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1.
ACS Biomater Sci Eng ; 2024 Jul 16.
Artículo en Inglés | MEDLINE | ID: mdl-39011938

RESUMEN

Disturbing cellular redox homeostasis within malignant cells, particularly improving reactive oxygen species (ROS), is one of the effective strategies for cancer therapy. The ROS generation based on nanozymes presents a promising strategy for cancer treatment. However, the therapeutic efficacy is limited due to the insufficient catalytic activity of nanozymes or their high dependence on hydrogen peroxide (H2O2) or oxygen. Herein, we reported a nanozyme (CSA) based on well-defined CuSe hollow nanocubes (CS) uniformly covered with Ag nanoparticles (AgNPs) to disturb cellular redox homeostasis and catalyze a cascade of intracellular biochemical reactions to produce ROS for the synergistic therapy of breast cancer. In this system, CSA could interact with the thioredoxin reductase (TrxR) and deplete the tumor microenvironment-activated glutathione (GSH), disrupting the cellular antioxidant defense system and augmenting ROS generation. Besides, CSA possessed high peroxidase-mimicking activity toward H2O2, leading to the generation of various ROS including hydroxyl radical (•OH), superoxide radicals (•O2-), and singlet oxygen (1O2), facilitated by the Cu(II)/Cu(I) redox and H2O2 cycling, and plentiful catalytically active metal sites. Additionally, due to the absorption and charge separation performance of AgNPs, the CSA exhibited excellent photothermal performance in the second near-infrared (NIR-II, 1064 nm) region and enhanced the photocatalytic ROS level in cancer cells. Owing to the inhibition of TrxR activity, GSH depletion, high peroxidase-mimicking activity of CSA, and abundant ROS generation, CSA displays remarkable and specific inhibition of tumor growth.

2.
Crit Rev Biotechnol ; : 1-29, 2024 Jul 22.
Artículo en Inglés | MEDLINE | ID: mdl-39038957

RESUMEN

Microalgae and cyanobacteria are a rich source of carotenoids that are well known for their potent bioactivities, including antioxidant, anti-cancer, anti-proliferative, anti-inflammatory, and anti-obesity properties. Recently, many interests have also been focused on the biological activities of these microalgae/cyanobacteria-derived carotenoids, such as fucoxanthin and ß-carotene potential to be the salutary nutraceuticals, on treating or preventing human common diseases (e.g., cancers). This is due to their special chemical structures that demonstrate unique bioactive functions, in which the biologically active discrepancies might attribute to the different spatial configurations of their molecules. In addition, their abundance and bioaccessibilities make them more popularly applied in food and pharmaceutical industries, as compared to the macroalgal/fungal-derived ones. This review is focused on the recent studies on the bioactivities of fucoxanthin and some carotenoids derived from microalgae and cyanobacteria in relationship with human health and diseases, with emphasis on their potential applications as natural antioxidants. Various biotechnological approaches employed to induce the production of these specific carotenoids from the culture of microalgae/cyanobacteria are also critically reviewed. These well-developed and emerging biotechnologies present promise to be applied in food and pharmaceutical industries to facilitate the efficient manufacture of the bioactive carotenoid products derived from microalgae and cyanobacteria.

