FLRT3 and TGF-ß/SMAD4 signalling: Impacts on apoptosis, autophagy and ion channels in supraventricular tachycardia.

To explore the underlying molecular mechanisms of supraventricular tachycardia (SVT), this study aimed to analyse the complex relationship between FLRT3 and TGF-ß/SMAD4 signalling pathway, which affects Na+ and K+ channels in cardiomyocytes. Bioinformatics analysis was performed on 85 SVT samples and 15 healthy controls to screen overlapping genes from the key module and differentially expressed genes (DEGs). Expression profiling of overlapping genes, coupled with Receiver Operating Characteristic (ROC) curve analyses, identified FLRT3 as a hub gene. In vitro studies utilizing Ang II-stimulated H9C2 cardiomyocytes were undertaken to elucidate the consequences of FLRT3 silencing on cardiomyocyte apoptosis and autophagic processes. Utilizing a combination of techniques such as quantitative reverse-transcription polymerase chain reaction (qRT-PCR), western blotting (WB), flow cytometry, dual-luciferase reporter assays and chromatin immunoprecipitation polymerase chain reaction (ChIP-PCR) assays were conducted to decipher the intricate interactions between FLRT3, the TGF-ß/SMAD4 signalling cascade and ion channel gene expression. Six genes (AADAC, DSC3, FLRT3, SYT4, PRR9 and SERTM1) demonstrated reduced expression in SVT samples, each possessing significant clinical diagnostic potential. In H9C2 cardiomyocytes, FLRT3 silencing mitigated Ang II-induced apoptosis and modulated autophagy. With increasing TGF-ß concentration, there was a dose-responsive decline in FLRT3 and SCN5A expression, while both KCNIP2 and KCND2 expressions were augmented. Moreover, a direct interaction between FLRT3 and SMAD4 was observed, and inhibition of SMAD4 expression resulted in increased FLRT3 expression. Our results demonstrated that the TGF-ß/SMAD4 signalling pathway plays a critical role by regulating FLRT3 expression, with potential implications for ion channel function in SVT.

Novel Fluorinated Anion Exchange Membranes Based on Poly(Pentafluorophenyl-Carbazole) with High Ionic Conductivity and Alkaline Stability for Fuel Cell Applications.

Constructing good microphase separation structures by designing different polymer backbones and ion-conducting groups is an effective strategy for improving the ionic conductivity and chemical stability of anion exchange membranes (AEMs). In this study, a series of AEMs based on the poly(pentafluorophenylcarbazole) backbone grafted with different cationic groups are designed and prepared to construct well-defined microphase separation morphology and improve the trade-off between the properties of AEMs. Highly hydrophobic fluorinated backbone and alkyl spaces enhance phase separation and construct interconnected hydrophilic channels for anion transport. The ionic conductivity of the PC-PF-QA membrane is 123 mS cm-1 at 80 °C, and the ionic conductivity of the PC-PF-QA membrane decreased by only 6% after 960 h of immersion at 60 °C in 1 M NaOH aqueous solution. The maximum peak power density of the single cell based on PC-PF-QA is 214 mW cm-2 at 60 °C.

Sulfonated Polyimide Membranes Constructed by Main-Chain and Molecular-Network Engineering Strategy for Direct Methanol Fuel Cell.

Excessive swelling is one important factor that leads to high fuel permeability and limited operating concentration of methanol for proton exchange membranes. Herein, a collaborative strategy of main-chain and molecular-network engineering is applied to lower swelling ratio and improve methanol resistance for highly sulfonated polyimide. Two m-phenylenediamine monomers (4-(2,3,5,6-tetrafluoro-4-vinylphenoxy)benzene-1,3-diamine and 4,6-bis(2,3,5,6-tetrafluoro-4-vinylphenoxy)benzene-1,3-diamine) with tetrafluorostyrol groups are designed and synthesized. Two series of cross-linked sulfonated polyimides (CSPI-Ts, CSPI-Bs) are prepared from the two diamines, 4,4'-diaminostilbene-2,2'-disulfonic acid and 1,4,5,8-naphthalenetetracarboxylicdianhydride. The rigid main-chain structure is cornerstone for wet CSPI-Ts and CSPI-Bs remaining stable at elevated temperatures. The introduction of hydrophobic cross-linked network further improves their dimensional stability and methanol resistance. CSPI-Ts and CSPI-Bs show obviously improved performances containing high proton conductivity (121 ± 0.27-158 ± 0.35 S cm-1 ), low swelling ratio (9.6 ± 0.40%-16.1 ± 0.01%) and methanol permeability (4.14-7.69 × 10-7 cm2 s-1 ) at 80 °C. The direct methanol fuel cell (DMFC) is assembled from CSPI-T-10 with balanced properties, and it exhibits high maximum power density (PDmax ) of 82.3 and 72.6 mW cm-2 in 2 and 10 m methanol solution, respectively. The ratio of PDmax in 10 m methanol solution to the value in 2 m methanol solution is as high as 88%. The CSPI-T-10 is promising proton exchange membrane candidate for DMFC application.

