USP8-governed GPX4 homeostasis orchestrates ferroptosis and cancer immunotherapy.

Ferroptosis is an iron-dependent type of regulated cell death resulting from extensive lipid peroxidation and plays a critical role in various physiological and pathological processes. However, the regulatory mechanisms for ferroptosis sensitivity remain incompletely understood. Here, we report that homozygous deletion of Usp8 (ubiquitin-specific protease 8) in intestinal epithelial cells (IECs) leads to architectural changes in the colonic epithelium and shortens mouse lifespan accompanied by increased IEC death and signs of lipid peroxidation. However, mice with heterozygous deletion of Usp8 in IECs display normal phenotype and become resistant to azoxymethane/dextran sodium sulfate-induced colorectal tumorigenesis. Mechanistically, USP8 interacts with and deubiquitinates glutathione peroxidase 4 (GPX4), leading to GPX4 stabilization. Thus, USP8 inhibition destabilizes GPX4 and sensitizes cancer cells to ferroptosis in vitro. Notably, USP8 inhibition in combination with ferroptosis inducers retards tumor growth and enhances CD8+ T cell infiltration, which potentiates tumor response to anti-PD-1 immunotherapy in vivo. These findings uncover that USP8 counteracts ferroptosis by stabilizing GPX4 and highlight targeting USP8 as a potential therapeutic strategy to boost ferroptosis for enhancing cancer immunotherapy.

Comparative Transcriptome Analysis Reveals Inhibitory Roles of Strigolactone in Axillary Bud Outgrowth in Ratoon Rice.

Axillary bud outgrowth, a key factor in ratoon rice yield formation, is regulated by several phytohormone signals. The regulatory mechanism of key genes underlying ratoon buds in response to phytohormones in ratoon rice has been less reported. In this study, GR24 (a strigolactone analogue) was used to analyze the ratooning characteristics in rice cultivar Huanghuazhan (HHZ). Results show that the elongation of the axillary buds in the first seasonal rice was significantly inhibited and the ratoon rate was reduced at most by up to 40% with GR24 treatment. Compared with the control, a significant reduction in the content of auxin and cytokinin in the second bud from the upper spike could be detected after GR24 treatment, especially 3 days after treatment. Transcriptome analysis suggested that there were at least 742 and 2877 differentially expressed genes (DEGs) within 6 h of GR24 treatment and 12 h of GR24 treatment, respectively. Further bioinformatics analysis revealed that GR24 treatment had a significant effect on the homeostasis and signal transduction of cytokinin and auxin. It is noteworthy that the gene expression levels of OsCKX1, OsCKX2, OsGH3.6, and OsGH3.8, which are involved in cytokinin or auxin metabolism, were enhanced by the 12 h GR24 treatment. Taken overall, this study showed the gene regulatory network of auxin and cytokinin homeostasis to be regulated by strigolactone in the axillary bud outgrowth of ratoon rice, which highlights the importance of these biological pathways in the regulation of axillary bud outgrowth in ratoon rice and would provide theoretical support for the molecular breeding of ratoon rice.

Circulating Oxidized mtDNA is Associated Broadly with Cardiovascular Disease in a Longitudinal Cohort Study of Psoriasis.

Psoriasis (PSO) is a chronic and systemic inflammatory autoimmune disease associated with atherosclerosis and myocardial infarction. Given that atherosclerosis is both inflammation and immune driven, we sought to expand on known immune and inflammatory biomarkers in a PSO cohort. In this study, we focus on oxidized mtDNA (ox-mtDNA), a product of cells undergoing pyroptosis, including keratinocytes, which was quantified in patients with PSO and individuals without PSO by ELISA. Patients with PSO had significantly higher ox-mtDNA levels than healthy subjects (mean ± SD = 9246 ± 2518 pg/ml for patients with PSO vs 7382 ± 2506 pg/ml for those without; P = .006). Importantly, ox-mtDNA was positively associated with IL-17a (ß = 0.25; P = .03) and low-density granulocytes (ß = 0.37; P = .005) but negatively associated with high-density lipoprotein-cholesterol (ß = -0.29; P = .006). After adjusting for traditional cardiovascular risk factors, we found that ox-mtDNA was associated with noncalcified coronary burden, which was measured by coronary computed tomography angiography (ß = 0.19; P = .003). Biologic-naïve patients with PSO receiving anti-IL-17a therapy had a 14% decrease in ox-mtDNA (mean ± SD: 10540 ± 614 pg/ml at baseline to 9016 ± 477 pg/ml at 1 year; P = .016) and a 10% reduction in noncalcified coronary artery burden (mean ± SD: 1.06 ± 0.45 at baseline, reducing to 0.95 ± 0.35 at 1 year; P = .0037). In summary, levels of ox-mtDNA in PSO are associated with measures of coronary plaque formation, indicating that this biomarker may be an autoimmune-driven early atherosclerotic feature.