3.
Fish Shellfish Immunol ; 151: 109697, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38871139

RESUMEN

Myeloid differentiation factor-88 (MyD88) is a key adaptor of the toll-like receptor (TLR) signaling pathway and plays a crucial role in innate immune signal transduction in animals. However, the MyD88-mediated signal transduction mechanism in shellfish has not been well studied. In this study, a new MyD88 gene, CfMyD88-2, was identified in the Zhikong scallop, Chlamys farreri. The 1779 bp long open reading frame encodes 592 amino acids. The N-terminus of CfMyD88-2 contains a conserved death domain (DD), followed by a TIR (TLR/Interleukin-1 Receptor) domain. The results of the multi-sequence comparison showed that the TIR domain sequences were highly conserved. Phylogenetic analysis revealed that CfMyD88-2 was first associated with Mizuhopecten yessoensis MyD88-4 and Argopecten irradians MyD88-4. CfMyD88-2 mRNA was expressed in all scallop tissues, as detected by qRT-PCR, and the expression level was the highest in the mantle and hepatopancreas. In addition, CfMyD88-2 mRNA expression significantly increased after pathogen-associated molecular patterns (PAMPs, such as lipopolysaccharide, peptidoglycan, or polyinosinic-polycytidylic acid) stimulation. The results of the co-immunoprecipitation experiments in HEK293T cells showed that both CfMyD88-1 and CfMyD88-2 interacted with the TLR protein of scallops, suggesting the existence of more than one functional TLR-MyD88 signaling axis in scallops. Dual luciferase reporter gene assays indicated that the overexpressed CfMyD88-2 in HEK293T cells activated interferon (IFN) α, IFN-ß, IFN-γ, and NF-κB reporter genes, indicating that the protein has multiple functions. The results of the subcellular localization experiment uncovered that CfMyD88-2 was mainly localized in the cytoplasm of human cells. In summary, the novel identified CfMyD88-2 can respond to the challenge of PAMPs, participate in TLR immune signaling, and may activate downstream effector genes such as NF-κB gene. These research results will be useful in advancing the theory of innate immunity in invertebrates and provide a reference for the selection of disease-resistant scallops in the future.


Asunto(s)
Secuencia de Aminoácidos , Regulación de la Expresión Génica , Inmunidad Innata , Factor 88 de Diferenciación Mieloide , Pectinidae , Filogenia , Alineación de Secuencia , Receptores Toll-Like , Animales , Inmunidad Innata/genética , Factor 88 de Diferenciación Mieloide/genética , Factor 88 de Diferenciación Mieloide/inmunología , Factor 88 de Diferenciación Mieloide/metabolismo , Pectinidae/inmunología , Pectinidae/genética , Receptores Toll-Like/genética , Receptores Toll-Like/inmunología , Receptores Toll-Like/química , Alineación de Secuencia/veterinaria , Regulación de la Expresión Génica/inmunología , Perfilación de la Expresión Génica/veterinaria , Transducción de Señal/inmunología , Humanos , Células HEK293 , Secuencia de Bases
4.
Environ Res ; 257: 119350, 2024 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-38844035

RESUMEN

The FeOCl-based photo-Fenton heterojunction catalyst holds great promise for effective water pollution treatment. A novel heterojunction FeOCl/MOF-In2S3 (F/M-I) was fabricated by coating hollow MOF-In2S3 nanoflowers onto the surface of FeOCl. Under the optimal conditions, the maximum photo-Fenton degradation rate constants of FeOCl/MOF-In2S3 for oxytetracycline (OTC) within 20 min is 0.88192 L mg-1·min-1, which are 3.2 and 2.5 times that of pure FeOCl (0.27357 L mg-1·min-1) and MOF-In2S3 (0.35222 L mg-1·min-1). Density functional theory (DFT) results confirm that the electron-rich nature of MOF-In2S3 accelerates the cycle between Fe (III)/Fe (II)of FeOCl, promoting H2O2 adsorption by FeOCl/MOF-In2S3 and generating more hydroxyl radicals (·OH) for pollutant degradation. Based on the results of DFT, combined with the results of the reactive oxidation species scavenger (ROSs), electron paramagnetic resonance (EPR) and Mott-Schottky curves, the separation and transfer behavior of photoexcited charges in FeOCl/MOF-In2S3 heterojunction and the possible photocatalytic degradation mechanism were investigated. Finally, a Z-scheme heterostructure is proposed to elucidate the catalytic mechanism. This study provides a new perspective on designing and synthesizing semiconductor materials for water treatment by photo-Fenton catalysis.


Asunto(s)
Peróxido de Hidrógeno , Contaminantes Químicos del Agua , Peróxido de Hidrógeno/química , Adsorción , Contaminantes Químicos del Agua/química , Catálisis , Estructuras Metalorgánicas/química , Hierro/química , Purificación del Agua/métodos
6.
Cancer Lett ; 594: 216994, 2024 Jul 10.
Artículo en Inglés | MEDLINE | ID: mdl-38801885

