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This pioneering study introduces the use of transformer-based machine learning models and explainable AI approaches to explore the impact of nutrition on Alzheimer's disease (AD) mortality. Using data from the Third National Health and Nutrition Examination Survey (Nhanes iii 1988 to 1994) and the NHANES III Mortality-Linked File (2019) databases, we investigate the intricate relationship between various nutritional factors and AD mortality. Our approach features a novel application of transformer models, which are then benchmarked against established methods like random forests and support vector machines. This comparison not only underscores the strengths of transformer models in handling complex medical datasets but also highlights their potential for providing deeper insights into disease progression. Key findings, such as the significant roles of Platelet distribution width in AD mortality in transformer and Serum Vitamin B12 in random forest, are enhanced by the use of Explainable Artificial Intelligence (XAI), particularly the Shapley Additive Explanations (SHAP) and the integrated gradient methods. This study serves as a vital step forward in applying advanced AI techniques to medical research, offering new perspectives in understanding and combating Alzheimer's Disease.
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Ferrihydrite is omnipresent in nature, and its adsorption of As(III/V) decides the migration of arsenic. Although As(III) is commonly recognized as the more mobile species of inorganic arsenic, it sometimes exhibits less mobility in ferrihydrite systems, which calls for further insights. In this study, we elucidated the adsorption behavior and mechanisms of As(III/V) on ferrihydrite under different loading levels (molar ratio As/Fe = 0-0.38), solution pH (3-10), and coexisting ions [P(V) and Ca(II)] based on batch adsorption experiments, surface complexation modeling, density functional theory calculations, and X-ray photoelectron spectroscopy. Our results show that As(III) exhibits weaker adsorption affinity but a larger capacity compared with that of As(V). On ferrihydrite, As(III) and As(V) are adsorbed mainly as bidentate mononuclear complexes at type-a sites [≡Fe(OH-0.5)2] and bidentate binuclear complexes at type-b sites (2≡FeOH-0.5), respectively. As the dosage increases, As(III) further forms mononuclear monodentate complexes at both surface sites, resulting in a higher site utilization efficiency, while As(V) does not due to repulsive electrostatic interaction. The difference in surface species of As(III/V) also leads to complex responses when coexisting with high concentrations of P(V) and Ca(II). This study helps us to understand environmental behavior of As(III/V) and develop remediation strategy in As(III/V) contaminated systems.
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As a chemotherapy agent, doxorubicin is used to combat cancer. However, cardiotoxicity has limited its use. The existing strategies fail to eliminate doxorubicin-induced cardiotoxicity, and an in-depth exploration of its pathogenesis is in urgent need to address the issue. Endoplasmic reticulum stress (ERS) occurs when Endoplasmic Reticulum (ER) dysfunction results in the accumulation of unfolded or misfolded proteins. Adaptive ERS helps regulate protein synthesis to maintain cellular homeostasis, while prolonged ERS stimulation may induce cell apoptosis, leading to dysfunction and damage to tissue and organs. Numerous studies on doxorubicin-induced cardiotoxicity strongly link excessive activation of the ERS to mechanisms including oxidative stress, calcium imbalance, autophagy, ubiquitination, and apoptosis. The researchers also found several clinical drugs, chemical compounds, phytochemicals, and miRNAs inhibited doxorubicin-induced cardiotoxicity by targeting ERS. The present review aims to outline the interactions between ERS and other mechanisms in doxorubicin-induced cardiotoxicity and summarize ERS's role in this type of cardiotoxicity. Additionally, the review enumerates several clinical drugs, phytochemicals, chemical compounds, and miRNAs targeting ERS for considering therapeutic regimens that address doxorubicin-induced cardiotoxicity.
