Systems biology of electrogenic Pseudomonas putida - multi-omics insights and metabolic engineering for enhanced 2-ketogluconate production.

BACKGROUND: Pseudomonas putida KT2440 has emerged as a promising host for industrial bioproduction. However, its strictly aerobic nature limits the scope of applications. Remarkably, this microbe exhibits high bioconversion efficiency when cultured in an anoxic bio-electrochemical system (BES), where the anode serves as the terminal electron acceptor instead of oxygen. This environment facilitates the synthesis of commercially attractive chemicals, including 2-ketogluconate (2KG). To better understand this interesting electrogenic phenotype, we studied the BES-cultured strain on a systems level through multi-omics analysis. Inspired by our findings, we constructed novel mutants aimed at improving 2KG production. RESULTS: When incubated on glucose, P. putida KT2440 did not grow but produced significant amounts of 2KG, along with minor amounts of gluconate, acetate, pyruvate, succinate, and lactate. 13C tracer studies demonstrated that these products are partially derived from biomass carbon, involving proteins and lipids. Over time, the cells exhibited global changes on both the transcriptomic and proteomic levels, including the shutdown of translation and cell motility, likely to conserve energy. These adaptations enabled the cells to maintain significant metabolic activity for several weeks. Acetate formation was shown to contribute to energy supply. Mutants deficient in acetate production demonstrated superior 2KG production in terms of titer, yield, and productivity. The ∆aldBI ∆aldBII double deletion mutant performed best, accumulating 2KG at twice the rate of the wild type and with an increased yield (0.96 mol/mol). CONCLUSIONS: By integrating transcriptomic, proteomic, and metabolomic analyses, this work provides the first systems biology insight into the electrogenic phenotype of P. putida KT2440. Adaptation to anoxic-electrogenic conditions involved coordinated changes in energy metabolism, enabling cells to sustain metabolic activity for extended periods. The metabolically engineered mutants are promising for enhanced 2KG production under these conditions. The attenuation of acetate synthesis represents the first systems biology-informed metabolic engineering strategy for enhanced 2KG production in P. putida. This non-growth anoxic-electrogenic mode expands our understanding of the interplay between growth, glucose phosphorylation, and glucose oxidation into gluconate and 2KG in P. putida.

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.

MED12 and CDK8/19 modulate androgen receptor activity and enzalutamide response in prostate cancer.

Prostate cancer progression is driven by androgen receptor (AR) activity, which is a target for therapeutic approaches. Enzalutamide is an AR inhibitor that prolongs the survival of patients with advanced prostate cancer. However, resistance mechanisms arise and impair its efficacy. One of these mechanisms is the expression of AR-V7, a constitutively active AR splice variant. The Mediator complex is a multi-subunit protein that modulates gene expression on a genome-wide scale. MED12 and cyclin-dependent kinase 8 (CDK8), or its paralog CDK19, are components of the kinase module that regulates the proliferation of prostate cancer cells. In this study, we investigated how MED12 and CDK8/19 influence cancer-driven processes in prostate cancer cell lines, focusing on AR activity and the enzalutamide response. We inhibited MED12 expression and CDK8/19 activity in LNCaP (AR+, enzalutamide-sensitive), 22Rv1 (AR-V7+, enzalutamide-resistant), and PC3 (AR-, enzalutamide-insensitive) cells. Both MED12 and CDK8/19 inhibition reduced cell proliferation in all cell lines, and MED12 inhibition reduced proliferation in the respective 3D spheroids. MED12 knockdown significantly inhibited c-Myc protein expression and signaling pathways. In 22Rv1 cells, it consistently inhibited the AR response, prostate-specific antigen (PSA) secretion, AR target genes, and AR-V7 expression. Combined with enzalutamide, MED12 inhibition additively decreased the AR activity in both LNCaP and 22Rv1 cells. CDK8/19 inhibition significantly decreased PSA secretion in LNCaP and 22Rv1 cells and, when combined with enzalutamide, additively reduced proliferation in 22Rv1 cells. Our study revealed that MED12 and CDK8/19 regulate AR activity and that their inhibition may modulate response to enzalutamide in prostate cancer.

