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BACKGROUND: Posterior capsular opacification is a major complication following cataract surgery, marked by proliferation, migration, epithelial-mesenchymal transition, and fibrosis of residual epithelial cells. Various inflammatory cytokines are upregulated and contribute to the development of posterior capsular opacification. The effect of interleukin-8 on residual epithelial cells has not been fully determined. METHODS: Aqueous humor and anterior capsules samples were collected from cataract surgery. Capsular bags from rats and pigs were cultured in DMEM media. Protein and mRNA expressions were measured using immunoblot and qPCR. Cell migration was assessed using the transwell assay. RESULTS: Interleukin-8 is an early inflammatory factor secreted by residual lens epithelial cells. Migration of lens epithelial cells in aqueous humor positively correlates with interleukin-8 levels, and this effect is inhibited by the receptors of interleukin-8 CXCR1/2 blocker Reparaxin. The expression of tight-junction protein ZO-1 and cell-adhesion protein E-cadherin were down-regulated by administrating interleukin-8, and cell migration of both SRA01/04 cell line in vitro and capsular residual epithelial cells ex vivo were up-regulated via activating RhoA expression and RhoA/GTPase activity. The loss-of- function studies demonstrate that interleukin-8 binding to its receptor CXCR1/2 activates NF-κB/p65, which then turns on the RhoA's expression and RhoA/GTPase activity, and RhoA-modulated the downexpression of E-cadherin and ZO-1 and the increase of cell migration. CONCLUSIONS: The upregulation in interleukin-8 occurs early in posterior capsular opacification and contributes to down-regulating tight-junctions among epithelial cells and elevates cell migration via the CXCR1/2-NF-κB-RhoA signaling pathway. These demonstrated that interleukin-8 could be a potential target for preventing posterior capsular opacification.
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Wheat exhibits complex characteristics during its growth, such as extensive tillering, slender and soft leaves, and severe organ cross-obscuration, posing a considerable challenge in full-cycle phenotypic monitoring. To address this, this study presents a synthesized method based on SFM-MVS (Structure-from-Motion, Multi-View Stereo) processing for handling and segmenting wheat point clouds, covering the entire growth cycle from seedling to grain filling stages. First, a multi-view image acquisition platform was constructed to capture image sequences of wheat plants, and dense point clouds were generated using SFM-MVS technology. High-quality dense point clouds were produced by implementing improved Euclidean clustering combined with centroids, color filtering, and statistical filtering methods. Subsequently, the segmentation of wheat plant stems and leaves was performed using the region growth segmentation algorithm. Although segmentation performance was suboptimal during the tillering, jointing, and booting stages due to the glut leaves and severe overlap, there was a salient improvement in wheat leaf segmentation efficiency over the entire growth cycle. Finally, phenotypic parameters were analyzed across different growth stages, comparing automated measurements of plant height, leaf length, and leaf width with actual measurements. The results demonstrated coefficients of determination ( R 2 ) of 0.9979, 0.9977, and 0.995; root mean square errors (RMSE) of 1.0773 cm, 0.2612 cm, and 0.0335 cm; and relative root mean square errors (RRMSE) of 2.1858%, 1.7483%, and 2.8462%, respectively. These results validate the reliability and accuracy of our proposed workflow in processing wheat point clouds and automatically extracting plant height, leaf length, and leaf width, indicating that our 3D reconstructed wheat model achieves high precision and can quickly, accurately, and non-destructively extract phenotypic parameters. Additionally, plant height, convex hull volume, plant surface area, and Crown area were extracted, providing a detailed analysis of dynamic changes in wheat throughout its growth cycle. ANOVA was conducted across different cultivars, accurately revealing significant differences at various growth stages. This study proposes a convenient, rapid, and quantitative analysis method, offering crucial technical support for wheat plant phenotypic analysis and growth dynamics monitoring, applicable for precise full-cycle phenotypic monitoring of wheat.
