictive values for LAT/SEC after adjusting for PSM. In both the highest quartile groups of Lp(a) (>266 mg/L) and LAD (>39.5 mm), the occurrence of LAT/SEC was higher than that in the corresponding lowest quartile. By incorporating Lp(a) and the LAD, the predictive value of the CHA2DS2-VASc score for LAT/SEC was significantly improved. CONCLUSION: Elevated Lp(a) and enlarged LAD were independent risk factors for LAT/SEC among NVAF patients with low CHA2DS2-VASc scores. The prediction accuracy of the CHA2DS2-VASc score for LAT/SEC was significantly improved by the addition of Lp(a) and LAD. When evaluating the stroke risk in patients with NVAF, Lp(a) and LAD should be taken into account together with the CHA2DS2-VASc score. TRIAL REGISTRATION: Retrospectively registered.
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Fibrilación Atrial , Lipoproteína(a) , Trombosis , Femenino , Humanos , Masculino , Fibrilación Atrial/complicaciones , Fibrilación Atrial/diagnóstico por imagen , Estudios Transversales , Puntaje de Propensión , Trombosis/diagnóstico por imagen , Trombosis/etiologíaRESUMEN
We described a case of a double aortic arch (DAA) with a subaortic left brachiocephalic vein (LBCV) and right-side ductus arteriosus using high-definition (HD) flow render mode and spatiotemporal image correlation (STIC). We experienced uncertainty regarding this interesting case despite the diagnosis of right-sided ductus arteriosus. The ductus arteriosus originates from the right pulmonary artery (PA) and converges into the descending aorta (DAO), whereas the vessel originated from the PA and converged into the ascending aorta (AAO). Therefore, we assumed that the vessel connecting the PA to AAO may be a type-C persistent fifth aortic arch (PFAA).
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Conducto Arterioso Permeable , Conducto Arterial , Anillo Vascular , Embarazo , Femenino , Humanos , Conducto Arterial/diagnóstico por imagen , Aorta Torácica/diagnóstico por imagen , Conducto Arterioso Permeable/diagnóstico por imagen , AortaRESUMEN
OBJECTIVES: To evaluate the clinical utility of two dimensional (2D) ultrasound combined with spatiotemporal image correlation (STIC) in diagnosing interrupted aortic arch (IAA) in fetal life. METHODS: A total of 53 cases of fetal IAA were diagnosed using 2D ultrasound combined with STIC, and 53 normal fetuses of the same gestational week were selected. These cases were retrospectively analyzed to assess the utility of employing 2D ultrasound combined with STIC in the diagnosis of IAA. RESULTS: 2D ultrasound combined with STIC detected 22 cases of type A IAA, 24 cases of type B IAA, and seven cases of type C IAA. Furthermore, combining 2D ultrasound with STIC enabled dynamic visualization of the IAA, aiding in prenatal diagnosis. The diagnostic coincidence rate of IAA was found to be higher in the HD-flow combined with STIC than that in the 2D combined with HD-flow. CONCLUSION: HD-flow combined with STIC can assist in diagnosing fetal IAA, and this technique has important clinical value.
