Bidirectional Effects Research Articles

Regulatory mechanisms of steroid hormone receptors on gene transcription through chromatin interaction and enhancer reprogramming.

Regulation of steroid hormone receptors (SHRs) on transcriptional reprogramming is crucial for breast cancer progression. SHRs, including estrogen receptor (ER), androgen receptor (AR), progesterone receptor (PR), and glucocorticoid receptor (GR) play key roles in remodeling the transcriptome of breast cancer cells. However, the molecular mechanisms by which SHRs regulate chromatin landscape in enhancer regions and transcription factor interactions remain largely unknown. In this review, we summarized the regulatory effects of 3 types of SHRs (AR, PR, and GR) on gene transcription through chromatin interactions and enhancer reprogramming. Specifically, AR and PR exhibit bi-directional regulatory effects (both inhibitory and promoting) on ER-mediated gene transcription, while GR modulates the transcription of pro-proliferation genes in ER-positive breast cancer cells. In addition, we have presented four enhancer reprogramming mechanisms (transcription factor cooperation, pioneer factor binding, dynamic assisted loading, and tethering) and the multiple enhancer-promoter contact models. Based on these mechanisms and models, this review proposes that the combination of multiple therapy strategies such as agonists/antagonists of SHRs plus endocrine therapy and the adoption of the latest sequencing technologies are expected to improve the efficacy of ER positive breast cancer treatment.

Research on the efficiency and spatiotemporal evolution characteristics of agricultural green development in central cities of the Yangtze River Delta

IntroductionAgricultural green development (AGD) prioritizes sustainable growth by integrating economic, ecological, and social dimensions, aiming to harmonize agricultural economic development with environmental protection and social progress.MethodsThis study integrates the three-stage super-efficiency DEA-SBM model with the BP algorithm, creating an advanced DEA-SBM-BP model to overcome the shortcomings of traditional DEA in evaluation and management processes. The study further applies the Dagum Gini coefficient, kernel density estimation (KDE), and Moran’s index to assess and forecast the efficiency and spatiotemporal evolution patterns of green agricultural development in key cities within the Yangtze River Delta.ResultsThe analysis shows that AGD in the central city of the Yangtze River Delta is overall balanced; however, substantial variations exist among cities within individual provinces. Factors like macroeconomic conditions, workforce quality, and policy support play a crucial role in promoting the efficiency of AGD. Among these, macroeconomic development level has a negative impact, while labor quality and policy support exhibit bidirectional effects. Infrastructure construction, digitalization of agricultural economy, and rural security have become key factors in the green development of modern agriculture. The green advancement of agriculture in the central Yangtze River Delta region typically exhibits a marked clustering effect; however, the local clustering reveals a trend toward dispersed development.DiscussionDespite the emergence of new characteristics in agricultural production in China within the context of high-quality development, differences in resource endowments and economic structures among cities continue to be significant factors contributing to regional imbalances and changes in the agglomeration patterns of agricultural development.

Bidirectional interactions between Grosmannia abietina and hybrid white spruce: Pathogenicity, monoterpene defense responses, and fungal growth and reproduction

Bark beetle-vectored phytopathogenic fungi can play critical roles in how beetle outbreaks affect the health of forest trees. However, trees can defend themselves against fungal infection. How Grosmannia abietina, a symbiotic fungus of spruce beetle (Dendroctonus rufipennis), affects the health of mature hybrid white spruce (Picea engelmannii x glauca) and is in turn affected by the tree's defenses are unknown. We conducted field inoculations of this spruce to study the degree of pathogenicity of G. abietina, characterized the trees' resulting defensive monoterpene responses, and assessed monoterpene effects on fungal growth and reproduction in laboratory bioassays. Our results indicated that G. abietina is phytopathogenic to hybrid white spruce, which induced monoterpenes in response to infection. Dominant induced monoterpenes generally inhibited fungal growth but stimulated spore production. These findings provide insights into the bidirectional effects between spruce beetle-vectored fungi and host trees, highlighting the complex role of monoterpenes in modulating fungal activities.

Exploring the developmental changes in and the relationship between resilience and anxiety and depression in older gastric cancer survivors: A latent growth mixture model and random intercept cross-lagged panel model analysis.

