Environmental concern and eco-entrepreneurial intention: the mediating effects of nature-based solutions and self-efficacy.

Environmental responsibility is crucial in both consumption and production processes. Increasing environmental concerns of societies require eco-innovative and nature-based solutions (NBS) for entrepreneurs. Young people's intentions as potential innovators and entrepreneurs on eco-entrepreneurship with mediating effects have not been investigated, which is a shortcoming in the literature. This study was conducted with 920 respondents from a public university (Düzce University) students to determine the underlying motivations of eco-entrepreneurship intentions using structural equation modeling (SEM) and bootstrap methodology. SEM results show that environmental concerns have a positive direct effect (ß = 0.62) on students' eco-entrepreneurship intention. This study can serve the several sustainable development goals (SDGs) making suggestions for the efficient and effective use of production factors in terms of environmentally responsible behavior. Study results provide data for sustainable business applications and eco-innovative thinking. Study results intend the direction of modern environmental governance, policymakers, and SEM developers.

High-Valence Mn MOF Inspired by Laccase Mediators Enables Versatile Nature-Mimicking Catalysis.

In nature, active Mn3+ -ligand complexes produced by laccase catalyzed oxidation can act as the low-molecular mass, diffusible redox mediators to oxidize the phenolic substrates overcoming the limitations of natural enzymes. Learning from the metal-ligand coordination of natural functional units, high-valence Mn metal-organic framework (Mn MOF) is constructed to simulate the catalysis in natural mediator system. Benefiting from the characteristics of nanoscale size, rich metal coordination unsaturated sites, and mixed valence state dominated by Mn(III), Nano Mn(III)-TP exhibits superior laccase-mimicking activity, whose Vmax (maximal reaction rate) is much higher than that of natural laccase. Referring to natural systems, relevant free radical experiments prove that the material induces the production of active oxygen species with the assistance of carboxylic acid, and active oxygen species further oxidize phenolic substrates. Based on its robust performances, the primary oxidative degradation of an emerging pollutant triclosan (TCS) is creatively applied, an important antiasthmatic medicine terbutaline sulfate (TBT) detection, and the synthesis of non-toxic and black near-natural dyes for dyeing. By simulating the essential mediators of natural enzymatic catalysis, an Mn MOF-based material that demonstrates multiple novel applications is successfully developed, which introduces a new reliable strategy for achieving versatile nature-mimicking catalysis.

Cutting-Edge Progress in Aqueous Zn-S Batteries: Innovations in Cathodes, Electrolytes, and Mediators.

Rechargeable aqueous zinc-sulfur batteries (AZSBs) are emerging as prominent candidates for next-generation energy storage devices owing to their affordability, non-toxicity, environmental friendliness, non-flammability, and use of earth-abundant electrodes and aqueous electrolytes. However, AZSBs currently face challenges in achieving satisfied electrochemical performance due to slow kinetic reactions and limited stability. Therefore, further research and improvement efforts are crucial for advancing AZSBs technology. In this comprehensive review, it is delved into the primary mechanisms governing AZSBs, assess recent advancements in the field, and analyse pivotal modifications made to electrodes and electrolytes to enhance AZSBs performance. This includes the development of novel host materials for sulfur (S) cathodes, which are capable of supporting higher S loading capacities and the refinement of electrolyte compositions to improve ionic conductivity and stability. Moreover, the potential applications of AZSBs across various energy platforms and evaluate their market viability based on recent scholarly contributions is explored. By doing so, this review provides a visionary outlook on future research directions for AZSBs, driving continuous advancements in stable AZSBs technology and deepening the understanding of their charge-discharge dynamics. The insights presented in this review signify a significant step toward a sustainable energy future powered by renewable sources.

High Efficiency Alkaline Iodine Batteries with Multi-Electron Transfer Enabled by Bi/Bi2O3 Redox Mediator.

The multi-electron transfer I-/IO3- redox couple is attractive for high energy aqueous batteries. Shifting from an acidic to an alkaline electrolyte significantly enhances the IO3- formation kinetics due to the spontaneous disproportionation reaction, while the alkaline environment also offers more favorable Zn anode compatibility. However, sluggish kinetics during the reduction of IO3- persists in both acidic and alkaline electrolytes, compromising the energy efficiency of this glorious redox couple. Here, we establish the fundamental redox mechanism of the I-/IO3- couple in alkaline electrolytes for the first time and propose that Bi/Bi2O3 acts as a redox mediator (RM) to "catalyze" the reduction of IO3-. This mediation significantly reduces the voltage gap between charge/discharge from 1.6 V to 1 V with improved conversion efficiency and rate capability. By pairing the Zn anode and the Bi/Bi2O3 RM cathode, the full battery with I-/IO3- redox mechanism achieves high areal capacity of 12 mAh cm-2 and stable operation at 5 mAh cm-2 for over 400 cycles.