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Aorta Torácica , Ultrasonografía Prenatal , Humanos , Femenino , Ultrasonografía Prenatal/métodos , Embarazo , Aorta Torácica/diagnóstico por imagen , Aorta Torácica/anomalías , Aorta Torácica/embriología , Estudios Retrospectivos , Adulto , Reproducibilidad de los Resultados , Corazón Fetal/diagnóstico por imagenRESUMEN
OBJECTIVE: This study aimed to assess the use of two-dimensional (2D) ultrasound combined with high-definition flow (HD-flow) render mode and spatiotemporal image correlation (STIC) in diagnosing and classifying fetal persistent left superior vena cava (PLSVC). METHODS: Overall, 114 cases of fetal PLSVC were diagnosed using 2D ultrasound combined with STIC, and 114 normal fetuses of the same gestational week were selected. These cases were retrospectively analyzed to evaluate the effectiveness of the diagnostic approach. RESULTS: All 114 PLSVC cases were diagnosed using 2D ultrasound combined with STIC. Although the diagnostic coincidence rate of PLSVC in the HD-flow combined with STIC was similar to that in the 2D ultrasound combined with HD-flow (96.8 vs 96.2%), 2D ultrasound with STIC enabled dynamic visualization of the PLSVC, furthering prenatal diagnosis. These cases were classified as type I PLSVC: 80 cases of type Ia, 29 cases of type Ib, and 5 cases of type Ic. Seventy isolated PLSVC cases (61.4%) were noted, whereas 44 cases (35.6%) were associated with concomitant structural abnormalities. Intracardiac structural malformations accounted for the highest proportion (n = 53, 58.89%), followed by single umbilical artery and facial/bodily abnormalities (n = 10, 11.11%). CONCLUSION: Combining HD-flow and STIC complements 2D ultrasound in diagnosing and classifying fetal PLSVC, demonstrating significant clinical relevance.
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A novel ternary heterojunction material In2O3/In2S3/ZnIn2S4 was synthesized, and a photoelectrochemical sensor was fabricated for the non-invasive test of dopamine (DA) in sweat. In2O3 multihollow microtubules were synthesized and then In2S3 was formed on their surface to construct a type-I heterojunction between In2S3 and In2O3. ZnIn2S4 was further introduced to form a Z-scheme heterojunction between In2S3/ZnIn2S4. Under photoexcitation, the photogenerated holes of In2O3 transferred to the valence band of In2S3, superimposed with the holes produced by In2S3, leads to a significantly higher photocatalytic oxidation capacity of In2O3/In2S3/ZnIn2S4 ternary composites than that of In2O3/In2S3. The Z-scheme heterojunction accelerates the transfer of photogenerated electrons accumulated on the type-I heterojunction. In the presence of DA, it is rapidly oxidized into polydopamine (PDA) by In2O3/In2S3, and the benzoquinone groups of PDA compete for the photogenerated electrons to reduce the current in the external circuit, whereby DA determination is achieved. Owing to the combination of type-I and Z-scheme heterojunction, the sensor showed extremely high sensitivity, with a detection limit of 3.94 × 10-12 mol/L. It is one of the most sensitive methods for DA detection reported and has been applied to the determination of DA in human sweat.
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Dopamina , Sudor , Humanos , ElectronesRESUMEN
Given the escalating global crisis in feed protein availability, Jatropha curcas L. cake has attracted significant interest as a viable alternative protein source in animal feed. This experiment was conducted to investigate the effects of fermented Jatropha curcas L. cake (FJCC) as a protein feed in the diet of pigs. A total of 96 growing pigs with an average weight of 27.60 ± 1.59 kg were divided into three dietary groups with varying FJCC inclusion levels (0, 2.5, and 5%) for a 28 d trial. Results showed that the diet with 5% FJCC (FJCC5) demonstrated significant improvements in average daily gain (p = 0.009), feed-to-gain ratio (p = 0.036), nutrient digestibility, and intestinal morphology. Furthermore, the FJCC5 diet resulted in a decrease in pH values in different gut sections (jejunum p = 0.045, cecum p = 0.001, colon p = 0.012), and favorably altered the profile of short-chain fatty acids (SCFAs) with increased butyric acid content (p = 0.005) and total SCFAs (p = 0.019). Additionally, this diet notably decreased IL-6 levels in the jejunum (p = 0.008) and colon (=0.047), significantly reduced IL-1 levels in the hypothalamus (p < 0.001), and lowered IL-1, IL-6, and IL-10 levels in plasma (p < 0.05). Microbiota and metabolite profile analysis revealed an elevated abundance of beneficial microbes (p < 0.05) and key metabolites such as 4-aminobutyric acid (GABA) (p = 0.003) and serotonin (5-HT) (p = 0.022), linked to neuroactive ligand-receptor interaction. Moreover, FJCC5 significantly boosted circulating neurotransmitter levels of 5-HT (p = 0.006) and GABA (p = 0.002) in plasma and hypothalamus, with corresponding increases in precursor amino acids (p < 0.05). These findings suggest that FJCC, particularly at a 5% inclusion rate, can be an effective substitute for traditional protein sources like soybean meal, offering benefits beyond growth enhancement to gut health and potentially impacting the gut-brain axis. This research underscores FJCC's potential as a valuable component in sustainable animal nutrition strategies.
