Breaking law of overburden rock and key mining technology for narrow coal pillar working face in isolated island.

When conducting retreat mining in segmented coal pillars, the dynamic evolution of stress and overlying strata structure is more complex than conventional working faces due to the influence of adjacent working faces. Understanding and mastering the dynamic evolution patterns of overlying strata structure after retreat mining in segmented coal pillar working faces is essential for guiding the safe recovery of coal pillar resources under similar conditions. Through statistical analysis of the types of residual coal and the mining techniques, the current research status of residual coal mining system in China has been summarized. Based on the safety recovery technology system for multi-type residual coal pillar resources at Zhaogu No.2 Mine, this paper focuses on narrow coal pillar working faces in sections with fully mined-out areas on both sides. By using research methods such as on-site measurement, theoretical analysis, numerical simulation, and engineering experiments, starting from the stress state analysis and evolution law of coal seam mining, the dynamic evolution law of the overlying rock structure of sectional coal pillars has been mastered. On this basis, a stress arch mechanical model of the mining area is constructed, and the working resistance of the support is calculated and determined, ensuring the safe recovery of the working face. The research results show that before the backfilling of the sectional coal pillar working face, the working face is affected by the overlapping mining of the goaf on both sides, presenting a "bimodal" stress distribution pattern, with a stress concentration coefficient between 1.78 and 3.2. After the extraction of segmented coal pillars, stress arches consisting of high-stress zones form along both the strike and dip of the working face. The structural support provided by stress arches undergoes a dynamic evolution process of "formation-development-elevation-stabilization" as the working face advances. Following the instability and rupture of the lower basic roof hinge structure, the stress-bearing structure shifts to the higher basic roof, continuing to provide support for the surrounding rock stress in the mining space of the working face. A stress arch mechanical model for the dip and strike of the mining area is constructed , and the shape characteristics of the overlying rock stress arch in the coal pillar working face is mastered. Based on the stress distribution law and stress arch evolution characteristics of the surrounding rock of the coal pillar working face, the maximum working resistance of the support in the working face is theoretically calculated to be 9153.48kN. Compared with the measured mine pressure data, the selected support effectively ensures the safety production of the working face.

TFAM is an autophagy receptor that limits inflammation by binding to cytoplasmic mitochondrial DNA.

When cells are stressed, DNA from energy-producing mitochondria can leak out and drive inflammatory immune responses if not cleared. Cells employ a quality control system called autophagy to specifically degrade damaged components. We discovered that mitochondrial transcription factor A (TFAM)-a protein that binds mitochondrial DNA (mtDNA)-helps to eliminate leaked mtDNA by interacting with the autophagy protein LC3 through an autolysosomal pathway (we term this nucleoid-phagy). TFAM contains a molecular zip code called the LC3 interacting region (LIR) motif that enables this binding. Although mutating TFAM's LIR motif did not affect its normal mitochondrial functions, more mtDNA accumulated in the cell cytoplasm, activating inflammatory signalling pathways. Thus, TFAM mediates autophagic removal of leaked mtDNA to restrict inflammation. Identifying this mechanism advances understanding of how cells exploit autophagy machinery to selectively target and degrade inflammatory mtDNA. These findings could inform research on diseases involving mitochondrial damage and inflammation.

Nonlinear evolution characteristics and seepage mechanical model of fluids in broken rock mass based on the bifurcation theory.

With the deep extension of coal mining in China, fault water inrush has become one of the major disasters threatening the safety production of coal mine. Based on the control equations of steady state and non-Darcy seepage in fractured rock mass, the multi-parameter nonlinear dynamic seepage equations of fractured rock mass are established in this paper. Based on the nonlinear dynamics theory, the function of the state variable in the system is derived, and the influence of the gradual change of non-Darcy flow factors on the structural stability of seepage system is studied. The research achievements show that there are three branches in the equilibrium state of the seepage system. Specifically, the stability of the equilibrium state changes abruptly near the limit parameter. The seepage dynamic system of fractured rock mass has the delayed bifurcation, and the coal mine disaster such as fault water inrush occurs easily at the bifurcation point. The research results are of great significance to enrich the theory of fault water inrush in coal mine, and to reveal the disastrous mechanism of fault water inrush and guide its prevention and control technology in coal mine, which can provide the theoretical reference for predicting the water seepage stability in fractured rock mass.

