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Sleep loss robustly disrupts mood and emotion regulation in healthy individuals but can have a transient antidepressant effect in a subset of patients with depression. The neural mechanisms underlying this paradoxical effect remain unclear. Previous studies suggest that the amygdala and dorsal nexus (DN) play key roles in depressive mood regulation. Here, we used functional MRI to examine associations between amygdala- and DN-related resting-state connectivity alterations and mood changes after one night of total sleep deprivation (TSD) in both healthy adults and patients with major depressive disorder using strictly controlled in-laboratory studies. Behavioral data showed that TSD increased negative mood in healthy participants but reduced depressive symptoms in 43% of patients. Imaging data showed that TSD enhanced both amygdala- and DN-related connectivity in healthy participants. Moreover, enhanced amygdala connectivity to the anterior cingulate cortex (ACC) after TSD associated with better mood in healthy participants and antidepressant effects in depressed patients. These findings support the key role of the amygdala-cingulate circuit in mood regulation in both healthy and depressed populations and suggest that rapid antidepressant treatment may target the enhancement of amygdala-ACC connectivity.
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Transtorno Depressivo Maior , Adulto , Humanos , Transtorno Depressivo Maior/diagnóstico por imagem , Transtorno Depressivo Maior/tratamento farmacológico , Privação do Sono/diagnóstico por imagem , Tonsila do Cerebelo/diagnóstico por imagem , Giro do Cíngulo/diagnóstico por imagem , Antidepressivos/farmacologia , Antidepressivos/uso terapêutico , Imageamento por Ressonância Magnética/métodosRESUMO
Ionizing radiation such as X-rays and γ-rays has been extensively studied and used in various fields such as medical imaging, radiographic nondestructive testing, nuclear defense, homeland security, and scientific research. Therefore, the detection of such high-energy radiation with high-sensitivity and low-cost-based materials and devices is highly important and desirable. Halide perovskites have emerged as promising candidates for radiation detection due to the large light absorption coefficient, large resistivity, low leakage current, high mobility, and simplicity in synthesis and processing as compared with commercial silicon (Si) and amorphous selenium (a-Se). In this review, we provide an extensive overview of current progress in terms of materials development and corresponding device architectures for radiation detection. We discuss the properties of a plethora of reported compounds involving organic-inorganic hybrid, all-inorganic, all-organic perovskite and antiperovskite structures, as well as the continuous breakthroughs in device architectures, performance, and environmental stability. We focus on the critical advancements of the field in the past few years and we provide valuable insight for the development of next-generation materials and devices for radiation detection and imaging applications.
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Arterial spin-labeled perfusion and blood oxygenation level-dependent functional MRI are indispensable tools for noninvasive human brain imaging in clinical and cognitive neuroscience, yet concerns persist regarding the reliability and reproducibility of functional MRI findings. The circadian rhythm is known to play a significant role in physiological and psychological responses, leading to variability in brain function at different times of the day. Despite this, test-retest reliability of brain function across different times of the day remains poorly understood. This study examined the test-retest reliability of six repeated cerebral blood flow measurements using arterial spin-labeled perfusion imaging both at resting-state and during the psychomotor vigilance test, as well as task-induced cerebral blood flow changes in a cohort of 38 healthy participants over a full day. The results demonstrated excellent test-retest reliability for absolute cerebral blood flow measurements at rest and during the psychomotor vigilance test throughout the day. However, task-induced cerebral blood flow changes exhibited poor reliability across various brain regions and networks. Furthermore, reliability declined over longer time intervals within the day, particularly during nighttime scans compared to daytime scans. These findings highlight the superior reliability of absolute cerebral blood flow compared to task-induced cerebral blood flow changes and emphasize the importance of controlling time-of-day effects to enhance the reliability and reproducibility of future brain imaging studies.
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Encéfalo , Circulação Cerebrovascular , Imageamento por Ressonância Magnética , Descanso , Humanos , Masculino , Feminino , Adulto , Circulação Cerebrovascular/fisiologia , Reprodutibilidade dos Testes , Descanso/fisiologia , Encéfalo/diagnóstico por imagem , Encéfalo/fisiologia , Encéfalo/irrigação sanguínea , Adulto Jovem , Imageamento por Ressonância Magnética/métodos , Imagem de Perfusão/métodos , Desempenho Psicomotor/fisiologia , Ritmo Circadiano/fisiologia , Nível de Alerta/fisiologiaRESUMO
Sleep loss impacts a broad range of brain and cognitive functions. However, how sleep deprivation affects risky decision-making remains inconclusive. This study used functional MRI to examine the impact of one night of total sleep deprivation (TSD) on risky decision-making behavior and the underlying brain responses in healthy adults. In this study, we analyzed data from N = 56 participants in a strictly controlled 5-day and 4-night in-laboratory study using a modified Balloon Analogue Risk Task. Participants completed two scan sessions in counter-balanced order, including one scan during rested wakefulness (RW) and another scan after one night of TSD. Results showed no differences in participants' risk-taking propensity and risk-induced activation between RW and TSD. However, participants showed significantly reduced neural activity in the anterior cingulate cortex and bilateral insula for loss outcomes, and in bilateral putamen for win outcomes during TSD compared with RW. Moreover, risk-induced activation in the insula negatively correlated with participants' risk-taking propensity during RW, while no such correlations were observed after TSD. These findings suggest that sleep loss may impact risky decision-making by attenuating neural responses to decision outcomes and impairing brain-behavior associations.