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Demyelination is characterized by disruption of myelin sheath and disorders in myelin formation. Currently, there are no effective therapeutic treatments available. Microglia, especially anti-inflammatory phenotype microglia are critical for remyelination. Galectin-3 (Gal-3), which is known to modulate microglia activation, is correlated with myelination. In this study, we aimed to elucidate the roles of Gal-3 during myelin formation and explore the efficiency and mechanism of rGal-3 administration in remyelination. We enrolled Gal-3 knockout (Lgals3 KO) mice and demonstrated Lgals3 KO causes demyelination during spontaneous myelinogenesis. We performed a cuprizone (CPZ) intoxication model and found Lgals3 KO aggravates demyelinated lesions and favors microglial pro-inflammatory phenotype polarization. Recombinant Gal-3 (rGal-3) administration alleviates CPZ intoxication and drives microglial towards anti-inflammatory phenotype. Additionally, RNA sequencing results reveal the correlation between Gal-3 and the PPARγ-CD36 axis. Thus, we performed SSO and GW9662 administration to inhibit the activation of the PPARγ-CD36 axis and found that rGal-3 administration modulates microglial phenotype polarization by regulating the PPARγ-CD36 axis. Together, our findings highlight the importance of Gal-3 in myelination and provide insights into rGal-3 administration for modulating microglial anti-inflammatory phenotype polarization through the PPARγ-CD36 axis.
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Antígenos CD36 , Enfermedades Desmielinizantes , Galectina 3 , Ratones Noqueados , Microglía , PPAR gamma , Animales , Ratones , Antígenos CD36/metabolismo , Cuprizona/toxicidad , Enfermedades Desmielinizantes/metabolismo , Enfermedades Desmielinizantes/patología , Modelos Animales de Enfermedad , Galectina 3/metabolismo , Ratones Endogámicos C57BL , Microglía/metabolismo , Microglía/efectos de los fármacos , Vaina de Mielina/metabolismo , Vaina de Mielina/efectos de los fármacos , PPAR gamma/metabolismoRESUMEN
Shrimp fry counting is an important task for biomass estimation in aquaculture. Accurate counting of the number of shrimp fry in tanks can not only assess the production of mature shrimp but also assess the density of shrimp fry in the tanks, which is very helpful for the subsequent growth status, transportation management, and yield assessment. However, traditional manual counting methods are often inefficient and prone to counting errors; a more efficient and accurate method for shrimp fry counting is urgently needed. In this paper, we first collected and labeled the images of shrimp fry in breeding tanks according to the constructed experimental environment and generated corresponding density maps using the Gaussian kernel function. Then, we proposed a multi-scale attention fusion-based shrimp fry counting network called the SFCNet. Experiments showed that our proposed SFCNet model reached the optimal performance in terms of shrimp fry counting compared to CNN-based baseline counting models, with MAEs and RMSEs of 3.96 and 4.682, respectively. This approach was able to effectively calculate the number of shrimp fry and provided a better solution for accurately calculating the number of shrimp fry.
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Acuicultura , Penaeidae , Animales , Penaeidae/fisiología , Acuicultura/métodos , Algoritmos , Biomasa , Redes Neurales de la ComputaciónRESUMEN
As a highly regarded superconducting material with a concise layered structure, MgB2 has attracted significant scientific attention and holds vast potential for applications. However, its limited current-carrying capacity under high magnetic fields has greatly hindered its practical use. To address this issue, we have enhanced the superconducting performance of MgB2 by incorporating inhomogeneous phase nanostructures of p-n junctions with electroluminescent properties. Through temperature-dependent measurements of magnetization, electronic specific heat, and Hall coefficient under various magnetic fields, we have confirmed the crucial role of inhomogeneous phase electroluminescent nanostructures in improving the properties of MgB2. Experimental results demonstrate that the introduction of electroluminescent inhomogeneous phases effectively enhances the superconducting performance of MgB2. Moreover, by controlling the size of the electroluminescent inhomogeneous phases and optimizing grain connectivity, density, and microstructural uniformity, we can further improve the critical temperature (TC) and flux-pinning capability of MgB2 superconducting materials. Comprehensive studies on the physical properties of MgB2 superconducting structures added with p-n junction electroluminescent inhomogeneous phases also confirm the general effectiveness of electroluminescent inhomogeneous phases in enhancing the performance of superconducting materials.