Bridging the Knowledge Gap: Utilization of Mediator Subunits for Crop Improvement.

The Mediator complex is a multisubunit transcription coregulator that transfers regulatory signals from different transcription factors to RNA polymerase II (Pol II) to control Pol II-dependent transcription in eukaryotes. Studies on Arabidopsis Mediator subunits have revealed their unique or overlapping functions in various aspects of plant growth, stress adaptation and metabolite homeostasis. Therefore, the utilization of the plant Mediator complex for crop improvement has been of great interest. Advances in genome editing and sequencing techniques have expedited the characterization of Mediator subunits in economically important crops such as tomato, rice, wheat, soybean, sugarcane, pea, chickpea, rapeseed and hop. In this review, we summarize recent progress in understanding the molecular mechanisms of how the Mediator complex regulates crop growth, development and adaptation to environmental stress. We also discuss the conserved and diverse functions of the Mediator complex in different plant species. In addition, we propose several future research directions to deepen our understanding of the important roles of Mediator subunits and their interacting proteins, which would provide promising targets for genetic modification to develop new cultivars with desirable agronomic traits.

Uncoupling the CRMP2-CaV2.2 interaction reduces pain-like behavior in a preclinical joint-pain model.

Osteoarthritis (OA) represents a significant pain challenge globally, as current treatments are limited and come with substantial and adverse side effects. Voltage-gated calcium channels have proved to be pharmacologically effective targets, with multiple FDA-approved CaV2.2 modulators available for the treatment of pain. Although effective, drugs targeting CaV2.2 are complicated by the same obstacles facing other pain therapeutics- invasive routes of administration, narrow therapeutic windows, side effects, and addiction potential. We have identified a key regulator of CaV2.2 channels, collapsing response mediator protein 2 (CRMP2), that allows us to indirectly regulate CaV2.2 expression and function. We previously developed a peptidomimetic modulator of CRMP2, CBD3063, that effectively reverses neuropathic and inflammatory pain without negative side effects by reducing membrane expression of CaV2.2. The potent analgesic properties of CBD3063 combined with the lack of negative side effects prompted us to assess the efficacy of CBD3063 in a rodent model of OA pain. Here, we demonstrate the intraperitoneal administration of CBD3063 alleviates both evoked and non-evoked behavioral hallmarks of OA pain. Further, we reveal that CBD3063 reduces OA-induced increased neural activity in the parabrachial nucleus, a key supraspinal site modulating the pain experience. Together, these studies suggest CBD3063 is an effective analgesic for OA pain. PERSPECTIVE: Despite the high prevalence of osteoarthritis pain worldwide, current treatment options remain limited. We demonstrate that CBD3063-mediated disruption of the CaV2.2-CRMP2 interaction alleviates pain in a preclinical joint pain model, providing a promising basis for the development of new osteoarthritis pain treatments.

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. Whereas 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.

ERFVII-controlled hypoxia responses are in part facilitated by MEDIATOR SUBUNIT 25 in Arabidopsis thaliana.

Flooding impairs plant growth through oxygen deprivation, which activates plant survival and acclimation responses. Transcriptional responses to low oxygen are generally associated with the activation of group VII ETHYLENE-RESPONSE FACTOR (ERFVII) transcription factors. However, the exact mechanisms and molecular components by which ERFVII factors initiate gene expression are not fully elucidated. Here, we show that the ERFVII factors RELATED TO APETALA 2.2 (RAP2.2) and RAP2.12 cooperate with the Mediator complex subunit AtMED25 to coordinate gene expression under hypoxia in Arabidopsis thaliana. Respective med25 knock-out mutants display reduced low-oxygen stress tolerance. AtMED25 physically associates with a distinct set of hypoxia core genes and its loss partially impairs transcription under hypoxia due to decreased RNA polymerase II recruitment. Association of AtMED25 with target genes requires the presence of ERFVII transcription factors. Next to ERFVII protein stabilisation, also the composition of the Mediator complex including AtMED25 is potentially affected by hypoxia stress as shown by protein-complex pulldown assays. The dynamic response of the Mediator complex to hypoxia is furthermore supported by the fact that two subunits, AtMED8 and AtMED16, are not involved in the establishment of hypoxia tolerance, whilst both act in coordination with AtMED25 under other environmental conditions. We furthermore show that AtMED25 function under hypoxia is independent of ethylene signalling. Finally, functional conservation at the molecular level was found for the MED25-ERFVII module between A. thaliana and the monocot species Oryza sativa, pointing to a potentially universal role of MED25 in coordinating ERFVII-dependent transcript responses to hypoxia in plants.

