N-type Cells Research Articles

N-type and P-type series integrated hydrogel thermoelectric cells for low-grade heat harvesting

Low-grade heat is abundant and ubiquitous, but it is generally discarded due to the lack of cost-effective recovery technologies. Ion thermoelectric cells are an affordable and straightforward approach of converting low-grade heat into usable electricity for sustainable power. Despite their potential, ion thermoelectric cells face challenges such as limited Seebeck coefficient and required series integration. Here, we demonstrate that the N-type and P-type conversion of ion thermoelectric cells can be achieved through the phase transition of temperature-sensitive hydrogel containing the triiodide/iodide redox couple. Through the strong interaction between the hydrophobic region of the hydrogel and triiodide, the hydrophobic side selectively captures triiodide and the hydrophilic side repels triiodide, raising the concentration difference of triiodide and thereby increasing the Seebeck coefficient. Specifically, the Seebeck coefficient of the N-type ion thermoelectric cells is 7.7 mV K−1, and the Seebeck coefficient of P-type ion thermoelectric cells is −6.3 mV K−1 (ΔT = 15 K). By connecting 10 pairs of the N-type and P-type ion thermoelectric cells, we achieve a voltage of 1.8 V and an output power of 85 μW, surpassing the reported triiodide/iodide-based ion thermoelectric cells. Our work proposes a phase transition strategy for the N-P conversion of ion thermoelectric cells, and highlights the prospect of series integrated hydrogel ion thermoelectric cells for low-grade heat harvesting.

Development of Semi-Empirical and Machine Learning Models for Photoelectrochemical Cells

We introduce a theoretical model for the photocurrent-voltage (I-V) characteristics designed to elucidate the interfacial phenomena in photoelectrochemical cells (PECs). This model investigates the sources of voltage losses and the distribution of photocurrent across the semiconductor–electrolyte interface (SEI). It calculates the whole exchange current parameter to derive cell polarization data at the SEI and visualizes the potential drop across n-type cells. The I-V model’s simulation outcomes are utilized to distinguish between the impacts of bulk recombination and space charge region (SCR) recombination within semiconductor cells. Furthermore, we develop an advanced deep neural network model to analyze the electron–hole transfer dynamics using the I-V characteristic curve. The model’s robustness is evaluated and validated with real-time experimental data, demonstrating a high degree of concordance with observed results.

Calmodulin kinase II inhibition suppresses atrioventricular conduction by regulating intracellular Ca2+ homeostasis

BackgroundCa2+/calmodulin-dependent protein kinase II (CaMKII) inhibition decelerates atrioventricular node (AVN) conduction, providing a potential treatment of tachycardia. However, the effectiveness of CaMKII inhibition on tachycardia and its underlying mechanism remains unclear. ObjectiveWe aimed to assess the effectiveness of CaMKII inhibition in reducing ventricular rates during atrial fibrillation and to elucidate the underlying mechanism in affecting AVN electrophysiology. MethodsCardiac CaMKII inhibition (AC3-I) mice were used. Transesophageal atrial pacing was performed to evaluate AVN conduction function and to induce atrial fibrillation. Patch-clamp techniques were employed to record action potentials and ionic currents in AVN cells. Intracellular Ca2+ transients and sarcomere length measurements were obtained with the IonOptix system. Masson trichrome stain was used to evaluate fibrosis in the AVN region. Western blotting and immunofluorescence techniques were employed to detect connexin expression and localization. ResultsCaMKII inhibition decreased the ventricular rate during atrial fibrillation and isoproterenol-induced tachycardia. Esophageal electrocardiogram results from AC3-I mice showed longer AVN conduction than in wild-type mice. AN- and N-type AVN cells from AC3-I mice exhibited slower action potential frequencies and diastolic depolarization rates than those of wild-type mice. The study revealed that CaMKII inhibition reduced AVN cell sarcoplasmic reticulum (SR) Ca2+ content, Ca2+ release rate from the SR during diastole, Ca2+ transient amplitude, and SR Ca2+ uptake rate. In addition, CaMKII inhibition prolonged the sarcomere diastole duration and enhanced the sensitivity of sarcomeres to Ca2+. ConclusionCaMKII inhibition effectively decreases the ventricular rate during atrial fibrillation and tachycardia by slowing down AVN conduction through suppressing Ca2+ overload in AVN cells.

