Stress Model Research Articles

Design and analysis of a thin sleeve for high-speed magnet drums in eddy current separation systems

Eddy current separators, which are widely used in the recycling industry for the separation of non-ferrous metals, rely on the electromagnetic repulsion generated by eddy currents induced by a rotating magnet drum. As such, enhancing the separation rate of the magnet drum is vital for the recycling industry. Despite the existence of various studies aimed at improving the separation rate, the issues associated with the magnet drum’s sleeve remain unaddressed. This study introduces a comprehensive methodology for designing magnet drum sleeves for use in eddy current separation systems. A stress model was developed to analyze the relationships between the sleeve’s primary design parameters, such as interference fit and thickness, and various secondary parameters, such as rotation speed, size, material properties, and manufacturing processes. This study proposes optimal design points to minimize sleeve thickness, potentially enhancing both separation efficiency and design flexibility. The study’s findings emphasize the importance of maximizing the interference fit to maintain compressive stress between the magnet and core, preventing magnet scattering. However, there is a limit to increasing the interference fit due to sleeve breakage, and there are also certain constraints, such as the fact that material properties and manufacturing tolerances often require increased sleeve thickness. The analysis used in this study integrates these factors, emphasizing the sleeve’s critical role in eddy current separation systems. The results demonstrate the potential for more precise and improved designs that will enable higher rotation speeds, stronger magnetic fields and induced force, and narrower gaps between the magnet drum and the target objects, thereby enhancing the separation performance to a significant degree.

Workflow Helps Predict Casing Deformation During Hydraulic Fracturing in Shale Gas

_ This article, written by JPT Technology Editor Chris Carpenter, contains highlights of paper URTeC 4043054, “Casing-Deformation-Risk Prediction With Numerical Simulation During Hydraulic Fracturing in Deep Shale Gas Reservoirs,” by Jianfa Wu, Xuewen Shi, and Qiyong Gou, PetroChina, et al. The paper has not been peer reviewed. _ In this study, a numerical simulation workflow was established based on comprehensive modeling of a time-lapse stress field, hydraulic fracturing simulation, natural fractures, and other weak interfaces to analyze casing-deformation mechanisms of shale gas horizontal wells during the multistage hydraulic fracturing process. The authors write that they aim to guide the prediction of, and provide mitigating solutions for, casing-deformation risks while improving stimulation efficiency. Introduction The burial depth of deep shale gas reservoirs in the southern Sichuan Basin is approximately 3500 to 4500 m. These have complex geological conditions with developed faults and fractures and high in-situ horizontal stresses. During multistage hydraulic fracturing operations in horizontal wells, establishing an effective prediction method for casing-deformation risks in these reservoirs is a challenge. An integrated workflow is proposed to evaluate and predict casing-deformation risks, effectively support hydraulic fracturing operations, and reduce and mitigate casing failure in these reservoirs. Modeling Methodology It is essential to consider the effects of multiscale natural fractures when constructing a 3D stress model. Natural-fracture stability can be evaluated and used to identify unstable fractures that may cause casing failures. The fundamental workflow of predicting and preventing the casing failure is as follows: 1. Build a 3D geological model characterizing the spatial distribution and geometry of faults and natural fractures 2. Construct a 3D stress model to characterize the in-situ stress state 3. Perform numerical simulations of hydraulic fracturing and 4D coupled stress simulation to obtain the stress field during and after hydraulic fracturing 4. Quantitatively analyze the shear slip risks of natural fractures by calculating slip tolerance as an indicator to determine risk levels of casing deformation 5. Optimize and adjust engineering parameters for hydraulic fracturing to reduce and mitigate casing deformation Natural-Fracture Distribution and Model Construction. In this study, natural fractures parameters such as density, strike, inclination, length of extension, and height were obtained. The natural fractures were calibrated and verified with cores and wellbore images. Natural-fracture distribution was then validated with the expected tectonic history and present-day stress regime. In Fig. 1, the left-hand plot depicts the ant-tracking results by seismic attribute, the central plot portrays natural fractures validated by microseismic events, and the right-hand plot illustrates the 3D natural-fracture model. Results showed two major fracture strikes, one in the northeast and the other in the northwest, forming a mesh network distribution that will be used in the stress model, fracturing simulation, and slip analysis.

