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Objectives: This study aims to assess the predictive capability of synthetic MRI in assessing neurodevelopmental outcomes for extremely preterm neonates with low-grade Germinal Matrix-Intraventricular Hemorrhage (GMH-IVH). The study also investigates the potential enhancement of predictive performance by combining relaxation times from different brain regions. Materials and methods: In this prospective study, 80 extremely preterm neonates with GMH-IVH underwent synthetic MRI around 38 weeks, between January 2020 and June 2022. Neurodevelopmental assessments at 18 months of corrected age categorized the infants into two groups: those without disability (n = 40) and those with disability (n = 40), with cognitive and motor outcome scores recorded. T1, T2 relaxation times, and Proton Density (PD) values were measured in different brain regions. Logistic regression analysis was utilized to correlate MRI values with neurodevelopmental outcome scores. Synthetic MRI metrics linked to disability were identified, and combined models with independent predictors were established. The predictability of synthetic MRI metrics in different brain regions and their combinations were evaluated and compared with internal validation using bootstrap resampling. Results: Elevated T1 and T2 relaxation times in the frontal white matter (FWM) and caudate were significantly associated with disability (p < 0.05). The T1-FWM, T1-Caudate, T2-FWM, and T2-Caudate models exhibited overall predictive performance with AUC values of 0.751, 0.695, 0.856, and 0.872, respectively. Combining these models into T1-FWM + T1-Caudate + T2-FWM + T2-Caudate resulted in an improved AUC of 0.955, surpassing individual models (p < 0.05). Bootstrap resampling confirmed the validity of the models. Conclusion: Synthetic MRI proves effective in early predicting adverse outcomes in extremely preterm infants with GMH-IVH. The combination of T1-FWM + T1-Caudate + T2-FWM + T2-Caudate further enhances predictive accuracy, offering valuable insights for early intervention strategies.
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Cancer remains a significant risk to human health. Nanomedicine is a new multidisciplinary field that is garnering a lot of interest and investigation. Nanomedicine shows great potential for cancer diagnosis and treatment. Specifically engineered nanoparticles can be employed as contrast agents in cancer diagnostics to enable high sensitivity and high-resolution tumor detection by imaging examinations. Novel approaches for tumor labeling and detection are also made possible by the use of nanoprobes and nanobiosensors. The achievement of targeted medication delivery in cancer therapy can be accomplished through the rational design and manufacture of nanodrug carriers. Nanoparticles have the capability to effectively transport medications or gene fragments to tumor tissues via passive or active targeting processes, thus enhancing treatment outcomes while minimizing harm to healthy tissues. Simultaneously, nanoparticles can be employed in the context of radiation sensitization and photothermal therapy to enhance the therapeutic efficacy of malignant tumors. This review presents a literature overview and summary of how nanotechnology is used in the diagnosis and treatment of malignant tumors. According to oncological diseases originating from different systems of the body and combining the pathophysiological features of cancers at different sites, we review the most recent developments in nanotechnology applications. Finally, we briefly discuss the prospects and challenges of nanotechnology in cancer.
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Neoplasias , Humanos , Neoplasias/diagnóstico , Neoplasias/terapia , Neoplasias/diagnóstico por imagen , Neoplasias/genética , Nanopartículas/uso terapéutico , Nanopartículas/química , Nanotecnología/tendencias , Nanomedicina/tendencias , Sistemas de Liberación de MedicamentosRESUMEN
Inflammation is a protective stress response triggered by external stimuli, with 5-lipoxygenase (5LOX) playing a pivotal role as a potent mediator of the leukotriene (Lts) inflammatory pathway. Nordihydroguaiaretic acid (NDGA) functions as a natural orthosteric inhibitor of 5LOX, while 3-acetyl-11-keto-ß-boswellic acid (AKBA) acts as a natural allosteric inhibitor targeting 5LOX. However, the precise mechanisms of inhibition have remained unclear. In this study, Gaussian accelerated molecular dynamics (GaMD) simulation was employed to elucidate the inhibitory mechanisms of NDGA and AKBA on 5LOX. It was found that the orthosteric inhibitor NDGA was tightly bound in the protein's active pocket, occupying the active site and inhibiting the catalytic activity of the 5LOX enzyme through competitive inhibition. The binding of the allosteric inhibitor AKBA induced significant changes at the distal active site, leading to a conformational shift of residues 168-173 from a loop to an α-helix and significant negative correlated motions between residues 285-290 and 375-400, reducing the distance between these segments. In the simulation, the volume of the active cavity in the stable conformation of the protein was reduced, hindering the substrate's entry into the active cavity and, thereby, inhibiting protein activity through allosteric effects. Ultimately, Markov state models (MSM) were used to identify and classify the metastable states of proteins, revealing the transition times between different conformational states. In summary, this study provides theoretical insights into the inhibition mechanisms of 5LOX by AKBA and NDGA, offering new perspectives for the development of novel inhibitors specifically targeting 5LOX, with potential implications for anti-inflammatory drug development.
