Bivalent affinity binding-inspired PPARγ immobilization with selective conformation and improved ligand-binding activity.

Functional protein immobilization forms the basis for bio-detections. A series of one-point, site-specific immobilization methods have been developed, however, it still remains as a challenge how to avoid the proteins to move in all directions as well as conveniently regenerate the bio-devices. Herein, we have developed a bivalent affinity binding-inspired method for PPARγ immobilization using DNA aptamer and nickel-nitrilotriacetic acid (Ni2+-NTA) chelation. The specific DNA aptamer (Apt 2) was selected by an on-column systematic evolution of ligands by exponential enrichment (SELEX) method with affinity of (1.57 ± 0.15) × 105 M-1, determined by isothermal titration calorimetry (ITC). Apt 2 and nickel-nitrilotriacetic acid (Ni2+-NTA) were modified on macroporous silica gels via L-α-allylglycine as a linker. They respectively interacted with PPARγ and 6×His tag via bivalent affinity binding for the receptor immobilization. After comprehensive surface characterization, PPARγ was proved to be successful immobilized. Chromatographic studies revealed that the immobilized PPARγ has conformation selectivity, which discriminated agonist and antagonist of the receptor. Ligand-binding parameters (affinity and rate constant) of four agonists (rosiglitazone, pioglitazone, troglitazone, and magnolol) with PPARγ were determined. Troglitazone showed the lowest dissociation rate constant. The binding affinities (3.28 × 107, 1.91 × 106, 2.25 × 107, and 2.43 × 107 M-1) were highly consistent with the data obtained using purified receptor in solution (2.16 × 107, 4.52 × 106, 1.20 × 107, and 1.56 × 107 M-1), offering reliable bio-detection method for PPARγ and its ligands. Due to the biocompatibility of nuclear receptor with DNA, it is conceivable that the bivalent affinity-based method will be a general method for the immobilization of other nuclear receptors, which may provide selective conformation and improved ligand-binding activity for the receptors.

The double-edged effect of social mobility belief on socioeconomically disadvantaged adolescents' health: The mediating role of intentional self-regulation.

PURPOSE: This study aimed to examine the double-edged effect of social mobility belief on socioeconomically disadvantaged adolescents' mental and physical health and further explore whether intentional self-regulation is the common psychological mechanism of social mobility belief affecting physical and mental health. METHOD: A total of 469 adolescents (Mage = 13.96 years, 49.3% boys) from two rural public schools in China were included in this study. Adolescents completed questionnaires measuring social mobility belief and mental health (life satisfaction, self-esteem, and depression). Physical health (allostatic load) was reflected by six indicators (resting diastolic and systolic blood pressure, body mass index, epinephrine, norepinephrine, and cortisol). RESULTS: Social mobility belief was positively correlated with adolescents' life satisfaction and self-esteem but negatively correlated with depression. Intentional self-regulation mediated the relationships between social mobility belief and mental health. In addition, the results showed that intentional self-regulation mediated the relationship between social mobility belief and adolescents' physical health. CONCLUSIONS: Social mobility belief may be a "skin-deep" resilience resource positively related to mental health but negatively correlated with physical health through intentional self-regulation among socioeconomically disadvantaged adolescents. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Perceived social support mitigates the associations among household chaos and health and well-being in rural early adolescents.

PURPOSE: Previous studies have demonstrated that early adolescents residing in chaotic households experience adverse health and well-being outcomes. However, the potential protective factors that mitigate the relationship between household chaos and early adolescents' health and well-being remain unknown. Accordingly, this study aims to investigate whether perceived social support moderates the link between household chaos and the health and well-being among Chinese rural early adolescents. METHODS: Physical health difficulties were assessed using two measures: general health and allostatic load (AL). Mental health difficulties were measured by depression. Well-being was reflected by life satisfaction. Specifically, this study included early adolescents (N = 337; Mage = 10.88 ± 1.36 years) from rural counties in China who reported their household chaos, perceived social support, general health, depression, and life satisfaction. AL scores were determined based on six physiological indices. RESULTS: Household chaos exhibited a negative relationship with the general health and life satisfaction while a positive correlation with depression. Moreover, perceived social support was found to moderate the association between household chaos and these health and well-being indicators of early adolescents. Specifically, early adolescents who reported higher levels of perceived social support exhibited weaker negative connections among household chaos and their general health, depression, and life satisfaction. Furthermore, no significant relationships were observed between the adolescents' AL and household chaos, perceived social support, or their interactions. CONCLUSIONS: Household chaos poses a significant risk to health and well-being. Furthermore, the findings indicate that perceived social support can mitigate these negative effects.

Long-term Neighborhood Poverty Effects on Internalizing Symptoms in Adolescents: Mediated Through Allostatic Load and Pubertal Timing.

