Laccase/caffeic acid-catalyzed crosslinking coupled with galactomannan alters the conformational structure of ovalbumin and alleviates Th2-mediated allergic asthma

Ovalbumin(OVA)is the major allergenic protein that can induce T helper 2(Th2)-allergic reactions,for which current treatment options are inadequate.In this study,we developed a polymerized hypoallergenic OVA product via laccase/caffeic acid(Lac/CA)-catalyzed crosslinking in conjunction with galactomannan(Man).The formation of high molecular weight crosslinked polymers and the Ig G-binding were analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis(SDS-PAGE)and Western blotting.The study indicated that Lac/CA-catalyzed crosslinking plus Man conjugation substantially altered secondary and tertiary structures of OVA along with the variation in surface hydrophobicity.Gastrointestinal digestion stability assay indicated that crosslinked OVA exhibited less resistance in simulated gastric fluid(SGF)and simulated intestinal fluid(SIF).Mouse model study indicated that Lac-Man/OVA ameliorated eosinophilic airway inflammatory response and efficiently downregulated the expression of Th2-related cytokines(interleukin(IL)-4,IL-5,and IL-13),and upregulated IFN-γand IL-10 expression.Stimulation of bone marrow-derived dendritic cells with Lac-Man/OVA suppressed the expression of phenotypic maturation markers(CD80 and CD86)and MHC class II molecules,and suppressed the expression levels of proinflammatory cytokines.The knowledge obtained in the present study offers an effective way to acquire a hypoallergenic OVA product that can have a therapeutic effect in alleviating OVA-induced allergic asthma.

Heterostructured nickel-cobalt metal alloy and metal oxide nanoparticles as a polysulfide mediator for stable lithium-sulfur full batteries with lean electrolyte

Batteries that utilize low-cost elemental sulfur and light metallic lithium as electrodes have great potential in achieving high energy density.However,building a lithium-sulfur(Li-S)full battery by controlling the electrolyte volume generally produces low practical energy because of the limited electrochemical Li-S redox.Herein,the high energy/high performance of a Li-S full battery with practical sulfur loading and minimum electrolyte volume is reported.A unique hybrid architecture configured with Ni-Co metal alloy(NiCo)and metal oxide(NiCoO_(2))nanoparticles heterogeneously anchored in carbon nanotube-embedded selfstanding carbon matrix is fabricated as a host for sulfur.This work demonstrates the considerable improvement that the hybrid structure's high conductivity and satisfactory porosity promote the transport of electrons and lithium ions in Li-S batteries.Through experimental and theoretical validations,the function of NiCo and NiCoO_(2) nanoparticles as an efficient polysulfide mediator is established.These particles afford polysulfide anchoring and catalytic sites for Li-S redox reaction,thus improving the redox conversion reversibility.Even at high sulfur loading,the nanostructured Ni-Co metal alloy and metal oxide enable to have stable cycling performance under lean electrolyte conditions both in half-cell and full-cell batteries using a graphite anode.

Analysis of the electron transfer pathway in small laccase by EPR and UV-vis spectroscopy coupled with redox titration