Research on overburden structural characteristics and support adaptability in cooperative mining of sectional coal pillar and bottom coal seam.

In the mining process of the II1 coal seam at Zhaogu No. 2 coal mine, a method of stratified mining is employed, leaving relatively wide coal pillars in sections. To enhance the resource recovery rate, the mine carries out the cooperative mining of the sectional coal pillars and the lower layer coal seam. The 14,022 cooperative working face of fully-mechanized and fully-mechanized top-coal caving at Zhaogu No. 2 coal mine is taken as the research object. Through numerical simulation, theoretical calculations, and on-site industrial trials, a comprehensive analysis of the overburden structural characteristics and the support adaptability at the working face is conducted. It is clarified that a stress arch bearing structure can be formed above the sectional coal pillars during cooperative mining, and this structure is controlled by key strata. The formation of a stress arch bearing structure in the overburden above the sectional coal pillars provides protection for the underlying mining area. A formula for calculating the working resistance of hydraulic supports under the stress arch in sectional coal pillar is derived. Based on these results, the working resistance of hydraulic supports in the coal pillar area is calculated and selected. Field application shows that the working resistance of the support is 10,000 kN in the fully-mechanized top-coal caving working face, and is 9000 kN in fully-mechanized working face, meeting the support requirements and ensuring safe mining at the working face. This study provides a valuable engineering reference for achieving cooperative mining of abandoned sectional coal pillars and lower layer coal seam in stratified mining method.

Fracture propagation and pore pressure evolution characteristics induced by hydraulic and pneumatic fracturing of coal.

A two-dimensional unsteady seepage model for coal using a finite element program is developed, and the temporal variations of key factors such as water pressure and hydraulic gradient are analyzed in this paper. Additionally, the triaxial rock mechanical experiment and utilized pneumatic fracturing equipment on raw coal samples to investigate both hydraulic and pneumatic fracturing processes are conducted. Through these experiments, the relationship between pressure and crack formation and expansion are examined. The analysis reveals that the pore pressure gradient at the coal inlet reaches its peak during rapid surges in water pressure but diminishes over time. Conversely, the pore pressure gradient at the outlet side exhibits a gradual increase. Hydraulic fracturing is most likely to occur at the water inlet during sudden increases in water pressure. Besides, as the permeability of coal decreases, the duration for seepage stabilization prolongs due to the intensified pore pressure gradient resulting from sudden increases in water pressure. Moreover, an extended period of high hydraulic gradient further increases the risk of hydraulic fracturing. The experimental findings indicate that coal samples initially experience tensile failure influenced by water and air pressure. Subsequently, mode I cracks form under pressure, propagating along the fracture surface and becoming visible. The main types of failure observed in hydraulic and pneumatic fracturing are diametrical tensile failure, and the development of fractures can be categorized into three distinct stages, which contains the initial stage characterized by slight volume changes while water pressure increases, the expansion stage when pressure reaches the failure strength, and the crack closure stage marked by little or even decreasing volume changes during pressure unloading. The acoustic emission signal accurately corresponds to these three stages.

Endothelial NLRP3 inflammasome regulation in atherosclerosis.