RESUMEN

Increasing evidence suggests the importance of CD24 in tumor progression, but its role and mechanism in esophageal squamous cell carcinoma (ESCC) remain unclear. The present study aims to explore the potential of CD24 as a novel predictive biomarker in ESCC, as well as its mechanism and therapeutic implications in metastasis and 5-FU chemoresistance. By using tissue microarray and immunohistochemistry, we found that CD24 expression was higher in ESCC tumor tissues than paired non-tumor tissues, further indicating that CD24 was markedly associated with poor prognosis. CD24 significantly promoted metastasis and 5-FU chemoresistance in vitro and in vivo. Mechanistically, CD24 competes with GIT2 to bind to Arf6, and stabilizes Arf6-GTP to activate the subsequent ERK pathway, thus promoting cancer progression. In addition, a significant positive correlation between CD24 and p-ERK was observed in clinical ESCC tissues. In summary, this study not only reveals CD24 as a regulatory factor for Arf6 activity, but also uncovers CD24-Arf6-ERK signaling axis as a novel mechanism of ESCC progression. Our findings suggest CD24 as a promising biomarker and therapeutic target in ESCC.


Asunto(s)
Factor 6 de Ribosilación del ADP , Factores de Ribosilacion-ADP , Antígeno CD24 , Resistencia a Antineoplásicos , Neoplasias Esofágicas , Carcinoma de Células Escamosas de Esófago , Humanos , Neoplasias Esofágicas/patología , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/metabolismo , Neoplasias Esofágicas/tratamiento farmacológico , Antígeno CD24/metabolismo , Carcinoma de Células Escamosas de Esófago/patología , Carcinoma de Células Escamosas de Esófago/genética , Carcinoma de Células Escamosas de Esófago/metabolismo , Carcinoma de Células Escamosas de Esófago/tratamiento farmacológico , Factores de Ribosilacion-ADP/metabolismo , Factores de Ribosilacion-ADP/genética , Animales , Línea Celular Tumoral , Masculino , Femenino , Ratones , Sistema de Señalización de MAP Quinasas , Fluorouracilo/farmacología , Regulación Neoplásica de la Expresión Génica , Biomarcadores de Tumor/metabolismo , Biomarcadores de Tumor/genética , Pronóstico , Persona de Mediana Edad , Ratones Desnudos
7.
ACS Biomater Sci Eng ; 10(6): 4009-4017, 2024 06 10.
Artículo en Inglés | MEDLINE | ID: mdl-38722972

RESUMEN

It still remains challenging to design multifunctional therapeutic reagents for effective cancer therapy under a unique tumor microenvironment including insufficient endogenous H2O2 and O2, low pH, and a high concentration of glutathione (GSH). In this work, a CO-based phototherapeutic system triggered by photogenerated holes, which consisted of ionic liquid (IL), the CO prodrug Mn2(CO)10, and iridium(III) porphyrin (IrPor) modified carbonized ZIF-8-doped graphitic carbon nitride nanocomposite (IL/ZCN@Ir(CO)), was designed for cascade hypoxic tumors. Upon light irradiation, the photogenerated holes on IL/ZCN@Ir(CO) oxidize water into H2O2, which subsequently induces Mn2(CO)10 to release CO. Meanwhile, IrPor can convert H2O2 to hydroxyl radical (•OH) and subsequent singlet oxygen (1O2), which further triggers CO release. Moreover, the degraded MnO2 shows activity for glutathione (GSH) depletion and mimics peroxidase, leading to GSH reduction and •OH production in tumors. Thus, this strategy can in situ release high concentrations of CO and reactive oxygen species (ROS) and deplete GSH to efficiently induce cell apoptosis under hypoxic conditions, which has a high inhibiting effect on the growth of tumors, offering an attractive strategy to amplify CO and ROS generation to meet therapeutic requirements in cancer treatment.


Asunto(s)
Monóxido de Carbono , Glutatión , Monóxido de Carbono/metabolismo , Monóxido de Carbono/química , Monóxido de Carbono/farmacología , Humanos , Glutatión/metabolismo , Glutatión/química , Animales , Línea Celular Tumoral , Peróxido de Hidrógeno/química , Peróxido de Hidrógeno/metabolismo , Neoplasias/tratamiento farmacológico , Neoplasias/metabolismo , Neoplasias/radioterapia , Hipoxia Tumoral/efectos de los fármacos , Ratones , Iridio/química , Iridio/farmacología , Grafito/química , Grafito/farmacología , Especies Reactivas de Oxígeno/metabolismo , Apoptosis/efectos de los fármacos , Nanocompuestos/química , Nanocompuestos/uso terapéutico , Compuestos de Nitrógeno
8.
Nano Lett ; 24(19): 5920-5928, 2024 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-38708934