YUCCA2 (YUC2)-Mediated 3-Indoleacetic Acid (IAA) Biosynthesis Regulates Chloroplast RNA Editing by Relieving the Auxin Response Factor 1 (ARF1)-Dependent Inhibition of Editing Factors in Arabidopsis thaliana.

Although recent research progress on the abundant C-to-U RNA editing events in plant chloroplasts and mitochondria has uncovered many recognition factors and their molecular mechanisms, the intrinsic regulation of RNA editing within plants remains largely unknown. This study aimed to establish a regulatory relationship in Arabidopsis between the plant hormone auxin and chloroplast RNA editing. We first analyzed auxin response elements (AuxREs) present within promoters of chloroplast editing factors reported to date. We found that each has more than one AuxRE, suggesting a potential regulatory role of auxin in their expression. Further investigation unveiled that the depletion of auxin synthesis gene YUC2 reduces the expression of several editing factors. However, in yuc2 mutants, only the expression of CRR4, DYW1, ISE2, and ECD1 editing factors and the editing efficiency of their corresponding editing sites, ndhD-2 and rps14-149, were simultaneously suppressed. In addition, exogenous IAA and the overexpression of YUC2 enhanced the expression of these editing factors and the editing efficiency at the ndhD-2 and rps14-149 sites. These results suggested a direct effect of auxin upon the editing of the ndhD-2 and rps14-149 sites through the modulation of the expression of the editing factors. We further demonstrated that ARF1, a downstream transcription factor in the auxin-signaling pathway, could directly bind to and inactivate the promoters of CRR4, DYW1, and ISE2 in a dual-luciferase reporter system, thereby inhibiting their expression. Moreover, the overexpression of ARF1 in Arabidopsis significantly reduced the expression of the three editing factors and the editing efficiency at the ndhD-2 and rps14-149 sites. These data suggest that YUC2-mediated auxin biosynthesis governs the RNA-editing process through the ARF1-dependent signal transduction pathway.

All layers patterned conical nanostructured thin-film silicon solar cells for light-trapping efficiency improvement.

Thin-film silicon solar cells (TSSC) has received great attention due to its advantages of low cost and eco-friendly. However, traditional single-layer patterned solar cells (SPSC) still fall short in light-trapping efficiency. This article presents an all layers patterned (ALP) conical nanostructured TSSC to enhance the low absorption caused by the thin absorption layers. The Finite-Difference Time-Domain result shows that a photocurrent density up to 41.27 mA/cm2 can be obtained for the structure, which is 31.39% higher than that of the SPSC. An electrical optimization simulation of doping concentration was carried out on the parameters of the optically optimal structure of the model. The power conversion efficiency is 17.15%, which is 1.72 times higher than that of the planar structure. These results demonstrate a success for the potential and prospect of the fully patterned nanostructures in thin-film photovoltaic devices.

Relationship of Soluble Lectin-Like Low-Density Lipoprotein Receptor-1 (sLOX-1) With Inflammation and Coronary Plaque Progression in Psoriasis.