AIM: The activation of Nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome in endothelial cells (ECs) contributes to vascular inflammation in atherosclerosis. Considering the high glycolytic rate of ECs, we delineated whether and how glycolysis determines endothelial NLRP3 inflammasome activation in atherosclerosis. METHODS AND RESULTS: Our results demonstrated a significant upregulation of 6-Phosphofructo-2-Kinase/Fructose-2,6-Biphosphatase 3 (PFKFB3), a key regulator of glycolysis, in human and mouse atherosclerotic endothelium, which positively correlated with NLRP3 levels. Atherosclerotic stimuli upregulated endothelial PFKFB3 expression via sterol regulatory element binding protein 2 (SREBP2) transactivation. EC-selective haplodeficiency of Pfkfb3 in Apoe-/- mice resulted in reduced endothelial NLRP3 inflammasome activation and attenuation of atherogenesis. Mechanistic investigations revealed that PFKFB3-driven glycolysis increased the NADH content and induced oligomerization of C-terminal binding protein 1 (CtBP1), an NADH-sensitive transcriptional co-repressor. The monomer form, but not the oligomer form, of CtBP1 was found to associate with the transcriptional repressor Forkhead box P1 (FOXP1) and acted as a transrepressor of inflammasome components, including NLRP3, caspase-1, and interleukin-1ß (IL-1ß). Interfering with NADH-induced CtBP1 oligomerization restored its binding to FOXP1 and inhibited the glycolysis-dependent upregulation of NLRP3, Caspase-1, and IL-1ß. Additionally, EC-specific overexpression of NADH-insensitive CtBP1 alleviates atherosclerosis. CONCLUSIONS: Our findings highlight the existence of a glycolysis-dependent NADH/CtBP/FOXP1-transrepression pathway that regulates endothelial NLRP3 inflammasome activation in atherogenesis. This pathway represents a potential target for selective PFKFB3 inhibitors or strategies aimed at disrupting CtBP1 oligomerization to modulate atherosclerosis.

Experimental research on mechanical performance of grouting plugging material with large amount of fly ash.

In order to achieve the purpose of long-term stable mining of roadway, the strength and stability of rock mass are improved by means of grouting of fractured rock mass. In this paper, orthogonal test and numerical simulation methods were used to study the plugging performance of large amount of fly ash grouting slurry. The fluidity, water separation rate, compressive strength, setting time, stone rate and viscosity of the slurry were analyzed, and the optimal slurry ratio scheme was obtained. Under the optimal ratio scheme, the slurry transport process of the fractured rock mass was simulated, and the dynamic evolution law of the permeability of the slurry in the fractured rock mass was obtained. The study shows that the proportions of fly ash, ordinary Portland cement, loess, accelerant, expansion agent, bentonite water reducer and solidifying agent were 52.65%, 27.70%, 13.85%, 3%, 0.7%, 0.8%, 0.6% and 0.7% in the slurry ratio scheme, respectively. The slurry migration in the fractured rock mass experienced three stages, namely the filling and diffusion stage, the percolation and deposition stage and the sealing stage. The initial permeability was 971.9 mD and decreased to 45.79 mD after 1800 s, with a decrease of 95.3%. The slurry sealing performance was significantly improved, which has certain guiding significance for the application of underground grouting reinforcement engineering.

Evolution mechanism of water-conducting fractures in overburden under the influence of water-rich fault in underground coal mining.

Based on the 7618 working face in Yaoqiao coal mine of Datun mining area, the activation mechanism of water-rich faults and the development characteristics of water-conducting fractures in overlying strata under the influence of faults are studied by theoretical analysis, numerical simulation and field measurement in this paper. The research results show that Anderson model and Mohr-Coulomb strength criterion are combined to establish the fault failure mechanical model, and the fault activation criterion under the influence of mining is obtained. FLAC3D numerical simulation results show that with the advance of the working face, the fault begins to be affected by the mining effect of the working face at the distance of 20 ~ 30 m from the fault. Meanwhile, with the advance of the working face, the overburden shear failure range also expands, and the fault fracture gradually expands from top to bottom. The failure zone of the working face roof is connected with the fault fracture zone. Then the fault is "activated" and causes the fault to become a water gushing channel, and finally the water gushing disaster occurs. Through numerical simulation and comparative analysis, the development height of water-conducting fracture is 73.2 m in the absence of fault, and 73.7 m in the presence of fault, indicating that the fault has little influence on the maximum development height of water-conducting fracture. The actual development height of the water-conducting fracture zone in the 7618 working face is 73.97 m and the fracture production ratio is 13.7. The research results can provide theoretical reference for the safe mining of similar working faces across faults.

Seepage evolution characteristics and water inrush mechanism in collapse column under mining influence.

