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AIM: Atrial fibrillation (AF), the most common arrhythmia, is characterized by atrial electrical and structural remodeling. Previous studies have found that sodium-glucose cotransporter 2 inhibitor (SGLT2i) can protect myocardium in a glucose independent mechanism. But the role of SGLT2i in regulating AF remains largely unknown. This study, we aimed to investigate the effect of Dapagliflozin (DAPA) in reducing AF susceptibility via inhibiting electrical and structural remodeling. METHOD: The mouse model was established by Angiotensin II (2000 ng/kg/min) infusion for 3 weeks, and an in vitro model was generated by stimulating HL-1 and primary mouse fibroblast with Ang II (1 µM) for 24 h. Programmed electrical stimulation, ECG and whole-cell patch clamp were used to detect DAPA effect on atrial electrical remodeling induced by Ang II. To observe DAPA effect on atrial structural remodeling induced by Ang II, we used echocardiographic, H&E and Masson staining to evaluate atrial dilation. To further explore the protective mechanism of DAPA, we adopt in silico molecular docking approaches to investigate the binding affinity of Ang II and CaMKII at Met-281 site. Western blot was to detect expression level of CaMKII, ox-CaMKII, Nav1.5, Kv4.3, Kv4.2, Kchip2, Kir2.1 and Cx40. RESULTS: Ang II induced AF, atrial dilatation and fibrosis, led to atrial electrical and structural remodeling. However, these effects were markedly abrogated by DAPA treatment, a specific SGLT2i. Our observation of atrial electrical activity in mice revealed that DAPA could rescue the prolonged action potential duration (APD) and the abnormal currents of IK1, Ito and INaL triggered by Ang II infusion. DAPA could reduce the binding affinity of Ang II and CaMKII at Met-281 site, which indicated that DAPA may directly alleviate the activation of CaMKII caused by Ang II. DAPA could reduce the upregulation of ox-CaMKII caused by Ang II infusion in atrial tissues. Moreover, DAPA also ameliorated the aberrant expression levels of electrical activity related proteins (Nav1.5, Kv4.3, Kv4.2, Kchip2, Kir2.1 and Cx40) and fibrosis related signal pathways (TGF-ß1, p-smad/smad) caused by Ang II. Furthermore, we confirmed that DAPA, as well as other SGLT2i (EMPA, CANA), could reverse these abnormalities caused by Ang II incubation in HL-1 cells and primary mouse fibroblasts, respectively. CONCLUSION: Overall, our study identifies DAPA, a widely used SGLT2i, contributes to inhibiting Ang II-induced ox-CaMKII upregulation and electrical and structural remodeling to reduce AF susceptibility, suggesting that DAPA may be a potential therapy of treating AF.
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Angiotensina II , Fibrilación Atrial , Remodelación Atrial , Compuestos de Bencidrilo , Proteína Quinasa Tipo 2 Dependiente de Calcio Calmodulina , Glucósidos , Atrios Cardíacos , Simulación del Acoplamiento Molecular , Inhibidores del Cotransportador de Sodio-Glucosa 2 , Animales , Angiotensina II/farmacología , Inhibidores del Cotransportador de Sodio-Glucosa 2/farmacología , Fibrilación Atrial/inducido químicamente , Fibrilación Atrial/metabolismo , Fibrilación Atrial/tratamiento farmacológico , Fibrilación Atrial/fisiopatología , Remodelación Atrial/efectos de los fármacos , Glucósidos/farmacología , Ratones , Proteína Quinasa Tipo 2 Dependiente de Calcio Calmodulina/metabolismo , Atrios Cardíacos/efectos de los fármacos , Atrios Cardíacos/metabolismo , Atrios Cardíacos/fisiopatología , Atrios Cardíacos/patología , Masculino , Compuestos de Bencidrilo/farmacología , Ratones Endogámicos C57BL , Modelos Animales de Enfermedad , Línea CelularRESUMEN
Understanding cellular coordination remains a challenge despite knowledge of individual pathways. The RNA exosome, targeting a wide range of RNA substrates, is often downregulated in cellular senescence. Utilizing an auxin-inducible system, we observed that RNA exosome depletion in embryonic stem cells significantly affects the transcriptome and proteome, causing pluripotency loss and pre-senescence onset. Mechanistically, exosome depletion triggers acute nuclear RNA aggregation, disrupting nuclear RNA-protein equilibrium. This disturbance limits nuclear protein availability and hinders polymerase initiation and engagement, reducing gene transcription. Concurrently, it promptly disrupts nucleolar transcription, ribosomal processes, and nuclear exporting, resulting in a translational shutdown. Prolonged exosome depletion induces nuclear structural changes resembling senescent cells, including aberrant chromatin compaction, chromocenter disassembly, and intensified heterochromatic foci. These effects suggest that the dynamic turnover of nuclear RNA orchestrates crosstalk between essential processes to optimize cellular function. Disruptions in nuclear RNA homeostasis result in systemic functional decline, altering the cell state and promoting senescence.