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Tomada de Decisões , Privação do Sono , Adulto , Humanos , Tomada de Decisões/fisiologia , Encéfalo , Cognição , Giro do Cíngulo , Imageamento por Ressonância Magnética , Assunção de RiscosRESUMO
Lauric acid (LA), a saturated fatty acid with 12 carbon atoms, is widely regarded as a healthy fatty acid that plays an important role in disease resistance and improving immune physiological function. The objective of this study was to determine the effects of dietary lauric acid on the growth performance, antioxidant capacity, non-specific immunity and intestinal microbiology, and evaluate the potential of lauric acids an environmentally friendly additive in swimming crab (Portunus trituberculatus) culture. A total of 192 swimming crabs with an initial body weight of 11.68 ± 0.02 g were fed six different dietary lauric acid levels, the analytical values of lauric acid were 0.09, 0.44, 0.80, 1.00, 1.53, 2.91 mg/g, respectively. There were four replicates per treatment and 8 juvenile swimming crabs per replicate. The results indicated that final weight, percent weight gain, specific growth rate, survival and feed intake were not significantly affected by dietary lauric acid levels; however, crabs fed diets with 0.80 and 1.00 mg/g lauric acid showed the lowest feed efficiency among all treatments. Proximate composition in hepatopancreas and muscle were not significantly affected by dietary lauric acid levels. The highest activities of amylase and lipase in hepatopancreas and intestine were found at crabs fed diet with 0.80 mg/g lauric acid (P < 0.05), the activity of carnitine palmityl transferase (CPT) in hepatopancreas and intestine significantly decreased with dietary lauric acid levels increasing from 0.09 to 2.91 mg/g (P < 0.05). The lowest concentration of glucose and total protein and the activity of alkaline phosphatase in hemolymph were observed at crabs fed diets with 0.80 and 1.00 mg/g lauric acid among all treatments. The activity of GSH-Px in hepatopancreas significantly increased with dietary lauric acid increasing from 0.09 to 1.53 mg/g, MDA in hepatopancreas and hemolymph was not significantly influenced by dietary lauric acid levels. The highest expression of cat and gpx in hepatopancreas were exhibited in crabs fed diet with 1.00 mg/g lauric acid, however, the expression of genes related to the inflammatory signaling pathway (relish, myd88, traf6, nf-κB) were up-regulated in the hepatopancreas with dietary lauric acid levels increasing from 0.09 to 1.00 mg/g, moreover, the expression of genes related to intestinal inflammatory, immune and antioxidant were significantly affected by dietary lauric acid levels (P < 0.05). Crabs fed diet without lauric acid supplementation exhibited higher lipid drop area in hepatopancreas than those fed the other diets (P < 0.05). The expression of genes related to lipid catabolism was up-regulated, however, and the expression of genes related to lipid synthesis was down-regulated in the hepatopancreas of crabs fed with 0.80 mg/g lauric acid. Lauric acid improved hepatic tubular integrity, and enhanced intestinal barrier function by increasing peritrophic membrane (PM) thickness and upregulating the expression of structural factors (per44, zo-1) and intestinal immunity-related genes. In addition, dietary 1.00 mg/g lauric acid significantly improved the microbiota composition of the intestinal, increased the abundance of Actinobacteria and Rhodobacteraceae, and decreased the abundance of Vibrio, thus maintaining the microbiota balance of the intestine. The correlation analysis showed that there was a relationship between intestinal microbiota and immune-antioxidant function. In conclusion, the dietary 1.00 mg/g lauric acid is beneficial to improve the antioxidant capacity and intestinal health of swimming crab.