RESUMEN

A significant challenge in direct seawater electrolysis is the rapid deactivation of the cathode due to the large scaling of Mg(OH)2. Herein, we synthesized a Pt-coated highly disordered NiCu alloy (Pt-NiCu alloy) electrode with superior solidophobic behavior, enabling stable hydrogen generation (100 mA cm-2, >1000 h durability) and simultaneous production of Mg(OH)2 (>99.0% purity) in electrolyte enriched with Mg2+ and Ca2+. The unconventional solidophobic property primarily stems from the high surface energy of the NiCu alloy substrate, which facilitates the adsorption of surface water and thereby compels the bulk formation of Mg(OH)2 via homogeneous nucleation. The discovery of this solidophobic electrode will revolutionarily simplify the existing techniques for seawater electrolysis and increase the economic viability for seawater electrolysis.

9.
Front Immunol ; 15: 1364957, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38650932

RESUMEN

Introduction: CARD11 is a lymphoid lineage-specific scaffold protein regulating the NF-κB activation downstream of the antigen receptor signal pathway. Defective CARD11 function results in abnormal development and differentiation of lymphocytes, especially thymic regulatory T cells (Treg). Method: In this study, we used patients' samples together with transgenic mouse models carrying pathogenic CARD11 mutations from patients to explore their effects on Treg development. Immunoblotting and a GFP receptor assay were used to evaluate the activation effect of CARD11 mutants on NF-κB signaling. Then the suppressive function of Tregs carrying distinct CARD11 mutations was measured by in vitro suppression assay. Finally, we applied the retroviral transduced bone marrow chimeras to rescue the Treg development in an NF-κB independent manner. Results and discuss: We found CARD11 mutations causing hyper-activated NF-κB signals also gave rise to compromised Treg development in the thymus, similar to the phenotype in Card11 deficient mice. This observation challenges the previous view that CARD11 regulates Treg lineage dependent on the NF-kB activation. Mechanistic investigations reveal that the noncanonical function CARD11, which negatively regulates the AKT/ FOXO1 signal pathway, is responsible for regulating Treg generation. Moreover, primary immunodeficiency patients carrying CARD11 mutation, which autonomously activates NF-κB, also represented the reduced Treg population in their peripheral blood. Our results propose a new regulatory function of CARD11 and illuminate an NF-κB independent pathway for thymic Treg lineage commitment.


Asunto(s)
Proteínas Adaptadoras de Señalización CARD , Guanilato Ciclasa , Mutación , FN-kappa B , Transducción de Señal , Linfocitos T Reguladores , Timo , Animales , Linfocitos T Reguladores/inmunología , Linfocitos T Reguladores/metabolismo , Proteínas Adaptadoras de Señalización CARD/genética , Proteínas Adaptadoras de Señalización CARD/metabolismo , FN-kappa B/metabolismo , Humanos , Ratones , Timo/inmunología , Timo/citología , Timo/metabolismo , Ratones Transgénicos , Diferenciación Celular/inmunología , Enfermedades de Inmunodeficiencia Primaria/inmunología , Enfermedades de Inmunodeficiencia Primaria/genética , Masculino
10.
Nat Commun ; 15(1): 3531, 2024 Apr 26.
Artículo en Inglés | MEDLINE | ID: mdl-38670961

RESUMEN

E6AP dysfunction is associated with Angelman syndrome and Autism spectrum disorder. Additionally, the host E6AP is hijacked by the high-risk HPV E6 to aberrantly ubiquitinate the tumor suppressor p53, which is linked with development of multiple types of cancer, including most cervical cancers. Here we show that E6AP and the E6AP/E6 complex exist, respectively, as a monomer and a dimer of the E6AP/E6 protomer. The short α1-helix of E6AP transforms into a longer helical structure when in complex with E6. The extended α1-helices of the dimer intersect symmetrically and contribute to the dimerization. The two protomers sway around the crossed region of the two α1-helices to promote the attachment and detachment of substrates to the catalytic C-lobe of E6AP, thus facilitating ubiquitin transfer. These findings, complemented by mutagenesis analysis, suggest that the α1-helix, through conformational transformations, controls the transition between the inactive monomer and the active dimer of E6AP.