Influence of boron doping profile on emitter and metal contact recombination for n-PERT silicon solar cells

Increasing interest in n-type silicon (Si) solar cells due to the high-quality material properties of the n-Si wafers, their relatively low sensitivity to donor-like impurities like iron and their resistance to light-induced degradation brings more recent attention to the studies on the p+ emitter and its metal contact. In this work, we investigate the effect of the Boron doping profile on the quality of p+ emitter and their contacts with screen-printed Ag/Al metal fingers. The emitters within the scope of this study are created with BBr3 diffusion in an atmospheric diffusion furnace on n-type Si wafers and also applied to n-PERT Si cells to analyze their effects on device performance. Our results highlight the significance of the doping profile for solar cell performance, as it considerably affects the contact resistivity at the emitter-metal interface and the saturation current densities for emitter (J0, emitter) and Ag/Al metal contacts (J0, AgAl). Reducing the Boron concentration within the emitter leads to a decrease in carrier recombination in the non-contacted region of the emitter, which in turn decreases J0, emitter. However, this reduction increases the recombination in the contacted areas of the emitter, consequently elevating the J0, AgAl, and increasing the contact resistance values. Besides, the power loss analysis and simulation results based on experimental values obtained for our best solar cells group show how much J0, emitter and J0, AgAl values contribute to and would improve solar cell efficiency. The manuscript presents a case study of experimental emitter doping profile optimization applicable to similar n-type PERT or TOPCon cells with varying design parameters.

Abstract LB015: Differential expression of deubiquitinating enzymes and its related DNA damage response genes in neuroblastoma heterogeneity

Abstract SK-N-AS and SK-N-DZ are two cell lines of pediatric solid tumors neuroblastomas well characterized to evaluate heterogeneity between different neuroblastomas and are presumed as models for differences between different neuroblastoma. Using this model system, we recently evaluated if radiation could improve efficacy of radiation therapy and to follow these studies later with animal models to determine decrease of tumor burden. Differences between the N-type and S-type neuroblastoma cell lines SK-N-DZ and SK-N-AS, respectively were observed to be high and their responses to radiation stress were equally heterogeneous. Ubiquitin signaling plays a key role during the DNA damage response in protein recruitment and protein interactions. Deubiquitinating enzymes (DUBs) deconjugate ubiquitin from ubiquitylated substrate proteins to control their activity and stability and are shown to regulate various biological processes. DUBs may play a role in regulating the radiosensitivity of cancer cells by modulating DNA damage response and repair pathways. Determination of specific DUBs that are involved in regulating radiosensitivity in cancer cells will provide opportunity for drug targeting and visa-vis enhance the efficacy of radiation therapy in neuroblastoma cancer treatment. Here, using bioinformatic tools, the differentially regulated DUBs were identified. The relationship between DEGs-DUBs with the genes involved in various DNA repair pathways (NHEJ, HR and Fanconi anemia pathway; KEGG pathway database) are described. We identified 32 DEGs (14 upregulated and 18 downregulated) with these neuroblastoma cell lines. USP22 and USP41 DUBs and its differential expression in these cell lines denotes the importance of such analysis. Especially considering USP22 a potentially biomarker for predicting the outcome of patients with neuroblastoma. These DEG-DUBs were likewise correlated with 91 DNA damage response (DDR) genes belonging to three different pathways (NHEJ, HR and Fanconi anemia pathway). Out of which 44 of the DDR genes showed significant correlation with DEG-DUBs. Further studies are needed to determine the mechanisms underlying the complex relationship of these DUBs and to determine the critical DUBs for drug targeting and to enhance the efficacy of radiation therapy in cancer treatment. Citation Format: Vaibhav Vaibhav, Fahika Nazeerulla, Tatjana Paunesku, Ekta Tripathi, Gayle Woloschak, Prashanthi Karyala, Rao V. Papineni. Differential expression of deubiquitinating enzymes and its related DNA damage response genes in neuroblastoma heterogeneity [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr LB015.