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Background and objectives: There is a scarcity of data stemming from large-scale epidemiological longitudinal studies focusing on potentially preventable and controllable risk factors for Alzheimer's disease (AD) and AD-related dementia (ADRD). This study aimed to examine the effect of multiple metabolic factors and cardiovascular disorders on the risk of cognitive decline and AD/ADRD. Methods: We analyzed a cohort of 6,440 participants aged 45-84 years at baseline. Multiple metabolic and cardiovascular disorder factors included the five components of the metabolic syndrome [waist circumference, high blood pressure (HBP), elevated glucose and triglyceride (TG) concentrations, and reduced high-density lipoprotein cholesterol (HDL-C) concentrations], C-reactive protein (CRP), fibrinogen, interleukin-6 (IL-6), factor VIII, D-dimer, and homocysteine concentrations, carotid intimal-medial thickness (CIMT), and urine albumin-to-creatinine ratio (ACR). Cognitive decline was defined using the Cognitive Abilities Screening Instrument (CASI) score, and AD/ADRD cases were classified using clinical diagnoses. Results: Over an average follow-up period of 13 years, HBP and elevated glucose, CRP, homocysteine, IL-6, and ACR concentrations were significantly associated with the risk of mortality in the individuals with incident AD/ADRD or cognitive decline. Elevated D-dimer and homocysteine concentrations, as well as elevated ACR were significantly associated with incident AD/ADRD. Elevated homocysteine and ACR were significantly associated with cognitive decline. A dose-response association was observed, indicating that an increased number of exposures to multiple risk factors corresponded to a higher risk of mortality in individuals with cognitive decline or with AD/ADRD. Conclusion: Findings from our study reaffirm the significance of preventable and controllable factors, including HBP, hyperglycemia, elevated CRP, D-dimer, and homocysteine concentrations, as well as, ACR, as potential risk factors for cognitive decline and AD/ADRD.
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Using the trapped rainbow effect to slow down or even stop light has been widely studied. However, high loss and energy leakage severely limited the development of rainbow devices. Here, we observed the negative Goos-Hänchen effect in film samples across the entire visible spectrum. We also discovered an amber rainbow ribbon and an optical black hole due to perfect back reflection in optical waveguides, where little light leaks out. Not only does the amber rainbow ribbon effect show an automatic frequency selection response, as predicted by single frequency theoretical models and confirmed by experiments, it also shows spatial periodic regulation, resulting from broadband omnidirectional visible metamaterials prepared by disordered assembly systems. This broadband light trapping system could play a crucial role in the fields of optical storage and information processing when being used to construct ultra-compact modulators and other tunable devices.
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Cardio-metabolic diseases, including a cluster of metabolic disorders and their secondary affections on cardiovascular physiology, are gradually brought to the forefront by researchers due to their high prevalence and mortality, as well as an unidentified pathogenesis. tRNA-derived small RNAs (tsRNAs), cleaved by several specific enzymes and once considered as some "metabolic junks" in the past, have been proved to possess numerous functions in human bodies. More interestingly, such a potential also seems to influence the progression of cardio-metabolic diseases to some extent. In this review, the biogenesis, classification and mechanisms of tsRNAs will be discussed based on some latest studies, and their relations with several cardio-metabolic diseases will be highlighted in sequence. Lastly, some future prospects, such as their clinical applications as biomarkers and therapeutic targets will also be mentioned, in order to provide researchers with a comprehensive understanding of the research status of tsRNAs as well as its association with cardio-metabolic diseases, thus presenting as a beacon to indicate directions for the next stage of study.