BACKGROUND: Psoriasis is a chronic inflammatory condition associated with coronary artery disease risk. Uptake of oxidized low-density lipoprotein by the lectin-like low-density lipoprotein receptor-1 triggers release of the soluble extracellular domain of the receptor (sLOX-1). We sought to characterize the relationship between sLOX-1, inflammation, and coronary plaque progression in psoriasis. METHODS AND RESULTS: A total of 327 patients with psoriasis had serum sLOX-1 levels measured at baseline by an ELISA-based assay. Stratification by high-sensitivity C-reactive protein ≥4.0 mg/L (quartile 4), identified 81 participants who had coronary plaque phenotyping at baseline and were followed longitudinally by coronary computed tomography angiography. Subjects within high-sensitivity C-reactive protein quartile 4 were middle-aged (51.47±12.62 years), predominantly men (54.3%) with moderate psoriasis disease severity (6.60 [interquartile range, 3.30-13.40]). In the study cohort, participants with sLOX-1 above the median displayed increased vulnerable coronary plaque features. At baseline, sLOX-1 was associated with total burden (rho=0.296; P=0.01), noncalcified burden (rho=0.286; P=0.02), fibro-fatty burden (rho=0.346; P=0.004), and necrotic burden (rho=0.394; P=0.002). A strong relationship between sLOX-1, noncalcified burden (ß=0.19; P=0.03), and fibro-fatty burden (ß=0.29; P=0.003) was found in fully adjusted models at baseline and 1- and 4-year follow-up. Finally, coronary plaque features progressed over 1 year regardless of biologic or systemic treatment in subjects with high sLOX-1. CONCLUSIONS: Patients with psoriasis with both high sLOX-1 and high-sensitivity C-reactive protein levels have increased coronary plaque burden associated with atherosclerotic plaque progression independent of biologic and systemic treatment. Thus, sLOX-1 might be considered as a promising marker in coronary artery disease risk estimation beyond traditional risk factors. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01778569.

Longitudinal association of epicardial and thoracic adipose tissues with coronary and cardiac characteristics in psoriasis.

Background: s: Psoriasis is a disease of systemic inflammation associated with increased cardiometabolic risk. Epicardial adipose tissue (EAT) and thoracic adipose tissue (TAT) are contributing factors for atherosclerosis and cardiac dysfunction. We strove to assess the longitudinal impact of the EAT and TAT on coronary and cardiac characteristics in psoriasis. Methods: The study consisted of 301 patients with baseline coronary computed tomography angiography (CTA), of which 139 had four-year follow up scans. EAT and TAT volumes from non-contrast computed tomography scans were quantified by an automated segmentation framework. Coronary plaque characteristics and left ventricular (LV) mass were quantified by CTA. Results: When stratified by baseline EAT and TAT volume quartiles, a stepwise significant increase in cardiometabolic parameters was observed. EAT and TAT volumes associated with fibro-fatty burden (FFB) (TAT: ρ = 0.394, P < 0.001; EAT: ρ = 0.459, P < 0.001) in adjusted models. Only EAT had a significant four-year time-dependent association with FFB in fully adjusted models (ß = 0.307 P = 0.003), whereas only TAT volume associated with myocardial injury in fully adjusted models (TAT: OR = 1.57 95 % CI = (1.00-2.60); EAT: OR = 1.46 95 % CI = (0.91-2.45). Higher quartiles of EAT and TAT had increased LV mass and developed strong correlation (TAT: ρ = 0.370, P < 0.001; EAT: ρ = 0.512, P < 0.001). Conclusions: Our study is the first to explore how both EAT and TAT volumes associate with increased cardiometabolic risk profile in an inflamed psoriasis cohorts and highlight the need for further studies on its use as a potential prognostic tool for high-risk coronary plaques and cardiac dysfunction.

Non-contrast computed tomography-based radiomics for staging of connective tissue disease-associated interstitial lung disease.

Rationale and introduction: It is of significance to assess the severity and predict the mortality of patients with connective tissue disease-associated interstitial lung disease (CTD-ILD). In this double-center retrospective study, we developed and validated a radiomics nomogram for clinical management by using the ILD-GAP (gender, age, and pulmonary physiology) index system. Materials and methods: Patients with CTD-ILD were staged using the ILD-GAP index system. A clinical factor model was built by demographics and CT features, and a radiomics signature was developed using radiomics features extracted from CT images. Combined with the radiomics signature and independent clinical factors, a radiomics nomogram was constructed and evaluated by the area under the curve (AUC) from receiver operating characteristic (ROC) analyses. The models were externally validated in dataset 2 to evaluate the model generalization ability using ROC analysis. Results: A total of 245 patients from two clinical centers (dataset 1, n = 202; dataset 2, n = 43) were screened. Pack-years of smoking, traction bronchiectasis, and nine radiomics features were used to build the radiomics nomogram, which showed favorable calibration and discrimination in the training cohort {AUC, 0.887 [95% confidence interval (CI): 0.827-0.940]}, the internal validation cohort [AUC, 0.885 (95% CI: 0.816-0.922)], and the external validation cohort [AUC, 0.85 (95% CI: 0.720-0.919)]. Decision curve analysis demonstrated that the nomogram outperformed the clinical factor model and radiomics signature in terms of clinical usefulness. Conclusion: The CT-based radiomics nomogram showed favorable efficacy in predicting individual ILD-GAP stages.