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BACKGROUND: Despite the recognized therapeutic potential of programmed cell death protein 1/programmed death-ligand 1 (PD-1/PD-L1) inhibitors in advanced esophageal squamous cell carcinoma (ESCC), their role in neoadjuvant therapy and reliable efficacy biomarkers remain elusive. MATERIALS AND METHODS: We retrospectively analyzed locally advanced ESCC patients who underwent surgery following a 2-cycle platinum and paclitaxel-based treatment, with or without PD-1 inhibitors (January 2020-March 2023). We assessed peripheral blood indexes and tertiary lymphoid structures (TLS) density to evaluate their impact on pathological response and prognosis, leading to a clinical prediction model for treatment efficacy and survival. RESULTS: Of the 157 patients recruited, 106 received immunochemotherapy (ICT) and 51 received chemotherapy (CT) alone. The ICT group demonstrated a superior pathological response rate (PRR) (47.2% vs. 29.4%, p = 0.034) with comparable adverse events and postoperative complications. The ICT group also showed a median disease-free survival (DFS) of 39.8 months, unattained by the CT group. The 1-year DFS and overall survival (OS) rates were 73% and 91% for the ICT group, and 68% and 81% for the CT group, respectively. We found higher baseline activated T cells, lower baseline Treg cells, and a decreased posttreatment total lymphocyte and CD4+/CD8+ ratio predicted an enhanced PRR. Reduced posttreatment CD4+/CD8+ ratio and increased NK cells were associated with prolonged survival, while higher TLS density indicated poorer prognosis. Among ICT group, a lower posttreatment CD4+/CD8+ ratio indicated longer DFS and reduced posttreatment B cells indicated longer OS. A nomogram integrating these predictors was developed to forecast treatment efficacy and survival. CONCLUSION: The combination of PD-1 inhibitors and chemotherapy appears promising for locally advanced ESCC. Evaluating the differentiation status and dynamic changes of peripheral blood immune cells may provide valuable predictive insights into treatment efficacy and prognosis.
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Neoplasias Esofágicas , Carcinoma de Células Escamosas de Esófago , Terapia Neoadyuvante , Humanos , Masculino , Carcinoma de Células Escamosas de Esófago/terapia , Carcinoma de Células Escamosas de Esófago/mortalidad , Carcinoma de Células Escamosas de Esófago/inmunología , Carcinoma de Células Escamosas de Esófago/patología , Carcinoma de Células Escamosas de Esófago/tratamiento farmacológico , Femenino , Terapia Neoadyuvante/métodos , Estudios Retrospectivos , Persona de Mediana Edad , Neoplasias Esofágicas/terapia , Neoplasias Esofágicas/mortalidad , Neoplasias Esofágicas/inmunología , Neoplasias Esofágicas/patología , Neoplasias Esofágicas/tratamiento farmacológico , Anciano , Inmunoterapia/métodos , Subgrupos Linfocitarios/inmunología , Pronóstico , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Resultado del Tratamiento , Paclitaxel/administración & dosificación , Paclitaxel/uso terapéutico , Adulto , EsofagectomíaRESUMEN
Pulmonary hypertension (PH) is a progressive cardiovascular disease, which may lead to severe cardiopulmonary dysfunction. As one of the main PH disease groups, pulmonary artery hypertension (PAH) is characterized by pulmonary vascular remodeling and right ventricular dysfunction. Increased pulmonary artery resistance consequently causes right heart failure, which is the major reason for morbidity and mortality in this disease. Although various treatment strategies have been available, the poor clinical prognosis of patients with PAH reminds us that further studies of the pathological mechanism of PAH are still needed. Inflammation has been elucidated as relevant to the initiation and progression of PAH, and plays a crucial and functional role in vascular remodeling. Many immune cells and cytokines have been demonstrated to be involved in the pulmonary vascular lesions in PAH patients, with the activation of downstream signaling pathways related to inflammation. Consistently, this influence has been found to correlate with the progression and clinical outcome of PAH, indicating that immunity and inflammation may have significant potential in PAH therapy. Therefore, we reviewed the pathogenesis of inflammation and immunity in PAH development, focusing on the potential targets and clinical application of anti-inflammatory and immunosuppressive therapy.
