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How do play and playfulness contribute to adult mental health? We evaluated empirical evidence from 20 psychological interventions through a lens emphasizing playfulness in participants and playing processes as a putative change agent. We found (1) preliminary evidence supporting play as a causal agent of positive changes in adult mental health, likely via two mechanisms—as a mediator and as a medium, and (2) limited, unclear evidence surrounding the moderating effect of participant playfulness on intervention effectiveness. Our findings highlight the need for more rigorous quantitative assessment of play-related processes and health outcomes, and a clearer trait-state distinction when examining playfulness as an intervention outcome. We call for greater theoretical integration and a more holistic, developmentally-sensitive approach, emphasizing understanding boundary-crossing change mechanisms to harness play's transformative, therapeutic power for improving adult health and wellbeing. [ABSTRACT FROM AUTHOR]

Obesity is a pervasive public health problem that causes debilitating complications across the life course. One opportunity for preventing the onset of obesity is to focus on its social determinants. Socioeconomic status (SES), which includes factors such as income, educational attainment, occupational prestige, and access to resources, is a key determinant of obesity. In this scoping mini-review, we summarized review articles and meta-analyses of the SES-obesity association. From the 1980s to the present, cross-sectional studies have demonstrated a persistent socioeconomic gradient in obesity in which the association is negative in developed countries and positive in developing countries. Longitudinal studies have revealed the bidirectionality of the SES-obesity association; some studies demonstrate that socioeconomic adversity precedes the onset of obesity, while others provide evidence of reverse causality. While earlier studies relied on anthropometric assessments of weight and height to define obesity, the use of modern technologies like dual-energy x-ray absorptiometry and bioelectrical impedance have demonstrated that the socioeconomic gradient in obesity is robust across multiple indicators of body composition, including direct measures of lean and fat mass. More recently, examination of mediators and moderators of the SES-obesity association have highlighted causal pathways and potential intervention targets, with a focus on health behaviors, environmental conditions, psychological factors, and biological processes. We describe current gaps in knowledge and propose opportunities for future innovation to reduce the burden of obesity and related socioeconomic disparities. [ABSTRACT FROM AUTHOR]

The eukaryotic transcriptional Mediator comprises a large core (cMED) and a dissociable CDK8 kinase module (CKM). cMED recruits RNA polymerase II (RNA Pol II) and promotes pre-initiation complex formation in a manner repressed by the CKM through mechanisms presently unknown. Herein, we report cryoelectron microscopy structures of the complete human Mediator and its CKM. The CKM binds to multiple regions on cMED through both MED12 and MED13, including a large intrinsically disordered region (IDR) in the latter. MED12 and MED13 together anchor the CKM to the cMED hook, positioning CDK8 downstream and proximal to the transcription start site. Notably, the MED13 IDR obstructs the recruitment of RNA Pol II/MED26 onto cMED by direct occlusion of their respective binding sites, leading to functional repression of cMED-dependent transcription. Combined with biochemical and functional analyses, these structures provide a conserved mechanistic framework to explain the basis for CKM-mediated repression of cMED function. [Display omitted] • Structures of the complete human Mediator and its CDK8 kinase module (CKM) are presented • CKM binds cMED through MED12 and the intrinsically disordered region (IDR) of MED13 • MED13 IDR blocks RNA Pol II/MED26 from binding to cMED by occupying their binding sites • Human and yeast MED13 share a conserved mechanism for transcriptional repression Chao and Chen et al. present cryo-EM structures of the complete human Mediator and its CDK8 kinase module (CKM). The CKM uses its MED13 IDR to occupy RNA-polymerase-II- and MED26-binding sites, blocking their interactions with Mediator and repressing Mediator-dependent transcription—a mechanism conserved in humans and yeast. [ABSTRACT FROM AUTHOR]

The main aim of this study was to investigate adolescents' eustress–distress and mindfulness by examining mental toughness (MT) using network and mediator analyses. The study included 414 adolescents. The results showed that MT was positively related to eustress and mindfulness, but distress was negatively related to MT. Based on the network analysis findings, we tested mindfulness' mediating role in the relationship between eustress–distress and MT. The findings showed that mindfulness played a significant mediating role. However, the mediating role of mindfulness was negative for the relationship between distress and toughness and positive for eustress. These findings advance eustress, distress, and mindfulness as mechanisms for understanding the effects of MT. Considering current knowledge of MT, eustress, distress, and mindfulness, the results are discussed. [ABSTRACT FROM AUTHOR]

This study investigated the decolorization and detoxification of a dye originating from a feather-dyeing house using the laccase enzyme. Efficient decolorization was achieved under a wide range of environmental conditions, including pH, temperature, enzyme loading, and dye concentration. The decolorization rate reached up to 98% within 10 min when the mediator acetosyringone was present. Decolorization was attributed to the degradation of the dye by laccase, as analyzed using liquid chromatography-mass spectrometry (LC–MS). At least three dominant intermediates (m/z 167.993, 194.475, 118.040) were identified, deriving from the original dye (m/z 521.044). Compared to the non-decolorized dye solution, the decolorized dye ones at various concentrations exhibited lower toxicity towards aerobic activated sludge (AS). This was evident from the significantly higher respiratory intensity of AS, with an O₂ uptake of 35 mg for the decolorized solution versus 11 mg for the non-decolorized solution after 12 h at a 100 mg/L dye concentration. The results suggest that laccase-catalyzed decolorization could serve as an effective pretreatment method for traditional activated sludge (AS)-based processes, thereby enhancing the overall treatment performance of dye wastewater. [ABSTRACT FROM AUTHOR]

Mediator, a multiprotein complex, is an important component of the transcription machinery. In plants, the latest studies have established that it functions as a signal processor that conveys transcriptional signals from transcription factors to RNA polymerase II. Mediator has been found to be involved in different developmental and stress-adaptation conditions, ranging from embryo, root, and shoot development to flowering and senescence, and also in responses to different biotic and abiotic stresses. In the last decade, significant progress has been made in understanding the role of Mediator subunits in root development. They have been shown to transcriptionally regulate development of almost all the components of the root system architecture—primary root, lateral roots, and root hairs. They also have a role in nutrient acquisition by the root. In this review, we discuss all the known functions of Mediator subunits during root development. We also highlight the role of Mediator as a nodal point for processing different hormone signals that regulate root morphogenesis and growth. [ABSTRACT FROM AUTHOR]

Objective Methods Results Conclusion Describe the current status of illness perception, depression, and self‐management behaviors among women with gestational diabetes mellitus (GDM) during the COVID‐19 pandemic, and explore the role of depression in the relationship between illness perception and self‐management behaviors among women with GDM.Pregnant women diagnosed with GDM were recruited at the obstetrics clinic of a Grade‐A tertiary hospital in Wuhan, through convenience sampling. Self‐reported questionnaires including basic information, illness perception, depression, and self‐management behaviors were used to collect data from April 2021 to February 2022. Mediation analysis was performed by SPSS Process macro.Among GDM pregnant women, the mean self‐management behaviors score was 73.89 (SD = 12.21), the mean illness perception score was 31.80 (SD = 8.77), and 44.3% had depression scores of 10 or higher. The indirect effect of illness perception on self‐management behaviors mediated by depression was significant (path a * b, β = −0.045), accounting for 26.6% of the total effect.GDM pregnant women have a certain negative illness perception of GDM, and the detection rate of depression symptoms is relatively high. The level of self‐management behaviors among GDM pregnant women is notably suboptimal and warrants improvement. Depression partially mediates the relationship between illness perception and self‐management behaviors. Improving positive illness perception and decreasing depression are important strategies to improve self‐management behaviors in women with GDM. [ABSTRACT FROM AUTHOR]