A new quantitative mapping criterion to localize the ablation target of right ventricular outflow tract arrhythmias.

PURPOSE: (1) To explore the electrophysiological characteristics of the bipolar and unipolar electrogram (UEGM) of ablation targets for RVOT arrhythmias. (2) To optimize the diagnostic criteria of RVOT arrhythmia ablation targets. METHODS AND RESULTS: A consecutive series of 111 patients with RVOT arrhythmias who underwent radiofrequency catheter ablation (RFCA) were studied. The voltage of bipolar potential for ablation targets were evaluated by three-dimensional voltage mapping procedure. The max slope of the descending limb (MSDL)、local activation preceding time (LAPT), the interval of the descending limb (IDL) and the interval of MSDL (IMSDL) of the unipolar potential were then calculated and analyzed for successful targets(ST) and failed targets(FT)groups. Successful ablation was achieved in 102 patients and 9 patients failed. LAPT was higher in the ST group than that in FT group (30.0 ± 4.3 ms vs 22.8 ± 6.3 ms, P < 0.001). IMSDL was lower in the ST group than that in FT group (9.93 ± 6.32 ms vs 21.7 ± 16.1 ms, P < 0.001). IMSDL and LAPT have a predictive value for a ST (AUC 75% and 83.7%). The optimal cut off value for LAPT and IMSDL were 24.5 ms and 20 ms respectively. A better predictive value can be acquired when IMSDL and LAPT were used in combination (AUC 93.9%, Sensibility/Specificity 92.3%/84.2%). CONCLUSION: A combined use of LAPT and IMSDL may be helpful as an additional criterion for ST judgement.

Near-infrared photodetection with plasmon-induced hot electrons using silicon nanopillar array structure.

A plasmon-induced hot-electron photodetector based on silicon nanopillar array is developed. The nanostructure is fabricated by reactive ion etching with a monolayer of self-assembled polystyrene nanosphere in hexagonal close-packed lattice as the mask. Light absorption and hot-electron generation are mainly enhanced by the surface plasmon polaritons formed at the surface of the gold film on the nanopillar sidewalls. The photoresponse spans two telecom wavebands, viz. the range of 1250-1600 nm, and has a value of 2.5 mA W-1 at 1310 nm. The proposed silicon nanopillar-based hot-electron infrared detector has great potentials for device integration in silicon photonics relying on the economic large-area fabrication process.

Process optimization for enhancing production of cis-4-hydroxy-L-proline by engineered Escherichia coli.

BACKGROUND: Understanding the bioprocess limitations is critical for the efficient design of biocatalysts to facilitate process feasibility and improve process economics. In this study, a proline hydroxylation process with recombinant Escherichia coli expressing L-proline cis-4-hydroxylase (SmP4H) was investigated. The factors that influencing the metabolism of microbial hosts and process economics were focused on for the optimization of cis-4-hydroxy-L-proline (CHOP) production. RESULTS: In recombinant E. coli, SmP4H synthesis limitation was observed. After the optimization of expression system, CHOP production was improved in accordance with the enhanced SmP4H synthesis. Furthermore, the effects of the regulation of proline uptake and metabolism on whole-cell catalytic activity were investigated. The improved CHOP production by repressing putA gene responsible for L-proline degradation or overexpressing L-proline transporter putP on CHOP production suggested the important role of substrate uptake and metabolism on the whole-cell biocatalyst efficiency. Through genetically modifying these factors, the biocatalyst activity was significantly improved, and CHOP production was increased by twofold. Meanwhile, to further improve process economics, a two-strain coupling whole-cell system was established to supply co-substrate (α-ketoglutarate, α-KG) with a cheaper chemical L-glutamate as a starting material, and 13.5 g/L of CHOP was successfully produced. CONCLUSIONS: In this study, SmP4H expression, and L-proline uptake and degradation, were uncovered as the hurdles for microbial production of CHOP. Accordingly, the whole-cell biocatalysts were metabolically engineered for enhancing CHOP production. Meanwhile, a two-strain biotransformation system for CHOP biosynthesis was developed aiming at supplying α-KG more economically. Our work provided valuable insights into the design of recombinant microorganism to improve the biotransformation efficiency that catalyzed by Fe(II)/α-KG-dependent dioxygenase.

