Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 148
Filtrar
Más filtros

Banco de datos
País/Región como asunto
Tipo del documento
Intervalo de año de publicación
1.
PLoS Biol ; 21(4): e3002078, 2023 04.
Artículo en Inglés | MEDLINE | ID: mdl-37079499

RESUMEN

Down syndrome (DS) is caused by the trisomy of human chromosome 21 (HSA21). A major challenge in DS research is to identify the HSA21 genes that cause specific symptoms. Down syndrome cell adhesion molecule (DSCAM) is encoded by a HSA21 gene. Previous studies have shown that the protein level of the Drosophila homolog of DSCAM determines the size of presynaptic terminals. However, whether the triplication of DSCAM contributes to presynaptic development in DS remains unknown. Here, we show that DSCAM levels regulate GABAergic synapses formed on neocortical pyramidal neurons (PyNs). In the Ts65Dn mouse model for DS, where DSCAM is overexpressed due to DSCAM triplication, GABAergic innervation of PyNs by basket and chandelier interneurons is increased. Genetic normalization of DSCAM expression rescues the excessive GABAergic innervations and the increased inhibition of PyNs. Conversely, loss of DSCAM impairs GABAergic synapse development and function. These findings demonstrate excessive GABAergic innervation and synaptic transmission in the neocortex of DS mouse models and identify DSCAM overexpression as the cause. They also implicate dysregulated DSCAM levels as a potential pathogenic driver in related neurological disorders.


Asunto(s)
Síndrome de Down , Neocórtex , Animales , Humanos , Ratones , Modelos Animales de Enfermedad , Síndrome de Down/genética , Síndrome de Down/metabolismo , Síndrome de Down/patología , Drosophila , Interneuronas/metabolismo , Terminales Presinápticos/metabolismo , Sinapsis/metabolismo
2.
Plant J ; 119(1): 100-114, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38600835

RESUMEN

As global climate change persists, ongoing warming exposes plants, including kiwifruit, to repeated cycles of drought stress and rewatering, necessitating the identification of drought-resistant genotypes for breeding purposes. To better understand the physiological mechanisms underlying drought resistance and recovery in kiwifruit, moderate (40-45% field capacity) and severe (25-30% field capacity) drought stresses were applied, followed by rewatering (80-85% field capacity) to eight kiwifruit rootstocks in this study. We then conducted a multivariate analysis of 20 indices for the assessment of drought resistance and recovery capabilities. Additionally, we identified four principal components, each playing a vital role in coping with diverse water conditions. Three optimal indicator groups were pinpointed, enhancing precision in kiwifruit drought resistance and recovery assessment and simplifying the evaluation system. Finally, MX-1 and HW were identified as representative rootstocks for future research on kiwifruit's responses to moderate and severe drought stresses. This study not only enhances our understanding of the response mechanisms of kiwifruit rootstocks to progressive drought stress and recovery but also provides theoretical guidance for reliable screening of drought-adaptive kiwifruit genotypes.


Asunto(s)
Actinidia , Sequías , Genotipo , Actinidia/genética , Actinidia/fisiología , Análisis Multivariante , Estrés Fisiológico/genética , Raíces de Plantas/fisiología , Raíces de Plantas/genética , Agua/metabolismo , Frutas/genética , Frutas/fisiología , Resistencia a la Sequía
3.
Exp Cell Res ; 439(2): 114100, 2024 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-38797258