Background: Since nurses are at the frontline of healthcare delivery, their actions and understanding of the environment have a big impact on how long healthcare systems can last. It is essential to comprehend the elements that impact nurses' sustainability consciousness to encourage ecologically conscious actions in the healthcare industry. Aim: This study aimed to explore the relationship between pro-social leader behaviors and nurses' sustainability consciousness and testify to the mediating role of organizational culture in this relationship. Design: A cross-sectional descriptive correlational design by STROBE criteria was used. Methods and tools: An approach to a judgmental non-probability sampling technique was employed to obtain data from 350 nurses in an Egyptian hospital. Three measurement surveys were employed: Organizational Culture Survey, Prosociality Scale, and, Sustainability Consciousness Questionnaire (SCQ-S). Relationships were shown using structural equation modeling and descriptive and inferential statistics. Results: 53.4% of nurses have high perceptions of organizational culture, and the majority of nurses (85.7%) have high perceptions of prosocial leader behaviors. Furthermore, 60.9% of nurses have high perceptions of sustainability consciousness. Additionally, Prosocial leader behaviors positively correlated with organizational culture (r = 0.129) and nurses' sustainability consciousness (r = 0.274). The indirect effect of prosocial leader behaviors on nurses' sustainability consciousness through organizational culture is calculated by multiplying the coefficients of both direct effects (0.129 * 0.159 = 0.811). This means that for each unit increase in prosocial leader behaviors, we would expect a 0.811 unit increase in nurses' sustainability consciousness through the mediating effect of organizational culture. The model appears to match the data well based on the model fit parameters (CFI = 1.000, IFI = 1.000, RMSEA = 0.114). Conclusions: The study highlights the impact of pro-social leader behaviors on nurses' sustainability consciousness through the organizational culture as a mediating factor. Nursing Implications: Findings from this research can promote environmental stewardship and sustainable practices in the healthcare sector by illuminating the elements that can encourage and support a sustainability-oriented mindset among nurses. To promote a more sustainable future for the nursing profession, the findings can guide activities in nursing education, corporate culture transformation, and leadership development. [ABSTRACT FROM AUTHOR]

Objective: To investigate the causal relationship between lipidome and malignant melanoma of skin (MMOS), while identifying and quantifying the role of metabolites as potential mediators. Methods: A two-sample Mendelian randomization (MR) analysis of lipid species (n=7174) and MMOS was performed using pooled data from genome-wide association studies (GWAS). In addition, we quantified the proportion of metabolite-mediated lipidome effects on MMOS by two-step MR. Results: This study identified potential causal relationships between 11 lipids and MMOS, and 40 metabolites and MMOS, respectively. Phosphatidylethanolamine (18:0_18:2) levels mined from 179 lipids by MR Analysis increased the risk of MMOS (OR: 1.962; 95%CI:1.298,2.964; P=0.001). There is no strong evidence for a relationship between genetically predicted MMOS and phosphatidylethanolamine (18:0_18:2) levels (P=0.628). The proportion of gene predictions for phosphatidylethanolamine (18:0_18:2) levels mediated by 1-stearoyl-(glycosylphosphatidylinositol) GPI (18:0) levels was 12.40%. Conclusion: This study identifies 1-stearoyl-GPI (18:0) levels as a potentialmediator that may mediate the causal relationship between phosphatidylethanolamine (18:0_18:2) levels and MMOS, This provides direction for the investigation of MMOS, but further research of other possible potential mediators is still needed. [ABSTRACT FROM AUTHOR]

Background: Although the negative impact of smoking and health-related quality of life (HRQoL) on depression has been confirmed in various studies, There has been little exploration of how HRQoL mediates the relationship between smoking and depression. The purpose of the current study was to examine the relationship between smoking and depression in the Chinese current smokers with nicotine dependence and the mediating role of HRQoL. Methods: A cross-sectional study named "Psychology and Behavior Investigation of Chinese Residents" was conducted from July 10 to September 15, 2021 in China. Nicotine dependence, HRQoL and depression were measured by Fagerstrom Test for Nicotine Dependence (FTND), the European Five Dimensional Five Level Health scale (EQ-5D-5L) and the 9-item Patient Health Questionnaire (PHQ-9) respectively. Information on age, gender, place of residence, household registration, education level, marital status, employment status, average family monthly income, drinking frequency, living status, BMI, multiple chronic conditions were also collected. Pearson's correlation test and logistic regression analysis were conducted to explore the association between nicotine dependence, HRQoL and depression and a mediation analysis was applied to explore the mediating effect of the HRQoL on this relationship. Results: A total of 1,381 current smokers were included in the study. The participants showed a moderate level of nicotine dependence with a mean of 1.36(SD=1.50), a relatively high level of HRQoL scores (Mean=0.94, SD=0.13), and a depression score with a mean of 6.48(SD=6.09). Approximately 22.74% (314/1,381) of the participants were considered to indicate depression. In the univariable regression model, it was found that nicotine dependence was positively associated with depression (OR:1.094, 95%CI: 1.008-1.187), while HRQoL was negatively associated with depression (OR:0.011, 95%CI: 0.004-0.033). In the multivariable regression model, HRQoL was still notably associated with depression (OR:0.008, 95%CI: 0.002-0.027), however, the positive association was not observed between nicotine dependence and depression. The Pearson's correlation test demonstrated that nicotine dependence was negatively correlated with HRQoL(rs= -0.147, P<0.001) and HRQoL was negatively correlated with depression(rs= -0.275, P<0.001). In contrast, nicotine dependence was positively correlated with depression(rs= 0.136, P<0.001). Mediation analysis found that HRQoL moderated the relationship between nicotine dependence and depression with a mediating effect of 26.49%. Conclusions: The findings support that nicotine dependence is positively associated with depression and HRQoL is negatively associated with depression in current smokers. HRQoL mediated the relationship between nicotine dependence and depression. The well-established imperative interventions aimed at promoting smoking cessation and improving quality of life may benefit for alleviation of depression in current smokers. [ABSTRACT FROM AUTHOR]

Background: Diabetes complications are prevalent in people with diabetes, causing considerable individual suffering and increased health costs. However, the relationships of multidimensional, modifiable, and nonmodifiable factors to diabetes complications and the role of diabetes distress have been rarely examined. Objective: The aims of this study were to examine the associations of age, sex, knowledge, self-efficacy, self-compassion, resilience, self-esteem, depressive symptoms, diabetes distress, social support, and body mass index with diabetes complications and to investigate the mediating role of diabetes distress. Methods: In this cross-sectional, correlational study, data on all study variables were collected from 148 people with diabetes through REDCap in 2023. Multiple regression analysis and the PROCESS macro for SPSS were used to address the aims. Results: Older age and higher levels of diabetes distress were associated with more diabetes complications. Depressive symptoms were associated with diabetes distress; and diabetes distress, but not depressive symptoms, was associated with diabetes complications, controlling for all other variables. Conclusions: Depressive symptoms and diabetes distress were directly or indirectly associated with diabetes complications, and diabetes distress was a mediator in the relationship between depressive symptoms and diabetes complications. Health care providers can target reduction of depressive symptoms and diabetes distress to reduce diabetes complications. [ABSTRACT FROM AUTHOR]