Comparative transcriptional analyses of the striatum in the chronic social defeat stress model in C57BL/6J male mice and the gut microbiota-dysbiosis model in Kumming mice

Depression is a complex disorder with multiple contributing factors, and chronic stress has previously been recognized as a major causative factor, while gut microbes have also been found to be involved in depression recently. However, gene expression in depression models with different etiologies is unclear. Here, we compared the transcriptomes of the striatum in chronic social defeat stress (CSDS) model of C57BL/6J male mice and fecal microbiota transplant (FMT) model of Kumming male mice. We found that the proportion of shared differentially expressed genes (DEGs) between the two models was only 24 %. The specific DEGs of FMT model were enriched in immune and inflammatory, and are associated with changes in vascular and ciliated ependymal cells. The specific DEGs of CSDS model were enriched in neuron and synapse. The results of network analysis suggested the expression patterns and biological function of depressive-like behaviors-related modules in the two models are different. Further, the alternative splicing events of CSDS are more than FMT. Our results suggested models of depression induced by different etiologies differ significantly in gene expression and biological function. Our study also suggested us to pay attention to the characteristics of models of depression of different etiologies and provided a more comprehensive understanding of the heterogeneity of depression.

Research on adhesion properties of tidal flat soil on metal surface and discrete element simulation

The adhesion property of soil on the metal surface was tested by the orthogonal experiment with 4 factors and 3 levels based on piston pull out method. A regression model of adhesion stress and the factors including moisture content(X1), pressing time(X2), settling time(X3) and separation velocity (X4) was established. The experiment results show that the influence of each factor on adhesion stress is ranked as X1≈X2≈X3>X4>X3X4, and the adhesion stress shows an ‘S’ curve with the increase of separation velocity. The DEM parameters of the soil were calibrated based on the test results, and the contact and disturbance state of soil particles during the test were studied by discrete element method (DEM) using JKR model. The simulation tests show that the maximum adhesion stress occurs when the particles are about to separate from the probe surface, and the soil disturbance state is hierarchical.

StressMatic: Bridging Innovation and Reliability in Animal Models of Stress

Preclinical research involving animal models of stress exposure typically rely on traditional manual protocols, which are laborious and time-consuming and may compromise reproducibility and the effective translation of findings into clinical applications. StressMatic is an automated stress exposure system (auCMS), designed to improve the standardization and reproducibility of stress-induction methodologies. The auCMS demonstrated consistent efficacy, with animals subjected to automated stressors displaying similar responses to those exposed to conventional manual methods, thus confirming its validity as a reliable tool. While some stressors still require human involvement, the automation of key processes has markedly enhanced efficiency and minimized operational time. This innovative approach reduces the introduction of human error, increases precision, and standardizes experimental workflows, resulting in a more robust preclinical research platform. By streamlining repetitive tasks, the auCMS promotes adaptability in experimental design, particularly in the study of mood disorders. Ultimately, this automated protocol not only enhances the reliability of pharmaceutical screening processes but also strengthens the drug discovery pipeline, facilitating deeper insights into behavioral outcomes and informing therapeutic strategies.

Breaking the cycle between caregiver mental health and child behavioral issues: Does food insecurity matter?