RESUMEN

Widespread metastasis is the primary reason for the high mortality associated with ovarian cancer (OC), and effective targeted therapy for tumor aggressiveness is still insufficient in clinical practice. Therefore, it is urgent to find new targets to improve prognosis of patients. PDE4A is a cyclic nucleotide phosphodiesterase that plays a crucial role in the occurrence and development in various malignancies. Our study firstly reported the function of PDE4A in OC. Expression of PDE4A was validated through bioinformatics analysis, RT-qPCR, Western blot, and immunohistochemistry. Additionally, its impact on cell growth and motility was assessed via in vitro and in vivo experiments. PDE4A was downregulated in OC tissues compared with normal tissues and low PDE4A expression was correlated with poor clinical outcomes in OC patients. The knockdown of PDE4A significantly promoted the proliferation, migration and invasion of OC cells while overexpression of PDE4A resulted in the opposite effect. Furthermore, smaller and fewer tumor metastatic foci were observed in mice bearing PDE4A-overexpressing OVCAR3 cells. Mechanistically, downregulation of PDE4A expression can induce epithelial-mesenchymal transition (EMT) and nuclear translocation of Snail, which suggests that PDE4A plays a pivotal role in suppressing OC progression. Notably, Rolipram, the PDE4 inhibitor, mirrored the effects observed with PDE4A deletion. In summary, the downregulation of PDE4A appears to facilitate OC progression by modulating the Snail/EMT pathway, underscoring the potential of PDE4A as a therapeutic target against ovarian cancer metastasis.


Asunto(s)
Movimiento Celular , Proliferación Celular , Fosfodiesterasas de Nucleótidos Cíclicos Tipo 4 , Transición Epitelial-Mesenquimal , Regulación Neoplásica de la Expresión Génica , Neoplasias Ováricas , Factores de Transcripción de la Familia Snail , Humanos , Femenino , Fosfodiesterasas de Nucleótidos Cíclicos Tipo 4/metabolismo , Fosfodiesterasas de Nucleótidos Cíclicos Tipo 4/genética , Neoplasias Ováricas/patología , Neoplasias Ováricas/genética , Neoplasias Ováricas/metabolismo , Animales , Proliferación Celular/genética , Factores de Transcripción de la Familia Snail/metabolismo , Factores de Transcripción de la Familia Snail/genética , Ratones , Movimiento Celular/genética , Transición Epitelial-Mesenquimal/genética , Línea Celular Tumoral , Progresión de la Enfermedad , Ratones Desnudos , Ratones Endogámicos BALB C , Núcleo Celular/metabolismo , Pronóstico
4.
Inorg Chem ; 63(13): 5945-5951, 2024 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-38502918

RESUMEN

Alkali-metal rare-earth carbonates (ARECs) find great potential in nonlinear optical applications. As the most common method, the hydrothermal reaction is widely used in synthesizing ARECs. The black-box nature of the hydrothermal reaction makes it difficult for understanding the formation processes and therefore may slow down the pace of structural discovery. Here, by simply soaking the rare-earth carbonates in Na2CO3 solutions, we successfully obtain a series of noncentrosymmetric Na3RE(CO3)3·6H2O (RE = Tb 1, Sm 2, Eu 3, Gd 4, Dy 5, Ho 6, and Er 7) compounds without using the high-temperature hydrothermal method. The transformation process, investigated by powder X-ray diffraction and scanning electron microscopy, is governed by the concentration of the soaking solutions. Na3Tb(CO3)3·6H2O, as an example, is studied structurally, and its physical properties are characterized. It exhibits a second harmonic generation effect of 0.5 × KDP and a short UV cutoff edge of 222 nm (5.8 eV). Our study provides insights for exploring new AREC structures, which may further advance the development of carbonate nonlinear optical crystals.

5.
Environ Sci Technol ; 58(11): 5129-5138, 2024 Mar 19.
Artículo en Inglés | MEDLINE | ID: mdl-38385684

RESUMEN

Attention has been drawn to the associations between PFASs and human cognitive decline. However, knowledge on the occurrence and permeability of PFASs in the brains of patients with cognitive impairment has not been reported. Here, we determined 30 PFASs in paired sera and cerebrospinal fluids (CSFs) from patients with cognitive impairment (n = 41) and controls without cognitive decline (n = 18). We revealed similar serum PFAS levels but different CSF PFAS levels, with lower CSF PFOA (median: 0.125 vs 0.303 ng/mL, p < 0.05), yet higher CSF PFOS (0.100 vs 0.052 ng/mL, p < 0.05) in patients than in controls. Blood-brain transfer rates also showed lower RCSF/Serum values for PFOA and higher RCSF/Serum values for PFOS in patients, implying potential heterogeneous associations with cognitive function. The RCSF/Serum values for C4-C14 perfluoroalkyl carboxylates exhibited a U-shape trend with increasing chain length. Logistic regression analyses demonstrated that CSF PFOS levels were linked to the heightened risk of cognitive impairment [odds ratio: 3.22 (1.18-11.8)] but not for serum PFOS. Toxicity inference results based on the Comparative Toxicogenomics Database suggested that PFOS in CSF may have a greater potential to impair human cognition than other PFASs. Our results contribute to a better understanding of brain PFAS exposure and its potential impact on cognitive function.