Nomogram based on computed tomography images and clinical data for distinguishing between primary intestinal lymphoma and Crohn's disease: a retrospective multicenter study.

Background: Differential diagnosis of primary intestinal lymphoma (PIL) and Crohn's disease (CD) is a challenge in clinical diagnosis. Aims: To investigate the validity of the nomogram based on clinical and computed tomography (CT) features to identify PIL and CD. Methods: This study retrospectively analyzed laboratory parameters, demographic characteristics, clinical manifestations, and CT imaging features of PIL and CD patients from two centers. Univariate logistic analysis was performed for each variable, and laboratory parameter model, clinical model and imaging features model were developed separately. Finally, a nomogram was established. All models were evaluated using the area under the curve (AUC), accuracy, sensitivity, specificity, and decision curve analysis (DCA). Results: This study collected data from 121 patients (PIL = 69, CD = 52) from Center 1. Data from 43 patients (PIL = 24, CD = 19) were collected at Center 2 as an external validation cohort to validate the robustness of the model. Three models and a nomogram were developed to distinguish PIL from CD. Most models performed well from the external validation cohort. The nomogram showed the best performance with an AUC of 0.921 (95% CI: 0.838-1.000) and sensitivities, specificities, and accuracies of 0.945, 0.792, and 0.860, respectively. Conclusion: A nomogram combining clinical data and imaging features was constructed, which can effectively distinguish PIL from CD.

Association of oxidized ApoB and oxidized ApoA-I with high-risk coronary plaque features in cardiovascular disease.

BACKGROUND: Oxidized apolipoprotein B (oxLDL) and oxidized ApoA-I (oxHDL) are proatherogenic. Their prognostic value for assessing high-risk plaques by coronary computed tomography angiography (CCTA) is missing. METHODS: In a prospective, observational study, 306 participants with cardiovascular disease (CVD) had extensive lipoprotein profiling. Proteomics analysis was performed on isolated oxHDL, and atherosclerotic plaque assessment was accomplished by quantitative CCTA. RESULTS: Patients were predominantly White, overweight men (58.5%) on statin therapy (43.5%). Increase in LDL-C, ApoB, small dense LDL-C (P < 0.001 for all), triglycerides (P = 0.03), and lower HDL function were observed in the high oxLDL group. High oxLDL associated with necrotic burden (NB; ß = 0.20; P < 0.0001) and fibrofatty burden (FFB; ß = 0.15; P = 0.001) after multivariate adjustment. Low oxHDL had a significant reverse association with these plaque characteristics. Plasma oxHDL levels better predicted NB and FFB after adjustment (OR, 2.22; 95% CI, 1.27-3.88, and OR, 2.80; 95% CI, 1.71-4.58) compared with oxLDL and HDL-C. Interestingly, oxHDL associated with fibrous burden (FB) change over 3.3 years (ß = 0.535; P = 0.033) when compared with oxLDL. Combined Met136 mono-oxidation and Trp132 dioxidation of HDL showed evident association with coronary artery calcium score (r = 0.786; P < 0.001) and FB (r = 0.539; P = 0.012) in high oxHDL, whereas Met136 mono-oxidation significantly associated with vulnerable plaque in low oxHDL. CONCLUSION: Our findings suggest that the investigated oxidized lipids are associated with high-risk coronary plaque features and progression over time in patients with CVD. CLINICALTRIALS: gov NCT01621594. FUNDING: National Heart, Lung, and Blood Institute at the NIH Intramural Research Program.

The cell-centered Finite-Volume self-consistent approach for heterostructures: 1D electron gas at the Si-SiO2interface.

Achieving self-consistent convergence with the conventional effective-mass approach at ultra-low temperatures (below 4.2 K) is a challenging task, which mostly lies in the discontinuities in material properties (e.g. effective-mass, electron affinity, dielectric constant). In this article, we develop a novel self-consistent approach based on cell-centered finite-volume discretization of the Sturm-Liouville form of the effective-mass Schrödinger equation and generalized Poisson's equation (FV-SP). We apply this approach to simulate the one-dimensional electron gas formed at the Si-SiO2interface via a top gate. We find excellent self-consistent convergence from high to extremely low (as low as 50 mK) temperatures. We further examine the solidity of FV-SP method by changing external variables such as the electrochemical potential and the accumulative top gate voltage. Our approach allows for counting electron-electron interactions. Our results demonstrate that FV-SP approach is a powerful tool to solve effective-mass Hamiltonians.