Food insecurity is a key determinant of not only caregiver’s mental health but also children’s emotional problems and hyperactivity symptoms. Although substantial studies have explored such a relationship, it is unclear to us whether this relation would vary when considering that caregiver’s mental health and aforementioned children’s behavioral issues can be the cause and effect of each other. Addressing this research gap is a key to advancing our understanding of how to promote a healthier family dynamic, especially for those facing material needs. This research applies the family stress model to explore how food insecurity affects caregiver psychological distress and child emotional problems and hyperactivity symptoms, while considering the reciprocal relationships between caregiver mental health and these child behavioral issues. Utilizing data from the 2019 Panel Study of Income Dynamic and 2019-2020 Child Development Supplements, this study conducts path analyses applied with propensity score weighting to support causal inference. Results support the family stress model framework, where food insecurity significantly predicts an increase in psychological distress in caregivers, which in turn leads to more severe child emotional problems and hyperactivity symptoms. This study also shows that food insecurity is a risk factor resulting in a reciprocal association between caregiver psychological distress and child emotional problems, where the strength of both directions is similarly harmful to each other. These findings underscore the need to address food insecurity, not only to meet material needs but also to break the harmful cycle of mental health and behavioral issues within families

How can we build structural resilience? Integration of social-ecological and minority stress models.

As the United States contends with racism and a social justice reckoning, the need to advance our understanding of how to build structural resilience continues to be pressing. This article proposes a culturally and structurally informed model of resilience for individuals with minoritized identities that integrates social-ecological and minority stress models. First, common stressors and traumas experienced by minoritized individuals at multiple levels of proximal/distal influence are reviewed: microsystem (e.g., family rejection), mesosystem (e.g., community-based discrimination), exosystem (e.g., barriers to health care), macrosystem (e.g., harmful legal policies), and chronosystem (e.g., historical legacy). Next, how these exposures have cascading effects on minority stress processes (e.g., discriminatory policies in the macrosystem affect how a child is socialized in the microsystem) are considered. Then, modifiable factors (e.g., community cohesion) that promote resiliency in the face of ongoing exposures are discussed. To conclude, guidelines are offered for advancing the psychological science of resilience in minoritized groups including mixed methods to reflect participants' experiences, ecological approaches to assess resilience, and multilevel modeling to understand the interplay between the social-ecological context and individual factors. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Understanding interfacial failure mechanisms of advanced high strength automotive steels resistance spot welds under opening-mode loading

This paper addresses interfacial failure (IF) of automotive steel resistance spot welds under opening mode loading (i.e., Mode I), simulated through the cross-tension test. Two modeling approaches were developed to predict cross-tension strength (CTS) during IF: one based on structural stress and the other on fracture mechanics. The structural stress model correlates CTS with the hardness of the fusion zone, while the fracture mechanics model links CTS to the fusion zone’s toughness. Our evaluation of these models across various automotive steels reveals that the hardness-based model is suitable for steels with fusion zone hardness below 350 HV, where IF typically results in ductile fracture. In contrast, for higher-grade steels with fusion zone hardness exceeding 400 HV, the toughness-based model is more appropriate, as IF occurs through brittle crack propagation. The transition in the interfacial failure mechanism of spot welds under Mode I loading—from ductile tensile failure to brittle crack propagation—is governed by the ratio of toughness and hardness of the fusion zone. These insights not only refine the prediction of CTS but also inform the design of effective post-weld heat treatments aimed at enhancing CTS without sacrificing strength under shear loading mode particularly through martensite refining strategy.

A long chain fatty acid receptor signaling as a new therapeutic target for stress-induced chronic pain

Psychological and social stresses are known to be risk factors for psychiatric disorders, including depression and anxiety. On the other hand, exposure to these stresses can also cause prolonged and severe pain. However, the pathological mechanism for stress-induced chronic pain is complex, and there are many unresolved aspects, and no effective therapeutic drugs have been established. Since the discovery of the long-chain fatty acid receptor GPR40/FFAR1 about 20 years ago, research on the mechanism that promotes insulin secretion in the pancreas has progressed. Previously, we have worked to elucidate the physiological effects of GPR40/FFAR1 in the central nervous system and has found that it is involved in the regulation of pain and emotion. Based on these findings, they are now investigating the involvement of fatty acid receptors signaling in the development of stress-related chronic pain. In this review, we discuss the status of psychological stress-related chronic pain and the GPR40/FFAR1-mediated and -striking regulatory mechanisms of stress-induced chronic pain, based on our findings using a mouse model of chronic pain created by loading postoperative pain to a social defeat stress model mouse that mimics psychosocial stress. We summarized about the involvement of fatty acid receptor signaling as a new therapeutic candidate for chronic pain in this review.

