Enhanced Charge Balance for Efficient Electroluminescence from Cesium Copper Halides.

Cesium copper halides have the advantages of high photoluminescence quantum efficiency and good stability, making them attractive for replacing toxic lead halides in the field of perovskite light-emitting diodes (LEDs). However, due to their shallow conduction band and the lack of electron transport layers compatible with it, it remains a great challenge to achieve charge balance in LED devices. This drawback manifests as the accumulation of holes at the interface between the emitting layer and electron transport layer, resulting in nonradiative recombination. Here, we demonstrate an effective approach to address this issue by suppressing hole injection, which is realized through modification of the poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) layer with polyethylenimine. This leads to cesium-copper-halide LEDs with a high external quantum efficiency of 5.6%, representing an advance in device architecture for efficient electroluminescence from cesium copper halides.

Phloretin ameliorates heart function after myocardial infarction via NLRP3/Caspase-1/IL-1ß signaling.

OBJECTIVES/AIMS: Inflammation is crucial in structural and electrical remodeling after myocardial infarction (MI), affecting cardiac pump function and conduction pathways. Phloretin possesses an anti-inflammation role by inhibiting the NLRP3/Caspase-1/IL-1ß pathway. However, the effects of Phloretin on cardiac contractile and electrical conduction function after MI remained unclear. Therefore, we aimed to investigate the potential role of Phloretin in a rat model of MI. METHODS: Rats were assigned into four groups: Sham, Sham+Phloretin, MI and MI+Phloretin, with ad libitum food and water. In the MI and MI+Phloretin groups, the left anterior descending coronary artery was occluded for 4 weeks, while the Sham and Sham+Phloretin groups received sham operation. The Sham+Phloretin group and the MI+Phloretin group received oral administration of Phloretin. In vitro, H9c2 cells were subjected to hypoxic conditions to simulate an MI model, with Phloretin for 24 h. Cardiac electrophysiological properties were assessed following MI, including the effective refractory period (ERP), action potential duration (APD)90 and ventricular fibrillation (VF) incidence. Echocardiography evaluated left ventricular ejection fraction (LVEF), left ventricular fraction shortening (LVFS), left ventricular internal diameter at end-diastole (LVIDd), left ventricular internal diameter at end-systole (LVIDs), left ventricular end-systolic volume (LVESV) and left ventricular end-diastolic volume (LVEDV) to assess cardiac function. Serum type B natriuretic peptide (BNP) level was applied to evaluate the degree of Heart failure (HF). The fibrosis area and severity were assessed by Masson staining and protein expression levels of collagen 3, collagen 1, TGF-ß and α-SMA. Western blot analysis estimated the protein expression levels of NLRP3, Pro Caspase-1, Caspase-1, ASC, IL-18, IL-1ß, pp38, p38, and Connexin43(Cx43) to elucidate the influence of inflammation on electrical remodeling after MI. RESULTS: Our findings demonstrate that Phloretin inhibits the NLRP3/Caspase-1/IL-1ß pathway, leading to the upregulation of Cx43 by limiting p38 phosphorylation, which further decreases susceptibility to ventricular arrhythmias (VAs). Additionally, Phloretin attenuated fibrosis by inhibiting inflammation to prevent HF. In vitro experiments also provided strong evidence supporting the inhibitory effects of Phloretin on the NLRP3/Caspase-1/IL-1ß pathway. CONCLUSION: Our results suggest that Phloretin could suppress the NLRP3/Caspase-1/IL-1ß pathway to reverse structural and electrical remodeling after MI to prevent the occurrence of VAs and HF.

Regional differences of the sclera in the ocular hypertensive rat model induced by circumlimbal suture.