A computed tomography-based radiomics nomogram for predicting overall survival in patients with connective tissue disease-associated interstitial lung disease.

OBJECTIVES: Accurate prognostic prediction is beneficial for the management of patients with connective tissue disease-associated interstitial lung disease (CTD-ILD). The purpose of the present study was to develop and validate a nomogram using clinical features and computed tomography (CT) based radiomics features to predict overall survival (OS) in patients with CTD-ILD, and to assess the incremental prognostic value the radiomics might add to clinical risk factors. MATERIALS & METHODS: Patients from two clinical centers with CTD-ILD were enrolled in the present retrospective study. A radiomics signature, a clinical model and a combined nomogram were developed and assessed in the cohorts. The incremental value of radiomics signature to the clinical independent risk factors in survival prediction was evaluated. The models were externally validated to evaluate the model generalization ability. RESULTS: A total of 215 patients (mean age, 53 years ± 14 [standard deviation], 45 men) were evaluated. Patients with higher radiomics scores had higher mortality risk than those with lower radiomics scores (Hazard ratio, 12.396; 95% CI, 3.364-45.680; P < 0.001). The combined nomogram showed better predictive capability than the clinical model did with higher C-indices (0.800, 0.738, 0.742 vs. 0.747, 0.631, 0.587 in the training, internal- and external-validation cohort, respectively), time-AUCs and overall net-benefit. CONCLUSION: The radiomics signature is a potential prognostic biomarker of CTD-ILD and add incremental value to the clinical independent risk factors. The combined nomogram can provide a more accurate estimation of OS than the clinical model for CTD-ILD patients. CLINICAL RELEVANCE STATEMENT: The developed combined nomogram showed accurate prognostic prediction performance, which is beneficial for the management of CTD-ILD patients. It also proved radiomics could extract prognostic information from CT images.

Probing Two Driven Double Quantum Dots Strongly Coupled to a Cavity.

We experimentally and theoretically study a driven hybrid circuit quantum electrodynamics (cQED) system beyond the dispersive coupling regime. Treating the cavity as part of the driven system, we develop a theory applicable to such strongly coupled and to multiqubit systems. The fringes measured for a single driven double quantum dot (DQD)-cavity setting and the enlarged splittings of the hybrid Floquet states in the presence of a second DQD are well reproduced with our model. This opens a path to study Floquet states of multiqubit systems with arbitrarily strong coupling and reveals a new perspective for understanding strongly driven hybrid systems.

Collective Microwave Response for Multiple Gate-Defined Double Quantum Dots.

We fabricate and characterize a hybrid quantum device that consists of five gate-defined double quantum dots (DQDs) and a high-impedance NbTiN transmission resonator. The controllable interactions between DQDs and the resonator are spectroscopically explored by measuring the microwave transmission through the resonator in the detuning parameter space. Utilizing the high tunability of the system parameters and the high cooperativity (Ctotal > 17.6) interaction between the qubit ensemble and the resonator, we tune the charge-photon coupling and observe the collective microwave response changing from linear to nonlinear. Our results present the maximum number of DQDs coupled to a resonator and manifest a potential platform for scaling up qubits and studying collective quantum effects in semiconductor-superconductor hybrid cavity quantum electrodynamics systems.

Undoped Strained Ge Quantum Well with Ultrahigh Mobility of Two Million.

We develop a method to fabricate an undoped Ge quantum well (QW) under a 32 nm relaxed Si0.2Ge0.8 shallow barrier. The bottom barrier contains Si0.2Ge0.8 (650 °C) and Si0.1Ge0.9 (800 °C) such that variation of Ge content forms a sharp interface that can suppress the threading dislocation density (TDD) penetrating into the undoped Ge quantum well. The SiGe barrier introduces enough in-plane parallel strain (ε∥ strain -0.41%) in the Ge quantum well. The heterostructure field-effect transistors with a shallow buried channel obtain an ultrahigh two-dimensional hole gas (2DHG) mobility over 2 × 106 cm2/(V s) and a very low percolation density of (5.689 ± 0.062) × 1010 cm-2. The fractional indication is also observed at high density and high magnetic fields. This strained germanium as a noise mitigation material provides a platform for integration of quantum computation with a long coherence time and fast all-electrical manipulation.