Bacterial small laccases(SLAC) are promising industrial biocatalysts due to their ability to oxidize a broad range of substrates with exceptional thermostability and tolerance for alkaline p H. Electron transfer between substrate, copper centers, and O2is one of the key steps in the catalytic turnover of SLAC. However, limited research has been conducted on the electron transfer pathway of SLAC and SLAC-catalyzed reactions, hindering further engineering of SLAC to produce tunable biocatalysts for novel applications. Herein, the combinational use of electron paramagnetic resonance(EPR) and ultraviolet-visible(UV-vis) spectroscopic methods coupled with redox titration were employed to monitor the electron transfer processes and obtain further insights into the electron transfer pathway in SLAC. The reduction potentials for type 1 copper(T1Cu), type 2 copper(T2Cu) and type 3copper(T3Cu) were determined to be 367 ± 2 mV, 378 ± 5 m V and 403 ± 2 mV,respectively. Moreover, the reduction potential of a selected substrate of SLAC, hydroquinone(HQ), was determined to be 288 mV using cyclic voltammetry(CV). In this way, an electron transfer pathway was identified based on the reduction potentials. Specifically,electrons are transferred from HQ to T1Cu, then to T2Cu and T3Cu, and finally to O2.Furthermore, superhyperfine splitting observed via EPR during redox titration indicated a modification in the covalency of T2Cu upon electron uptake, suggesting a conformational alteration in the protein environment surrounding the copper sites, which could potentially influence the reduction potential of the copper sites during catalytic processes. The results presented here not only provide a comprehensive method for analyzing the electron transfer pathway in metalloenzymes through reduction potential measurements, but also offer valuable insights for further engineering and directed evolution studies of SLAC in the aim for biotechnological and industrial applications.

Pro-resolving lipid mediator reduces amyloid-β42–induced gene expression in human monocyte–derived microglia

Specialized pro-resolving lipid mediators including maresin 1 mediate resolution but the levels of these are reduced in Alzheimer's disease brain, suggesting that they constitute a novel target for the treatment of Alzheimer's disease to prevent/stop inflammation and combat disease pathology. Therefore, it is important to clarify whether they counteract the expression of genes and proteins induced by amyloid-β. With this objective, we analyzed the relevance of human monocyte–derived microglia for in vitro modeling of neuroinflammation and its resolution in the context of Alzheimer's disease and investigated the pro-resolving bioactivity of maresin 1 on amyloid-β42–induced Alzheimer's disease–like inflammation. Analysis of RNA-sequencing data and secreted proteins in supernatants from the monocyte-derived microglia showed that the monocyte-derived microglia resembled Alzheimer's disease–like neuroinflammation in human brain microglia after incubation with amyloid-β42. Maresin 1 restored homeostasis by down-regulating inflammatory pathway related gene expression induced by amyloid-β42 in monocyte-derived microglia, protection of maresin 1 against the effects of amyloid-β42 is mediated by a re-balancing of inflammatory transcriptional networks in which modulation of gene transcription in the nuclear factor-kappa B pathway plays a major part. We pinpointed molecular targets that are associated with both neuroinflammation in Alzheimer's disease and therapeutic targets by maresin 1. In conclusion, monocyte-derived microglia represent a relevant in vitro microglial model for studies on Alzheimer's disease-like inflammation and drug response for individual patients. Maresin 1 ameliorates amyloid-β42–induced changes in several genes of importance in Alzheimer's disease, highlighting its potential as a therapeutic target for Alzheimer's disease.

Scarcity and Mental Health—Multiple Mediators of Sleep Quality and Life Satisfaction

Background:In the current social environment,scarcity,as a universally present objective state,profoundly impacts individuals’decision-making and health through the subjective feeling it induces,known as a“scarcity mindset.”Particularly,the feeling of scarcity related to money and sleep time is not only widespread but also directly linked to an individual’s mental health.Purpose:This study aims to delve into the relationship between the feeling of scarcity and mental health,with a specific focus on the relationship between the feeling of money scarcity or sleep time scarcity and mental health,as well as the role of sleep quality or life satisfaction in this relationship.Procedure:We determined the sampling quotas based on the population and economic development levels of each province in the“China Statistical Yearbook(2021)”(National Bureau of Statistics,2021).Participants were selected using the Probability Proportional to Size(PPS)sampling method.Data was collected by distributing online questionnaires to participants,and the relationships between the main variables were explored using structural equation modeling.Results:1.In China,the feeling of sleep time scarcity is stronger than the feeling of money scarcity among the public.2.The feeling of money scarcity is positively correlated with depression and anxiety,whereas the feeling of sleep time scarcity is only positively correlated with depression.3.The feeling of scarcity mainly leads to depression and self-denial through reducing life satisfaction,and it leads to anxiety through reducing sleep quality.Conclusion:The feeling of scarcity in money and sleep time is related to different dimensions of mental health.Therefore,reasonably planning financial allocation and ensuring an adequate amount of sleep can reduce the sense of scarcity,thereby improving mental health.Additionally,improving sleep quality and increasing life satisfaction can alleviate the adverse effects of scarcity on mental health.