Effect of Sertraline and Vortioxetine on Stress-Induced Brain Injury in Rats: Biochemical and Histopathological Evaluations

Objectives Our aim was to evaluate the comparative effects of sertraline and vortioxetine against stress-induced brain injury in rats. Methods The rats were assigned to a nonstress group (NSG), stress-treated control (StC), sertraline + stress (SSt), and vortioxetine + stress (VSt) groups. Sertraline and vortioxetine (10 mg/kg) were given orally by gavage to the SSt and VSt groups. One hour later, all animals (except NSG) underwent forced immobilization to establish a stress model (2 hours). The drugs were given once a day for 30 days. The animals were killed with ketamine 150 mg/kg, and tissues were removed from the cerebral cortex. One-way analysis of variance and Fisher post hoc least significant difference were conducted for the analysis. Results The malondialdehyde (nmol/mL) level was 2.58 ± 0.48 in the NSG, 8.09 ± 0.57 in the StC, 3.84 ± 0.53 in the SSt, and 2.84 ± 0.20 in the VSt group (P < 0.0002). The total glutathione (mmol/g) was 7.15 ± 0.59 in the NSG, 2.41 ± 0.43 in the StC, 4.58 ± 0.26 in the SSt, and 5.98 ± 0.13 in the VSt (P < 0.0002). The total oxidant status (mmol H2O2Eq/L) level was 3.56 ± 0.20 in the NSG, 9.99 ± 0.74 in the StC, 4.97 ± 0.39 in the SSt, and 3.81 ± 0.31 in the VSt (P < 0.0002). The total antioxidant status (mmolTroloxEq/L) level was 8.65 ± 0.37 in the NSG, 3.04 ± 0.22 in the StC, 6.29 ± 0.34 in the SSt, and 7.61 ± 0.40 in the VSt (P < 0.0002). Sertraline reduced pericellular edema in astrocytes and oligodendrocytes and decreased perivascular edema, dilatation, and congestion of blood vessels, whereas these were not seen with vortioxetine. Conclusions Compared with sertraline, vortioxetine is a neuroprotective antidepressant with higher antioxidant activity and can more effectively prevent stress-induced brain tissue injury.

Mare Volcanism in Apollo Basin Evaluating the Mare Basalt Genesis Models on the Moon

The Apollo basin is a well-preserved double-ringed impact basin located on the northeastern edge of the South Pole–Aitken (SPA) basin. The Apollo basin has been flooded and filled with large volumes of mare lavas, indicating an active volcanism history. Based on orbital data, we reveal that the Apollo basin exhibits an overall asymmetric configuration in the distribution of mare basalts as well as its topography, chemical compositions, and crustal thickness. The Apollo basin is an excellent example for assessing the influences of the above factors on mare basalts petrogenesis and evaluating mare basalt genesis models. It was found that the generation of mare basalt magmas and their emplacement in the Apollo basin seems to be strongly related to local thin crust (<30 km), but the formation of basaltic magmas should be independent of the decompression melting because the mare units (3.34–1.79 Ga) are much younger than the pre-Nectarian Apollo basin. The mare basalts filled in the Apollo basin exhibits a large variation of TiO2 abundances, indicating the heterogeneity of mantle sources, which is possible due to the lunar mantle overturn after the LMO solidification or the impact-induced mantle convection and migration. However, the prolonged mare volcanic history of the Apollo basin is not well explained, especially considering the low Th abundance (<2 ppm) of this region. In addition, the central mare erupted earlier than other mare units within the Apollo basin, which seems to contradict the predictions of the postbasin loading-induced stresses model. Laboratory investigations of the Chang’E-6 mare basalt samples could possibly answer the above questions and provide new insight into the mare volcanic history of the lunar farside and the connections between mare volcanism and impact basin formation/evolution.