Performance degradation and reliability technology of high-efficiency N-type TOPCon photovoltaic cells and their encapsulated components based on TRIZ innovative model

Performance degradation and reliability technology of high-efficiency N-type TOPCon photovoltaic cells and their encapsulated components based on TRIZ innovative model

Continuous electricity generation from diurnal and seasonal air temperature variation

Limited research has been conducted on green and effective approaches for harnessing thermal energy from diurnal and seasonal air temperature variation. Thermally regenerative electrochemical cycle, with high low-grade heat-to-electricity conversion efficiency, is desirable for generating electricity through periodical temperature variation because of its separate charging and discharging processes. However, the cell merely discharges at a limited period with intermittent power output. Herein, a novel continuous power output system, combining p-type and n-type cells, is proposed and investigated to harness heat from periodical temperature variation and convert it into electricity. In this instance, electricity generation relies solely on the energy derived from air without solar radiation or outer space cooling. Based on operating principles and experiment results, the system concept, operating processes, and mathematic models are well developed. The p-type and n-type cell characteristics, diurnal performance, and seasonal performance are investigated and analysed. The results suggest that the average power density is 0.15 W/kg and 0.69 W/kg in the diurnal and seasonal periodic conditions, respectively, in Urumqi city. This indicates the proposed idea is an effective technology for obtaining electricity continuously from air temperature variation.

Realizing a high-performance n-type thermogalvanic cell by tailoring the thermodynamic equilibrium

Judiciously designed anionic polymer (AP) tunes the thermodynamic equilibrium between hydroquinone and benzoquinone via self-regulating pH and selective transport of mobile species in the AP, leading to high-performance n-type thermogalvanic cells.

Enhancement of efficiency in monocrystalline silicon solar cells

As the representative of the first generation of solar cells, crystalline silicon solar cells still dominate the photovoltaic market, including monocrystalline and polycrystalline silicon cells. With the development of silicon materials and cut-silicon wafer technologies, monocrystalline products have become more cost-effective, accelerating the replacement of polycrystalline products. In addition, the conversion efficiency of monocrystalline products increases gradually through high-efficiency cell technologies such as Passivated Emitter and Rear Cell (PERC). This paper will start with the solar cell efficiency and combine cost factor, the P-type PERC cell and additional four types of high-efficiency N-type cell technologies to improve the conversion efficiency for exploration, and will analyze and predict the future solar cell industrialization technologies. The study finally concludes that the N-type Tunnel Oxide Passivated Contact solar cell technology has a large industrial potential and could become a mainstream technology after the perc cell technology. At the same time, Interdigitated back contact cell structure and selective all-passive contact technologies are reliable paths to obtain solar cells with high conversion efficiency, integrated cost, and efficiency, depending on the advantages and compatibility of various cells. It can create conditions for the industrialization of low- cost and high-efficiency monocrystalline silicon solar cells.

An N-Type Pseudo-Static eDRAM Macro with Reduced Access Time for High-Speed Processing-in-Memory in Intelligent Sensor Hub Applications

This paper introduces an n-type pseudo-static gain cell (PS-nGC) embedded within dynamic random-access memory (eDRAM) for high-speed processing-in-memory (PIM) applications. The PS-nGC leverages a two-transistor (2T) gain cell and employs an n-type pseudo-static leakage compensation (n-type PSLC) circuit to significantly extend the eDRAM’s retention time. The implementation of a homogeneous NMOS-based 2T gain cell not only reduces write access times but also benefits from a boosted write wordline technique. In a comparison with the previous pseudo-static gain cell design, the proposed PS-nGC exhibits improvements in write and read access times, achieving 3.27 times and 1.81 times reductions in write access time and read access time, respectively. Furthermore, the PS-nGC demonstrates versatility by accommodating a wide supply voltage range, spanning from 0.7 to 1.2 V, while maintaining an operating frequency of 667 MHz. Fabricated using a 28 nm complementary metal oxide semiconductor (CMOS) process, the prototype features an efficient active area, occupying a mere 0.284 µm2 per bitcell for the 4 kb eDRAM macro. Under various operational conditions, including different processes, voltages, and temperatures, the proposed PS-nGC of eDRAM consistently provides speedy and reliable read and write operations.

