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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.
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Síndrome de Down , Neocórtex , Animais , Humanos , Camundongos , Modelos Animais de Doenças , Síndrome de Down/genética , Síndrome de Down/metabolismo , Síndrome de Down/patologia , Drosophila , Interneurônios/metabolismo , Terminações Pré-Sinápticas/metabolismo , Sinapses/metabolismoRESUMO
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.
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Actinidia , Resistência à Seca , Actinidia/genética , Actinidia/fisiologia , Resistência à Seca/genética , Frutas/genética , Frutas/fisiologia , Genótipo , Análise Multivariada , Raízes de Plantas/fisiologia , Raízes de Plantas/genética , Estresse Fisiológico/genéticaRESUMO
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.
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Movimento Celular , Proliferação de Células , Nucleotídeo Cíclico Fosfodiesterase do Tipo 4 , Transição Epitelial-Mesenquimal , Regulação Neoplásica da Expressão Gênica , Neoplasias Ovarianas , Fatores de Transcrição da Família Snail , Humanos , Feminino , Nucleotídeo Cíclico Fosfodiesterase do Tipo 4/metabolismo , Nucleotídeo Cíclico Fosfodiesterase do Tipo 4/genética , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/metabolismo , Animais , Proliferação de Células/genética , Fatores de Transcrição da Família Snail/metabolismo , Fatores de Transcrição da Família Snail/genética , Camundongos , Movimento Celular/genética , Transição Epitelial-Mesenquimal/genética , Linhagem Celular Tumoral , Progressão da Doença , Camundongos Nus , Camundongos Endogâmicos BALB C , Núcleo Celular/metabolismo , PrognósticoRESUMO
Camellia fascicularis has important ornamental, medicinal, and food value. It also has tremendous potential for exploiting bioactivities. However, the bioactivities of secondary metabolites in C. fascicularis have not been reported. The structures of compounds were determined by spectral analysis and nuclear magnetic resonance (NMR) combined with the available literature on secondary metabolites of C. fascicularis leaves. In this study, 15 compounds were identified, including 5 flavonoids (1-5), a galactosylglycerol derivative (6), a terpenoid (7), 4 lignans (8-11), and 4 phenolic acids (12-15). Compounds 6-7 and 9-12 were isolated from the genus Camellia for the first time. The remaining compounds were also isolated from C. fascicularis for the first time. Evaluation of antioxidant and antimicrobial activities revealed that compounds 5 and 8-11 exhibited stronger antioxidant activity than the positive drug ascorbic acid, while compounds 7, 13, and 15 showed similar activity to ascorbic acid. The minimum inhibitory concentration (MIC) of antibacterial activity for compounds 5, 7, 9, 11, and 13 against Pseudomonas aeruginosa was comparable to that of the positive control drug tetracycline at a concentration of 62.50 µg/mL; other secondary metabolites inhibited Escherichia coli and Staphylococcus aureus at concentrations ranging from 125-250 µg/mL.
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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.
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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.
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Ácidos Alcanossulfônicos , Disfunção Cognitiva , Poluentes Ambientais , Fluorocarbonos , Humanos , Ácidos Alcanossulfônicos/toxicidade , Fluorocarbonos/toxicidade , Ácidos Carboxílicos , PermeabilidadeRESUMO
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 â 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.
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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.
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Alpinia , Depressão , Diabetes Mellitus Experimental , Simulação de Acoplamento Molecular , Farmacologia em Rede , Animais , Camundongos , Masculino , Depressão/tratamento farmacológico , Depressão/metabolismo , Diabetes Mellitus Experimental/tratamento farmacológico , Alpinia/química , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Cromatografia Líquida de Alta Pressão , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Antidepressivos/uso terapêutico , Antidepressivos/farmacologiaRESUMO
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.
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Receptor ErbB-2 , Animais , Feminino , Humanos , Camundongos , Albuminas/metabolismo , Repetição de Anquirina , Linhagem Celular Tumoral , Lutécio , Ligação Proteica , Domínios Proteicos , Radioisótopos , Compostos Radiofarmacêuticos/metabolismo , Receptor ErbB-2/antagonistas & inibidores , Proteínas Recombinantes de Fusão/metabolismo , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/química , Distribuição Tecidual , Terapia de Alvo MolecularRESUMO
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.
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Indústrias , Vento , Política Pública , Modelos Teóricos , Investimentos em SaúdeRESUMO
Human activities and climate change impact ecosystem services, thereby affecting economic and social sustainable development. Measuring the heterogeneity in space and time of how human activities affect ecosystem services poses a challenge for the sustainable management of land resources. Based on "human appropriation of net primary production (HANPP) - Fractional Vegetation Cover (FVC) - Soil Conservation Service (SCS)" cascading effect, first, a geographically and temporally weighted regression (GTWR) model was employed to assess the impact of HANPP in percent of potential NPP (hereafter HANPP%) on the FVC; second, changes in the FVC caused by human activities were quantified; and third, the potential soil conservation service (SCSp) and actual soil conservation service (SCSa) were estimated using the Revised Universal Soil Loss Equation (RUSLE) model, and the difference between them represented the changes in soil conservation service caused by human activities (SCSh). Taking the Qinghai-Tibet Plateau as a case study, we found that the GTWR model was well suited for analyzing the relationship between the HANPP% and the FVC (R2 = 0.897). The HANPP resulted in a decrease in the FVC from 0.222 in 2001 to 0.199 in 2019 and correspondingly resulted in a decrease in the ratio of SCSh to SCSp from 8.95% to 7.24%. This study provides a quantitative method that allows quantifying the influence of human activity on ecosystem services closely related to the FVC.
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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.
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Células-Tronco Pluripotentes Induzidas , Síndrome Uveomeningoencefálica , Humanos , Síndrome Uveomeningoencefálica/tratamento farmacológico , Avaliação Pré-Clínica de Medicamentos , Leucócitos Mononucleares , Epitélio Pigmentado da RetinaRESUMO
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).
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Linfoma de Células B , Receptores de Antígenos Quiméricos , Humanos , Recidiva Local de Neoplasia , Imunoterapia Adotiva/efeitos adversos , Imunoterapia Adotiva/métodos , Linfócitos T , Sistema Nervoso Central , Antígenos CD19RESUMO
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.
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Neoplasias de Mama Triplo Negativas , Humanos , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/genética , RNA Interferente Pequeno , Proteína Potenciadora do Homólogo 2 de Zeste/genética , Doxorrubicina/farmacologia , Doxorrubicina/uso terapêutico , Fenômenos Magnéticos , Linhagem Celular TumoralRESUMO
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.
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Porfirinas , Animais , Criança , Humanos , Feminino , Gravidez , Heme/metabolismo , Ferro/metabolismo , Carne , Trato Gastrointestinal/metabolismoRESUMO
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.
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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.
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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.
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Eletroencefalografia , Modelos Estatísticos , Simulação por Computador , Processos EstocásticosRESUMO
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.
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Vírus Oncolíticos , Humanos , Animais , Camundongos , Vírus Oncolíticos/genética , Linfócitos do Interstício Tumoral , Células Apresentadoras de AntígenosRESUMO
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.