Endocardial focal activation originating from Purkinje fibers plays a role in the maintenance of long duration ventricular fibrillation.

AIM: To determine the role of repetitive endocardial focal activations and Purkinje fibers in the maintenance of long duration ventricular fibrillation (LDVF, VF>1 minute) in canine hearts in vivo. METHODS: The study was conducted in electrophysiological laboratory of Shanghai Ruijin hospital from July 2010 to August 2012. A 64-electrode basket was introduced through a carotid artery into the left ventricle (LV) of 11 beagle dogs for global endocardial electrical mapping. In the Lugol's solution group (n=5), the subendocardium was ablated by washing with Lugol's solution. In the control group, (n=6) saline was used for ablation. Before and after saline or Lugol ablation, we determined QRS duration and QT/QTc interval in sinus rhythm (SR). We also measured the activation rates in the first 2 seconds of each minute during 7 minutes of VF for each group. If VF terminated spontaneously in less than 7 minutes, the VF segments used in activation rate analysis were reduced accordingly. RESULTS: At the beginning of VF there was no difference between the groups in the activation rate. However, after 1 minute of LDVF the Lugol's solution group had significantly slower activation rate than the control group. In the control group, all episodes of LDVF (6/6) were successfully sustained for 7 minutes, while in the Lugol's solution group 4/5 episodes of LDVF spontaneously terminated before 7 minutes (4.8±1.4 minutes) (P=0.015). In the control group, at 5.1±1.3 minutes of LDVF, a successive, highly organized focal LV endocardial activation pattern was observed. During this period, activations partly arose in PF and spread to the working ventricular myocardium. Mapping analysis showed that these events were consistent with repetitive endocardial focal activations. No evidence of similar focal activations was observed in the Lugol's solution group. CONCLUSIONS: Repetitive endocardial focal activations in the LV endocardium may be associated with activation of subendocardial PFs. This mechanism may play an important role in the maintenance of LDVF.

Integrative analysis of transcriptomics and metabolomics reveals the protective effect and mechanism of salidroside on testicular ischemia-reperfusion injury.

Testicular torsion is a critical urologic condition for which testicular detorsion surgery is considered irreplaceable as well as the golden method of reversal. However, the surgical treatment is equivalent to a blood reperfusion process, and no specific drugs are available to treat blood reperfusion injuries. Salidroside (SAL) is one of the main effective substances in rhodiola, which has been shown to have antioxidant and antiapoptosis activities. This study was designed to determine whether SAL exerted a protective effect on testicular ischemia-reperfusion (I/R) injury. In this study, the I/R injury model of the testes and reoxygenation (OGD/R) model were used for verification, and SAL was administered at doses of 100 mg/kg and 0.05 mmol/L, respectively. After the experiments, the testicular tissue and TM4 Sertoli cells were collected for histopathologic and biochemical analyses. The results revealed that SAL improves the structure of testicular tissue and regulates the oxidation-antioxidation system. To further understand the molecular mechanisms of SAL in treating testicular I/R injuries, transcriptomics and metabonomics analyses were integrated. The results show that the Nfr2/HO-1/GPX4/ferroptosis signaling pathway is enriched significantly, indicating that it may be the main regulatory pathway for SAL in the treatment of testicular I/R injuries. Thereafter, transfection with Nrf2 plasmid-liposome was used to reverse verify that the Nfr2/HO-1/GPX4/ferroptosis signaling pathway was the main pathway for SAL anti-testicular I/R injury treatment. Thus, it is suggested that SAL can protect against testicular I/R injuries by regulating the Nfr2/HO-1/GPX4 signaling pathway to inhibit ferroptosis and that SAL may be a potential drug for the treatment of testicular I/R injuries.