Asunto(s)
Ácidos Alcanesulfónicos , Disfunción Cognitiva , Contaminantes Ambientales , Fluorocarburos , Humanos , Ácidos Alcanesulfónicos/toxicidad , Fluorocarburos/toxicidad , Ácidos Carboxílicos , Permeabilidad
6.
Artículo en Inglés | MEDLINE | ID: mdl-38850333

RESUMEN

AIM: To explore the molecular mechanism underlying the protective effect of hypothermic perfusion on the corneal endothelium during phacoemulsification. METHODS: Phacoemulsification was performed on New Zealand white rabbits. Perfusate at different temperatures was used during the operation, and the aqueous humor was collected for proteomic sequencing after the operation. Corneal endothelial cell injury was simulated by a corneal endothelial cell oxygen-glucose deprivation/reoxygenation (OGD/R) model in vitro. Flow cytometry and evaluation of fluorescent LC3B puncta were used to detect apoptosis and autophagy, and western blotting was used to detect protein expression. RESULTS: A total of 381 differentially expressed proteins were identified between the two groups. In vitro, 4 ℃ hypothermia significantly reduced apoptosis and promoted autophagy. Apoptosis increased after autophagy was inhibited by 3-Methyladenine (3-MA). Furthermore, adiponectin (ADIPOQ) knockdown inhibited phospho-AMPK and blocked the protective effect of hypothermia on corneal endothelial cells. CONCLUSIONS: We investigated the differential expression of proteins between the hypothermia group and normothermia group by proteomics. Moreover, hypothermia-induced ADIPOQ can reduce apoptosis by promoting AMPK-mediated autophagy.

7.
Metab Brain Dis ; 2024 Jul 02.
Artículo en Inglés | MEDLINE | ID: mdl-38954241

RESUMEN

The growing incidence of diabetes mellitus (DM) and depression is a global public health issue. Alpiniae oxyphyllae Fructus (AOF) is a kind of medicinal and edible plant which be found with anti-diabetic property, and could improve depression-like symptoms. This study aimed to screen active targets and potential mechanisms of AOF in treating DM with depression. Injection of streptozotocin (STZ) and exposure to chronic unpredictable mild stress (CUMS) for 4 weeks were used to conduct the DM with depression mice model. Behavioral tests, indexes of glucose metabolism, monoamine neurotransmitters, inflammatory cytokine and oxidative stress were measured. Histopathological change of hippocampus tissue was observing by HE and Nissl staining. UPLC-Q-Exactive Orbitrap/MS, network pharmacology and molecular docking were used to explore the chemical components and mechanisms of AOF on the DM with depression. AOF showed a reversed effect on body weight in DM with depression mice. Glucose metabolism and insulin resistance could be improved by treatment of AOF. In addition, AOF could alleviate depression-like behaviors based on the results of behavior tests and monoamine neurotransmitters. AOF also attenuated STZ-CUMS induced neuron injury in hippocampus. Next, a total of 61 chemical components were identified in the UPLC-Q-Exactive Orbitrap/MS analysis of the extract of AOF. Network pharmacology analysis suggested that 12 active components and 227 targets were screened from AOF, and 1802 target genes were screened from DM with depression, finally 126 intersection target genes were obtained. Drug-disease targets network was constructed and implied that the top five components with a higher degree value includes quercetin, nootkatone, baicalein, (-)-epicatechin and nootkatol. Protein-protein interaction (PPI) network showed that MAPK1, FOS, AKT1, IL6 and TP53 may be the core intersection targets. The mechanism of the effect of AOF on DM with depression was analyzed through gene ontology (GO), and kyoto encyclopedia of genes and genomes (KEGG) enrichment analysis, mainly involved in AGE/RAGE, PI3K/AKT, and MAPK signaling pathways. The results of molecular docking indicated that quercetin, nootkatone, baicalein, (-)-epicatechin and nootkatol all had good binding to the core intersection targets. Overall, our experimental researches have demonstrated that AOF could exert the dual effects of anti-diabetic and anti-depression on DM with depression mice, through multi-targets and multi-pathways.