PURPOSE: To describe the regional differences of the sclera in ocular hypertension (OHT) models with the inappropriate extension of the ocular axis. METHODS: To discover the regional differences of the sclera at the early stage, OHT models were established using circumlimbal suture (CS) or sclerosant injection (SI). Axial length (AL) was measured by ultrasound and magnetic resonance imaging. The glaucoma-associated distinction was determined by intraocular pressure (IOP) and retrograde tracing of retinal ganglion cells (RGCs). The central thickness of the ganglion cell complex (GCC) was measured by optical coherence tomography. RGCs and collagen fibrils were detected using a transmission electron microscope, furthermore, anti-alpha smooth muscle actin (αSMA) was determined in the early stage after the operation. RESULTS: Compared with the control group, the eyes in OHT models showed an increased IOP (P < 0.001 in the CS group, P = 0.001 in the SI group), growing AL (P = 0.026 in the CS group, P = 0.043 in the SI group), reduction of central RGCs (P < 0.001 in the CS group, P = 0.017 in the SI group), thinning central GCC (P < 0.001 in the CS group), and a distinctive expression of αSMA in the central sclera in the early 4-week stage after the operation (P = 0.002 in the CS group). Compared with the SI group, the eye in the CS group showed a significantly increased AL (7.1 ± 0.4 mm, P = 0.031), reduction of central RGCs (2121.1 ± 87.2 cells/mm2, P = 0.001), thinning central GCC (71.4 ± 0.8 pixels, P = 0.015), and a distinctive expression of αSMA (P = 0.005). Additionally, ultrastructural changes in RGCs, scleral collagen fibers, and collagen crimp were observed in the different regions. Increased collagen volume fraction in the posterior segment of the eyeball wall (30.2 ± 3.1%, P = 0.022) was observed by MASSON staining in the CS group. CONCLUSION: Regional differences of the sclera in the ocular hypertensive rat model induced by CS may provide a reference for further treatment of scleral-related eye disorders.

Propionate alleviated post-infarction cardiac dysfunction by macrophage polarization in a rat model.

BACKGROUND: The propionate (C3), the important components of short-chain fatty acids (SCFAs), had the effect of inhibiting pro-inflammatory macrophages. Earlier macrophages phenotypic transition from pro-inflammatory M1 to reparative M2 in early stage was a central juncture of cardiac dysfunction mitigation after myocardial infarction (MI). METHODS: 160 Sprague-Dawley rats were assigned to 4 groups: sham group (n = 40), sham + C3 group (n = 40), MI group (n = 40) and MI + C3 group (n = 40). The rats in sham + C3 and MI + C3 group were treated with oral sodium propionate (200 mM), and equivalent concentration of sodium chloride was administered in sham and MI group as control. After 7 days of propionate adaptive feeding, rats were anesthetized and induced the MI by coronary occlusion. The classification of macrophages, the level of inflammatory factors and inflammatory signaling were estimated at 3rd days after thoracotomy, and the extent of myocardial fibrosis was evaluated at 7th and 28th days after operation. Echocardiography was estimated on 28th day after surgery. RAW264.7 cells, stimulated by LPS + IFN-γ with or without propionate, were harvested for western blot and supernatants were collected for cytokine analysis by ELISA. RESULTS: Propionate administration reduced the MI-induced myocardial fibrosis in infarcted border and attenuated cardiac function deterioration compared with MI group. In comparison with MI group, propionate promoted macrophages reduction, macrophage M2-like polarization, and inflammatory cytokines decrease in infarcted border zone following MI, which partly depends on the inhibition of JNK/P38/NFκB signaling pathways. CONCLUSIONS: Oral propionate in early stage, as a nutritional intervention, alleviated post-MI chronic cardiac remodeling and cardiac dysfunction at least in part by modulating macrophages polarization and pro-inflammatory cytokine, which were associated with reduction of JNK/P38/NFκB phosphorylation.

The short-chain fatty acid propionate improved ventricular electrical remodeling in a rat model with myocardial infarction.