Fulvic acid mediated highly efficient heterotrophic nitrification-aerobic denitrification by Paracoccus denitrificans XW11 with reduced C/N ratio.

Reducing the C/N ratio requirements for heterotrophic nitrification-aerobic denitrification (HNAD) is crucial for its practical application; however, it remains underexplored. In this study, a highly efficient HNAD bacterium, Paracoccus denitrificans XW11, was isolated. The HNAD characteristics of XW11 were studied, and the redox mediator fulvic acid (FA) was used to reduce the C/N requirements. Whole-genome sequencing revealed multiple denitrification genes in XW11; however, nitrification genes were not identified, because heterotrophic nitrification-related gene sequences were not included in the database. However, the nitrogen removal related enzyme activity test revealed complete nitrification and denitrification pathways. Reverse transcription PCR showed that the membrane-bound nitrate reductase (NarG), rather than the periplasmic nitrate reductase, was responsible for aerobic denitrification. The conventional nitrite reductase (NirS) also does not mediate nitrite denitrification. When the C/N ratio was 10, the ammonia removal efficiency of the Control was 71.71 % and the addition of FA increased it to 86.12 %. Transcriptomic analysis indicated electron flow from the carbon source to FA without proton transmembrane transport, and the presence of FA constructs another electron transfer system. The redox potential of oxidized FA/reduced FA is 0.3679 V, avoiding competition for electrons from Complex III. Thus, ammonia monooxygenase obtains electrons more easily, thereby promoting nitrification. The enzyme activity test of the nitrification process confirmed this view. In addition, NarG expression increased, and the denitrification process was enhanced. Overall, FA improved HNAD efficiency by facilitating electron transfer to the nitrogen dissimilation process, offering a novel approach to reduce the C/N requirement of HNAD.

Induction of long-term hyperexcitability by memory-related cAMP signaling in isolated nociceptor cell bodies.

Persistent hyperactivity of nociceptors is known to contribute significantly to long-lasting sensitization and ongoing pain in many clinical conditions. It is often assumed that nociceptor hyperactivity is mainly driven by continuing stimulation from inflammatory mediators. We have tested an additional possibility: that persistent increases in excitability promoting hyperactivity can be induced by a prototypical cellular signaling pathway long known to induce late-phase long-term potentiation (LTP) of synapses in brain regions involved in memory formation. This cAMP-PKA-CREB-gene transcription-protein synthesis pathway was tested using whole-cell current clamp methods on small dissociated sensory neurons (primarily nociceptors) from dorsal root ganglia (DRGs) excised from previously uninjured ("naïve") male rats. Six-hour treatment with the specific Gαs-coupled 5-HT4 receptor agonist, prucalopride, or with the adenylyl cyclase activator forskolin induced long-term hyperexcitability (LTH) in DRG neurons that manifested 12-24 h later as action potential (AP) discharge (ongoing activity, OA) during artificial depolarization to -45 mV, a membrane potential that is normally subthreshold for AP generation. Prucalopride treatment also induced significant long-lasting depolarization of resting membrane potential (from -69 to -66 mV), enhanced depolarizing spontaneous fluctuations (DSFs) of membrane potential, and produced trends for reduced AP threshold and rheobase. LTH was prevented by co-treatment of prucalopride with inhibitors of PKA, CREB, gene transcription, or protein synthesis. As in the induction of synaptic memory, many other cellular signals are likely to be involved. However, the discovery that this prototypical memory induction pathway can induce nociceptor LTH, along with reports that cAMP signaling and CREB activity in DRGs can induce hyperalgesic priming, suggest that early, temporary, cAMP-induced transcriptional and translational mechanisms can induce nociceptor LTH that might last for long periods. The present results also raise the question of whether reactivation of primed signaling mechanisms by re-exposure to inflammatory mediators linked to cAMP synthesis during subsequent challenges to bodily integrity can "reconsolidate" nociceptor memory, extending the duration of persistent hyperexcitability.

Arabidopsis MORC1 and MED9 Interact to Regulate Defense Gene Expression and Plant Fitness.

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, postinfection, 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.

Community voices in health literacy: a qualitative exploration into perceptions of a health literacy mediator.