This study aims to investigate the independent and joint trajectories of resilience, anxiety, and depression symptoms and research the interaction between older gastric cancer survivors' resilience and anxiety-depression during the period of 1 year after surgery. The participants were 381 older gastric cancer survivors, with a mean age of 69 years. Resilience, anxiety, and depression symptoms were assessed immediately after surgery, and at 3, 6, and 12 months post-surgery, respectively. A longitudinal design was employed to capture the dynamic changes in resilience, anxiety, and depression levels among older gastric cancer survivors post-surgery. Latent growth mixture model and random intercept cross-lagged panel model were used to analyse the trajectories of resilience and anxiety-depression and the interaction between them. Two latent trajectories were identified for the resilience, four latent trajectories were identified for the anxiety, and five latent trajectories were identified for the depression, respectively, with three joint trajectories identified: gradual-increasing resilience, gradual-decreasing anxiety, and depression group (10.0%); gradual-decreasing resilience, gradual-increasing anxiety, and depression group (21.2%); and rapid-growth resilience, rapid-decline anxiety, and depression group (68.8%). Resilience among older gastric cancer survivors exhibits significant bidirectional and negative predictive effects on anxiety and depression. Individual differences in resilience, anxiety, and depression trajectories exist among older gastric cancer survivors, with heterogeneous joint progression patterns, and the relationship between resilience and anxiety-depression appears bidirectional. More sophisticated intervention programmes tailored to the unique characteristics of the relevant trajectories are necessary to enhance resilience and mitigate the risk of anxiety and depression.

Early life social predictors of longitudinal relations between childhood BMI and overeating

Abstract Introduction The progression of obesity is a continuous process involving a complex system of genetic, environmental, and behavioural factors. Socioeconomic disadvantage as well as psychological distress may lead to overeating, subsequently associated with increased energy intake and weight gain. Recent evidence indicated that the association between childhood obesity and overeating might be bidirectional. Therefore, this study aimed to longitudinally investigate the directionality of the association between childhood BMI and overeating and to identify antecedent early childhood predictors. Methods The study sample included 5,777 children from the European Longitudinal Study of Parents and Children (ELSPAC), collected between 18 months and 11 years of child age. The outcomes were child BMI and overeating. Predictors included maternal BMI, maternal education, single-parent households, financial difficulties, and adverse childhood experiences (ACEs). The random intercept cross-lagged panel model (RI-CLPM) was applied. Results The results showed temporal stability in the development of overeating and BMI, with a bidirectional relationship that strengthened over time. The child’s BMI was predicted by maternal BMI (β = 0.37, p < 0.001). The child’s overeating was predicted by maternal BMI (β = 0.13, p < 0.001), but a stronger effect was found for ACEs (β = 0.24, p < 0.001). ACEs mediated the impact of maternal education, financial difficulties, and single parenthood on overeating with indirect effects of β = -0.01 (p = 0.005), β = 0.04, (p < 0.001), and β = 0.07 (p < 0.001), respectively. Conclusions We observed stable bidirectional longitudinal effects, with a stronger association from BMI to overeating. The results suggested two main pathways: one linked to maternal BMI and early childhood BMI increase followed by overeating, and the other associated with ACEs mediating the effect of early childhood socioeconomic factors on overeating, leading to gradual BMI gain. #NGEU Key messages • The study revealed a stable bidirectional association between childhood BMI and overeating, with a stronger association from BMI to overeating. • There are two potential pathways in childhood obesity development, one involving maternal BMI, and the second associated with social disadvantage and ACEs.

Bidirectional enhancement of output performance of nanogenerators by M-COFs materials

The emergence of nanogenerators, which have the ability to capture mechanical energy from the environment and to collect and transmit tiny energy, is rapidly becoming a hot research topic. The performance of electrode materials is the key to the efficiency of nanogenerators. Covalent organic skeletons (COFs), a class of crystalline organic porous materials with the advantages of large specific surface area, high porosity, tunable structure, and flexible tailorability, have very significant advantages in being used as nanogenerator materials. In this paper, we synthesised two COF materials to investigate the effect of the introduction of active metals on the friction power generation performance of COFs without changing their topology, COF-2 containing zinc ions is capable of generating a short-circuit current of 107.5 µA during friction. The porous structure increases the effective contact area to form a larger charge density, and the introduction of metal ions can accelerate the charge separation and transport. The two bidirectional synergistic effects of the materials significantly improve the output performance of the nanogenerator, and a simple and efficient method is explored for the enhancement of the output performance of COF-based triboelectric nanogenerators.