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Inmunoterapia , Hipertensión Arterial Pulmonar , Humanos , Hipertensión Arterial Pulmonar/terapia , Hipertensión Arterial Pulmonar/etiología , Inmunoterapia/métodos , Animales , Inflamación/terapia , Inflamación/patología , Hipertensión Pulmonar/terapia , Hipertensión Pulmonar/etiología , Hipertensión Pulmonar/inmunología , Remodelación VascularRESUMEN
Streptococcus pneumoniae (Sp), a leading cause of community-acquired pneumonia, can spread from the lung into the bloodstream to cause septicemia and meningitis, with a concomitant threefold increase in mortality. Limitations in vaccine efficacy and a rise in antimicrobial resistance have spurred searches for host-directed therapies that target pathogenic immune processes. Polymorphonuclear leukocytes (PMNs) are essential for infection control but can also promote tissue damage and pathogen spread. The major Sp virulence factor, pneumolysin, triggers acute inflammation by stimulating the 12-lipoxygenase (12-LOX) eicosanoid synthesis pathway in epithelial cells. This pathway is required for systemic spread in a mouse pneumonia model and produces a number of bioactive lipids, including hepoxilin A3 (HXA3), a hydroxy epoxide PMN chemoattractant that has been hypothesized to facilitate breach of mucosal barriers. To understand how 12-LOX-dependent inflammation promotes dissemination during Sp lung infection and dissemination, we utilized bronchial stem cell-derived air-liquid interface cultures that lack this enzyme to show that HXA3 methyl ester (HXA3-ME) is sufficient to promote basolateral-to-apical PMN transmigration, monolayer disruption, and concomitant Sp barrier breach. In contrast, PMN transmigration in response to the non-eicosanoid chemoattractant N-formyl-L-methionyl-L-leucyl-phenylalanine (fMLP) did not lead to epithelial disruption or bacterial translocation. Correspondingly, HXA3-ME but not fMLP increased the release of neutrophil elastase (NE) from Sp-infected PMNs. Pharmacologic blockade of NE secretion or activity diminished epithelial barrier disruption and bacteremia after pulmonary challenge of mice. Thus, HXA3 promotes barrier-disrupting PMN transmigration and NE release, pathological events that can be targeted to curtail systemic disease following pneumococcal pneumonia.IMPORTANCEStreptococcus pneumoniae (Sp), a leading cause of pneumonia, can spread from the lung into the bloodstream to cause systemic disease. Limitations in vaccine efficacy and a rise in antimicrobial resistance have spurred searches for host-directed therapies that limit pathologic host immune responses to Sp. Excessive polymorphonuclear leukocyte (PMN) infiltration into Sp-infected airways promotes systemic disease. Using stem cell-derived respiratory cultures that reflect bona fide lung epithelium, we identified eicosanoid hepoxilin A3 as a critical pulmonary PMN chemoattractant that is sufficient to drive PMN-mediated epithelial damage by inducing the release of neutrophil elastase. Inhibition of the release or activity of this protease in mice limited epithelial barrier disruption and bacterial dissemination, suggesting a new host-directed treatment for Sp lung infection.
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Bacteriemia , Elastasa de Leucocito , Neutrófilos , Streptococcus pneumoniae , Animales , Ratones , Streptococcus pneumoniae/inmunología , Elastasa de Leucocito/metabolismo , Bacteriemia/microbiología , Neutrófilos/inmunología , Neutrófilos/metabolismo , Ácido 8,11,14-Eicosatrienoico/análogos & derivados , Ácido 8,11,14-Eicosatrienoico/metabolismo , Pulmón/microbiología , Pulmón/inmunología , Humanos , Células Epiteliales/microbiología , Células Epiteliales/metabolismo , Proteínas Bacterianas/metabolismo , Proteínas Bacterianas/genética , Neumonía Neumocócica/inmunología , Neumonía Neumocócica/microbiología , Modelos Animales de Enfermedad , Ratones Endogámicos C57BL , Estreptolisinas/metabolismo , Araquidonato 12-Lipooxigenasa/metabolismo , Araquidonato 12-Lipooxigenasa/genéticaRESUMEN
Streptococcus pneumoniae (Sp), a leading cause of community-acquired pneumonia, can spread from the lung into the bloodstream to cause septicemia and meningitis, with a concomitant three-fold increase in mortality. Limitations in vaccine efficacy and a rise in antimicrobial resistance have spurred searches for host-directed therapies that target pathogenic immune processes. Polymorphonuclear leukocytes (PMNs) are essential for infection control but can also promote tissue damage and pathogen spread. The major Sp virulence factor, pneumolysin (PLY), triggers acute inflammation by stimulating the 12-lipoxygenase (12-LOX) eicosanoid synthesis pathway in epithelial cells. This pathway is required for systemic spread in a mouse pneumonia model and produces a number of bioactive lipids, including hepoxilin A3 (HXA3), a hydroxy epoxide PMN chemoattractant that has been hypothesized to facilitate breach of mucosal barriers. To understand how 12-LOX-dependent inflammation promotes dissemination during Sp lung infection and dissemination, we utilized bronchial stem cell-derived air-liquid interface (ALI) cultures that lack this enzyme to show that HXA3 methyl ester (HXA3-ME) is sufficient to promote basolateral-to-apical PMN transmigration, monolayer disruption, and concomitant Sp barrier breach. In contrast, PMN transmigration in response to the non-eicosanoid chemoattractant fMLP did not lead to epithelial disruption or bacterial translocation. Correspondingly, HXA3-ME but not fMLP increased release of neutrophil elastase (NE) from Sp-infected PMNs. Pharmacologic blockade of NE secretion or activity diminished epithelial barrier disruption and bacteremia after pulmonary challenge of mice. Thus, HXA3 promotes barrier disrupting PMN transmigration and NE release, pathological events that can be targeted to curtail systemic disease following pneumococcal pneumonia.