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Senescencia Celular , Homeostasis , ARN Nuclear , Animales , ARN Nuclear/metabolismo , Ratones , Diferenciación Celular , Linaje de la Célula , Núcleo Celular/metabolismo , Transcriptoma/genética , HumanosRESUMEN
Sugar-free food has been gaining popularity because of low-calorie content. But sugar replacement by high-intensity sweeteners can negatively affect sensory. In this study, the effect of the addition of sucralose (Suc), stevioside (Ste), and erythritol (Ery) as sugar substitutes on the sensory profile and overall acceptance of ice cream were evaluated by penalty analysis (PA) based on the check-all-that apply (CATA) method, with those of the partial least squares (PLS) regression. Twelve sweetening agents of ice cream samples were presented to 106 consumers who answered on an overall liking question using the 15-point hedonic scale and a CATA question with 32 attributes that described the sensory characteristics of ice cream. The results showed that mixed sweeteners (60%Suc+20%Ste+20%Ery or 60%Suc+10%Ste+30%Ery) can present an advantageous performance when used separately, and making ice cream similar to that of sucrose (Sac) added. Adding Suc, Ste, and Ery to ice cream hardly felt bitterness, astringency, and chemical-like sensations of the sweetening agent. The significant difference between different sweeteners is the intensity and speed of sweetness. Developing combination of high-potency sweeteners that can make sweetness appear quickly could open up new ways to design sugar-free ice cream.
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Diterpenos de Tipo Kaurano , Glucósidos , Helados , Sacarosa/análogos & derivados , Edulcorantes , Eritritol/análisis , Helados/análisis , Gusto , CarbohidratosRESUMEN
Anxiety and depression are frequently noticed in glioma patients, while few studies report this issue in recurrent glioma patients. Hence, this study aimed to evaluate the prevalence of anxiety and depression, as well as their risk factors and prognostic value in recurrent glioma patients. Eighty recurrent glioma patients, 40 newly-diagnosed glioma patients, and 40 healthy controls were enrolled in this study. Then, the Hospital Anxiety and Depression Scale for anxiety (HADS-A) and for depression (HADS-D) were used to assess the anxiety and depression status of all subjects. The HADS-A score (8.6 ± 3.3 vs. 7.0 ± 2.9 vs. 4.3 ± 2.5), anxiety rate (58.8% vs. 32.5% vs. 10.0%), HADS-D score (7.9 ± 3.0 vs. 6.9 ± 3.1 vs. 4.0 ± 2.6), and depression rate (45.0% vs. 30.0% vs. 7.5%) were all highest in recurrent glioma patients, followed by newly-diagnosed glioma patients, and were lowest in healthy controls (all P < 0.001). Furthermore, female sex (vs. male sex) was independently correlated with anxiety (odds ratio (OR): 3.042, P = 0.029); meanwhile, higher World Health Organization (WHO) pathological grade was independently correlated with depression (OR: 2.573, P = 0.019) in recurrent glioma patients. Additionally, anxiety was correlated with shortened progression-free survival (PFS) (P = 0.028) and overall survival (OS) (P = 0.047), while depression only had a correlation trend with shortened PFS (without statistical significance) (P = 0.069) and was associated with shortened OS (P = 0.035) in recurrent glioma patients. The prevalence of anxiety and depression is high in recurrent glioma patients, which relates to gender, WHO pathological grade, and estimates worsen survival.
