Design, synthesis and biological evaluation of 5H-[1,2,4]triazino[5,6-b]indole derivatives bearing a pyridinocycloalkyl moiety as iron chelators.

The avidity of cancer cells for iron highlights the potential for iron chelators to be used in cancer therapy. Herein, we designed and synthesized a novel series of 5H-[1,2,4]triazino[5,6-b]indole derivatives bearing a pyridinocycloalkyl moiety using a ring-fusion strategy based on the structure of an iron chelator, VLX600. The antiproliferative activity evaluation against cancer cells and normal cells led to the identification of compound 3k, which displayed the strongest antiproliferative activity in vitro against A549, MCF-7, Hela and HepG-2 with IC50 values of 0.59, 0.86, 1.31 and 0.92 µM, respectively, and had lower cytotoxicity against HEK293 than VLX600. Further investigations revealed that unlike VLX600, compound 3k selectively bound to ferrous ions, but not to ferric ions, and addition of Fe2+ abolished the cytotoxicity of 3k. Flow cytometry assays demonstrated that 3k arrested the cell cycle at the G1 phase and induced significant apoptosis in A549 cells in dose and time-dependent manners, corresponding to JC-1 staining assay results. Western blot analysis of Bcl-2, Bax and cleaved caspase-3 proteins further provided evidences that induction of apoptosis by 3k in A549 cells might be at least via the mitochondria pathway. These above results highlight that 3k is a valuable lead compound that deserves further investigation as an iron chelator for the treatment of cancer.

Bullying Victimization and Malevolent Creativity in Rural Adolescents: The Longitudinal Mediational Role of Hostile Attribution.

Extensive research has documented bully victimization as a pivotal risk factor contributing to aggressive behaviors among adolescents. Particularly, the negative outcome of increased aggressive behaviors may be exacerbated when the aggressive actions are novel and difficult to detect. The present study aims to explore the complex relationships between cyberbullying and school bullying victimization and malevolent creativity and the potential mediating role of hostile attribution using two-wave longitudinal data. The present study analyzed data from 262 rural adolescents. The results revealed that cyberbullying victimization significantly predicted malevolent creativity, whereas school bullying victimization did not. Hostile attribution served as a mediator in the relationship between cyberbullying victimization and malevolent creativity in the longitudinal models. These findings provide significant implications for mitigating the negative influence of bullying victimization on the emergence of malevolent creativity in rural adolescents.

Exosomal EphA2 promotes tumor metastasis of triple-negative breast cancer by damaging endothelial barrier.

Many evidences show that exosomes play an important role in cancer development, invasion and metastasis. This study is based on the need to explore exosomal protein that promote breast cancer metastasis. We found that tyrosine kinase EphA2 was enriched in Triple-negative breast cancer -derived exosomes and it could disrupt the endothelial monolayer barrier through downregulating tight junction proteins of endothelial cells. These mechanisms were confirmed by in vivo experiments. After periodical injection of exosomal EphA2 into mice caudal vein, we found increased vascular permeability and breast cancer metastases in distant organs, and this phenomenon decreased dramatically after exosomal EphA2 knockdown. This study provides a new mechanism of exosome promoting breast cancer metastasis and suggests a new therapeutic target for the prevention and treatment of breast cancer metastasis.

The Impact of Emotional Intelligence on Domain-Specific Creativity: The Mediating Role of Resilience and the Moderating Effects of Gratitude.

Creativity incorporates both domain-general and domain-specific ideas. While previous studies have explored the impact of emotional intelligence (EI) on creativity in both domains, a consensus has not been reached, and the mechanism is currently unclear. In the present study, we examined which aspect of creativity EI was most strongly associated with in a group of undergraduates. Moreover, we explored the moderated mediation effect between EI and domain-specific creativity. In Study 1, 532 undergraduates completed questionnaires measuring EI, convergent and divergent creative thinking, and creative achievement. The results revealed that the most reliable positive correlations were between EI and domain-specific creativity. In Study 2, 926 undergraduates completed measurements of EI, resilience, gratitude, and creative achievement. The results revealed that resilience mediates the relationship between EI and creative achievement. Furthermore, gratitude moderated the indirect effect of EI on creative achievement through resilience. The indirect effect of EI on creative achievement was stronger for high-gratitude individuals than for low-gratitude individuals. This orientation and other results are discussed. Overall, our findings add further nuance to the relationship between EI and creativity in different domains. This study serves as a basis for other contributions aligned with these concepts.