Observation on Therapeutic Effect of Lotus Needle Cupping Therapy for Removing Blood Stasis in Zhuang Medicine on PHN and Its Influ-ence on Inflammatory Mediators

[Objectives]To observe the clinical effect of the lotus needle cupping therapy for removing blood stasis in Zhuang medicine in treating PHNand its influence on inflammatory factors.[Methods]96 patients with PHN were randomly divided into three groups:lotus nee-dle cupping therapy group,TCM surrounding acupuncture group and gabapentin group.Venous blood and acupoint blood were collected at 0,21 and 42 d of treatment,and the expression levels of 5-HT,SP and CGRPinflammatory mediators were detected before and after treatment.The changes of VAS scores before,during and after treatment and the clinical efficacy were observed.[Results]The total effective rate of the lotus needle cupping group was 87.50%,which was better than that of the TCM acupuncture group(81.25%)and the gabapentin group(62.50%);after treatment,the VAS scores and the expression of inflammatory mediators in the three groups of patients were lower than those before treatment,and the decrease was more significant in the treatment group(P<0.05).[Conclusions]The lotus needle cupping therapy for removing blood stasis in Zhuang medicine is effective in treating PHN,and its mechanism is to reduce the release of inflammatory media-tors,reduce hyperalgesia,relieve pain and improve the quality of life of patients.

ROLE OF FUNGAL LACCASE AND LOW MOLECULAR MEDIATORS ON DECOLOURIZATION OF AROMATIC DYES IN PAPER MILL EFFLUENTS

Several wood rotting fungi decolourized Remazol brilliant blue R (RBBR) and carminic acid (CA). Parallel activity of laccase in these fungi was studied. The addition of acetovanillone (AV) or acetosyringone (AS) intensified these processes: decolourization was more extensive than in the experiment omitting these compounds. At the presence of AS the decourization was more extensive than AV. However the level of decolorizing was relatively low in comparison to laccase activity on syringaldazine. The highly purified constitutive form of Cerrena unicolor and inducible form of Trametes versicolor laccases also destained both dyes. Anyway the addition of AV and AS improved the efficiency of dyes decolourization by wood rotting fungi and fungal laccase. Nitrogen starvation induced the laccase and decoloration activity in both organisms, irrespective of nitrogen availability. This fact indicates laccase not solely responsible for discoloration, and probably discoloration of dyes involves more than one mechanism.

The mechanism and relevant mediators associated with neuronal apoptosis and potential therapeutic targets in subarachnoid hemorrhage

Subarachnoid hemorrhage(SAH)is a dominant cause of death and disability wo rldwide.A sharp increase in intracranial pressure after SAH leads to a reduction in cerebral perfusion and insufficient blood supply for neuro ns,which subsequently promotes a series of pathophysiological responses leading to neuronal death.Many previous experimental studies have reported that excitotoxicity,mitochondrial death pathways,the release of free radicals,protein misfolding,apoptosis,nec rosis,autophagy,and inflammation are involved solely or in combination in this disorder.Among them,irreversible neuronal apoptosis plays a key role in both short-and long-term prognoses after SAH.Neuronal apoptosis occurs through multiple pathways including extrinsic,mitochondrial,endoplasmic reticulum,p53 and oxidative stress.Meanwhile,a large number of blood contents enter the subarachnoid space after SAH,and the secondary metabolites,including oxygenated hemoglo bin and heme,further aggravate the destruction of the blood-brain barrier and vasogenic and cytotoxic brain edema,causing early brain injury and delayed cerebral ischemia,and ultimately increasing neuronal apoptosis.Even there is no clear and effective therapeutic strategy for SAH thus far,but by understanding apoptosis,we might excavate new ideas and approaches,as targeting the upstream and downstream molecules of apoptosis-related pathways shows promise in the treatment of SAH.In this review,we summarize the existing evidence on molecules and related drugs or molecules involved in the apoptotic pathway after SAH,which provides a possible target or new strategy for the treatment of SAH.

