Effect of Food, Crushing of Tablets, and Antacid Coadministration on Maribavir Pharmacokinetics in Healthy Adult Participants: Results From 2 Phase 1, Open-Label, Randomized, Crossover Studies.

The effect of food composition, tablet crushing, and antacid coadministration on maribavir pharmacokinetics was assessed in 2 Phase 1 studies in healthy adults. In the first, a single maribavir 400-mg dose was administered under fasting conditions, with a low-fat/low-calorie or a high-fat/high-calorie meal. In the second, a single maribavir 100-mg dose was administered under fasting conditions, as a crushed tablet, or as a whole tablet alone or with an antacid. The 90% confidence intervals of the geometric mean ratios were within 80%-125% for area under the concentration-time curve (AUC), but not for maximum plasma concentration (Cmax) for low-fat/low-calorie and high-fat/high-calorie meals versus fasting or for whole tablet with antacid versus whole tablet alone. The 90% confidence intervals of the geometric mean ratios for AUC and Cmax were within 80%-125% for crushed versus whole tablet. Maribavir median time to Cmax value in plasma under fed conditions was delayed versus fasting conditions, but there was no statistical difference for crushed versus whole tablet or with versus without antacid. As the antiviral efficacy of maribavir is driven by AUC but not Cmax, findings suggest that maribavir can be administered with food or antacids or as a crushed tablet.

The Impact of Different Regions of Interest on Shear Wave Elastography Assessment of the Meniscus in the Knee Joint.

RATIONALE AND OBJECTIVES: To investigate the impact of different regions of interest (ROI) on the assessment of shear wave elastography (SWE) in evaluating the meniscus of the knee joint. MATERIALS AND METHODS: After ethical approval, a total of 141 participants were enrolled in this prospective study from February to October 2023. SWE was utilized to evaluate the anterior horn of the lateral meniscus (LM) and medial meniscus (MM), using two different ROIs (ROI-Small and ROI-Trace) to measure the elastic mean value (Emean) and elastic maximum value (Emax). The differences in elasticity values between the normal menisci and torn menisci were compared, and the impact of different ROI selection methods on the diagnostic performance of elastic parameters in the torn menisci was assessed using receiver operating characteristic (ROC) curves. RESULTS: In Emean comparison, only MM in the tear group showed higher ROI-S than ROI-T. When comparing Emax, all ROI-T values were higher than the ROI-S values, and this difference was statistically significant. Different sizes of ROI did not significantly impact the diagnostic performance of Emean in LM and MM, nor the diagnostic effectiveness of Emax in LM. However, only the area under the curve (AUC) of MM for Emax in both ROI-S and ROI-T showed a statistically significant difference. CONCLUSION: The shear wave elasticity values and diagnostic performance may vary depending on the ROI settings. Therefore, it is recommended to use a 2 mm diameter ROI placed at the central position of the meniscus, with Emean as the elasticity index.

m6A-Mediated Upregulation of Imprinted in Prader-Willi Syndrome Induces Aberrant Apical-Basal Polarization and Oxidative Damage in RPE Cells.

Purpose: To reveal the clinical significance, pathological involvement and molecular mechanism of imprinted in Prader-Willi syndrome (IPW) in RPE anomalies that contribute to AMD. Methods: IPW expression under pathological conditions were detected by microarrays and qPCR assays. In vitro cultured fetal RPE cells were used to study the pathogenicity induced by IPW overexpression and to analyze its upstream and downstream regulatory networks. Results: We showed that IPW is upregulated in the macular RPE-choroid tissue of dry AMD patients and in fetal RPE cells under oxidative stress, inflammation and dedifferentiation. IPW overexpression in fetal RPE cells induced aberrant apical-basal polarization as shown by dysregulated polarized markers, disrupted tight and adherens junctions, and inhibited phagocytosis. IPW upregulation was also associated with RPE oxidative damages, as demonstrated by intracellular accumulation of reactive oxygen species, reduced cell proliferation, and accelerated cell apoptosis. Mechanically, N6-methyladenosine level of the IPW transcript regulated its stability with YTHDC1 as the reader. IPW mediated RPE features by suppressing MEG3 expression to sequester its inhibition on the AKT serine-threonine kinase (AKT)/mammalian target of rapamycin (mTOR) pathway. We also noticed that the mTOR inhibitor rapamycin suppresses the AKT/mTOR pathway to alleviate the IPW-induced RPE anomalies. Conclusions: We revealed that IPW overexpression in RPE induces aberrant apical-basal polarization and oxidative damages, thus contributing to AMD progression. We also annotated the upstream and downstream regulatory networks of IPW in RPE. Our findings shed new light on the molecular mechanisms of RPE dysfunctions, and indicate that IPW blockers may be a promising option to treat RPE abnormalities in AMD.