Estimated sdLDL-C for predicting high-risk coronary plaque features in psoriasis: a prospective observational study.

BACKGROUND: Psoriasis (PSO) is a skin disorder with systemic inflammation and high coronary artery disease risk. A distinct lipid phenotype occurs in psoriasis, which is characterized by high plasma triglycerides (TGs) with typically normal or even low LDL-C. The extent to which cholesterol on LDL subfractions, such as small dense LDL-C (sdLDL-C), are associated with vulnerable coronary plaque characteristics in PSO remains elusive. METHODS: A recently developed equation for estimating sdLDL-C from the standard lipid panel was utilized in a PSO cohort (n = 200) with 4-year follow-up of 75 subjects. Coronary plaque burden was assessed by quantitative coronary computed tomography angiography (CCTA). Multivariate regression analyses were used for establishing associations and prognostic value of estimated sdLDL-C. RESULTS: Estimated sdLDL-C was positively associated with non-calcified burden (NCB) and fibro-fatty burden (FFB), which remained significant after multivariate adjustment for NCB (ß = 0.37; P = 0.050) and LDL-C adjustment for FFB (ß = 0.29; P < 0.0001). Of note, total LDL-C calculated by the Friedewald equation was not able to capture these associations in the study cohort. Moreover, in the regression modelling estimated sdLDL-C was significantly predicting necrotic burden progression over 4 years follow-up (P = 0.015), whereas LDL-C did not. Finally, small LDL particles (S-LDLP) and small HDL particles (S-HDLP), along with large and medium TG-rich lipoproteins (TRLPs) had the most significant positive correlation with estimated sdLDL-C. CONCLUSIONS: Estimated sdLDL-C has a stronger association than LDL-C with high-risk features of coronary atherosclerotic plaques in psoriasis patients. CLINICAL TRIAL REGISTRATION: URL: https://www. CLINICALTRIALS: gov . Unique identifiers: NCT01778569.

Ultrafast and Electrically Tunable Rabi Frequency in a Germanium Hut Wire Hole Spin Qubit.

Hole spin qubits based on germanium (Ge) have strong tunable spin-orbit interaction (SOI) and ultrafast qubit operation speed. Here we report that the Rabi frequency (fRabi) of a hole spin qubit in a Ge hut wire (HW) double quantum dot (DQD) is electrically tuned through the detuning energy (ϵ) and middle gate voltage (VM). fRabi gradually decreases with increasing ϵ; on the contrary, fRabi is positively correlated with VM. We attribute our results to the change of electric field on SOI and the contribution of the excited state in quantum dots to fRabi. We further demonstrate an ultrafast fRabi exceeding 1.2 GHz, which indicates the strong SOI in our device. The discovery of an ultrafast and electrically tunable fRabi in a hole spin qubit has potential applications in semiconductor quantum computing.

The Relationship between Circulating APOA-1 and Atherosclerosis Initiation and Progression in Psoriasis.

APOA-1 is central to the high-density lipoprotein function of reverse cholesterol transport measured by cholesterol efflux capacity. Psoriasis is a systemic inflammatory disease associated with poor cholesterol efflux capacity and accelerated noncalcified coronary burden (NCB) as measured by coronary computed tomographic angiography. In this study, we characterized the relationship between APOA-1, cholesterol efflux capacity, and progression of NCB over 4 years. Consecutively recruited participants with psoriasis underwent coronary computed tomographic angiography for NCB quantification (Medis QAngio, Leiden, The Netherlands) at baseline (n = 310) and at four years (n = 124). Blood was assessed for cardiometabolic biomarkers. The lowest quartile of APOA-1 was associated with cardiometabolic blood markers (insulin, homeostatic model assessment for insulin resistance, and cholesterol efflux capacity) and higher NCB (P < 0.001). The low APOA-1 quartile had higher NCB at 4 years (ß = -0.36, P = 0.02) in fully adjusted models. Finally, a 10-unit decrease of APOA-1 was associated with a 16% increase in NCB progression over 4 years (OR = 0.83, 95% confidence interval = 0.70-0.99, P = 0.04). In addition to being associated with cardiometabolic disease, low APOA-1 was associated with more NCB over time. These findings show that low APOA-1 is correlated with initiation and progression of coronary artery disease and may have clinical utility in identifying high-risk populations for development of cardiovascular disease.