Development of High Areal Capacity Electrolytic MnO_(2)-Zn Battery via an Iodine Mediator

The commercialization of electrolytic MnO_(2)-Zn batteries is highly applauded owing to the advantages of cost-effectiveness,high safety,high energy density,and durable working performance.However,due to the low reversibility of the cathode MnO_(2)/Mn^(2+)chemistry at high areal capacities and the severe Zn anode corrosion,the practical application of MnO_(2)-Zn batteries is hampered by inadequate lifespan.Leveraging the full advantage of an iodine redox mediator,here we design a highly rechargeable electrolytic MnO_(2)-Zn battery with a high areal capacity.The MnO_(2)-Zn battery coupled with an iodine mediator in a mild electrolyte shows a high discharge voltage of 1.85 V and a robust areal capacity of 10 mAh cm^(-2)under a substantial discharge current density of 160 mA cm^(-2).The MnO_(2)/I_(2)-Zn battery with an areal capacity of 10 mAh cm^(-2)exhibits prolonged stability of over 950 cycles under a high-capacity retention of~94%.The scaled-up MnO_(2)/I_(2)-Zn battery reveals a stable cycle life under a cell capacity of~600 mAh.Moreover,our constructed MnO_(2)/I_(2)-Zn battery demonstrates a practical energy density of~37 Wh kg^(-1)and a competitive energy cost of<18 US$kWh^(-1)by taking into account the cathode,anode,and electrolyte.The MnO_(2)/I_(2)-Zn battery,with its remarkable reversibility and reasonable energy density,enlightens a new arena of large-scale energy storage devices.

Intraoperative Blood Pressure Lability Acts as a Key Mediator in the Impacts of Goal-Directed Fluid Therapy on Postoperative Complications in Patients Undergoing Major Spine Surgery

Objective Although goal-directed fluid therapy(GDFT)has been proven to be effective in reducing the incidence of postoperative complications,the underlying mechanisms remain unknown.The aim of this study was to examine the mediating role of intraoperative hemodynamic lability in the association between GDFT and the incidence of postoperative complications.We further tested the role of this mediation effect using mean arterial pressure,a hemodynamic indicator.Methods This secondary analysis used the dataset of a completed nonrandomized controlled study to investigate the effect of GDFT on the incidence of postoperative complications in patients undergoing posterior spine arthrodesis.We used a simple mediation model to test whether there was a mediation effect of average real variability between the association of GDFT and postoperative complications.We conducted mediation analysis using the mediation package in R(version 3.1.2),based on 5,000 bootstrapped samples,adjusting for covariates.Results Among the 300 patients in the study,40%(120/300)developed postoperative complications within 30 days.GDFT was associated with fewer 30-day postoperative complications after adjustment for confounders(odds ratio:0.460,95%CI:0.278,0.761;P=0.003).The total effect of GDFT on postoperative complications was-0.18(95%CI:-0.28,-0.07;P<0.01).The average causal mediation effect was-0.08(95%CI:-0.15,-0.04;P<0.01).The average direct effect was-0.09(95%CI:-0.20,0.03;P=0.17).The proportion mediated was 49.9%(95%CI:18.3%,140.0%).Conclusions The intraoperative blood pressure lability mediates the relationship between GDFT and the incidence of postoperative complications.Future research is needed to clarify whether actively reducing intraoperative blood pressure lability can prevent postoperative complications.