Covalent Immobilization of Mediators on Photoelectrodes for NADH Regeneration.

The reduced nicotinamide adenine dinucleotide (NADH) is a vital biomolecule involved in many biocatalytic processes, and the high cost makes it significant to regenerate NADH in vitro. The photoelectrochemical approach is a promising and environmentally friendly method for sustainable NADH regeneration. However, the free Rh-based mediator ([Cp*Rh (bpy)H2O]2+) in the electrolyte suffers from low efficiency due to the sluggish charge transfer controlled by the diffusion process. Herein, we report an efficient and facile covalent bonding of the Rh-based mediator with the Si-based photocathode for NADH regeneration. The bipyridine-containing covalent organic framework (BpyCOF) layer ensures the even distribution of mediators throughout the surface of the photoelectrode. The graphene interlayer provides a pathway for charge transport and prevents silicon from corrosion. Furthermore, during the synthesis of BpyCOF, it functions as a substrate to promote the growth of the oriented BpyCOF film. The imitated contact between the components of the photocathode favors the charge transfer to the surface to participate in a chemical reaction, thus improving the catalytic performance and the NADH regeneration efficiency, which is four times higher than the reported photocathode modified by the Rh-based mediator. This study offers a new strategy for the construction of photoelectrochemical solar energy conversion devices.

Correlations among nicotine dependence, health-related quality of life, and depression in current smokers: a cross-sectional study with a mediation model.

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.

Rescue of dead MnO2 for stable electrolytic Zn-Mn redox-flow battery: a metric of mediated and catalytic kinetics.

The virtues of electrolytic MnO2 aqueous batteries are high theoretical energy density, affordability and safety. However, the continuous dead MnO2 and unstable Mn2+/MnO2 electrolysis pose challenges to the practical output energy and lifespan. Herein, we demonstrate bifunctional cationic redox mediation and catalysis kinetics metrics to rescue dead MnO2 and construct a stable and fast electrolytic Zn-Mn redox-flow battery (eZMRFB). Spectroscopic characterizations and electrochemical evaluation reveal the superior mediation kinetics of a cationic Fe2+ redox mediator compared with the anionic ones (e.g. I- and Br-), thus eliminating dead MnO2 effectively. With intensified oxygen vacancies, density functional theory simulations of the reaction pathways further verify the concomitant Fe-catalysed Mn2+/MnO2 electrolysis kinetics via charge delocalization and activated O 2p electron states, boosting its rate capability. As a result, the elaborated eZMRFB achieves a coulombic efficiency of nearly 100%, ultra-high areal capacity of 80 mAh cm-2, rate capability of 20 C and a long lifespan of 2500 cycles. This work may advance high-energy aqueous batteries to next-generation scalable energy storage.

Mendelian randomization of plasma lipidome, inflammatory proteome and heart failure.