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Depresión , Glioma , Humanos , Masculino , Femenino , Pronóstico , Depresión/epidemiología , Prevalencia , Recurrencia Local de Neoplasia/epidemiología , Ansiedad/epidemiología , Glioma/epidemiología , Factores de RiesgoRESUMEN
Since the expensive annotation of high-quality signals obtained from passive sonars and the weak generalization ability of the single feature in the ocean, this paper proposes the self-supervised acoustic representation learning under acoustic-embedding memory unit modified space autoencoder (ASAE) and performs the underwater target recognition task. In the manner of the animal-like acoustic auditory system, the first step is to design a self-supervised representation learning method called space autoencoder (SAE) to merge Mel filter-bank (FBank) with the acoustic discrimination and gammatone filter-bank (GBank) with the anti-noise robustness into SAE spectrogram (SAE Spec). Meanwhile, due to poor high-level semantic information in SAE Spec, an acoustic-embedding memory unit (AEMU) is introduced as the strategy of adversarial enhancement. During the auxiliary task, more negative samples are joined in the improved contrastive loss function to obtain adversarial enhanced features called ASAE spectrogram (ASAE Spec). Ultimately, the comprehensive contrast experiments and ablation experiments on two underwater datasets show that ASAE Spec increases by more than 0.96% in accuracy, convergence rate, and anti-noise robustness of other mainstream acoustic features. The results prove the potential value of ASAE in practical applications.
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Some studies have shown that sodium-glucose cotransporter (SGLT) 2 inhibitors can definitively attenuate the occurrence of cardiovascular diseases such as heart failure (HF), dilated cardiomyopathy (DCM), and myocardial infarction. With the development of research, SGLT2 inhibitors can also reduce the risk of arrhythmias. So in this review, how SGLT2 inhibitors play a role in reducing the risk of arrhythmia from the perspective of electrical remodeling and structural remodeling are explored and then the possible mechanisms are discussed. Specifically, we focus on the role of SGLT2 inhibitors in Na+ and Ca2 + homeostasis and the transients of Na+ and Ca2 +, which could affect electrical remodeling and then lead to arrythmia. We also discuss the protective role of SGLT2 inhibitors in structural remodeling from the perspective of fibrosis, inflammation, oxidative stress, and apoptosis. Ultimately, it is clear that SGLT2 inhibitors have significant benefits on cardiovascular diseases such as HF, myocardial hypertrophy and myocardial infarction. It can be expected that SGLT2 inhibitors can reduce the risk of arrhythmia.
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An online platform is a setting where users may express their attitude in text or visual content. The doctrine thinking in consumer psychology is that greater perceived product value (e.g., more product features or lower price) gives more positive consumer attitude. Because of different types of platforms, however, online users might form their product/brand attitudes in different ways. We gathered 7,264 lines of online reviews about two famous brands on two types of social media platforms: online text-based forums and live-streaming platforms. The data were collected through a web crawler, and semantic analysis was employed to process the data before hypothesis testing. The findings of this study indicate that users' perception of product features, price levels and brand culture significantly influence user attitude. The more product characteristics communicated on online platforms, the more difficult to formulate a positive user attitude, and users tend to have more positive attitude with higher perceived price. Compared with traditional text-based platforms, contents in live-streaming platforms (e.g., Tik Tok) with less product features, wider culture distance and lower perceived price are favored among users.
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Background: Recent clinical trials indicate that sodium-glucose cotransporter 2 (SGLT2) inhibitors improve cardiovascular outcomes in myocardial infarction (MI) patients, but the underlying mechanisms remain unknown. As arrhythmia often occurs during myocardial infarction, it is the main cause of death. Objective: The purpose of this study was to investigate the influence of empagliflozin (EMPA), an SGLT2 inhibitor, on cardiac electrophysiological remodeling and arrhythmia susceptibility of myocardial infarction mice. Methods: ECG was obtained from mice 1 week after MI to determine the QT interval. In an electrophysiological study and optical mapping was performed to evaluate the function of EMPA and underlying mechanisms of post-myocardial-infarction in mice. Results: EMPA treatment significantly reduced the QT interval of MI mice (MI + EMPA 50.24 ms vs. MI 64.68 ms). The membrane potential and intracellular Ca [Cai] were mapped from 13 MI hearts and five normal hearts using an optical mapping technique. A dynamic pacing protocol was used to determine action potential duration and [Cai] at baseline and after EMPA (10 umol/L) infusion. EMPA perfusion did not change the APD80 and CaT80 in normal ventricles while shortening them in an infarct zone, bordering zone, and remote zone of MI hearts at 200 ms, 150 ms, 120 ms, and 100 ms pacing cycle length. The conduction velocity of infarcted ventricles was 0.278 m/s and 0.533 m/s in normal ventricles at baseline (p < 0.05). After EMPA administration, the conduction velocity of infarcted ventricles increased to 0.363 m/s, whereas no significant changes were observed in normal ventricles. The action potential rise time, CaT rise time, and CaT tau time were improved after EMPA perfusion in infarcted ventricles, whereas no significant changes were observed in normal ventricles. EMPA decreases early afterdepolarizations premature ventricular beats, and ventricular fibrillation (VF) in infarcted ventricles. The number of phase singularities (baseline versus EMPA, 6.26 versus 3.25), dominant frequency (20.52 versus 10.675 Hz), and ventricular fibrillation duration (1.072 versus 0.361 s) during ventricular fibrillation in infarcted ventricles were all significantly decreased by EMPA. Conclusion: Treatment with EMPA improved post-MI electrophysiological remodeling and decreased substrate for VF of MI mice. The inhibitors of SGLT2 may be a new class of agents for the prevention of ventricle arrhythmia after chronic MI.