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Ração Animal , Antioxidantes , Braquiúros , Dieta , Suplementos Nutricionais , Microbioma Gastrointestinal , Ácidos Láuricos , Animais , Braquiúros/imunologia , Braquiúros/efeitos dos fármacos , Braquiúros/crescimento & desenvolvimento , Braquiúros/microbiologia , Ácidos Láuricos/farmacologia , Ácidos Láuricos/administração & dosagem , Ração Animal/análise , Antioxidantes/metabolismo , Dieta/veterinária , Suplementos Nutricionais/análise , Microbioma Gastrointestinal/efeitos dos fármacos , Imunidade Inata/efeitos dos fármacos , Intestinos/efeitos dos fármacos , Intestinos/imunologia , Distribuição Aleatória , Relação Dose-Resposta a DrogaRESUMO
This experiment was conducted to explore the effects of dietary vitamin C supplementation on non-specific immune defense, antioxidant capacity and resistance to low-temperature stress of juvenile mud crab (Scylla paramamosain). Mud crabs with an initial weight of 14.67 ± 0.13 g were randomly divided into 6 treatments and fed diets with 0.86 (control), 44.79, 98.45, 133.94, 186.36 and 364.28 mg/kg vitamin C, respectively. The experiment consisted of 6 treatments, each treatment was designed with 4 replicates and each replicate was stocked with 8 crabs. After 42 days of feeding experiment, 2 crabs were randomly selected from each replicate, and a total of 8 crabs in each treatment were carried out 72 h low-temperature challenge experiment. The results showed that crabs fed diets with 186.36 and 364.28 mg/kg vitamin C significantly improved the activities of alkaline phosphatase (AKP) and acid phosphatase (ACP) in hemolymph and hepatopancreas (P < 0.05). Crabs fed diet with 133.94 mg/kg vitamin C significantly decreased the concentration of nitric oxide (NO) and the activity of nitric oxide synthase (NOS) in hemolymph (P < 0.05). Diet with 133.94 mg/kg vitamin C was improved the activity of polyphenol oxidase (PPO) and the concentration of albumin (ALB) in hemolymph. Crabs fed diet with 133.94 mg/kg vitamin C showed lower concentration of malondialdehyde (MDA) in hemolymph and hepatopancreas than those fed the other diets. Meanwhile, crabs fed diet with 98.45 mg/kg vitamin C showed higher activity of total superoxide dismutase (T-SOD) in hemolymph, and crabs fed diet with 133.94 mg/kg vitamin C showed higher activity of T-SOD in hepatopancreas. Crabs fed diet with 186.36 mg/kg vitamin C significantly decreased the concentration of reduced glutathione (GSH) and the activity of glutathione peroxidase (GSH-PX) in hepatopancreas (P < 0.05). In normal temperature, crabs fed diets with 133.94 mg/kg vitamin C significantly up-regulated the expression levels of gpx (glutathione peroxidase) and trx (thioredoxin) in hepatopancreas compared with the control treatment (P < 0.05). The highest expression levels of relish, il16 (interleukin 16), caspase 2 (caspase 2), p38 mapk (p38 mitogen-activated protein kinases) and bax (bcl-2 associated x protein) in hepatopancreas were found at crabs fed control diet (P < 0.05). Moreover, crabs fed diet with 133.94 mg/kg vitamin C showed higher expression levels of alf-3 (anti-lipopolysaccharide factor 3) and bcl-2 (B-cell lymphoma 2) in hepatopancreas than those fed the other diets (P < 0.05). Under low-temperature stress, crabs fed diet with 133.94 mg/kg vitamin C significantly improved the expression levels of hsp90 (heat shock protein 90), cat (catalase), gpx, prx (thioredoxin peroxidase) and trx in hepatopancreas (P < 0.05). In addition, dietary with 133.94 vitamin C significantly up-regulated the expression levels of alf-3 and bcl-2 (P < 0.05). Based on two slope broken-line regression analysis of activity of PPO against the dietary vitamin C level, the optimal dietary vitamin C requirement was estimated to be 144.81 mg/kg for juvenile mud crab. In conclusion, dietary 133.94-144.81 mg/kg vitamin C significantly improved the non-specific immune defense, antioxidant capacity and resistance to low-temperature stress of juvenile mud crab.
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BACKGROUND: Childhood-onset systemic lupus erythematosus (cSLE) is a chronic autoimmune disease that is often more severe than adult-onset SLE and is challenging to diagnose due to its variable presentation and lack of specific diagnostic tests. OBJECTIVES: This study aimed to identify potential diagnostic biomarkers for cSLE by analyzing differentially expressed genes (DEGs) using machine learning algorithms. METHODS: In this study, we utilized the Gene Expression Omnibus database to investigate the DEGs between cSLE and normal samples, conducting a functional enrichment analysis on DEGs. Subsequently, we employed machine learning algorithms, including Least Absolute Shrinkage and Selection Operator regression and Support Vector Machine-Recursive Feature Elimination, to identify hub DEGs, which serve as crucial biomarkers. We delved into the role of these hub DEGs in the pathogenesis of the disease and the correlation between these hub DEGs and immune infiltration by comprehensive immune infiltration analysis using the CIBERSORT algorithm. RESULTS: We identified 110 DEGs in cSLE, including 95 upregulated and 15 downregulated genes. Functional annotation revealed that these DEGs were involved in immune response processes, viral defense mechanisms, and regulation of interferon responses. Machine learning algorithms identified CCR1 and SAMD9L as hub DEGs, which were validated in multiple datasets and demonstrated high diagnostic value for cSLE. Mechanistic exploration suggested that CCR1 and SAMD9L are involved in immune response modulation, particularly in interferon signaling and the innate immune system. Assessment of immune cell infiltration revealed significant differences in immune cell composition between cSLE patients and healthy controls, with cSLE patients exhibiting a higher proportion of neutrophils. Moreover, CCR1 and SAMD9L expression levels showed positive correlations with neutrophil infiltration and other immune cell types. CONCLUSION: CCR1 and SAMD9L were identified as potential diagnostic biomarkers for cSLE using machine learning and were validated in multiple datasets. These findings provide novel insights into the biological underpinnings of cSLE.