An electrochemical bioassay based on rotating droplet electrochemistry by using an electron-transfer mediator was developed for the evaluation of a wide variety of pollutants such as antibiotics, heavy metals, and pesticides in the water environment. Ferricyanide was used as an electron-transfer mediator for obtaining the catalytic response of Escherichia coli. The electrochemical response of E. coli was measured via hydrodynamic chronoamperometry in a microdroplet on a screen-printed carbon electrode (SPCE). The constructed electrode system successfully evaluates the catalytic response of E. coli solution in the presence of ferricyanide. An assay for antibiotic toxicity on E. coli was carried out. The EC50 for ampicillin, sulfamonomethoxine, chlorotetracycline, tetracycline, and oxytetracycline evaluated by the pre-incubation method were 0.26, 0.77, 5.25, 18.5, and 19.0 µM, respectively. The toxicity order was ampicillin > sulfamonomethoxine > chlorotetracycline > tetracycline > oxytetracycline. The proposed method can be used to evaluate the antibiotic toxicities in different real samples, such as pond water, powder, and raw milk. Recoveries were found in the range of 90 and 99%. The developed methods do not require additional incubation time to evaluate toxicity. [ABSTRACT FROM AUTHOR]

There is a growing emphasis on acknowledging the significance of mediation within English language classrooms, reflecting an increased interest in recognizing its importance as one of the teachers' new roles (Rezaeian, 2022). According to mediation theory, "helping learners to find ways of moving into their next level of understanding of the language" is the teachers' role (Williams & Burden, 1997, p. 66). This paper aims to investigate English teachers' perception of mediation and their teaching practices as mediators and raise an awareness about mediated learning among English teachers. Data for this study was collected from Mediation Questionnaire for Language Teachers designed by Williams and Burden (1997). The questionnaire includes two sections each containing 12 individual questions. First section focuses on teachers' perspectives on the significance of mediation. In the second section, teachers are asked to evaluate the frequency with which they believe they perform practices of mediation. The questionnaire was applied to 45 Turkish EFL teachers working at Ministry of National Education in Kütahya province. Results of the questionnaire survey suggest that to some extent, EFL teachers have capability to facilitate students' learning. They believe that mediation is important to some extent in language classrooms. However, their implementation is lower compared to what they think. Although we as English teachers are trying to facilitate our students' learning, we may need to have a deeper understanding of mediation theory to improve ourselves as mediators. Findings of this study are expected to contribute to field of Foreign Language Education. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study is to examine the linear and non-linear relationship between capital structure (CS) and firm performance (FP) and the moderating and mediating roles of agency costs in the CS-FP nexus. Design/methodology/approach: This study used static and quadratic panel data regression models to examine the linear and non-linear relationships and structured equation models to analyze the mediating effect of agency costs in the CS-FP nexus of 38 listed non-financial Mauritian firms from 2009 to 2019. Findings: Leverage has a significant negative effect on FP supporting the pecking order theory. Agency costs are significantly and positively associated with FP. There is a strong non-linear relationship between leverage and FP supporting the trade-off and agency cost theories. Agency costs are an important moderator and mediator in the CS-FP nexus. Overall, the sensitivity analyses showed that the results were robust. Practical implications: Firms need to carefully consider the levels and types of debt and equity in their CS involving the use of dynamic strategies to adjust CS in response to changing economic conditions and FP. The moderating effect of agency costs may guide firms in optimizing CS and may contribute to corporate governance discussions, emphasizing the importance of aligning interests to foster sustainable business practices. Originality/value: This study adds to the extant literature by providing new evidence on the non-linear relationship between leverage and FP and the moderating and mediating roles of agency costs in the CS-FP nexus in emerging capital markets, where such studies are rare. [ABSTRACT FROM AUTHOR]

Arabidopsis MORC1 (Microrchidia) is required for multiple levels of immunity. We identified 14 MORC1-interacting proteins (MIPs) via yeast two-hybrid screening, eight of which have confirmed or putative nuclear-associated functions. While a few MIP mutants displayed altered bacterial resistance, MIP13 was unusual. The MIP13 mutant was susceptible to Pseudomonas syringae, but when combined with morc1/2, it regained wild-type resistance; notably, morc1/2 is susceptible to the same pathogen. MIP13 encodes MED9, a mediator complex component that interfaces with RNA polymerase II and transcription factors. Expression analysis of defense genes PR1, PR2, and PR5 in response to avirulent P. syringae revealed that morc1/2 med9 expressed these genes in a slow but sustained manner, unlike its lower-order mutants. This expression pattern may explain the restored resistance and suggests that the interplay of MORC1/2 and MED9 might be important in curbing defense responses to maintain fitness. Indeed, repeated challenges with avirulent P. syringae triggered significant growth inhibition in morc1/2 med9, indicating that MED9 and MORC1 may play an important role in balancing defense and growth. Furthermore, the in planta interaction of MED9 and MORC1 occurred 24 h, not 6 h, post-infection, suggesting that the interaction functions late in the defense signaling. Our study reveals a complex interplay between MORC1 and MED9 in maintaining an optimal balance between defense and growth in Arabidopsis.

Abstract Background Since nurses are at the frontline of healthcare delivery, their actions and understanding of the environment have a big impact on how long healthcare systems can last. It is essential to comprehend the elements that impact nurses’ sustainability consciousness to encourage ecologically conscious actions in the healthcare industry. Aim This study aimed to explore the relationship between pro-social leader behaviors and nurses’ sustainability consciousness and testify to the mediating role of organizational culture in this relationship. Design A cross-sectional descriptive correlational design by STROBE criteria was used. Methods and tools An approach to a judgmental non-probability sampling technique was employed to obtain data from 350 nurses in an Egyptian hospital. Three measurement surveys were employed: Organizational Culture Survey, Prosociality Scale, and, Sustainability Consciousness Questionnaire (SCQ-S). Relationships were shown using structural equation modeling and descriptive and inferential statistics. Results 53.4% of nurses have high perceptions of organizational culture, and the majority of nurses (85.7%) have high perceptions of prosocial leader behaviors. Furthermore, 60.9% of nurses have high perceptions of sustainability consciousness. Additionally, Prosocial leader behaviors positively correlated with organizational culture (r = 0.129) and nurses’ sustainability consciousness (r = 0.274). The indirect effect of prosocial leader behaviors on nurses’ sustainability consciousness through organizational culture is calculated by multiplying the coefficients of both direct effects (0.129 * 0.159 = 0.811). This means that for each unit increase in prosocial leader behaviors, we would expect a 0.811 unit increase in nurses’ sustainability consciousness through the mediating effect of organizational culture. The model appears to match the data well based on the model fit parameters (CFI = 1.000, IFI = 1.000, RMSEA = 0.114). Conclusions The study highlights the impact of pro-social leader behaviors on nurses’ sustainability consciousness through the organizational culture as a mediating factor. Nursing Implications: Findings from this research can promote environmental stewardship and sustainable practices in the healthcare sector by illuminating the elements that can encourage and support a sustainability-oriented mindset among nurses. To promote a more sustainable future for the nursing profession, the findings can guide activities in nursing education, corporate culture transformation, and leadership development.