Changes in economic deprivation and parental self-efficacy: Unemployment, poverty, and the mediating effect of psychological distress

Objective: The article investigates the influence of three aspects of economic deprivation on parental self-efficacy, and whether, or to what extent, these effects are mediated by psychological distress. Background: Scholarship shows that psychological resources such as parental self-efficacy can attenuate the negative repercussions of poverty for families. The article builds on the family stress model that higlights the role of economic deprivation for family functioning by Conger and colleagues. It focuses on the consequences of transitioning into unemployment, objective poverty, and subjective poverty for parental self-efficacy, and the potential mediating effect of psychological distress. Method: Using data from the German Family Panel (pairfam) Waves 4 to 12 (2011–2020), Baron and Kenny mediation analyses are conducted based on fixed effects regressions with standard errors based on clustered bootstrap procedure. Results: The results show that transitioning into subjective poverty significantly decreases parental self-efficacy, and that only a marginal part of this effect is mediated by psychological distress. A transition into objective poverty, by contrast, has no effect on parental self-efficacy. Likewise, unemployment has no direct effect on parental self-efficacy. However, transitioning into short-term unemployment reduces psychological distress and thereby buffers parent’s self-efficacy. This does by contrast not apply for long-term unemployment. Conclusion: The findings demonstrate the importance of differentiating between specific aspects of economic deprivation when investigating its consequences for parental self-efficacy and considering psychological distress as a potential mediator. Moreover, the findings provide longitudinal evidence for the consequences of a transition into economic deprivation for parental self-efficacy and point to the presence of gender effects with regard to unemployment.

Plastic Workability and Rheological Stress Model Based on an Artificial Neural Network of SiCp/Al-7.75Fe-1.04V-1.95Si Composites.

SiCp/Al-Fe-V-Si composites exhibit complex deformation behaviors at both room and high temperatures because of the presence of SiC reinforcement particles and numerous fine dispersed Al12(Fe, V)3Si heat-resistant phases. In this work, an artificial neural network (ANN) constitutive model was established to study the deformation behavior of SiCp/Al-7.75Fe-1.04V-1.95Si composites over a wide temperature range based on uniaxial compression. Then, microstructural observation, finite element analysis, and processing maps were utilized to investigate the plastic workability. The results showed that the ANN model fit the experimental stress-strain curves with high accuracy, achieving an R2 value of 0.999. The ANN model was embedded into finite element software to study plastic deformation behaviors, which indicated that this model could accurately compute the plastic and mechanical response during the compressing process. Finally, a thermomechanical processing diagram was developed, revealing that the optimal processing parameters of the SiCp/Al-7.75Fe-1.04V-1.95Si composites were a deformation temperature of 450-500 °C and a deformation rate of 0.1-0.2 s-1.

Parent conversations with young children: Implications for child well-being during the COVID-19 pandemic.

Parent-child conversations may minimize the impact of stressful situations on children's well-being. Parents were encouraged to talk with their children about the coronavirus (COVID-19) pandemic, yet research suggests that parent stress in response to the pandemic was associated with disruptions in parenting and increased child emotional distress. In the present study, 205 parents of children aged 3-6 years (50.7% girls, 56.6% White) reported on conversations about the pandemic and responded to measures of parent stress and child emotional distress in the fall of 2020. Qualitative analysis revealed that talk about mitigation strategies was frequent; most parents offered an explanation for pandemic changes, whereas fewer parents reported communicating support. Guided by the family stress model, we then examined whether different conversation types moderated the association between parent stress and child emotional distress. Only talk about pandemic changes and explanations that COVID-19 was dangerous acted as moderators, suggesting that these conversation types strengthened the association between parent stress and child emotional distress. A main effect of self-protective explanations being associated with lower child emotional distress was also found. We discuss the implications of these findings for future research on parent-child conversations about stressful situations. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Moringa oleifera Lam. seed lectin (WSMoL) reduces chronic stress-induced anxiety and depression in mice by lessening inflammation and balancing brain chemicals