The short-chain fatty acid (SCFA) propionate (C3), a microorganism metabolite produced by gut microbial fermentation, has parasympathetic-activation effects. The cardiac autonomic rebalancing strategy is considered as an important therapeutic approach to myocardial infarction (MI)-produced ventricular arrhythmias (VAs). Thus, our research was designed to clarify the potential functions of the SCFA propionate in VAs and cardiac electrophysiology in MI rats. A hundred adult Sprague-Dawley rats were allocated to four groups: the sham group (200 mM sodium chloride), the sham + C3 group (200 mM propionate), the MI group (200 mM sodium chloride) and the MI + C3 group (200 mM propionate). In comparison with the sham group, propionate significantly increased the parasympathetic components heart rate variability (HRV) and acetylcholine levels, prolonged cardiac repolarization, induced STAT3 phosphorylation and up-regulated the c-fos expression in nodose ganglia and solitary nucleus. Propionate intake reduced the susceptibility to VAs. MI induced by coronary ligation caused a significant increase in the sympathetic components HRV, abnormal repolarization, global repolarization dispersion, norepinephrine and inflammatory cytokines, reduction and redistribution of Connexin 43 in the infarcted border zone, and activation of NFκB, which were attenuated in the MI + C3 group. Oral propionate supplementation, as a nutritional intervention, protected the heart against MI-induced VAs and cardiac electrophysiology instability partly by parasympathetic activation based on the gut-brain axis.

Resiniferatoxin reduces cardiac sympathetic nerve activation to exert a cardioprotective effect during myocardial infarction.

BACKGROUND AND OBJECTIVE: Myocardial infarction (MI) is a common critical disease of the cardiovascular system. The process of MI is often accompanied by the excessive activation of cardiac sympathetic nerves, which leads to arrhythmia. Resiniferatoxin (RTX) is a transient receptor potential vanilloid 1 (TRPV1), involved in the cardiac sympathetic afferent reflex. However, whether RTX can reduce the occurrence of arrhythmia and exert a cardioprotective effect by inhibiting the sympathetic reflex during MI is still unknown. METHODS: The left anterior descending artery of cardiac was clamped to construct a model of MI. RTX (50 µg/ml) was used by epicardial application in MI rats. Ventricular electrophysiologic properties were continuously monitored by a body surface ECG. Yrosine hydroxylase (TH) and growth associated protein 43 (GAP43) were detected by Immunofluorescence staining. Connexin43 and transforming growth factor beta receptor 1 (TGF-ß1) were detected by western blot. Norepinephrine (NE) and BNP levels in blood and tissue were determined by ELISA. Cardiac function was assessed by echocardiography. RESULTS: The ERP, APD90, QRS, QT and the Tend-Tpeak intervals in MI rats were all prolonged, but decreased after RTX treatment (n = 3, P<0.05). In contrast, the RR interval was shortened in the MI group, but prolonged in the MI+RTX group (n = 3, P<0.05). RTX treatment significantly reduced ventricular arrhythmias after MI. TH- and GAP43-positive nerve densities and TGF-ß1, and cx-43 protein expression were up-regulated in the MI group compared to the sham group, and they were decreased in the MI+RTX group compared to the MI group (n = 3, P<0.05). RTX can decrease serum and tissue NE and BNP levels (n = 3, P<0.05). RTX pretreatment significantly decreased heart rate, HW/BW ratio and LVIDS, and increased LVEF andLVFS values (n = 3, P<0.05). CONCLUSION: RTX improved cardiac dysfunction, ventricular electrophysiologic properties, and sympathetic nerve remodeling in rats with MI by inhibiting the excessive cardiac sympathetic drive.

C-type natriuretic peptide suppresses ventricular arrhythmias in rats with acute myocardial ischemia.

This study aimed to investigate the effects of C-type natriuretic peptide (CNP) on ventricular arrhythmias in rats with acute myocardial ischemia (AMI). Forty male Sprague-Dawley rats were randomly divided into sham group (n = 10), AMI group (n = 15) and AMI + CNP group (n = 15). AMI model was induced by ligating the left anterior descending branch of the coronary artery, and CNP was pumped through the femoral vein starting 30 min before ischemia and continuing until 1 h after AMI. The occurrence of ventricular arrhythmias after ischemia and heart rate variability (HRV) were recorded and analyzed. The plasma norepinephrine level was detected at 15 min after AMI. Ventricular electrophysiological parameters including ventricular effective refractory period (ERP), ERP dispersion, ventricular action potential duration (APD) alternans and ventricular fibrillation threshold (VFT) were measured one hour after AMI. Then, the expressions of cyclic guanosine monophosphate in myocardial tissue and left stellate ganglion were examined. Compared to sham group, AMI significantly shortened the ERP, augmented ERP dispersion, elevated APD alternans cycle length, reduced VFT, and increased the incidence of ventricular arrhythmias. Moreover, AMI increased the sympathetic component of HRV, raised plasma norepinephrine levels, and decreased the cyclic guanosine monophosphate levels in myocardium and left stellate ganglion. All those changes were attenuated by CNP treatment. These findings suggest that CNP protected against ventricular arrhythmias in rats with AMI, potentially by inhibiting ischemia-induced cardiac sympathetic hyperactivity and cardiac electrophysiology instability.