Lactylation-driven FTO targets CDK2 to aggravate microvascular anomalies in diabetic retinopathy.

Diabetic retinopathy (DR) is a leading cause of irreversible vision loss in working-age populations. Fat mass and obesity-associated protein (FTO) is an N6-methyladenosine (m6A) demethylase that demethylates RNAs involved in energy homeostasis, though its influence on DR is not well studied. Herein, we detected elevated FTO expression in vitreous fibrovascular membranes of patients with proliferative DR. FTO promoted cell cycle progression and tip cell formation of endothelial cells (ECs) to facilitate angiogenesis in vitro, in mice, and in zebrafish. FTO also regulated EC-pericyte crosstalk to trigger diabetic microvascular leakage, and mediated EC-microglia interactions to induce retinal inflammation and neurodegeneration in vivo and in vitro. Mechanistically, FTO affected EC features via modulating CDK2 mRNA stability in an m6A-YTHDF2-dependent manner. FTO up-regulation under diabetic conditions was driven by lactate-mediated histone lactylation. FB23-2, an inhibitor to FTO's m6A demethylase activity, suppressed angiogenic phenotypes in vitro. To allow for systemic administration, we developed a nanoplatform encapsulating FB23-2 and confirmed its targeting and therapeutic efficiency in mice. Collectively, our study demonstrates that FTO is important for EC function and retinal homeostasis in DR, and warrants further investigation as a therapeutic target for DR patients.

Difficulties in eating out of home while diagnosed with inflammatory bowel disease: A qualitative interview study from China.

BACKGROUND: Meeting healthy dietary needs while eating out can be a challenging experience for adults with inflammatory bowel disease. This study examined the barriers experienced by adults with inflammatory bowel disease (IBD) when eating out. OBJECTIVE: This study aimed to explore the perceptions of people with IBD on eating out barriers. DESIGN: A qualitative study among individuals affected by IBD was conducted through semi-structured interviews. RESULTS: Sixteen adults from China were diagnosed with IBD between 6 months and 20 years prior to the study. They were recruited from four tertiary care hospitals in Nanjing, China. The participants completed a semi-structured interview between April and September 2022. Self-perceived difficulties with eating and drinking when eating out were varied. After thematic analysis of the data, five main themes emerged: limited access to healthy and hygiene food; no pleasure of food enjoyment; financial strain; not feeling loved, supported or understood; and coping strategies for not meeting demand. CONCLUSIONS: This study highlights the various barriers encountered by patients with inflammatory bowel disease when eating out. These findings will help people with IBD to encourage the formation of targeted health and well-being-related interventions. Knowledge of nutrition and diet should be provided in education and training programs administered to IBD.

Assessment of Knee Menisci in Healthy Adults Using Shear Wave Elastography.

OBJECTIVES: The aim of this study was to explore the application value of shear wave elastography in healthy adults with knee meniscus. METHODS: One hundred adult subjects who underwent health checkups at our hospital from December 2022 to February 2023 were selected as research participants. Shear wave elastography was used to evaluate the periphery of the lateral and medial meniscus in both knees. To assess the mean differences in Young's modulus values between male and female groups, a one-way analysis of variance (ANOVA) and independent samples t-test were conducted. In addition, a Pearson correlation coefficient test was used to analyze the correlation between the elastic values of the meniscus and age, height, weight, and body mass index (BMI). RESULTS: There were no significant differences in elastic values between the lateral meniscus of the left and right sides or between the medial meniscus of the left and right sides within the same gender group (P > .05). Stiffness values of the medial meniscus were higher in each gender group than those of the lateral meniscus (P < .01). Additionally, males demonstrated higher stiffness values than females (P < .01). As age increased, the Young's modulus of the meniscus increased significantly (r > .75, P < .01). CONCLUSION: Shear wave elastography can serve as an adjunctive tool to aid in the assessment of knee meniscal elasticity.

High-Accuracy Maize Disease Detection Based on Attention Generative Adversarial Network and Few-Shot Learning.