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We developed a workflow for the search and screening of natural products by drawing from worldwide experiences shared by online platform users, illustrated how to cope with COVID-19 with a text-mining approach, and statistically tested the natural product identified. We built a knowledge base, which consists of three ontologies pertaining to 7653 narratives. Mustard emerged from texting mining and knowledge engineering as an important candidate relating to COVID-19 outcomes. The findings indicate that, after controlling for the containment index, the net import of mustard is related with reduced total and new deaths of COVID-19 for the non-vaccination time period, with considerable effect size (>0.2).
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INTRODUCTION: Anxiety and depression exhibit a high prevalence in systemic lupus erythematosus (SLE) patients, while this issue is seldom explored in lupus nephritis (LN). Hence, the current study aimed to investigate the prevalence of anxiety and depression, and the risk factors for these mental disorders in LN patients. METHODS: Fifty LN patients, 50 non-LN SLE patients, and 50 health control (HCs) were enrolled. The Hospital Anxiety and Depression Scale (HADS) for anxiety (HADS-A) score and HADS for depression (HADS-D) score were evaluated. RESULTS: HADS-A score was highest in LN patients (median 7.0, interquartile range [IQR]: 6.0-10.0), followed by non-LN SLE patients (median 6.0, IQR: 5.0-8.0), and lowest in HCs (median 5.0, IQR: 3.0-7.0) (p < .001). Besides, the anxiety rate was most frequent in LN patients (38.0%), followed by non-LN SLE patients (28.0%), least common in HCs (12.0%) (p = .011). HADS-D score was highest in LN patients (median 7.5, IQR: 6.0-11.0), followed by non-LN SLE patients (median 6.0, IQR: 5.0-8.3), and lowest in HCs (median 4.0, IQR: 2.0-6.3) (p < .001). Similarly, the depression rate was most prevalent in LN patients (50.0%), subsequently the non-LN SLE patients (30.0%), and rarest in HCs (10.0%) (p < .001). Furthermore, in LN patients, age (p = .009), LN activity index (p = .020), alopecia (p = .023), 24 h proteinuria (p = .044), and C-reactive protein (p = .049) were independently correlated with higher anxiety risk; meanwhile, age (p = .001) and LN activity index (p = .009) were independently correlated with higher depression risk. CONCLUSION: Anxiety and depression are highly prevalent, which link to aging, alopecia, inflammation, and severe renal involvement in LN patients.
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Lupus Eritematoso Sistémico , Nefritis Lúpica , Alopecia , Ansiedad/epidemiología , Estudios de Casos y Controles , Depresión/epidemiología , Depresión/etiología , Humanos , Nefritis Lúpica/epidemiología , Prevalencia , Factores de RiesgoRESUMEN
Chrysanthemum has a long history of being used to attenuate various oxidative stress-related discomforts and diseases; however, its mechanisms remain unclear. In this study, the antioxidant effect of chrysanthemum aqueous extract was investigated, and the potential mechanisms were explored via a metabolomics study. Chrysanthemum extract could significantly inhibit hydrogen peroxide (H2O2)-mediated cell death in L-O2 hepatocytes. Propidium iodide staining and annexin V-PI dual staining revealed that the antioxidant effect of chrysanthemum extract was related to the relief of cell cycle arrest and inhibition of non-apoptotic cell damage. The activities of antioxidant enzymes including superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) were also upregulated by chrysanthemum extract. Through metabolomics studies, it was found that chrysanthemum extract mainly targeted the arginine synthesis pathway and purine metabolism pathway, in which antioxidation-related endogenous substrates including L-arginosuccinate, citrulline and inositol monophosphate were significantly upregulated by chrysanthemum extract. These results indicated that chrysanthemum extract can antagonize oxidative stress through multiple pathways and have potential therapeutic applications.