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Biomarcadores , Lúpus Eritematoso Sistêmico , Aprendizado de Máquina , Humanos , Lúpus Eritematoso Sistêmico/genética , Lúpus Eritematoso Sistêmico/imunologia , Biomarcadores/metabolismo , Biomarcadores/análise , Criança , Algoritmos , Bases de Dados Genéticas , Perfilação da Expressão Gênica , Máquina de Vetores de SuporteRESUMO
BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) infection has many neurological manifestations, and its effects on the nervous system are increasingly recognized. There has been no systematic analysis of electroencephalography (EEG) characteristics in children exhibiting neurological symptoms of Coronavirus disease 2019 (COVID-19). The primary aim of this study was to describe the EEG characteristics caused by COVID-19 infection in children who were showing neurological symptoms and to assess the relationship between COVID-19-related EEG changes and clinical features in these children. METHOD: This study included 125 pediatric patients infected with SARS-CoV2 and showing neurological symptoms, and their continuous EEG was recorded. In addition, the demographic and clinical characteristics of these patients were analyzed and the correlation between the two was investigated. RESULTS: Abnormal EEG findings were detected in 31.20% (N = 39) of the patients. Abnormal discharges (43.59%) were the most common EEG abnormalities, followed by background abnormalities (41.03%). The proportion of patients diagnosed with febrile seizure was higher in the normal EEG group than in the abnormal EEG group (P = 0.002), while the opposite was true for epilepsy and encephalitis/encephalopathy (P = 0.016 and P = 0.003, respectively). The independent associated factors of abnormal EEG were age and total length of stay (P < 0.001 and P = 0.003, respectively). Non-specific EEG abnormalities were found in COVID-19-related encephalitis/encephalopathy. CONCLUSION: Our study corroborated that a small group of pediatric patients infected by COVID-19 and showing neurological symptoms may exhibit abnormal EEG. This study could help improve the understanding of clinical and EEG characteristics in children with COVID-19 and inform triage policies in other hospitals during the COVID-19 pandemic.
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Encefalopatias , COVID-19 , Encefalite , Humanos , Criança , SARS-CoV-2 , Pandemias , RNA Viral , EletroencefalografiaRESUMO
Hepatocellular carcinoma (HCC) is one of the most prevalent and deadly cancers in the world, which is frequently diagnosed at a late stage. HCC patients have a poor prognosis due to the lack of an efficacious therapeutic strategy. Approved drug repurposing is a way for accelerating drug discovery and can significantly reduce the cost of drug development. Carfilzomib (CFZ) is a second-generation proteasome inhibitor, which is highly efficacious against multiple myeloma and has been reported to possess potential antitumor activities against multiple cancers. However, the underlying mechanism of CFZ on HCC is still unclear. Here, we show that CFZ inhibits the proliferation of HCC cells through cell cycle arrest at the G2/M phase and suppresses the migration and invasion of HCC cells by inhibiting epithelial-mesenchymal transition. We also find that CFZ promotes reactive oxygen species production to induce endoplasmic reticulum (ER) stress and activate JNK/p38 MAPK signaling in HCC cells, thus inducing cell death in HCC cells. Moreover, CFZ significantly inhibits HCC cell growth in a xenograft mouse model. Collectively, our study elucidates that CFZ impairs mitochondrial function and activates ER stress and JNK/p38 MAPK signaling, thus inhibiting HCC cell and tumor growth. This indicates that CFZ has the potential as a therapeutic drug for HCC.
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Apoptose , Carcinoma Hepatocelular , Estresse do Retículo Endoplasmático , Neoplasias Hepáticas , Oligopeptídeos , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Humanos , Oligopeptídeos/farmacologia , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/patologia , Animais , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Camundongos , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Proliferação de Células/efeitos dos fármacos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Ensaios Antitumorais Modelo de Xenoenxerto , Camundongos Nus , Movimento Celular/efeitos dos fármacos , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Camundongos Endogâmicos BALB CRESUMO
The carbon-fiber-reinforced polymer (CFRP) bending structure is widely used in aviation. The emergence and spread of delamination damage will decrease the safety of in-service bending structures. Lamb waves can effectively identify delamination damage as a high-damage-sensitivity detection tool. For this present study, the signal difference coefficient (SDC) was introduced to quantify delamination damage and evaluate the sensitivity of A0-mode and S0-mode Lamb waves to delamination damage. The simulation results show that compared with the S0-mode Lamb wave, the A0-mode Lamb wave exhibits higher delamination damage sensitivity. The delamination damage can be quantified based on the strong correlation between the SDC and the delamination damage size. The control effect of the linear array PZT phase time-delay method on the Lamb wave mode was investigated by simulation. The phase time-delay method realizes the generation of a single-mode Lamb wave, which can separately excite the A0-mode and S0-mode Lamb wave to identify delamination damage of different sizes. The A0-mode Lamb wave was excited by the developed one-dimensional miniaturized linear comb transducer (LCT), which was used to conduct the detection experiment on the CFRP bending plate with delamination damage sizes of Φ6.0 mm, Φ10.0 mm, and Φ15.0 mm. The experimental results verify the correctness of the simulation. According to the Hermite interpolation results of the finite-element simulation data, the relationship between the delamination damage size and the SDC was fitted by the Gaussian function and Rational function, which can accurately quantify the delamination damage. The absolute error of the delamination damage quantification with Gaussian and Rational fitting expression does not exceed 0.8 mm and 0.7 mm, and the percentage error is not more than 8% and 7%. The detection and signal processing methods employed in the present research are easy to operate and implement, and accurate delamination damage quantification results have been obtained.