The Bidirectional Effects of Periodontal Disease and Oral Dysbiosis on Gut Inflammation in Inflammatory Bowel Disease.

Inflammatory bowel disease (IBD) flares can lead to excessive morbidity and mortality. This study aimed to determine whether oral dysbiosis/periodontal disease (PD) is common in IBD and is associated with disease activity in IBD. This single-center, prospective, cross-sectional, proof-of-concept, observational study assessed the frequency of periodontal inflammatory disease and interrogated oral and stool microbiota using 16S rRNA gene amplicon sequencing of active-IBD (aIBD), inactive-IBD (iIBD), and healthy controls (HC). Questionnaires assessed diet, alcohol usage, oral hygiene behavior, and disease activity. A subset of participants underwent comprehensive dental examinations to evaluate PD. PD was severer in aIBD subjects than in HC, as aIBD had poorer quality diets (lower Mediterranean diet scores) than iIBD and HC. Significant differences in microbial community structure were observed in unstimulated saliva, stimulated saliva, gingiva, and stool samples, primarily between aIBD and HC. Saliva from aIBD had higher relative abundances of putative oral pathobionts from the genera Streptococcus, Granulicatella, Rothia, and Actinomyces relative to HC, despite similar oral hygiene behaviors between groups. Our study suggests that patients with aIBD have severer periodontal disorders and higher relative abundances of putative "pro-inflammatory" microbiota in their oral cavity, despite normal oral hygiene behaviors. Our data are consistent with the potential presence of an oral-gut inflammatory-axis that could trigger IBD flare-ups in at-risk patients. Routine dental health assessments in all IBD patients should be encouraged as part of the health maintenance of IBD and as a potential strategy to decrease the risk of IBD flares.

Bidirectional effects of morphine on pancreatic cancer progression via the p38/JNK pathway

Cancer patients commonly use morphine to alleviate advanced pain. Studies have shown that morphine may influence and intervene in the malignancy of various cancers, but its role and effects on pancreatic cancer are less studied. This study aims to examine how morphine affects pancreatic cancer and its possible mechanisms. In vitro experiments were conducted using the CCK-8 experiment, colony formation experiment, EdU test, wound healing experiment, and transwell migration and invasion experiment. Tumor xenograft tests were employed to investigate the in vivo impact of morphine on pancreatic cancer. The Western blot (WB) assay was used to detect possible changes in key proteins of the related signaling pathway. Our experimental results showed that low concentrations of morphine (25 µM) promoted the progression of pancreatic cancer, while high concentrations of morphine (100 µM) inhibited its progression. Further, we demonstrated that morphine may interfere with the progression of pancreatic cancer by acting on the p38/JNK signaling pathway. Morphine may affect pancreatic cancer progression through the p38/JNK pathway in a bidirectional manner at different concentrations.

Breaking the Loop: A Meta‐Analysis on the Bidirectional Effects of Materialism on Social Well‐Being Outlining Future Research Directions

ABSTRACTThis meta‐analysis examines correlational and experimental research linking materialism—broadly understood as an excessive focus on acquiring wealth and possessions that convey status—and social well‐being—characterised by healthy interpersonal relationships and a sense of social support and integration. We identified 55 reports containing 72 independent studies and 123 effect sizes (N = 44,376). Meta‐analytic calculations yielded a pooled effect of r = −0.18, suggesting that the effects of materialism on social well‐being (e.g., loneliness or relationship satisfaction) may be greater than the effects of materialism on individual well‐being (e.g., self‐esteem or life satisfaction). Moderation analyses revealed that the effects are bi‐directional, consistent across genders and cultures and significantly stronger in children and adolescents. These findings emphasise the universal and reciprocal link between materialism and social well‐being and highlight the particular vulnerability of younger populations. Based on the results, we propose suggestions for further research to address the existing gaps and strengthen the current evidence, and recommend a sample size of 240 participants for correlational studies and 50 participants per group for experimental research. This work calls for targeted interventions and policies to tackle the adverse social effects of materialism, particularly among young populations.

Bidirectional effects of parenting and ADHD symptoms in young children: Effects of comorbid oppositional symptoms.