Asunto(s)
Multimerización de Proteína , Ubiquitina-Proteína Ligasas , Ubiquitina-Proteína Ligasas/metabolismo , Ubiquitina-Proteína Ligasas/química , Ubiquitina-Proteína Ligasas/genética , Humanos , Ubiquitina/metabolismo , Ubiquitina/química , Ubiquitinación , Modelos Moleculares , Cristalografía por Rayos X , Proteínas Oncogénicas Virales/metabolismo , Proteínas Oncogénicas Virales/química , Proteínas Oncogénicas Virales/genética , Proteína p53 Supresora de Tumor/metabolismo , Proteína p53 Supresora de Tumor/química , Proteína p53 Supresora de Tumor/genética , Unión Proteica , Conformación Proteica en Hélice alfa
11.
Biomed Pharmacother ; 174: 116460, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38520864

RESUMEN

Ischemic stroke is a common intravascular disease and one of the leading causes of death and disability. The salidroside derivative SHPL-49, which we previously synthesized, significantly attenuates cerebral ischemic injury in a rat model of permanent middle cerebral artery occlusion. To explore the neuroprotective mechanism of SHPL-49, the effects of SHPL-49 on the expression levels of neurotrophic factors in neurons and microglia and the polarization of microglia were investigated in the present study. SHPL-49 activated the brain-derived neurotrophic factor (BDNF) pathway, decreased the number of degenerated neurons, and accelerated neurogenesis in rats with cerebral ischemia. In addition, SHPL-49 promoted the polarization of microglia toward the M2 phenotype to alleviate neuroinflammation. In BV2 cells, SHPL-49 upregulated CD206 mRNA and protein levels and inhibited CD86 mRNA and protein levels. SHPL-49 also increased neurotrophic factor secretion in BV2 cells, which indirectly promoted the survival of primary neurons after oxygen-glucose deprivation (OGD). Proteomics analysis revealed that SHPL-49 promoted growth-associated protein 43 (Gap43) expression. SHPL-49 enhanced synaptic plasticity and increased Gap43 protein levels via activation of the BDNF pathway in the OGD primary neuron model. These results indicate that SHPL-49 prevents cerebral ischemic injury by activating neurotrophic factor pathways and altering microglial polarization. Thus, SHPL-49 is a potential neuroprotective agent.


Asunto(s)
Isquemia Encefálica , Factor Neurotrófico Derivado del Encéfalo , Proteína GAP-43 , Glucósidos , Microglía , Neuronas , Fármacos Neuroprotectores , Fenoles , Ratas Sprague-Dawley , Receptor trkB , Transducción de Señal , Animales , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Fármacos Neuroprotectores/farmacología , Glucósidos/farmacología , Fenoles/farmacología , Masculino , Ratas , Proteína GAP-43/metabolismo , Microglía/efectos de los fármacos , Microglía/metabolismo , Isquemia Encefálica/tratamiento farmacológico , Isquemia Encefálica/metabolismo , Transducción de Señal/efectos de los fármacos , Neuronas/efectos de los fármacos , Neuronas/metabolismo , Neuronas/patología , Receptor trkB/metabolismo , Infarto de la Arteria Cerebral Media/tratamiento farmacológico , Infarto de la Arteria Cerebral Media/patología , Infarto de la Arteria Cerebral Media/metabolismo , Línea Celular , Modelos Animales de Enfermedad , Neurogénesis/efectos de los fármacos , Ratones
12.
Front Immunol ; 15: 1295472, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38500883