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Individuals exhibit considerable variability in their capacity to learn and retain new information, including novel vocabulary. Prior research has established the importance of vigilance and electroencephalogram (EEG) alpha rhythm in the learning process. However, the interplay between vigilant attention, EEG alpha oscillations, and an individual's word learning ability (WLA) remains elusive. To address this knowledge gap, here we conducted two experiments with a total of 140 young and middle-aged adults who underwent resting EEG recordings prior to completing a paired-associate word learning task and a psychomotor vigilance test (PVT). The results of both experiments consistently revealed significant positive correlations between WLA and resting EEG alpha oscillations in the occipital and frontal regions. Furthermore, the association between resting EEG alpha oscillations and WLA was mediated by vigilant attention, as measured by the PVT. These findings provide compelling evidence supporting the crucial role of vigilant attention in linking EEG alpha oscillations to an individual's learning ability.
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BACKGROUND: Several COVID-19 vaccines are in widespread use in China. Few data exist on comparative immunogenicity of different COVID-19 vaccines given as booster doses. We aimed to assess neutralizing antibody levels raised by injectable and inhaled aerosolized recombinant adenovirus type 5 (Ad5)-vectored COVID-19 vaccine as a heterologous booster after an inactivated COVID-19 vaccine two-dose primary series. METHODS: Using an open-label prospective cohort design, we recruited 136 individuals who had received inactivated vaccine primary series followed by either injectable or inhaled Ad5-vectored vaccine and measured neutralizing antibody titers against ancestral SARS-CoV-2 virus and Omicron BA.1 and BA.5 variants. We also measured neutralizing antibody levels in convalescent sera from 39 patients who recovered from Omicron BA.2 infection. RESULTS: Six months after primary series vaccination, neutralizing immunity against ancestral SARS-CoV-2 was low and neutralizing immunity against Omicron (B.1.1.529) was lower. Boosting with Ad5-vectored vaccines induced a high immune response against ancestral SARS-CoV-2. Neutralizing responses against Omicron BA.5 were ≥ 80% lower than against ancestral SARS-CoV-2 in sera from prime-boost subjects and in convalescent sera from survivors of Omicron BA.2 infection. Inhaled aerosolized Ad5-vectored vaccine was associated with greater neutralizing titers than injectable Ad5-vectored vaccine against ancestral and Omicron SARS-CoV-2 variants. CONCLUSIONS: These findings support the current strategy of heterologous boosting with injectable or inhaled Ad5-vectored SARS-CoV-2 vaccination of individuals primed with inactivated COVID-19 vaccine.
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Vacinas contra COVID-19 , COVID-19 , Humanos , Anticorpos Neutralizantes , Anticorpos Antivirais , Estudos Prospectivos , SARS-CoV-2RESUMO
BACKGROUND AND PURPOSE: Ki-67 labeling index (LI) is an important indicator of tumor cell proliferation in glioma, which can only be obtained by postoperative biopsy at present. This study aimed to explore the correlation between Ki-67 LI and apparent diffusion coefficient (ADC) parameters and to predict the level of Ki-67 LI noninvasively before surgery by multiple MRI characteristics. METHODS: Preoperative MRI data of 166 patients with pathologically confirmed glioma in our hospital from 2016 to 2020 were retrospectively analyzed. The cut-off point of Ki-67 LI for glioma grading was defined. The differences in MRI characteristics were compared between the low and high Ki-67 LI groups. The receiver operating characteristic (ROC) curve was used to estimate the accuracy of each ADC parameter in predicting the Ki-67 level, and finally a multivariate logistic regression model was constructed based on the results of ROC analysis. RESULTS: ADCmin, ADCmean, rADCmin, rADCmean and Ki-67 LI showed a negative correlation (r = - 0.478, r = - 0.369, r = - 0.488, r = - 0.388, all P < 0.001). The Ki-67 LI of low-grade gliomas (LGGs) was different from that of high-grade gliomas (HGGs), and the cut-off point of Ki-67 LI for distinguishing LGGs from HGGs was 9.5%, with an area under the ROC curve (AUROC) of 0.962 (95%CI 0.933-0.990). The ADC parameters in the high Ki-67 group were significantly lower than those in the low Ki-67 group (all P < 0.05). The peritumoral edema (PTE) of gliomas in the high Ki-67 LI group was higher than that in the low Ki-67 LI group (P < 0.05). The AUROC of Ki-67 LI level assessed by the multivariate logistic regression model was 0.800 (95%CI 0.721-0.879). CONCLUSIONS: There was a negative correlation between ADC parameters and Ki-67 LI, and the multivariate logistic regression model combined with peritumoral edema and ADC parameters could improve the prediction ability of Ki-67 LI.
