FUT2 promotes colorectal cancer metastasis by reprogramming fatty acid metabolism via YAP/TAZ signaling and SREBP-1.

Colorectal cancer (CRC) ranks as the second most lethal cancer worldwide because of its high rate of metastasis, and approximately 20% of CRC patients have metastases at initial diagnosis. Metabolic reprogramming, a hallmark of cancer cells, has been implicated in the process of metastasis. We previously demonstrated that fucosyltransferase 2 (FUT2) promotes the malignancy of CRC cells, however, the underlying mechanisms remain unclear. Here, bioinformatic analysis revealed that FUT2 is associated with the malignant phenotype and fatty acid metabolism in CRC. FUT2 knockdown decreased glucose uptake and de novo fatty acid synthesis, which in turn inhibited the proliferation and metastasis of CRC cells. Mechanistically, FUT2 promotes YAP1 nuclear translocation and stabilizes mSREBP-1 by fucosylation, thus promoting de novo fatty acid synthesis in CRC cells. In summary, this study demonstrates that FUT2 promotes the proliferation and metastasis of CRC cells by reprogramming fatty acid metabolism via YAP/TAZ signaling and SREBP-1, indicating that FUT2 might be a potential target for developing therapeutic strategies against CRC.

Deciphering Dormant Cells of Lung Adenocarcinoma: Prognostic Insights from O-glycosylation-Related Tumor Dormancy Genes Using Machine Learning.

Lung adenocarcinoma (LUAD) poses significant challenges due to its complex biological characteristics and high recurrence rate. The high recurrence rate of LUAD is closely associated with cellular dormancy, which enhances resistance to chemotherapy and evasion of immune cell destruction. Using single-cell RNA sequencing (scRNA-seq) data from LUAD patients, we categorized the cells into two subclusters: dormant and active cells. Utilizing high-density Weighted Gene Co-expression Network Analysis (hdWGCNA) and pseudo-time cell trajectory, aberrant expression of genes involved in protein O-glycosylation was detected in dormant cells, suggesting a crucial role for O-glycosylation in maintaining the dormant state. Intercellular communication analysis highlighted the interaction between fibroblasts and dormant cells, where the Insulin-like Growth Factor (IGF) signaling pathway regulated by O-glycosylation was crucial. By employing Gene Set Variation Analysis (GSVA) and machine learning, a risk score model was developed using hub genes, which showed high accuracy in determining LUAD prognosis. The model also demonstrated robust performance on the training dataset and excellent predictive capability, providing a reliable basis for predicting patient clinical outcomes. The group with a higher risk score exhibited a propensity for adverse outcomes in the tumor microenvironment (TME) and tumor mutational burden (TMB). Additionally, the 50% inhibitory concentration (IC50) values for chemotherapy exhibited significant variations among the different risk groups. In vitro experiments demonstrated that EFNB2, PTTG1IP, and TNFRSF11A were upregulated in dormant tumor cells, which also contributed greatly to the diagnosis of LUAD. In conclusion, this study highlighted the crucial role of O-glycosylation in the dormancy state of LUAD tumors and developed a predictive model for the prognosis of LUAD patients.

Structural and functional neural patterns among sub-threshold bulimia nervosa: Abnormalities in dorsolateral prefrontal cortex and orbitofrontal cortex.

BACKGROUND: Disordered eating behaviors are prevalent among youngsters and highly associated with dysfunction in neurocognitive systems. We aimed to identify the potential changes in individuals with bulimia symptoms (sub-BN) to generate insights to understand developmental pathophysiology of bulimia nervosa. METHODS: We investigated group differences in terms of degree centrality (DC) and gray matter volume (GMV) among 145 undergraduates with bulimia symptoms and 140 matched control undergraduates, with the secondary analysis of the whole brain connectivity in these regions of interest showing differences in static functional connectivity (FC). RESULTS: The sub-BN group exhibited abnormalities of the right dorsolateral prefrontal cortex and right orbitofrontal cortex in both GMV and DC, and displayed decreased FC between these regions and the precuneus. We also observed that sub-BN presented with reduced FC between the calcarine and superior temporal gyrus, middle temporal gyrus and inferior parietal gyrus. Additionally, brain-behavioral associations suggest a distinct relationship between these FCs and psychopathological symptoms in sub-BN group. CONCLUSIONS: Our study demonstrated that individuals with bulimia symptoms present with aberrant neural patterns that mainly involved in cognitive control and reward processing, as well as attentional and self-referential processing, which could provide important insights into the pathology of BN.