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Araquidonato 5-Lipooxigenasa , Inhibidores de la Lipooxigenasa , Cadenas de Markov , Simulación de Dinámica Molecular , Araquidonato 5-Lipooxigenasa/metabolismo , Araquidonato 5-Lipooxigenasa/química , Inhibidores de la Lipooxigenasa/farmacología , Inhibidores de la Lipooxigenasa/química , Humanos , Dominio Catalítico , Unión Proteica , Masoprocol/farmacología , Masoprocol/química , Conformación ProteicaRESUMEN
Background: Elevated PPP4C expression has been associated with poor prognostic implications for patients suffering from lung adenocarcinoma (LUAD). The extent to which PPP4C affects immune cell infiltration in LUAD, as well as the importance of associated genes in clinical scenarios, still requires thorough investigation. Methods: In our investigation, we leveraged both single-cell and comprehensive RNA sequencing data, sourced from LUAD patients, in our analysis. This study also integrated datasets of immune-related genes from InnateDB into the framework. Our expansive evaluation employed various analytical techniques; these included pinpointing differentially expressed genes, constructing WGCNA, implementing Cox proportional hazards models. We utilized these methods to investigate the gene expression profiles of PPP4C within the context of LUAD and to clarify its potential prognostic value for patients. Subsequent steps involved validating the observed enhancement of PPP4C expression in LUAD samples through a series of experimental approaches. The array comprised immunohistochemistry staining, Western blotting, quantitative PCR, and a collection of cell-based assays aimed at evaluating the influence of PPP4C on the proliferative and migratory activities of LUAD cells. Results: In lung cancer, elevated expression levels of PPP4C were observed, correlating with poorer patient prognoses. Validation of increased PPP4C levels in LUAD specimens was achieved using immunohistochemical techniques. Experimental investigations have substantiated the role of PPP4C in facilitating cellular proliferation and migration in LUAD contexts. Furthermore, an association was identified between the expression of PPP4C and the infiltration of immune cells in these tumors. A prognostic framework, incorporating PPP4C and immune-related genes, was developed and recognized as an autonomous predictor of survival in individuals afflicted with LUAD. This prognostic tool has demonstrated considerable efficacy in forecasting patient survival and their response to immunotherapeutic interventions. Conclusion: The involvement of PPP4C in LUAD is deeply intertwined with the tumor's immune microenvironment. PPP4C's over-expression is associated with negative clinical outcomes, promoting both tumor proliferation and spread. A prognostic framework based on PPP4C levels may effectively predict patient prognoses in LUAD, as well as the efficacy of immunotherapy strategy. This research sheds light on the mechanisms of immune interaction in LUAD and proposes a new strategy for treatment.
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Adenocarcinoma del Pulmón , Inmunoterapia , Neoplasias Pulmonares , Fosfoproteínas Fosfatasas , Microambiente Tumoral , Femenino , Humanos , Masculino , Adenocarcinoma del Pulmón/inmunología , Adenocarcinoma del Pulmón/terapia , Biomarcadores de Tumor/genética , Línea Celular Tumoral , Perfilación de la Expresión Génica , Regulación Neoplásica de la Expresión Génica , Inmunoterapia/métodos , Neoplasias Pulmonares/inmunología , Neoplasias Pulmonares/terapia , Multiómica , Fosfoproteínas Fosfatasas/genética , Pronóstico , Análisis de la Célula Individual/métodos , Transcriptoma , Microambiente Tumoral/genética , Microambiente Tumoral/inmunologíaRESUMEN
OBJECTIVES: To investigate potential of enhancing image quality, maintaining interobserver consensus, and elevating disease diagnostic efficacy through the implementation of deep learning-based reconstruction (DLR) processing in 3.0 T cervical spine fast magnetic resonance imaging (MRI) images, compared with conventional images. METHODS: The 3.0 T cervical spine MRI images of 71 volunteers were categorized into two groups: sagittal T2-weighted short T1 inversion recovery without DLR (Sag T2w-STIR) and with DLR (Sag T2w-STIR-DLR). The assessment covered artifacts, perceptual signal-to-noise ratio, clearness of tissue interfaces, fat suppression, overall image quality, and the delineation of spinal cord, vertebrae, discs, dopamine, and joints. Spanning canal stenosis, neural foraminal stenosis, herniated discs, annular fissures, hypertrophy of the ligamentum flavum or vertebral facet joints, and intervertebral disc degeneration were evaluated by three impartial readers. RESULTS: Sag T2w-STIR-DLR images exhibited markedly superior performance across quality indicators (median = 4 or 5) compared to Sag T2w-STIR sequences (median = 3 or 4) (p < 0.001). No statistically significant differences were observed between the two sequences in terms of diagnosis and grading (p > 0.05). The interobserver agreement for Sag T2w-STIR-DLR images (0.604-0.931) was higher than the other (0.545-0.853), Sag T2w-STIR-DLR (0.747-1.000) demonstrated increased concordance between reader 1 and reader 3 in comparison to Sag T2w-STIR (0.508-1.000). Acquisition time diminished from 364 to 197 s through the DLR scheme. CONCLUSIONS: Our investigation establishes that 3.0 T fast MRI images subjected to DLR processing present heightened image quality, bolstered diagnostic performance, and reduced scanning durations for cervical spine MRI compared with conventional sequences.