Single-cell sequencing of immune cells from the coronary sinus reveals immune mechanisms of the progression of persistent atrial fibrillation.

Identifying the atlas of immune cells from coronary sinus circulation (CSC) of patients with persistent atrial fibrillation (PerAF) may provide new insights into the role of immune cells in the progression of AF. Single-cell sequencing revealed substantial alterations in immune cells from CSCs of patients with PerAF, especially a markedly elevated abundance of T cells, after which we identified a T cell subset: FGFBP2(+)TRDC(-)CD4(-) T cells (Ftc-T cells), which can promote the proliferation of cardiac fibroblasts (CFs),and the proportion of Ftc-T had a positive linear with AF recurrence post catheter ablation (CA). Moreover, IFI27 was found to be highly enriched in Ftc-T cells and promoted CFs proliferation and collagen expression. Altogether, our findings represent a unique resource providing in-depth insights into the heterogeneity of the immune cell from CSC of patients with PerAF and highlight the potential role of Ftc-T cells and IFI27 for AF progression.

Simultaneous ST-elevation in lead augmented vector right (aVR) and III in non-ST-elevation acute coronary syndromes.

Background: The value of ST-elevation in lead augmented vector right (aVR) remains controversial in clinical practice. This study aimed to investigate the association of simultaneous ST-elevation in lead aVR and III with angiographic findings and clinical outcomes in patients with non-ST-elevation acute coronary syndromes (NSTEACS). Methods: In this observational study, patients who had been diagnosed with NSTEACS and presented with ST-elevation in lead aVR and without ST-elevation in any other two contiguous leads were enrolled from January 2018 to June 2019. Demographic, baseline clinical, angiographic and interventional characteristics as well as clinical outcomes were collected and recorded on standardized case report forms. Results: A total of 157 patients meeting the criteria were finally enrolled in this study and classified into two groups according to the presence of ST-elevation in lead III. Patients in the two groups were similar in average age and previous history of hypertension, diabetes mellitus, hyperlipidemia, chronic kidney disease, stroke, and peripheral vascular diseases (all P>0.05). Patients with ST-elevation in lead III tended to present with myocardial hypertrophy in the echocardiography (P=0.02). The cases with ST-elevation in lead III showed higher high sensitivity troponin T (hs-TnT; P=0.08) and creatinine kinase MB isoenzyme (CK-MB; P<0.01) whereas those without ST-elevation in lead III showed higher N-terminal pro brain natriuretic peptide (NT-proBNP; P=0.02). Of note, patients with ST-elevation in lead III presented with more ST-depression in multiple leads [especially in lead I, augmented vector left (aVL), V3-V6] as well as higher degree of ST-depression (all P<0.05) and were more likely to develop multi-vessel and left main trunk (LM) lesions (P=0.04), with 20% of the cases having a LM lesion and 60% having triple vessel lesions. Patients with ST-elevation in lead III were at increased risk of 3-year major adverse cardiovascular events (MACEs), despite no significant statistical difference between the two groups (hazard ratio =1.29; P=0.26). Conclusions: The NSTEACS cases with simultaneous ST-elevation in lead III and aVR tended to present with more multiple leads with ST-depression, higher degree of ST-depression, and more LM or multi-vessel lesions, suggesting a broader range of severe myocardial ischemia. The concurrent presentation of ST-elevation in lead III and aVR may play a vital role in the diagnosis, risk-stratification, and prediction of poor prognosis during the management of NSTEACS patients.

Defibrillation threshold varies during different stages of ventricular fibrillation in canine hearts.