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The efficient extraction recovery of scandium (Sc(iii)) is crucial for its application in high-end technology. Two novel hydrophobic carboxylic acid ionic liquids (ILs), namely, [lauryl betaine][bis(trifluoromethanesulphonyl)imide] ([Laur][Tf2N]) and [cocamidopropyl betaine][bis(trifluoromethanesulphonyl)imide] ([Coca][Tf2N]), were synthesized using two inexpensive amphoteric surfactants as cation sources. [Laur][Tf2N] (257 °C) and [Coca][Tf2N] (251 °C) exhibited good thermal stability and strong hydrophobicity. The viscosity of [Coca][Tf2N] (4.29 × 103 mP s) was higher than that of [Laur][Tf2N] (2.55 × 103 mPa s) at 25 °C. The optimal extraction conditions were an extraction equilibrium time of 40 min, an initial Sc(iii) concentration of 0.001 mol L-1, a sodium nitrate concentration of 0.5 mol L-1, and a pH of 3. The extraction efficiency of [Laur][Tf2N] and [Coca][Tf2N] could even exceed 98.7% and 96.0%, respectively. The cation exchange extraction mechanism was studied by slope analysis, IR spectroscopy and 13C NMR spectroscopy. Sc(iii) extracted using [Laur][Tf2N] and [Coca][Tf2N] could be completely stripped with 0.1 mol L-1 and 0.2 mol L-1 HNO3 once, respectively. The structure of the ILs was not broken after stripping, and the extraction efficiency of the ILs remained almost unchanged after five cycles. In addition, the extraction differences at different pH levels made it possible to separate Sc(iii) from other rare earths using ionic liquids [Laur][Tf2N] and [Coca][Tf2N].
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The classroom video has a complex background and dense targets. This study utilizes small object detection technology to analyze and evaluate students' behavior in the classroom, aiming to objectively and accurately assess classroom quality. Firstly, noise is removed from the images using a median filter, and the contrast of the images is enhanced through histogram equalization. Label smoothing is applied to reduce the model's sensitivity to labels. Then, features are extracted from the preprocessed images, and multi-scale feature fusion is employed to enhance semantic expression across multiple scales. Finally, a combination loss function is utilized to improve the accuracy of multi-object recognition tasks. Real-time detection of students' behaviors in the classroom is performed based on the small object detection model. The average head-up rate in the classroom is calculated, and the quality of teaching is evaluated and analyzed. This study explores the methods and applications of small object detection technology based on actual teaching cases and analyzes and evaluates its effectiveness in evaluating the quality of higher education classroom teaching. The research findings demonstrate the significant importance of small object detection technology in effectively evaluating students' learning conditions in higher education classrooms, leading to improved teaching quality and personalized education.
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To enhance the model's generalization ability in unsupervised domain adaptive segmentation tasks, most approaches have primarily focused on pixel-level local features, but neglected the clue in category information. This limitation results in the segmentation network only learning global inter-domain invariant features but ignoring the category-specific inter-domain invariant features, which degenerates the segmentation performance. To address this issue, we present an Unsupervised Domain Adaptive algorithm based on two-level Category Alignment in two different spaces for semantic segmentation tasks, denoted as UDAca+. The first level is image-level category alignment based on class activation map (CAM), and the second one is pixel-level category alignment based on pseudo label. By utilizing category information, UDAca+ can effectively capture domain-invariant yet category-discriminative feature representations to improve segmentation accuracy. In addition, an adversarial learning-based strategy in mixed domain is designed to train the proposed network. Moreover, a confidence calculation method is introduced to mitigate the misleading issues of negative transfer and over-alignment caused by the noise in image-level pseudo labels. UDAca+ achieves the state-of-the-art (SOTA) performance on two synthetic-to-real adaptative tasks, and verifies its effectiveness for image segmentation.