AIMS: Heart failure (HF) is a global health issue, with lipid metabolism and inflammation critically implicated in its progression. This study harnesses cutting-edge, expanded genetic information for lipid and inflammatory protein profiles, employing Mendelian randomization (MR) to uncover genetic risk factors for HF. METHODS: We assessed genetic susceptibility to HF across 179 lipidomes and 91 inflammatory proteins using instrumental variables (IVs) from recent genome-wide association studies (GWASs) and proteome-wide quantitative trait loci (pQTL) studies. GWASs involving 47 309 HF cases and 930 014 controls were obtained from the Heart Failure Molecular Epidemiology for Therapeutic Targets (HERMES) Consortium. Data on 179 lipids from 7174 individuals in a Finnish cohort and 91 inflammatory proteins from a European pQTL study involving 14 824 individuals are available in the HGRI-EBI catalogue. A two-sample MR approach evaluated the associations, and a two-step mediation analysis explored the mediation role of inflammatory proteins in the lipid-HF pathway. Sensitivity analyses, including MR-RAPS (robust adjusted profile score) and MR-Egger, ensured result robustness. RESULTS: Genetic IVs for 162 lipids and 74 inflammatory proteins were successfully identified. MR analysis revealed a genetic association between HF and 31 lipids. Among them, 18 lipids, including sterol ester (27:1/18:0), cholesterol, 9 phosphatidylcholines, phosphatidylinositol (16:0_20:4) and 6 triacylglycerols, were identified as HF risk factors [odds ratio (OR) = 1.037-1.368]. Cholesterol exhibited the most significant association with elevated HF risk [OR = 1.368, 95% confidence interval (CI) = 1.044-1.794, P = 0.023]. In the inflammatory proteome, leukaemia inhibitory factor receptor (OR = 0.841, 95% CI = 0.789-0.897, P = 1.08E-07), fibroblast growth factor 19 (OR = 0.905, 95% CI = 0.830-0.988, P = 0.025) and urokinase-type plasminogen activator (OR = 0.938, 95% CI = 0.886-0.994, P = 0.030) were causally negatively correlated with HF, whereas interleukin-20 receptor subunit alpha (OR = 1.333, 95% CI = 1.094-1.625, P = 0.004) was causally positively correlated with HF. Mediation analysis revealed leukaemia inhibitory factor receptor (mediation proportion: 23.5%-25.2%) and urokinase-type plasminogen activator (mediation proportion: 9.5%-10.7%) as intermediaries in the lipid-inflammation-HF pathway. No evidence of directional horizontal pleiotropy was observed (P > 0.05). CONCLUSIONS: This study identifies a genetic connection between certain lipids, particularly cholesterol, and HF, highlighting inflammatory proteins that influence HF risk and mediate this relationship, suggesting new therapeutic targets and insights into genetic drivers in HF.

Role of microbial laccases in valorization of lignocellulosic biomass to bioethanol.

The persistent expansion in world energy and synthetic compounds requires the improvement of renewable alternatives in contrast to non-sustainable energy wellsprings. Lignocellulose is an encouraging feedstock to be utilized in biorefineries for its conversion into value-added products, including biomaterials, biofuels and several bio-based synthetic compounds. Aside from all categories, biofuel, particularly bioethanol is the most substantial fuel derived from lignocellulosic biomass and can be obtained through microbial fermentation. Generally, extreme settings are required for lignocellulosic pretreatment which results in the formation of inhibitors during biomassdegradation. Occasionally, lignin polymers also act as inhibitors and are left untreated during the pretreatment, engendering inefficient hydrolysis. The valorization of lignocellulosic biomass by laccases can be viewed as a fundamental trend for improving bioethanol production. However, one of the main obstacles for developing commercially viable biofuel industries is the cost of enzymes, which can be resolved by utilizing laccases derived from microbial sources. Microbial laccases have been considered an exceptionally integral asset for delignification and detoxification of pretreated LCB, which amplify the resultant fermentation and saccharification processes. This review provides a summary of microbial laccases and their role in valorizing LCB to bioethanol, compelling enthralling applications in bio-refining industries all across the globe.

Effects of humic electron mediators on reductive dechlorination of polychlorinated biphenyl by consortia enriched from terrestrial and marine environments.