An electrochemical bioassay based on rotating droplet electrochemistry by using an electron-transfer mediator was developed for the evaluation of a wide variety of pollutants such as antibiotics, heavy metals, and pesticides in the water environment. Ferricyanide was used as an electron-transfer mediator for obtaining the catalytic response of Escherichia coli. The electrochemical response of E. coli was measured via hydrodynamic chronoamperometry in a microdroplet on a screen-printed carbon electrode (SPCE). The constructed electrode system successfully evaluates the catalytic response of E. coli solution in the presence of ferricyanide. An assay for antibiotic toxicity on E. coli was carried out. The EC50 for ampicillin, sulfamonomethoxine, chlorotetracycline, tetracycline, and oxytetracycline evaluated by the pre-incubation method were 0.26, 0.77, 5.25, 18.5, and 19.0 µM, respectively. The toxicity order was ampicillin > sulfamonomethoxine > chlorotetracycline > tetracycline > oxytetracycline. The proposed method can be used to evaluate the antibiotic toxicities in different real samples, such as pond water, powder, and raw milk. Recoveries were found in the range of 90 and 99%. The developed methods do not require additional incubation time to evaluate toxicity.

Abstract Background Drug addiction is a significant public health concern, and aggression is common among people with drug addiction. Despite mounting evidence showing that the Dark Triad is a risk factor for aggression, the mediating and moderating mechanisms underlying this relationship are less known. This study tested the mediation effect of self-control in the association between the Dark Triad and aggression and whether this mediation was moderated by physical exercise. Methods A cross-sectional study was conducted in two compulsory drug rehabilitation centers in Nanning, China. A convenience sample of 564 drug abstainers completed a questionnaire to assess their Dark Triad, self-control, aggression, and physical exercise levels. Mediation and moderation analyses were carried out in SPSS macro-PROCESS. Results Self-control partially mediated the positive association between the Dark Triad and aggression. Physical exercise moderated the indirect effect of the Dark Triad on aggression via self-control, with the effect decreasing with the increase in physical exercise levels. Conclusions This study offers fresh insights into the underlying mediating and moderating mechanisms between the Dark Triad and aggression. The findings provide important practical implications for future intervention and prevention programs to address aggression among drug abstainers, which may be realized through strengthening self-control and physical exercise.

Abstract Background and Aims Digital smoking cessation interventions have been shown to be effective in helping individuals achieve prolonged smoking abstinence. Nonetheless, the mechanisms that drive such effects are unclear. The current study aimed to estimate a digital smoking cessation intervention's natural direct and indirect effects. Methods This secondary analysis of mediated effects uses data from a randomised controlled trial which included participants who smoked at least one cigarette a week, had access to a mobile phone, and were 18 years or older. The comparator was existing smoking cessation support available to all members of the Swedish public. Primary outcomes were prolonged smoking abstinence and point prevalence of smoking abstinence, measured at 3- and 6-months post-randomisation. A counterfactual framework was used to estimate three hypothesised mediators of the intervention's effects: importance, knowledge of how to change (know-how), and confidence. Results Between 18/09/20 and 16/06/22, 1012 participants were randomised. The intervention led to improved confidence and know-how, which both partially mediated the effects of the digital intervention on smoking abstinence at 3- and 6 months post-randomisation. Conclusions A digital smoking cessation intervention was found to partially affect smoking abstinence by improving individuals’ confidence in their ability to quit smoking and developing knowledge on how to quit. Face-value single-item mediator measures, lack of blinding, and attrition limit the study. Future studies should address these limitations and assess additional mechanisms mediating intervention effects. Trial registration ISRCTN13455271.

ObjectiveTo examine the association between physical activity and risk of all-cause mortality and related mediators in middle-aged and elderly people in China to provide evidence for reducing mortality in the population. MethodsData were collected from 5 727 individuals aged ≥ 45 years who completed baseline and 3 follow-up surveys in the China Health and Retirement Longitudinal Study (CHARLS) from 2011 to 2018. We used multivariable Cox proportional hazards regression models and restricted cubic spline models to examine the association between physical activity levels and risk of all-cause mortality. In addition, we conducted a mediation analysis based on body mass index (BMI), blood pressure, and blood biochemical indicators collected during follow-up. ResultsOf all the individuals analyzed, 1 813 (31.66%) were classified as having physical activity (measured in metabolic equivalents [METs]-min/week) in the lowest quartile (

Background: Drug addiction is a significant public health concern, and aggression is common among people with drug addiction. Despite mounting evidence showing that the Dark Triad is a risk factor for aggression, the mediating and moderating mechanisms underlying this relationship are less known. This study tested the mediation effect of self-control in the association between the Dark Triad and aggression and whether this mediation was moderated by physical exercise. Methods: A cross-sectional study was conducted in two compulsory drug rehabilitation centers in Nanning, China. A convenience sample of 564 drug abstainers completed a questionnaire to assess their Dark Triad, self-control, aggression, and physical exercise levels. Mediation and moderation analyses were carried out in SPSS macro-PROCESS. Results: Self-control partially mediated the positive association between the Dark Triad and aggression. Physical exercise moderated the indirect effect of the Dark Triad on aggression via self-control, with the effect decreasing with the increase in physical exercise levels. Conclusions: This study offers fresh insights into the underlying mediating and moderating mechanisms between the Dark Triad and aggression. The findings provide important practical implications for future intervention and prevention programs to address aggression among drug abstainers, which may be realized through strengthening self-control and physical exercise. [ABSTRACT FROM AUTHOR]

We report the development of a four‐component electrochemical method for the synthesis of CF3‐oxazoles, utilizing alkynes and NaSO2CF3 in MeCN. The method leverages the simplicity and mildness of the reaction conditions, despite the inherent complexity of utilizing four distinct components through aminotrifluoromethylation of alkyne followed by in‐situ cyclization. Notably, in addition to MeCN solvent, the presence of residual water in the reaction mixture also contributed as a coupling partner. The synthesis involves a sequence of four controlled oxidation steps under constant potential with graphite electrodes, facilitated by the mediator TMEDA, highlighting the precision achievable in electrochemistry. [ABSTRACT FROM AUTHOR]