Association and potential mediators between socioeconomic status and childhood obesity in China:findings from a national cohort study

Objective:Socioeconomic status(SES)is associated with childhood obesity,but the underlying factors remain unknown.This study aimed to identify mediators that may explain SES disparities in childhood obesity in China.Methods:Nationally representative longitudinal data from the China Education Panel Survey of 11 o019 children(13.03±0.79)collected from 2013-2014 to 2016-2017 academic years.Overweight/obesity was defined using Chinese national body mass index cut-points.Principal component analysis was used to convert the four SES indicators(maternal and paternal education,and occupation)into one comprehensive variable.Mediation analysis for SES disparities in childhood obesity was conducted using structure equation models.Results:The prevalence of overweight/obesity was 12.8%,and was higher in boys than in girls(17.8%vs.7.6%,P<0.001)at baseline.Among boys,relative risk(RR)of obesity was 1.23(95%CI:1.09 to 1.40,P<O.001)for per unit change in SES.There was no significant association between obesity and SES among girls.Mediation analyses showed that among boys,birth weight,being the only child in the family and children's selfperceived weight status mediated 70.0%of the effects of SES on obesity.No mediation effect was detected in girls.Conclusions:Chinese boys are more likely to be overweight or obese than girls.SES may impact childhood obesity through birth weight,being the only child in the family and children's self-perceived body weight status in boys,but not in girls.More attention should be made to address childhood obesity in high SES families among boys.Interventions targeting at these mediators are needed.

METTL7A-mediated m6A modification of corin reverses bisphosphonates-impaired osteogenic differentiation of orofacial BMSCs

Bisphosphonate-related osteonecrosis of jaw(BRONJ)is characterized by impaired osteogenic differentiation of orofacial bone marrow stromal cells(BMSCs).Corin has recently been demonstrated to act as a key regulator in bone development and orthopedic disorders.However,the role of corin in BRONJ-related BMSCs dysfunction remains unclarified.A m6A epitranscriptomic microarray study from our group shows that the CORIN gene is significantly upregulated and m6A hypermethylated during orofacial BMSCs osteogenic differentiation.Corin knockdown inhibits BMSCs osteogenic differentiation,whereas corin overexpression or soluble corin(sCorin)exerts a promotion effect.Furthermore,corin expression is negatively regulated by bisphosphonates(BPs).Corin overexpression or sCorin reverses BPs-impaired BMSCs differentiation ability.Mechanistically,we find altered expression of phos-ERK in corin knockdown/overexpression BMSCs and BMSCs under sCorin stimulation.PD98059(a selective ERK inhibitor)blocks the corin-mediated promotion effect.With regard to the high methylation level of corin during osteogenic differentiation,we apply a non-selective m6A methylase inhibitor,Cycloleucine,which also blocks the corin-mediated promotion effect.Furthermore,we demonstrate that METTL7A modulates corin m6A modification and reverses BPs-impaired BMSCs function,indicating that METTL7A regulates corin expression and thus contributes to orofacial BMSCs differentiation ability.To conclude,our study reveals that corin reverses BPs-induced BMSCs dysfunction,and METTL7A-mediated corin m6A modification underlies corin promotion of osteogenic differentiation via the ERK pathway.We hope this brings new insights into future clinical treatments for BRONJ.

Linear paired electrolysis of furfural to furoic acid at both anode and cathode in a multiple redox mediated system

Implementing a new energy-saving electrochemical synthesis system with high commercial value is a strategy of the sustainable development for upgrading the bulk chemicals preparation technology in the future.Here,we report a multiple redox-mediated linear paired electrolysis system,combining the hydrogen peroxide mediated cathode process with the I2 mediated anode process,and realize the conversion of furfural to furoic acid in both side of the dividedflow cell simultaneously.By reasonably controlling the cathode potential,the undesired water splitting reaction and furfural reduction side reactions are avoided.Under the galvanostatic electrolysis,the two-mediated electrode processes have good compatibility,which reduce the energy consumption by about 22%while improving the electronic efficiency by about 125%.This system provides a green electrochemical synthesis route with commercial prospects.