The oriental armyworm genome yields insights into the long-distance migration of noctuid moths.

The oriental armyworm, Mythimna separata, is known for its long-distance seasonal migration and environment-dependent phase polymorphisms. Here, we present a chromosome-level genome reference and integrate multi-omics, functional genetics, and behavioral assays to explore the genetic bases of the hallmark traits of M. separata migration. Gene family comparisons show expansion of gustatory receptor genes in this cereal crop pest. Functional investigation of magnetoreception-related genes and associated flight behaviors suggest that M. separata may use the geomagnetic field to guide orientation in its nocturnal flight. Comparative transcriptome characterizes a suite of genes that may confer the observed plasticity between phases, including genes involved in protein processing, hormone regulation, and dopamine metabolism. We further report molecular signatures that underlie the dynamic regulation of a migratory syndrome coordinating reproduction and flight. Our study yields insights into environment-dependent developmental plasticity in moths and advances our understanding of long-distance migration in nocturnal insect pests.

Regional gray matter volume mediates the relationship between neuroticism and depressed emotion.

The underlying psychological mechanism of the effect of neuroticism on depressed emotion has been widely studied. However, the neural mechanism of this relationship remains unclear. Therefore, the present study aimed to apply voxel-based morphometry (VBM) to explore the neural mechanism of the relationship between depressed emotion and neuroticism in healthy and young participants through longitudinal tracking research. The behavioral results showed that neuroticism was positively related to depressed emotion at T1 and T2 (6 months later). The VBM analysis revealed that neuroticism positively associated with the gray matter volume (GMV) in the dorsal medial prefrontal cortex (dmPFC). Mediation analysis was conducted to investigate the neural basis of the association between depressed emotion and neuroticism. The mediation result revealed that GMV of the dmPFC partially mediates the relationship between neuroticism and depressed emotion at T1 but not T2. Together, these findings suggest that the gray matter volume of dmPFC could may affect the relationship between depressed emotion and neuroticism.

E2F1 Affects the Therapeutic Response to Neoadjuvant Therapy in Breast Cancer.

This study is aimed at screening genes for predicting the sensitivity response and favorable outcome of neoadjuvant therapy in breast cancer. We downloaded neoadjuvant therapy genetic data of breast cancer and separated it into the pathological complete response (pCR) group and the non-pCR group. Differential expression analysis was performed to select the differentially expressed genes (DEGs). After that, we investigated the enriched biological processes and pathways of DEGs. Then, core up/down protein-protein interaction (PPI) network was, respectively, constructed to identify the hub genes. A transcription factor-target gene regulation network was built to screen core transcription factors (TFs). We found one upregulated DEG (KLHDC7B) and four downregulated DEGs (TFF1, LOC440335, SLC39A6, and MLPH) overlapped in three datasets. All DEGs were mainly enriched in pathways related to DNA biosynthesis, cell cycle, immune response, metabolism, and angiogenesis. The hub genes were KRT18, IL7R, HIST1H1A, and E2F1. The core TFs were HOXA9, SPDEF, FOXA1, E2F1, and PGR. RT-qPCR suggested that E2F1 was overexpressed in MCF-7, but HOXA9 was low-expressed. Western blot suggested that the MAPK signal pathway was inhibited in MCF-7/ADR. That is to say, some genes and core TFs can predict the sensitivity response of neoadjuvant therapy in breast cancer. And E2F1 may be involved in the process of drug resistance by regulating the MAPK signaling pathway. These might be useful as sensitive genes for the efficacy evaluation of neoadjuvant chemotherapy in breast cancer.

Current status of cancer starvation therapy.

Conventional therapies for malignant tumors have limitations and disadvantages. In recent years, the cancer starvation therapy has emerged which intends to deprive cancer cells of nutritional supply. There are several approaches to"starve" cancer cells: to intervene tumor angiogenesis by targeted inhibition of angiogenic factors or their receptors and integrins; to block the blood supply of cancer cells by embolizing or compressing blood vessels; to intervene metabolic process of cancer cells by inhibition of the signal pathways of mitochondrial serine-glycine-one earbon metabolism, glycolysis and amino acid metabolism; cancer starvation therapy can be employed with oxidation therapy, chemotherapy, sonodynamic therapy, anti-autophagy therapy or other therapies to achieve synergistic effects. This article reviews the research progress of cancer starvation therapy in recent years and discusses the existing problems.