PURPOSE: The long-term effect of neighborhood poverty on internalizing symptoms in adolescents and the biological mechanisms underlying this association remain unclear. We defined neighborhood poverty at the village level in two dimensions: intensity (i.e., poverty rate) and duration. This study investigated how the poverty rate and duration of exposure to neighborhood poverty interact to predict internalizing symptoms in adolescents through biological mechanisms (i.e., allostatic load and early pubertal timing). METHODS: A total of 418 adolescents (50.2% girls; 11-14 years old; mean age = 12.57 years) living in rural China participated in two waves of data collection. Path analysis was conducted to examine the mediating role of allostatic load and pubertal timing in the relationship between the duration of exposure to neighborhood poverty and internalizing symptoms. Moreover, the interactive effect between the poverty rate and duration of neighborhood poverty on the allostatic load was tested. RESULTS: The positive association between the duration of exposure to neighborhood poverty and internalizing symptoms of adolescents was explained by elevated allostatic load and early pubertal timing after adjusting for gender, age, prior family socioeconomic states and internalizing symptoms. The duration in neighborhood poverty was a stronger predictor of allostatic load for adolescents living in high poverty rate neighborhoods than for those living in low poverty rate neighborhoods. DISCUSSION: Neighborhood poverty gets "under the skin" through biological pathways and affects internalizing symptoms among adolescents. The findings highlight the importance of considering different dimensions of neighborhood poverty (e.g., intensity and duration) on adolescents' health.

ECC-PolypDet: Enhanced CenterNet With Contrastive Learning for Automatic Polyp Detection.

Accurate polyp detection is critical for early colorectal cancer diagnosis. Although remarkable progress has been achieved in recent years, the complex colon environment and concealed polyps with unclear boundaries still pose severe challenges in this area. Existing methods either involve computationally expensive context aggregation or lack prior modeling of polyps, resulting in poor performance in challenging cases. In this paper, we propose the Enhanced CenterNet with Contrastive Learning (ECC-PolypDet), a two-stage training & end-to-end inference framework that leverages images and bounding box annotations to train a general model and fine-tune it based on the inference score to obtain a final robust model. Specifically, we conduct Box-assisted Contrastive Learning (BCL) during training to minimize the intra-class difference and maximize the inter-class difference between foreground polyps and backgrounds, enabling our model to capture concealed polyps. Moreover, to enhance the recognition of small polyps, we design the Semantic Flow-guided Feature Pyramid Network (SFFPN) to aggregate multi-scale features and the Heatmap Propagation (HP) module to boost the model's attention on polyp targets. In the fine-tuning stage, we introduce the IoU-guided Sample Re-weighting (ISR) mechanism to prioritize hard samples by adaptively adjusting the loss weight for each sample during fine-tuning. Extensive experiments on six large-scale colonoscopy datasets demonstrate the superiority of our model compared with previous state-of-the-art detectors.

Household Income and Early Adolescents' Executive Function: The Different Roles of Perceived Discrimination and Shift-and-Persist.

Household income predicts early adolescents' cognitive development. However, the mechanism underlying this association and protective factors are unclear. This study assessed one-year longitudinal data to examine whether perceived discrimination mediated the association between household income and executive function and the moderating role of shift-and-persist. 344 early adolescents in rural China were included in the study (mean = 10.88 years, SD = 1.32 years, girls: 51.74%). The latent variable model revealed that household income predicted early adolescents' cognitive flexibility and working memory in the subsequent year through perceived discrimination. Shift-and-persist moderated the negative effects of perceived discrimination on cognitive flexibility: perceived discrimination impeded cognitive flexibility only among early adolescents with low shift-and-persist. The findings highlight perceived discrimination in the relation between household income and early adolescents' executive function and underscore the protective role of shift-and-persist.

Integration of miRNA and mRNA analysis reveals the role of ribosome in to anti-artificial aging in sweetcorn.

Sweetcorn is a kind of maize with high sugar content and has poor seed aging tolerance, which seriously limits its production. However, few studies have explored the artificial aging (AA) tolerance by miRNA-mRNA integration analysis in sweetcorn. Here, we characterized the physiological, biochemical and transcriptomic changes of two contrasting lines K62 and K107 treated with AA during time series. Both the germination indexes and antioxidant enzymes showed significant difference between two lines. The MDA content of AA-tolerant genotype K62 was significantly lower than that of K107 on the fourth and sixth day. Subsequently, 157 differentially expressed miRNAs (DEMIs) and 8878 differentially expressed mRNAs (DEMs) were identified by RNA-seq analysis under aging stress. The "ribosome" and "peroxisome" pathways were enriched to respond to aging stress, genes for both large units and small ribosomal subunits were significantly upregulated expressed and higher translation efficiency might exist in K62. Thirteen pairs of miRNA-target genes were obtained, and 8 miRNA-mRNA pairs might involve in ribosome protein and translation process. Our results elucidate the mechanism of sweetcorn response to AA at miRNA-mRNA level, and provide a new insight into sweetcorn AA response to stress.