The impact of social hierarchies on neural response to feedback evaluations after advice giving.

Advisors generally evaluate advisee-relevant feedback after advice giving. The response to these feedback-(1) whether the advice is accepted and (2) whether the advice is optimal-usually involves prestige. Prior literature has found that prestige is the basis by which individuals attain a superior status in the social hierarchy. However, whether advisors are motivated to attain a superior status when engaging in advice giving remains uncharacterized. Using event-related potentials, this study investigates how advisors evaluate feedback after giving advice to superior (vs. inferior) status advisees. A social hierarchy was first established based on two advisees (one was ranked as superior status and another as inferior status) as well as participants' performance in a dot-estimation task in which all participants were ranked as medium status. Participants then engaged in a game in which they were assigned roles as advisors to a superior or inferior status advisee. Afterward, the participants received feedback in two phases. In Phase 1, participants were told whether the advisees accepted the advice provided. In Phase 2, the participants were informed whether the advice they provided was correct. In these two phases, when the advisee was of superior status, participants exhibited stronger feedback-related negativity and P300 difference in response to (1) whether their advice was accepted, and (2) whether their advice was correct. Moreover, the P300 was notably larger when the participants' correct advice led to a gain for a superior-status advisee. In the context of advice giving, advisors are particularly motivated to attain a superior status when the feedback involving social hierarchies, which is reflected in higher sensitivity to feedback associated with superior status advisees at earlier and later stages during feedback evaluations in brains.

The causal relationship between psoriasis and chronic obstructive pulmonary disease: A bidirectional mendelian randomization study.

PURPOSE: Although many studies have investigated the association between psoriasis and chronic obstructive pulmonary disease (COPD), the causal relationship between psoriasis and COPD is still unknown. METHODS: We employed bidirectional Mendelian randomization to investigate the causal relationship between psoriasis and COPD. Genetic instruments for exposure were selected from two distinct genome-wide association study databases. Single nucleotide polymorphisms associated with exposures at the genome-wide significance level (p < 5 × 10^-8 ) and exhibiting low linkage disequilibrium (r^2  < 0.001) were chosen as instrumental variables. Causality was assessed using multiple MR methods, including Inverse-Variance Weighted (IVW), MR-Egger, Weighted Median, Simple Mode, and Weighted Mode. A significance level of p < 0.05 was considered statistically significant. Heterogeneity was examined using Cochran's Q test, and MR-Egger regression was employed to detect pleiotropy. The robustness and reliability of the results were further evaluated through leave-one-out analysis. RESULTS: We found a positive causal association between psoriasis and COPD [IVW: odds ratio (OR): 1.0006; p = 0.0056]. Heterogeneity and pleiotropy have not been discovered, so the results of the study are reliable. In the reverse analysis, no causal association between CPOD and psoriasis was found. CONCLUSION: Our findings revealed that psoriasis was associated with an elevated risk of COPD. However, no causal association between COPD and psoriasis was identified in our study.

Nuclear Factor Erythroid 2 Related Factor 2 and Mitochondria Form a Mutually Regulating Circuit in the Prevention and Treatment of Metabolic Syndrome.

Significance: Metabolic syndrome (MetS) has become a major global public health problem and there is an urgent need to elucidate its pathogenesis and find more effective targets and modalities for intervention. Recent Advances: Oxidative stress and inflammation are two of the major causes of MetS-related symptoms such as insulin resistance and obesity. Nuclear factor erythroid 2 related factor 2 (Nrf2) is one of the important systems responding to oxidative stress and inflammation. As cells undergo stress, cysteines within Kelch-like ECH-associated protein 1 (Keap1) are oxidized or electrophilically modified, allowing Nrf2 to escape ubiquitination and be translocated from the cytoplasm to the nucleus, facilitating the initiation of the antioxidant transcriptional program. Meanwhile, a growing body of evidence points out a specific modulation of mitochondrial homeostasis by Nrf2. After nuclear translocation, Nrf2 activates downstream genes involved in various aspects of mitochondrial homeostasis, including mitochondrial biogenesis and dynamics, mitophagy, aerobic respiration, and energy metabolism. In turn, mitochondria reciprocally activate Nrf2 by releasing reactive oxygen species and regulating antioxidant enzymes. Critical Issues: In this review, we first summarize the interactions between Nrf2 and mitochondria in the modulation of oxidative stress and inflammation to ameliorate MetS, then propose that Nrf2 and mitochondria form a mutually regulating circuit critical to maintaining homeostasis during MetS. Future Directions: Targeting the Nrf2-mitochondrial circuit may be a promising strategy to ameliorate MetS, such as obesity, diabetes, and cardiovascular diseases.

Integrated bioinformatics combined with machine learning to analyze shared biomarkers and pathways in psoriasis and cervical squamous cell carcinoma.