BACKGROUND: Recent studies have shown that short duration ventricular fibrillation (SDVF) and long duration ventricular fibrillation (LDVF) are maintained by different mechanisms. The objective of this study is to evaluate how the defibrillation threshold (DFT) varies over the duration of fibrillation since the mechanism of VF maintenance changes as VF progresses. METHODS: Twelve canines were randomly divided into two groups (Group A and B, n=6 each). DFTs were measured three times in each group: SDVF (20s), LDVF (3min in Group A and 7min in Group B) and the first episode of refibrillation after successful defibrillation for LDVF. Two 64-electrode baskets used to globally map the endocardium were deployed into the left ventricle and right ventricle, respectively. RESULTS: LDVF-DFT in Group A was significantly higher than that of Group B (628±98V vs 313±81V, P<0.001). In Group B, the DFT of refibrillation was significantly increased compared with the LDVF-DFT (570±199V vs 313±81V, P=0.035) but did not differ from the DFT of refibrillation in Group A (570±199V vs 638±116V, P=0.39). Highly synchronised activation patterns on the left ventricular endocardium were observed between 3 and 7min of LDVF in Group B but not within 3min-LDVF in Group A or during refibrillation in each group. CONCLUSIONS: DFT varied during different stages of VF. The highly synchronised activation patterns exhibiting after 3min VF might contribute to the decreased LDVF-DFT.

A new insight into the different approaches for the ablation of para-Hisian accessory pathways: safety, effectiveness, and mechanism.

BACKGROUND: To compare the safety, effectiveness, electrophysiological characteristics, and mechanisms of different approaches for the ablation of para-Hisian accessory pathways (APs). METHOD: Eighteen consecutive patients with para-Hisian APs were enrolled in this study. Detailed mapping of retrograde conduction as well as antegrade conduction (if possible) in both the right sided His bundle region and non-coronary cusp (NCC) region was performed before ablation. Ten patients underwent initial ablation in the right septal (RS) region while the remaining 8 patients were ablated in NCC region. Repeat ablation was attempted in an alternative region if ablation at the first site failed. RESULTS: Among the patients whose procedures were successful, 7 cases were successfully ablated with a NCC approach while 10 were conventionally ablated in RS region. For successful procedures targeting the NCC region, the earliest atrial activation (EAA) in NCC region preceded that at RS region by 4-13 ms. The distance between NCC targets and near-field His potential (NFH) points was longer than that between RS targets and NFH points. Additionally, the risk of complication after ablation in NCC region was lower compared with that following RS-targeted procedure. CONCLUSION: NCC approach provided a high success rate and low risk of complication for the ablation of para-Hisian APs as long as EAA was observed in NCC region. Sites of successful para-Hisian AP ablation in NCC region had different retrograde mapping patterns in comparison with successful ablation sites in the RS region.

Cryoballoon ablation for atrial fibrillation in patients with heart failure with mildly reduced and preserved ejection fraction.

AIMS: Limited data are available on the outcomes of cryoballoon ablation (CBA)-based pulmonary vein isolation (PVI) for atrial fibrillation (AF) in patients with heart failure (HF) with preserved ejection fraction (HFpEF) and mildly reduced ejection fraction (HFmrEF). The present study aimed to evaluate the safety and effectiveness of CBA in such patients. METHODS AND RESULTS: Consecutive patients with AF referred for CBA-based PVI from two highly experienced electrophysiology centres were included in this retrospective study. Of 651 patients undergoing CBA, 471 cases were divided into four groups: No HF (n = 255), HFpEF (n = 101), HFmrEF (n = 78), and HF with reduced ejection fraction (n = 37). Similar early recurrence of atrial arrhythmia was found among groups (16.2% vs. 15.4% vs. 14.9% vs. 12.2%, P = 0.798), and no significant difference of long-term sinus rhythm (SR) maintenance was identified among the HFmrEF, HFpEF, and No HF groups (71.8% vs. 75.2% vs. 79.6%, P = 0.334). CBA is safe for patients with HFmrEF and HFpEF with similar complications compared with the No HF group (3.8% vs. 4.0% vs. 3.1%, P = 0.814). The reassessment of cardiac function after CBA showed that patients with HF indicated beneficial outcomes. Left atrial diameter (LAD) and left ventricular ejection fraction were significantly improved in the HFmrEF group. There were 41.6% of patients in the HFpEF group who were completely relieved from HF. LAD and New York Heart Association (NYHA) were associated with recurrence in the HFpEF and HFmrEF groups, and the maintenance of SR was an independent predictor of NYHA improvement for all HF groups. CONCLUSIONS: Patients with HFmrEF and HFpEF could benefit from CBA with high SR maintenance and significant HF improvement.