To obtain the seepage evolution rule and water inrush mechanism of the collapse column, a multi-field coupled mechanical model for water inrush disasters caused by the collapse column is established in this paper, on the basis of the specific engineering conditions of the 1908 working face in the Qianjin coal mine. The mechanical model is composed of internal column elements within the collapse column and surrounding rock masses. The research focuses on the seepage evolution rule in the roof collapse column under different mining conditions and investigates the permeation instability mechanism of collapse column based on the transition of flow state. The research results indicate that the seepage pathway evolves continuously, ultimately forming a channel for water inrush, as the working face advances towards the collapse column. Besides, the water inflow increases rapidly when the working face advances 100 m, then gradually stabilizes, indicating that the seepage channel entry of the collapse column is in a stable stage. Meanwhile, mass loss in the collapse column gradually moves upward. the collapse column remains stable as a whole in the initial stage of water flow, with a small permeability, exhibiting linear flow. As time steps increases, particle loss in collapse column gradually extends to the upper part, forming a stable seepage channel. The flow velocity shows fluctuations with a slow declining trend over time.

The Báa nnilah Program: Results of a Chronic-Illness Self-Management Cluster Randomized Trial with the Apsáalooke Nation.

Indigenous people in Montana are disproportionately affected by chronic illness (CI), a legacy of settler colonialism. Existing programs addressing CI self-management are not appropriate because they are not consonant with Indigenous cultures in general and the Apsáalooke culture specifically. A research partnership between the Apsáalooke (Crow Nation) non-profit organization Messengers for Health and Montana State University co-developed, implemented, and evaluated a CI self-management program for community members. This article examines qualitative and quantitative program impacts using a pragmatic cluster randomized clinical trial design with intervention and waitlist control arms. The quantitative and qualitative data resulted in different stories on the impact of the Báa nnilah program. Neither of the quantitative hypotheses were supported with one exception. The qualitative data showed substantial positive outcomes across multiple areas. We examine why the data sets led to two very different stories, and provide study strengths and limitations, recommendations, and future directions.

Migration mechanism of grouting slurry and permeability reduction in mining fractured rock mass.

In order to solve the water and gas discharge hazard caused by gob water and harmful gases (such as CO), the method of grouting overburden fractures is adopted to achieve the purpose of safe and efficient mining production in coal mines. This paper carries out the experimental research on the permeability reduction effect of grouting in fractured rock mass, expounds the relationship between gas flow rate and pressure gradient, seepage pressure and permeability, confining pressure and permeability, and analyzes the permeability change law of fractured rock mass before and after grouting. Besides, the grouting migration and permeability reduction model of fractured fine-grained sandstone is constructed by combining grouting test and numerical simulation, which reveals the dynamic evolution law of rock mass permeability in the grouting process. The results show that the permeability of the grouting rock sample decreases from 700-13,000 to 15-300 mD than that of the ungrouting rock sample, and the decrease is more than 95%, which indicates that the sealing performance of grouting slurry is better. Besides, numerical simulations show that the initial permeability of rock samples is 971.9 mD, and the permeability decreases to 45.79 mD after 1800s, and the permeability decreases to 95.3%, which is basically consistent with the experimental results after grouting. The greater the grouting pressure is, the better the grouting effect is. With the increase of the grouting pressure, the increase of the grouting effect is no longer obvious.

Metabolic Syndrome, Modifiable Lifestyle Factors, and Sleep-Disordered Breathing: The Hispanic Community Health Study.

BACKGROUND: US Hispanics/Latinos are disproportionately susceptible to metabolic syndrome (MetS), attributed in part to systemic inequities related to health and lifestyle factors such as low physical activity (PA) levels, diet quality, alcohol use, tobacco use, and sleep disorder. Gender and heritage group differences are vastly understudied and need to be examined in this heterogeneous population. PURPOSE: To examine the relationships between select health and lifestyle factors and MetS among Hispanic gender and heritage subgroups (Hypothesis 1) and determine whether gender and heritage moderate those relationships (Hypothesis 2). METHODS: Participants included 14,155 Hispanic Americans aged 18-76 (59% female, mean age 45.92 ± 13.97) from seven heritage subgroups. This secondary analysis of cross-sectional data from the observational Hispanic Community Health Study/Study of Latinos (HCHS/SOL) dataset used hierarchical multinomial logistic regression to test Hypothesis 1; the dependent variable, MetS, included three categories delineating absence of MetS and presence of MetS with or without related medication use. Hayes' PROCESS macro tested Hypothesis 2. RESULTS: Low PA and sleep-disordered breathing (SDB) each had significant (p < .001) predictive value of MetS group membership, whereas both low and high alcohol use (p < .001) were associated with decreased MetS risk. Cigarette pack-years were not significantly associated with MetS outcomes. Gender moderated the association between MetS and alcohol use (p < .001), cigarette pack-years (p < .001), and SDB (p < .001) such that the effects on MetS were higher in females than males. The association between MetS and diet quality (p < .001) was stronger among males than in females. CONCLUSIONS: Gender and heritage differences were prominent among study variables.