Will the patient's double eyelid shape be like that of the surgeon performing the procedure? A study of surgeons' aesthetics in East Asian Blepharoplasty.

BACKGROUND: No reports of the potential areas of surgeons' aesthetics in blepharoplasty. AIMS: To explore the association between the surgeons' own double eyelid morphology and their aesthetics and surgical outcome. METHODS: An investigation of 1605 patients was carried collecting the data of double eyelid shape, based on which to propose a preliminary double eyelid classification for analyzing the aesthetics of surgeons. Ten double eyelid surgical cases were randomly collected from each surgeon according to the inclusion criteria, whose double eyelid shape, ideal shape, the selection tendency of surgical approach, most cared factor during surgery, and design concept of eyelid shape were collected. Structural equation modeling (SEM) was performed to assess the association between participants' double eyelid shape, aesthetics, and blepharoplasty outcome. RESULTS: Fifty-three double eyelid surgeons were enrolled for study, whose double eyelids shapes mostly were obviously fan-shaped (37.74%) and low-parallel eyelid (26.42%), and the ideal shapes were obviously fan-shaped (41.51%) and high-parallel eyelid (24.53%). 54.72% of the subjects preferred to use the full-incisional method. 45.28% cared for long-term outcome most. Regarding blepharoplasty outcome style, 49.06% of the subjects preferred obviously fan-shaped type and 24.53% for high-parallel type. SEM showed that aesthetics rank increased by 0.692 points for surgeons' shape (P < .001), and surgical outcome rank increased by 0.861 points for aesthetics (P < .001). However, their eyelid shape had no direct contribution to surgical outcome (P = .96). CONCLUSIONS: The findings indicated that surgeons' double eyelid shape positively affected their aesthetics, which affected their surgical outcomes further, but their double eyelid shape failed to affect the surgical outcomes directly.

Critical thinking and regional gray matter volume interact to predict representation connection in scientific problem solving.

Representation connection (RC) is a stable ability that significantly predicts the accuracy of scientific innovation problem solving while critical thinking has been strongly related to problem solving. However, the neural mechanisms underlying this relationship have not been assessed. Using voxel-based morphometry (VBM) and scientific innovation problem solving materials, we investigated the correlation between RC and regional gray matter volume (rGMV) in healthy young participants. We found that RC was positively correlated with rGMV in the right superior temporal gyrus (STG) and in a cluster in the left medial frontal gyrus (MFG). These results indicate that increased rGMV in the right STG may lead to the ability to overcome misdirection more easily, which may result in better semantic integration of the "certain construction" of heuristic prototypes. Increased rGMV in the left MFG may be associated with forming novel associations and retrieving matched unsolved technical problems from memory. Further analysis revealed that the interaction between critical thinking and rGMV predicted RC in insightful problem solving, and found that higher rGMV was correlated with higher RC in participants with lower cognitive maturity, but not in participants with higher cognitive maturity. These findings suggest that rGMV could interact with cognitive maturity to modulate RC in insightful problem solving.

Probiotics as antifungal agents: Experimental confirmation and future prospects.

Fungal burden throughout the world is very high and it keeps escalating due to increasing numbers of immunocompromised individuals. In contrast, the drugs used in management of fungal infections are so few some with high toxicity. Furthermore, highly resistant fungal pathogens are emerging for example Candida auris, Candida glabrata, Candida gullemondii and Aspergillus species among others. Thus now, more than ever, there is a need for combined efforts and an all round search for possible solutions to curb these problems. Therefore, the role of probiotics in management of fungal infections is indispensable. In fact, the antimicrobial activity of probiotics has been screened with promising results against microbial pathogens. Although, recent reports indicated that probiotics may also contribute to protect against fungal infections, the research done in checking antifungal activity of probiotics has used varied technology. This calls for harmonization of the methods used to screen and confirm the antimicrobial activity of probiotics and other candidate microorganisms. We therefore sought to address issues of disparity in probiotic research and their outcomes. Thus this paper is in order as it comprehensively reviews' publications, provides a summary of the methods and future prospects of probiotics as antifungal agents.

Eps15 homology domain 1 promotes the evolution of papillary thyroid cancer by regulating endocytotic recycling of epidermal growth factor receptor.