RESUMEN

Background: Data with fine granularity about COVID-19-related outcomes and risk factors were still limited in the idiopathic inflammatory myopathies (IIMs) population. This study aimed to investigate clinical factors associated with hospitalized and severe COVID-19 in patients with IIMs, particularly those gauged by myositis-specific antibodies. Methods: This retrospective cohort study was conducted in the Renji IIM cohort in Shanghai, China, under an upsurge of SARS-CoV-2 omicron variant infections from December 2022 to January 2023. Clinical data were collected and analyzed by multivariable logistic regression to determine risk factors. High-dimensional flow cytometry analysis was performed to outline the immunological features. Results: Among 463 infected patients in the eligible cohort (n=613), 65 (14.0%) were hospitalized, 19 (4.1%) suffered severe COVID-19, and 10 (2.2%) died. Older age (OR=1.59/decade, 95% CI 1.18 to 2.16, p=0.003), requiring family oxygen supplement (2.62, 1.11 to 6.19, 0.028), patients with anti-synthetase syndrome (ASyS) (2.88, 1.12 to 7.34, 0.027, vs. other dermatomyositis), higher IIM disease activity, and prednisone intake >10mg/day (5.59, 2.70 to 11.57, <0.001) were associated with a higher risk of hospitalization. Conversely, 3-dose inactivated vaccination reduced the risk of hospitalization (0.10, 0.02 to 0.40, 0.001, vs. incomplete vaccination). Janus kinase inhibitor (JAKi) pre-exposure significantly reduced the risk of severe COVID-19 in hospitalized patients (0.16, 0.04 to 0.74, 0.019, vs. csDMARDs). ASyS patients with severe COVID-19 had significantly reduced peripheral CD4+ T cells, lower CD4/CD8 ratio, and fewer naive B cells but more class-switched memory B cells compared with controls. Conclusion: ASyS and family oxygen supplement were first identified as risk factors for COVID-19-related hospitalization in patients with IIMs. JAKi pre-exposure might protect IIM patients against severe COVID-19 complications.


Asunto(s)
COVID-19 , Miositis , Humanos , Estudios Retrospectivos , Ligasas , COVID-19/terapia , COVID-19/complicaciones , SARS-CoV-2 , China/epidemiología , Miositis/complicaciones , Miositis/epidemiología , Oxígeno
13.
Comput Biol Med ; 171: 108137, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38447499

RESUMEN

Lesion segmentation in ultrasound images is an essential yet challenging step for early evaluation and diagnosis of cancers. In recent years, many automatic CNN-based methods have been proposed to assist this task. However, most modern approaches often lack capturing long-range dependencies and prior information making it difficult to identify the lesions with unfixed shapes, sizes, locations, and textures. To address this, we present a novel lesion segmentation framework that guides the model to learn the global information about lesion characteristics and invariant features (e.g., morphological features) of lesions to improve the segmentation in ultrasound images. Specifically, the segmentation model is guided to learn the characteristics of lesions from the global maps using an adversarial learning scheme with a self-attention-based discriminator. We argue that under such a lesion characteristics-based guidance mechanism, the segmentation model gets more clues about the boundaries, shapes, sizes, and positions of lesions and can produce reliable predictions. In addition, as ultrasound lesions have different textures, we embed this prior knowledge into a novel region-invariant loss to constrain the model to focus on invariant features for robust segmentation. We demonstrate our method on one in-house breast ultrasound (BUS) dataset and two public datasets (i.e., breast lesion (BUS B) and thyroid nodule from TNSCUI2020). Experimental results show that our method is specifically suitable for lesion segmentation in ultrasound images and can outperform the state-of-the-art approaches with Dice of 0.931, 0.906, and 0.876, respectively. The proposed method demonstrates that it can provide more important information about the characteristics of lesions for lesion segmentation in ultrasound images, especially for lesions with irregular shapes and small sizes. It can assist the current lesion segmentation models to better suit clinical needs.


Asunto(s)
Procesamiento de Imagen Asistido por Computador , Nódulo Tiroideo , Humanos , Procesamiento de Imagen Asistido por Computador/métodos , Ultrasonografía , Mama
14.
Neuroimage ; 291: 120586, 2024 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-38548039

RESUMEN

Creativity, a high-order cognitive ability, has received wide attention from researchers and educators who are dedicated to promoting its development throughout one's lifespan. Currently, creativity is commonly assessed with divergent thinking tasks, such as the Alternative Uses Task. Recent advancements in neuroimaging techniques have enabled the identification of brain markers for high-order cognitive abilities. One such brain structure of interest in this regard is the hippocampus, which has been found to play an important role in generating creative thoughts in adulthood. However, such role of the hippocampus in childhood is not clear. Thus, this study aimed to investigate the associations between creativity, as measured by divergent thinking, and both the volume of the hippocampus and its resting-state functional connectivity in 116 children aged 8-12 years. The results indicate significant relations between divergent thinking and the volume of the hippocampal head and the hippocampal tail, as well as the volume of a subfield comprising cornu ammonis 2-4 and dentate gyrus within the hippocampal body. Additionally, divergent thinking was significantly related to the differences between the anterior and the posterior hippocampus in their functional connectivity to other brain regions during rest. These results suggest that these two subregions may collaborate with different brain regions to support diverse cognitive processes involved in the generation of creative thoughts. In summary, these findings indicate that divergent thinking is significantly related to the structural and functional characteristics of the hippocampus, offering potential insights into the brain markers for creativity during the developmental stage.