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Neoplasias Encefálicas , Glioma , Humanos , Antígeno Ki-67 , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/patologia , Estudos Retrospectivos , Gradação de Tumores , Glioma/diagnóstico por imagem , Glioma/patologia , Imageamento por Ressonância Magnética/métodos , Imagem de Difusão por Ressonância Magnética/métodosRESUMO
Galacturonosyltransferase (GalAT) is required for the synthesis of pectin, an important component of plant cell walls that is also involved in signal transduction. Here, we describe the rice (Oryza sativa) male-sterile mutant O. sativa pectin-defective tapetum1 (ospdt1), in which GalAT is mutated. The ospdt1 mutant exhibited premature programmed cell death (PCD) of the tapetum and disordered pollen walls, resulting in aborted pollen grains. Pectin distribution in the anther sac was comparable between the mutant and the wild-type, suggesting that the structural pectin was not dramatically affected in ospdt1. Wall-associated kinases are necessary for the signal transduction of pectin, and the intracellular distribution of O. sativa indica WALL-ASSOCIATED KINASE1 (OsiWAK1), which binds pectic polysaccharides to its extracellular domain, was affected in ospdt1. OsiWAK1 RNA interference lines exhibited earlier tapetal PCD, similar to ospdt1. Furthermore, overexpression of OsiWAK1 in ospdt1 lines partially rescued the defects observed in ospdt1, suggesting that OsiWAK1 plays pivotal roles in the function of OsPDT1. These results suggest that the mutation of OsPDT1 does not dramatically affect structural pectin but affects components of the pectin-mediated signaling pathway, such as OsiWAK1, and causes male sterility.
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Oryza , Flores , Regulação da Expressão Gênica de Plantas , Oryza/metabolismo , Pectinas/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Transdução de SinaisRESUMO
Platelet extracellular vesicles (PEVs) are an emerging delivery vehi for anticancer drugs due to their ability to target and remain in the tumor microenvironment. However, there is still a lack of understanding regarding yields, safety, drug loading efficiencies, and efficacy of PEVs. In this study, various methods were compared to generate PEVs from clinical-grade platelets, and their properties were examined as vehicles for doxorubicin (DOX). Sonication and extrusion produced the most PEVs, with means of 496 and 493 PEVs per platelet (PLT), respectively, compared to 145 and 33 by freeze/thaw and incubation, respectively. The PEVs were loaded with DOX through incubation and purified by chromatography. The size and concentration of the PEVs and PEV-DOX were analyzed using dynamic light scattering and nanoparticle tracking analysis. The results showed that the population sizes and concentrations of PEVs and PEV-DOX were in the ranges of 120-150 nm and 1.2-6.2 × 1011 particles/mL for all preparations. The loading of DOX determined using fluorospectrometry was found to be 2.1 × 106, 1.7 × 106, and 0.9 × 106 molecules/EV using freeze/thaw, extrusion, and sonication, respectively. The internalization of PEVs was determined to occur through clathrin-mediated endocytosis. PEV-DOX were more efficiently taken up by MDA-MB-231 breast cancer cells compared to MCF7/ADR breast cancer cells and NIH/3T3 cells. DOX-PEVs showed higher anticancer activity against MDA-MB-231 cells than against MCF7/ADR or NIH/3T3 cells and better than acommercial liposomal DOX formulation. In conclusion, this study demonstrates that PEVs generated by PLTs using extrusion, freeze/thaw, or sonication can efficiently load DOX and kill breast cancer cells, providing a promising strategy for further evaluation in preclinical animal models. The study findings suggest that sonication and extrusion are the most efficient methods to generate PEVs and that PEVs loaded with DOX exhibit significant anticancer activity against MDA-MB-231 breast cancer cells.
What is the context?â Current synthetic drug delivery systems can have limitations and side effects.â Platelet extracellular vesicles (PEVs) are a natural and potentially safer alternative for delivering cancer drugs to tumors.â However, there is still a lack of understanding about how to produce PEVs and how effective they are in delivering drugs.What is new?â We compared different methods for producing PEVs from clinical-grade platelets and found that sonication and extrusion were the most effective methods.â The PEVs were loaded with a cancer drug called doxorubicin (DOX) and tested their ability to kill breast cancer cells.What is the impact?â PEVs loaded with DOX were effective at killing cancer cells, especially MDA-MB-231 breast cancer cells.â This study demonstrates that PEVs are a promising strategy for delivering cancer drugs to tumors and that sonication and extrusion are the most efficient methods for producing PEVs.â The results suggest that further evaluation of PEVs in preclinical animal models is warranted to determine their potential as a cancer drug delivery system.Abbreviations: ADP: adenosine diphosphate; bFGF: basic fibroblast growth factor; BSA: bovine serum albumin; CD41: platelet glycoprotein IIb; CD62P: P-selectin; CFDASE: 5-(and-6)-carboxyfluorescein diacetate: succinimidyl ester; CPLT: cryopreserved platelet; CPZ: chlorpromazine hydrochloride; CTC: circulating tumor cell; DMSO: dimethyl sulfoxide; DDS: drug delivery system; DOX: doxorubicin; EPR: enhanced permeability and retention; EV: extracellular vesicle; FBS: fetal bovine serum; GMP: good manufacturing practice; GF: growth factor; HER2: human epidermal growth factor receptor 2; HGF: hepatocyte growth factor; Lipo-DOX: liposomal doxorubicin; MDR: multi-drug resistance; MMP-2: matrix metalloproteinase-2; MP: microparticle; MSC: mesenchymal stromal cell; NP: nanoparticle; NTA: nanoparticle tracking analysis; PAR-1: protease activated receptor-1; PAS: platelet additive solution; PBS: phosphate-buffered saline; PC: platelet concentrate; PEG: polyethylene glycol; PEV: platelet-derived extracellular vesicle; DOX-PEV: doxorubicin-loaded platelet-derived extracellular vesicle-encapsulated; PFA: paraformaldehyde; PF4: platelet factor 4; P-gp: P-glycoprotein; PLT: platelet; PS: phosphatidylserine; SDS-PAGE: sodium dodecylsulfate polyacrylamide gel electrophoresis; SEM: scanning electron microscopy; TCIPA: tumor cell-induced PLT aggregation; TDDS: targeted drug delivery system; TEG: thromboelastography; TF: tissue factor; TF-EV: extracellular vesicle expressing tissue factor; TME: tumor microenvironment; TNBC: triple-negative breast cancer; TXA2: thromboxane-A2; VEGF: vascular endothelial growth factor; WHO: World Health Organization.