Background: Suicidal ideation is a pressing public health concern, particularly among adolescents. The objective of this study was to examine the prevalence of and factors associated with suicidal ideation in Chinese adolescents, addressing an important gap in current research. Methods: This study employed an online survey of 3443 adolescents in Lianyungang, using a cross-sectional design. The assessment included the use of the Patient Health Questionnaire-9, the seven-item Generalized Anxiety Disorder instrument, and the Perceived Social Support Scale to evaluate suicidal ideation, anxiety symptoms, and social support in adolescents, respectively. Results: In adolescents, the prevalence of suicidal ideation was 22.1%, with a significantly higher proportion among female adolescents than among males (27.9% vs 16.9%, P < 0.001). Binary regression analysis identified (OR = 1.788, 95% CI: 1.467-2.177, P < 0.001), anxiety symptoms (OR = 10.035, 95% CI: 7.441-13.534, P < 0.001), total PHQ-9 scores of mothers (OR = 1.040, 95%CI: 1.003 - 1.078, P = 0.034), total GAD-7 scores of mothers (OR = 0.958, 95%CI: 0.919 - 0.998, P = 0.039), and moderate parental relationships (OR = 2.042, 95% CI: 1.630-2.557, P < 0.001) to be risk factors for suicidal ideation; family support was a protective factor (OR = 0.888, 95% CI: 0.859-0.918, P < 0.001). Furthermore, family support partially mediates the relationship between anxiety symptoms and suicidal ideation among adolescents (9.28%). Conclusions: This study highlights high adolescent suicidal ideation rates and recommends gender-specific interventions, anxiety management, and family support for improvement in mental health status. [ABSTRACT FROM AUTHOR]

Background: The gut microbiota (GM) has been implicated in neurological disorders, but the relationship with hydrocephalus, especially the underlying mechanistic pathways, is unclear. Using Mendelian randomization (MR), we aim to discover the mediating role of inflammatory factors in the relationship between GM and hydrocephalus. Methods: After removing confounders, univariable and multivariable MR analyses were performed using summary statistics to assess the causal relationships between GM, inflammatory factors (IL-17A and IL-27), and types of hydrocephalus. Meta-analyses were used to reconcile the differences in MR results between different hydrocephalus sources. Finally, mediator MR analyses were applied to determine the mediating effect of inflammatory factors. Various sensitivity analysis methods were employed to ensure the reliability and stability of the results. Results: After correction for P-values, Firmicutes (phylum) (OR, 0.34; 95%CI, 0.17-0.69; P = 2.71E-03, PFDR = 2.44E-02) significantly reduced the risk of obstructive hydrocephalus. The remaining 18 different taxa of GM had potential causal relationships for different types of hydrocephalus. In addition, Firmicutes (phylum) decreased the risk of obstructive hydrocephalus by increasing levels of IL-17A (mediating effect = 21.01%), while Eubacterium ruminantium group (genus) increased the risk of normal-pressure hydrocephalus by decreasing levels of IL-27 (mediating effect = 7.48%). Conclusion: We reveal the connection between GM, inflammatory factors (IL-17A and IL-27), and hydrocephalus, which lays the foundation for unraveling the mechanism between GM and hydrocephalus. [ABSTRACT FROM AUTHOR]

Background and Aims: Digital smoking cessation interventions have been shown to be effective in helping individuals achieve prolonged smoking abstinence. Nonetheless, the mechanisms that drive such effects are unclear. The current study aimed to estimate a digital smoking cessation intervention's natural direct and indirect effects. Methods: This secondary analysis of mediated effects uses data from a randomised controlled trial which included participants who smoked at least one cigarette a week, had access to a mobile phone, and were 18 years or older. The comparator was existing smoking cessation support available to all members of the Swedish public. Primary outcomes were prolonged smoking abstinence and point prevalence of smoking abstinence, measured at 3- and 6-months post-randomisation. A counterfactual framework was used to estimate three hypothesised mediators of the intervention's effects: importance, knowledge of how to change (know-how), and confidence. Results: Between 18/09/20 and 16/06/22, 1012 participants were randomised. The intervention led to improved confidence and know-how, which both partially mediated the effects of the digital intervention on smoking abstinence at 3- and 6 months post-randomisation. Conclusions: A digital smoking cessation intervention was found to partially affect smoking abstinence by improving individuals' confidence in their ability to quit smoking and developing knowledge on how to quit. Face-value single-item mediator measures, lack of blinding, and attrition limit the study. Future studies should address these limitations and assess additional mechanisms mediating intervention effects. Trial registration: ISRCTN13455271. [ABSTRACT FROM AUTHOR]

Most cervical cancers are caused by human papillomavirus (HPV) infection. In HeLa cells, the HPV18 viral genome is integrated at chromosome 8q24.21 and activates transcription of the proto‐oncogene c‐Myc. However, the mechanism of how the integrated HPV genome and its transcribed RNAs exhibit transcription activation function has not been fully elucidated. In this study, we found that HPV18 transcripts contain an enhancer RNA‐like function to activate proximal genes including CCAT1‐5L and c‐Myc. We showed that the human genome‐integrated HPV18 genes are activated by transcription coregulators including BRD4 and Mediator. The transcribed HPV18 RNAs form a liquid‐like condensate at chromosome 8q24.21 locus, which in turn accumulates RNA polymerase II. Moreover, we focused on a relatively uncharacterized transcript from the upstream region of CCAT1, named URC. The URC RNA is transcribed as a chimera RNA with HPV18 and is composed of the 3′‐untranslated region of the HPV18 transcript. We experimentally showed that the URC contributes to stabilization of HPV18 RNAs by supplying a polyadenylation site for the HPV18 transcript. Our findings suggest that integrated HPV18 at 8q24.21 locus produces HPV18‐URC chimera RNA and promotes tumorigenesis through RNA‐based condensate formation. [ABSTRACT FROM AUTHOR]

Features of mathematical models of thermodynamic systems, typical formulations of problems on the optimum control of them, and possibilities of using the indicated features in solving these problems were considered. Solutions of the problems on the interaction of two subsystems exchanging scalar and vector flows of any nature in the process of their direct contact or contact through a mediator have been found for any kinetics of these flows. Conditions of minimum dissipation of the energy of a vector flow having a definite average rate were determined. Solutions of the indicated problems define the realizability boundary of a great number of regimes of thermodynamic systems. [ABSTRACT FROM AUTHOR]

This study explores the intricate relationships between perceived value, customer satisfaction, trust, and loyalty in the context of the dynamic online entertainment platform industry. As the entertainment landscape has evolved from traditional formats to digital and interactive experiences, businesses face intense competition and the need to innovate to attract and retain users. This study introduces a comprehensive research model that defines perceived value in three dimensions: utilitarian, hedonic, and social. It also investigates the roles of customer satisfaction and trust as mediators in the connection between perceived value and loyalty. A survey of entertainment platform users reveals that enhancing utilitarian and hedonic values can increase customer satisfaction and that all three perceived value dimensions positively influence trust. Customer satisfaction partially mediates the relationship between utilitarian value and loyalty and fully mediates the relationship between hedonic value and loyalty; however, trust does not act as a mediator in this context. The theoretical implications enhance our understanding of these relationships while the managerial implications provide actionable insights for businesses seeking to refine their customer-focused approaches in the competitive online entertainment landscape. [ABSTRACT FROM AUTHOR]