Abnormal ore pressure mechanism of working face under the influence of overlying concentrated coal pillar.

Shenfu Dongsheng coal field is a cross-century energy base which is developed and constructed in China. In recent years, some mines have successively entered to the coal seam of the second layer. Due to the reasons of early mining, many coal pillars are left in the coal seam of the first layer, resulting in the phenomenon of strong ore pressure in the mining range before and after the coal pillar in the lower coal seam and even causing the buckling accident. In order to solve such safety problems, this paper takes the 22,307 working face in Bulianta coal mine as the research object, adopts physical similarity simulation experiment and theoretical analysis to systematically study the overlying rock characteristics and abnormal ore pressure manifestation mechanism of shallow and close coal seam in different working stages. The results show that the roof overburden of the key layer in the lower group bends and sinks when the coal pillar is mined, resulting in the activation and instability of the "masonry beam" structure formed by the roof of the upper coal seam. When the coal pillar is discharged, the residual concentrated coal pillar and the room type coal pillar are unstable under the action of high supporting stress, resulting in shear failure of the inter-layer rock in the upper part of 22,307 working face, causing the strong dynamic pressure of the working face to appear and then leading to the buckling accident. The working resistance of the support in each stage is obtained by establishing the structure diagram of the overlying rock under each stage and the corresponding mechanical structure model. Finally, the working resistance required by the support in the mining stage under the goaf is 16,692.6 kN, the working resistance required by the support in the coal pillar stage is 19,692.6 kN, the working resistance required by the support in the mining stage under the concentrated coal pillar is 13,150.6 kN, and the working resistance required by the support in the coal pillar stage is 19,215.6 kN.

Research on slurry diffusion and seepage law in mining overburden fractures based on CFD numerical method.

It is of great theoretical significance and engineering application value to research the diffusion law of slurry in mining fractures of rock strata to enrich grouting theory and improve grouting sealing effect. In this paper, the law of grout diffusion in fractures under different working conditions is systematically explored and analyzed, and a numerical simulation scheme of grout diffusion in a single slab crack is established. Then, the diffusion law of grouting slurry in crack under different rheological index and different consistency index is further investigated. The results show that the diffusion time of grouting slurry has no relation with the rheological index. The grout pressure at the same point increases with the increase of rheological index. When the rheological index increases by 0.1, the grout pressure increases by about 12.5%. The closer the grouting mouth is, the more the grouting pressure is affected by the rheological index. There is little relationship between the diffusion time of grouting slurry and consistency index. The grout pressure at each measurement point increases with the increase of the consistency index. When the consistency index increases by 1, the grout pressure increases by about 15% on the basis of the origin. The closer the grouting mouth is, the more the grouting pressure is affected by the consistency index. In engineering practice, when grouting slurry with large rheological index or consistency index exists, it is necessary to moderately increase the grouting pressure value.

Glycolysis Promotes Angiotensin II-Induced Aortic Remodeling Through Regulating Endothelial-to-Mesenchymal Transition via the Corepressor C-Terminal Binding Protein 1.