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Vértebras Cervicales , Aprendizaje Profundo , Imagen por Resonancia Magnética , Espondilosis , Humanos , Espondilosis/diagnóstico por imagen , Imagen por Resonancia Magnética/métodos , Masculino , Adulto , Femenino , Vértebras Cervicales/diagnóstico por imagen , Persona de Mediana Edad , Anciano , Procesamiento de Imagen Asistido por Computador/métodosRESUMEN
Diffusion Kurtosis Imaging (DKI)-derived metrics are recognized as indicators of maturation in neonates with low-grade germinal matrix and intraventricular hemorrhage (GMH-IVH). However, it is not yet known if these factors are associated with neurodevelopmental outcomes. The objective of this study was to acquire DKI-derived metrics in neonates with low-grade GMH-IVH, and to demonstrate their association with later neurodevelopmental outcomes. In this prospective study, neonates with low-grade GMH-IVH and control neonates were recruited, and DKI were performed between January 2020 and March 2021. These neonates underwent the Bayley Scales of Infant Development test at 18 months of age. Mean kurtosis (MK), radial kurtosis (RK) and gray matter values were measured. Spearman correlation analyses were conducted for the measured values and neurodevelopmental outcome scores. Forty controls (18 males, average gestational age (GA) 30 weeks ± 1.3, corrected GA at MRI scan 38 weeks ± 1) and thirty neonates with low-grade GMH-IVH (13 males, average GA 30 weeks ± 1.5, corrected GA at MRI scan 38 weeks ± 1). Neonates with low-grade GMH-IVH exhibited lower MK and RK values in the PLIC and the thalamus (P < 0.05). The MK value in the thalamus was associated with Mental Development Index (MDI) (r = 0.810, 95% CI 0.695-0.13; P < 0.001) and Psychomotor Development Index (PDI) (r = 0.852, 95% CI 0.722-0.912; P < 0.001) scores. RK value in the caudate nucleus significantly and positively correlated with MDI (r = 0.496, 95% CI 0.657-0.933; P < 0.001) and PDI (r = 0.545, 95% CI 0.712-0.942; P < 0.001) scores. The area under the curve (AUC) were used to assess diagnostic performance of MK and RK in thalamus (AUC = 0.866, 0.787) and caudate nucleus (AUC = 0.833, 0.671) for predicting neurodevelopmental outcomes. As quantitative neuroimaging markers, MK in thalamus and RK in caudate nucleus may help predict neurodevelopmental outcomes in neonates with low-grade GMH-IVH.
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Imagen de Difusión Tensora , Humanos , Masculino , Recién Nacido , Femenino , Imagen de Difusión Tensora/métodos , Estudios Prospectivos , Hemorragia Cerebral/diagnóstico por imagen , Trastornos del Neurodesarrollo/diagnóstico por imagen , Trastornos del Neurodesarrollo/etiología , Lactante , Hemorragia Cerebral Intraventricular/diagnóstico por imagen , Edad Gestacional , Desarrollo Infantil , Sustancia Gris/diagnóstico por imagen , Sustancia Gris/patologíaRESUMEN
Customizing the engineering targeted thermal deformations is of vital significance for dimensional stability or shape morphing in materials and structures. However, current metamaterials are designed solely in the homogeneous form to respond only to the time-variant temperature (TVT) stimuli, far behind the practical engineering scenario and demands. Here, a new strategy is originally proposed and experimentally verified to design a series of both homogeneous and inhomogeneous multimaterial metamaterials, which uniquely output various thermal deformation modes, responding to time-variant and space-variant temperature (SVT) stimuli. Specifically, in addition to the regular isotropic thermal deformations, the metamaterials could exclusively output the entirely different positive and negative thermal deformations along the two orthotropic directions. Besides, stimulated by both TVT and SVT, the metamaterials provide more flexibility to customize the targeted thermal deformations. That is, the uniform thermal deformations could be well customized by the metamaterials stimulated by either TVT or SVT. More importantly, the customizability is remarkably broadened, as the nonuniform, specifically, mathematicized linear and nonlinear thermal deformations, are elaborately customized. Overall, these originally devised metamaterials open a new avenue for the purpose of customizing the engineering targeted thermal deformations in various modes under both TVT and SVT stimuli.