Causal association of obesity-related anthropometric traits with myopia and the mediating role of educational attainment:a Mendelian randomization study

AIM:To study the causal relationship between obesityrelated anthropometric traits and myopia and the mediating role of educational attainment(EA).METHODS:Univariable Mendelian randomization(UVMR)was performed to evaluate the causal association between body mass index(BMI),height,waist-hip ratio(WHR,adjusted for BMI),and mean spherical equivalent(MSE).BMI was divided into fat and fat-free mass and included in multivariable Mendelian randomization(MVMR)to explore the roles of different BMI components in the causal relationship between BMI and MSE.A mediation analysis based on two-step Mendelian randomization(MR)was carried out.Specifically,UVMR was conducted to estimate the causal effect of BMI on EA.The direct effect of EA on MSE was estimated from MVMR.The mediation effect of EA in the BMI-EA-MSE model was calculated by the product of coefficients method.Expression quantitative trait loci(eQTL)-MR,reverse MR,and Linkage Disequilibrium Score Regression(LDSC)were performed to assess the robustness.RESULTS:Genetically predicted higher BMI had a positive total effect on MSE(βIVW=0.26 D,95%CI=0.14 to 0.37 D,P<0.001),whereas there was no significant association between height,WHR,and MSE.Fat mass was found to play a significant role in the effect of body mass on MSE(βIVW=0.50 D,95%CI=0.21 to 0.78 D,P=0.001),but there was no significant association between fat-free mass and MSE.The causal effect of BMI on EA was-0.14(95%CI=-0.16 to-0.11,P<0.001),and the direct effect of EA on MSE was-0.63 D(95%CI=-0.81 to-0.44 D,P<0.001).The mediating effect of EA in the BMI-EA-MSE model was 0.09 D(95%CI=0.06 to 0.12 D),with a mediation proportion of 33%(95%CI=22.1%to 44.6%).No reverse causal associations were detected except for BMI on EA.The results of eQTL-MR and LDSC were consistent with each MR analysis.CONCLUSION:Genetically predicted higher BMI decreases the degree of myopia with a 33%mediation proportion by EA,and fat mass provides a dominant protective role in body mass-myopia.As a supplement to previous observational studies,it provides strong evidence for the relationship between anthropometric traits and refractive errors and offers a theoretical basis for future measures to prevent and control myopia.

Interoception mediates the association between social support and sociability in patients with major depressive disorder

BACKGROUND Interoception dysfunction has an important impact on the onset and development of major depressive disorder(MDD).Social support serves as a protective factor against MDD,and sociability also plays a significant role in this condition.These interconnected constructs-social support and sociability-play pivotal roles in MDD.However,no research on the mechanisms underlying the associations be-tween social support and sociability,particularly the potential role of interocep-tion,have been reported.ception,social support,and sociability,respectively.A mediation analysis model for the eight dimensions of intero-ception(noticing,not distracting,not worrying,attention regulation,emotional awareness,self-regulation,body listening,and trust),social support,and sociability were established to evaluate the mediating effects.RESULTS A partial correlation analysis of eight dimensions of the MAIA-2,SSRS,and TSBI scores,with demographic data as control variables,revealed pairwise correlations between the SSRS score and both the MAIA-2 score and TSBI score.In the major depression(MD)group,the SSRS score had a positive direct effect on the TSBI score,while the scores for body listening,emotional awareness,self-regulation,and trust in the MAIA-2C had indirect effects on the TSBI score.In the HC group,the SSRS score had a positive direct effect on the TSBI score,and the scores for attention regulation,emotional awareness,self-regulation,and trust in the MAIA-2C had indirect effects on the TSBI score.The proportion of mediators in the MD group was lower than that in the HC group.CONCLUSION Interoceptive awareness is a mediating factor in the association between social support and sociability in both HCs and depressed patients.Training in interoceptive awareness might not only help improve emotional regulation in depressed patients but also enhance their social skills and support networks.