8.
Int J Mol Sci ; 25(8)2024 Apr 11.
Artículo en Inglés | MEDLINE | ID: mdl-38673831

RESUMEN

Designed ankyrin repeat protein (DARPin) G3 is an engineered scaffold protein. This small (14.5 kDa) targeting protein binds with high affinity to human epidermal growth factor receptor 2 (HER2). HER2 is overexpressed in several cancers. The use of the DARPin G3 for radionuclide therapy is complicated by its high renal reabsorption after clearance via the glomeruli. We tested the hypothesis that a fusion of the DARPin G3 with an albumin-binding domain (ABD) would prevent rapid renal excretion and high renal reabsorption resulting in better tumour targeting. Two fusion proteins were produced, one with the ABD at the C-terminus (G3-ABD) and another at the N-terminus (ABD-G3). Both variants were labelled with 177Lu. The binding properties of the novel constructs were evaluated in vitro and their biodistribution was compared in mice with implanted human HER2-expressing tumours. Fusion with the ABD increased the retention time of both constructs in blood compared with the non-ABD-fused control. The effect of fusion with the ABD depended strongly on the order of the domains in the constructs, resulting in appreciably better targeting properties of [177Lu]Lu-G3-ABD. Our data suggest that the order of domains is critical for the design of targeting constructs based on scaffold proteins.


Asunto(s)
Receptor ErbB-2 , Animales , Femenino , Humanos , Ratones , Albúminas/metabolismo , Repetición de Anquirina , Línea Celular Tumoral , Lutecio , Unión Proteica , Dominios Proteicos , Radioisótopos , Radiofármacos/metabolismo , Receptor ErbB-2/antagonistas & inhibidores , Proteínas Recombinantes de Fusión/metabolismo , Proteínas Recombinantes de Fusión/genética , Proteínas Recombinantes de Fusión/química , Distribución Tisular , Terapia Molecular Dirigida
9.
J Environ Manage ; 357: 120647, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38583385

RESUMEN

Subsidy policies are instrumental in driving the development of new energy. However, the effective allocation of new energy subsidies over time is challenging given fiscal constraints. This study addresses this challenge by considering the learning effect associated with the new energy industry. A two-stage dynamic programming model is proposed to capture the investment decision-making process of companies under new energy subsidy policies and government subsidy setups. Theoretical findings suggest that company investment decisions in new energy are influenced by a guiding principle: The subsidy rate should be negatively correlated with the variation rate of production scale increment (VRPSI). We calibrate this investment decision principle using wind power data from 14 countries. According to this principle, excessive subsidy rates may result in a low VRPSI, thereby diminishing future investment profitability in the new energy industry and leading to subsidy inefficiency. Upon investigating the efficiency of annual subsidy allocation, we find that the subsidy rates were potentially set too high in 2014, 2016, and 2017. Furthermore, the government should exercise caution regarding an inefficient subsidy pattern whereby companies invest in new energy only when the subsidy rate exceeds a certain threshold, neglecting traditional power sources. It is crucial to note that although this study uses wind power industry data for calibration and simulation, the theoretical model can be broadly applied to other new energy industries and emerging industries with increasing marginal net profit.