BACKGROUND: Endothelial dysfunction plays a crucial role in aortic remodeling. Aerobic glycolysis and endothelial-to-mesenchymal transition (EndoMT) have, respectively, been suggested to contribute to endothelial dysfunction in many cardiovascular diseases. Here, we tested the hypothesis that glycolytic reprogramming is critical for EndoMT induction in aortic remodeling through an epigenetic mechanism mediated by a transcriptional corepressor CtBP1 (C-terminal binding protein 1), a sensor of glycolysis-derived NADH. METHODS: EndoMT program, aortic remodeling, and endothelial expression of the glycolytic activator PFKFB3 (6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase isoform 3) were evaluated in Ang (angiotensin) II-infused mice. Mice with endothelial-specific Pfkfb3 deficiency or CtBP1 inactivation, immunoprecipitation, chromatin immunoprecipitation, and luciferase reporter assay were employed to elucidate whether and how PFKFB3/CtBP1 epigenetically controls EndoMT. RESULTS: The EndoMT program and increased endothelial PFKFB3 expression were induced in remodeled thoracic aortas. In TGF-ß (transforming growth factor-ß)-treated human endothelial cells, activated SMAD2/3 (SMAD Family Member 2/3) transcriptionally upregulated PFKFB3 expression. In turn, the TGF-ß/SMAD signaling and EndoMT were compromised by silencing or inhibition of PFKFB3. Mechanistic studies revealed that PFKFB3-mediated glycolysis increased NADH content and activated the NADH-sensitive CtBP1. Through interaction with the transcription repressor E2F4 (E2F Transcription Factor 4), CtBP1 enhanced E2F4-mediated transcriptional repression of SMURF2 (SMAD ubiquitin regulatory factor 2), a negative regulator of TGF-ß/SMAD2 signaling. Additionally, EC-specific Pfkfb3 deficiency or CtBP1 inactivation in mice led to attenuated Ang II-induced aortic remodeling. CONCLUSIONS: Our results demonstrate a glycolysis-mediated positive feedback loop of the TGF-ß signaling to induce EndoMT and indicate that therapeutically targeting endothelial PFKFB3 or CtBP1 activity could provide a basis for treating EndoMT-linked aortic remodeling.

Preoperative prediction model for microvascular invasion in HBV-related intrahepatic cholangiocarcinoma.

BACKGROUND AND AIMS: Preoperative prediction of microvascular invasion (MVI) using a noninvasive method remain unresolved, especially in HBV-related in intrahepatic cholangiocarcinoma (ICC). This study aimed to build and validate a preoperative prediction model for MVI in HBV-related ICC. METHODS: Patients with HBV-associated ICC undergoing curative surgical resection were identified. Univariate and multivariate logistic regression analyses were performed to determine the independent risk factors of MVI in the training cohort. Then, a prediction model was built by enrolling the independent risk factors. The predictive performance was validated by receiver operator characteristic curve (ROC) and calibration in the validation cohort. RESULTS: Consecutive 626 patients were identified and randomly divided into the training (418, 67%) and validation (208, 33%) cohorts. Multivariate analysis showed that TBIL, CA19-9, tumor size, tumor number, and preoperative image lymph node metastasis were independently associated with MVI. Then, a model was built by enrolling former fiver risk factors. In the validation cohort, the performance of this model showed good calibration. The area under the curve was 0.874 (95% CI: 0.765-0.894) and 0.729 (95%CI: 0.706-0.751) in the training and validation cohort, respectively. Decision curve analysis showed an obvious net benefit from the model. CONCLUSION: Based on clinical data, an easy model was built for the preoperative prediction of MVI, which can assist clinicians in surgical decision-making and adjuvant therapy.

Chemical mitophagy modulators: Drug development strategies and novel regulatory mechanisms.

Maintaining mitochondrial homeostasis is a potential therapeutic strategy for various diseases, including neurodegenerative diseases, cardiovascular diseases, metabolic disorders, and cancer. Selective degradation of mitochondria by autophagy (mitophagy) is a fundamental mitochondrial quality control mechanism conserved from yeast to humans. Indeed, small-molecule modulators of mitophagy are valuable pharmaceutical tools that can be used to dissect complex biological processes and turn them into potential drugs. In the past few years, pharmacological regulation of mitophagy has shown promising therapeutic efficacy in various disease models. However, with the increasing number of chemical mitophagy modulator studies, frequent methodological flaws can be observed, leading some studies to draw unreliable or misleading conclusions. This review attempts (a) to summarize the molecular mechanisms of mitophagy; (b) to propose a Mitophagy Modulator Characterization System (MMCS); (c) to perform a comprehensive analysis of methods used to characterize mitophagy modulators, covering publications over the past 20 years; (d) to provide novel targets for pharmacological intervention of mitophagy. We believe this review will provide a panorama of current research on chemical mitophagy modulators and promote the development of safe and robust mitophagy modulators with therapeutic potential by introducing high methodological standards.