The Influence of Pulmonary Veins' Anatomic Features and Catheter Coaxiality on Cryoballoon Ablation Results for Paroxysmal Atrial Fibrillation.

A total of 172 consecutive patients with sympathetic paroxysmal atrial fibrillation who received cryoballoon (CB) ablation from 2020 to 2021 were retrospectively analyzed in this study. Catheter coaxiality and anatomic features of pulmonary veins (PVs) on computed tomography images were explored by several parameters and their influence on the cryoablation results was then analyzed. The rate of incomplete CB occlusion was significantly higher for inferior than superior PVs. A multivariate analysis revealed that a short distance (<6.3 mm) from PV ostium to first branch (D-PVB) and a small angle (<32.5°) of first branch were independent predict factors for an incomplete CB occlusion in right inferior PVs (RIPVs). A combination of D-PVB and angle of first branch could elevate the predictor value for an incomplete balloon occlusion with a sensitivity of 0.85 and specificity of 1.0 for RIPVs. For PVs with a perfect balloon occlusion, the best catheter coaxiality was observed in right superior PV while the worst catheter coaxiality was observed in RIPV. A more aggressive catheter manipulation with a "7" or "reverse-U" shape of long sheath could obtain a better catheter coaxiality compared with conventional manipulation strategy for RIPVs. In Conclusion, a short D-PVB and a small angle of first branch were independent predict factors for an incomplete CB occlusion in RIPVs. A more aggressive catheter manipulation strategy was recommended to achieve a complete balloon occlusion and a better catheter coaxiality for RIPVs.

The effect of pinacidil on postshock activation and ventricular defibrillation threshold in canine hearts.

AIM: To determine the postshock activation patterns with both successful and failed shocks in a canine model of ventricular fibrillation, and whether piniacidil, an early after-depolarization (EAD) inhibitor, altered the defibrillation threshold (DFT) and postshock activation patterns. METHODS: In 6 beagles, a basket catheter with 64 unipolar electrodes was placed in the LV for global endocardial mapping, a monophasic action potential catheter was inserted into the LV apex, and a catheter with the negative electrode in the right ventricle and the positive electrode in the superior vena cava was inserted for defibrillation. The DFT, 90% action potential duration (APD(90)) and activation recovery interval (ARI) were evaluated before and after pinacidil administration (loading dosage 0.5 mg/kg and maintenance dosage 0.5 mg·kg(-1)·h(-1), iv). Electrical heterogeneities were defined with the dispersion of ARI. After successful and failed shocks with near-DFT strength, the earliest postshock activation patterns (focal or nonfocal endocardial activation), interval and location were detected. RESULTS: Pinacidil significantly decreased APD(90) (from 178±16 ms to 168±18 ms) and ARI from (152±10 ms to 143±10 ms) at pacing cycle length of 300 ms. The drug significantly increased VF activation rate (from 10.0±1.9 Hz to 10.8±2.0 Hz). The drug did not affect the dispersion of ARI, neither it changed DFT (baseline: 480±110 V; pinacidil: 425±55 V, P>0.05). The earliest postshock activation arose locally on the LV apical endocardium before and after the drug treatment. Pinacidil significantly prolonged the postshock cycle length of cycles 2 to 5 for the successful episodes but not for the failed episodes. CONCLUSION: Pinacidil increases the postshock cycle length suggesting that EAD may play a role in postshock activation, while it fails to alter DFT suggesting that EAD produced by shock does not determine a defibrillation success or failure.

Different approaches for ablation of RVOT-type arrhythmia: comparison between the choice of RVOT and pulmonary sinus cusp region for the first ablation attempt.