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Antineoplásicos , Vesículas Extracelulares , Nanopartículas , Camundongos , Animais , Plaquetas , Antineoplásicos/farmacologia , Doxorrubicina/farmacologiaRESUMO
Tumor-infiltrating immune cells as integral component of the tumor microenvironment are associated with tumor progress, prognosis and responses to immunotherapy. Genetic variants have been demonstrated to impact tumor-infiltrating, underscoring the heritable character of immune landscape. Therefore, identification of immunity quantitative trait loci (immunQTLs), which evaluate the effect of genetic variants on immune cells infiltration, might present a critical step toward fully understanding the contribution of genetic variants in tumor development. Although emerging studies have demonstrated the determinants of germline variants on immune infiltration, no database has yet been developed to systematically analyze immunQTLs across multiple cancer types. Using genotype data from TCGA database and immune cell fractions estimated by CIBERSORT, we developed a computational pipeline to identify immunQTLs in 33 cancer types. A total of 913 immunQTLs across different cancer types were identified. Among them, 5 immunQTLs are associated with patient overall survival. Furthermore, by integrating immunQTLs with GWAS data, we identified 527 immunQTLs overlapping with known GWAS linkage disequilibrium regions. Finally, we constructed a user-friendly database, CancerImmunityQTL (http://www.cancerimmunityqtl-hust.com/) for users to browse, search and download data of interest. This database provides an informative resource to understand the germline determinants of immune infiltration in human cancer and benefit from personalized cancer immunotherapy.
Assuntos
Bases de Dados Genéticas , Imunidade/genética , Neoplasias/genética , Polimorfismo de Nucleotídeo Único , Locos de Características Quantitativas/genética , Microambiente Tumoral/genética , Mineração de Dados/métodos , Regulação Neoplásica da Expressão Gênica , Estudo de Associação Genômica Ampla/métodos , Genótipo , Humanos , Internet , Desequilíbrio de Ligação , Neoplasias/imunologia , Prognóstico , Locos de Características Quantitativas/imunologia , Microambiente Tumoral/imunologia , Interface Usuário-ComputadorRESUMO
OBJECTIVES: To perform a correlation analysis on the structural and functional changes of the carotid artery in patients with H-type hypertension. METHODS: Outpatients and inpatients with hypertension in our hospital between 2017 and 2018 were selected and divided into the H-type hypertension group (primary hypertension + plasma homocysteine ≥ 10 umol/l) (n = 30) and the simple hypertension group (primary hypertension + plasma Hcy < 10 umol/l) (n = 30) based on the plasma homocysteine (Hcy), and 30 healthy people were included in the control group. Thickness and stiffness parameters of the intima of the carotid artery (compliance coefficient [CC], stiffness index [ß], and pulse wave velocity [PWV]) were measured for all study participants using ultrasound radiofrequency signal-based quality intima-media thickness (QIMT) and quantitative arterial stiffness (QAS) for contrast analysis. RESULTS: Indexes such as QIMT, ß, and PWV of the carotid artery were significantly higher, and the CC was significantly lower in the H-type hypertension group and simple hypertension group than the control group (p < .05), and the difference was statistically significant; these indexes were significantly higher in the H-type hypertension group than in the simple hypertension group, and the CC was significantly lower than in the control group (p < .05), and the difference was statistically significant. CONCLUSIONS: Hypertension can accelerate structural and functional changes of the carotid artery intima, with these changes being more significant in H-type hypertension. The ultrasound radiofrequency technique can be used to quantitatively evaluate the structure and function of the carotid artery in patients with H-type hypertension.