Improvement of solder interconnections applied on back contact solar cells with low-temperature copper paste busbars

This work addresses the solderability and the reliability of n-type IBC ZEBRA cells with screen printed copper paste busbars. Improvement of the solderability by Sn60Pb40 solder alloy coated PV ribbon using an industrial automated IR stringer is reported. For qualification of the module reliability, climate chamber thermal cycling (TC) and damp heat tests (DH) were performed on mini modules with variations in material combinations: low temperature silver and copper pastes, each of them demanding dedicated soldering process parameters and two different encapsulation materials: polyolefin elastomers (POE) and ethylene vinyl acetate (EVA). All tested modules passed 3 x IEC TC and 2 x IEC DH, while the modules with EVA encapsulant passed DH 3000 as well. The copper paste metallized modules with EVA encapsulant showed no degradation in pseudo fill factor (pFF) and open circuit voltage (VOC), proving the statement that no copper diffuses into the silicon bulk.

Corrosion effects in bifacial crystalline silicon PV modules; interactions between metallization and encapsulation

This study addresses the influence of different encapsulation materials on performance losses in bifacial PV modules after extended damp heat testing. The widely used ethylene vinyl acetate (EVA) is compared to polyolefin elastomers (POE) and thermoplastic polyolefins (TPO). We show that modules based on n-type bifacial solar cells (tunnel oxide passivated contact, TOPCON) are more prone to degradation than p-type (Passivated emitter rear cell, PERC) based laminates. More specifically, the front side metallization of these n-type cells corrodes under extended damp heat testing, yielding a decreased fill factor in the I–V characteristics and the appearance of dark spots and dark areas in electroluminescence imaging. The newer generation of encapsulant materials (POE and TPO), slowly replacing EVA in the modules commercialized today, demonstrate an improved protection of the metallization. Apart from the nature of the encapsulant, the cell type and the presence or absence of glass cover plates are also shown to influence the metal grid corrosion. To better understand the mechanisms at play, post-mortem analysis was carried out on small sized degraded PV laminates, by drilling out circular samples (“coring”) that could be analyzed in depth. The analyses revealed a weakened bond between the metallization and the silicon emitter, ultimately causing metal grid delamination. The proposed mechanism behind this delamination starts with the degradation of lead glass, which is part of the cell metallization grid and contains lead oxide (PbO). This compound is susceptible to dissolution in acidic environment.

Multiple low-dose radiation-induced neuronal cysteine transporter expression and oxidative stress are rescued by N-acetylcysteine in neuronal SH-SY5Y cells

Recently, several studies have demonstrated that low-dose radiation (LDR) therapy has positively impacts on the treatment of Alzheimer’s disease (AD). LDR suppresses the production of pro-neuroinflammation molecules and improves cognitive function in AD. However, it is unclear whether direct exposure to LDR causes beneficial effects and what mechanism is involved in neuronal cells. In this study, we first determined the effect of high-dose radiation (HDR) alone on C6 cells and SH-SY5Y cells. We found that SH-SY5Y cells were more vulnerable than C6 cells to HDR. Moreover, in neuronal SH-SY5Y cells exposed to single or multiple LDR, N-type cells showed decreased cell viability with increasing radiation exposure time and frequency, but S-type cells were unaffected. Multiple LDR increased proapoptotic molecules such as p53, Bax and cleaved caspase-3, and decreased anti-apoptotic molecule (Bcl2). Multiple LDR also generated free radicals in neuronal SH-SY5Y cells. We detected a change in the expression of the neuronal cysteine transporter EAAC1. Pretreatment with N-acetylcysteine (NAC) rescued the increased in EAAC1 expression and the generation of ROS in neuronal SH-SY5Y cells after multiple LDR. Furthermore, we verified whether the increased in EAAC1 expression induces cell defense or cell death promotion signaling. We showed that transient overexpression of EAAC1 reduced the multiple LDR-induced p53 overexpression in neuronal SH-SY5Y cells. Our results indicate that neuronal cells can be injured by increased production of ROS not only by HDR but also by multiple LDR, which suggests that combination treatment with anti-free radical agents such as NAC may be useful in multiple LDR therapy.

Polarization-Type Potential-Induced Degradation in Front-Emitter p-Type and n-Type Crystalline Silicon Solar Cells.