Selective chemical ablation of transient receptor potential vanilloid 1 expressing neurons in the left stellate ganglion protects against ischemia-induced ventricular arrhythmias in dogs.

OBJECTIVES: Findings from prior investigations show that left stellate ganglion (LSG) inhibitory approaches protect the heart from ventricular arrhythmias (VAs) caused by acute myocardial infarction (AMI), which still remain many side effects. Targeted transient receptor potential vanilloid 1/tyrosine hydroxylase (TRPV-1/TH) expressing sympathetic neurons ablation is a novel neuro-ablative strategy. The aim of this investigation was to explore if targeted molecular neuro-ablative strategy by resiniferatoxin (RTX) stellate microinjection could protect against ischemia-induced VAs. METHODS: Twenty-four anesthetized beagles were assigned to a control group (n = 12) and RTX group (n = 12) in a random manner. Targeted molecular neuro-ablative was produced by RTX stellate microinjection and DMSO was microinjected into LSG in the same way as control. Plasma norepinephrine (NE) level, heart rate variability (HRV), Tpeak-Tend interval (Tp-Te), LSG neural activity and function, ventricular effective refractory period (ERP), beat-to-beat variability of repolarization (BVR) and ventricular action potential duration (APD) were measured at baseline and 60 min after RTX or DMSO microinjection. AMI model was established by the ligation of left anterior descending coronary artery and 60-minute electrocardiography was continuously recorded for VAs analysis. Subsequently, HRV, Tp-Te, plasma NE level from jugular vein and coronary sinus, LSG neural activity and function, ventricular ERP, ventricular APD, BVR, action potential duration alternans (APDA) cycle length and ventricular fibrillation threshold (VFT) were evaluated after AMI. Finally, tissue collection of LSG was performed for examining the TRPV-1, nerve growth factor (NGF) protein and c-fos protein. RESULTS: TRPV-1 was highly expressed in the TH-expressing neurons and RTX injection significantly ablated TRPV-1/TH-positive neurons in LSG. Compared with baseline, RTX stellate microinjection significantly reduced plasma NE level, the sympathetic component of HRV, LSG neural activity and LSG function, shortened Tp-Te, prolonged ventricular ERP and APD, but there were no remarkable differences existed for control group. AMI resulted in the significant raise in plasma NE level from jugular vein and coronary sinus, the sympathetic component of HRV, LSG neural activity and LSG function, the marked prolongation in Tp-Te and BVR, the significant decrease in ERP and APD from ischemia area, and the increase in APDA cycle length in the ischemic region of the control group, which were remarkably attenuated in the RTX group. RTX pretreatment markedly rose the VFT in the RTX group. Furthermore, the AMI-triggered VAs was significantly prevented by RTX injection in the RTX group. RTX microinjection down-regulated significantly TRPV-1, NGF and c-fos expression in the LSG compared with the control group. CONCLUSION: Targeted ablation of TRPV-1/TH positive sympathetic neurons induced by RTX stellate microinjection could suppress ischemia-induced cardiac autonomic imbalances and cardiac electrophysiology instability to protect against AMI-induced VAs.

Cardiac Sympathetic Afferent Denervation Protects Against Ventricular Arrhythmias by Modulating Cardiac Sympathetic Nerve Activity During Acute Myocardial Infarction.