Background: Psoriasis extends beyond its dermatological inflammatory manifestations, encompassing systemic inflammation. Existing studies have indicated a potential risk of cervical cancer among patients with psoriasis, suggesting a potential mechanism of co-morbidity. This study aims to explore the key genes, pathways, and immune cells that may link psoriasis and cervical squamous cell carcinoma (CESC). Methods: The cervical squamous cell carcinoma dataset (GSE63514) was downloaded from the Gene Expression Omnibus (GEO). Two psoriasis-related datasets (GSE13355 and GSE14905) were merged into one comprehensive dataset after removing batch effects. Differentially expressed genes were identified using Limma and co-expression network analysis (WGCNA), and machine learning random forest algorithm (RF) was used to screen the hub genes. We analyzed relevant gene enrichment pathways using GO and KEGG, and immune cell infiltration in psoriasis and CESC samples using CIBERSORT. The miRNA-mRNA and TFs-mRNA regulatory networks were then constructed using Cytoscape, and the biomarkers for psoriasis and CESC were determined. Potential drug targets were obtained from the cMAP database, and biomarker expression levels in hela and psoriatic cell models were quantified by RT-qPCR. Results: In this study, we identified 27 key genes associated with psoriasis and cervical squamous cell carcinoma. NCAPH, UHRF1, CDCA2, CENPN and MELK were identified as hub genes using the Random Forest machine learning algorithm. Chromosome mitotic region segregation, nucleotide binding and DNA methylation are the major enrichment pathways for common DEGs in the mitotic cell cycle. Then we analyzed immune cell infiltration in psoriasis and cervical squamous cell carcinoma samples using CIBERSORT. Meanwhile, we used the cMAP database to identify ten small molecule compounds that interact with the central gene as drug candidates for treatment. By analyzing miRNA-mRNA and TFs-mRNA regulatory networks, we identified three miRNAs and nine transcription factors closely associated with five key genes and validated their expression in external validation datasets and clinical samples. Finally, we examined the diagnostic effects with ROC curves, and performed experimental validation in hela and psoriatic cell models. Conclusions: We identified five biomarkers, NCAPH, UHRF1, CDCA2, CENPN, and MELK, which may play important roles in the common pathogenesis of psoriasis and cervical squamous cell carcinoma, furthermore predict potential therapeutic agents. These findings open up new perspectives for the diagnosis and treatment of psoriasis and squamous cell carcinoma of the cervix.

A Novel Synthesized Cyclohexane-Hydroxytyrosol Derivative Suppresses Ovarian Cancer Cell Growth Through Inducing Reactive Oxidative Species and Blocking Autophagic Flux.

Aims: Drug resistance in ovarian cancer (OC) cells often leads to recurrence, metastasis, and high mortality rates among OC patients. Hydroxytyrosol (HT) has been reported to inhibit the proliferation of ovarian and other types of cancer cells. Here we synthesized a novel cyclohexane-hydroxytyrosol derivative (Chx-HT) for enhanced anticaner efficacy. We examined the growth-suppressing effect of Chx-HT on OC cells in vitro and in a xenograft mouse model and investigated the underlying mechanism. Results: We demonstrated that Chx-HT inhibits proliferation, promotes apoptosis, and remodels glucose and lipid metabolism by reducing fatty acid ß-oxidation while increasing glycolysis, de novo fatty acid synthesis (FAS), and lipid droplet (LD) accumulation, impairs mitochondrial respiration, and induces oxidative stress both in vitro and in vivo. In addition, Chx-HT blocks autophagic flux by obstructing the maturation of lysosomal cathepsins in the late stage, but also activates autophagy through the p-AMPK/p-mTOR/p-ULK1 pathway in response to energy deficit. Innovation and Conclusion: Reactive oxidative species (ROS) play a critical role in mediating the effects of Chx-HT on proliferation, apoptosis, autophagy, tricarboxylic acid (TCA) cycle, fatty acid ß-oxidation, and mitochondrial respiration, and the autophagic activation underlies the effects of Chx-HT on glycolysis, de novo FAS, and LD accumulation in OC cells. Cotreating OC cells with Chx-HT and autophagic inhibitor or glycolytic inhibitor results in an additive inhibition of proliferation. Our study indicates that Chx-HT stands for a promising OC therapeutic by ROS and autophagy blockade-mediated metabolic remodeling.

RARRES1 identified by comprehensive bioinformatic analysis and experimental validation as a promising biomarker in Skin Cutaneous Melanoma.

Skin cutaneous melanoma (SKCM) is a highly malignant form of skin cancer, known for its unfavorable prognosis and elevated mortality rate. RARRES1, a gene responsive to retinoic acid receptors, displays varied functions in various cancer types. However, the specific role and underlying mechanisms of RARRES1 in SKCM are still unclear. GSE15605 was utilized to analyze the expression of RARRES1 in SKCM. Subsequently, the TCGA and GEO databases were employed to investigate the relationships between RARRES1 and clinicopathological parameters, as well as the prognostic implications and diagnostic efficacy of RARRES1 in SKCM. GO, KEGG, and GSEA analyses were conducted to explore the potential functions of RARRES1. Furthermore, the associations between RARRES1 and immune infiltration were examined. Genomic alterations and promoter methylation levels of RARRES1 in SKCM were assessed using cBioPortal, UALCAN, and the GEO database. Finally, RARRES1 expression in SKCM was validated through immunohistochemistry, and its functional role in SKCM progression was elucidated via in vivo and in vitro experiments. We found that RARRES1 was downregulated in SKCM compared with normal tissues, and this low expression was associated with worse clinicopathological features and poor prognosis of SKCM. The diagnostic efficacy of RARRES1, as determined by ROC analysis, was 0.732. Through GO, KEGG, and GSEA enrichment analysis, we identified 30 correlated genes and pathways that were mainly enriched in the tumor immune microenvironment, proliferation, apoptosis, and autophagy. Additionally, RARRES1 expression was found to be positively related to the infiltration of various immune cells in SKCM, particularly macrophages and T helper cells, among others. Analysis of genomic alterations and promoter methylation revealed that shallow deletion and hypermethylation of the RARRES1 promoter could lead to reduced RARRES1 expression. IHC validation confirmed the downregulation of RARRES1 in SKCM. Moreover, overexpression of RARRES1 inhibited the proliferation and migration of A375 cells, promoted apoptosis, and inhibited autophagic flux. In the mouse xenograft model, RARRES1 overexpression also suppressed SKCM tumor growth. Collectively, these findings suggest that RARRES1 may function as a suppressor and could potentially serve as a prognostic biomarker and therapeutic target for SKCM.