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Background: Messenger RNA (mRNA)-based immunogene therapy holds significant promise as an emerging tumor therapy approach. However, the delivery efficiency of existing mRNA methods and their effectiveness in stimulating anti-tumor immune responses require further enhancement. Tumor cell lysates containing tumor-specific antigens and biomarkers can trigger a stronger immune response to tumors. In addition, strategies involving multiple gene therapies offer potential optimization paths for tumor gene treatments. Methods: Based on the previously developed ideal mRNA delivery system called DOTAP-mPEG-PCL (DMP), which was formed through the self-assembly of 1.2-dioleoyl-3-trimethylammonium-propane (DOTAP) and methoxypoly (ethylene glycol)-b-poly (ε-caprolactone) (mPEG-PCL), we introduced a fused cell-penetrating peptide (fCPP) into the framework and encapsulated tumor cell lysates to form a novel nanovector, termed CLSV system (CLS: CT26 tumor cell lysate, V: nanovector). This system served a dual purpose of facilitating the delivery of two mRNAs and enhancing tumor immunogene therapy through tumor cell lysates. Results: The synthesized CLSV system had an average size of 241.17 nm and a potential of 39.53 mV. The CLSV system could not only encapsulate tumor cell lysates, but also deliver two mRNAs to tumor cells simultaneously, with a transfection efficiency of up to 60%. The CLSV system effectively activated the immune system such as dendritic cells to mature and activate, leading to an anti-tumor immune response. By loading Bim-encoded mRNA and IL-23A-encoded mRNA, CLSV/Bim and CLSV/IL-23A complexes were formed, respectively, to further induce apoptosis and anti-tumor immunity. The prepared CLSV/dual-mRNA complex showed significant anti-cancer effects in multiple CT26 mouse models. Conclusion: Our results suggest that the prepared CLSV system is an ideal delivery system for dual-mRNA immunogene therapy.
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Neoplasias del Colon , Terapia Genética , Inmunoterapia , Nanopartículas , ARN Mensajero , Animales , ARN Mensajero/genética , ARN Mensajero/administración & dosificación , Línea Celular Tumoral , Neoplasias del Colon/terapia , Neoplasias del Colon/genética , Terapia Genética/métodos , Inmunoterapia/métodos , Nanopartículas/química , Ratones , Ratones Endogámicos BALB C , Péptidos de Penetración Celular/química , Polietilenglicoles/química , Humanos , Poliésteres/química , Femenino , Compuestos de Amonio Cuaternario , Ácidos Grasos MonoinsaturadosRESUMEN
Introduction: Sensorineural hearing loss (SNHL) can arise from a diverse range of congenital and acquired factors. Detecting it early is pivotal for nurturing speech, language, and cognitive development in children with SNHL. In our study, we utilized synthetic magnetic resonance imaging (SyMRI) to assess alterations in both gray and white matter within the brains of children affected by SNHL. Methods: The study encompassed both children diagnosed with SNHL and a control group of children with normal hearing {1.5-month-olds (n = 52) and 3-month-olds (n = 78)}. Participants were categorized based on their auditory brainstem response (ABR) threshold, delineated into normal, mild, moderate, and severe subgroups.Clinical parameters were included and assessed the correlation with SNHL. Quantitative analysis of brain morphology was conducted using SyMRI scans, yielding data on brain segmentation and relaxation time.Through both univariate and multivariate analyses, independent factors predictive of SNHL were identified. The efficacy of the prediction model was evaluated using receiver operating characteristic (ROC) curves, with visualization facilitated through the utilization of a nomogram. It's important to note that due to the constraints of our research, we worked with a relatively small sample size. Results: Neonatal hyperbilirubinemia (NH) and children with inner ear malformation (IEM) were associated with the onset of SNHL both at 1.5 and 3-month groups. At 3-month group, the moderate and severe subgroups exhibited elevated quantitative T1 values in the inferior colliculus (IC), lateral lemniscus (LL), and middle cerebellar peduncle (MCP) compared to the normal group. Additionally, WMV, WMF, MYF, and MYV were significantly reduced relative to the normal group. Additionally, SNHL-children with IEM had high T1 values in IC, and LL and reduced WMV, WMF, MYV and MYF values as compared with SNHL-children without IEM at 3-month group. LL-T1 and WMF were independent risk factors associated with SNHL. Consequently, a prediction model was devised based on LL-T1 and WMF. ROC for training set, validation set and external set were 0.865, 0.806, and 0.736, respectively. Conclusion: The integration of T1 quantitative values and brain volume segmentation offers a valuable tool for tracking brain development in children affected by SNHL and assessing the progression of the condition's severity.