Health literacy is a vital asset needed to empower individuals to take control of their health. An individual's health literacy is the ability to find, use and apply health information and services to manage their health. They interact with the health services and members of their community who can offer additional support. Creating the role of a health literacy mediator (HLM) may help to improve health literacy outcomes for all. For this role to be accepted by individuals within a community, the community itself should be involved in the development of the roles and associated responsibilities. The aim of this study was to engage with community members to acquire their perspectives on the potential of this role. Qualitative semi-structured online interviews were used to engage in discussions with local community members. This study implemented a constructivist epistemology with qualitative research design. Data were thematically analysed to identify evolving themes that were important to the HLM role. The analysis identified three main themes that need to be considered when adopting an HLM role: (i) health empowerment of individuals, organizations and communities, (ii) meeting the needs of the community and (iii) addressing the existing barriers in navigating and accessing the healthcare system. Those working in the health promotion space must adopt novel and innovative ways to improve HL on both a local and an international scale. This study concluded that for the role of a HLM to be accepted, it would need to encompass these attributes.

Amino Acid-Based Protein-Mimic Hydrogel Incorporating Pro-Regenerative Lipid Mediator and Microvascular Fragments Promotes the Healing of Deep Burn Wounds.

Pro-regenerative lipid mediator 1 (PreM1) is a specialized pro-resolving lipid mediator that promotes wound healing and regenerative functions of mesenchymal stem cells (MSCs), endothelial cells, and macrophages. The healing of third-degree (3°) burns and regenerative functions of MSCs are enhanced by ACgel1, an arginine-and-chitosan-based protein-mimic hybrid hydrogel. Adipose-tissue derived microvascular fragments (MVFs) are native vascularization units and a rich source of MSCs, endothelial cells, and perivascular cells for tissue regeneration. Here we describe an innovative PreM1-MVFs-ACgel1 construct that incorporated PreM1 and MVFs into ACgel1 via optimal design and fabrication. This construct delivered PreM1 to 3°-burn wounds at least up to 7 days-post-burn (dpb), and scaffolded and delivered MVFs. PreM1-MVFs-ACgel1 promoted the healing of 3°-burns in mice, including vascularization and collagen formation. The re-epithelization and closure of 3° burn wounds were promoted by ACgel1, MVFs, PreM1, MVFs-ACgel1, PreM1-ACgel1, or PreM1-MVFs-ACgel1 at certain time-point(s), while PreM1-MVFs-ACgel1 was most effective with 97% closure and 4.69% relative epithelial gap at 13 dpb compared to saline control. The PreM1-ACgel1 and MVFs-ACgel1 also promoted blood vessel regeneration of 3°-burns although PreM1-MVFs-ACgel1 is significantly more effective. These PreM1- and/or MVF-functionalized ACgel1 have nonexistent or minimal graft-donor requirements and are promising adjuvant therapeutic candidates for treating deep burns.

Moesin contributes to heat shock gene response through direct binding to the Med15 subunit of the Mediator complex in the nucleus.

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.

Inspiring nurses' sustainability mindset: Exploring the Mediating Role of Organizational Culture on the relationship between Pro-social Leader behaviors and nurses' sustainability consciousness.

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.

Relationship between illness perception and self-management behaviors among women with gestational diabetes mellitus in China during the COVID-19 pandemic: A mediating role of depression.

OBJECTIVE: 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. METHODS: 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. RESULTS: 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, ß = -0.045), accounting for 26.6% of the total effect. CONCLUSION: 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.

A Novel Ferrocene-Linked Thionine as a Dual Redox Mediator for the Electrochemical Detection of Dopamine and Hydrogen Peroxide.

We introduce a novel dual redox mediator synthesized by covalently linking ferrocene dicarboxylic acid (FcDA) and thionine (TH) onto a pre-treated glassy carbon electrode. This unique structure significantly enhances the electro-oxidation of dopamine (DA) and the reduction of hydrogen peroxide (H2O2), offering a sensitive detection method for both analytes. The electrode exhibits exceptional sensitivity, selectivity, and stability, demonstrating potential for practical applications in biosensing. It facilitates rapid electron transfer between the analyte and the electrode surface, detecting H2O2 concentrations ranging from 1.5 to 60 µM with a limit of detection (LoD) of 0.49 µM and DA concentrations from 0.3 to 230 µM with an LoD of 0.07 µM. The electrode's performance was validated through real-sample analyses, yielding satisfactory results.

Effects of Temperature and Time on the Denaturation of Transforming Growth Factor Beta-1 and Cytokines from Bovine Platelet-Rich Gel Supernatants.