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Algoritmos , Redes Neurales de la Computación , Aprendizaje Automático no Supervisado , Humanos , Procesamiento de Imagen Asistido por Computador/métodos , SemánticaRESUMEN
OBJECTIVE: The aim of this study was to explore the effects of Ninjurin 2 (NINJ2) polymorphisms on susceptibility to coronary heart disease (CHD). METHODS: We conducted a case-control study with 499 CHD cases and 505 age and gender-matched controls. Five single nucleotide polymorphisms (SNPs) in NINJ2 (rs118050317, rs75750647, rs7307242, rs10849390, and rs11610368) were genotyped by the Agena MassARRAY platform. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using logistic regression analysis to assess the association of NINJ2 polymorphisms and CHD risk-adjusted for age and gender. What's more, risk genes and molecular functions were screened via protein-protein interaction (PPI) network and functional enrichment analysis. RESULTS: Rs118050317 in NINJ2 significantly increased CHD risk in people aged more than 60 years and women. Rs118050317 and rs7307242 had strong relationships with hypertension risk in CHD patients. Additionally, rs75750647 exceedingly raised diabetes risk in cases under multiple models, whereas rs10849390 could protect CHD patients from diabetes in allele, homozygote, and additive models. We also observed two blocks in NINJ2. Further interaction network and enrichment analysis showed that NINJ2 played a greater role in the pathogenesis and progression of CHD. CONCLUSION: Our results suggest that NINJ2 polymorphisms are associated with CHD risk.
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Moléculas de Adhesión Celular Neuronal , Enfermedad Coronaria , Predisposición Genética a la Enfermedad , Polimorfismo de Nucleótido Simple , Humanos , Femenino , Masculino , Polimorfismo de Nucleótido Simple/genética , Moléculas de Adhesión Celular Neuronal/genética , Predisposición Genética a la Enfermedad/genética , Persona de Mediana Edad , Enfermedad Coronaria/genética , Estudios de Casos y Controles , Anciano , Factores de Riesgo , GenotipoRESUMEN
The safety of Jatropha curcas L. cake (JCC) in animal feed remains under scrutiny, despite the advent of low phorbol ester (PE) variants. This study investigates the impact of low PE JCC on swine health when used as a protein feed. Pigs were fed a 5% JCC diet with a PE concentration of 0.98 mg/kg, which surprisingly still induced toxicity. Symptoms included depression, decreased food intake, increased diarrhea, along with hypothalamus and colon lesions. The toxicity was associated with a decrease in antioxidant enzymes, an increase in inflammatory cytokines in the hypothalamus, plasma, and colon, and a rise in pro-inflammatory colon microbes and metabolites. Disturbances in neurotransmitters further suggest that this toxicity is related to disruption of the microbiota-gut-brain axis, indicating that JCC's toxic elements are not solely due to PE. The sensitivity of pigs to JCC underscores the need for thorough detoxification prior to its use as feed. These findings significantly contribute to the discourse on the safety of low PE JCC in animal feed, highlighting implications for both the feed industry and public health.