For SiO2 layers underneath the SiNx antireflection/passivation layers of front-emitter p-type c-Si solar cells, this paper presents an investigation into their effects on polarization-type potential-induced degradation (PID), in addition to a comparison of polarization-type PID behavior in front-emitter p-type c-Si cells and front-emitter n-type c-Si cells. After PID tests with a bias of +1000 V, p-type c-Si cells without SiO2 layers underneath the SiNx layers showed no degradation, although p-type c-Si cells with approx. 10 nm thick SiO2 layers showed polarization-type PID, which is characterized by a reduction of the short-circuit current density and the open-circuit voltage. This result implies that highly insulating layers such as SiO2 layers play an important role in the occurrence of polarization-type PID. Comparison of polarization-type PID in p-type and n-type c-Si cells with SiO2 layers indicated that degradation in the n-type cells is greater and saturates in a shorter time than in the p-type cells. This result is consistent with an earlier proposed model based on the assumption that polarization-type PID is caused by charge accumulation at K centers in SiNx layers. The findings described herein are crucially important for elucidating polarization-type PID and verifying the degradation model.

Tunnel Oxide Deposition Techniques and Their Parametric Influence on Nano-Scaled SiOx Layer of TOPCon Solar Cell: A Review

In addition to the different technologies of silicon solar cells in crystalline form, TOPCon solar cells have an exceptionally great efficiency of 26%, accomplished by the manufacturing scale technique for industrialization, and have inordinate cell values of 732.3 mV open-circuit voltage (Voc) and a fill factor (FF) of 84.3%. The thickness of tunnel oxide, which is less than 2 nm in the TOPCon cell, primarily affects the electrical properties and efficiency of the cell. In this review, various techniques of deposition were utilized for the layer of SiOx tunnel oxide, such as thermal oxidation, ozone oxidation, chemical oxidation, and plasma-enhanced chemical vapor deposition (PECVD). To monitor the morphology of the surface, configuration of annealing, and rate of acceleration, a tunnel junction structure of oxide through a passivation quality of better Voc on a wafer of n-type cell might be accomplished. The passivation condition of experiments exposed to rapid thermal processing (RTP) annealing at temperatures more than 900 °C dropped precipitously. A silicon solar cell with TOPCon technology has a front emitter with boron diffusion, a tunnel-SiOx/n+-poly-Si/ SiNx:H configuration on the back surface, and electrodes on both sides with screen printing technology. The saturation current density (J0) for such a configuration on a refined face remains at 1.4 fA/cm2 and is 3.8 fA/cm2 when textured surfaces of the cell are considered, instead of printing with silver contacts. Following the printing of contacts with Ag, the J0 of the current configuration improves to 50.8 fA/cm2 on textured surface of silicon, which is moderately lesser for the metal contact. Tunnel oxide layers were deposited using many methods such as chemical, ozone, thermal, and PECVD oxidation are often utilized to deposit the thin SiOx layer in TOPCon solar cells. The benefits and downsides of each approach for developing a SiOx thin layer depend on the experiment. Thin SiOx layers may be produced using HNO3:H2SO4 at 60 °C. Environmentally safe ozone oxidation may create thermally stable SiOx layers. Thermal oxidation may build a tunnel oxide layer with low surface recombination velocity (10 cm/s). PECVD oxidation can develop SiOx on several substrates at once, making it cost-effective.

Novel porous thermosensitive gel electrolytes for wearable thermo-electrochemical cells

Thermo-electrochemical cells (TECs) represent an efficient and low-cost heat-harvesting device that can directly convert human body heat energy into electricity. However, the flexible, solid-state gelled electrolytes used in wearable thermocell devices suffer from poor mass transport of electrolyte. Here, a novel porous gel is developed via sodium acetate (NaAc) templates and freeze-drying treatment that is applied in p-type gelled electrolyte: poly-acrylamide (PAM) - K3/4[Fe(CN)6] and integrated into platinum (Pt) electrodes for wearable devices. Moreover, the guanidinium ([Gdm]+) is initially introduced into gelled electrolytes, and the p-type cell effectively boosts the maximum power density from 4.01 to 7.68 mW m−2 at ΔT = 10 °C, and exhibits a quick thermosensitive response under a broad temperature range (15 – 55 °C), which is sufficient for working conditions of wearable devices. The optimised porous gel host was also utilized in series with an n-type: PAM-FeCl2/3-HCl gelled electrolyte. The multiple thermocells (12 pairs) were further fabricated into a device by alternating p- and n-type cells in series. This device was found to output nearly 0.23 V at ΔT = 10 °C, and was manufactured into a flexible wearable device that was demonstrated to successfully harvest human body heat by both charging a supercapacitor (100 mF), and illuminating an LED, demonstrating the potential of actual application of our n-p-type in series devices.