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Objective: This study revealed a core regulator and common upstream mechanisms for the multifaceted pathological processes of age-related macular degeneration (AMD) and provided proof-of-concept for this new therapeutic target. Methods: Comprehensive gene expression analysis was performed using RNA sequencing of eye cup from old mice as well as laser-induced choroidal neovascularization (CNV) mouse model. Through integrative analysis and protein-protein interaction (PPI) analysis, common pathways and key transcription factor was identified simultaneously engaged in age-related retinal degeneration and CNV, the two typical pathological process of AMD. Subsequently, the expression changes of Spi1, the key regulator, as well as the alternation of the downstream mechanisms were validated in both models through qRT-PCR, Elisa, flow cytometry and immunofluorescence. Further, we assessed the impact of Spi1 knockdown in vitro and in vivo using gene intervention vectors carried by adeno-associated virus or lentivirus to test its potential as a therapeutic target. Results: Compared to corresponding controls, we found 1,939 and 1,319 genes differentially expressed in eye cups of old and CNV mice respectively. The integrative analysis identified a total of 275 overlapping DEGs, of which 150 genes were co-upregulated. PPI analysis verified a central transcription factor, SPI1. The significant upregulation of Spi1 expression was then validated in both models, accompanied by macrophage polarization towards the M1 phenotype. Finally, SPI1 suppression significantly inhibited M1 polarization of BMDMs and attenuated neovascularization in CNV mice. Conclusion: This study demonstrates that SPI1 exerts a pivotal role in AMD by regulation of macrophage polarization and innate immune response, offering promise as an innovative target for treating AMD.
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Neovascularización Coroidal , Modelos Animales de Enfermedad , Macrófagos , Degeneración Macular , Transactivadores , Animales , Degeneración Macular/inmunología , Degeneración Macular/metabolismo , Degeneración Macular/genética , Degeneración Macular/patología , Ratones , Macrófagos/inmunología , Macrófagos/metabolismo , Neovascularización Coroidal/inmunología , Neovascularización Coroidal/genética , Neovascularización Coroidal/metabolismo , Transactivadores/genética , Transactivadores/metabolismo , Proteínas Proto-Oncogénicas/genética , Proteínas Proto-Oncogénicas/metabolismo , Ratones Endogámicos C57BL , Activación de Macrófagos/genética , Humanos , Perfilación de la Expresión Génica , MasculinoRESUMEN
BACKGROUND: Life-threatening, space-occupying mass effect due to cerebral edema and/or hemorrhagic transformation is an early complication of patients with middle cerebral artery stroke. Little is known about longitudinal trajectories of laboratory and vital signs leading up to radiographic and clinical deterioration related to this mass effect. METHODS: We curated a retrospective data set of 635 patients with large middle cerebral artery stroke totaling 95,463 data points for 10 longitudinal covariates and 40 time-independent covariates. We assessed trajectories of the 10 longitudinal variables during the 72 h preceding three outcomes representative of life-threatening mass effect: midline shift ≥ 5 mm, pineal gland shift (PGS) > 4 mm, and decompressive hemicraniectomy (DHC). We used a "backward-looking" trajectory approach. Patients were aligned based on outcome occurrence time and the trajectory of each variable was assessed before that outcome by accounting for cases and noncases, adjusting for confounders. We evaluated longitudinal trajectories with Cox proportional time-dependent regression. RESULTS: Of 635 patients, 49.0% were female, and the mean age was 69 years. Thirty five percent of patients had midline shift ≥ 5 mm, 24.3% of patients had PGS > 4 mm, and 10.7% of patients underwent DHC. Backward-looking trajectories showed mild increases in white blood cell count (10-11 K/UL within 72 h), temperature (up to half a degree within 24 h), and sodium levels (1-3 mEq/L within 24 h) before the three outcomes of interest. We also observed a decrease in heart rate (75-65 beats per minute) 24 h before DHC. We found a significant association between increased white blood cell count with PGS > 4 mm (hazard ratio 1.05, p value 0.007). CONCLUSIONS: Longitudinal profiling adjusted for confounders demonstrated that white blood cell count, temperature, and sodium levels appear to increase before radiographic and clinical indicators of space-occupying mass effect. These findings will inform the development of multivariable dynamic risk models to aid prediction of life-threatening, space-occupying mass effect.