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Alimentación Animal , Eje Cerebro-Intestino , Microbioma Gastrointestinal , Jatropha , Ésteres del Forbol , Animales , Porcinos , Ésteres del Forbol/efectos adversos , Eje Cerebro-Intestino/fisiología , Dieta/veterinaria , Ingestión de Alimentos , Citocinas/metabolismo , Colon/metabolismo , Hipotálamo/metabolismo , Depresión/metabolismo , Neurotransmisores/metabolismoRESUMEN
Objective: Peripheral blood routine parameters (PBRPs) are simple and easily acquired markers to identify ulcerative colitis (UC) and Crohn's disease (CD) and reveal the severity, whereas the diagnostic performance of individual PBRP is limited. We, therefore used four machine learning (ML) models to evaluate the diagnostic and predictive values of PBRPs for UC and CD. Methods: A retrospective study was conducted by collecting the PBRPs of 414 inflammatory bowel disease (IBD) patients, 423 healthy controls (HCs), and 344 non-IBD intestinal diseases (non-IBD) patients. We used approximately 70 % of the PBRPs data from both patients and HCs for training, 30 % for testing, and another group for external verification. The area under the receiver operating characteristic curve (AUC) was used to evaluate the diagnosis and prediction performance of these four ML models. Results: Multi-layer perceptron artificial neural network model (MLP-ANN) yielded the highest diagnostic performance than the other three models in six subgroups in the training set, which is helpful for discriminating IBD and HCs, UC and CD, active CD and remissive CD, active UC and remissive UC, non-IBD and HCs, and IBD and non-IBD with the AUC of 1.00, 0.988, 0.942, 1.00, 0.986, and 0.97 in the testing set, as well as the AUC of 1.00, 1.00, 0.773, 0.904, 1.00 and 0.992 in the external validation set. Conclusion: PBRPs-based MLP-ANN model exhibited good performance in discriminating between UC and CD and revealing the disease activity; however, a larger sample size and more models need to be considered for further research.
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BACKGROUND: The aim of this experiment was to investigate the effect of different levels of betaine (Bet) inclusion in the diet on the intestinal health of growing rabbits under summer heat. A total of 100 weaned Qixing meat rabbits aged 35 d with body weight of 748.61 ± 38.59 g were randomly divided into 5 treatment groups: control group (basal diet) and Bet groups (basal diet + 0.75, 1.0, 1.5 or 2.0 g/kg Bet). The average daily temperature in the rabbitry during the experiment was 30.48 °C and the relative humidity was 69.44%. RESULTS: Dietary addition of Bet had no significant effect on growth performance and health status of growing rabbits (P > 0.05), but it increased ileal secretory immunoglobulin A content compared to the control under summer heat (P < 0.05). Addition of 0.75 g/kg Bet up-regulated jejunal IL-4, down-regulated ileal TNF-α expression (P < 0.05). The addition of 1.0 g/kg Bet increased the villi height (VH) in the jejunum (P < 0.05). Serum glucose levels were reduced, and the expression of SLC6A20 was up-regulated in jejunum and ileum of rabbits fed with 1.5 g/kg Bet (P < 0.05). When added at 2.0 g/kg, Bet reduced serum HSP70 content, increased jejunal VH, and up-regulated duodenal SLC7A6, SLC38A2, mTOR and 4EBP-2 expression (P < 0.05). Correlation analysis revealed that intestinal mTOR expression was significantly and positively correlated with SLC7A6, SLC38A2, SLC36A1 and IL-4 expression (P < 0.05). CONCLUSIONS: Dietary addition of Bet can up-regulate the expression of anti-inflammatory factors through the AAT/mTOR pathway, improve the intestinal immune function, alleviate intestinal damage in growing rabbits caused by summer heat, and improve intestinal health.