Asunto(s)
Industrias , Viento , Política Pública , Modelos Teóricos , Inversiones en Salud
10.
Clin Immunol ; 246: 109205, 2023 01.
Artículo en Inglés | MEDLINE | ID: mdl-36509389

RESUMEN

Vogt-Koyanagi-Harada (VKH) disease, a major blinding eye disease, is characterized by an autoimmune response against melanocytes in multiple organs throughout the body. Currently, the aetiology and pathogenesis of VKH disease are unclear, and the treatment strategy needs to be further optimized. The retinal pigment epithelium (RPE), a monolayer of pigmented cells of the fundus, is essential for maintaining normal visual function and is involved in both the acute and chronic stages of VKH disease. Therefore, the functions of the RPE may play a critical role in the aetiology and treatment of VKH disease. Herein, we established a human induced pluripotent stem cell (hiPSC) RPE model of VKH disease by reprogramming peripheral blood mononuclear cells (PBMCs) into iPSCs and then differentiating them into RPE cells. Patient-derived RPE cells exhibited barrier disruption, impaired phagocytosis, and depigmentation compared with those from normal controls, which was consistent with the features of VKH disease. Furthermore, a small molecular compound targeting EGR2 was found to rescue the barrier and phagocytic functions of the hiPSC-RPE cells through high-throughput virtual screening and functional studies, suggesting a promising strategy for the treatment of VKH disease.


Asunto(s)
Células Madre Pluripotentes Inducidas , Síndrome Uveomeningoencefálico , Humanos , Síndrome Uveomeningoencefálico/tratamiento farmacológico , Evaluación Preclínica de Medicamentos , Leucocitos Mononucleares , Epitelio Pigmentado de la Retina
11.
Cancer Immunol Immunother ; 72(1): 211-221, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-35796863

RESUMEN

BACKGROUND: Chimeric antigen receptor (CAR) T cells are used to treat refractory and recurrent B-cell lymphoma. When administered intravenously, CAR T cells can be detected in cerebrospinal fluid, and thus represent a promising method for the treatment of central nervous system lymphoma (CNSL). This meta-analysis aimed to clarify the effectiveness and safety of CAR T-cell therapy in the treatment of CNSL. METHODS: Studies involving patients with CNSL who received CAR T-cell therapy that reported overall response (OR), complete response (CR), and partial response (PR) were included. A random-effects or fixed-effects model with double arcsine transformation was used for the pooled analysis and 95% confidence intervals (CI) were determined for all outcomes. RESULTS: Eight studies, comprising 63 patients, were identified and were included in the meta-analysis. The pooled OR and CR rates after treatment with CAR T cells were 69% (95% CI, 56-81%) and 51% (95% CI, 37-64%), respectively. The pooled rate of progressive disease after remission was 38% (95% CI, 21-55%). The pooled rate for neurotoxicity grade 3 or above was 12% (95% CI, 3-24%, I2 = 0.00%, p = 0.53). No treatment-related deaths were reported. CONCLUSIONS: CAR T-cell therapy is a promising option for the treatment of CNSL owing to a high short-term remission rate and controllable side effects. However, the high recurrence rate after remission must be addressed. Long-term follow-up data with large sample sizes are also needed to better assess the effectiveness and safety of CAR T-cell therapy. REGISTRATION: This meta-analysis was registered in the international prospective register of systematic reviews (PROSPERO) (CRD42022301332).


Asunto(s)
Linfoma de Células B , Receptores Quiméricos de Antígenos , Humanos , Recurrencia Local de Neoplasia , Inmunoterapia Adoptiva/efectos adversos , Inmunoterapia Adoptiva/métodos , Linfocitos T , Sistema Nervioso Central , Antígenos CD19
12.
Small ; 19(43): e2301307, 2023 10.
Artículo en Inglés | MEDLINE | ID: mdl-37376877

RESUMEN

Triple-negative breast cancer (TNBC), one of the most aggressive types of breast cancer, currently lacks a targeted therapy and has a high clinical recurrence rate. The present study reports an engineered magnetic nanodrug based on Fe3 O4 vortex nanorods coated with a macrophage membrane loaded with doxorubicin (DOX) and Enhancer of zeste 2 polycomb repressive complex 2 subunit (EZH2) siRNA. This novel nanodrug displays excellent tissue penetration and preferential tumor accumulation. More importantly, it significantly increases tumor suppression compared to chemotherapy, suggesting the synergistic activity of the combination of doxorubicin and EZH2-inhibition. Importantly, owing to tumor-targeted delivery, nanomedicine shows an excellent safety profile after systemic delivery, unlike conventional chemotherapy. In summary, chemotherapy and gene therapy are combined into a novel magnetic nanodrug carrying doxorubicin and EZH2 siRNA, which shows promising clinical application potential in TNBC therapy.