Humic electron mediators can facilitate the reductive dehalogenation of organohalogenated compounds by accelerating electron transfer. To investigate the effect of humic electron mediators on the microbial anaerobic reductive dechlorination of Polychlorinated biphenyls (PCBs), three types of humic electron mediators, humin (HM), humic acid (HA), and anthraquinone-2,6-disulfonic acid (AQDS, HA analogs), were added to PCB dechlorination cultures enriched from different sources in terrestrial and marine environments (T and M cultures). The results showed that meta- and para-site dechlorination occurred in the M culture, while only meta-site dechlorination occurred in the T culture. The dechlorination process N and the dechlorination process H or H' are presented in both cultures. HM enhanced PCB dechlorination metabolic activity in both cultures mainly by promoting meta-site dechlorination. HA showed a weak promoting effect on the M culture by promoting para-chlorine removal but inhibited the dechlorination metabolism of the terrestrial-origin culture, inhibiting meta-chlorine removal. AQDS showed inhibitory effects on both cultures by inhibiting the microbial removal of meta-chlorine. High-throughput sequencing and qPCR results suggest that HM is not a carbon source for the potential dechlorinating metabolism of Dehalococcoides but may promote reductive dechlorination by changing the community structure, and AQDS may inhibit anaerobic reductive dechlorination of PCBs by inhibiting the growth of Dehalococcoides. This study provides insights into the mechanism of enhancing PCB microbial dechlorination mediated by humic substances and plays a significant role in extending the application prospects of PCBs bioremediation technology.

The SEMA3F-NRP1/NRP2 axis is a key factor in the acquisition of invasive traits in in situ breast ductal carcinoma.

BACKGROUND: A better understanding of ductal carcinoma in situ (DCIS) is urgently needed to identify these preinvasive lesions as distinct clinical entities. Semaphorin 3F (SEMA3F) is a soluble axonal guidance molecule, and its coreceptors Neuropilin 1 (NRP1) and NRP2 are strongly expressed in invasive epithelial BC cells. METHODS: We utilized two cell line models to represent the progression from a healthy state to the mild-aggressive or ductal carcinoma in situ (DCIS) stage and, ultimately, to invasive cell lines. Additionally, we employed in vivo models and conducted analyses on patient databases to ensure the translational relevance of our results. RESULTS: We revealed SEMA3F as a promoter of invasion during the DCIS-to-invasive ductal carcinoma transition in breast cancer (BC) through the action of NRP1 and NRP2. In epithelial cells, SEMA3F activates epithelialmesenchymal transition, whereas it promotes extracellular matrix degradation and basal membrane and myoepithelial cell layer breakdown. CONCLUSIONS: Together with our patient database data, these proof-of-concept results reveal new SEMA3F-mediated mechanisms occurring in the most common preinvasive BC lesion, DCIS, and represent potent and direct activation of its transition to invasion. Moreover, and of clinical and therapeutic relevance, the effects of SEMA3F can be blocked directly through its coreceptors, thus preventing invasion and keeping DCIS lesions in the preinvasive state.

Suicidal ideation in Chinese adolescents: prevalence, risk factors, and partial mediation by family support, a cross-sectional study.

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.

Resolvin D5 Protects Female Hairless Mouse Skin from Pathological Alterations Caused by UVB Irradiation.

Resolvin D5 (RvD5) is a lipid mediator that has been reported to present anti-inflammatory and pro-resolution properties. Evidence also supports its capability to enhance reactive oxygen species (ROS) production during bacterial infections, which would be detrimental in diseases driven by ROS. The biological activity of RvD5 and mechanisms against UVB irradiation skin pathology have not been investigated so far. Female hairless mice were treated intraperitoneally with RvD5 before UVB stimulus. RvD5 reduced skin edema in a dose-dependent manner as well as oxidative stress by increasing antioxidants (endogenous tissue antioxidant scavenging of cationic radical, iron reduction, catalase activity and reduced glutathione levels) and decreasing pro-oxidants (superoxide anion and lipid peroxidation). RvD5 antioxidant activity was accompanied by enhancement of Nrf2, HO-1 and NQO1 mRNA expression. RvD5 reduced the production of IL-1ß, TNF-α, TGF-ß, and IL-10. RvD5 also reduced the inflammatory cell counts, including mast cells and neutrophils/macrophages. The reduction of oxidative stress and inflammation resulted in diminished matrix metalloproteinase 9 activity, collagen degradation, epidermal thickening and sunburn cell development. Therefore, this study demonstrates, to our knowledge, the first body of evidence that RvD5 can be used to treat UVB skin pathology and unveils, at least in part, its mechanisms of action.