This study addresses the problem of maize disease detection in agricultural production, proposing a high-accuracy detection method based on Attention Generative Adversarial Network (Attention-GAN) and few-shot learning. The method introduces an attention mechanism, enabling the model to focus more on the significant parts of the image, thereby enhancing model performance. Concurrently, data augmentation is performed through Generative Adversarial Network (GAN) to generate more training samples, overcoming the difficulties of few-shot learning. Experimental results demonstrate that this method surpasses other baseline models in accuracy, recall, and mean average precision (mAP), achieving 0.97, 0.92, and 0.95, respectively. These results validate the high accuracy and stability of the method in handling maize disease detection tasks. This research provides a new approach to solving the problem of few samples in practical applications and offers valuable references for subsequent research, contributing to the advancement of agricultural informatization and intelligence.

ALKBH5 causes retinal pigment epithelium anomalies and choroidal neovascularization in age-related macular degeneration via the AKT/mTOR pathway.

Retinal pigment epithelium (RPE) dysfunction and choroidal neovascularization (CNV) are predominant features of age-related macular degeneration (AMD), with an unclear mechanism. Herein, we show that RNA demethylase α-ketoglutarate-dependent dioxygenase alkB homolog 5 (ALKBH5) is up-regulated in AMD. In RPE cells, ALKBH5 overexpression associates with depolarization, oxidative stress, disturbed autophagy, irregular lipid homeostasis, and elevated VEGF-A secretion, which subsequently promotes proliferation, migration, and tube formation of vascular endothelial cells. Consistently, ALKBH5 overexpression in mice RPE correlates with various pathological phenotypes, including visual impairments, RPE anomalies, choroidal neovascularization (CNV), and interrupted retinal homeostasis. Mechanistically, ALKBH5 regulates retinal features through its demethylation activity. It targets PIK3C2B and regulates the AKT/mTOR signaling pathway with YTHDF2 as the N6-methyladenosine reader. IOX1, an ALKBH5 inhibitor, suppresses hypoxia-induced RPE dysfunction and CNV progression. Collectively, we demonstrate that ALKBH5 induces RPE dysfunction and CNV progression in AMD via PIK3C2B-mediated activation of the AKT/mTOR pathway. Pharmacological inhibitors of ALKBH5, like IOX1, are promising therapeutic options for AMD.

High-Precision Tomato Disease Detection Using NanoSegmenter Based on Transformer and Lightweighting.

With the rapid development of artificial intelligence and deep learning technologies, their applications in the field of agriculture, particularly in plant disease detection, have become increasingly extensive. This study focuses on the high-precision detection of tomato diseases, which is of paramount importance for agricultural economic benefits and food safety. To achieve this aim, a tomato disease image dataset was first constructed, and a NanoSegmenter model based on the Transformer structure was proposed. Additionally, lightweight technologies, such as the inverted bottleneck technique, quantization, and sparse attention mechanism, were introduced to optimize the model's performance and computational efficiency. The experimental results demonstrated excellent performance of the model in tomato disease detection tasks, achieving a precision of 0.98, a recall of 0.97, and an mIoU of 0.95, while the computational efficiency reached an inference speed of 37 FPS. In summary, this study provides an effective solution for high-precision detection of tomato diseases and offers insights and references for future research.

Circulating antibodies to Helicobacter pylori are associated with biomarkers of neurodegeneration in cognitively intact adults.

Helicobacter pylori (H. pylori) infection confers risk for Alzheimer's Disease (AD), with the mechanisms unknown. Infections are linked to the etiology of AD partly through modulating the humoral immunity post-infection. This study found increased plasma levels of tTau and pTau181 in H. Pylori infected individuals with intact cognition. Plasma antibodies to H. pylori were positively associated with Aß40, Aß42, tTau, and pTau181, adjusting for age, sex, education level, BMI, ApoE ε4 genotype, hypertension, diabetes mellitus, and hypercholesteremia. This study presents novel insights into the relationship between H. pylori infection and AD from an autoimmune perspective.

Focusing light with a metal film coated patchy particle.