Papillary thyroid cancer (PTC) is the most common type of thyroid malignancy, and it is often observed to overexpress epidermal growth factor receptor (EGFR). Previous research has indicated that EH domain-containing 1 (EHD1) is associated with EGFR-mediated endocytotic recycling in multiple tumor types. The objective of the present study was to determine the protein expression levels and clinical significance of EHD1, EGFR, caveolin-1 (CAV-1) and RAB11 family interacting protein 3 (RAB11FIP3) in PTC. PTC specimens were analyzed for EHD1, EGFR, CAV-1 and RAB11FIP3 expression via immunohistochemistry and western blotting. The associations between protein expression and clinicopathological features were assessed. EHD1, EGFR, CAV-1 and RAB11FIP3 expression levels were increased in human PTC. Additionally, the expression level of EHD1 protein was significantly associated with tumor size, lymph node metastasis and EGFR expression (P<0.05). CAV-1 was associated with tumor size and EGFR expression (P<0.05). EGFR was only associated with lymph node metastasis (P=0.027) and RAB11FIP3 was not associated with any clinicopathological characteristics. The correlations between EHD1 and EGFR (r=0.564, P<0.05), CAV-1 (r=0.865, P<0.01) and RAB11FIP3 (r=0.504, P<0.05) were statistically significant. Overall, EHD1, CAV-1 and RAB11FIP3, which are key proteins in endocytotic recycling, promote PTC tumorigenesis through the regulation of the transport of EGFR.

Combined caveolin-1 and epidermal growth factor receptor expression as a prognostic marker for breast cancer.

Previous studies have indicated that caveolin-1 (Cav-1) is able to bind the signal transduction factor epidermal growth factor receptor (EGFR) to regulate its tyrosine kinase activity. The aim of the present study was to evaluate the clinical significance of Cav-1 gene expression in association with the expression of EGFR in patients with breast cancer. Primary breast cancer samples from 306 patients were analyzed for Cav-1 and EGFR expression using immunohistochemistry, and clinical significance was assessed using multivariate Cox regression analysis, Kaplan-Meier estimator curves and the log-rank test. Stromal Cav-1 was downregulated in 38.56% (118/306) of tumor tissues, whereas cytoplasmic EGFR and Cav-1 were overexpressed in 53.92% (165/306) and 44.12% (135/306) of breast cancer tissues, respectively. EGFR expression was positively associated with cytoplasmic Cav-1 and not associated with stromal Cav-1 expression in breast cancer samples; however, low expression of stromal Cav-1 was negatively associated with cytoplasmic Cav-1 expression in total tumor tissues, and analogous results were identified in the chemotherapy group. Multivariate Cox's proportional hazards model analysis revealed that, for patients in the estrogen receptor (ER)(+) group, the expression of stromal Cav-1 alone was a significant prognostic marker of breast cancer. However, in the chemotherapy, human epidermal growth factor receptor 2 (HER-2)(-), HER-2(+) and ER(-) groups, the use of combined markers was more effective prognostic marker. Stromal Cav-1 has a tumor suppressor function, and the combined marker stromal Cav-1/EGFR expression was identified as an improved prognostic marker in the diagnosis of breast cancer. Parenchymal expression of Cav-1 is able to promote EGFR signaling in breast cancer, potentially being required for EGFR-mediated initiation of mitosis.

TRIB1 promotes colorectal cancer cell migration and invasion through activation MMP-2 via FAK/Src and ERK pathways.

Colorectal cancer (CRC) is the third most common cancer in the world and distant metastasis is the leading cause of death among CRC patients. However, the underlying mechanisms of distant metastasis remain largely unknown. Amplification of 8q24 is a common chromosomal abnormality in CRC. In the present study, a putative oncogene at 8q24, TRIB1, was characterized for its role in CRC metastasis and underlying molecular mechanisms. Higher expression of TRIB1 protein was detected in 58/83 (69.9%) of CRC tissues, compared with adjacent non-tumor tissues. Moreover, the expression of TRIB1 was significantly associated with distant metastasis (P=0.043) and advanced staging (P=0.008) in CRC tissues. TRIB1 overexpression was also correlated with poor prognosis in CRC patients as analyzed in PrognoScan database. In addition, elevated expression of TRIB1 promoted CRC cell motility and adhesive ability, while silencing of TRIB1 reduced those effects. Further study revealed that TRIB1-mediated migration and invasion of CRC cells required up-regulation of MMP-2 through the activation of FAK/Src and ERK pathway. Collectively, the results suggest that TRIB1 promotes CRC cell motility by activation MMP-2 via the FAK/Src and ERK pathways. It may provide a potential diagnostic and therapeutic target for CRC.