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An RNA-involved phase-separation model has been proposed for transcription control. However, the molecular links that connect RNA to the transcription machinery remain missing. Here we find that RNA-binding proteins (RBPs) constitute half of the chromatin proteome in embryonic stem cells (ESCs), some being colocalized with RNA polymerase (Pol) II at promoters and enhancers. Biochemical analyses of representative RBPs show that the paraspeckle protein PSPC1 inhibits the RNA-induced premature release of Pol II, and makes use of RNA as multivalent molecules to enhance the formation of transcription condensates and subsequent phosphorylation and release of Pol II. This synergistic interplay enhances polymerase engagement and activity via the RNA-binding and phase-separation activities of PSPC1. In ESCs, auxin-induced acute degradation of PSPC1 leads to genome-wide defects in Pol II binding and nascent transcription. We propose that promoter-associated RNAs and their binding proteins synergize the phase separation of polymerase condensates to promote active transcription.
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ARN Polimerasa II/metabolismo , Proteínas de Unión al ARN/metabolismo , Transcripción Genética , Regulación de la Expresión Génica , Fosforilación , Regiones Promotoras Genéticas , Unión ProteicaRESUMEN
Compared with red and green organic light-emitting diodes (OLEDs), blue is the bottleneck that restricts the wide development of OLEDs from being the next-generation technology for displays and lighting. As a new type of emitter, a Ce(III) complex shows many satisfactory advantages, such as a short excited-state lifetime, 100% theoretical exciton utilization efficiency, and tunable emission color. Herein we synthesized three heteroleptic Ce(III) complexes Ce(TpMe2)2(dtfpz), Ce(TpMe2)2(dmpz), and Ce(TpMe2)2(dppz) with the hydrotris(3,5-dimethylpyrazolyl)borate (TpMe2) main ligand and different substituted pyrazole ancillary ligands, namely, 3,5-di(trifluomethyl)pyrazolyl (dtfpz), 3,5-dimethylpyrazolyl (dmpz), and 3,5-diphenylpyrazolyl (dppz), and studied their structures and luminescence properties. All the Ce(III) complexes exhibited a near-unity photoluminescence quantum yield both in solution and as a powder with maximum emission wavelengths in the range of 450-486 nm. The OLED employing Ce(TpMe2)2(dppz) as the emitter showed the best performance, including a turn-on voltage, maximum luminance, and external quantum efficiency of 3.2 V, 29â¯200 cd m-2, and 12.5%, respectively.
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In the field of RGB diodes, development of a blue organic light-emitting diode (OLED) is a challenge because of the lack of an emitter which simultaneously has a short excited state lifetime and a high theoretical external quantum efficiency (EQE). We demonstrate herein a blue emissive rare earth cerium(III) complex Ce-2 showing a high photoluminescence quantum yield of 95% and a short excited state lifetime of 52.0 ns in doped film, which is considerably faster than that achieved in typical efficient phosphorescence or thermally activated delayed fluorescence emitters (typical lifetimes >1 µs). The corresponding OLED shows a maximum EQE up to 20.8% and a still high EQE of 18.2% at 1000 cd m-2, as well as an operation lifetime 70 times longer than that of a classic phosphorescence OLED. The excellent performance indicates that cerium(III) complex could be a candidate for efficient and stable blue OLEDs because of its spin- and parity-allowed d-f transition from the Ce3+ ion.