Association between high levels of body-esteem and increased degree of midcingulate cortex global connectivity: A resting-state fMRI study.

Multiple neuroimaging studies have examined the neural underpinnings of body image disturbances in patients with eating disorders. However, key brain regions related to body image, such as body-esteem (BE), among healthy individuals are understudied. Given the extremely crucial role of BE in eating behaviors and physical and mental health, the current study conducted data-driven analysis and characterized the neurobiological correlates of BE with the network properties of the resting brain using the voxel-wise degree centrality (DC) measures of resting-state functional magnetic resonance imaging (rs-fMRI) data and seed-based resting-state functional connectivity (RSFC). A total of 694 healthy young adults (females = 474, mean age = 18.38 years, range = 17-22) underwent rs-fMRI, and completed the Body-Esteem Scale for Adolescents and Adults, the Eating Disorder Diagnosis Scale, and the Restraint Scale. After correcting for differences in age, gender, body mass index, and head motion, whole-brain correlation analyses revealed that a high level of BE was associated with increased DC within the right midcingulate cortex (MCC) and subsequent high levels of MCC-based RSFC strengths. Furthermore, MCC connectivity patterns related to BE were inversely associated with disordered eating behaviors. These findings suggest that adaptive cognitive and emotional regulation (i.e., self-evaluation and emotion based on body image) may explain the potential relationship between MCC connectivity patterns and BE to a certain extent. As such, future studies should investigate these interesting possibilities.

Influence of negative mood on restrained eaters' memory suppression of food cues: An event-related potentials study.

Negative mood has been found to be a critical trigger for overeating in restrained eaters. The ability to suppress thinking of palatable food cues is crucial to control hedonic eating; nevertheless, little research has been conducted to explore inhibitory control in cognitive processes among restrained eaters. To address this gap, this study primed restrained eaters with negative (n = 23) or neutral emotions (n = 24) and applied a Think/No-think paradigm to explore their retrieval facilitation/suppression ability for food cues, while recording Electroencephalogram (EEG) data. Results indicated that the recall rate of the No-think condition (retrieval suppressing task) was higher than the Think condition (retrieval task). Negative affect did not influence the recall rate, but it did evoke smaller N2 amplitudes, larger P2 and P3 amplitudes, as well as late positive component (LPC) amplitudes. Among these components, P2 evoked by the No-think and Think conditions was larger than the perceptual control condition. Our findings suggested that in negative moods, restrained eaters need to allocate more attentional resources to suppress food cues. The findings further demonstrated that the influence of negative moods appeared at an early stage of cognitive processing and caused a resource depletion in memory suppression. This research provides a neurophysiological basis for understanding emotional influences on the process of restrained eaters' inhibition control for external food cues.

Episodic memory for food and non-food cues in females with obesity.

Episodic memory is typically thought of as the memory system that makes possible mental time travel through subjective time. This may serve an important function in allowing us to use recent dietary information to predict future food needs and integrate this information with current food availability to adapt motivation accordingly. Growing evidence has suggested that episodic memory influences and is influenced by obesity. However, there is limited available evidence on the characteristics of episodic memory for food and non-food cues in people with obesity. The present study attempts to address this association and apply an episodic memory task to evaluate item memory and source memory for food and non-food cues in females with obesity. Participants were 26 females with obesity and 30 females with healthy weight, who were undergraduate students aged 17-24 years. They completed the Dutch Eating Behavior Questionnaire, hunger visual analog scale, fullness visual analog scale, desire-to-eat visual analog scale, and an episodic memory task including item memory and source memory. Results showed that the episodic memory patterns of females with and without obesity changed according to the type of stimuli. Specifically, females with obesity outperformed females with healthy weight in item memory for food cues, but showed deficits in item memory for non-food cues and source memory for both food and non-food cues. Taken together, based on the obesity and suboptimal food-related decision theoretical model, these findings are of great theoretical and clinical significance to explore episodic memory pattern differences between people with and without obesity.