Asunto(s)
Encéfalo , Imagen por Resonancia Magnética , Niño , Humanos , Imagen por Resonancia Magnética/métodos , Encéfalo/diagnóstico por imagen , Creatividad , Cognición , Mapeo Encefálico/métodos , Hipocampo/diagnóstico por imagen
15.
Small ; 20(29): e2311087, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38335310

RESUMEN

Herein, a type of light- and heat-driven flexible supramolecular polymer with reversibly long-lived phosphorescence and photochromism is constructed from acrylamide copolymers with 4-phenylpyridinium derivatives containing a cyano group (P-CN, P-oM, P-mM), sulfobutylether-ß-cyclodextrin (SBCD), and polyvinyl alcohol (PVA). Compared to their parent solid polymers, these flexible supramolecules based on the non-covalent cross-linking of copolymers, SBCD, and PVA efficiently boost the phosphorescence lifetimes (723.0 ms for P-CN, 623.0 ms for P-oM, 945.8 ms for P-mM) through electrostatic interaction and hydrogen bonds. The phosphorescence intensity/lifetime, showing excellent responsiveness to light and heat, sharply decreased after irradiation with a 275 nm flashlight or sunlight and gradually recovered through heating. This is accompanied by the occurrence and fading of visible photochromism, manifesting as dark green for P-CN and pink for P-oM and P-mM. These reversible photochromism and phosphorescence behaviors are mainly attributed to the generation and disappearance of organic radicals in the 4-phenylpyridinium derivatives with a cyano group, which can guide tunable luminescence and photochromism.

16.
Adv Healthc Mater ; 13(14): e2302767, 2024 06.
Artículo en Inglés | MEDLINE | ID: mdl-38381808

RESUMEN

Low immunogenicity, absence of tumor-infiltrating lymphocytes and immunosuppressive microenvironment of immune cold tumors are the main bottlenecks leading to unfavorable prognosis. Here, an integrated tumor bioimaging and multimodal therapeutic strategy is developed, which converts immune cold into hot by modulating oxidative stress levels, enhancing photo-killing efficacy, inducing immunogenic cell death and inhibiting the immune checkpoint. On that occasion, the unique tumor microenvironment can be harnessed to biosynthesize in situ self-assembly iron complexes and fluorescent gold nanoclusters from metal ions Fe(II) and Au(III) for active targeting and real-time visualization of the tumors, simultaneously regulating reactive oxygen species levels within tumors via peroxidase-like activity. Furthermore, methylene blue (MB)-mediated photodynamic therapy promotes the release of damage-associated molecular patterns (DAMPs), which acts as in situ tumor vaccine and further induces dendritic cells maturation, augments the infiltration of antitumor T cells and significantly impedes the primary tumor growth and proliferation. More strikingly, by synergizing with the programmed cell death receptor-1 (PD-1) checkpoint inhibitor, the immunosuppressive microenvironment is remodeled and the survival time of model mice is prolonged. In summary, this paradigm utilizes the tumor-specific microenvironment to boost robust and durable systemic antitumor immunity, providing a novel opportunity for precision cancer theranostics.


Asunto(s)
Oro , Muerte Celular Inmunogénica , Azul de Metileno , Microambiente Tumoral , Animales , Oro/química , Azul de Metileno/química , Azul de Metileno/farmacología , Ratones , Muerte Celular Inmunogénica/efectos de los fármacos , Microambiente Tumoral/efectos de los fármacos , Línea Celular Tumoral , Fotoquimioterapia/métodos , Humanos , Especies Reactivas de Oxígeno/metabolismo , Nanopartículas del Metal/química , Nanopartículas del Metal/uso terapéutico , Femenino , Hierro/química
17.
Adv Mater ; : e2311322, 2024 Jan 25.
Artículo en Inglés | MEDLINE | ID: mdl-38299450