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Enfermedades Metabólicas , ARN de Transferencia , Humanos , ARN de Transferencia/genética , ARN de Transferencia/metabolismo , ARN/genética , Enfermedades Metabólicas/genéticaRESUMEN
Cardiomyopathies (CMs) are highly heterogeneous progressive heart diseases characterised by structural and functional abnormalities of the heart, whose intricate pathogenesis has resulted in a lack of effective treatment options. Mitsugumin 53 (MG53), also known as Tripartite motif protein 72 (TRIM72), is a tripartite motif family protein from the immuno-proteomic library expressed primarily in the heart and skeletal muscle. Recent studies have identified MG53 as a potential cardioprotective protein that may play a crucial role in CMs. Therefore, the objective of this review is to comprehensively examine the underlying mechanisms mediated by MG53 responsible for myocardial protection, elucidate the potential role of MG53 in various CMs as well as its dominant status in the diagnosis and prognosis of human myocardial injury, and evaluate the potential therapeutic value of recombinant human MG53 (rhMG53) in CMs. It is expected to yield novel perspectives regarding the clinical diagnosis and therapeutic treatment of CMs.
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Cardiomiopatías , Miocardio , Humanos , Miocardio/metabolismo , Músculo Esquelético/metabolismo , Cardiomiopatías/tratamiento farmacológico , Cardiomiopatías/metabolismo , Corazón , Resultado del TratamientoRESUMEN
Polyethylene (PE) mulch films are an important source of microplastics (MPs) in agricultural soils, which may further affect the bioavailability of coexisting pollutants. In this study, white (WM), black (BM), and silver-black (SM) PE mulch films were aged on the soil surface and under soil burial to simulate the two exposure patterns of abandoned mulch films in the field. Results indicated that the soil-surface exposure induced more pronounced aging characteristics, and WM seemed the most susceptible. Serious surface deterioration by aging led to a drastic decrease in the tensile properties of the films, suggesting the tendency to fragment. Oxygen-containing functional groups were generated on the film surfaces, with oxygen/carbon ratios increasing by up to 29 times, which contributed to the prominent increase in Pb adsorption on the film-derived MPs. Additionally, the film surface became more hydrophobic when exposed to the soil surface but more hydrophilic in the soil-burial exposure, which was in agreement with the change in triclosan adsorption, i.e., promotion and suppression, respectively. Aging generally decreased the desorption potential of the adsorbed pollutants in simulated gastrointestinal solutions due to increased interactions. By comparison, exposure patterns were revealed to be the critical factor for these changes, regardless of film types.
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Metformin is a synthetic biguanide proven to have beneficial effects against various human diseases. Research has confirmed that metformin exerts its effects by regulating the composition of intestinal microbiota. The composition of intestinal microbiota influences the efficacy of anti-PD-L1 immunotherapy. We assume that the regulation of metformin on intestinal microbiota could enhance the therapeutic efficiency of anti-PD-L1 antibodies. In Lewis lung cancer-bearing C57BL/6J mice, we find that metformin enhances PD-L1 antibody efficacy mainly depending on the existence of gut microbiota, and metformin increases the anti-tumor immunity through modulation of intestinal microbiota and affects the integrity of the intestinal mucosa. Antibiotic depletion of gut microbiota abolished the combination efficacy of PD-L1 antibody and metformin, implying the significance of intestinal microbiota in metformin's antitumor action. Combining anti-PD-L1 antibody with metformin provoked tumor necrosis by causing increased CD8 T-cell infiltration and IFN-γ expression. In conclusion, metformin could be employed as a microecological controller to prompt antitumor immunity and increase the efficacy of anti-PD-L1 antibodies. Our study provided reliable evidence that metformin could be synergistically used with anti-PD-L1 antibody to enhance the anti-cancer effect.
