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The processes that govern human haematopoietic stem cell (HSC) self-renewal and engraftment are poorly understood and challenging to recapitulate in culture to reliably expand functional HSCs1-3. Here we identify MYC target 1 (MYCT1; also known as MTLC) as a crucial human HSC regulator that moderates endocytosis and environmental sensing in HSCs. MYCT1 is selectively expressed in undifferentiated human haematopoietic stem and progenitor cells (HSPCs) and endothelial cells but becomes markedly downregulated during HSC culture. Lentivirus-mediated knockdown of MYCT1 prevented human fetal liver and cord blood (CB) HSPC expansion and engraftment. By contrast, restoring MYCT1 expression improved the expansion and engraftment of cultured CB HSPCs. Single-cell RNA sequencing of human CB HSPCs in which MYCT1 was knocked down or overexpressed revealed that MYCT1 governs important regulatory programmes and cellular properties essential for HSC stemness, such as ETS factor expression and low mitochondrial activity. MYCT1 is localized in the endosomal membrane in HSPCs and interacts with vesicle trafficking regulators and signalling machinery. MYCT1 loss in HSPCs led to excessive endocytosis and hyperactive signalling responses, whereas restoring MYCT1 expression balanced culture-induced endocytosis and dysregulated signalling. Moreover, sorting cultured CB HSPCs on the basis of lowest endocytosis rate identified HSPCs with preserved MYCT1 expression and MYCT1-regulated HSC stemness programmes. Our work identifies MYCT1-moderated endocytosis and environmental sensing as essential regulatory mechanisms required to preserve human HSC stemness. Our data also pinpoint silencing of MYCT1 as a cell-culture-induced vulnerability that compromises human HSC expansion.
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Autorrenovação Celular , Células-Tronco Hematopoéticas , Proteínas Nucleares , Animais , Feminino , Humanos , Masculino , Camundongos , Células Cultivadas , Endocitose , Endossomos/metabolismo , Células Endoteliais/citologia , Células Endoteliais/metabolismo , Sangue Fetal/citologia , Técnicas de Silenciamento de Genes , Células-Tronco Hematopoéticas/citologia , Células-Tronco Hematopoéticas/metabolismo , Fígado/citologia , Fígado/metabolismo , Fígado/embriologia , Mitocôndrias/metabolismo , Proteínas Nucleares/metabolismo , Transdução de Sinais , Proteínas Proto-Oncogênicas c-ets/genética , Proteínas Proto-Oncogênicas c-ets/metabolismo , Análise da Expressão Gênica de Célula ÚnicaRESUMO
Psychosocial experiences affect brain health and aging trajectories, but the molecular pathways underlying these associations remain unclear. Normal brain function relies on energy transformation by mitochondria oxidative phosphorylation (OxPhos). Two main lines of evidence position mitochondria both as targets and drivers of psychosocial experiences. On the one hand, chronic stress exposure and mood states may alter multiple aspects of mitochondrial biology; on the other hand, functional variations in mitochondrial OxPhos capacity may alter social behavior, stress reactivity, and mood. But are psychosocial exposures and subjective experiences linked to mitochondrial biology in the human brain? By combining longitudinal antemortem assessments of psychosocial factors with postmortem brain (dorsolateral prefrontal cortex) proteomics in older adults, we find that higher well-being is linked to greater abundance of the mitochondrial OxPhos machinery, whereas higher negative mood is linked to lower OxPhos protein content. Combined, positive and negative psychosocial factors explained 18 to 25% of the variance in the abundance of OxPhos complex I, the primary biochemical entry point that energizes brain mitochondria. Moreover, interrogating mitochondrial psychobiological associations in specific neuronal and nonneuronal brain cells with single-nucleus RNA sequencing (RNA-seq) revealed strong cell-type-specific associations for positive psychosocial experiences and mitochondria in glia but opposite associations in neurons. As a result, these "mind-mitochondria" associations were masked in bulk RNA-seq, highlighting the likely underestimation of true psychobiological effect sizes in bulk brain tissues. Thus, self-reported psychosocial experiences are linked to human brain mitochondrial phenotypes.
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Encéfalo , Mitocôndrias , Fosforilação Oxidativa , Humanos , Mitocôndrias/metabolismo , Masculino , Feminino , Encéfalo/metabolismo , Idoso , Estresse Psicológico/metabolismo , Pessoa de Meia-Idade , Córtex Pré-Frontal/metabolismo , Neurônios/metabolismo , Proteômica/métodos , Afeto/fisiologiaRESUMO
Nutrient sensing and adaptation in the placenta are essential for pregnancy viability and proper fetal growth. Our recent study demonstrated that the placenta adapts to nutrient insufficiency through mechanistic target of rapamycin (mTOR) inhibition-mediated trophoblast differentiation toward syncytiotrophoblasts (STBs), a highly specialized multinucleated trophoblast subtype mediating extensive maternal-fetal interactions. However, the underlying mechanism remains elusive. Here, we unravel the indispensable role of the mTORC1 downstream transcriptional factor TFEB in STB formation both in vitro and in vivo. TFEB deficiency significantly impaired STB differentiation in human trophoblasts and placenta organoids. Consistently, systemic or trophoblast-specific deletion of Tfeb compromised STB formation and placental vascular construction, leading to severe embryonic lethality. Mechanistically, TFEB conferred direct transcriptional activation of the fusogen ERVFRD-1 in human trophoblasts and thereby promoted STB formation, independent of its canonical function as a master regulator of the autophagy-lysosomal pathway. Moreover, we demonstrated that TFEB directed the trophoblast syncytialization response driven by mTOR complex 1 (mTORC1) signaling. TFEB expression positively correlated with the reinforced trophoblast syncytialization in human fetal growth-restricted placentas exhibiting suppressed mTORC1 activity. Our findings substantiate that the TFEB-fusogen axis ensures proper STB formation during placenta development and under nutrient stress, shedding light on TFEB as a mechanistic link between nutrient-sensing machinery and trophoblast differentiation.
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Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos , Diferenciação Celular , Alvo Mecanístico do Complexo 1 de Rapamicina , Trofoblastos , Trofoblastos/metabolismo , Humanos , Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos/metabolismo , Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos/genética , Feminino , Gravidez , Camundongos , Animais , Alvo Mecanístico do Complexo 1 de Rapamicina/metabolismo , Placenta/metabolismo , Transdução de Sinais , Autofagia/fisiologiaRESUMO
Escherichia coli K1 is the leading cause of neonatal Gram-negative bacterial meningitis, but the pathogenesis of E. coli K1 meningitis remains unclear. Blood-brain barrier (BBB) penetration is a crucial step in E. coli meningitis development. Here, we uncovered the crucial role of CsiR, a GntR family regulator, in E. coli K1 virulence. During infection, csiR expression was induced due to the derepression by Fur in the blood and human brain microvascular endothelial cells (HBMECs). CsiR positively regulated ilvB expression, which is associated with branched chain amino acid synthesis. Furthermore, we revealed that IlvB activated the FAK/PI3â K pathway of HBMECs to induce actin cytoskeleton rearrangements, thereby promoting the bacterial invasion and penetration of the BBB. Overall, this study reveals a CsiR-mediated virulence regulation pathway in E. coli K1, which may provide a useful target for the prevention or therapy of E. coli meningitis.
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BACKGROUND: Pancreatic adenocarcinoma (PC) is an aggressive malignancy with limited treatment options. The poor prognosis primarily stems from late-stage diagnosis and when the disease has become therapeutically challenging. There is an urgent need to identify specific biomarkers for cancer subtyping and early detection to enhance both morbidity and mortality outcomes. The addition of the EGFR tyrosine kinase inhibitor (TKI), erlotinib, to gemcitabine chemotherapy for the first-line treatment of patients with advanced pancreatic cancer slightly improved outcomes. However, restricted clinical benefits may be linked to the absence of well-characterized criteria for stratification and dependable biomarkers for the prediction of treatment effectiveness. METHODS AND RESULTS: We examined the levels of various cancer hallmarks and identified glycolysis as the primary risk factor for overall survival in PC. Subsequently, we developed a glycolysis-related score (GRS) model to accurately distinguish PC patients with high GRS. Through in silico screening of 4398 compounds, we discovered that erlotinib had the strongest therapeutic benefits for high-GRS PC patients. Furthermore, we identified ARNTL2 as a novel prognostic biomarker and a predictive factor for erlotinib treatment responsiveness in patients with PC. Inhibition of ARNTL2 expression reduced the therapeutic efficacy, whereas increased expression of ARNTL2 improved PC cell sensitivity to erlotinib. Validation in vivo using patient-derived xenografts (PDX-PC) with varying ARNTL2 expression levels demonstrated that erlotinib monotherapy effectively halted tumor progression in PDX-PC models with high ARNTL2 expression. In contrast, PDX-PC models lacking ARNTL2 did not respond favorably to erlotinib treatment. Mechanistically, we demonstrated that the ARNTL2/E2F1 axis-mediated cellular glycolysis sensitizes PC cells to erlotinib treatment by activating the PI3K/AKT signaling pathway. CONCLUSIONS: Our investigations have identified ARNTL2 as a novel prognostic biomarker and predictive indicator of sensitivity. These results will help to identify erlotinib-responsive cases of PC and improve treatment outcomes. These findings contribute to the advancement of precision oncology, enabling more accurate and targeted therapeutic interventions.
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Adenocarcinoma , Neoplasias Pulmonares , Neoplasias Pancreáticas , Humanos , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/genética , Fatores de Transcrição ARNTL/metabolismo , Biomarcadores/metabolismo , Linhagem Celular Tumoral , Receptores ErbB/metabolismo , Cloridrato de Erlotinib/farmacologia , Neoplasias Pulmonares/patologia , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/patologia , Fosfatidilinositol 3-Quinases/metabolismo , Fosforilação , Medicina de Precisão , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/uso terapêutico , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de SinaisRESUMO
OBJECTIVE: To construct a prognostic model based on MR features and clinical data to evaluate the progression free survival (PFS), overall survival (OS) and objective response rate (ORR) of pancreatic cancer patients with hepatic metastases who received chemoimmunotherapy. METHODS: 105 pancreatic cancer patients with hepatic metastases who received chemoimmunotherapy were assigned to the training set (n = 52), validation set (n = 22), and testing set (n = 31). Multi-lesion volume of interest were delineated, multi-sequence radiomics features were extracted, and the radiomics models for predicting PFS, OS and ORR were constructed, respectively. Clinical variables were extracted, and the clinical models for predicting PFS, OS and ORR were constructed, respectively. The nomogram was jointly constructed by radiomics model and clinical model. RESULT: The ORR exhibits no significant correlation with either PFS or OS. The area under the curve (AUC) of nomogram for predicting 6-month PFS reached 0.847 (0.737-0.957), 0.786 (0.566-1.000) and 0.864 (0.735-0.994) in the training set, validation set and testing set, respectively. The AUC of nomogram for predicting 1-year OS reached 0.770 (0.635-0.906), 0.743 (0.479-1.000) and 0.818 (0.630-1.000), respectively. The AUC of nomogram for predicting ORR reached 0.914 (0.828-1.00), 0.938 (0.840-1.00) and 0.846 (0.689-1.00), respectively. CONCLUSION: The prognostic models based on MR imaging features and clinical data are effective in predicting the PFS, OS and ORR of chemoimmunotherapy in pancreatic cancer patients with hepatic metastasis, and can be used to evaluate the prognosis of patients.
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Neoplasias Hepáticas , Neoplasias Pancreáticas , Humanos , Nomogramas , Radiômica , Prognóstico , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Pancreáticas/diagnóstico por imagem , Neoplasias Pancreáticas/tratamento farmacológico , Estudos RetrospectivosRESUMO
BACKGROUND: The homodomain-leucine zipper (HD-Zip) is a conserved transcription factor family unique to plants that regulate multiple developmental processes including lignificaion. Stone cell content is a key determinant negatively affecting pear fruit quality, which causes a grainy texture of fruit flesh, because of the lignified cell walls. RESULTS: In this study, a comprehensive bioinformatics analysis of HD-Zip genes in Chinese white pear (Pyrus bretschneideri) (PbHBs) was performed. Genome-wide identification of the PbHB gene family revealed 67 genes encoding PbHB proteins, which could be divided into four subgroups (I, II, III, and IV). For some members, similar intron/exon structural patterns support close evolutionary relationships within the same subgroup. The functions of each subgroup of the PbHB family were predicted through comparative analysis with the HB genes in Arabidopsis and other plants. Cis-element analysis indicated that PbHB genes might be involved in plant hormone signalling and external environmental responses, such as light, stress, and temperature. Furthermore, RNA-sequencing data and quantitative real-time PCR (RT-qPCR) verification revealed the regulatory roles of PbHB genes in pear stone cell formation. Further, co-expression network analysis revealed that the eight PbHB genes could be classified into different clusters of co-expression with lignin-related genes. Besides, the biological function of PbHB24 in promoting stone cell formation has been demonstrated by overexpression in fruitlets. CONCLUSIONS: This study provided the comprehensive analysis of PbHBs and highlighted the importance of PbHB24 during stone cell development in pear fruits.
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Frutas , Proteínas de Plantas , Pyrus , Fatores de Transcrição , Pyrus/genética , Pyrus/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Frutas/genética , Frutas/crescimento & desenvolvimento , Regulação da Expressão Gênica de Plantas , Genoma de Planta , Filogenia , Zíper de Leucina/genética , Genes de Plantas , Família Multigênica , População do Leste AsiáticoRESUMO
In this paper, a highly sensitive sensor consisting of a silicon nanorod and symmetric rings (SNSR) is presented. Theoretically, three Fano resonances with high Q-factors are excited in the near-infrared range by breaking the symmetry structure based on quasi-bound states in the continuum (Q-BICs). The electromagnetic near-field analysis confirms that the resonances are mainly controlled by toroidal dipole (TD) resonance. The structure is optimized by adjusting different geometrical parameters, and the maximum Q-factor of the Fano resonances can reach 7427. To evaluate the sensing performance of the structure, the sensitivity and the figure of merit (FOM) are calculated by adjusting the environmental refractive index: the maximum sensitivity of 474â nm/RIU and the maximum FOM of 3306 RIU-1. The SNSR can be fabricated by semiconductor-compatible processes, which is experimentally evaluated for changes in transmission spectra at different solution concentrations. The results show that the sensitivity and the Q-factor of the designed metasurface can reach 295â nm/RIU and 850, while the FOM can reach 235 RIU-1. Therefore, the metasurface of SNSR is characterized by high sensitivity and multi-wavelength sensing, which are current research hotspots in the field of optics and can be applied to biomedical sensing and multi-target detection.
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OBJECTIVE: The objective of this study was to evaluate the association between hyperthyroidism and the risk of developing erectile dysfunction (ED). METHODS: A comprehensive search of multiple databases, including PubMed, Embase, Cochrane, and Web of Science, was conducted to identify relevant studies investigating the relationship between hyperthyroidism and ED in men. The quality of the included studies was assessed using the NewcastleâOttawa Quality Rating Scale, and a meta-analysis was performed using Stata 16.0 and RevMan 5.3 software. RESULTS: A total of four papers encompassing 25,519 study subjects were included in the analysis. Among these, 6,429 individuals had hyperthyroidism, while 19,090 served as controls. The overall prevalence of ED in patients with hyperthyroidism was determined to be 31.1% (95% CI 0.06-0.56). In patients with uncomplicated hyperthyroidism, the incidence of ED was 21.9% (95% CI 0.05-0.38). The combined odds ratio (OR) for the four studies was 1.73 (OR: 1.73; 95% CI [1.46-2.04]; p < .00001). CONCLUSION: Our findings demonstrate a higher incidence of ED in patients with hyperthyroidism. These results provide valuable information for healthcare professionals and can facilitate discussions surrounding appropriate treatment options for ED in patients with hyperthyroidism.
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Disfunção Erétil , Hipertireoidismo , Humanos , Hipertireoidismo/epidemiologia , Hipertireoidismo/complicações , Disfunção Erétil/epidemiologia , Disfunção Erétil/etiologia , Masculino , PrevalênciaRESUMO
Purpose: To investigate morphological and hemodynamic characteristics of the ophthalmic artery (OA) in patients with white matter hyperintensity (WMH), and the association of the presence and severity of WMH with OA characteristics. Methods: This cross-sectional study included 44 eyes of 25 patients with WMH and 38 eyes of 19 controls. The Fazekas scale was adopted as criteria for evaluating the severity of white matter hyperintensities. The morphological characteristics of the OA were measured on the basis of three-dimensional reconstruction. The hemodynamic parameters of the OA were calculated using computational fluid dynamics simulations. Results: Compared with the control group, the diameter (16.0±0.27 mm vs. 1.71±0.18 mm, P=0.029), median blood flow velocity (0.12 m/s vs. 0.22 m/s, P<0.001), mass flow ratio (2.16% vs. 3.94%, P=0.012) and wall shear stress (2.65 Pa vs. 9.31 Pa, P<0.001) of the OA in patients with WMH were significantly decreased. After adjusting for confounding factors, the diameter, blood flow velocity, wall shear stress, and mass flow ratio of the OA were significantly associated with the presence of WMH. Male sex and high low-density protein level were associated with moderate-to-severe total WMH, and smoking was associated with the moderate-to-severe periventricular WMH. Conclusions: The diameter, blood flow velocity, mass flow ratio, and wall shear stress of the OA were independently associated with the presence of WMH. Atherosclerosis might be involved in the common mechanism of the occurrence of WMH and the OA changes.
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Hemodinâmica , Artéria Oftálmica , Substância Branca , Humanos , Masculino , Feminino , Artéria Oftálmica/diagnóstico por imagem , Artéria Oftálmica/fisiopatologia , Substância Branca/diagnóstico por imagem , Substância Branca/fisiopatologia , Substância Branca/irrigação sanguínea , Substância Branca/patologia , Estudos Transversais , Hemodinâmica/fisiologia , Pessoa de Meia-Idade , Idoso , Velocidade do Fluxo Sanguíneo , Imageamento por Ressonância Magnética , AdultoRESUMO
OBJECTIVE: To do the etiological analysis of ocular herps virus infection, revealing the pathogen species and the distribution of different virus types within the eye. METHODS: Samples were collected from 2017 to 2021 at the Department of Ophthalmology, Peking University Third Hospital and tested using real-time PCR for common ocular viruses: herpes simplex virus 1 (HSV-1), cytomegalovirus (CMV), varicella-zoster virus (VZV) and Epstein-Barr virus (EBV). The pathogenesis of the different viruses was classified and analyzed according to the site of infection. RESULTS: Viral PCR detections were performed on 3627 samples collected over the 5-years and 649 (17.89%) samples contained one or more of the viruses tested. The overall detection rate of CMV was highest at 9.93%. Of all sample types, aqueous humor was the most common (1752 cases), of which 340 were positive (19.41% positive rate). Corneal samples were the next most common, with 1481 cases and 250 positive results (16.88% positive rate). CMV positivity was higher in aqueous humor and corneal samples than other viruses; vitreous body had the highest positive rate at 36.36% (20/55), among which 18 cases were VZV positive. CONCLUSIONS: Distribution of virus types differed among infection sites, with CMV the most common virus type detected in the cornea and aqueous humor, while VZV was the most common virus detected in the vitreous body.
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This article shows an all-dielectric metasurface consisting of "H"-shaped silicon disks with tilted splitting gaps, which can detect the temperature and refractive index (RI). By introducing asymmetry parameters that excite the quasi-BIC, there are three distinct Fano resonances with nearly 100% modulation depth, and the maximal quality factor (Q-factor) is over 104. The predominant roles of different electromagnetic excitations in three distinct modes are demonstrated through near-field analysis and multipole decomposition. A numerical analysis of resonance response based on different refractive indices reveals a RI sensitivity of 262 nm/RIU and figure of merit (FOM) of 2183 RIU-1. This sensor can detect temperature fluctuations with a temperature sensitivity of 59.5 pm/k. The proposed metasurface provides a novel method to induce powerful TD resonances and offers possibilities for the design of high-performance sensors.
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INTRODUCTION: The É4 allele of the apolipoprotein E gene (APOE É4) is the strongest genetic risk factor for Alzheimer's disease (AD), but the mechanisms connecting APOE É4 to AD are not clear. METHODS: Participants (n = 596) were from two clinical-pathological studies. Tissues from dorsolateral prefrontal cortex were examined to identify 8425 proteins. Post mortem pathological assessment used immunohistochemistry to obtain amyloid beta (Aß) load and tau tangle density. RESULTS: In separate models, APOE É4 was associated with 18 proteins, which were associated with Aß and tau tangles. Examining the proteins in a single model identified Netrin-1 and secreted frizzled-related protein 1 (SFRP1) as the two proteins linking APOE É4 with Aß with the largest effect sizes and Netrin-1 and testican-3 linking APOE É4 with tau tangles. DISCUSSION: We identified Netrin-1, SFRP1, and testican-3 as the most promising proteins that link APOE É4 with Aß and tau tangles. HIGHLIGHTS: Of 8425 proteins extracted from prefrontal cortex, 18 were related to APOE É4. The 18 proteins were also related to amyloid beta (Aß) and tau. The 18 proteins were more related to APOE É4 than other AD genetic risk variants. Netrin-1 and secreted frizzled-related protein 1 were the two most promising proteins linking APOE É4 with Aß. Netrin-1 and testican-3 were two most promising proteins linking APOE É4 with tau.
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Doença de Alzheimer , Apolipoproteína E4 , Proteínas de Membrana , Netrina-1 , Emaranhados Neurofibrilares , Córtex Pré-Frontal , Proteoglicanas , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Doença de Alzheimer/genética , Doença de Alzheimer/metabolismo , Peptídeos beta-Amiloides/metabolismo , Apolipoproteína E4/genética , Netrina-1/metabolismo , Netrina-1/genética , Emaranhados Neurofibrilares/metabolismo , Emaranhados Neurofibrilares/patologia , Córtex Pré-Frontal/metabolismo , Proteínas tau/metabolismo , Proteínas de Membrana/metabolismo , Proteoglicanas/metabolismoRESUMO
INTRODUCTION: Dietary patterns are associated with dementia risk, but the underlying molecular mechanisms are largely unknown. METHODS: We used RNA sequencing data from post mortem prefrontal cortex tissue and annual cognitive evaluations from 1204 participants in the Religious Orders Study and Memory and Aging Project. We identified a transcriptomic profile correlated with the MIND diet (Mediterranean-Dietary Approaches to Stop Hypertension Intervention for Neurodegenerative Delay) among 482 individuals who completed ante mortem food frequency questionnaires; and examined its associations with cognitive health in the remaining 722 participants. RESULTS: We identified a transcriptomic profile, consisting of 50 genes, correlated with the MIND diet score (p = 0.001). Each standard deviation increase in the transcriptomic profile score was associated with a slower annual rate of decline in global cognition (ß = 0.011, p = 0.003) and lower odds of dementia (odds ratio = 0.76, p = 0.0002). Expressions of several genes (including TCIM and IGSF5) appeared to mediate the association between MIND diet and dementia. DISCUSSION: A brain transcriptomic profile for healthy diets revealed novel genes potentially associated with cognitive health. HIGHLIGHTS: Why healthy dietary patterns are associated with lower dementia risk are unknown. We integrated dietary, brain transcriptomic, and cognitive data in older adults. Mediterranean-Dietary Approaches to Stop Hypertension Intervention for Neurodegenerative Delay (MIND) diet intake is correlated with a specific brain transcriptomic profile. This brain transcriptomic profile score is associated with better cognitive health. More data are needed to elucidate the causality and functionality of identified genes.
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This study aims to explore the interaction of glycemic control and statin use on the treatment outcomes of pulmonary tuberculosis-diabetes comorbidity (PTB-DM) patients. A nested case-control study was conducted in a tuberculosis patients' cohort. We defined cases as patients who experienced unfavorable outcomes. Glycemic control was estimated at the baseline. Statin use was obtained from medical records. The multivariate logistic regression models were developed, and the interaction table invented by Andersson was adopted to analyze the interaction of glycemic control and statin use on treatment outcomes. A total of 2,047 patients were included in this study. There was a significant interaction between glycemic control and statin use on the treatment outcomes. Patients with good glycemic control and no statin use (OR = 0.464, 95% CI: 0.360-0.623) had a lower risk of unfavorable outcomes than those with poor glycemic control and statin use (OR = 0.604, 95% CI: 0.401-0.734). Patients with good glycemic control and statin use had the lowest risk of unfavorable outcomes (OR = 0.394, 95% CI: 0.264-0.521). Glycemic control in diabetes-tuberculosis treatment should be paid considerable attention. Patients can benefit from statin use even if they have poor glycemic control. Patients with good glycemic control and statin use can have the best outcomes.
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BACKGROUND: With the alterations of the Chinese epidemic prevention policy, China experienced a nationwide wave of the Coronavirus disease 2019 (COVID-19) pandemic from December 2022 to January 2023.The impact of the COVID-19 pandemic extends beyond individual perceptions of the meaning of life and attitudes toward life and death; it also affects the professional identity of nursing students.This study explored nursing students' professional identity and life meaning of affected by the pandemic. METHODS: An online survey was conducted using the Chinese version of the Nursing Student Career Identity Scale and the Chinese version of the Meaning in Life Questionnaire to assess the current status of nursing students' professional identity and sense of life meaning. Data were also collected on participant gender, education, clinical practice experience, and COVID-19 infection. RESULTS: The scores for nursing students' sense of professional identity (61.58 ± 16.16) and sense of life meaning (45.29 ± 12.65) were both at an intermediate level. Compared to the scores before the COVID-19 pandemic, Chinese nursing students' professional identity scores increased, while their sense of life meaning scores decreased. Moreover, we found a positive correlation between professional identity and sense of life meaning (p < 0.001); nursing students exhibited a stronger professional identity when they had a relatively higher sense of life meaning than those with a relatively lower sense of life meaning. CONCLUSION: Enhancing nursing students' sense of meaning in life is crucial for maintaining their professional identity. Attention should be given to life education for nursing students and the development of relevant educational curricula.
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The intestinal microbiota is associated with defense against respiratory viral infections. In this issue of Cell Host & Microbe, Ngo and colleagues1 show that intestinal commensal segmented filamentous bacteria reprogram alveolar macrophages with improved influenza-viral-neutralizing and phagocytic functions while maintaining inflammatory anergy to better protect the lung.
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Microbioma Gastrointestinal , Orthomyxoviridae , Macrófagos Alveolares , PulmãoRESUMO
Mucosal tissues are frequent targets of both primary and metastatic cancers. This has highlighted the significance of both innate and adaptive anti-cancer immunity at mucosal sites. Trained innate immunity (TII) is an emerging concept defined as enhanced reactivity of innate leukocytes long after a previous stimulation that induces prolonged epigenetic, transcriptional, and metabolic changes. Trained innate leukocytes can respond to heterologous targets due to their lacking of antigen-specificity in most cases. Emerging experimental and clinical data suggest that certain microbes or their products induce TII in mucosal-associated innate leukocytes which endows heterologous anti-tumor innate immunity, in both prophylactic and therapeutic scenarios. In this mini-review, we summarize updated findings on the significance of TII in mucosal cancers. We also attempt to raise a few key questions critical to our further understanding on the roles of TII in mucosal cancers, and to the potential application of TII as anti-cancer strategy.
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Imunidade Inata , Neoplasias , Imunidade Treinada , Imunidade Adaptativa , Mucosa , Imunidade nas MucosasRESUMO
Aims: Influenza infection is a health burden in children, and the influenza vaccine is an important prevention strategy for flu illness. Parents play a crucial role in children's influenza vaccination. The study aimed to assess parental knowledge, attitudes, and practices (KAP) related to influenza illness for their children and explore factors that may impact their decisions. Methods: This cross-sectional study was conducted in a tertiary hospital in Guangzhou from November 2022 to April 2023. Answers to KAP questions regarding influenza illness and vaccination were summed, with a total KAP score of 20. Univariate and multivariate logistic regression models and linear regression models were conducted to explore the factors associated with influenza vaccination. The results were presented as odds ratios (ORs), ß, and 95% confidence intervals (CIs). Results: Overall, 530 parents were respondents, of whom 162 (30.56%) had vaccinated their children during the past year. The mean KAP score (standard deviation) was 13.40 (3.57). Compared to parents who reported non-vaccinated for their children in the past year, the parents who reported an influenza vaccination have higher knowledge scores, attitude scores, practice scores, and total scores. Child body mass index, parental education level (under college), parental work (part-time), and more than two family members over 60 years old were negatively correlated with knowledge score. Child health condition and knowledge score were positively correlated with attitude score. Parental age was negatively associated with attitude score. Conclusion: Though high awareness about influenza illness and vaccination for parents, the coverage rate of influenza vaccination in children was lower in Guangzhou. Implementing public health policies is necessary to spread knowledge about influenza illness and vaccination and to promote the practice of receiving the influenza vaccine in children. Education campaigns would help change the attitudes of parents toward vaccinating their children against the flu.