EFFECT OF M2 MACROPHAGE-DERIVED SOLUBLE FACTORS ON DIFFERENTIATION OF SH-SY5Y CELLS

Macrophages play a key role in triggering and regulation of neuroregeneration. The characteristic feature of macrophages is pronounced plasticity, which manifests itself in the ability of macrophages to change their functional phenotype depending on the micromilieu. Apoptotic cell clearance (efferocytosis) is an important inducer of a macrophage polarization to M2 phenotype under pathological settings. Previously, we have developed an original protocol for the generation of M2-like macrophages, polarized by efferocytosis under serum-deprived conditions (M2 (LS), Low Serum). The present study was aimed to assess a neuroregenerative potential of M2 (LS) macrophages. We studied their effect on the differentiation of SH-SY5Y cells in comparison with retinoic acid (RA). As the morphological criteria of differentiation we have assessed the relative content of differentiated cells, i.e., cells with a neurite length exceeding the cell body length, and the average neurite length on days 3, 7, and 13. The ratio of neuron-like (N-type) and epithelial-like (S-type) cells in cultures was also assessed. SH-SY5Y cells were characterized by a low level of spontaneous differentiation, both under standard conditions (10% FBS) and serum deprivation (1% FBS). Upon RA treatment, SH-SY5Y cells stopped proliferating and underwent neuronal differentiation. Cultivation of SH-SY5Y cells in the presence of M2 (LS) conditioned medium also led to a significant increase in the relative content of differentiated cells, the average length of neurite-like processes, as well as a change in the balance of S- and N-type cells towards a pronounced predominance of the latter. The morphological features of differentiation were significantly less pronounced at early stage (day 3) of differentiation as compared with the RA-induced changes and reached the level of positive control only at later stages (day 13) (p < 0.05). In contrast to retinoic acid, M2 (LS) conditioned medium induced neuronal differentiation of SH-SY5Y cells without suppressing their proliferative activity. The data obtained may indicate a high neuroregenerative potential of M2 macrophages in vitro, which is realized through soluble factors and manifests itself in promoting SH-SY5Y differentiation.

Illumination Dependence of Reverse Leakage Current in Silicon Solar Cells

In the modeling of PV modules under shading and low illumination, a complete description of reverse bias behavior at the cell level is critical to understanding module response. This is particularly important when dealing with high voltage configurations such as tandem and shingled modules. Current simulation studies often do not account for the effects of incident light when dealing with operating voltages approaching cell breakdown. In this article, we investigate the illumination dependence of leakage current at the onset of breakdown in crystalline silicon solar cells. A study of the most popular cell technologies in the market today reveals a light induced effect under reverse bias that is prominent for p-type and small for n-type cells. Additionally, this effect is found to be larger in mono c-Si than multi c-Si cells. Because this phenomenon is not captured in current breakdown models such as Bishop's equation, we propose a split-cell model to describe partial shading in p-type cells. The outlined approach divides the cell into two parallel regions and is advantageous for its procedural simplicity as well as its ability to generalize effects from complex shading profiles.