The article is devoted to the study of organizational and legal forms of mediator activity in the context of their application by business entities for hiring mediators. The author considered two main approaches to conducting mediator activities: 1) for hire, through an entity, that ensures the conduct of mediation, or through an association of mediators; 2) individually, as an individual, that conducts independent professional activities, or as an individual entrepreneur. Taking into account the mentioned approaches, the legal and practical aspects of choosing one or another approach for hiring mediators by business entities were analyzed. It is noted that according to the first approach, the business entity must obtain the status of the entity, that ensures the conduct of mediation. At the same time, this approach, due to the presence of gaps in the legislation, causes discussions about its practical applicability and is also limited by the possibilities of resolving conflicts (disputes) in which the relevant business entity is not a party to the conflict (dispute). Making an analogy with the experience of business entities interacting with «in-house attorneys-at-law», the possibilities of applying the second approach to hiring mediators were considered. In particular, the author analyzes positions from the tax authorities, the Bar Council of Ukraine and the Supreme Court regarding the possibility of an employee who holds a position that does not involve the activity of an attorneyat- law, but at the same time has a certificate of the right to practice the activity of an attorneyat- law, to represent his employer in court as an attorney-at-law. Special attention is given to the accounting of an attorney-at-law as a selfemployed individual, who is also an employee in a position that does not involve the activity of an attorney-at-law. Additionally, problematic issues related to the calculation and payment of a unified social contribution in these legal relationships are highlighted. Based on the analyzed experience, the author draws conclusions about the possibilities of hiring a mediator by a business entity to settle internal conflicts (disputes) in the context of the second approach and also emphasizes the shortcomings of the legal regulation of mediators' performance of their activities for hire, which causes the need for making legislative amendments. [ABSTRACT FROM AUTHOR]

The article analyzes the essence of mediation as one of the alternative ways of resolving disputes. The importance of alternative methods of dispute resolution as an institution of extrajudicial conflict resolution, which is a fairly popular method of protecting violated rights in most countries of the world, is emphasized. The author emphasized the proposition that mediation is not the only alternative way to resolve disputes, this group includes negotiations, arbitration, arbitration courts, independent assessment of facts, conciliation, medical-arb, etc. The actuality of the issue is determined by the fact that this institute is quite new for Ukraine, and is only now becoming widespread. The Law of Ukraine «On Mediation» is quite young, and the relevant legislative provisions are the latest for citizens. Doctrinal definitions of the concept of «mediation» are characterized, both on the example of European and Ukrainian legislation. The stages of mediation are highlighted. Examples of practical application of mediation between parties to a dispute are given. It has been established that mediation is an alternative way of resolving a civil dispute, which is aimed at reaching a mutually acceptable solution based on the mutually agreed will of the parties with the participation of an independent and impartial person (mediator). The use of mediation as a method of dispute resolution has certain advantages. First, saving money; secondly, the decision on the merits of the dispute is made by the parties themselves by mutual agreement; thirdly, saving time, since the preparation and consideration of the case in court is a longer process; fourth, confidentiality; fifth, preservation of partnership relations between the parties. The advantages and disadvantages of this type of alternative dispute resolution are analyzed. It was concluded that in order to spread mediation, it is necessary to create a wide circle of information about this topic, to raise the awareness of citizens about the presented type of alternative method of dispute resolution, to introduce mandatory mediation for certain categories of cases (for example, family, in particular, in the field of private legal relations ), create a single register of mediators, organize special courses (specialization) for judges to develop approaches to resolving disputes, especially in the private law sphere. [ABSTRACT FROM AUTHOR]

Purpose - Due to the dynamic nature of schools, the Department of Education currently faces significant issues including low teaching quality, teacher shortages, absenteeism, poor school climate, lack of well-trained and motivated instructors, and instability. Total Quality Management (TQM) is often linked to the school environment, teacher satisfaction, and performance, playing a crucial role in improving the quality of education. This paper aims to identify how teacher job satisfaction and school climate influence the relationship between TQM and school performance. Methodology - A total of 346 teachers from Pakistan's highperformance schools and low-performance schools, with diverse positions and wage scales, were chosen as participants in this study using stratified random sampling. Data was collected quantitatively using a survey inquiry and SPSS version 24 was utilized to analyze the data and answers the study questions. The mediation procedure was evaluated using the Sobel test. Findings - Findings showed that the TQM variable has the highest mean value (mean=4.87) compared to the other variables tested, namely job satisfaction, school performance and school climate. According to the study's findings, TQM, job satisfaction, and school climate all have a favourable and significant direct influence on school performance. Additionally, school climate and job satisfaction variables were found to be partial mediators linking TQM and school performance. Significance - This study significantly enhances school quality management through a positive environment and capable human resources. The findings are also anticipated to encourage the Pakistan government to establish organizational management and educational leadership training courses to emphasise the significance of TQM and its most efficient use in the education sector. [ABSTRACT FROM AUTHOR]

Herein, an electrochemical biosensor based on carbon nanofibers (CNF) and ferrocene carboxylic acid (FcA) modified glassy carbon electrode (GCE) was fabricated for xanthine determination. Xanthine oxidase (XO) was further immobilized onto the FcA/CNF/GCE for the fabrication of the biosensor. The morphologic appearance of the XO/FcA/CNF/GCE was studied by scanning electron microscopy (SEM) and energy-dispersive X-ray spectroscopy (EDX). Electrochemical impedance spectroscopy (EIS) and cyclic voltammetry (CV) measurements were also performed to determine the electrochemical characteristics of the modified electrode. The XO/FcA/CNF/GCE biosensor exhibited linear response for xanthine in the concentration range of 6.0 × 10–7 to 2.0 × 10–4 M with a sensitivity of 6.04 µAmM−1 and a detection limit of 1.7 × 10–7 M. The xanthine biosensor also exhibited the advantages of high reproducibility, anti-interference ability and good long-term stability. Furthermore, the XO/FcA/CNF/GCE was used for the determination of xanthine in fish meat and the satisfactory results indicated that the FcA/CNF matrix is a promising candidate for electrode modification. [ABSTRACT FROM AUTHOR]

While family functioning is crucial to adolescent developmental outcomes, the mediating role of spirituality in the relationship between family functioning and academic-related outcomes of adolescents has been sparsely explored, particularly in non-Western contexts. To address this gap, based on a short-term longitudinal study, we examined the influence of family functioning on the academic values and academic anxiety of 4,981 Chinese adolescents in Sichuan, China, with spirituality as the mediator. We gathered data from students aged 11 and above at Wave 1 and at six months later (Wave 2). Analysis utilizing structural equation modeling indicated that prior family functioning positively and negatively predicted subsequent academic values and academic anxiety respectively, with spirituality as a significant mediator. Theoretically, this study helps to build up a conceptual model on how family functioning and spirituality of adolescents shape academic values and academic anxiety of adolescents. Practically, the present findings highlight the significance of enhancing family functioning and adolescent spirituality to help adolescents strive for academic success. [ABSTRACT FROM AUTHOR]

Lithium sulfide (Li2S) is a promising electrode material with high specific capacity and can be paired with commercial anode materials such as graphite. However, bulk Li2S requires a high activation energy during the initial charge due to its inert electrochemical activity, resulting in high charge overpotential. Here, lithium phenyl selenide (PhSeLi) is proposed as a mediator that can effectively activate Li2S by altering the oxidation pathway in the initial charge process. It enables Li2S to release normal capacity over the general voltage range (1.5–3 V). The composite cathode with the Li2S:PhSeLi molar ratio of 4:1 exhibits a high reversible capacity of 615.9 mAh g−1 at 0.2 A g−1 after 400 cycles in all‐solid‐state batteries with Li7P3S11 sulfide electrolyte and In–Li anode (the corresponding capacity based on Li2S is 1016.6 mAh g−1). In a full cell with a partially pre‐lithiated silicon anode, it can still provide an average discharge capacity of 524 mAh g−1 at 0.1 A g−1 (the capacity based on Li2S is 844.2 mAh g−1). This work will contribute to the further development of Li2S‐based all‐solid‐state Li–S batteries. [ABSTRACT FROM AUTHOR]