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Microbioma Gastrointestinal , Metformina , Ratones , Animales , Humanos , Metformina/farmacología , Metformina/uso terapéutico , Antígeno B7-H1 , Ratones Endogámicos C57BL , Linfocitos T CD8-positivos , Línea Celular TumoralRESUMEN
Arsenic (As) contamination is widespread in soil and poses a threat to agricultural products and human health due to its high susceptibility to absorption by rice. Fe-bearing materials (Fe-Mat) display significant potential for reducing As bioavailability in soil and bioaccumulation in rice. However, the remediation effect of various Fe-Mat is often inconsistent, and the response to diverse environmental factors is ambiguous. Here, we conducted a meta-analysis to quantitatively assess the effects of As in soils, rice roots, and grains based on 673, 321, and 305 individual observations from 67 peer-reviewed articles, respectively. On average, Fe-Mat reduced As bioavailability in soils, rice roots, and grains by 28.74 %, 33.48 %, and 44.61 %, respectively. According to the analysis of influencing factors, the remediation efficiency of Fe-Mat on As-contaminated soil was significantly enhanced with increasing Fe content in the material, in which the industry byproduct was the most effective in soils (-42.31 %) and rice roots (-44.57 %), while Fe-biochar was superior in rice grains (-54.62 %). The efficiency of Fe-Mat in minimizing soil As mobility was negatively correlated with soil Fe content, CEC, and pH. In addition, applying Fe-Mat in alkaline soils with higher silt, lower clay and available P was more effective in reducing As in rice grains. A higher efficiency of applying Fe-Mat under continuous flooding conditions (27.39 %) compared with alternate wetting and drying conditions (23.66 %) was also identified. Our results offer an important reference for the development of remediation strategies and methods for various As-contaminated paddy soils.
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Arsénico , Oryza , Contaminantes del Suelo , Humanos , Arsénico/análisis , Suelo/química , Disponibilidad Biológica , Contaminación Ambiental , Contaminantes del Suelo/análisis , Cadmio/análisisRESUMEN
Superconducting materials exhibit unique physical properties and have great scientific value and vast industrial application prospects. However, due to limitations, such as the critical temperature (TC) and critical current density (JC), the large-scale application of superconducting materials remains challenging. Chemical doping has been a commonly used method to enhance the superconductivity of B(P)SCCO. However, satisfactory enhancement results have been difficult to achieve. In this study, we introduce green-light GaN p-n junction particles as inhomogeneous phases into B(P)SCCO polycrystalline particles to form a smart meta-superconductor (SMSC) structure. Based on the electroluminescence properties of the p-n junction, the Cooper pairs were stimulated and strengthened to enhance the superconductivity of B(P)SCCO. The experimental results demonstrate that the introduction of inhomogeneous phases can indeed enhance the critical temperature TC, critical current density JC, and complete diamagnetism (Meissner effect) of B(P)SCCO superconductors. Moreover, when the particle size of the raw material of B(P)SCCO is reduced from 30 to 5 µm, the grain size of the sintered samples also decreases, and the optimal doping concentration of the inhomogeneous phases increases from 0.15 wt.% to 0.2 wt.%, further improving the superconductivity.
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The preparation of the vast majority of nonlinear optical metal metasurfaces currently relies on complex top-down methods such as electron beam or ion beam etching, which are expensive and difficult to meet the requirement of large area preparation. In this paper, an easily prepared quasi-periodic silver dendritic metasurface model with highQfactor is established in the near-infrared band based on a simple and easy-to-operate electrochemical deposition method. The simulations prove that the silver dendritic metasurface has a highQfactor (exceeds 104) because of its strong electric field localization ability, which is analogous to the superposition of multiple split-ring resonators. It is demonstrated that the second harmonic generation (SHG) intensity of the dendritic metasurface at a large incident angle (such as 85°) is about 30 times that of the metasurface at a small incident angle when thex-polarized pump light is incident obliquely to break the centrosymmetry of the metasurface. The influences of the incident angle or dendritic structure's dimensions on theQfactor and SHG efficiency have also been researched through a lot of simulation. This easily prepared quasi-periodic silver dendritic metasurface SHG device may provide a new avenue for the development and application of miniature, integratable nonlinear optical devices.