Microsphere-assisted super-resolution imaging is a promising technique that can significantly enhance the resolution of conventional optical microscopes. The focus of a classical microsphere is called photonic nanojet, which is a symmetric high-intensity electromagnetic field. Recently, patchy microspheres have been reported to have superior imaging performance than pristine microspheres, and coating microspheres with metal films leads to the formation of photonic hooks, which can enhance the imaging contrast of microspheres. Understanding the influence of metal patches on the near-field focusing of patchy particles is important for the rational design of a nanostructured microlens. In this work, we theoretically and experimentally showed that the light waves can be focused and engineered using patchy particles. When coating dielectric particles with Ag films, light beams with a hook-like structure or S-shaped structure can be generated. Simulation results show that the waveguide ability of metal films and the geometric asymmetry of patchy particles cause the formation of S-shaped light beams. Compared with classical photonic hooks, S-shaped photonic hooks have a longer effective length and a smaller beam waist at far-field region. Experiments were also carried out to demonstrate the generation of classical and S-shaped photonic hooks from patchy microspheres.

Anti-oxidative-initiated cognitive impairment amelioration in Alzheimer's disease model rats through preventive transcutaneous electrical acupoint stimulation.

Background: Alzheimer's disease (AD) is a chronic and irreversible neurodegenerative disease. Oxidative stress emerges at the early AD stage. As a non-invasive therapy with few adverse reactions, transcutaneous electrical acupoint stimulation (TEAS) combines acupuncture points of traditional Chinese medicine (TCM) and electrical stimulation. This study aimed to investigate the amelioration effects of preventive TEAS treatment (P-TEAS) on cognitive impairment and oxidative stress in AD model rats. Methods: The AD model was established via subcutaneous injections of D-galactose (D-gal, 120 mg/kg/d) into the back of neck for 9 weeks in Sprague Dawley (SD) rats to simulate the oxidative stress in the early AD stage. On the first day of the 10th week, Aß1-42 (1 µg/µl) was injected into the CA1 regions of the bilateral hippocampus. P-TEAS was synchronized from the first day of subcutaneous D-gal injections for 9 weeks. Results: Empirical measurements showed that P-TEAS can improve the spatial memory ability of AD model rats in the Morris water maze. Superoxide dismutase (SOD) was upregulated in the P-TEAS group. Through the detection of the anti-oxidative stress signaling pathway, namely, Kelch-like ECH-associated protein 1 (Keap1)/ NFE2-related factor 2 (Nrf2), it was found that P-TEAS could promote Nrf2 entering into the nucleus and upregulating the production of protective factors heme oxygenase 1 (HO-1) and NADPH quinone oxidoreductase 1 (NQO1). It was also found that P-TEAS could downregulate the expressions of BCL2-associated X-protein (Bax), caspase 3, and caspase 9 to inhibit neuronal apoptosis. Conclusions: P-TEAS has similar efficacy to electroacupuncture in preventing AD occurrence and development. P-TEAS is a new non-invasive intervention therapy for the prevention of AD.

Parallel synthetic aperture transport-of-intensity diffraction tomography with annular illumination.

Transport-of-intensity diffraction tomography (TIDT) is a recently developed label-free computational microscopy technique that retrieves high-resolution three-dimensional (3D) refractive index (RI) distribution of biological specimens from 3D intensity-only measurements. However, the non-interferometric synthetic aperture in TIDT is generally achieved sequentially through the acquisition of a large number of through-focus intensity stacks captured at different illumination angles, resulting in a very cumbersome and redundant data acquisition process. To this end, we present a parallel implementation of a synthetic aperture in TIDT (PSA-TIDT) with annular illumination. We found that the matched annular illumination provides a mirror-symmetric 3D optical transfer function, indicating the analyticity in the upper half-plane of the complex phase function, which allows for recovery of the 3D RI from a single intensity stack. We experimentally validated PSA-TIDT by conducting high-resolution tomographic imaging of various unlabeled biological samples, including human breast cancer cell lines (MCF-7), human hepatocyte carcinoma cell lines (HepG2), Henrietta Lacks (HeLa) cells, and red blood cells (RBCs).

A bibliometric analysis of the global trends and hotspots for the ketogenic diet based on CiteSpace.

The ketogenic diet (KD) is a potential nutritional therapy that is frequently utilized in various conditions. More and more studies are being done on KD in recent years. However, as far as we know, few studies have made an effort to offer a thorough synthesis and assessment of this topic. This paper aims to do a rigorous and thorough evaluation of the knowledge structure, development trend, and research hotspot of scientific outputs connected to KD. The bibliographic records connected to KD from January 1, 2001 to April 22, 2022 were collected using the core collection database of Web of Science. The complex data input, that consisted of the amount of publications, journals, authors, institutions, countries, keywords and cited references, was generated and analyzed visually using CiteSpace. A total of 2676 literatures on the KD were published between 2001 and 2022. The most KD-related publications were found in Epilepsia and Epilepsia Research. The authors with the most KD-related papers are Kossoff EH and Rho J. The United States is the country with the most publications, and Johns Hopkins University, Johns Hopkins University Hospital, and Johns Hopkins Medical Institutions are the institutions with the most articles. The high frequency keywords are "KD," "ketone body," "children," "efficacy," "weight loss," "low carbohydrate diet," "metabolism," "epilepsy," "beta hydroxybutyrate," and "modified atkins diet." The 2018 study by Kossoff EH on epilepsia and the 2017 study by Puchalska P on ketone body metabolism earned 127 and 114 citations, respectively. The results of this bibliometric analysis provide information on the state and trends in KD and may be used by researchers to pinpoint hot issues and discover new areas of study.