Asunto(s)
Neoplasias de la Mama Triple Negativas , Humanos , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Neoplasias de la Mama Triple Negativas/genética , ARN Interferente Pequeño , Proteína Potenciadora del Homólogo Zeste 2/genética , Doxorrubicina/farmacología , Doxorrubicina/uso terapéutico , Fenómenos Magnéticos , Línea Celular Tumoral
13.
Crit Rev Food Sci Nutr ; 63(10): 1390-1405, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-34387535

RESUMEN

Iron-porphyrin is a very important substance in organisms, especially in animals. It is not only the source of iron in human body, but is also the catalytic center of many reactions. Previous studies suggested that adequate intake of iron was important for the health of human, especially for children and pregnant women. However, associated diseases caused by iron over-intake and excessive meat consumption suggested its potential harmfulness for human health. During meat processing, Iron-porphyrin will cause the oxidation of proteins and fatty acids. In the gastrointestinal tract, iron-porphyrin can induce the production of malondialdehyde, fats oxidation, and indirectly cause oxidation of amino acids and nitrates etc. Iron-porphyrin enters the intestinal tract and disturbs the balance of intestinal flora. Finally, some common measures for inhibiting its activity are introduced, including the use of chelating agent, antioxidants, competitive inhibitor, etc., as well as give the hypothesis that sodium chloride increases the catalytic activity of iron-porphyrin. The purpose of this review is to present an overview of current knowledge about the changes of iron-porphyrin in the whole technico- and gastrointesto- processing axis and to provide ideas for further research in meat nutrition.


Asunto(s)
Porfirinas , Animales , Niño , Humanos , Femenino , Embarazo , Hemo/metabolismo , Hierro/metabolismo , Carne , Tracto Gastrointestinal/metabolismo
14.
Crit Rev Food Sci Nutr ; : 1-20, 2023 Jan 06.
Artículo en Inglés | MEDLINE | ID: mdl-36606553

RESUMEN

Lycopene as a natural antioxidant that have been studied for ultraviolet radiation (UVR) photo protection and is one of the most effective carotenoids to scavenge reactive oxygen species (ROS). This review aims to summarize the protective effect of tomato and lycopene on skin photo damage and skin photoaging in healthy subjects by reviewing the existing population intervention experiments. A total of five electronic databases including PubMed, Scopus, EBSCO, Web of Science and Cochrane Library were searched from inceptions to January 2021 without any restriction. Out of 19336 publications identified, 21 fulfilled the inclusion criteria and were meta-analysis. Overall, interventions supplementing tomato and lycopene were associated with significant reductions in Δa*, MMP-1, ICAM-1 and skin pigmentation; while tomato and lycopene supplementation were associated with significant increase in MED, skin thickness and skin density. Based on the results of this systematic review and meta-analysis, supplementation with tomato and lycopene could reduce skin erythema formation and improve the appearance and pigmentation of the skin, thereby preventing light-induced skin photodamage and skin photoaging. Lycopene-rich products could be used as endogenous sun protection and may be a potential nutraceutical for sun protection.