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The quantitative characterization of rock mass and stress changes induced by mining activities is crucial for structural stability monitoring and disaster early warning. This paper investigates the time-space-intensity distribution of microseismic sources during the pillar-free large-area continuous extraction. Furthermore, it explores a method involving collaborative evolution patterns of the velocity field and spatial b-value to identify stress and structural changes at the panel stope. Results show that anomalous zones in wave velocities and b-values form at the intersections of extraction drifts, strike drifts, cross drifts, and connection roadways influenced by mining activities, as well as in footwall ore-rock contacts, often accompanied by the nucleation of microseismic events. The synergistic use of wave velocity fields and spatial b-value models reveals the relationship between stress migration behavior and stope structure changes due to mining disturbances. The velocity field primarily reflects macroscopic changes in the structure and stress distribution, while spatial b-values further explain stress gradients in specific areas. Additionally, we have advanced the identification of an instability disaster at the connection roadway and cross drift intersection based on increases in wave velocity and abnormal changes in b-value. This paper demonstrates the potential of risk identification using the proposed method, providing insights into predicting geotechnical engineering disasters in complex stress environments.
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The P2Y14 receptor has been proven to be a potential target for IBD. Herein, we designed and synthesized a series of 4-amide-thiophene-2-carboxyl derivatives as novel potent P2Y14 receptor antagonists based on the scaffold hopping strategy. The optimized compound 39 (5-((5-fluoropyridin-2-yl)oxy)-4-(4-methylbenzamido)thiophene-2-carboxylic acid) exhibited subnanomolar antagonistic activity (IC50: 0.40 nM). Moreover, compound 39 demonstrated notably improved solubility, liver microsomal stability, and oral bioavailability. Fluorescent ligand binding assay confirmed that 39 has the binding ability to the P2Y14 receptor, and molecular dynamics (MD) simulations revealed the formation of a unique intramolecular hydrogen bond (IMHB) in the binding conformation. In the experimental colitis mouse model, compound 39 showed a remarkable anti-IBD effect even at low doses. Compound 39, with a potent anti-IBD effect and favorable druggability, can be a promising candidate for further research. In addition, this work lays a strong foundation for the development of P2Y14 receptor antagonists and the therapeutic strategy for IBD.
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Enfermedades Inflamatorias del Intestino , Receptores Purinérgicos P2 , Tiofenos , Animales , Tiofenos/farmacología , Tiofenos/síntesis química , Tiofenos/química , Tiofenos/uso terapéutico , Humanos , Ratones , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Receptores Purinérgicos P2/metabolismo , Relación Estructura-Actividad , Antagonistas del Receptor Purinérgico P2/farmacología , Antagonistas del Receptor Purinérgico P2/química , Antagonistas del Receptor Purinérgico P2/síntesis química , Antagonistas del Receptor Purinérgico P2/uso terapéutico , Masculino , Descubrimiento de Drogas , Amidas/química , Amidas/farmacología , Amidas/síntesis química , Amidas/uso terapéutico , Microsomas Hepáticos/metabolismo , Simulación de Dinámica Molecular , Colitis/tratamiento farmacológicoRESUMEN
With high aphid-repellent activity but low stability, (E)-ß-farnesene (EßF), the major component of the aphid alarm pheromone, can be used as a synergist to insecticides. Some EßF analogues possess both good aphid-repellent activity and stability, but the synergistic effect and related mechanism are still unclear. Therefore, this study investigated the synergistic effect and underlying mechanism of the EßF and its analogue against the aphid Myzus persicae. The results indicated that EßF and the analogue showed significantly synergistic effects to different insecticides, with synergism ratios from 1.524 to 3.446. Mechanistic studies revealed that EßF and the analogue exhibited effective repellent activity, significantly upregulated target OBP genes by 161 to 731%, increased aphid mobility, and thereby enhanced contact with insecticides. This research suggests that the EßF analogue represents a novel synergist for insecticides, with the potential for further application in aphid control owing to its enhanced bioactivity and the possibility of reducing insecticide doses.