The Dark Triad and aggression among drug abstainers: a moderated mediation model of self-control and physical exercise.

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.

From alcohol and other drug treatment mediator to mechanism to implementation: A systematic review and the cases of self-efficacy, social support, and craving.

Research designed to establish alcohol and other drug (AOD) mechanisms of behavioral change (MOBC) has centered on what variables mediate the relation between AOD treatment and outcomes. The purpose of this paper was to review this research evidence to identify empirically supported mediators of alcohol and other drug use and related outcomes and then to evaluate their potential as being AOD treatment MOBC. The first phase was a systematic review of reviews (2008-2023) to identify the variables with the strongest empirical support as mediators of AOD treatment effects. Eligible reviews focused on AOD treatment modalities, included empirically tested mediators, and targeted adult samples. The second phase was a systematic review of empirical studies (1990-2023) testing the hypothesis that variables identified in phase one were AOD treatment mediators/mechanisms and then evaluating each eligible stage two study according to the Kazdin and Nock (Journal of Child Psychology and Psychiatry, 44, 1116) criteria. Eligible articles included empirical studies with adult samples attending AOD treatment and empirically tested one of the three treatment mechanisms as a mediator of an AOD-related outcome. Databases were searched in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. This systematic review was not preregistered. The first review of 11 eligible review articles identified self-efficacy, social support, and craving as having the strongest empirical support. The second review captured 48 individual studies. An evaluation of each of these studies by the Kazdin and Nock criteria suggested that they likely are MOBC and therefore are ready for implementation. The implementation of self-efficacy, social support, and craving into clinical practice and training is warranted. Six directions for future research to solidify and generalize empirical support for the case that self-efficacy, social support, and craving are MOBC are presented, as are five implications for clinical practice and training.

A New Generation of Postbiotics for Skin and Scalp: In Situ Production of Lipid Metabolites by Malassezia.

Effects of pre- and probiotics on intestinal health are well researched and microbiome-targeting solutions are commercially available. Even though a trend to appreciate the presence of certain microbes on the skin is seeing an increase in momentum, our understanding is limited as to whether the utilization of skin-resident microbes for beneficial effects holds the same potential as the targeted manipulation of the gut microflora. Here, we present a selection of molecular mechanisms of cross-communication between human skin and the skin microbial community and the impact of these interactions on the host's cutaneous health with implications for the development of skin cosmetic and therapeutic solutions. Malassezia yeasts, as the main fungal representatives of the skin microfloral community, interact with the human host skin via lipid mediators, of which several are characterized by exhibiting potent anti-inflammatory activities. This review therefore puts a spotlight on Malassezia and provides a comprehensive overview of the current state of knowledge about these fungal-derived lipid mediators and their capability to reduce aesthetical and sensory burdens, such as redness and itching, commonly associated with inflammatory skin conditions. Finally, several examples of current skin microbiome-based interventions for cosmetic solutions are discussed, and models are presented for the use of skin-resident microbes as endogenous bio-manufacturing platforms for the in situ supplementation of the skin with beneficial metabolites.

Metallic Impurities in Electrolysis: Catalytic Effect of Pb Traces in Reductive Amination and Acetone Reduction.

The electrochemical hydrogenation (e-hydrogenation) of unsaturated compounds like imines or carbonyls presents a benign reduction method. It enables direct use of electrons as reducing agent, water as proton source, while bypassing the need for elevated temperatures or pressures. In this contribution, we discuss the nature of active sites in electrocatalytic reductive amination with the transformation of acetone and methylamine as model reaction. Surprisingly, lead impurities in the ppm-range proved to possess a significant effect in e-hydrogenation. Accordingly, the influence of applied potential and cathode material in presence of 1 ppm Pb was investigated. Finally, we transferred the insights to the reduction of acetone manifesting comparable observations as for imine reduction. The results suggest that previous studies on electrochemical reduction in the presence of lead electrodes should be re-evaluated.