Resilience provides mediating effect of resilience between fear of progression and sleep quality in patients with hematological malignancies

BACKGROUND Hematological tumors are common malignant tumors,with high morbidity and mortality rates.Most patients with hematological malignancies develop sleep disorders that seriously affect their life and health because of acute onset of disease,rapid progression,high recurrence rates,complex treatment methods,and treatment costs.AIM To explore the mediating effect of resilience on fear of disease progression and sleep quality in patients with hematological malignancies.METHODS A cross-sectional analysis of 100 patients with hematological malignancies,treated in the First Affiliated Hospital of Jinzhou Medical University between August 2022 and August 2023,was conducted.Patients were assessed using a general data survey,a simplified scale for the fear of progression(FoP)of disease,a resilience scale,and the Pittsburgh Sleep Quality Index.Statistical analysis was conducted to determine the relationship between various patient characteristics and FoP,resilience,and sleep quality.Spearman’s correlation analysis was used to examine the correlations between mental resilience,FoP,and sleep quality.RESULTS The total FoP score mean value in patients with hematological malignancies was 38.09±5.16;the total resilience score mean value was 40.73±7.04;and the Pittsburgh Sleep Quality Index score mean value was 10.72±1.90.FoP,resilience,and sleep quality of the patients were associated with family per capita monthly income and patient education level(P<0.05).Spearman correlation analysis revealed that FoP was negatively correlated with resilience and sleep quality scores(r=-0.560,-0.537,P<0.01),respectively,and resilience was significantly associated with sleep quality scores(r=0.688,P<0.01).Mediation analysis showed that the mediating effect of resilience between FoP and sleep quality in patients with hematological malignancies was-0.100 and accounted for 50.51%of the total effect.This indicated that FoP directly and indirectly affected sleep quality through the mesomeric effect of resilience.CONCLUSION Resilience is an intermediary variable between FoP and sleep quality in patients with hematological malignancies.Medical staff should evaluate and follow-up FoP and resilience to implement measures to improve sleep quality.

Association of education with cholelithiasis and mediating effects of cardiometabolic factors:A Mendelian randomization study

BACKGROUND Education,cognition,and intelligence are associated with cholelithiasis occurrence,yet which one has a prominent effect on cholelithiasis and which cardiometabolic risk factors mediate the causal relationship remain unelucidated.AIM To explore the causal associations between education,cognition,and intelligence and cholelithiasis,and the cardiometabolic risk factors that mediate the associations.METHODS Applying genome-wide association study summary statistics of primarily European individuals,we utilized two-sample multivariable Mendelian randomization to estimate the independent effects of education,intelligence,and cognition on cholelithiasis and cholecystitis(FinnGen study,37041 and 11632 patients,respectively;n=486484 participants)and performed two-step Mendelian randomization to evaluate 21 potential mediators and their mediating effects on the relationships between each exposure and cholelithiasis.RESULTS Inverse variance weighted Mendelian randomization results from the FinnGen consortium showed that genetically higher education,cognition,or intelligence were not independently associated with cholelithiasis and cholecystitis;when adjusted for cholelithiasis,higher education still presented an inverse effect on cholecystitis[odds ratio:0.292(95%CI:0.171-0.501)],which could not be induced by cognition or intelligence.Five out of 21 cardiometabolic risk factors were perceived as mediators of the association between education and cholelithiasis,including body mass index(20.84%),body fat percentage(40.3%),waist circumference(44.4%),waist-to-hip ratio(32.9%),and time spent watching television(41.6%),while time spent watching television was also a mediator from cognition(20.4%)and intelligence to cholelithiasis(28.4%).All results were robust to sensitivity analyses.CONCLUSION Education,cognition,and intelligence all play crucial roles in the development of cholelithiasis,and several cardiometabolic mediators have been identified for prevention of cholelithiasis due to defects in each exposure.