Oxidative balance score was negatively associated with the risk of metabolic syndrome, metabolic syndrome severity, and all-cause mortality of patients with metabolic syndrome.

Background: The oxidative balance score (OBS), an encompassing scoring mechanism for assessing oxidative stress, is formulated based on nutritional and lifestyle components. The emergence of metabolic syndrome (MetS) is intricately linked to oxidative stress. Nonetheless, the correlation between OBS and MetS displays variability within distinct cohorts. Objective: We worked on the relationships between OBS and the risk of MetS, MetS severity, and all-cause mortality of MetS patients. Methods: A total of 11,171 adult participants were collected from the U.S. National Health Examination Survey (NHANES) 2007-2018. Employing survey-weighted logistic models, we evaluated the relationship between OBS and MetS risk. Furthermore, survey-weighted linear models were utilized to investigate the connection between OBS and MetS severity. Among the participants, 3,621 individuals had their survival status recorded, allowing us to employ Cox proportional hazards regression models in order to ascertain the association between OBS and the all-cause mortality within the subset of individuals with MetS. The OBS (where a higher OBS signified an increased prevalence of anti- or pro-oxidant exposures) weighed the 20 factors, while the MetS severity score weighed the five factors. Results: After multivariable adjustment, individuals with elevated OBS were found to exhibit a decreased susceptibility to MetS [odds ratio (OR) 0.95; 95% CI 0.94-0.96]. The adjusted OR was 0.42 (95% CI 0.33-0.53) for MetS risk in the fourth OBS quartile compared with those in the first OBS quartile (P for trend < 0.001). A one-unit increase in OBS was linked to a 3% reduction in MetS severity score by 3% (mean difference, -0.03; 95% CI, -0.04 to -0.03). Moreover, increased OBS correlated with decreased hazard of all-cause mortality risk among MetS subjects (adjusted hazard ratio, 0.95; 95% CI, 0.93-0.98). These associations retained their strength even subsequent to the introduction of sensitivity analyses. There existed a statistically significant negative correlation between diet/lifestyle OBS and both MetS risk as well as MetS severity. Conclusions: An inverse correlation was observed between OBS and the susceptibility to MetS, MetS severity, and all-cause mortality of MetS patients. Health outcomes for MetS patients were positively related to antioxidant diets and lifestyles.

m6A modification of circSPECC1 suppresses RPE oxidative damage and maintains retinal homeostasis.

Age-related macular degeneration (AMD) is a leading cause of irreversible vision loss in the elderly population with unclear pathogenic mechanism. Herein, we detect downregulated circSPECC1 expression in retinal pigment epithelium (RPE) of AMD patients. In RPE cells, circSPECC1 insufficiency leads to oxidative stress-induced ferroptosis, depolarization, and irregular lipid metabolism. Consistently, in mice, circSPECC1 deficiency induces visual impairments and RPE anomalies and interrupts retinal homeostasis. Mechanically, nuclear export of circSPECC1 transcript depends on its N6-methyladenosine (m6A) level with YTHDC1 as the reader. CircSPECC1 directly sponges miR-145-5p to block its interaction with CDKN1A. Overexpressing miR-145-5p aggravates RPE dysfunctions, mimicking circSPECC1 silencing effects. Retinal phenotypes induced by circSPECC1 insufficiency are alleviated by miR-145-5p inhibition and are aggravated by miR-145-5p overexpression. Collectively, circSPECC1, mediated by m6A modification and sponging miR-145-5p, resists oxidative stress injuries and maintains lipid metabolism in RPE. Pharmacological supplementation of circSPECC1 is a promising therapeutic option for atrophic retinopathies like AMD.

The Role of N6-Methyladenosine Modification in Microvascular Dysfunction.