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This study investigates abnormalities in cerebellar-cerebral static and dynamic functional connectivity among patients with acute pontine infarction, examining the relationship between these connectivity changes and behavioral dysfunction. Resting-state functional magnetic resonance imaging was utilized to collect data from 45 patients within seven days post-pontine infarction and 34 normal controls. Seed-based static and dynamic functional connectivity analyses identified divergences in cerebellar-cerebral connectivity features between pontine infarction patients and normal controls. Correlations between abnormal functional connectivity features and behavioral scores were explored. Compared to normal controls, left pontine infarction patients exhibited significantly increased static functional connectivity within the executive, affective-limbic, and motor networks. Conversely, right pontine infarction patients demonstrated decreased static functional connectivity in the executive, affective-limbic, and default mode networks, alongside an increase in the executive and motor networks. Decreased temporal variability of dynamic functional connectivity was observed in the executive and default mode networks among left pontine infarction patients. Furthermore, abnormalities in static and dynamic functional connectivity within the executive network correlated with motor and working memory performance in patients. These findings suggest that alterations in cerebellar-cerebral static and dynamic functional connectivity could underpin the behavioral dysfunctions observed in acute pontine infarction patients.
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Infartos del Tronco Encefálico , Cerebelo , Imagen por Resonancia Magnética , Vías Nerviosas , Puente , Humanos , Masculino , Femenino , Persona de Mediana Edad , Cerebelo/fisiopatología , Cerebelo/diagnóstico por imagen , Vías Nerviosas/fisiopatología , Vías Nerviosas/diagnóstico por imagen , Puente/diagnóstico por imagen , Puente/fisiopatología , Infartos del Tronco Encefálico/fisiopatología , Infartos del Tronco Encefálico/diagnóstico por imagen , Anciano , Adulto , Corteza Cerebral/fisiopatología , Corteza Cerebral/diagnóstico por imagen , Red Nerviosa/fisiopatología , Red Nerviosa/diagnóstico por imagenRESUMEN
In natural kaolinite lattices, Al3+ can potentially be substituted by cations such as Mg2+, Ca2+, and Fe3+, thereby influencing its adsorption characteristics towards rare earth elements like Sc3+. Density functional theory (DFT) has emerged as a crucial tool in the study of adsorption phenomena, particularly for understanding the complex interactions of rare earth elements with clay minerals. This study employed DFT to investigate the impact of these three dopant elements on the adsorption of hydrated Sc3+ on the kaolinite (001) Al-OH surface. We discerned that the optimal adsorption configuration for hydrated Sc3+ is Sc(H2O)83+, with a preference for adsorption at the deprotonated Ou sites. Among the dopants, Mg doping exhibited superior stability with a binding energy of -4.311 eV and the most negative adsorption energy of -1104.16 kJ/mol. Both Mg and Ca doping enhanced the covalency of the Al-O bond, leading to a subtle shift in the overall density of states towards higher energies, thereby augmenting the reactivity of the O atoms. In contrast, Fe doping caused a pronounced shift in the density of states towards lower energies. Compared to the undoped kaolinite, Mg and Ca doping further diminished the adsorption energy of hydrated Sc3+ and increased its coordination number, while Fe doping elevated the adsorption energy. This study offers profound insights into understanding the role of dopant elements in the adsorption of hydrated Sc3+ on kaolinite.