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A polymerized ionic liquid (PIL) provides a platform for the development of a high-performance water-free polyelectrolyte-based electrorheological fluid (ERF) because of the presence of large-size hydrophobic ion pairs. However, the large-size hydrophobic ion pairs also easily result in a low glass-transition temperature of an ordinary linear PIL, and consequently, the PIL-based ERF has to be subject to a high leaking current density and a narrow working temperature range. In this paper, we prepared a kind of core-shell-structured polymerized ionic liquid@doubly polymerized ionic liquid (PIL@D-PIL) microsphere with a linear PIL as the core and a physically cross-linked D-PIL as the shell via an evaporation-assisted dispersion polymerization method. The core-shell structure of the sample was observed by scanning electron microscopy and transmission electron microscopy. The thermal properties of the sample were tested by differential scanning calorimetery and thermogravimetric analysis. The ER effect and dielectric polarization of PIL@D-PIL microspheres when dispersed in an insulating nonpolar liquid were studied by a rheometer and dielectric spectroscopy. It shows that the glass-transition temperature and thermal stability of a PIL increased after coating with the D-PIL shell. Under electric fields, the ERF of the PIL@D-PIL microspheres exhibits a significantly reduced leaking current density and an enhanced operating temperature range compared to the ERF of single-PIL microspheres. The PIL@D-PIL microspheres can still maintain good ER effect even if the temperature is higher than the glass-transition point of the PIL core due to the protection of the D-PIL shell.
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To investigate sexual dimorphism of serum pigment epithelium-derived factor (PEDF) and its influencing factors in healthy individuals. A total of 162 healthy people (69 males, 93 females) who underwent health examinations in our department were selected. Serum PEDF, estradiol and other metabolic indices were measured, and homeostasis model assessment of insulin resistance (HOMA-IR) and homeostasis model assessment of ß-cell function (HOMA-ß) were calculated to evaluate insulin resistance and ß-cell function, respectively. Subjects were divided intoâ <â 50 years andâ ≥â 50 years groups to explore the sexual dimorphism of serum PEDF in different age groups. We found no statistically significant difference in serum PEDF levels between men and women in total. However, in the group of subjects under 50 years old, men had significantly higher PEDF levels than women (9.32â ±â 2.07 µg/mL vs 8.24â ±â 2.29 µg/mL, Pâ <â .05), and no sex difference was found in theâ ≥â 50 years group. In women, serum PEDF levels were significantly higher in subjects aged 50 years and over than in those younger than 50 years of age (9.56â ±â 3.05 µg/mL vs 8.25â ±â 2.30 µg/mL, Pâ <â .05). In men, there was no significant difference in serum PEDF levels between the 2 age groups. In women, correlation analysis showed that serum PEDF levels were significantly correlated with body mass index, waist circumference, diastolic blood pressure (DBP), 2-h postprandial glucose, fasting and 2-h postprandial insulin, HOMA-ß, HOMA-IR, aminotransferase, triacylglycerol, and estradiol. Elevated triacylglycerol and aminotransferase and decreased estradiol were significant predictors of increased PEDF concentrations in women. There is sexual dimorphism in circulating PEDF levels, which may be related to estrogen status.
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Serpinas , Caracteres Sexuales , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estradiol , Proteínas del Ojo , Resistencia a la Insulina , Serpinas/metabolismoRESUMEN
Being a broad-spectrum anticancer drug, doxorubicin is indispensable for clinical treatment. Unexpectedly, its cardiotoxic side effects have proven to be a formidable obstacle. Numerous studies are currently devoted to elucidating the pathological mechanisms underlying doxorubicin-induced cardiotoxicity. Nrf2 has always played a crucial role in oxidative stress, but numerous studies have demonstrated that it also plays a vital part in pathological mechanisms like cell death and inflammation. Numerous studies on the pathological mechanisms associated with doxorubicin-induced cardiotoxicity demonstrate this. Several clinical drugs, natural and synthetic compounds, as well as small molecule RNAs have been demonstrated to prevent doxorubicin-induced cardiotoxicity by activating Nrf2. Consequently, this study emphasizes the introduction of Nrf2, discusses the role of Nrf2 in doxorubicin-induced cardiotoxicity, and concludes with a summary of the therapeutic modalities targeting Nrf2 to ameliorate doxorubicin-induced cardiotoxicity, highlighting the potential value of Nrf2 in doxorubicin-induced cardiotoxicity.