15.
Crit Rev Food Sci Nutr ; : 1-18, 2023 May 19.
Artículo en Inglés | MEDLINE | ID: mdl-37204758

RESUMEN

Several randomized controlled trials (RCTs) have investigated the effects of fermented foods on metabolic outcomes in adult patients suffering from diabetes and prediabetes. However, the results of these RCTs are conflicting. This systematic review and meta-analysis was carried out on data from RCTs to evaluate the effects of fermented foods in patients with diabetes and prediabetes. The PubMed, Web of Science, Embase, the Cochrane Library and Scopus databases were searched up to 21 June, 2022. English-language RCTs of fermented foods consumption were included which gave metabolic outcomes on body composition, glucose control, insulin sensitivity, lipid profile, as well as blood pressure. Eighteen RCTs met the inclusion criteria and 843 participants were included in the final analysis. The pooled results showed a significant reduction of fasting blood glucose (FBG), the homeostatic model assessment of insulin resistance (HOMA-IR), total cholesterol (TC), low density lipid cholesterol (LDL-C) and diastolic blood pressure (DBP) in the intervention group versus the control group. The results of this research showed that fermented foods have the potential to improve some metabolic outcomes, including FBG, HOMA-IR, TC, LDL-C, and DBP in patients with diabetes and prediabetes.

16.
Biometrics ; 79(4): 3307-3318, 2023 12.
Artículo en Inglés | MEDLINE | ID: mdl-37661821

RESUMEN

For multivariate functional data, a functional latent factor model is proposed, extending the traditional latent factor model for multivariate data. The proposed model uses unobserved stochastic processes to induce the dependence among the different functions, and thus, for a large number of functions, may provide a more parsimonious and interpretable characterization of the otherwise complex dependencies between the functions. Sufficient conditions are provided to establish the identifiability of the proposed model. The performance of the proposed model is assessed through simulation studies and an application to electroencephalography data.


Asunto(s)
Electroencefalografía , Modelos Estadísticos , Simulación por Computador , Procesos Estocásticos
17.
Mol Ther ; 30(12): 3658-3676, 2022 12 07.
Artículo en Inglés | MEDLINE | ID: mdl-35715953

RESUMEN

The full potential of tumor-infiltrating lymphocyte (TIL) therapy has been hampered by the inadequate activation and low persistence of TILs, as well as inefficient neoantigen presentation by tumors. We transformed tumor cells into artificial antigen-presenting cells (aAPCs) by infecting them with a herpes simplex virus 1 (HSV-1)-based oncolytic virus encoding OX40L and IL12 (OV-OX40L/IL12) to provide local signals for optimum T cell activation. The infected tumor cells displayed increased expression of antigen-presenting cell-related markers and induced enhanced T cell activation and killing in coculture with TILs. Combining OV-OX40L/IL12 and TIL therapy induced complete tumor regression in patient-derived xenograft and syngeneic mouse tumor models and elicited an antitumor immunological memory. In addition, the combination therapy produced aAPC properties in tumor cells, activated T cells, and reprogrammed macrophages to a more M1-like phenotype in the tumor microenvironment. This combination strategy unleashes the full potential of TIL therapy and warrants further evaluation in clinical studies.


Asunto(s)
Virus Oncolíticos , Humanos , Animales , Ratones , Virus Oncolíticos/genética , Linfocitos Infiltrantes de Tumor , Células Presentadoras de Antígenos
18.
Appetite ; 191: 107048, 2023 Oct 05.
Artículo en Inglés | MEDLINE | ID: mdl-37804604

RESUMEN

Memory about food and eating is crucial in regulating appetite and eating behaviors. Successfully stopping vivid imagination of delicious food could help reduce food craving and thus reduce the possibility of further intake. Memory inhibition is a cognitive process that involves intentional suppression of certain memories coming to consciousness. Successful memory suppression derives from inhibitory control. Although considerable work has consistently observed the impairment in motor or response inhibitory control among individuals with obesity, there has been a lack of investigation into the influence of bodyweight status on memory inhibitory control. To fill this gap, current study investigated behavioral and neurophysiological correlates of memory suppression in young women. Using Think/No-Think task and event-related potentials among 47 females, we found that participants with higher visceral adipose tissue (VAT) showed a tendency towards decreased suppression ability for memories related to food but not memories related to nonfood items. In depth analysis showed that decrease in the differences in P2 amplitudes between suppression vs. retrieval of food-related memories mediated the impairment of suppression ability by high VAT. We then tested whether individual differences in memory suppression ability as well as ERP correlates predicted future BMI or VAT change over 1-year follow-up. Results showed that P2 amplitudes when retrieving food-related memory could predict VAT change at 1-year follow-up among participants with healthy BMI. These observations suggest a hypersensitivity inference hypothesis underlying memory control impairments. To be specific, deficits in memory suppression may be in part resulted from elevated sensitivity to the cues coupling with food-related memory. It extends previous studies of memory suppression with food rewards and provides the first evidence to help understand the relationship between inhibitory control on food-related memory and obesity.