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Lead halide perovskites (LHPs) containing organic parts are emerging optoelectronic materials with a wide range of applications thanks to their high optical absorption, carrier mobility, and easy preparation methods. They possess spin-dependent properties, such as strong spin-orbit coupling (SOC), and are promising for spintronics. The Rashba effect in LHPs can be manipulated by a magnetic field and a polarized light field. Considering the surfaces and interfaces of LHPs, light polarization-dependent optoelectronics of LHPs has attracted attention, especially in terms of spin-dependent photocurrents (SDPs). Currently, there are intense efforts being made in the identification and separation of SDPs and spin-to-charge interconversion in LHP. Here, we provide a comprehensive review of second-order nonlinear photocurrents in LHP in regard to spintronics. First, a detailed background on Rashba SOC and its related effects (including the inverse Rashba-Edelstein effect) is given. Subsequently, nonlinear photo-induced effects leading to SDPs are presented. Then, SDPs due to the photo-induced inverse spin Hall effect and the circular photogalvanic effect, together with photocurrent due to the photon drag effect, are compared. This is followed by the main focus of nonlinear photocurrents in LHPs containing organic parts, starting from fundamentals related to spin-dependent optoelectronics. Finally, we conclude with a brief summary and future prospects.
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Chiral plasmonic nanocrystals have recently attracted increasing attention in circular polarization-dependent photocatalysis driven by hot carriers. While being concealed in traditional ensemble measurements, the individual chiral photocatalytic activity of nanocrystals can exclusively be revealed by directly correlating the circular differential photocurrent response to helical morphologies using single-particle techniques. Herein, we develop a method named circular differential photocurrent mapping (CDPM) and demonstrate that CDPM can be used to characterize the circular differential hot electron (CDHE) response from individual Au nanohelicoids (AuNHs) on a TiO2 photoanode in a photoelectrochemical cell. The single-particle circular differential scattering and CDHE measurements were interpreted with calculations performed on a model in direct correlation to the helical morphologies of the nanocrystal. While CDHE response was found inactive at a dipolar resonance of 750 nm, helicity-convoluted sites of HE generation were identified on the AuNH at a specific higher-order mode of 550 nm, resulting in a significant response of CDHE in association with the handedness of the AuNH. Details of circular differential contributions were further resolved by examining the efficiencies of individual AuNHs in terms of g-factors. Our study provides a powerful microscopic method at the single-particle level for the photocatalytic characterization of chiral nanocrystals, gaining fundamental insights into the photocatalysis of chirality, especially toward plasmon-induced asymmetrical photochemistry or photoelectrochemistry.
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Movement dynamics in the nucleus involve various biological processes, including DNA repair, which is crucial for cancer prevention. Changes in the movement of the components of the nucleus indicate the changes in movement dynamics in the nucleus. In Schizosaccharomyces pombe, the inner nuclear membrane protein Bqt4 plays an essential role in attaching telomeres to the nuclear envelope. We observed that the deletion of bqt4+ caused a significant decrease in the mean square displacement (MSD) calculated from the distance between the nucleolar center and spindle pole body (SPB), hereafter referred to as MSD(SPB-Nucleolus). The MSD(SPB-Nucleolus) decrease in bqt4Δ was microtubule-dependent. The Rap1-binding ability loss mutant, bqt4F46A, and nonspecific DNA-binding ability mutants, bqt43E-A, did not exhibit an MSD(SPB-Nucleolus) decrease compared to the WT. Moreover, the bqt43E-Arap1Δ double mutant and 1-262 amino acids truncated mutant bqt4ΔN (263-432), which does not have either Rap1-binding or nonspecific DNA-binding abilities, did not exhibit the MSD(SPB-Nucleolus) decrease to the same extent as bqt4Δ. These results suggest that the unknown function of Bqt4 in the C-terminal domain is essential for the maintenance of the pattern of relative movement between SPB and the nucleolus.