Microvascular dysfunction (MVD) has long plagued the medical field despite improvements in its prevention, diagnosis, and intervention. Microvascular lesions from MVD increase with age and further lead to impaired microcirculation, target organ dysfunction, and a mass of microvascular complications, thus contributing to a heavy medical burden and rising disability rates. An up-to-date understanding of molecular mechanisms underlying MVD will facilitate discoveries of more effective therapeutic strategies. Recent advances in epigenetics have revealed that RNA methylation, an epigenetic modification, has a pivotal role in vascular events. The N6-methylation of adenosine (m6A) modification is the most prevalent internal RNA modification in eukaryotic cells, which regulates vascular transcripts through splicing, degradation, translation, as well as translocation, thus maintaining microvascular homeostasis. Conversely, the disruption of the m6A regulatory network will lead to MVD. Herein, we provide a review discussing how m6A methylation interacts with MVD. We also focus on alterations of the m6A regulatory network under pathological conditions. Finally, we highlight the value of m6A regulators as prognostic biomarkers and novel therapeutic targets, which might be a promising addition to clinical medicine.

Associations of Naturally Occurring Antibodies to Presenilin-1 with Brain Amyloid-ß Load and Cognitive Impairment in Alzheimer's Disease.

BACKGROUND: Imbalance between the production and clearance of amyloid-ß (Aß) promotes the development of Alzheimer's disease (AD). Presenilin-1 (PS1) is the catalytic subunit of γ-secretase, which is involved in the process of Aß production. The profiles of autoantibodies are dysregulated in AD patients. OBJECTIVE: This study aims to investigate the relative levels and clinical relevance of naturally occurring antibodies to PS1 (NAbs-PS1) in AD. METHODS: A total of 55 subjects with AD (including both dementia and mild cognitive impairment due to AD), 28 subjects with cognitive impairment (including both dementia and mild cognitive impairment) not due to AD (non-AD CI), and 70 cognitively normal (CN) subjects were recruited. One-site ELISA was utilized to determine the relative levels of NAbs-PS1 in plasma. RESULTS: AD subjects had lower plasma levels of NAbs-PS1 than CN and non-AD CI subjects. Plasma NAbs-PS1 were negatively associated with the brain Aß load, as reflected by PET-PiB SUVR, and were positively associated with cognitive functions of participants. Plasma NAbs-PS1 discriminated AD patients from CN with an area under the curve (AUC) of 0.730, a sensitivity of 69.09%, and a specificity of 67.14%, and they discriminated AD patients from non-AD CI subjects with an AUC of 0.750, a specificity of 70.91%, and a sensitivity of 71.43%. CONCLUSION: This study found an aberrant immunological phenotype in AD patients. Further investigations are needed to determine the pathophysiological functions of NAbs-PS1 in AD.

Regulation of the Keap1-Nrf2 Signaling Axis by Glycyrrhetinic Acid Promoted Oxidative Stress-Induced H9C2 Cell Apoptosis.

Excessive reactive oxygen species (ROS) could interfere with the physiological capacities of H9C2 cells and cause cardiomyocyte apoptosis. Glycyrrhetinic acid (GA), one of the main medicinal component of Glycyrrhetinic Radix et Rhizoma, shows toxic and adverse side effects in the clinic setting. In particular, some studies have reported that GA exerts toxic effects on H9C2 cells. The purpose of this study is to assess the effect of GA-induced oxidative stress on cultured H9C2 cells and reveal the relevant signaling pathways. LDH assay was used to assess cell damage. Apoptosis was detected using Hoechst 33242 and a propidium iodide (PI) assay. An Annexin V-fluorescein isothiocyanate/PI double-staining assay was utilized to investigate GA-induced apoptosis in H9C2 cells. The expression level of specific genes/proteins was evaluated by RT-qPCR and Western blotting. Flow cytometry and DCFH-DA fluorescent testing were used to determine the ROS levels of H9C2 cells. The potential mechanism of GA-induced cardiomyocyte injury was also investigated. GA treatment increased ROS generation and mitochondrial membrane depolarization and triggered caspase-3/9 activation and apoptosis. GA treatment also caused the nuclear translocation of NF-E2-related factor 2 after its dissociation from Keap1. This change was accompanied by a dose-dependent decline in the expression of the downstream target gene heme oxygenase-1. The findings demonstrated that GA could regulate the Keap1-Nrf2 signaling axis and induce oxidative stress to promote the apoptosis of H9C2 cells.