There is a lack of information about transforming growth factor beta-1 (TGF-ß1) and cytokines contained in pure platelet-rich plasma (P-PRP) and release from pure-platelet-rich gel supernatants (P-PRGS) might be affected by the temperature and time factors; P-PRP from 6 heifers was activated with calcium gluconate. Thereafter, P-PRG and their supernatants (P-PRGS) were maintained at -80, -20, 4, 21, and 37 °C and collected at 3, 6, 12, 24, 48, 96, 144, 192, 240, and 280 h for subsequent determination of TGF-ß1, tumor necrosis factor alfa (TNF-α), interleukin (IL)-2, and IL-6; TGF-ß1 concentrations were significantly (p < 0.05) higher in PRGS maintained at 21 and 37 °C when compared to PRGS maintained at 4, -20, and -80 °C; PRGS TNF-α concentrations were not influenced by temperature and time factors. However, PRGS maintained at 4 °C showed significantly (p < 0.05) higher concentrations when compared to PRGS maintained at -20, and -80 °C at 144, and 192 h. IL-6 concentrations were significantly (p < 0.05) higher in PRGS stored at -20, and -80 over the first 48 h and at 10 days when compared to PRGS stored at 4, 21, and 37 °C. These results could suggest that P-PRP/P-PRGS could be maintained and well preserved for at least 12 days at room temperature for clinical use in bovine therapeutic massive protocols.

Mediator complex subunit 1 promotes oral squamous cell carcinoma progression by activating MMP9 transcription and suppressing CD8+ T cell antitumor immunity.

BACKGROUND: The role of Mediator complex subunit 1 (MED1), a pivotal transcriptional coactivator implicated in diverse biological pathways, remains unexplored in the context of oral squamous cell carcinoma (OSCC). This study aims to elucidate the contributory mechanisms and potential impact of MED1 on the progression of OSCC. METHODS: The expression and clinical significance of MED1 in OSCC tissues were evaluated through the bioinformatics analyses. The effects of MED1 on the biological behavior of OSCC cancer cells were assessed both in vitro and in vivo. Dual-luciferase reporter assay, chromatin immunoprecipitation (ChIP) assay, bioinformatic analysis, CD8+ T cell isolation experiment, coculture experiment, enzyme-linked immunosorbent assay (ELISA), and flow cytometric analysis were employed to elucidate the underlying mechanism through which MED1 operates in the progression of OSCC. RESULTS: MED1 exhibited upregulation in both OSCC tissues and multiple OSCC cell lines, which correlated with decreased overall survival in patients. In vitro experiments demonstrated that knockdown of MED1 in metastatic OSCC cell lines SCC-9 and UPCI-SCC-154 hindered cell migration and invasion, while overexpression of MED1 promoted these processes. Whereas, MED1 knockdown had no impact on proliferation of cell lines mentioned above. In vivo studies further revealed that downregulation of MED1 effectively suppressed distant metastasis in OSCC. Mechanistically, MED1 enhanced the binding of transcription factors c-Jun and c-Fos to the matrix metalloprotein 9 (MMP9) promoters, resulting in a significant upregulation of MMP9 transcription. This process contributes to the migration and invasion of SCC-9 and UPCI-SCC-154 cells. Furthermore, MED1 modulated the expression of programmed death-ligand 1 (PD-L1) through the Notch signaling pathway, consequently impacting the tumor-killing capacity of CD8+ T cells in the tumor microenvironment. CONCLUSIONS: Our findings indicate that MED1 plays a pivotal role in OSCC progression through the activation of MMP9 transcription and suppression of CD8+ T cell antitumor immunity, suggesting that MED1 may serve as a novel prognostic marker and therapeutic target in OSCC.

Enhancing the nitrogen removal of anammox sludge by setting up novel redox mediators-mediated anammox process.