BACKGROUND Augmented cardiac sympathetic afferent reflex (CSAR) plays a role in enhanced sympathetic activity. Given that a strategy for abolishing augmented CSAR-induced sympathetic activation may be beneficial for protecting against ventricular arrhythmias (VAs) triggered by acute myocardial infarction (AMI), we investigated whether cardiac sympathetic afferent denervation (CSAD) could protect against VAs by modulating cardiac sympathetic nerve activity in an AMI dog model. MATERIAL AND METHODS Twenty-two anesthetized dogs were assigned to the CSAD group (n=9) and the sham group (n=13) randomly. CSAD was produced by epicardial application of resiniferatoxin. Heart rate variability (HRV), ventricular action potential duration (APD), APD dispersion, beat-to-beat variability of repolarization (BVR), effective refractory period (ERP) of ventricles, ERP dispersion, plasma norepinephrine (NE) concentration, and left stellate ganglion (LSG) neural activity were determined at baseline and after CSAD. We designed an AMI model by occluding the left anterior coronary artery, and performed analysis of VAs for 60 minutes using electrocardiography. Then, levels of c-fos and nerve growth factor (NGF) were determined. RESULTS Relative to baseline values, CSAD prolonged ERP and APD of ventricles, increased HRV, decreased APD dispersion, BVR, ERP dispersion and serum NE concentration, and attenuated LSG activity in the CSAD group. AMI triggered a remarkable increase in LSG activity and function but decreased the HRV of the sham group animals relative to the CSAD group. Moreover, the CSAD group had higher levels of VAs relative to the sham group. This was accompanied by a corresponding decrease in proteins quantities of NGF and c-fos in the CSAD group in the LSG after AMI compared to the sham group. CONCLUSIONS CSAD can suppress LSG neural activity, hence enhance the electrophysiological stability and protect the heart from AMI-triggered VAs.

Suppression of GABAergic neurons through D2-like receptor secures efficient conditioning in Drosophila aversive olfactory learning.

The GABAergic system serves as a vital negative modulator in cognitive functions, such as learning and memory, while the mechanisms governing this inhibitory system remain to be elucidated. In Drosophila, the GABAergic anterior paired lateral (APL) neurons mediate a negative feedback essential for odor discrimination; however, their activity is suppressed by learning via unknown mechanisms. In aversive olfactory learning, a group of dopaminergic (DA) neurons is activated on electric shock (ES) and modulates the Kenyon cells (KCs) in the mushroom body, the center of olfactory learning. Here we find that the same group of DA neurons also form functional synaptic connections with the APL neurons, thereby emitting a suppressive signal to the latter through Drosophila dopamine 2-like receptor (DD2R). Knockdown of either DD2R or its downstream molecules in the APL neurons results in impaired olfactory learning at the behavioral level. Results obtained from in vivo functional imaging experiments indicate that this DD2R-dependent DA-to-APL suppression occurs during odor-ES conditioning and discharges the GABAergic inhibition on the KCs specific to the conditioned odor. Moreover, the decrease in odor response of the APL neurons persists to the postconditioning phase, and this change is also absent in DD2R knockdown flies. Taken together, our findings show that DA-to-GABA suppression is essential for restraining the GABAergic inhibition during conditioning, as well as for inducing synaptic modification in this learning circuit. Such circuit mechanisms may play conserved roles in associative learning across species.

Targeted ablation of cardiac sympathetic neurons attenuates adverse postinfarction remodelling and left ventricular dysfunction.

