RNA Targets Ribogenesis Factor WDR43 to Chromatin for Transcription and Pluripotency Control.

Transcription regulation underlies stem cell function and development. Here, we elucidate an unexpected role of an essential ribogenesis factor, WDR43, as a chromatin-associated RNA-binding protein (RBP) and release factor in modulating the polymerase (Pol) II activity for pluripotency regulation. WDR43 binds prominently to promoter-associated noncoding/nascent RNAs, occupies thousands of gene promoters and enhancers, and interacts with the Pol II machinery in embryonic stem cells (ESCs). Nascent transcripts and transcription recruit WDR43 to active promoters, where WDR43 facilitates releases of the elongation factor P-TEFb and paused Pol II. Knockdown of WDR43 causes genome-wide defects in Pol II release and pluripotency-associated gene expression. Importantly, auxin-mediated rapid degradation of WDR43 drastically reduces Pol II activity, precluding indirect consequences. These results reveal an RNA-mediated recruitment and feedforward regulation on transcription and demonstrate an unforeseen role of an RBP in promoting Pol II elongation and coordinating high-level transcription and translation in ESC pluripotency.

Phase separation of RNA-binding protein promotes polymerase binding and transcription.

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.

Prevalence, risk factors and prognostic value of anxiety and depression in recurrent glioma patients.

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.

Self-supervised acoustic representation learning via acoustic-embedding memory unit modified space autoencoder for underwater target recognition.

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.

Rutaecarpine targets hERG channels and participates in regulating electrophysiological properties leading to ventricular arrhythmia.

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.

Highly Efficient Heteroleptic Cerium(III) Complexes with a Substituted Pyrazole Ancillary Ligand and Their Application in Blue Organic Light-Emitting Diodes.

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, 29 200 cd m-2, and 12.5%, respectively.

Highly Efficient and Air-Stable Lanthanide EuII Complex: New Emitter in Organic Light Emitting Diodes.

Luminescent EuII complexes with a characteristic 5d-4f transition have potential applications in many fields. However, their instability in ambient conditions impedes further exploration and application. Herein, we report two new EuII complexes, bis[hydrotris(3-trifluoromethylpyrazolyl)borate]europium(II) (Eu-1) and bis[hydrotris(3-methylpyrazolyl)borate]europium(II) (Eu-2). Intriguingly, the blue emissive Eu-1 showed high air stability arising from fluorine protection and close molecular packing, as maintaining a photoluminescence quantum yield (PLQY) of 91 % (initial 96 %) upon exposure to air over 2200 hours. While the orange emissive Eu-2 showed a maximum luminance of 30620 cd m-2 , and a maximum external quantum efficiency (EQE) of 6.5 %, corresponding to an exciton utilization efficiency around 100 % in organic light-emitting diodes (OLEDs). These results could inspire further research on stable and efficient EuII complexes and their application in OLEDs.

Analysis of C. elegans muscle transcriptome using trans-splicing-based RNA tagging (SRT).

Current approaches to profiling tissue-specific gene expression in C. elegans require delicate manipulation and are difficult under certain conditions, e.g. from dauer or aging worms. We have developed an easy and robust method for tissue-specific RNA-seq by taking advantage of the endogenous trans-splicing process. In this method, transgenic worms are generated in which a spliced leader (SL) RNA gene is fused with a sequence tag and driven by a tissue-specific promoter. Only in the tissue of interest, the tagged SL RNA gene is transcribed and then trans-spliced onto mRNAs. The tag allows enrichment and sequencing of mRNAs from that tissue only. As a proof of principle, we profiled the muscle transcriptome, which showed high coverage and efficient enrichment of muscle specific genes, with low background noise. To demonstrate the robustness of our method, we profiled muscle gene expression in dauer larvae and aging worms, revealing gene expression changes consistent with the physiology of these stages. The resulting muscle transcriptome also revealed 461 novel RNA transcripts, likely muscle-expressed long non-coding RNAs. In summary, the splicing-based RNA tagging (SRT) method provides a convenient and robust tool to profile trans-spliced genes and identify novel transcripts in a tissue-specific manner, with a low false positive rate.