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Áfidos , Sinergismo Farmacológico , Insecticidas , Sesquiterpenos , Áfidos/efectos de los fármacos , Animales , Insecticidas/química , Insecticidas/farmacología , Sesquiterpenos/farmacología , Sesquiterpenos/química , Proteínas de Insectos/química , Proteínas de Insectos/genética , Proteínas de Insectos/metabolismo , Prunus persica/química , Prunus persica/parasitología , Repelentes de Insectos/química , Repelentes de Insectos/farmacologíaRESUMEN
Common flue-cured tobacco (Nicotiana tabacum L.) primarily accumulates nicotine, and its flue-cured leaves exhibit a lemon appearance. In contrast, a spontaneous cherry-red variant (CR60) primarily accumulates nornicotine, accompanied by distinctive red dapples on the cured leaves. In this study, suppression of conversion of nicotine to nornicotine by genome editing resulted in decreased nornicotine and N-acyl nornicotines (NacNNs), and the subsequent disappearance of red dapples in CR60. Conversely, overexpression of CYP82E4 increased nornicotine and NacNNs accumulation, inducing a red dapple phenotype in common tobacco. Notably, nicotine conversion triggered significant alterations in leaf total sugars, alkaloids, and nitrogens. Metabolome analyses using 1352 identified compounds indicated nicotine conversion dramatically affected the entire metabolic network and induced unique metabolic responses across diverse genetic backgrounds. Further WGCNA analysis revealed that nicotine conversion caused substantial contents variation of alkaloids, flavonoids and amino acids and derivatives in cured leaves. Overall, this research provides valuable insights into the mechanisms underlying red dapple formation in cherry-red tobacco, elucidating profound influence of nicotine conversion on entire metabolic network.
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Nicotiana , Nicotina , Hojas de la Planta , Proteínas de Plantas , Nicotiana/genética , Nicotiana/metabolismo , Hojas de la Planta/metabolismo , Hojas de la Planta/genética , Nicotina/metabolismo , Nicotina/análogos & derivados , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genética , Sistema Enzimático del Citocromo P-450/metabolismo , Sistema Enzimático del Citocromo P-450/genética , Alcaloides/metabolismo , Regulación de la Expresión Génica de las PlantasRESUMEN
Red palm oil, a natural repository abundant in tocotrienols, tocopherols and carotenoids, is frequently employed as a pigment and nutritional enhancer in food products. The principal aim of this study is to explore the disparities in vitamin A levels, fatty acid profiles and gut microbiota among healthy adults who consume carotenoid-enriched eggs compared to those who consume normal eggs. A total of 200 hens were randomly assigned to either the red palm oil group or the soybean oil group, with the objective of producing carotenoid-enriched eggs and normal eggs. Throughout a six-month, double-blinded, randomized controlled trial, participants were instructed to consume one carotenoid-enriched or normal egg daily at a fixed time. Fecal and blood samples were collected from the participants at the start and conclusion of the six-month intervention period for further analysis. Our findings indicated that there was no significant change in the vitamin A level for daily supplementation with one carotenoid-enriched egg, but there were significant changes in some indicators of fatty acid profiles and gut microbiota compared to the control group of the population. Nonetheless, the consumption of eggs, regardless of carotenoid-enriched eggs or normal eggs, positively influenced dietary habits by reducing the intake of saturated fatty acids and enhancing the intake of monounsaturated and polyunsaturated fatty acids of the population.
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Carotenoides , Pollos , Huevos , Microbioma Gastrointestinal , Vitamina A , Huevos/análisis , Carotenoides/metabolismo , Humanos , Femenino , Microbioma Gastrointestinal/efectos de los fármacos , Animales , Adulto , Método Doble Ciego , Vitamina A/administración & dosificación , Masculino , Ácidos Grasos/metabolismo , Persona de Mediana Edad , Heces/microbiología , Heces/química , Alimentos Fortificados , Aceite de Palma , Adulto JovenRESUMEN
Direct seawater electrolysis technology for sustainable hydrogen production has garnered significant attention, owing to its abundant resource supply and economic potential. However, the complex composition and high chloride concentration of seawater have hindered its practical implementation. In this study, we report an in situ-synthesized dual-phase electrocatalyst (HPS-NiMo), comprising an amorphous phosphide protective outer phase and a crystalline alloy inner phase with supplementary sulfur active sites, to improve the kinetics of direct seawater electrolysis. The HPS-NiMo exhibits long-term stability, remaining stable for periods exceeding 120 h at 200 mA cm-2; moreover, it lowers the required operating voltage to â¼1.8 V in natural seawater. The chlorine chemistry, corrosion during direct natural seawater electrolysis, and mechanism behind the high-performing catalysts are discussed. We also investigated the possibility of recovering the anode precipitates, which inevitably occurs during seawater electrolysis.