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Nucléolo Celular , Proteínas de Unión al ADN , Proteínas Nucleares , Proteínas de Schizosaccharomyces pombe , Schizosaccharomyces , Cuerpos Polares del Huso , Schizosaccharomyces/genética , Schizosaccharomyces/metabolismo , Proteínas de Schizosaccharomyces pombe/metabolismo , Proteínas de Schizosaccharomyces pombe/genética , Nucléolo Celular/metabolismo , Cuerpos Polares del Huso/metabolismo , Mutación , Microtúbulos/metabolismo , Proteínas de la Membrana/metabolismo , Proteínas de la Membrana/genética , Unión ProteicaRESUMEN
Background: Accelerated magnetic resonance imaging sequences reconstructed using the vendor-provided Recon deep learning algorithm (DL-MRI) were found to be more likely than conventional magnetic resonance imaging (MRI) sequences to detect subacromial (SbA) bursal thickening. However, the extent of this thickening was not extensively explored. This study aimed to compare the image quality of DL-MRI with conventional MRI sequences reconstructed via conventional pipelines (Conventional-MRI) for shoulder examinations and evaluate the effectiveness of DL-MRI in accurately demonstrating the degree of SbA bursal and subcoracoid (SC) bursal thickening. Methods: This prospective cross-sectional study enrolled 41 patients with chronic shoulder pain who underwent 3-T MRI (including both Conventional-MRI and accelerated MRI sequences) of the shoulder between December 2022 and April 2023. Each protocol consisted of oblique axial, coronal, and sagittal images, including proton density-weighted imaging (PDWI) with fat suppression (FS) and oblique coronal T1-weighted imaging (T1WI) with FS. The image quality and degree of artifacts were assessed using a 5-point Likert scale for both Conventional-MRI and DL-MRI. Additionally, the degree of SbA and SC bursal thickening, as well as the relative signal-to-noise ratio (rSNR) and relative contrast-to-noise ratio (rCNR) were analyzed using the paired Wilcoxon test. Statistical significance was defined as P<0.05. Results: The utilization of accelerated sequences resulted in a remarkable 54.7% reduction in total scan time. Overall, DL-MRI exhibited superior image quality scores and fewer artifacts compared to Conventional-MRI. Specifically, DL-MRI demonstrated significantly higher measurements of SC bursal thickenings in the oblique sagittal PDWI sequence compared to Conventional-MRI [3.92 (2.83, 5.82) vs. 3.74 (2.92, 5.96) mm, P=0.028]. Moreover, DL-MRI exhibited higher detection of SbA bursal thickenings in the oblique coronal PDWI sequence [2.61 (1.85, 3.46) vs. 2.48 (1.84, 3.25) mm], with a notable trend towards significant differences (P=0.071). Furthermore, the rSNRs of the muscle in DL-MRI images were significantly higher than those in Conventional-MRI images across most sequences (P<0.001). However, the rSNRs of bone on Conventional-MRI of oblique axial and oblique coronal PDWI sequences showed adverse results [oblique axial: 1.000 (1.000, 1.000) vs. 0.444 (0.367, 0.523); and oblique coronal: 1.000 (1.000, 1.000) vs. 0.460 (0.387, 0.631); all P<0.001]. Additionally, all DL-MRI images exhibited significantly greater rSNRs and rCNRs compared to accelerated MRI sequences reconstructed using traditional pipelines (P<0.001). Conclusions: In conclusion, the utilization of DL-MRI enhances image quality and improves diagnostic capabilities, making it a promising alternative to Conventional-MRI for shoulder imaging.
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BACKGROUND AND PURPOSE: Pancreatic islets are modulated by cross-talk among different cell types and paracrine signalling plays important roles in maintaining glucose homeostasis. Urocortin 3 (UCN3) secreted by pancreatic ß cells activates the CRF2 receptor (CRF2R) and downstream pathways mediated by different G protein or arrestin subtypes in δ cells to cause somatostatin (SST) secretion, and constitutes an important feedback circuit for glucose homeostasis. EXPERIMENTAL APPROACH: Here, we used Arrb1-/-, Arrb2-/-, Gsfl/fl and Gqfl/fl knockout mice, the G11-shRNA-GFPfl/fl lentivirus, as well as functional assays and pharmacological characterization to study how the coupling of Gs, G11 and ß-arrestin1 to CRF2R contributed to UCN3-induced SST secretion in pancreatic δ cells. KEY RESULTS: Our study showed that CRF2R coupled to a panel of G protein and arrestin subtypes in response to UCN3 engagement. While RyR3 phosphorylation by PKA at the S156, S2706 and S4697 sites may underlie the Gs-mediated UCN3- CRF2R axis for SST secretion, the interaction of SYT1 with ß-arrestin1 is also essential for efficient SST secretion downstream of CRF2R. The specific expression of the transcription factor Stat6 may contribute to G11 expression in pancreatic δ cells. Furthermore, we found that different UCN3 concentrations may have distinct effects on glucose homeostasis, and these effects may depend on different CRF2R downstream effectors. CONCLUSIONS AND IMPLICATIONS: Collectively, our results provide a landscape view of signalling mediated by different G protein or arrestin subtypes downstream of paracrine UCN3- CRF2R signalling in pancreatic ß-δ-cell circuits, which may facilitate the understanding of fine-tuned glucose homeostasis networks.
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Receptores de Hormona Liberadora de Corticotropina , Transducción de Señal , Somatostatina , Urocortinas , Animales , Masculino , Ratones , Proteínas de Unión al GTP/metabolismo , Ratones Endogámicos C57BL , Ratones Noqueados , Receptores de Hormona Liberadora de Corticotropina/metabolismo , Somatostatina/metabolismo , Células Secretoras de Somatostatina/metabolismo , Urocortinas/metabolismoRESUMEN
A simple twin-core D-shape photonic crystal fiber sensor based on surface plasmon resonance (SPR) is designed for the measurement of refractive indices (RI). The twin-core D-shape structure enhances the SPR effect, and the M g F 2-Au dual-layer film narrows the linewidth in the loss spectrum, consequently improving both the sensitivity and figure of merit (FOM). The properties of the sensor are analyzed by the finite element method. In the RI range of 1.32-1.42, the maximum wavelength sensitivity, FOM, and resolution are 62,000 nm/RIU, 1281R I U -1, and 1.61×10-6, respectively.