NUBPL, a novel metastasis-related gene, promotes colorectal carcinoma cell motility by inducing epithelial-mesenchymal transition.

Nucleotide binding protein-like, NUBPL, is an assembly factor for human mitochondrial complex I, which is the biggest member of the mitochondrial respiratory chain. However, the relationship between NUBPL and carcinoma progression remains unknown. In this study, NUBPL was characterized for its role in colorectal cancer (CRC) and the underlying molecular mechanisms. Data (n = 197) from the Oncomine database revealed that mRNA levels of NUBPL were remarkably overexpressed in CRC tissues compared with normal tissues. In addition, immunohistochemical analysis of 75 pairs of CRC and non-tumor tissues showed that the expression level of NUBPL was significantly higher in CRC tissues, and its expression level was positively associated with lymph node metastasis (P = 0.028) and advanced staging (P = 0.030). Expression of NUBPL in metastatic lymph nodes of CRC patients was also detected by immunohistochemical staining and high expression levels of NUBPL were observed. Overexpression of NUBPL significantly promoted the migration and invasion ability of CRC cell lines SW480 and SW620, whereas knockdown of NUBPL lead to an opposite effect. Our further study found that NUBPL could induce epithelial-mesenchymal transition (EMT), characterized by downregulation of epithelial markers (E-cadherin) and upregulation of mesenchymal markers (N-cadherin and vimentin). Moreover, NUBPL was able to activate ERK, which is believed to promote EMT and tumor metastasis. Inhibition of ERK suppressed the NUBPL-induced changes in EMT and cell motility. These data showed that NUBPL plays a vital role in CRC migration and invasion by inducing EMT and activating ERK. It might be a novel therapeutic target for CRC.

Increased Eps15 homology domain 1 and RAB11FIP3 expression regulate breast cancer progression via promoting epithelial growth factor receptor recycling.

Recent research indicates that the C-terminal Eps15 homology domain 1 is associated with epithelial growth factor receptor-mediated endocytosis recycling in non-small-cell lung cancer. The aim of this study was to determine the clinical significance of Eps15 homology domain 1 gene expression in relation to phosphorylation of epithelial growth factor receptor expression in patients with breast cancer. Primary breast cancer samples from 306 patients were analyzed for Eps15 homology domain 1, RAB11FIP3, and phosphorylation of epithelial growth factor receptor expression via immunohistochemistry. The clinical significance was assessed via a multivariate Cox regression analysis, Kaplan-Meier curves, and the log-rank test. Eps15 homology domain 1 and phosphorylation of epithelial growth factor receptor were upregulated in 60.46% (185/306) and 53.92% (165/306) of tumor tissues, respectively, as assessed by immunohistochemistry. The statistical correlation analysis indicated that Eps15 homology domain 1 overexpression was positively correlated with the increases in phosphorylation of epithelial growth factor receptor ( r = 0.242, p < 0.001) and RAB11FIP3 ( r = 0.165, p = 0.005) expression. The multivariate Cox proportional hazard model analysis demonstrated that the expression of Eps15 homology domain 1 alone is a significant prognostic marker of breast cancer for the overall survival in the total, chemotherapy, and human epidermal growth factor receptor 2 (-) groups. However, the use of combined expression of Eps15 homology domain 1 and phosphorylation of epithelial growth factor receptor markers is more effective for the disease-free survival in the overall population, chemotherapy, and human epidermal growth factor receptor 2 (-) groups. Moreover, the combined markers are also significant prognostic markers of breast cancer in the human epidermal growth factor receptor 2 (+), estrogen receptor (+), and estrogen receptor (-) groups. Eps15 homology domain 1 has a tumor suppressor function, and the combined marker of Eps15 homology domain 1/phosphorylation of epithelial growth factor receptor expression was identified as a better prognostic marker in breast cancer diagnosis. Furthermore, RAB11FIP3 combines with Eps15 homology domain 1 to promote the endocytosis recycling of phosphorylation of epithelial growth factor receptor.

miR-136 suppresses tumor invasion and metastasis by targeting RASAL2 in triple-negative breast cancer.