Psychosocial factors play an important role in the manifestation of attention-deficit/hyperactivity disorder (ADHD) symptoms and accompanying impairment levels in children. In a community sample of 796 children evaluated at 4, 5, and 6 years of age, bidirectional effects were examined for each of three components of parenting (parental support, hostility, scaffolding skills) and ADHD-specific symptoms that are not associated with symptoms of oppositional defiant disorder. Results indicated that (a) age 4 parenting factors were not associated with changes in ADHD-I (inattention) or ADHD-H (hyperactive-impulsive) symptoms in the subsequent year, (b) ADHD-I and ADHD-H symptoms at age 4 were not associated with changes in parenting factors at age 5, (c) age 5 ADHD-I and ADHD-H symptoms were associated with decreases in parental scaffolding skills and increases in parental hostility from ages 5 to 6 years, and (d) parental support at age 5 was associated with a decrease in ADHD-H symptoms at age 6. Findings suggest that ADHD symptoms can lead to poorer parenting attitudes and behavior, while parental support during kindergarten has a small effect on decreasing ADHD-H symptoms over time.

Cultivating the imagination: Caregiver input during pretend play with toddlers at elevated likelihood for autism.

Toddlers with autism spectrum disorder (ASD) may exhibit less pretend play than their neurotypical counterparts. Previous research suggests that caregivers' input during play influences children's play behavior, and children's behavior may in turn prompt caregivers of differently developing children to talk about play in different ways. Caregiver input about pretend play during toy play at home was examined at 18- and 36-months in toddlers with an older sibling with ASD, who are at elevated likelihood (EL) for ASD (n = 40), and toddlers with typical likelihood (TL) for ASD (n = 12). EL toddlers were classified into three outcome groups: EL-ASD (n = 10), EL-no diagnosis (EL-ND; n = 14), or EL-language delays (EL-LD, n = 16). Caregiver utterances were categorized according to the types of pretend and non-pretend play suggested (e.g., pretending with inanimate objects vs. using objects for their intended function). Pretend utterances were further categorized as related or unrelated to the child's own actions. All caregivers produced proportionately more utterances about complex types of pretend play over time. At 36 months, caregivers of autistic toddlers produced proportionately fewer pretend play utterances, and proportionately fewer pretend play utterances were related to EL-ASD toddlers' actions compared to their neurotypical peers. These findings highlight bidirectional effects between caregivers and toddlers during play. While EL-ASD toddlers may provide less frequent opportunities for caregivers to talk about complex types of pretend play, the current study highlights caregivers' high levels of attunement to their toddlers' play skills.

Review article: The role of the gut-brain axis in inflammatory bowel disease and its therapeutic implications.

Treatments targeting the gut-brain axis (GBA) are effective at reducing symptom burden in irritable bowel syndrome (IBS). The prevalence of common mental disorders and IBS-type symptom reporting is significantly higher in inflammatory bowel disease (IBD) than would be expected, suggesting potential GBA effects in this setting. Manipulation of the GBA may offer novel treatment strategies in selected patients with IBD. We present a narrative review of the bi-directional effects of the GBA in IBD and explore the potential for GBA-targeted therapies in this setting. We searched MEDLINE, EMBASE, EMBASE Classic, PsychINFO, and the Cochrane Central Register of Controlled Trials for relevant articles published by March 2024. The bi-directional relationship between psychological well-being and adverse longitudinal disease activity outcomes, and the high prevalence of IBS-type symptom reporting highlight the presence of GBA-mediated effects in IBD. Treatments targeting gut-brain interactions including brain-gut behavioural treatments, neuromodulators, and dietary interventions appear to be useful adjunctive treatments in a subset of patients. Psychological morbidity is prevalent in patients with IBD. The relationship between longitudinal disease activity outcomes, IBS-type symptom reporting, and poor psychological health is mediated via the GBA. Proactive management of psychological health should be integrated into routine care. Further clinical trials of GBA-targeted therapies, conducted in selected groups of patients with co-existent common mental disorders, or those who report IBS-type symptoms, are required to inform effective integrated models of care in the future.