This study was designed to examine the mediating role of social support in relationships from social competence to psychological distress and wellbeing. A cross-sectional survey design was employed. A sample of 276 university students with disabilities was participated in the study from three selected public higher education institutions in Ethiopia. The data were collected through questionnaire. Data were analyzed using IBM® SPSS 23.0® and IBM® Amos 23.0®. Structural Equation Modeling was used to examine the mediating role of social support in the association from social competence to psychological distress and psychological wellbeing. The model provided a good fit to the sample data. The results of the study indicated that social support fully mediated the relationships from social competence to psychological distress and wellbeing among university students with disabilities in Ethiopia. Developing intervention strategies that can enhance and maintain effective social interaction and social support among students with disabilities is a promising and important step for promoting psychological wellbeing of students with disabilities. [ABSTRACT FROM AUTHOR]

Information systems played a key role in keeping pace with the transformations and developments that institutions have known in various fields, forming a new vital space that enabled the production and dissemination of knowledge and changed the concept of the organization that is active in the field of information, and with the increased need for these systems, economic institutions had to attach importance It is well connected with information systems to ensure their optimal management at all levels, especially at the economic level. Thus, information systems have become a space not only to provide and disseminate knowledge, but also allow linking the user with information and documents while giving him independence in dealing with the documentary balance and disposing of it according to what the policy allows. Working to make information and documents available to everyone. [ABSTRACT FROM AUTHOR]

Ferritins are multimeric nanocage proteins that sequester/concentrate excess of free iron and catalytically synthesize a hydrated ferric oxyhydroxide bio-mineral. Besides functioning as the primary intracellular iron storehouses, these supramolecular assemblies also oversee the controlled release of iron to meet physiologic demands. By virtue of the reducing nature of the cytosol, reductive dissolution of ferritin-iron bio-mineral by physiologic reducing agents might be a probable pathway operating in vivo. Herein, to explore this reductive iron-release pathway, a series of quinone analogs differing in size, position/nature of substituents and redox potentials were employed to relay electrons from physiologic reducing agent, NADH, to the ferritin core. Quinones are well known natural electron/proton mediators capable of facilitating both 1/2 electron transfer processes and have been implicated in iron/nutrient acquisition in plants and energy transduction. Our findings on the structure–reactivity of quinone mediators highlight that iron release from ferritin is dictated by electron-relay capability (dependent on E1/2 values) of quinones, their molecular structure (i.e., the presence of iron-chelation sites and the propensity for H-bonding) and the type/amount of reactive oxygen species (ROS) they generate in situ. Juglone/Plumbagin released maximum iron due to their intermediate E1/2 values, presence of iron chelation sites, the ability to inhibit in situ generation of H2O2 and form intramolecular H-bonding (possibly promotes semiquinone formation). This study may strengthen our understanding of the ferritin-iron-release process and their significance in bioenergetics/O2-based cellular metabolism/toxicity while providing insights on microbial/plant iron acquisition and the dynamic host–pathogen interactions. [ABSTRACT FROM AUTHOR]

Maladaptive metacognitive thoughts about sleep often precede incidences of sleep disturbances. While the relationship between sleep disturbances and khat dependence is known, no research has examined the function of metacognition as a potential mediator between khat dependency and sleep problems in polysubstance users. This study used a brief structured questionnaire to measure the sleep problems, the severity of khat dependence (SDS-khat), and a metacognition score on khat-chewing polysubstance users (n = 374, age = 26.95 ± 3.80 years). The association was determined using Baron and Kenny's mediation effect model. The average SDS-khat score was 6.66 ± 1.41, and the metacognition score was 26.40 ± 4.09. Severity of khat dependence showed significant negative correlation with metacognition (b = −.53, standard error (SE) =.15, p <.001), and metacognition showed significant negative correlation with complaints of sleep disturbances, sleep deficit-related daytime problems, and sleep deficit-related socio-occupational disturbances (b = −.17, SE =.03, p <.001), (b = −.19, SE =.03, p <.001), (b = −.12, SE =.05, p <.05) respectively. Polysubstance users with khat dependence and comorbid sleep disturbances were more likely to have poor metacognition. [ABSTRACT FROM AUTHOR]

Background: Adverse childhood experiences (ACEs) are associated with posttraumatic and complex posttraumatic stress disorder symptoms in adulthood (PTSD/cPTSD), as well as reduced epistemic trust (trust in the authenticity and personal relevance of interpersonally transmitted information) and impaired personality functioning. The present work aims to investigate the predictive value of epistemic trust--the capacity for social learning--on the mediating effect of personality functioning in the association of ACEs and PTSD/cPTSD. Methods: We conducted structural equation modeling (SEM) based on representative data of the German population (N = 2,004). Personality functioning (OPD-SQS) was applied as a mediator between ACEs and PTSD/cPTSD (ITQ), while epistemic trust (ETMCQ) was added as predictor for OPD-SQS. TLI, CFI, and RMSEA (95%-CI) determined the models' fit. Results: N = 477 (23.8%) participants reported at least one ACE and n = 218 (10.9%) reported ≥4 ACEs. Fit indices were good for both PTSD (TLI = 0.96; CFI = 0.99; RMSEA = 0.06; 95%CI: 0.041-0.078) and cPTSD (TLI = 0.96; CFI = 0.99; RMSEA = 0.06; 95%CI: 0.043-0.081). ACEs were significantly associated with cPTSD (b = 0.44, p < 0.001) and PTSD (b = 0.29, p < 0.001), explaining 20 and 8% of its variance. Adding personality functioning as a mediator increased the explained variance of cPTSD and PTSD to 47 and 19% while the direct association between ACEs and cPTSD/PTSD decreased (b = 0.21/b = 0.17), thus, indicating a partial mediation. Including epistemic trust substantially increased the explained variance for personality functioning (41%) compared to ACEs as a single predictor (16%). Conclusion: We add to previous research emphasizing the association between ACEs and PTSD/cPTSD symptoms. Offering insights on underlying mechanisms, we show that epistemic trust and personality functioning are relevant mediators. Since both are modifiable by psychotherapy, knowledge about the role of these constructs can inform research on psychotherapeutic interventions and prevention. [ABSTRACT FROM AUTHOR]

Copyright of Environmental & Social Management Journal / Revista de Gestão Social e Ambiental is the property of Environmental & Social Management Journal and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Jurnal Ilmu Ekonomi Terapan is the property of Universitas Airlangga and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