NEW FINDINGS: What is the central question of this study? Can targeted ablation of cardiac sympathetic neurons suppress myocardial infarction-induced adverse cardiac remodelling and left ventricular dysfunction? What is the main finding and its importance? Targeted ablation of cardiac sympathetic neurons significantly alleviated sympathetic remodelling and neuroendocrine activation, attenuated cardiac hypertrophy and fibrosis and improved left ventricular function. Thus, targeted ablation of cardiac sympathetic neurons might have a beneficial effect on adverse postinfarction remodelling and left ventricular dysfunction. ABSTRACT: Sympathetic overactivation is crucial in the development and progression of adverse cardiac remodelling and dysfunction. Targeted ablation of cardiac sympathetic neurons (TACSN) is an effective approach to inhibit overactivation of the sympathetic nervous system. The aim of this study was to investigate whether TACSN could suppress myocardial infarction (MI)-induced adverse cardiac remodelling and dysfunction, thereby producing protective effects. Thirty-eight dogs were randomly assigned into the sham-operated, MI or MI-TACSN group. The TACSN was induced by injecting cholera toxin B subunit-saporin compound into the stellate ganglia 1 week after MI. Five weeks after MI surgery, echocardiographic and haemodynamic parameters of cardiac function were significantly improved in the TACSN group compared with the MI group. In addition, TACSN attenuated the extent of cardiac hypertrophy and fibrosis and suppressed the increase in the plasma concentrations of noradrenaline, nerve growth factor, atrial natriuretic peptide, brain natriuretic peptide, angiotensin II and aldosterone. Furthermore, TACSN alleviated the growth associated protein-43-positive and tyrosine hydroxylase-positive nerve densities in the infarcted border zone and restored protein expression of the ß1 -adrenergic receptor in the left ventricular myocardium. These findings indicate that TACSN might have a beneficial effect on adverse postinfarction remodelling and left ventricular dysfunction, which might be attributable, at least in part, to the attenuation of both sympathetic remodelling and the cardiac neuroendocrine system.

Targeted ablation of cardiac sympathetic neurons improves ventricular electrical remodelling in a canine model of chronic myocardial infarction.

Aims: The purpose of this study was to evaluate the cardiac electrophysiologic effects of targeted ablation of cardiac sympathetic neurons (TACSN) in a canine model of chronic myocardial infarction (MI). Methods and results: Thirty-eight anaesthetized dogs were randomly assigned into the sham-operated, MI, and MI-TACSN groups, respectively. Myocardial infarction-targeted ablation of cardiac sympathetic neuron was induced by injecting cholera toxin B subunit-saporin compound in the left stellate ganglion (LSG). Five weeks after surgery, the cardiac function, heart rate variability (HRV), ventricular electrophysiological parameters, LSG function and neural activity, serum norepinephrine (NE), nerve growth factor (NGF), and brain natriuretic peptide (BNP) levels were measured. Cardiac sympathetic innervation was determined with immunofluorescence staining of growth associated protein-43 (GAP43) and tyrosine hydroxylase (TH). Compared with MI group, TACSN significantly improved HRV, attenuated LSG function and activity, prolonged corrected QT interval, decreased Tpeak-Tend interval, prolonged ventricular effective refractory period (ERP), and action potential duration (APD), decreased the slopes of APD restitution curves, suppressed the APD alternans, increased ventricular fibrillation threshold, and reduced serum NE, NGF, and BNP levels. Moreover, the densities of GAP43 and TH-positive nerve fibres in the infarcted border zone in the MI-TACSN group were lower than those in the MI group. Conclusion: Targeted ablation of cardiac sympathetic neuron attenuates sympathetic remodelling and improves ventricular electrical remodelling in the chronic phase of MI. These data suggest that TACSN may be a novel approach to treating ventricular arrhythmias.

Go signaling in mushroom bodies regulates sleep in Drosophila.

STUDY OBJECTIVES: Sleep is a fundamental physiological process and its biological mechanisms are poorly understood. In Drosophila melanogaster, heterotrimeric Go protein is abundantly expressed in the brain. However, its post-developmental function has not been extensively explored. DESIGN: Locomotor activity was measured using the Drosophila Activity Monitoring System under a 12:12 LD cycle. Sleep was defined as periods of 5 min with no recorded activity. RESULTS: Pan-neuronal elevation of Go signaling induced quiescence accompanied by an increased arousal threshold in flies. By screening region-specific GAL4 lines, we mapped the sleep-regulatory function of Go signaling to mushroom bodies (MBs), a central brain region which modulates memory, decision making, and sleep in Drosophila. Up-regulation of Go activity in these neurons consolidated sleep while inhibition of endogenous Go via expression of Go RNAi or pertussis toxin reduced and fragmented sleep, indicating that the Drosophila sleep requirement is affected by levels of Go activity in the MBs. Genetic interaction results showed that Go signaling serves as a neuronal transmission inhibitor in a cAMP-independent pathway. CONCLUSION: Go signaling is a novel signaling pathway in MBs that regulates sleep in Drosophila.