Psychotic experiences and psychological distress in adolescents: an examination of longitudinal bidirectional effects across sex

BackgroundAlthough the co-occurrence of psychotic experiences (PEs) and psychological distress symptoms is growingly recognized in several previous studies, there is still a lack of literature, which clearly outlines how these two psychopathological entities affect each other over time. This study is intended to add to the literature by examining: (a) the longitudinal, bidirectional associations between PEs and psychological distress in a sample of Tunisian adolescents, and (b) whether these associations are moderated by sex.Methods510 adolescent students (mean age of 16.05 ± 1.01 years, 61.2% females) took part in a prospective longitudinal study. PEs and psychological distress were measured at three occasions over a one-year period. The cross-lagged panel modeling approach was adopted.ResultsThe current results showed that the experience of PEs at baseline tended to temporally precede prospective increases in psychological distress (at 6 months), which had in turn led to further exacerbation of psychological distress at 12 months of follow-up. Temporally primary psychological distress symptoms were not a significant predictor for the development of later psychotic symptoms in the whole sample. However, temporal patterns between adolescent distress and psychotic symptoms differed for girls and boys. Endorsing PEs at baseline was followed by greater psychological distress at 6 months, which was in turn associated with a significant increased risk of subsequent exacerbation of PEs at 12 months in boys, whereas psychological distress at 12-month follow-up was significantly predicted by pre-existing PEs in girls.ConclusionThese findings suggest that clinicians and support workers are recommended to take into account different social risk profiles for boys and girls when considering interventions to address PEs and distress in adolescents.

Art for health’s sake or health for art’s sake: Disentangling the bidirectional relationships between arts engagement and mental health

Abstract Increasing evidence links arts engagement with mental health, but the directionality of the link remains unclear. Applying a novel approach to causal inference, we used nonrecursive instrumental variable models to analyze two waves of data from the United Kingdom Household Longitudinal Study (n = 17,927). Our findings reveal bidirectional causal relationships between arts engagement (arts participation, cultural attendance, and heritage visits) and mental health (GHQ-12 mental distress and SF-12 Mental Component Summary mental well-being). After adjusting for time 1 measures and identifying confounders, cultural attendance and heritage visits were reciprocally associated with mental distress and mental well-being, while arts participation was only reciprocally associated with mental well-being. The bidirectional effects between arts engagement and mental health are modest but clearly demonstrated not only from mental health to arts but also from arts to mental health. Our findings indicate that previous evidence of an association between arts engagement and mental health is due to bidirectional causal effects. Interventions that boost arts participation, cultural attendance, and heritage visits may help break the negative feedback loop and enhance mental health.

Spillover and dependence between Chinese carbon and new energy stock markets: A cross-quantile perspective

The interplay between China's carbon emissions trading market and the new energy stock market has attracted increasing scholarly attention, given their alignment with green and sustainable development goals. This study utilizes the Cross-Quantilogram methodology to assess predictability and spillover dynamics in the Chinese carbon markets and the new energy stock markets across various quantiles. The analysis yields some significant findings: (1) Despite the small magnitude, bidirectional spillover effects are discernible between China's carbon market and the Chinese new energy market, with heterogeneous correlation among the three pilot carbon markets. (2) The cross-quantile correlation among markets exhibits varying dynamics with increasing lag orders. (3) During market downturns, the new energy market poses short-term abnormal extreme risks as a spillover source for the Guangdong carbon market, while exhibiting a stronger spillover effect on the Hubei carbon market during longer lag periods. (4) Certain sectors, such as the wind power, nuclear power, and photovoltaic sectors, stand out with a more pronounced cross-quantile in relation to the carbon market. (5) Both risk events and policy changes play a significant role in shaping market interactions. (6) Including Guangdong and Hubei carbon asset in a portfolio can effectively reduce the volatility risk of new energy stock portfolios. A valuable comprehension of the intricate interdependencies between China's carbon market and new energy assets is provided by this research, benefiting policymakers and investors in the energy and environmental sectors.

Protocol of a drug-drug interaction study between bictegravir/emtricitabine/tenofovir alafenamide and feminizing hormones in trans women living with HIV.