ObjectiveInvestigating the causal connection that exists between inflammatory bowel disease (IBD) and hypertension (HT). To gain a deeper insight into the correlation among IBD, gut microbiota, and HT, we conducted a two-step, two-sample Mendelian randomization study.MethodsAn investigation of genome-wide association study (GWAS) summary-level data was utilized to conduct a two-sample Mendelian randomization (MR) analysis of genetically predicted inflammatory bowel disease: (12,882cases, 21,770controls) on Systolic/Diastolic blood pressure (N = 2,564). Subsequently, two-step MR analyses revealed that the relationship between IBD and SBP was partly mediated by Faecalicatena glycyrrhizinilyticum. The robustness of the findings was confirmed through several sensitivity assessments.ResultsThis MR study showed that increase in genetically predicted IBD was associated with higher risk of genetically predicted SBP (OR: 1.08, 95% CI: 1.01–1.16, P

The members of the evolutionary conserved actin-binding Ezrin, Radixin and Moesin (ERM) protein family are involved in numerous key cellular processes in the cytoplasm. In the last decades, ERM proteins, like actin and other cytoskeletal components, have also been shown to be functional components of the nucleus; however, the molecular mechanism behind their nuclear activities remained unclear. Therefore, our primary aim was to identify the nuclear protein interactome of the single Drosophila ERM protein, Moesin. We demonstrate that Moesin directly interacts with the Mediator complex through direct binding to its Med15 subunit, and the presence of Moesin at the regulatory regions of the Hsp70Ab heat shock gene was found to be Med15-dependent. Both Moesin and Med15 bind to heat shock factor (Hsf), and they are required for proper Hsp gene expression under physiological conditions. Moreover, we confirmed that Moesin, Med15 and Hsf are able to bind the monomeric form of actin and together they form a complex in the nucleus. These results elucidate a mechanism by which ERMs function within the nucleus. Finally, we present the direct interaction of the human orthologues of Drosophila Moesin and Med15, which highlights the evolutionary significance of our finding.

Fungi and laccase mediator systems (LMSs) have a proven track record of oxidizing recalcitrant organic compounds. There has been considerable interest in applying LMSs to the treatment of perfluoroalkyl acids (PFAAs), a class of ubiquitous and persistent environmental contaminants. Some laboratory experiments have indicated modest losses of PFAAs over extended periods, but there have been no clear demonstrations of a transformation mechanism or the kinetics that would be needed for remediation applications. We set out to determine if this was a question of identifying and optimizing a rate-limiting step but discovered that observed losses of PFAAs were experimental artifacts. While unable to replicate the oxidation of PFAAs, we show that interactions of the PFAA compounds with laccase and laccase mediator mixtures could cause an artifact that mimics transformation (≲60%) of PFAAs. Furthermore, we employed a surrogate compound, carbamazepine (CBZ), and electron paramagnetic resonance spectroscopy to probe the formation of the radical species that had been proposed to be responsible for contaminant oxidation. We confirmed that under conditions where sufficient radical concentrations were produced to oxidize CBZ, no PFAA removal took place.

Abstract Three mediators for the laccase mediator system, 3-hydroxyanthranilic acid (3-HAA), 4-hydroxybenzoic acid (HBA), and phenol red (PR) were investigated as mediators in an electrolytic mediator system (EMS) for the degradation of guaiacyl synthetic lignin (G-DHP). All the electron-oxidations of G-DHP with 3-HAA, HBA and PR in the absence of 2,6-lutidine proceeded to give the electrolysis residues in moderate yields. The significant β-β and β-5 linkage loss was found in all the electrolysis residues, especially the residue in the electro-oxidation with PR was significant. The addition of 2,6-lutidine as a base increased the yields of the electrolysis residues and influenced the relative ratio of β-O-4, β-5 and β-β linkages to some extent, that is, increase of β-O-4 linkage loss and decrease of β-β linkages loss (in the electro-oxidation with 3-HAA), increase of β-O-4 linkage loss (in that with 3-HBA), increase of β-5 linkages loss (in that with PR at 0.35 V) and decrease of β-O-4 and β-β linkages loss (in that with PR at 0.70 V). Thus, the base such as 2,6-lutidine was also one of the critical factors for reaction efficiency and reaction selectivity in the EMS. Consequently,3-HAA, HBA, and PR could be used as mediators in EMS for lignin degradation, especially 3-HAA is the most preferable because of the low applied potential.

Abstract Background Chronic headache disorders are disabling. The CHESS trial studied the effects of a short non-pharmacological intervention of education with self-management support for people affected by migraine and/or tension type headache for at least 15 days per month for at least three months. There were no statistically significant effects on the Headache Impact Test-6 (HIT-6) at 12-months. However, we observed improvement in pain self-efficacy questionnaire (PSEQ) and short-term HIT-6. We explored the impact of the CHESS intervention on PSEQ, and subsequently, on the HIT-6 and chronic headache quality of life questionnaire (CH-QLQ) at four, eighth and 12 months. Methods We included all 736 participants from the CHESS trial. We used simple linear regression models to explore the change of HIT-6 and CH-QLQ with treatment and PSEQ at baseline (predictor analysis), and the interaction between treatment and baseline PSEQ (moderator analysis). We considered the change of PSEQ from baseline to four months as a mediator in the mediation analysis. Results Baseline PSEQ neither predicted nor moderated outcomes. The prediction effect on change of HIT-6 from baseline to 12 months was 0.01 (95% CI, -0.03 to 0.04) and the interaction (moderation) effect was −0.07 (95% CI, -0.15 to 0.002). However, the change of PSEQ from baseline to 4-month mediated the HIT-6 (baseline to 8-, and 12-month) and all components of CH-QLQ (baseline to 8-, and 12-month). The CHESS intervention improved the mediated variable, PSEQ, by 2.34 (95% CI, 0.484 to 4.187) units and this corresponds to an increase of 0.21 (95% CI, 0.03 to 0.45) units in HIT-6 at 12-months. The largest mediated effect was observed on the CH-QLQ Emotional Function, an increase of 1.12 (95% CI, 0.22 to 2.20). Conclusions PSEQ was not an effective predictor of outcome. However, change of short-term PSEQ mediated all outcomes, albeit minimally. Future behavioural therapy for chronic headache may need to consider how to achieve larger, and more sustained increases level of self-efficacy than that achieved within the CHESS trial. Trial registration ISRCTN79708100.

Abstract Diminished cognitive and physical functions negatively affect the daily functions of individuals. Although combined cognitive and physical training prevents instrumental activities of daily living (IADL) disability in older adults, no predictive model or mediation analysis of IADL after combined training exists. This study aims to employ prediction and mediation analysis to identify the predictors of IADL performance and to elucidate the mediators of the association between baseline global cognition and subsequent IADL performance following combined cognitive and physical training. This study involved 177 participants aged 60 years and older who underwent combined training. Cognitive function was measured with the Montreal Cognitive Assessment (MoCA), Digit Symbol Substitution Test (DSST), Color Trails Test, Word List, and a dual task; physical function with the Timed Up and Go (TUG) test; daily function with the Lawton IADL Scale. We conducted regression analyses to identify the predictors of IADL performance, and mediation analysis to examine whether DSST and TUG mediate the relationship between MoCA and IADL. The pre-intervention DSST and TUG were significant independent predictors of post-intervention IADL. The association between the pre-intervention MoCA and post-intervention IADL was mediated by pre-intervention DSST and TUG. This study highlighted the importance of measuring and improving processing speed and functional mobility before and during interventions to enhance IADL outcomes. Trial registration: NCT03619577, 23/07/2018; NCT04689776, 29/12/2020.