Mediating role of social support in dysphoria,despondency,and quality of life in patients undergoing maintenance hemodialysis

BACKGROUND Dysphoria and despondency are prevalent psychological issues in patients undergoing Maintenance Hemodialysis(MHD)that significantly affect their quality of life(QOL).High levels of social support can significantly improve the physical and mental well-being of patients undergoing MHD.Currently,there is limited research on how social support mediates the relationship between dysphoria,despondency,and overall QOL in patients undergoing MHD.It is imperative to investigate this mediating effect to mitigate dysphoria and despondency in patients undergoing MHD,ultimately enhancing their overall QOL.AIM To investigate the mediating role of social support in relationships between dysphoria,despondency,and QOL among patients undergoing MHD.METHODS Participants comprised 289 patients undergoing MHD,who were selected using a random sampling approach.The Social Support Rating Scale,Self-Rating Anxiety Scale,Self-Rating Depression Scale,and QOL Scale were administered.Correlation analysis was performed to examine the associations between social support,dysphoria,despondency,and QOL in patients undergoing MHD.To assess the mediating impact of social support on dysphoria,despondency,and QOL in patients undergoing MHD,a bootstrap method was applied.RESULTS Significant correlations among social support,dysphoria,despondency,and quality in patients undergoing MHD were observed(all P<0.01).Dysphoria and despondency negatively correlated with social support and QOL(P<0.01).Dysphoria and despondency had negative predictive impacts on the QOL of patients undergoing MHD(P<0.05).The direct effect of dysphoria on QOL was statistically significant(P<0.05).Social support mediated the relationship between dysphoria and QOL,and this mediating effect was significant(P<0.05).Similarly,the direct effect of despondency on QOL was significant(P<0.05).Moreover,social support played a mediating role between despondency and QOL,with a significant mediating effect(P<0.05).CONCLUSION These findings suggest that social support plays a significant mediating role in the relationship between dysphoria,despondency,and QOL in patients undergoing MHD.

Parental Psychological Control and Internet Gaming Disorder Tendency:A Moderated Mediation Model of Core Self-Evaluation and Intentional Self-Regulation

Internet gaming disorder(IGD)among junior high school students is an increasingly prominent mental health concern.It is important to look for influences behind internet gaming disorder tendency(IGDT)in the junior high school student population.The present study aimed to reveal the explanatory mechanisms underlying the association between parental psychological control(PPC)and internet gaming disorder tendency among junior high school students by testing the mediating role of core self-evaluation(CSE)and the moderating role of intentional self-regulation(ISR).Participants in present study were 735 Chinese junior high school students who completed offline self-report questionnaires on parental psychological control,core self-evaluation,intentional self-regulation,and Internet gaming disorder tendency.Analyses were conducted via mediation and moderated mediation.The results showed that:(1)Parental psychological control was positively related to junior high school students’Internet gaming disorder tendency.Core self-evaluation,and intentional self-regulation were negatively related to junior high school students’Internet gaming disorder tendency,respectively.(2)Core self-evaluation partially mediated the relationship between parental psychological control and junior high school students’Internet gaming disorder tendency.(3)Intentional self-regulation moderated the association between parental psychological control and Internet gaming disorder tendency,as well as the relationships between parental psychological control and core self-evaluation and core self-evaluation and Internet gaming disorder tendency in the mediated model.Based on these findings,we believe that there is a need to weaken parental psychological control,strengthen junior high school students’core self-evaluation and intentional self-regulation,and to recognize the important role of parents as well as their children’s personal positive traits in the healthy development of junior high school students.

The Influence of Academic Self-Efficacy on Learning Engagement in Online Education in China:The Mediating Role of Effort

The shift towards online intelligent learning has become the norm in education and is now a fundamental part of modern educational activities.However,this new model can influence students’learning behavior and lead to changes in their approach to learning.Based on online intelligent learning,we investigated how the academic self-efficacy of nursing students affects their engagement with learning and explored the role of academic attribution as a mediator.Five hundred fifty-three nursing college students from Hebei and Hunan provinces in China participated in the online questionnaire.The results revealed that effort plays a mediating role in the relationship between academic self-efficacy and learning engagement.