Tumour‐derived substrate‐adherent cells promote neuroblastoma survival through secreted trophic factors

Neuroblastoma (NB) is the most common extracranial solid tumour in children. NB is highly heterogeneous and is comprised of a mixture of neuroblastic cancer cells and stromal cells. We previously reported that N‐type cells (neuroblastic cells) and S‐type cells (substrate‐adherent cells) in the SK‐N‐SH cell line shared almost identical genetic backgrounds. Sublines of N‐ and S‐type cells were isolated from an early passage (P35) of SK‐N‐SH. Sequencing analysis revealed that all sublines harboured the anaplastic lymphoma kinase (ALK) F1174L mutation, indicating that they were tumour derived. Surprisingly, over 74% resembled S‐type cells. In coculture experiments, S‐type cells protected N‐type cells from apoptosis induced by the oncogenic ALK inhibitor TAE684. Western blotting analyses showed that ALK, protein kinase A (AKT) and STAT3 signalling were stimulated in the cocultures. Furthermore, the conditioned medium from S‐type cells activated these downstream signalling molecules in the N‐type cells. The activation of STAT3 in the N‐type cells was ALK‐independent, while AKT was regulated by the ALK activation status. To identify the responsible soluble factors, we used a combination of transcriptomic and proteomic analysis and found that plasminogen activator inhibitor 1, secreted protein acidic and cysteine rich, periostin and galectin‐1 were potential mediators of STAT3 signalling. The addition of recombinant proteins to the tumour cells treated with the ALK inhibitor partially enhanced cell viability. Overall, the tumour‐derived S‐type cells prevented apoptosis in the N‐type cells via ALK‐independent STAT3 activation triggered by secreted factors. The inhibition of these factors in combination with ALK inhibition could provide a new direction for targeted therapies to treat high‐risk NB.

Hydrogen peroxide accelerates ventricular arrhythmogenesis by inactivating N‐type calcium channels in cardiac vagal postganglionic neurons in type 2 diabetic rats

Withdrawal of cardiac vagal activity is a common complication in patients with type 2 diabetes mellitus (T2DM), and is associated with arrhythmia-related sudden cardiac death and high mortality in T2DM patients. Although our recent study has demonstrated that reduction of N-type calcium (Cav2.2) currents and cell excitability of cardiac vagal postganglionic (CVP) neurons exacerbates myocardial infarction-evoked ventricular arrhythmias and mortality in T2DM rats, the mechanisms responsible for T2DM-reduced Cav2.2 channel activity in CVP neurons remain unclear. Since reactive oxygen species (ROS) has been reported to modulate calcium channel activity in peripheral postganglionic neurons, here we tested if hydrogen peroxide (H2O2, a type of ROS) overproduction inactivates Cav2.2 channels and further contributes to ventricular vagal dysfunction and ventricular arrhythmogenesis in T2DM. Rat T2DM was induced by a high-fat diet plus streptozotocin injection. Adenoviral catalase gene (Ad.CAT, 2 µl, 1 x 1010 pfu/ml) was microinjected into CVP neurons to scavenge local H2O2 production. Reduced catalase expression accompanied by overproduction of H2O2 was detected in the CVP neurons in T2DM rats. In vivo transfection of Ad.CAT not only increased protein expression of catalase but also attenuated H2O2 production in CVP neurons in T2DM rats. Data from reverse-phase protein array also demonstrated that overexpression of catalase by transfection of Ad.CAT into CVP neurons markedly increased T2DM-reduced protein expression of Cav2.2 in CVP neurons. Local microinjection of Ad.CAT into CVP neurons also significantly restored T2DM-blunted ventricular vagal activity, as demonstrated by an improvement in the response of left ventricular systolic pressure to left vagal efferent nerve stimulation. Additionally, in the power spectral analysis of heart rate variability (HRV), transfection of Ad.CAT into CVP neurons increased the T2DM-attenuated high frequency power (an index of vagal activity), leading to further restoration of the low frequency to high frequency ratio. Moreover, the inducibility of ventricular arrhythmia measured in anesthetized condition was significantly reduced in T2DM rats transfected with Ad.CAT, compared with T2DM rats (0.75±0.48 in T2DM+Ad.CAT group vs. 3.0±1.38 in T2DM group). Transfection of Ad. vector into CVP neurons had no effects on protein expression of catalase and Cav2.2, ventricular vagal activity, HRV, as well as susceptibility to ventricular arrhythmias in T2DM. Based on above data, we conclude that H2O2 overproduction inactivates Cav2.2 channels and further contributes to ventricular vagal dysfunction and ventricular arrhythmogenesis in T2DM, suggesting that H2O2 signaling pathway might be an effective therapeutic target to suppress ventricular arrhythmias in patients with T2DM.