MicroRNAs play an important role in the regulation of cancer migration, invasion and metastasis. Patients with triple-negative breast cancer (TNBC) have a high incidence of early relapse and metastasis; however, the molecular basis for metastasis and recurrence in these individuals remains largely unknown. Herein, we demonstrate that miR-136 is an anti-invasive microRNA in TNBC and suppresses mesenchymal invasion and metastasis. Our results demonstrated that miR-136 was downregulated in TNBC and negative correlated with the WHO grades. However, RASAL2 was identified as a functional target of miR-136, and was overexpressed in TNBC and correlates with pathological grades. Moreover, overexpression of RASAL2 in a breast cancer cell line rescued miR-136-mediated cell migration and invasion. In conclusion, these results indicate that the miR-136/RASAL2/MET axis act as a suppressor of TNBC metastasis.

Ribosomal L22-like1 (RPL22L1) Promotes Ovarian Cancer Metastasis by Inducing Epithelial-to-Mesenchymal Transition.

Double minute chromosomes (DMs) have important implications for cancer progression because oncogenes frequently amplified on them. We previously detected a functionally undefined gene amplified on DMs, Ribosomal L22-like1 (RPL22L1). The relationship between RPL22L1 and cancer progression is unknown. Here, RPL22L1 was characterized for its role in ovarian cancer (OC) metastasis and its underlying mechanism was examined. DNA copy number and mRNA expression of RPL22L1 in OC cells was analyzed using data obtained from The Cancer Genome Atlas and the Gene Expression Omnibus database. An immunohistochemical analysis of clinical OC specimens was performed and the relationships between expression level and clinicopathological factors were evaluated. Additionally, in vivo and in vitro assays were performed to understand the role of RPL22L1 in OC. RPL22L1 expression was higher in OC specimens than in normal tissues, and its expression level was highly positively correlated with invasion and lymph node metastasis (P < 0.05). RPL22L1 over-expression significantly enhanced intraperitoneal xenograft tumor development in nude mice and promoted invasion and migration in vitro. Additionally, RPL22L1 knockdown remarkably inhibited UACC-1598 cells invasion and migration. Further, RPL22L1 over-expression up-regulated the mesenchymal markers vimentin, fibronectin, and α-SMA, reduced expression of the epithelial markers E-cadherin, α-catenin, and ß-catenin. RPL22L1 inhibition reduced expression of vimentin and N-cadherin. These results suggest that RPL22L1 induces epithelial-to-mesenchymal transition (EMT). Our data showed that the DMs amplified gene RPL22L1 is critical in maintaining the aggressive phenotype of OC and in triggering cell metastasis by inducing EMT. It could be employed as a novel prognostic marker and/or effective therapeutic target for OC.

Habitual suppression relates to difficulty in regulating emotion with cognitive reappraisal.

One common strategy to cope with the difficulties of daily life is suppression. Habitual users of suppression tend to suppress their feelings rather than expressing them. Although this strategy may reduce outward response to emotion, it is not thought to lessen induced negative affect. Moreover, it remains unclear whether people with high suppression scores can reduce negative affect through cognitive reappraisal. In the present study, twenty-nine healthy participants differing in suppression scores were directed to reappraise aversive stimuli during functional magnetic resonance imaging (fMRI). Results showed that higher suppression scores correlated with decreased response of dorsomedial prefrontal cortex (dmPFC) during cognitive reappraisal. Further, high suppression scores related to enhanced negative affect to stimuli with greater negative affect correlating with decreased dmPFC response during cognitive reappraisal. This study suggests that people with high suppression scores experience difficulty in reducing negative affect through cognitive reappraisal and implicates neurobiological processes that may underlie this difficulty.

Association between regional white and gray matter volume and ambiguity tolerance: Evidence from voxel-based morphometry.

The concept of tolerance of ambiguity (AT) is defined as the way in which an individual tends to perceive and deal with confusing, vague, and unclear situations. AT is generally considered as an important personality trait, but the neural mechanisms underlying individual differences in AT have never been investigated. Using voxel-based morphometry and MSTAT-II scale, we investigated the correlations between AT and regional white matter volume (rWMV) and regional gray matter volume (rGMV) in 351 young healthy subjects. We found AT to be positively correlated with rGMV in the dorsolateral prefrontal cortex (DLPFC), and negatively correlated with rGMV in the precuneus. These results indicate that increased rGMV in the left DLPFC may lead to characteristics of ambiguous stimuli consideration from multiple contexts and risk taking. Decreased rGMV in the left precuneus may be associated with a high tolerance for ambiguity, which attributes uncertainty to self-related factors.