19.
Arch Gynecol Obstet ; 308(2): 351-362, 2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-35947146

RESUMEN

OBJECTIVE: To evaluate the efficacy and safety of high-intensity focused ultrasound (HIFU) combined with the levonorgestrel intrauterine system (LNG-IUS) for adenomyosis. METHODS: We searched PubMed, Embase, Cochrane Library, Web of Science, CNKI, SinoMed, Wanfang, and VIP databases from their inception to Nov 20, 2021 for relevant articles that compared HIFU combined with LNG-IUS vs. HIFU alone in patients with adenomyosis. RevMan5.4 software was used for the data analysis. The primary outcome was changes in volume of the uterine. Secondary outcomes included visual analog scale (VAS) scores for dysmenorrhea, serum CA125 level, recurrence rate, changes in volume of the adenomyotic lesion, menstrual volume scores, and adverse reactions. Data synthesis was conducted using a random-effects model with significant heterogeneity (I2 > 50%), and using a fixed-effects model otherwise. This study is registered on the PROSPERO platform (CRD42021295214). RESULTS: The final analysis included 13 studies, with a total of 1861 patients. Results of analysis revealed that there was no significant difference in uterine volume reduction between the HIFU control group and the HIFU/LNG-IUS group at 3 months after procedure (MD:30.63). Compared with the HIFU control group, the HIFU/LNG-IUS group had more pronounced reduction in uterine volume at 6 (MD:29.04) and 12 months (MD:22.10) after procedure. The HIFU/LNG-IUS group has lower VAS scores for dysmenorrhea than the HIFU control group at 3 (MD:1.68), 6 (MD:1.69), and 12 months (MD:1.30) after procedure. Serum CA125 level in the HIFU/LNG-IUS group decreased more significantly than the HIFU control group at 6 (MD:18.34) and 12 months (MD:18.49) after procedure. The recurrence rate in the HIFU/LNG-IUS group was lower than that in the HIFU control group (RR:0.20). CONCLUSIONS: Compared to HIFU control group, HIFU/LNG-IUS group for the management of adenomyosis had more advantages in alleviating symptoms and decreasing the volumes of the uterine and adenomyotic lesions. However, since the number of the included studies was too small and some of them were not RCT, this conclusion needs to be referenced with caution.


Asunto(s)
Adenomiosis , Dispositivos Intrauterinos Medicados , Femenino , Humanos , Levonorgestrel/uso terapéutico , Adenomiosis/cirugía , Adenomiosis/patología , Dismenorrea/terapia , Útero/patología , Menstruación
20.
Nano Lett ; 22(13): 5584-5591, 2022 Jul 13.
Artículo en Inglés | MEDLINE | ID: mdl-35733084

RESUMEN

Vibration is an omnipresent energy source that is renewable and has the potential to cause damage to transmission lines. Harvesting harmful vibration energy can achieve vibration attenuation. Here, a vibration-driven triboelectric nanogenerator (V-TENG) with the potential for vibration attenuation is proposed as a power source for monitoring the operating condition of transmission lines. The V-TENG with structural optimization and frequency response range improvement is first discussed, indicating that it has a simple structural design with a good output performance. Then an energy management circuit is used to improve the charging efficiency of large capacitors. The vibration attenuation effect and wireless transmission system are verified in the simulation environment, benefiting from the well-designed structure and outstanding electric performance. This work demonstrates an efficient strategy for harvesting vibration energy through the TENG, which provides valuable guidance for further construction of online monitoring of transmission lines.

SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA