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The olfactory tubercle (TUB), also called the tubular striatum, receives direct input from the olfactory bulb and, along with the nucleus accumbens, is one of the two principal components of the ventral striatum. As a key component of the reward system, the ventral striatum is involved in feeding behavior, but the vast majority of research on this structure has focused on the nucleus accumbens, leaving the TUB's role in feeding behavior understudied. Given the importance of olfaction in food seeking and consumption, olfactory input to the striatum should be an important contributor to motivated feeding behavior. Yet the TUB is vastly understudied in humans, with very little understanding of its structural organization and connectivity. In this study, we analyzed macrostructural variations between the TUB and the whole brain and explored the relationship between TUB structural pathways and feeding behavior, using body mass index (BMI) as a proxy in females and males. We identified a unique structural covariance between the TUB and the periaqueductal gray (PAG), which has recently been implicated in the suppression of feeding. We further show that the integrity of the white matter tract between the two regions is negatively correlated with BMI. Our findings highlight a potential role for the TUB-PAG pathway in the regulation of feeding behavior in humans.
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Conducta Alimentaria , Tubérculo Olfatorio , Sustancia Gris Periacueductal , Humanos , Masculino , Femenino , Conducta Alimentaria/fisiología , Adulto , Sustancia Gris Periacueductal/fisiología , Tubérculo Olfatorio/fisiología , Imagen por Resonancia Magnética/métodos , Adulto Joven , Vías Nerviosas/fisiologíaRESUMEN
Vascular calcification is a major risk factor for cardiovascular disease mortality, with a significant prevalence in chronic kidney disease (CKD). Pharmacological inhibition of histone acetyltransferase has been proven to protect against from vascular calcification. However, the role of Histone Deacetylase 2 (HDAC2) and molecular mechanisms in vascular calcification of CKD remains unknown. An in vivo model of CKD was established using mouse fed with a high adenine and phosphate diet, and an in vitro model was produced using human aortic vascular smooth muscle cells (VSMCs) stimulated with ß-glycerophosphate (ß-GP). HDAC2 expression was found to be reduced in medial artery of CKD mice and ß-GP-induced VSMCs. Overexpression of HDAC2 attenuated OPN and OCN upregulation, α-SMA and SM22α downregulation, and calcium deposition in aortas of CKD. The in vitro results also demonstrated that ß-GP-induced osteogenic differentiation was inhibited by HDAC2. Furthermore, we found that HDAC2 overexpression caused an increase in LC3II/I, a decrease in p62, and an induction of autophagic flux. Inhibition of autophagy using its specific inhibitor 3-MA blocked HDAC2's protective effect on osteogenic differentiation in ß-GP-treated VSMCs. Taken together, these results suggest that HDAC2 may protect against vascular calcification by the activation of autophagy, laying out a novel insight for the molecular mechanism in vascular calcification of CKD.
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Glicerofosfatos , Insuficiencia Renal Crónica , Calcificación Vascular , Humanos , Animales , Ratones , Histona Desacetilasa 2/genética , Osteogénesis , AutofagiaRESUMEN
Studies of neuronal oscillations have contributed substantial insight into the mechanisms of visual, auditory, and somatosensory perception. However, progress in such research in the human olfactory system has lagged behind. As a result, the electrophysiological properties of the human olfactory system are poorly understood, and, in particular, whether stimulus-driven high-frequency oscillations play a role in odor processing is unknown. Here, we used direct intracranial recordings from human piriform cortex during an odor identification task to show that 3 key oscillatory rhythms are an integral part of the human olfactory cortical response to smell: Odor induces theta, beta, and gamma rhythms in human piriform cortex. We further show that these rhythms have distinct relationships with perceptual behavior. Odor-elicited gamma oscillations occur only during trials in which the odor is accurately perceived, and features of gamma oscillations predict odor identification accuracy, suggesting that they are critical for odor identity perception in humans. We also found that the amplitude of high-frequency oscillations is organized by the phase of low-frequency signals shortly following sniff onset, only when odor is present. Our findings reinforce previous work on theta oscillations, suggest that gamma oscillations in human piriform cortex are important for perception of odor identity, and constitute a robust identification of the characteristic electrophysiological response to smell in the human brain. Future work will determine whether the distinct oscillations we identified reflect distinct perceptual features of odor stimuli.
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Ondas Encefálicas/fisiología , Electrocorticografía/métodos , Percepción Olfatoria/fisiología , Corteza Piriforme/fisiología , Señales (Psicología) , Epilepsia , Humanos , Odorantes , OlfatoRESUMEN
Non-invasive neuroimaging has revealed specific network-based resting-state dynamics in the human brain, yet the underlying neurophysiological mechanism remains unclear. We employed intracranial electroencephalography to characterize local field potentials within the default mode network (DMN), frontoparietal network (FPN), and salience network (SN) in 42 participants. We identified stronger within-network phase coherence at low frequencies (θ and α band) within the DMN, and at high frequencies (γ band) within the FPN. Hidden Markov modeling indicated that the DMN exhibited preferential low frequency phase coupling. Phase-amplitude coupling (PAC) analysis revealed that the low-frequency phase in the DMN modulated the high-frequency amplitude envelopes of the FPN, suggesting frequency-dependent characterizations of intrinsic brain networks at rest. These findings provide intracranial electrophysiological evidence in support of the network model for intrinsic organization of human brain and shed light on the way brain networks communicate at rest.
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Acute myeloid leukemia (AML) can manifest as de novo AML (dn-AML) or secondary AML (s-AML), with s-AML being associated with inferior survival and distinct genomic characteristics. The underlying reasons for this disparity remain to be elucidated. In this multicenter study, next-generation sequencing (NGS) was employed to investigate the mutational landscape of AML in 721 patients from June 2020 to May 2023.Genetic mutations were observed in 93.34% of the individuals, with complex variations (more than three gene mutations) present in 63.10% of them. TET2, ASXL1, DNMT3A, TP53 and SRSF2 mutations showed a higher prevalence among older individuals, whereas WT1 and KIT mutations were more commonly observed in younger patients. BCOR, BCORL1, ZRSR2, ASXL1 and SRSF2 exhibited higher mutation frequencies in males. Additionally, ASXL1, NRAS, PPMID, SRSF2, TP53 and U2AF1 mutations were more common in patients with s-AML, which PPM1D was more frequently associated with therapy-related AML (t-AML). Advanced age and hyperleukocytosis independently served as adverse prognostic factors for both types of AML; however, s-AML patients demonstrated a greater number of monogenic adverse prognostic factors compared to dn-AML cases (ASXL1, PPM1D, TP53 and U2AF1 in s-AML vs. FLT3, TP53 and U2AF1 in dn-AML). Age and sex-related gene mutations suggest epigenetic changes may be key in AML pathogenesis. The worse prognosis of s-AML compared to dn-AML could be due to the older age of s-AML patients and more poor-prognosis gene mutations. These findings could improve AML diagnosis and treatment by identifying potential therapeutic targets and risk stratification biomarkers.
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BACKGROUND: Medial vascular calcification is commonly identified in chronic kidney disease (CKD) patients and seriously affects the health and life quality of patients. This study aimed to investigate the effects of protein arginine methyltransferase 3 (PRMT3) on vascular calcification induced by CKD. METHODS: A mice model of CKD was established with a two-step diet containing high levels of calcium and phosphorus. Vascular smooth muscle cells (VSMCs) were subjected to ß-glycerophosphate (ß-GP) treatment to induce the osteogenic differentiation as an in vitro CKD model. RESULTS: PRMT3 was upregulated in VSMCs of medial artery of CKD mice and ß-GP-induced VSMCs. The inhibitor of PRMT3 (SGC707) alleviated the vascular calcification and inhibited the glycolysis of CKD mice. Knockdown of PRMT3 alleviated the ß-GP-induced osteogenic transfomation of VSMCs by the repression of glycolysis. Next, PRMT3 interacted with hypoxia-induced factor 1α (HIF-1α), and the knockdown of PRMT3 downregulated the protein expression of HIF-1α by weakening its methylation. Gain of HIF-1α reversed the PRMT3 depletion-induced suppression of osteogenic differentiation and glycolysis of VSMCs. CONCLUSION: The inhibitory role of PRMT3 depletion was at least mediated by the regulation of glycolysis upon repressing the methylation of HIF-1α.
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Glicerofosfatos , Insuficiencia Renal Crónica , Calcificación Vascular , Animales , Humanos , Ratones , Hipoxia , Osteogénesis/genética , Proteína-Arginina N-Metiltransferasas/genética , Insuficiencia Renal Crónica/genética , Calcificación Vascular/etiologíaRESUMEN
BACKGROUND: The immune reconstitution after allogeneic hematopoietic stem cell transplantation (allo-HSCT) is crucial for preventing infections and relapse and enhancing graft-versus-tumor effects. B cells play an important role in humoral immunity and immune regulation, but their reconstitution after allo-HSCT has not been well studied. METHODS: In this study, we analyzed the dynamics of B cells in 252 patients who underwent allo-HSCT for 2 years and assessed the impact of factors on B-cell reconstitution and their correlations with survival outcomes, as well as the development stages of B cells in the bone marrow and the subsets in the peripheral blood. RESULTS: We found that the B-cell reconstitution in the bone marrow was consistent with the peripheral blood (p = 0.232). B-cell reconstitution was delayed by the male gender, age >50, older donor age, the occurrence of chronic and acute graft-versus-host disease, and the infections of fungi and cytomegalovirus. The survival analysis revealed that patients with lower B cells had higher risks of death and relapse. More importantly, we used propensity score matching to obtain the conclusion that post-1-year B-cell reconstitution is better in females. Meanwhile, using mediation analysis, we proposed the age-B cells-survival axis and found that B-cell reconstitution at month 12 posttransplant mediated the effect of age on patient survival (p = 0.013). We also found that younger patients showed more immature B cells in the bone marrow after transplantation (p = 0.037). CONCLUSION: Our findings provide valuable insights for optimizing the management of B-cell reconstitution and improving the efficacy and safety of allo-HSCT.
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Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Femenino , Humanos , Masculino , Trasplante Homólogo , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Enfermedad Injerto contra Huésped/etiología , Enfermedad Injerto contra Huésped/prevención & control , Enfermedad Injerto contra Huésped/epidemiología , Linfocitos B , RecurrenciaRESUMEN
BACKGROUND: Prenatal depression is associated with adverse health outcomes for both mothers and their children. The worldwide COVID-19 pandemic has presented new risks and challenges for expectant mothers. The aims of the study were to investigate the underlying mechanism between COVID-19 risk perception of Chinese pregnant women and their prenatal depressive symptoms and potential protective factors such as family sense of coherence (FSOC). METHOD: A total of 181 Chinese pregnant women (Mage = 31.40 years, SD = 3.67, ranged from 23 to 43) participated in an online survey from April 22 to May 16, 2020. Risk perception and negative emotions (fear and anxiety) related with COVID-19, FSOC, and prenatal depressive symptoms were assessed. RESULTS: The experience of maternal COVID-19 related negative emotion fully mediated the positive relationship between COVID-19 risk perception and prenatal depressive symptoms of pregnant women (ß = 0.12, 95% CI [0.06, 0.19]). When confronting COVID-19 related fear and anxiety, expectant mothers from higher coherent families experienced a significantly lower level of prenatal depressive symptoms. CONCLUSIONS: Contextual negative emotional experience was demonstrated to explain how risk perception impacts depressive symptoms during severe public health crisis for pregnant women. FSOC may be a psychological resource protecting pregnant women from experiencing adverse psychological outcomes during COVID-19 pandemic.
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COVID-19 , Depresión , Emociones , Mujeres Embarazadas , SARS-CoV-2 , Humanos , COVID-19/psicología , COVID-19/epidemiología , Femenino , China/epidemiología , Adulto , Embarazo , Depresión/psicología , Depresión/epidemiología , Mujeres Embarazadas/psicología , Sentido de Coherencia , Ansiedad/psicología , Ansiedad/epidemiología , Encuestas y Cuestionarios , Madres/psicología , Pandemias , Percepción , Miedo/psicología , Adulto JovenRESUMEN
Informed by the interaction of person-affect-cognition-execution (I-PACE) theory, the present studies examined the association between peer rejection, peer popularity, and social media addiction (SMA) at both between-person and within-person levels. Two distinct processes, the fear-driven/compensation-seeking process and the reward-driven process were explored. In Study 1, using a cross-sectional sample of high school students (N = 318), both processes were supported via different cognitive mediators. Support for the fear-driven/compensation-seeking process was demonstrated by finding that avoidance expectancy was a significant cognitive mediator between peer-nominated rejection and SMA. In turn, the reward-driven process was supported by the significant mediation of reward expectancy between peer-nominated popularity and SMA. In Study 2, using ecological momentary assessment with college students (N = 54), we found the fear-driven/compensation-seeking process partially supported through both between-person and within-person mediations. Specifically, negative affect and social media craving were two affective mediators that linked peer rejection and addictive social media use behaviors. On the other hand, the reward-driven process was predominantly supported by within-person mediations, in which positive affect and social media craving were found to be mediators of the relationship between peer popularity and addictive social media use behaviors. The results underscore that adolescents experiencing rejection tend to use social media to avoid negative feelings and compensate for interpersonal deficits, while adolescents experiencing popularity tend to use social media to maintain positive feelings and gain social rewards. Implications for the assessment, case formulation, and treatment of SMA in counseling practice are discussed. (PsycInfo Database Record (c) 2024 APA, all rights reserved).
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To address the lightweight and real-time issues of coal sorting detection, an intelligent detection method for coal and gangue, Our-v8, was proposed based on improved YOLOv8. Images of coal and gangue with different densities under two diverse lighting environments were collected. Then the Laplacian image enhancement algorithm was proposed to improve the training data quality, sharpening contours and boosting feature extraction; the CBAM attention mechanism was introduced to prioritize crucial features, enhancing more accurate feature extraction ability; and the EIOU loss function was added to refine box regression, further improving detection accuracy. The experimental results showed that Our-v8 for detecting coal and gangue in a halogen lamp lighting environment achieved excellent performance with a mean average precision (mAP) of 99.5%, was lightweight with FLOPs of 29.7, Param of 12.8, and a size of only 22.1 MB. Additionally, Our-v8 can provide accurate location information for coal and gangue, making it ideal for real-time coal sorting applications.
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The human sense of smell plays an important role in appetite and food intake, detecting environmental threats, social interactions, and memory processing. However, little is known about the neural circuity supporting its function. The olfactory tracts project from the olfactory bulb along the base of the frontal cortex, branching into several striae to meet diverse cortical regions. Historically, using diffusion magnetic resonance imaging (dMRI) to reconstruct the human olfactory tracts has been prevented by susceptibility and motion artifacts. Here, we used a dMRI method with readout segmentation of long variable echo-trains (RESOLVE) to minimize image distortions and characterize the human olfactory tracts in vivo We collected high-resolution dMRI data from 25 healthy human participants (12 male and 13 female) and performed probabilistic tractography using constrained spherical deconvolution (CSD). At the individual subject level, we identified the lateral, medial, and intermediate striae with their respective cortical connections to the piriform cortex and amygdala (AMY), olfactory tubercle (OT), and anterior olfactory nucleus (AON). We combined individual results across subjects to create a normalized, probabilistic atlas of the olfactory tracts. We then investigated the relationship between olfactory perceptual scores and measures of white matter integrity, including mean diffusivity (MD). Importantly, we found that olfactory tract MD negatively correlated with odor discrimination performance. In summary, our results provide a detailed characterization of the connectivity of the human olfactory tracts and demonstrate an association between their structural integrity and olfactory perceptual function.SIGNIFICANCE STATEMENT This study provides the first detailed in vivo description of the cortical connectivity of the three olfactory tract striae in the human brain, using diffusion magnetic resonance imaging (dMRI). Additionally, we show that tract microstructure correlates with performance on an odor discrimination task, suggesting a link between the structural integrity of the olfactory tracts and odor perception. Lastly, we generated a normalized probabilistic atlas of the olfactory tracts that may be used in future research to study its integrity in health and disease.
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Imagen de Difusión por Resonancia Magnética/métodos , Procesamiento de Imagen Asistido por Computador/métodos , Bulbo Olfatorio/anatomía & histología , Vías Olfatorias/anatomía & histología , Adulto , Femenino , Humanos , MasculinoRESUMEN
In lithium-ion batteries (LIBs), the stabilized capacities of transition metal compound anodes usually exhibit higher values than their theoretical values due to the interfacial charge storage, the formation of reversible electrolyte-derived surface layer, or interfacial magnetization. But the effectively utilizing the mechanisms to achieve novel anodes is rarely explored. Herein, a novel nanosized cobalt ditelluride (CoTe2 ) anodes with ultra-high capacity and long term stability is reported. Electrochemical tests show that the lithium storage capacity of the best sample reaches 1194.7 mA h g-1 after 150 cycles at 0.12 A g-1 , which increases by 57.8% compared to that after 20 cycles. In addition, the sample offers capacities of 546.6 and 492.1 mA h g-1 at 0.6 and 1.8 A g-1 , respectively. During cycles, CoTe2 particles (average size 20 nm) are gradually pulverized into the smaller nanoparticles (<3 nm), making the magnetization more fully due to the larger contact area of Co/Li2 Te interface, yielding an increased capacity. The negative capacity fading is observed, and verified by ex situ structural characterizations and in situ electrochemical measurements. The proposed strategy can be further extended to obtain other high-performance ferromagnetic metal based electrodes for energy storage applications.
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Anticipating an odor improves detection and perception, yet the underlying neural mechanisms of olfactory anticipation are not well understood. In this study, we used human intracranial electroencephalography (iEEG) to show that anticipation resets the phase of delta oscillations in piriform cortex prior to odor arrival. Anticipatory phase reset correlates with ensuing odor-evoked theta power and improvements in perceptual accuracy. These effects were consistently present in each individual subject and were not driven by potential confounds of pre-inhale motor preparation or power changes. Together, these findings suggest that states of anticipation enhance olfactory perception through phase resetting of delta oscillations in piriform cortex.
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Anticipación Psicológica/fisiología , Percepción Olfatoria/fisiología , Corteza Piriforme/fisiología , Adolescente , Adulto , Relojes Biológicos , Electroencefalografía , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto JovenRESUMEN
To keep pace with the demands of semiconductor integration technology, a semiconductor device should offer a small footprint. Here, we demonstrate a compact electro-optic modulator by controlling the spatial distribution of carrier density in indium tin oxide (ITO). The proposed structure is mainly composed of a symmetrical metal electrode layer, calcium fluoride dielectric layer, and an ITO propagating layer. The carrier density on the surface of the ITO exhibits a periodical distribution when the voltage is applied on the electrode, which greatly enhances the interaction between the surface plasmon polaritons (SPPs) and the ITO. This structure can not only effectively improve the modulation depth of the modulator, but also can further reduce the device size. The numerical results indicate that when the length, width, and height of the device are 14 µm, 5 µm, and 8 µm, respectively, the modulation depth can reach 37.1 dB at a wavelength of 3.66 µm. The structure can realize a broadband modulation in theory only if we select a different period of the electrode corresponding to the propagating wavelength of SPPs because the modulator is based on the scattering effect principle. This structure could potentially have high applicability for optoelectronic integration, optical communications, and optical sensors in the future.
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BACKGROUND: Emotional distress, including depressive and anxiety symptoms, is a common concern among pregnant individuals and has negative impacts on maternal and offspring's health. Previous studies indicated the heterogeneity of perinatal emotional distress. Moreover, during the pandemic of COVID-19, expectant mothers are faced with more tough challenges, which could exacerbate their emotional distress. OBJECTIVE: The aim of present study is to examine potential subgroups with distinct profiles on emotional distress and relationship resources during the pandemic. METHODS: A total of 187 pregnant people in China were recruited from April 22 to May 16 in 2020. Latent profile analysis was applied based on prenatal depressive and anxiety symptoms, COVID-19-related negative emotions, prenatal attachment, marital satisfaction and family sense of coherence. RESULTS: Four subgroups were identified. Group 1 and Group 2 shared with low levels of emotional distress and COVID-19-related negative emotions, among which Group 1 had plenty of relationship resources, while Group 2 had insufficient support. Group 3 had moderate levels of emotional distress but above-average prenatal attachment. Group 4 was a highly distressed subtype with severe emotional distress and poor states across all domains. CONCLUSION: Our findings support that emotion distress among expecting mothers is heterogeneous, highlighting the need for tailed interventions to address the specific needs of subgroups during pregnancy.
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Personal hygiene including wearing facemask and washing hands are instrumental to reduce transmission of COVID-19. The present study applied the health action process approach (HAPA) to examine the process from intention to protective behaviors in the early stages of the COVID-19 pandemic. A longitudinal online survey study was conducted among 229 individuals (61.6% females; M age = 25.37 years, SD age = 8.34 years) living in Hubei province, China. Action self-efficacy, outcome expectancy, risk perception, intention, planning and action control regarding facemask wearing and hand washing were assessed at baseline (Time 1), and behaviors were assessed a week later (Time 2). Data were collected from 30 January to 16 February 2020. Two structural equation models were specified to test the theory-driven determinants of the facemask wearing and hand washing respectively. The results showed that action self-efficacy predicted intentions to wear facemasks and wash hands. Intention and action control predicted both behaviors at Time 2. Associations between planning and behaviors were mixed. Mediation analyses revealed that action control significantly mediated the relationship between intention and both behaviors (facemask wearing: 90% CI [0.01, 0.12]; hand washing: 95% CI [0.01, 0.21]). Planning did not mediate the relationship between intention and the two behaviors. The findings illustrate that action self-efficacy is positively associated with intention to facemask wearing and hand washing, and action control contributes to bridging intention to behaviors. Both motivational and volitional factors warrant consideration in interventions to improve adherence to facemask wearing and hand washing in COVID-19.
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BACKGROUND: Aberrant DNA methylation may offer opportunities in revolutionizing cancer screening and diagnosis. We sought to identify a non-invasive DNA methylation-based screening approach using cell-free DNA (cfDNA) for early detection of hepatocellular carcinoma (HCC). METHODS: Differentially, DNA methylation blocks were determined by comparing methylation profiles of biopsy-proven HCC, liver cirrhosis, and normal tissue samples with high throughput DNA bisulfite sequencing. A multi-layer HCC screening model was subsequently constructed based on tissue-derived differentially methylated blocks (DMBs). This model was tested in a cohort consisting of 120 HCC, 92 liver cirrhotic, and 290 healthy plasma samples including 65 hepatitis B surface antigen-seropositive (HBsAg+) samples, independently validated in a cohort consisting of 67 HCC, 111 liver cirrhotic, and 242 healthy plasma samples including 56 HBsAg+ samples. RESULTS: Based on methylation profiling of tissue samples, 2321 DMBs were identified, which were subsequently used to construct a cfDNA-based HCC screening model, achieved a sensitivity of 86% and specificity of 98% in the training cohort and a sensitivity of 84% and specificity of 96% in the independent validation cohort. This model obtained a sensitivity of 76% in 37 early-stage HCC (Barcelona clinical liver cancer [BCLC] stage 0-A) patients. The screening model can effectively discriminate HCC patients from non-HCC controls, including liver cirrhotic patients, asymptomatic HBsAg+ and healthy individuals, achieving an AUC of 0.957(95% CI 0.939-0.975), whereas serum α-fetoprotein (AFP) only achieved an AUC of 0.803 (95% CI 0.758-0.847). Besides detecting patients with early-stage HCC from non-HCC controls, this model showed high capacity for distinguishing early-stage HCC from a high risk population (AUC=0.934; 95% CI 0.905-0.963), also significantly outperforming AFP. Furthermore, our model also showed superior performance in distinguishing HCC with normal AFP (< 20ng ml-1) from high risk population (AUC=0.93; 95% CI 0.892-0.969). CONCLUSIONS: We have developed a sensitive blood-based non-invasive HCC screening model which can effectively distinguish early-stage HCC patients from high risk population and demonstrated its performance through an independent validation cohort. TRIAL REGISTRATION: The study was approved by the ethic committee of The Second Xiangya Hospital of Central South University (KYLL2018072) and Chongqing University Cancer Hospital (2019167). The study is registered at ClinicalTrials.gov(# NCT04383353 ).