Trans/transfeminine women are disproportionally affected by HIV. Concerns regarding negative drug-drug interactions (DDIs) between ART drugs and gender-affirming hormone therapy (GAHT), specifically feminizing hormone therapy (FHT), may contribute to the lower ART uptake by trans women with HIV compared with their cis counterparts. The aim of this study is to investigate the bidirectional pharmacokinetic effects of components of FHT regimens (oral oestradiol and androgen-suppressing medications) with the ART regimen (bictegravir/emtricitabine/tenofovir alafenamide [B/F/TAF)]. We present a protocol for a three-armed, parallel-group, longitudinal (6-month), DDI study. Group 1 includes 15 3trans women with HIV taking FHT and ART; group 2 includes 15 premenopausal cis women with HIV taking ART; group 3 includes 15 trans women without HIV taking FHT. Women with HIV must be on or switch to B/F/TAF at baseline and be virally suppressed for ≥3months. Trans women must be taking a stable regimen of ≥2mg daily oral oestradiol and an anti-androgen (pharmaceutical, and/or surgical, and/or medical) for ≥3months. Plasma ART drug concentrations will be sampled at Month 2 and compared between groups 1 and 2. Serum oestradiol concentrations will be sampled at baseline and Month 2 visits and compared between groups 1 and 3. The primary outcomes are B/F/TAF pharmacokinetic parameters (Cmin, Cmax and AUC) and oestradiol concentrations (Cmin, C4h, Cmax and AUC) at month 2. This study is of global importance as it provides critical information regarding safe coadministration of B/F/TAF and FHT, both of which are life-saving therapies for trans women with HIV.

Genomic Correlation, Shared Loci, and Causal Relationship Between Bullous Pemphigoid and Atopic Dermatitis: A Large-Scale Genome-Wide Cross-Trait Analysis.

Bullous pemphigoid (BP) and atopic dermatitis (AD) are currently thought to be tightly related, yet studies of the mechanisms of co-morbidities are lacking. We obtained GWAS data for BP (N = 376,274) and AD (N = 796,661) from the Finnish Genetic Research Program dataset and the UK Biobank, separately. Then, the following four analyses were performed: (1) cross-trait linkage disequilibrium score regression (LDSC) to assess the genetic correlation between BP and AD, (2) cross-phenotype association analysis (CPASSOC) to identify multiple effector loci shared by BP and AD, (3) transcriptome-wide association study (TWAS) to determine whether their cross-organizational expression patterns share genes with a common biological mechanism of relevance, and (4) bidirectional Mendelian randomization (MR) analysis to assess bidirectional causal effects of BP and AD. We found a positive genetic association between BP and AD (rg = 0.5476, p = 0.0495) as well as identified four pleiotropic loci and 59 common genes affecting BP and AD. Bidirectional MR analysis suggested that BP promotes the risk of AD. We revealed a genetic link between BP and AD, which is associated with biological pleiotropy and causality. Awareness of the association between BP and AD helps dermatologists manage patients with these illnesses.

Mapping Risk–Return Linkages and Volatility Spillover in BRICS Stock Markets through the Lens of Linear and Non-Linear GARCH Models

This paper explores the influence of the risk–return relationship and volatility spillover on stock market returns of emerging economies, with a particular focus on the BRICS countries. This research is undertaken in a context where discussions on de-dollarization and the expansion of BRICS membership are gaining momentum, making it a novel and distinct exercise compared to prior studies. Utilizing econometric techniques to investigate daily market returns from 1 April 2008 to 31 March 2023, a period that witnessed major events like the global financial crisis, the COVID-19 pandemic, and the Russia–Ukraine conflict, linear and non-linear models like ARCH, GARCH, GARCH-M, EGARCH, and TGARCH, are employed to assess stock return volatility behaviour, assuming a Gaussian distribution of error terms. The diagnostic test confirms that the distribution is non-normal, stationary, and heteroscedastic. The key findings indicate a lack of the risk–return relationship across all BRICS stock markets, except for South Africa; a more pronounced effect of unpleasant news over pleasant news; a slow mean-reverting process in volatility; the EGARCH model is the best fit model as evidenced by a higher log likelihood and lower Akaike information criterion and Schwardz information criterion parameters; and finally, the presence of significant bidirectional and unidirectional spillover effects in the majority of instances. These findings are valuable for investors, regulators, and policymakers in enhancing returns and mitigating risk through portfolio diversification and informed decision making.