Anaerobic ammonium oxidizing (anammox) bacteria have been proven weak-electroactive. However, the impact of exogenous anthraquinone-2,6-disulfonate (AQDS) on the anammox activity, although it usually plays essential roles in the life activities of many other electroactive microorganisms, is still unknown. Therefore, this study further explored the influences of AQDS on the anammox activity and the interaction mechanism with anammox bacteria, as well as the behaviors of NH4+, NO2-, and NO3-. The results showed that exogenous AQDS increased the ammonium and total nitrogen removal rates by 12.8% and 10.7%, respectively. Interestingly, the conversion from NO2- to NO3- was significantly reduced after adding AQDS, resulting in a 40.1% reduction in NO3- production of anammox process. In this study, we found for the first time that anammox bacteria could not only carry out the conventional anammox process but also perform a weak redox mediator-mediated anammox process, which could achieve the 1:1 consumption of NH4+ and NO2-. The redox mediator-mediated anammox process was related to an endogenous redox mediator (ERM) synthesized and secreted by anammox bacteria, whose redox midpoint potential was around -0.26 V (vs. Ag/AgCl). After adding AQDS, not only the ERM-mediated anammox process was enhanced, but also two novel redox mediator-mediated anammox processes were introduced, including the AQDS-mediated anammox process and ERM-AQDS-mediated anammox process. These three redox mediator-mediated anammox processes significantly improved the nitrogen removal performance of anammox bacteria and reduced energy consumption. These findings will help reduce the dependence of anammox technology on NO2-, reduce the cost of subsequent treatment of NO3-, and provide new visions for optimizing and applying anammox technology.

Uterine prostaglandin DP receptor-induced upon implantation contributes to decidualization together with EP4 receptor.

To investigate the yet-unknown roles of prostaglandins (PGs) in the uterus, we analyzed the expression of various PG receptors in the uterus. We found that three types of Gs-coupled PG receptors, DP, EP2, and EP4, were expressed in luminal epithelial cells from the peri-implantation period to late pregnancy. DP expression was also induced in stromal cells within the mesometrial region, whereas EP4 was expressed in stromal cells within the anti-mesometrial region during the peri-implantation period. The timing of DP induction after embryo attachment correlated well with that of cyclooxygenase-2 (COX-2); however, COX-2-expressing stromal cells were located in the vicinity of the embryo, whereas DP-expressing stromal cells surrounded these cells on the mesometrial side. Specific [3H]PGD2-binding activity was detected in the decidua of uteri, with PGD2 synthesis comparable to that of PGE2 detected in the uteri during the peri-implantation period. Administration of the COX-2-specific inhibitor celecoxib caused adverse effects on decidualization, as demonstrated by the attenuated weight of the implantation sites, which was recovered by the simultaneous administration of a DP agonist. Such a rescuing effect of the DP agonist was mimicked by an EP4 agonist, but not an EP2 agonist. While the importance of DP signaling was shown pharmacologically, DP/EP2 double deficiency did not affect implantation and decidualization, suggesting the contribution of EP4 to these processes. Indeed, administration of an EP4 antagonist substantially affected decidualization in DP/EP2-deficient mice. These results suggest that COX-2-derived PGD2 and PGE2 contribute to decidualization via a coordinated pathway of DP and EP4 receptors.

Relationships between mental toughness, eustress-distress, and mindfulness in adolescents: A network analysis and mediator model testing.

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.

Structural basis of the human transcriptional Mediator regulated by its dissociable kinase module.

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.

Identifying the plasma metabolome responsible for mediating immune cell action in severe COVID-19: a Mendelian randomization investigation.

Introduction: The immune response regulates the severity of COVID-19 (sCOVID-19). This study examined the cause-and-effect relationship between immune cell traits (ICTs) and the risk of severe COVID-19. Additionally, we discovered the potential role of plasma metabolome in modulating this risk. Methods: Employing data from a genome-wide association study (GWAS), we conducted a two-sample Mendelian randomization (MR) assessment of 731 genetic ICTs and sCOVID-19 (5,101 cases, 1,383,241 controls) incidence. The MR analysis was utilized to further quantitate the degree of plasma metabolome-mediated regulation of immune traits in sCOVID-19. Results: The inverse variance weighted method recognized 2 plasma metabolites (PMs) responsible for casual associations between immune cells and sCOVID-19 risk. These included Tridecenedioate (C13:1-DC) which regulated the association between CD27 on IgD- CD38br (OR 0.804, 95% CI 0.699-0.925, p = 0.002) and sCOVID-19 risk (mediated proportion: 18.7%); arginine to citrulline ratio which controlled the relationship of CD39 on monocyte (OR 1.053, 95% CI 1.013-1.094, p = 0.009) with sCOVID-19 risk (mediated proportion: -7.11%). No strong evidence that genetically predicted sCOVID-19 influenced the aforementioned immune traits. Conclusion: In this study, we have successfully identified a cause-and-effect relationship between certain ICTs, PMs, and the likelihood of contracting severe COVID-19. Our findings can potentially improve the accuracy of COVID-19 prognostic evaluation and provide valuable insights into the underlying mechanisms of the disease.