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Cypermethrin (CP) is a neurotoxic insecticide found accumulated in oysters, one of the most commonly consumed seafoods, posing potential health risks to the human body. We designed a gastrointestinal tracing method allowing for accurate quantification of the propulsion of chyme and further established the mouse in vivo digestion model to explore the behavior of CP in the digestion of raw, steamed, and roasted oysters. The results showed that bioaccumulation of CP in oysters may be accompanied by the biotransformation of CP. Thermal processing decreased both the CP content in oysters and its bioaccessibility. The small intestine is the main site for CP digestion and absorption. The cis-isomers of CP might finally accumulate in the body at a higher ratio and further become the predominant configuration for toxic effects. Taken together, the study contributes to the risk assessment of the dietary exposure of CP from aquatic products.
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Crassostrea , Digestión , Tracto Gastrointestinal , Insecticidas , Piretrinas , Animales , Piretrinas/metabolismo , Piretrinas/análisis , Crassostrea/metabolismo , Crassostrea/química , Tracto Gastrointestinal/metabolismo , Ratones , Insecticidas/metabolismo , Insecticidas/química , Isomerismo , Mariscos/análisis , Contaminación de Alimentos/análisis , Humanos , Masculino , Manipulación de Alimentos/métodosRESUMEN
BACKGROUND: Ototoxicity is a major side effect of many broadly used aminoglycoside antibiotics (AGs) and no FDA-approved otoprotective drug is available currently. The zebrafish has recently become a valuable model to investigate AG-induced hair cell toxicity and an expanding list of otoprotective compounds that block the uptake of AGs have been identified from zebrafish-based screening; however, it remains to be established whether inhibiting intracellular cell death pathway(s) constitutes an effective strategy to protect against AG-induced ototoxicity. RESULTS: We used the zebrafish model as well as in vitro cell-based assays to investigate AG-induced cell death and found that ferroptosis is the dominant type of cell death induced by neomycin. Neomycin stimulates lipid reactive oxygen species (ROS) accumulation through mitochondrial pathway and blocking mitochondrial ferroptosis pathway effectively protects neomycin-induced cell death. We screened an alkaloid natural compound library and identified seven small compounds that protect neomycin-induced ototoxicity by targeting ferroptosis pathway: six of them are radical-trapping agents (RTAs) while the other one (ellipticine) regulates intracellular iron homeostasis, which is essential for the generation of lipid ROS to stimulate ferroptosis. CONCLUSIONS: Our study demonstrates that blocking intracellular ferroptosis pathway is an alternative strategy to ameliorate neomycin-induced ototoxicity and provides multiple hit compounds for further otoprotective drug development.
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Due to the increase in emission requirements for non-road vehicles in many countries and the reduction of agricultural personnel, tractors are developing towards high horsepower and electrification. According to the working conditions of high-horsepower tractors, a hydromechanical continuously variable transmission (HMCVT) is designed for hybrid tractors. Taking a tractor equipped with this transmission as the research object, an equivalent factor global optimization model was established and a genetic algorithm was used to optimize the equivalent factor S offline to obtain the optimal equivalent factor of the tractor under different operating mileage and the initial state of charge (SOC) of battery. By using the optimized equivalent factor, the tractor can be in the charge depleting (CD) mode for a longer time on the premise of making full use of the energy in the battery, so as to improve the auxiliary ability of the motor in the whole operation cycle to reduce the fuel consumption of the tractor. The effectiveness of the control strategy is verified by MATLAB/Simulink and hardware in the loop (HIL) tests, and the fuel economy of tractors is improved by 2.939% and 3.909% respectively in the two tests.