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There is increasing evidence of abnormal neurodevelopmental outcomes in preterm infants with low-grade intraventricular hemorrhage (IVH). The purpose of the study was to explore whether brain microstructure and volume are associated with neuro-behavioral outcomes at 40 weeks corrected gestational age in preterm infants with low-grade IVH. MR imaging at term-equivalent age (TEA) was performed in 25 preterm infants with mild IVH (Papile grading I/II) and 40 control subjects without IVH. These subjects all had neonatal behavioral neurological assessment (NBNA) at 40 weeks' corrected age. Microstructure and volume evaluation of the brain were performed by using diffusion kurtosis imaging (DKI) and Synthetic MRI. Correlations among microstructure parameters, volume, and developmental outcomes were explored by using Spearman's correlation. In preterm infants with low-grade IVH, the volume of brain parenchymal fraction (BPF) was reduced. In addition, mean kurtosis (MK), fractional anisotropy (FA), radial kurtosis (RK), axial kurtosis (AK) in several major brain regions were reduced, while mean diffusivity (MD) was increased (P < 0.05). BPF, RK in the cerebellum, MK in the genu of the corpus callosum, and MK in the thalamus of preterm infants with low-grade IVH were associated with lower NBNA scores (r = 0.831, 0.836, 0.728, 0.772, P < 0.05). DKI and Synthetic MRI can quantitatively evaluate the microstructure alterations and brain volumes in preterm infants with low-grade IVH, which provides clinicians with a more comprehensive and accurate neurobehavioral assessment of preterm infants with low-grade IVH.
Asunto(s)
Enfermedades del Prematuro , Recien Nacido Prematuro , Lactante , Humanos , Recién Nacido , Encéfalo/diagnóstico por imagen , Hemorragia Cerebral/diagnóstico por imagen , Hemorragia Cerebral/complicaciones , Imagen de Difusión Tensora/métodos , Imagen por Resonancia Magnética , Enfermedades del Prematuro/diagnóstico por imagenRESUMEN
The introduction of molecularly woven three-dimensional (3D) covalent organic framework (COF) crystals into polymers of varying types invokes different forms of contact between filler and polymer. Whereas the combination of woven COFs with amorphous and brittle polymethyl methacrylate results in surface interactions, the use of the liquid-crystalline polymer polyimide induces the formation of polymer-COF junctions. These junctions are generated by the threading of polymer chains through the pores of the nanocrystals, thus allowing for spatial arrangement of polymer strands. This offers a programmable pathway for unthreading polymer strands under stress and leads to the in situ formation of high-aspect-ratio nanofibrils, which dissipate energy during the fracture. Polymer-COF junctions also strengthen the filler-matrix interfaces and lower the percolation thresholds of the composites, enhancing strength, ductility, and toughness of the composites by adding small amounts (~1 weight %) of woven COF nanocrystals. The ability of the polymer strands to closely interact with the woven framework is highlighted as the main parameter to forming these junctions, thus affecting polymer chain penetration and conformation.
RESUMEN
Gout, a painful condition marked by elevated uric acid levels often linked to the diet's high purine and alcohol content, finds a potential treatment target in xanthine oxidase (XO), a crucial enzyme for uric acid production. This study explores the therapeutic properties of alkaloids extracted from sunflower (Helianthus annuus L.) receptacles against gout. By leveraging computational chemistry and introducing a novel R-based clustering algorithm, "TriDimensional Hierarchical Fingerprint Clustering with Tanimoto Representative Selection (3DHFC-TRS)," we assessed 231 alkaloid molecules from sunflower receptacles. Our clustering analysis pinpointed six alkaloids with significant gout-targeting potential, particularly emphasizing the fifth cluster's XO inhibition capabilities. Through molecular docking and the BatchDTA prediction model, we identified three top compounds-2-naphthylalanine, medroxalol, and fenspiride-with the highest XO affinity. Further molecular dynamics simulations assessed their enzyme active site interactions and binding free energies, employing MM-PBSA calculations. This investigation not only highlights the discovery of promising compounds within sunflower receptacle alkaloids via LC-MS but also introduces medroxalol as a novel gout treatment candidate, showcasing the synergy of computational techniques and LC-MS in drug discovery.