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Carcinoma Hepatocelular , Ácidos Nucleicos Libres de Células , Neoplasias Hepáticas , Biomarcadores de Tumor/genética , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/genética , Ácidos Nucleicos Libres de Células/genética , Metilación de ADN , Diagnóstico Diferencial , Humanos , Cirrosis Hepática/diagnóstico , Cirrosis Hepática/genética , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/genéticaRESUMEN
BACKGROUND: Little is known on the tumor microenvironment (TME) response after neoadjuvant chemotherapy (NACT) in gastric cancer on the molecular level. METHODS: Here, we profiled 33,589 cell transcriptomes in 14 samples from 11 gastric cancer patients (4 pre-treatment samples, 4 post-treatment samples and 3 pre-post pairs) using single-cell RNA sequencing (scRNA-seq) to generate the cell atlas. The ligand-receptor-based intercellular communication networks of the single cells were also characterized before and after NACT. RESULTS: Compered to pre-treatment samples, CD4+ T cells (P = 0.018) and CD8+ T cells (P = 0.010) of post-treatment samples were significantly decreased, while endothelial cells and fibroblasts were increased (P = 0.034 and P = 0.005, respectively). No significant difference observed with respect to CD4+ Tregs cells, cycling T cells, B cells, plasma cells, macrophages, monocytes, dendritic cells, and mast cells (P > 0.05). In the unsupervised nonnegative matrix factorization (NMF) analysis, we revealed that there were three transcriptional programs (NMF1, NMF2 and NMF3) shared among these samples. Compared to pre-treatment samples, signature score of NMF1 was significantly downregulated after treatment (P = 0.009), while the NMF2 signature was significantly upregulated after treatment (P = 0.013). The downregulated NMF1 and upregulated NMF2 signatures were both associated with improved overall survival outcomes based on The Cancer Genome Atlas (TCGA) database. Additionally, proangiogenic pathways were activated in tumor and endothelial cells after treatment, indicating that NACT triggers vascular remodeling by cancer cells together with stromal cells. CONCLUSIONS: In conclusion, our study provided transcriptional profiles of TME between pre-treatment and post-treatment for in-depth understanding on the mechanisms of NACT in gastric cancer and empowering the development of potential optimized therapy procedures and novel drugs.
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Neoplasias Gástricas , Microambiente Tumoral , Humanos , Terapia Neoadyuvante , Neoplasias Gástricas/tratamiento farmacológico , Neoplasias Gástricas/genética , Células EndotelialesRESUMEN
Obesity, a global epidemic, is one of the critical causes of chronic kidney disease (CKD). R-spondin1 (RSPO1) possessing the potential to activate Wnt/ß-catenin pathway was reported to be elevated in circulation of obesity objects. However, the function of RSPO1 and the latent mechanism in obesity-related CKD are still left to be revealed. In the present study, renal RSPO1 expression was increased in mice fed on high-fat diet (HFD) for 12 weeks. Lentivirus-mediated RSPO1 knockdown partly recovered obesity-related metabolic symptoms, while distinctly remitted kidney dysfunction and renal fibrosis in obesity mice. In vitro, recombinant RSPO1 was found to elevate leucine-rich repeat-containing G protein coupled receptor 4 (LGR4) expression, promote Wnt/ß-catenin signaling pathway activation, facilitate epithelial-mesenchymal transition (EMT) and increase collagen deposition in HK2 renal tubular cells. Such pro-fibrotic effect of RSPO1 was diminished by LGR4 siRNA in HK2 cells. In summary, we demonstrate that RSPO1/LGR4 axis is involved in obesity-related renal fibrosis at least through activating Wnt/ß-catenin signaling pathway, providing a potential therapeutic target for this disease.
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Fibrosis/metabolismo , Obesidad/complicaciones , Trombospondinas/metabolismo , Vía de Señalización Wnt/fisiología , beta Catenina/metabolismo , Animales , Células Epiteliales/metabolismo , Transición Epitelial-Mesenquimal/fisiología , Masculino , Ratones Endogámicos C57BL , Receptores Acoplados a Proteínas G/metabolismoRESUMEN
Metal sorting is the first step in scrap metal recycling. The traditional magnetic separation method can classify ferromagnetic metals, but it is not applicable to some nonmagnetic metals with higher value. To address this situation, we propose an eddy current testing (ECT) technology-based method for classifying nonmagnetic metals. In this study, a triple-coil electromagnetic sensor, which works as two coil pairs, is tested. By analyzing the physical model of the sensor, a feature related to the conductivity of the sample under test is obtained as the difference in the tangent of the impedance changes in the two coil pairs. Additionally, we derive a linear relationship between this feature and the lift-off height, which is verified experimentally and will help to solve the classification error caused by the variation in the lift-off height. In addition, we find that the excitation frequency does not affect this linear feature. Moreover, in this study, the spectrum scanning method is converted into a single-frequency measurement, and the time consumption is greatly reduced, which improves the efficiency of the real-time metal classification system.