Phyto-based treatments for anxiety and depression are gaining attention. The efficacy of the water-soluble Moringa oleifera seed lectin (WSMoL) in reducing acute anxiolytic and depressive-like behaviors in mice has been previously demonstrated. In the present study, it was evaluated the effects of WSMoL on reducing anxiety and depressive-like symptoms in a mouse model of unpredictable chronic mild stress (UCMS). The animals were divided into groups and exposed to a four-week UCMS regimen. Following this, the mice received daily intraperitoneal injections of vehicle (non-stressed and UCMS control groups), WSMoL (2 or 4 mg/kg), or fluoxetine (10 mg/kg) for 21 days. Neurobehavioral tests included the open field test and elevated plus maze test to assess anxiety-like behavior, and the tail suspension test and sucrose preference test to evaluate depression-like behavior. Biochemical analyses measured serum corticosterone and cytokines as well brain levels of cytokines and monoamines. All tests indicated that WSMoL significantly (p < 0.05) reversed the anxiety and depression-like behaviors induced by UCMS. The stress protocol increased serum corticosterone levels and WSMoL treatment was not able to normalize corticosterone secretion. WSMoL treatment reduced serum and brain levels of IL-2, IL-6, and TNF-α, indicating reduced neuroinflammation, and increased brain levels of dopamine, serotonin, and noradrenaline. In summary, WSMoL mitigated UCMS-induced anxiety and depression-like behaviors by reducing neuroinflammation and modulating brain monoamine levels.

Impact of Workplace Bullying on Psychological Distress: Role of Perceived Organisational Support and Religious Coping

Despite the fact that perceived organisational support (POS) and religious coping have been advocated as a crucial component of the stress model, the roles remain unclear among academics that often associate with heavy workloads. Therefore, this study aims to examine the moderating role of POS, and the mediating role of religious coping between the relationship of workplace bullying and psychological distress among academics in higher educational institutions (HEIs). Data were collected from academic staff from private and public universities in Malaysia, and a total of 219 data were used. The results revealed that workplace bullying has a positive impact on academics’ psychological distress, and the POS significantly moderated the relationship between workplace bullying and psychological distress. However, this study failed to support the mediating role of religious coping. This study adds to our knowledge of the stress model, by focusing more on perceived organisational support in minimising psychological distress and less on personal resources (religious coping).

Depth–Strength In-Situ Stress Model for Granite in Southeastern Tibetan Plateau and Its Implications for Stress Estimation in the Upper Crust

Depth–Strength In-Situ Stress Model for Granite in Southeastern Tibetan Plateau and Its Implications for Stress Estimation in the Upper Crust

A DATA DRIVEN METHOD FOR THE DERIVATION OF EXPLICIT ALGEBRAIC REYNOLDS STRESS MODELS APPLIED TO THE WAKE LOSSES OF LOW-PRESSURE TURBINE CASCADES

Abstract This paper introduces and validates a data-driven approach to improve the prediction of linear eddy viscosity models (LEVMs). The general approach is adopted in order to improve the wake mixing of low-pressure turbine (LPT) cascades. The approach follows the rationale applied in the derivation of explicit algebraic Reynolds stress models (EARSMs) by including additional second-order tensors in the Boussinesq assumption. The unknown scalar functions that determine the contributions of each second-order tensor to the Reynolds stresses are approximated as polynomials. A metamodel-assisted multi-objective optimization determines the value of each of the polynomial coefficients by minimizing the difference between the result of the EARSM simulation and reference data provided by a high fidelity large eddy simulation (LES). In this study, tailor made EARSMs are calibrated to improve the prediction of the kinetic energy loss distribution in the wake of the T106C LPT cascade. We investigated the influence of each polynomial coefficient of the EARSM on the results. The models generated by the approach reduced the deviations in total kinetic energy loss between the LES reference solution and the baseline model by approximately 70%. The turbulent quantities are analyzed to identify the physical correlations between the model inputs and the improvement. The transferability of the models to unseen test cases was assessed using the MTU-T161 LPT cascade. In summary, the suggested approach was able to generate tailor made EARSM models that reduce the deviations between RANS and LES for the mixing of turbulent wake flows.