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Organic light-emitting diodes (OLEDs) have had commercial success in displays and lighting. Compared to red and green OLEDs, blue OLEDs are still the bottleneck because the high-energy and long-lived triplet exciton in traditional blue OLEDs causes the short operational lifetime of the device. As a new type emitter, lanthanide complexes with a 5d-4f transition could have short excited-state lifetimes on the order of nanoseconds. To achieve a high-efficiency 5d-4f transition, we systematically tuned the steric and electronic effects of tripodal tris(pyrazolyl)borate ligands and drew a full picture of their Ce(III) complexes. Intriguingly, all of these complexes show bright blue emission with high photoluminescence quantum yields exceeding 95% and short decay lifetimes of 35-73 ns both in the solid powder and in dichloromethane solutions. Using the Ce(III) complex emitter, we show a blue OLED with a maximum external quantum efficiency of 14.1% and a maximum luminance of 33,160 cd m-2, and the specific electroluminescence mechanism of direct exciton formation on the Ce(III) ion with a near-unity exciton utilization efficiency is also confirmed. The discovered photoluminescence and electroluminescence property-structure relationships may shed new light on the rational design of highly efficient lanthanide-based blue emitters and their optoelectronic devices such as OLEDs.
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Tin (Sn)-based perovskite is one of the most promising candidates for lead (Pb)-free perovskite light-absorbing materials applied in solar cells. However, the intrinsic Sn vacancy (VSn) defects seriously hinder the device performance, making the reported maximum power efficiency (PCE) of Sn-based perovskite solar cells (PSCs) far behind those of Pb-based ones. During the study, SnF2 has been demonstrated as an indispensable Sn compensator additive to improve the device performance. Considering that the default use of SnF2 and the selection of a Sn compensator has also been limited to tin(II) halides, i.e., SnCl2, SnBr2, and SnI2, the role and work mechanism of the Sn compensator have not yet been clarified clearly. Herein, a new type of Sn compensator, tin(II) acetylacetonate [Sn (acac)2], is introduced into Sn-based PSCs. It is found that in addition to tin compensation, the organic ligand acac- can coordinate with Sn2+ in the precursor solution and improve the crystallization process of perovskites. Consequently, the maximum PCE of formamidinium tin triiodide (FASnI3) solar cells is enhanced from 3.88 to 7.27% using Sn (acac)2 as the Sn compensator.
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Drug-mediated or medical condition-mediated disruption of hERG function accounts for the main cause of acquired long-QT syndrome (acLQTs), which predisposes affected individuals to ventricular arrhythmias (VA) and sudden death. Many Chinese herbal medicines, especially alkaloids, have risks of arrhythmia in clinical application. The characterized mechanisms behind this adverse effect are frequently associated with inhibition of cardiac hERG channels. The present study aimed to assess the potent effect of Rutaecarpine (Rut) on hERG channels. hERG-HEK293 cell was applied for evaluating the effect of Rut on hERG channels and the underlying mechanism. hERG current (IhERG ) was measured by patch-clamp technique. Protein levels were analysed by Western blot, and the phosphorylation of Sp1 was determined by immunoprecipitation. Optical mapping and programmed electrical stimulation were used to evaluate cardiac electrophysiological activities, such as APD, QT/QTc, occurrence of arrhythmia, phase singularities (PSs), and dominant frequency (DF). Our results demonstrated that Rut reduced the IhERG by binding to F656 and Y652 amino acid residues of hERG channel instantaneously, subsequently accelerating the channel inactivation, and being trapped in the channel. The level of hERG channels was reduced by incubating with Rut for 24 hours, and Sp1 in nucleus was inhibited simultaneously. Mechanismly, Rut reduced threonine (Thr)/ tyrosine (Tyr) phosphorylation of Sp1 through PI3K/Akt pathway to regulate hERG channels expression. Cell-based model unables to fully reveal the pathological process of arrhythmia. In vivo study, we found that Rut prolonged QT/QTc intervals and increased induction rate of ventricular fibrillation (VF) in guinea pig heart after being dosed Rut for 2 weeks. The critical reasons led to increased incidence of arrhythmias eventually were prolonged APD90 and APD50 and the increase of DF, numbers of PSs, incidence of early after-depolarizations (EADs). Collectively, the results of this study suggest that Rut could reduce the IhERG by binding to hERG channels through F656 and Y652 instantaneously. While, the PI3K/Akt/Sp1 axis may play an essential role in the regulation of hERG channels, from the perspective of the long-term effects of Rut (incubating for 24 hours). Importantly, the changes of electrophysiological properties by Rut were the main cause of VA.