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PURPOSE: To evaluate the association between facet joints cross-sectional area asymmetry (FCAA) and cervical intervertebral disc herniation (CDH). METHODS: Overall, we retrospectively recruited 390 consecutive patients with CDH who underwent surgical treatment at our institution and 50 normal participants. Clinical variables and radiological findings related to CDH were collected. RESULTS: Patients with CDH were more likely to have a higher absolute value of the facet asymmetry factor (FAF) (p < .001), in which the FAF value of the left group was significantly higher than the other groups (p < .001) and the right group was lower than the central group (p < .001). 9.62% (C3/4), 12.19% (C4/5), 8.70% (C5/6), and 8.14% (C6/7) were determined as cutoff values for each variable that maximized sensitivity and specificity. Furthermore, multivariate analysis showed that cross-sectional area asymmetry of the facet joint (FCAA) was an independent risk factor for the occurrence of CDH. Also, the Chi-square test showed a significant difference in the distribution of the degeneration classification of the disc between the facet-degenerated group and the nondegenerated group at C5/6 (p = 0.026) and C6/7 (p = 0.005) in the facet asymmetry (FA) group. CONCLUSIONS: FCAA is evaluated as an independent risk factor for CDH and associated with the orientation of disc herniation. And facet joint orientation may also play a role in cervical spine degeneration rather than facet joint tropism.
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Vértebras Cervicales , Desplazamiento del Disco Intervertebral , Articulación Cigapofisaria , Humanos , Desplazamiento del Disco Intervertebral/diagnóstico por imagen , Desplazamiento del Disco Intervertebral/cirugía , Masculino , Femenino , Persona de Mediana Edad , Articulación Cigapofisaria/diagnóstico por imagen , Articulación Cigapofisaria/cirugía , Vértebras Cervicales/diagnóstico por imagen , Vértebras Cervicales/cirugía , Adulto , Estudios Retrospectivos , AncianoRESUMEN
OBJECTIVE: Internet-Based Cognitive Behavioral Therapy (iCBT) is an innovative modality of cognitive-behavioral intervention that presents a promising therapeutic strategy for individuals diagnosed with binge spectrum eating disorders. This study employed a meta-analysis methodology to assess the clinical effectiveness and acceptability of iCBT. METHODS: We conducted searches in databases such as PubMed, Embase, Web of Science, Cochrane Library, and PsycINFO, collecting literature that met the inclusion criteria until August 5, 2023. RESULTS: A comprehensive analysis was conducted, encompassing a total of 11 randomized controlled studies that satisfied the predetermined criteria for inclusion. The summary results demonstrated that iCBT could significantly improve the pathological features related to eating in patients with binge spectrum eating disorders and also significantly reduce the frequency of binge episodes. Additionally, iCBT could ameliorate the depressive and anxious emotions of patients with binge spectrum eating disorders and boost their self-esteem. Furthermore, a notable disparity in dropout rates was seen in comparison to the control group. LIMITATION: Heterogeneity across studiesï¼limitations of self-assessment scales and potential publication bias. CONCLUSION: iCBT can effectively assist patients with binge spectrum eating disorders in improving clinical symptoms. However, it is important to use caution when interpreting the findings of this study, as there are limitations pertaining to the quantity and quality of the included studies.
Asunto(s)
Trastorno por Atracón , Terapia Cognitivo-Conductual , Humanos , Terapia Cognitivo-Conductual/métodos , Trastorno por Atracón/terapia , Trastorno por Atracón/psicología , Adulto , Resultado del Tratamiento , Intervención basada en la Internet , Internet , Ensayos Clínicos Controlados Aleatorios como Asunto , Autoimagen , FemeninoRESUMEN
Fearful, angry, and disgusted facial expressions are evolutionarily salient and convey different types of threat signals. However, it remains unclear whether these three expressions impact sensory perception and attention in the same way. The present ERP study investigated the temporal dynamics underlying the processing of different types of threatening faces and the impact of attentional resources employed during a perceptual load task. Participants were asked to judge the length of bars superimposed over faces presented in the center of the screen. A mass univariate statistical approach was used to analyze the EEG data. Behaviorally, task accuracy was significantly reduced following exposure to fearful faces relative to neutral distractors, independent of perceptual load. The ERP results revealed that the P1 amplitude over the right hemisphere was found to be enhanced for fearful relative to disgusted faces, reflecting the rapid and coarse detection of fearful cues. The N170 responses elicited by fearful, angry, and disgusted faces were larger than those elicited by neutral faces, suggesting the largely automatic and preferential processing of threats. Furthermore, the early posterior negativity (EPN) component yielded increased responses to fearful and angry faces, indicating prioritized attention to stimuli representing acute threats. Additionally, perceptual load exerted a pronounced influence on the EPN and late positive potential (LPP), with larger responses observed in the low perceptual load condition, indicating goal-directed cognitive processing. Overall, the early sensory processing of fearful, angry, and disgusted faces is characterized by differential sensitivity in capturing attention automatically, despite the importance of these facial signals for survival. Fearful faces produce a strong interference effect and are processed with higher priority than angry and disgusted ones.