The effects of all-trans retinoic acid on prednisolone-induced osteoporosis in zebrafish larvae

Glucocorticoids (GCs) are extensively used as anti-inflammatory and immunosuppressive medications in the long-term treatment of rheumatic disorders, respiratory diseases, renal diseases, and organ transplantation. Prolonged use of GCs can reduce bone mineral density, leading to osteoporosis (Glucocorticoid Induced Osteoporosis, GIOP) and fracture. All-trans retinoic acid (ATRA) is an active vitamin A metabolite that regulates embryonic development and adult organ function. ATRA has been found in studies to enhance osteogenesis. To examine the interventional effects of ATRA on GIOP and the mechanisms of ATRA activities, we first performed bioinformatic analysis to identify potential gene targets of ATRA. Zebrafish larvae were recruited as experimental animals, and the frequently used GC, prednisolone, was administered to larvae to construct a GIOP model. We evaluated the influence of exogenous ATRA on the activities of bone metabolic enzymes, the expression of genes linked to osteoblasts and osteoclasts, and the restoration of bone mineral density and bone mass in GIOP zebrafish larvae. Furthermore, we studied the influence of RBM14, a transcriptional coactivator and negative reciprocal factor of ATRA, on the regulation of osteoblastic gene expression during the anti-GIOP process of ATRA using the morpholino knockdown approach. The findings of bone metabolic enzyme activity (alkaline phosphatase, ALP and tartrate-resistant acid phosphatase, TRAP) and expression assays of osteoblastic marker genes (Runx2a, Runx2b, SP7, Csf1a, RANKL, and CTSK) indicated that ATRA had bidirectional effects on osteogenesis. However, in the GIOP model, ATRA reversed the GIOP-induced osteoporosis phenotype by inhibiting the GIOP-induced suppression of osteoblastic metabolic enzyme (ALP) activities and osteoblastic marker gene expression (Runx2a, Runx2b, and SP7), and this antagonism was concentration-dependent. We also observed that ATRA inhibited RBM14 expression in zebrafish larvae, while ATRA alone and RBM14 knockdown showed a consistent induction of osteoblast marker gene expression, implying that ATRA's inhibitory effect on RBM14 expression may underlie ATRA's osteogenic effects. Based on these data, we postulated that ATRA may ameliorate GIOP by decreasing RBM14 expression, thereby enhancing osteoblastic marker gene expression.

Exploring Moderation Dynamics: Callous-Unemotional Traits, Parental Practices and Conduct Problems in JuvenileDelinquency.

Callous-unemotional (CU) traits, parental practices and conduct problems (CP) have been consistently identified across numerous studies as significant predictors of the severity and persistence of juvenile delinquency. This study seeks to investigate the moderation dynamics underlying the relationships between these variables among Arab incarcerated youth. Specifically, the study aims to (1) explore whether parental practices moderate the relationship between CU traits and CP among incarcerated youth in Jordan and (2) examine the bidirectional moderating influence of CU traits in shaping the dynamic relationship between parental practices and CP within the context of Arab juvenile delinquency. An observational survey design was employed, gathering data from 184 incarcerated youth across 11 rehabilitation centres in Jordan. Latent profile analysis identified three parental practice classes: more positive, balanced and more negative. Moderation analyses indicated significant associations between CU traits, parental practices and CP. Parental practices, especially positive ones, moderated the relationship between CU traits and CP, highlighting the protective influence of balanced parenting. Furthermore, bidirectional moderation effects were observed: CU traits moderated the link between parental practices and CP, while CP influenced parenting practices, particularly in the presence of elevated CU traits. The findings of this study underscore the vital role mental health nurses can play in addressing the behavioural and psychological challenges faced by youth involved in the justice system and their families. Specifically, mental health nurses can aid in ameliorating mental distress by supporting parents in understanding and managing CU traits and CP. Nurses can provide targeted educational programmes that empower parents with strategies to reinforce positive parenting practices and reduce negative interactions. Furthermore, nurses can facilitate access to community resources and therapy options, helping families build a supportive environment conducive to the mental well-being of the youth. These interventions are crucial not only for the direct treatment of juveniles but also in providing holistic support to their families, thereby enhancing the overall efficacy of mental health care in juvenile delinquency. This study highlights the essential role that mental health nurses play in managing behavioural issues among youth, emphasising the significance of implementing culturally sensitive interventions. Mental health nurses possess a pivotal position in early detection and intervention, which enables them to guide families in fostering positive parenting practices, essential for preventing delinquent behaviours. Their efforts to promote understanding and responsiveness within family dynamics make a significant contribution to the mental well-being of individuals, highlighting the necessity of their role in global mental health.