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Potenciales de Acción , Arritmias Cardíacas/patología , Canal de Potasio ERG1/antagonistas & inhibidores , Alcaloides Indólicos/efectos adversos , Síndrome de QT Prolongado/patología , Quinazolinas/efectos adversos , Vasodilatadores/efectos adversos , Disfunción Ventricular/patología , Animales , Arritmias Cardíacas/inducido químicamente , Arritmias Cardíacas/metabolismo , Células Cultivadas , Fenómenos Electrofisiológicos , Cobayas , Células HEK293 , Humanos , Síndrome de QT Prolongado/inducido químicamente , Síndrome de QT Prolongado/metabolismo , Masculino , Disfunción Ventricular/inducido químicamente , Disfunción Ventricular/metabolismoRESUMEN
Organization of the genome into euchromatin and heterochromatin appears to be evolutionarily conserved and relatively stable during lineage differentiation. In an effort to unravel the basic principle underlying genome folding, here we focus on the genome itself and report a fundamental role for L1 (LINE1 or LINE-1) and B1/Alu retrotransposons, the most abundant subclasses of repetitive sequences, in chromatin compartmentalization. We find that homotypic clustering of L1 and B1/Alu demarcates the genome into grossly exclusive domains, and characterizes and predicts Hi-C compartments. Spatial segregation of L1-rich sequences in the nuclear and nucleolar peripheries and B1/Alu-rich sequences in the nuclear interior is conserved in mouse and human cells and occurs dynamically during the cell cycle. In addition, de novo establishment of L1 and B1 nuclear segregation is coincident with the formation of higher-order chromatin structures during early embryogenesis and appears to be critically regulated by L1 and B1 transcripts. Importantly, depletion of L1 transcripts in embryonic stem cells drastically weakens homotypic repeat contacts and compartmental strength, and disrupts the nuclear segregation of L1- or B1-rich chromosomal sequences at genome-wide and individual sites. Mechanistically, nuclear co-localization and liquid droplet formation of L1 repeat DNA and RNA with heterochromatin protein HP1α suggest a phase-separation mechanism by which L1 promotes heterochromatin compartmentalization. Taken together, we propose a genetically encoded model in which L1 and B1/Alu repeats blueprint chromatin macrostructure. Our model explains the robustness of genome folding into a common conserved core, on which dynamic gene regulation is overlaid across cells.
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Elementos de Nucleótido Esparcido Largo , Secuencias Repetitivas de Ácidos Nucleicos , Animales , Análisis por Conglomerados , Elementos de Nucleótido Esparcido Largo/genética , Ratones , ARN , Secuencias Repetitivas de Ácidos Nucleicos/genética , RetroelementosRESUMEN
Divalent europium 5d-4f transition has aroused great attention in many fields, in a way of doping Eu2+ ions into inorganic solids. However, molecular Eu2+ complexes with 5d-4f transition are thought to be too air-unstable to explore their applications. In this work, we synthesized four Eu2+-containing azacryptates EuX2-Nn (X = Br, I, n = 4, 8) and systematically studied the photophysical properties in crystalline samples and solutions. Intriguingly, the EuX2-N8 complexes exhibit near-unity photoluminescence quantum yield, good air-/thermal-stability and mechanochromic property (X = I). Furthermore, we proved the application of Eu2+ complexes in organic light-emitting diodes (OLEDs) with high efficiency and luminance. The optimized device employing EuI2-N8 as emitter has the best performance as the maximum luminance, current efficiency, and external quantum efficiency up to 25470 cd m-2, 62.4 cd A-1, and 17.7%, respectively. Our work deepens the understanding of structure-property relationship in molecular Eu2+ complexes and could inspire further research on application in OLEDs.
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Compared to red and green organic light-emitting diodes (OLEDs), blue OLEDs are still the bottleneck due to the lack of efficient emitters with simultaneous high exciton utilization efficiency (EUE) and short excited-state lifetime. Different from the fluorescence, phosphorescence, thermally activated delayed fluorescence (TADF), and organic radical materials traditionally used in OLEDs, we demonstrate herein a new type of emitter, cerium(III) complex Ce-1 with spin-allowed and parity-allowed d-f transition of the centre Ce3+ ion. The compound exhibits a high EUE up to 100% in OLEDs and a short excited-state lifetime of 42 ns, which is considerably faster than that achieved in efficient phosphorescence and TADF emitters. The optimized OLEDs show an average maximum external quantum efficiency (EQE) of 12.4% and Commission Internationale de L'Eclairage (CIE) coordinates of (0.146, 0.078).