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OBJECTIVE: To study the impact of Gx on quantification of hepatic fat contents under metabolic dysfunction-associated steatotic liver disease (MASLD) imaged on VIBE Dixon in hepatobiliary specific phase. METHODS: Forty-two rabbits were randomly divided into control group (n = 10) and high-fat diet group (n = 32). Imaging was performed before enhancement (Pre-Gx) and at the 13th (Post-Gx13) and 17th (Post-Gx17) min after Gx enhancement with 2E- and 6E-VIBE Dixon to determine hepatic proton density fat fractions (PDFF). PDFFs were compared with vacuole percentage (VP) measured under histopathology. RESULTS: 33 animals were evaluated and including control group (n = 11) and MASLD group (n = 22). Pre-Gx, Post-Gx13, Post-Gx17 PDFFs under 6E-VIBE Dixon had strong correlations with VPs (r2 = 0.8208-0.8536). PDFFs under 2E-VIBE Dixon were reduced significantly (P < 0.001) after enhancement (r2 = 0.7991/0.8014) compared with that before enhancement (r2 = 0.7643). There was no significant difference between PDFFs of Post-Gx13 and Post-Gx17 (P = 0.123) for which the highest consistency being found with 6E-VIBE Dixon before enhancement (r2 = 0.8536). The signal intensity of the precontrast compared with the postcontrast, water image under 2E-VIBE Dixon increased significantly (P < 0.001), fat image showed no significant difference (P = 0.754). CONCLUSION: 2E- and 6E-VIBE Dixon can obtain accurate PDFFs in the hepatobiliary specific phase from 13 to 17th min after Gx enhancement. On 2E-VIBE Dixon (FA = 10°), effective minimization of T1 Bias by the Gx administration markedly improved the accuracy of the hepatic PDFF quantification.
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Tumor-derived extracellular vesicles (tEVs) hold immense promise as potential biomarkers for the precise diagnosis of hepatocellular carcinoma (HCC). However, their clinical translation is hampered by their inherent characteristics, such as small size and high heterogeneity and complex environment, including non-EV particles and normal cell-derived EVs, which prolong separation procedures and compromise detection accuracy. In this study, we devised a DNA cascade reaction-triggered individual EV nanoencapsulation (DCR-IEVN) strategy to achieve the ultrasensitive and specific detection of tEV subpopulations via routine flow cytometry in a one-pot, one-step fashion. DCR-IEVN enables the direct and selective packaging of multiple tEV subpopulations in clinical serum samples into flower-like particles exceeding 600 nm. This approach bypasses the need for EV isolation, effectively reducing interference from non-EV particles and nontumor EVs. Compared with conventional analytical technologies, DCR-IEVN exhibits superior efficacy in diagnosing HCC owing to its high selectivity for tEVs. Integration of machine learning algorithms with DCR-IEVN resulted in differential diagnosis accuracy of 96.7% for the training cohort (n = 120) and 93.3% for the validation cohort (n = 30), effectively distinguishing HCC, cirrhosis, and healthy donors. This strategy offers a streamlined workflow and rapid assay completion and requires only small-volume serum samples and routine clinical devices, facilitating the clinical translation of tEV-based tumor diagnosis.
Asunto(s)
Carcinoma Hepatocelular , Vesículas Extracelulares , Neoplasias Hepáticas , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/sangre , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/sangre , Humanos , Vesículas Extracelulares/química , Vesículas Extracelulares/metabolismo , Diagnóstico Diferencial , ADN/química , Biomarcadores de Tumor/sangre , Aprendizaje AutomáticoRESUMEN
Four distinct CeO2 catalysts featuring varied morphologies (nanorods, nanocubes, nanoparticles, and nano spindle-shaped) were synthesized through a hydrothermal process and subsequently employed in the oxidation of dichloromethane (DCM). The findings revealed that the nano spindle-shaped CeO2 exhibited exposure of crystal faces (111), demonstrating superior catalytic oxidation performance for DCM with a T90 of 337 °C and notably excellent low-temperature catalytic activity (T50 = 192 °C). The primary reaction products were identified as HCl and CO2. Through obvious characterizations, it showed that the excellent catalytic activity presented by CeO2-s catalyst might be related to the higher oxygen vacancy concentration, surface active oxygen content, and superior redox performance caused by specific exposed crystal planes. Meanwhile, CeO2-s catalyst owned outstanding stability, reusability, and water inactivation regeneration, which had tremendous potential in practical treatment.