Mental health is related to metabolic syndrome: The Hispanic community health study/ study of Latinos.

OBJECTIVE: Metabolic syndrome (MetS) is associated with common mental health conditions. Using cross-sectional data from the observational Hispanic Community Health Study / Study of Latinos (HCHS/SOL), this study examined the relationship between MetS and depression and anxiety in addition to testing moderating effects of gender and Hispanic heritage subgroups. METHODS: Participants included 13,496 Hispanic Americans aged 18-74 (59% women, mean age 46.59 ± 13.65) from seven heritage subgroups. Depression was measured using the Center for Epidemiologic Studies Depression 10-item scale, and anxiety was assessed using the State-Trait Anxiety Inventory 10-item scale. A 3-level categorical variable was developed to assess the combined influence of depression and anxiety. The dependent variable is dichotomous, delineating the presence or absence of MetS as defined by the National Cholesterol Education Program Third Adult Treatment Panel. Logistic regression and Hayes' PROCESS macro assessed these relationships and the moderating effects of gender-heritage subgroups. RESULTS: Results suggest depression (p < .001) and anxiety (p < .001) were associated with an increased likelihood of MetS. Puerto Ricans had the highest, and South Americans had the lowest, levels of depression and anxiety. Gender moderated the relationship between mental health and MetS, with women having a significant increase in the probability of MetS with depression (p < .001), anxiety (p < .001), or both (p < .001). CONCLUSION: Elevated symptoms of depression and anxiety are associated with the presence of MetS in US Hispanic subgroups. Gender-heritage differences are present among the study variables. Strategies to manage psychological well-being must be employed to optimize cardiometabolic health in US Hispanics.

Glycolysis and de novo fatty acid synthesis cooperatively regulate pathological vascular smooth muscle cell phenotypic switching and neointimal hyperplasia.

Switching of vascular smooth muscle cells (VSMCs) from a contractile phenotype to a dedifferentiated (proliferative) phenotype contributes to neointima formation, which has been demonstrated to possess a tumor-like nature. Dysregulated glucose and lipid metabolism is recognized as a hallmark of tumors but has not thoroughly been elucidated in neointima formation. Here, we investigated the cooperative role of glycolysis and fatty acid synthesis in vascular injury-induced VSMC dedifferentiation and neointima formation. We found that the expression of hypoxia-inducible factor-1α (HIF-1α) and its target 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase (PFKFB3), a critical glycolytic enzyme, were induced in the neointimal VSMCs of human stenotic carotid arteries and wire-injured mouse carotid arteries. HIF-1α overexpression led to elevated glycolysis and resulted in a decreased contractile phenotype while promoting VSMC proliferation and activation of the mechanistic target of rapamycin complex 1 (mTORC1). Conversely, silencing Pfkfb3 had the opposite effects. Mechanistic studies demonstrated that glycolysis generates acetyl coenzyme A to fuel de novo fatty acid synthesis and mTORC1 activation. Whole-transcriptome sequencing analysis confirmed the increased expression of PFKFB3 and fatty acid synthetase (FASN) in dedifferentiated VSMCs. More importantly, FASN upregulation was observed in neointimal VSMCs of human stenotic carotid arteries. Finally, interfering with PFKFB3 or FASN suppressed vascular injury-induced mTORC1 activation, VSMC dedifferentiation, and neointima formation. Together, this study demonstrated that PFKFB3-mediated glycolytic reprogramming and FASN-mediated lipid metabolic reprogramming are distinctive features of VSMC phenotypic switching and could be potential therapeutic targets for treating vascular diseases with neointima formation. © 2023 The Pathological Society of Great Britain and Ireland.