Menstrual management in transgender and gender diverse individuals: psychiatric and psychosocial considerations.

Transgender and gender-diverse (TGD) menstruators are individuals assigned female at birth (AFAB)*, who retain the capacity to menstruate and have a gender identity that differs from their natal sex. Reports indicate up to 1.6 million individuals in the US identify as TGD. Until recently, the mainstream menstrual discourse has failed to capture the experience of transmenstruators. However, a better understanding of the menstrual experiences of TGD-AFAB will allow for more individualized patient-centered care. In this review, we provide the relevant data necessary to inform the psychiatric management of menstruation in TGD-AFAB individuals, including experiences of menstruation, preferences for menstrual management, and the impact on mental health. Our review indicates that menstrual care in TGD patients must be tailored to the individual; clinicians should remain open-minded to the unique experience of transmenstruators; gender-affirming menstrual care is necessary to reduce psychological burden. It should not be assumed that TGD-AFAB menstruators are utilizing appropriate contraceptive methods and should receive contraceptive and fertility preservation counseling. We highlight the importance of having these conversations early in the reproductive arch, even before puberty onset. Keeping in mind the gender minority stress model, in the upcoming sections, we discuss the limited body of literature on mood disorders in TGD-AFAB individuals who menstruate, undergo menstrual suppression, or continue to ovulate. The psychological impact of hormonal therapies is also reviewed.

The BET inhibitor Apabetalone protects against heart failure with preserved ejection fraction by suppressing myocardial inflammation

Abstract Background Posttranslational histone modifications, play a major role in cardiac hypertrophy and dysfunction. Apabetalone (APA), a selective inhibitor of bromodomain and extraterminal containing protein family (BET) proteins, prevents bromodomain-containing protein 4 (BRD4) interactions with chromatin thus modulating transcriptional programs in different organs. Purpose We sought to investigate whether APA could be beneficial in cardiometabolic heart failure with preserved ejection fraction (cHFpEF). Methods Mice were subjected to high fat diet feeding and L-NAME treatment for 15 weeks to induce cHFpEF. Histology, mouse echocardiography (Vevo3100) and Treadmill exhaustion test were performed. Unbiased gene expression profiling by PCR array and proteomics analysis (Olink) was employed in left ventricular (LV) myocardial specimens from HFpEF mice and control animals. Cultured cardiomyocytes (CMs) treated with palmitic acid (PA) were used as an in vitro model of metabolic stress. cHFpEF mice were chronically treated with the BET inhibitor APA (150mg/kg/day) or vehicle (DMSO). In order to translate our findings to the human setting, passive stiffness of skinned CMs collected from cHFpEF patients was assessed before and after APA treatment. Results HFpEF mice displayed LV hypertrophy, diastolic dysfunction, myocardial fibrosis, lung congestion and impaired exercise tolerance as compared to controls. Interestingly, diastolic dysfunction - assessed by E/A ratio and isovolumic relaxation time (IVRT) - and lung congestion were significantly reduced in HFpEF mice treated with APA, while exercise tolerance was improved. Transcriptomic analysis in PA-treated CMs and LV mouse specimens from cHFpEF mice showed a profound deregulation of genes controlling inflammation, namely IL-6, TNF-alpha, and IL-1beta. ChIP assays showed BRD4 occupancy on the promoter of several inflammatory genes, including IL6. Treatment with APA suppressed most of inflammatory genes, with a pronounced effect on IL6 expression. Moreover, APA reduced circulating levels of several inflammatory chemokines. The beneficial effects of APA were explained by modulation of IL-6/CaMKII/STAT3 pathway both in cHFpEF hearts and PA-treated CMs. In skinned CMs from cHFpEF patients, both APA and IL6 blockade were able to attenuate passive stiffness. Conclusions Our findings set the stage for preclinical studies and exploratory clinical trials testing APA in patients with cHFpEF.