RESUMEN

Seawater electrolysis for hydrogen production is a sustainable and economical approach that can mitigate the energy crisis and global warming issues. Although various catalysts/electrodes with excellent activities have been developed for high-efficiency seawater electrolysis, their unsatisfactory durability, especially for anodes, severely impedes their industrial applications. In this review, attention is paid to the factors that affect the stability of anodes and the corresponding strategies for designing catalytic materials to prolong the anode's lifetime. In addition, two important aspects-electrolyte optimization and electrolyzer design-with respect to anode stability improvement are summarized. Furthermore, several methods for rapid stability assessment are proposed for the fast screening of both highly active and stable catalysts/electrodes. Finally, perspectives on future investigations aimed at improving the stability of seawater electrolysis systems are outlined.

18.
Med Educ Online ; 29(1): 2303209, 2024 Dec 31.
Artículo en Inglés | MEDLINE | ID: mdl-38194435

RESUMEN

Medical professionalism and ethics (MPE) are critical components influencing how medical practitioners provide patients with the highest standard of care. As a result, a structured attempt has been undertaken to enhance the content and teaching delivery of the medical professionalism and ethics education (MPEE) in the undergraduate medical curriculum. Guided by Vygotsky's sociocultural learning theory, Harre and Van Langenhove's positioning theory and Taba's principles of curriculum development, a curriculum co-creation project was organized with the aim of developing a socio-culturally responsive MPEE. A total of fifteen medical students agreed to participate in the project where they co-created MPE curriculum with a medical educator over the course of three months. Upon completion of the project, a co-created, socio-culturally responsive MPE curriculum was presented. The thematic analysis revealed positive changes in the participants' attitudes, skills, and behaviors towards co-creating the MPE curriculum. They also reported feeling a sense of fulfilment after having a transformative experience as curriculum co-creators and after receiving positive feedback from the faculty, staff, and other students on the co-created MPE curriculum. The project's success demonstrates the importance of curriculum co-creation as a strategy to promote co-creation efforts among students and educators in developing a socio-culturally responsive curriculum. The project's framework and practical recommendations can be adopted by other medical educators and faculties to encourage students' participation and their role on curriculum development using the co-creation approach.


Asunto(s)
Educación Médica , Estudiantes de Medicina , Humanos , Profesionalismo , Ética Médica , Curriculum
19.
BMC Genomics ; 25(1): 117, 2024 Jan 26.
Artículo en Inglés | MEDLINE | ID: mdl-38279081

RESUMEN

BACKGROUND: In cellular activities, essential proteins play a vital role and are instrumental in comprehending fundamental biological necessities and identifying pathogenic genes. Current deep learning approaches for predicting essential proteins underutilize the potential of gene expression data and are inadequate for the exploration of dynamic networks with limited evaluation across diverse species. RESULTS: We introduce ECDEP, an essential protein identification model based on evolutionary community discovery. ECDEP integrates temporal gene expression data with a protein-protein interaction (PPI) network and employs the 3-Sigma rule to eliminate outliers at each time point, constructing a dynamic network. Next, we utilize edge birth and death information to establish an interaction streaming source to feed into the evolutionary community discovery algorithm and then identify overlapping communities during the evolution of the dynamic network. SVM recursive feature elimination (RFE) is applied to extract the most informative communities, which are combined with subcellular localization data for classification predictions. We assess the performance of ECDEP by comparing it against ten centrality methods, four shallow machine learning methods with RFE, and two deep learning methods that incorporate multiple biological data sources on Saccharomyces. Cerevisiae (S. cerevisiae), Homo sapiens (H. sapiens), Mus musculus, and Caenorhabditis elegans. ECDEP achieves an AP value of 0.86 on the H. sapiens dataset and the contribution ratio of community features in classification reaches 0.54 on the S. cerevisiae (Krogan) dataset. CONCLUSIONS: Our proposed method adeptly integrates network dynamics and yields outstanding results across various datasets. Furthermore, the incorporation of evolutionary community discovery algorithms amplifies the capacity of gene expression data in classification.


Asunto(s)
Mapas de Interacción de Proteínas , Saccharomyces cerevisiae , Animales , Ratones , Humanos , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Algoritmos , Proteínas/metabolismo , Caenorhabditis elegans/genética , Caenorhabditis elegans/metabolismo
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