Stereoselective Blockage of Quinidine and Quinine in the hERG Channel and the Effect of Their Rescue Potency on Drug-Induced hERG Trafficking Defect.

Diastereoisomers of quinidine and quinine are used to treat arrhythmia and malaria, respectively. It has been reported that both drugs block the hERG (human ether-a-go-go-related gene) potassium channel which is essential for myocardium repolarization. Abnormality of repolarization increases risk of arrhythmia. The aim of our research is to study and compare the impacts of quinidine and quinine on hERG. Results show that both drugs block the hERG channel, with quinine 14-fold less potent than quinidine. In addition, they presented distinct impacts on channel dynamics. The results imply their stereospecific block effect on the hERG channel. However, F656C-hERG reversed this stereoselectivity. The mutation decreases affinity of the two drugs with hERG, and quinine was more potent than quinidine in F656C-hERG blockage. These data suggest that F656 residue contributes to the stereoselective pocket for quinidine and quinine. Further study demonstrates that both drugs do not change hERG protein levels. In rescue experiments, we found that they exert no reverse effect on pentamidine- or desipramine-induced hERG trafficking defect, although quinidine has been reported to rescue trafficking-deficient pore mutation hERG G601S based on the interaction with F656. Our research demonstrated stereoselective effects of quinidine and quinine on the hERG channel, and this is the first study to explore their reversal potency on drug-induced hERG deficiency.

A Novel Sucrose-Regulatory MADS-Box Transcription Factor GmNMHC5 Promotes Root Development and Nodulation in Soybean (Glycine max [L.] Merr.).

The MADS-box protein family includes many transcription factors that have a conserved DNA-binding MADS-box domain. The proteins in this family were originally recognized to play prominent roles in floral development. Recent findings, especially with regard to the regulatory roles of the AGL17 subfamily in root development, have greatly broadened their known functions. In this study, a gene from soybean (Glycine max [L.] Merr.), GmNMHC5, was cloned from the Zigongdongdou cultivar and identified as a member of the AGL17 subfamily. Real-time fluorescence quantitative PCR analysis showed that GmNMHC5 was expressed at much higher levels in roots and nodules than in other organs. The activation of expression was first examined in leaves and roots, followed by shoot apexes. GmNMHC5 expression levels rose sharply when the plants were treated under short-day conditions (SD) and started to pod, whereas low levels were maintained in non-podding plants under long-day conditions (LD). Furthermore, overexpression of GmNMHC5 in transgenic soybean significantly promoted lateral root development and nodule building. Moreover, GmNMHC5 is upregulated by exogenous sucrose. These results indicate that GmNMHC5 can sense the sucrose signal and plays significant roles in lateral root development and nodule building.

Ice cream with sucralose, stevioside, and erythritol as sugar substitutes: Sensory profile and customer preference.

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.

Dapagliflozin: A sodium-glucose cotransporter 2 inhibitor, attenuates angiotensin II-induced atrial fibrillation by regulating atrial electrical and structural remodeling.

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.

Nuclear RNA homeostasis promotes systems-level coordination of cell fate and senescence.

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.

Anxiety and depression prevalence and their risk factors in lupus nephritis patients: A case-control study.

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.

Does platform type matter? A semantic analysis of user attitude formation on online platforms.

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.

The Relationship between Mustard Import and COVID-19 Deaths: A Workflow with Cross-Country Text Mining.

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).

Antioxidant Effect of Chrysanthemum morifolium (Chuju) Extract on H2O2-Treated L-O2 Cells as Revealed by LC/MS-Based Metabolic Profiling.

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.

Benefits of SGLT2 inhibitors in arrhythmias.

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.

Sodium-Glucose cotransporter 2 inhibitor empagliflozin decreases ventricular arrhythmia susceptibility by alleviating electrophysiological remodeling post-myocardial-infarction in mice.

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.

Efficient rare earth cerium(III) complex with nanosecond d-f emission for blue organic light-emitting diodes.

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.