RESUMO
Yangmai-13 (YM13) is a wheat cultivar with weak gluten fractions. In contrast, Zhenmai-168 (ZM168) is an elite wheat cultivar known for its strong gluten fractions and has been widely used in a number of breeding programs. However, the genetic mechanisms underlying the gluten signatures of ZM168 remain largely unclear. To address this, we combined RNA-seq and PacBio full-length sequencing technology to unveil the potential mechanisms of ZM168 grain quality. A total of 44,709 transcripts were identified in Y13N (YM13 treated with nitrogen) and 51,942 transcripts in Z168N (ZM168 treated with nitrogen), including 28,016 and 28,626 novel isoforms in Y13N and Z168N, respectively. Five hundred and eighty-four differential alternative splicing (AS) events and 491 long noncoding RNAs (lncRNAs) were discovered. Incorporating the sodium-dodecyl-sulfate (SDS) sedimentation volume (SSV) trait, both weighted gene coexpression network analysis (WGCNA) and multiscale embedded gene coexpression network analysis (MEGENA) were employed for network construction and prediction of key drivers. Fifteen new candidates have emerged in association with SSV, including 4 transcription factors (TFs) and 11 transcripts that partake in the post-translational modification pathway. The transcriptome atlas provides new perspectives on wheat grain quality and would be beneficial for developing promising strategies for breeding programs.
Assuntos
Glutens , Triticum , Glutens/genética , Glutens/metabolismo , Triticum/genética , Triticum/metabolismo , Melhoramento Vegetal , Grão Comestível/genética , Nitrogênio/metabolismoRESUMO
The purpose of this trial was to study the positive effects of bile acids (BAs) on growth performance and intestinal health of rice field eel fed with high-lipid diets (HLDs). Rice field eels (initial weight 17.00 ± 0.10 g) were divided into four groups, each group containing four repetitions and feeding with different isonitrogenous diet: control diet containing 7% lipid content, HLDs containing the lipid content increased to 13%, HLDs supplementing with 0.025% BAs and 0.05% BAs, respectively. After 8 weeks, compared control group, the fish fed HLDs had no significant effect on weight gain rate and specific growth rate (P > 0.05), but increased the lipid deposition in tissues and intestinal lipase activity, and damaged to intestinal oxidative stress, inflammatory response, physical barrier, and structural integrity (P < 0.05). Dietary BAs significantly increased weight gain rate and specific growth rate in fish fed with HL diets (P < 0.05) and reduced feed conversation rate (P < 0.05). Further, the eels fed with BAs reduced the total lipid content in liver, muscle, and whole body (P < 0.05). Dietary BAs decreased the activity of intestinal lipase (P < 0.05). Meanwhile, BAs supplemented in HLDs improved intestinal antioxidant capacity through increasing the activities of T-SOD (total superoxide dismutase), GSH-PX (glutathione peroxidase), CAT (catalase), T-AOC (total antioxidant capacity), whereas reducing MDA (malondialdehyde) content (P < 0.05). Moreover, dietary BAs regulated the mRNA expression related to inflammatory response, oxidative stress, and physical barrier in intestine, such as tnf-α, il-8, tlr-8, il-10, nrf2, keap1, claudin12, and claudin15 (P < 0.05). Dietary BAs supplementation also enhanced the intestinal structural integrity characterized by increased fold height and lamina propria width (P < 0.05). This study showed that dietary BAs supplemented in HLDs (13% lipid) could increase the growth performance of rice field eel, reduce lipid deposition in tissues and whole body, and enhance intestinal health.
RESUMO
The aim of this trial was to investigate the effects of apple polyphenols (AP) and taurine (TA) on the growth performance, tissue morphology, and lipid and glucose metabolism in rice field eel fed diets with high oxidized fish oil (OFO). A 10-week feeding experiment was conducted using juveniles (initial body weight 16.66 ± 0.02 g) fed five different diets. Three diets were formulated with various levels of OFO at 9.5, 600, and 800 meq·kg-1 and named as Control, POV600, and POV800 diet, respectively. The other two diets were POV600 and POV800 supplemented with 0.5% AP and 0.2% TA, respectively. Compared to the Control group, only the eels fed POV800 exhibited an increase in weight gain and specific growth rate along with a reduction in feed conversion ratio. AP and TA did not affect growth performance; juveniles fed AP, however, showed a decrease in liver weight. Both POV600 and POV800 decreased nuclei number and increased vacuoles size in the liver. POV800 damaged the intestinal structure integrity and reduced goblet cells number. AP repaired the liver damage on nuclei number and vacuoles size in fish fed with POV600 diet, while TA mitigated intestinal histopathological damage on intact structure and goblet cells number. The mRNA expression level of liver ampkα in fish fed AP was upregulated, while dietary TA upregulated the mRNA expression levels of liver ampkα and accα. In the muscle, POV600 downregulated mRNA expression levels of accα, cpt1, and lipin, whereas POV800 upregulated mRNA expression levels of accα, pparα, and lipin. Dietary AP and TA could counteract the effects of POV600 and POV800 diet on muscle lipid metabolism. Both POV600 and POV800 diets upregulated mRNA expression levels of liver pck1 and gsk3α. AP and TA both downregulated mRNA expression level of liver pck1, while only TA downregulated the expression of liver gsk3α. AP increased the mRNA expression level of gsk3α in muscle. In summary, inclusion of AP and TA did not affect growth performance but showed a potential to alleviate liver or intestinal damages induced by a high OFO diet. Dietary AP and TA were also found to regulate mRNA expression of genes related to lipid and glucose metabolism.