BACKGROUND: This study aimed (1) to explore the electrophysiological characteristics of the bipolar and unipolar electrograms of ablation targets for RVOT arrhythmias with different ablation methods and to access the clinical outcome with different ablation strategies. METHODS: A consecutive series of 106 patients with RVOT arrhythmias who underwent radiofrequency catheter ablation (RFCA) were studied. Conventional ablation method for RVOT targets and reverse U-curve technique for PSC targets were respectively used with different mapping outcomes. The electrophysiological characteristics of the bipolar and unipolar electrograms for ablation targets and clinical ablation outcome with different ablation strategies were evaluated. RESULTS: When there was an obvious difference (≥ 3 ms) of earliest targets (ETs) between the PSC and RVOT regions, conventional ablation technique in the RVOT region can achieve the same and high success rate compared with the reverse-U ablation technique in the PSC region as we choose the region with a better ET for first ablation attempt. When similar (< 3 ms) ETs were observed in the PSC and RVOT regions, ablation in the PSC region can achieve an apparently higher success rate compared with ablation in the RVOT region. ETs in the PSC region had a different pattern of bipolar potential compared with those in the RVOT region, as a discrete sharp near-field potential or a fractionated potential with low voltage was more frequently observed in the PSC region. CONCLUSIONS: Different mapping outcomes led to different success rate with two ablation strategies. When similar ETs were observed in the PSC and RVOT regions, ablation in the PSC region could achieve an apparently higher success rate. A discrete sharp or fractionated potential could help to identify the sites of PVCs' origination.

Application of Isotope Tracer in Cross-Well Nanometre Tracer Testing.

In order to understand the dynamic monitoring characteristics and heterogeneity characteristics of injection production wells in the monitoring area and judge the reservoir connectivity, this study puts forward the application method of isotope nanometre tracer in interwell nanometre tracer testing. The trace material nanometre tracer interwell monitoring technology was applied to well block J in a basin. Through the analysis of the morphological characteristics of the nanometre tracer production curve and the quantitative interpretation of trace material tracer, combined with the analysis of the advancing speed of the water line at the front edge of the nanometre tracer and the distribution of injected water wells, the nanometre tracer connectivity, and advancing speed, the characteristics of seepage channels and heterogeneity of the well groups in the study area were defined. The research results show that 8 oil wells in the monitoring area are controlled by water injection well J1, the injection water inrush direction is generally north, the main channel of injection water is mainly high-permeability strip, and the heterogeneity contradiction between layers is strong. It is recommended to adopt mild water injection. Conclusion. This study found that the dynamic connectivity between oil and water wells in the monitoring area is good.

Anomalous surface O3 changes in North China Plain during the northwestward movement of a landing typhoon.

As high impact weather in a large scale, typhoon movement from the northwest Pacific into inland regions influencing ambient O3 changes is unclear, especially in North China Plain (NCP). A landing Typhoon Ampil during July 17-24, 2018 was studied herein to characterize the surface O3 anomalies during its movement over NCP. Landing typhoons present large negative O3 anomalies at the center of the typhoon and positive O3 anomalies 600-1700 km away from the center. During the northwest movement of Typhoon Ampil to the NCP, the area and magnitude of both positive and negative O3 anomalies shrank, particularly in the western and northern periphery, where the typical diurnal change of O3 dissipated with nocturnal O3 enhancement in the NCP. The spatiotemporal patterns of surface O3 anomalies in the NCP were induced significantly during various stages of typhoon movement with a stable structure in the atmospheric boundary layer, strong solar radiation on sunny days, and stratosphere-to-troposphere transport (STT) in the typhoon periphery, depending on the changing intensity, distance, and orientation of the typhoon center. Among them, the STT played a considerable role and contributed 32% to the positive anomalies of surface O3 in the NCP. Under the influence of westerly jets and high pressure at mid-latitudes on the typhoon movement, strong wind convergences in the upper troposphere were formed intensifying the downdraft of O3-rich stratospheric air to the boundary layer in the NCP with an asymmetrical distribution of surface positive O3 anomalies over the periphery of typhoon. This study could improve our understanding of regional ozone changes with meteorological influences.

Moricizine prevents atrial fibrillation by late sodium current inhibition in atrial myocytes.

Background: Enhanced late sodium current (INaL) is reportedly related to an increased risk of atrial fibrillation (AF). Moricizine, as a widely used anti-arrhythmia drug for suppressing ventricular tachycardia, has also been shown to prevent paroxysmal AF. However, the mechanism of its therapeutic effect remains poorly understood. Methods: Angiotensin II (Ang II) was induced in C57Bl/6 mice (male wild-type) for 4 weeks to increase the susceptibility of AF, and acetylcholine-calcium chloride was used to induce AF. The whole-cell patch-clamp technique was used to detect INaL from isolated atrial myocytes. The expression of proteins in atrial of mice and HL-1 cells were examined by Western-blot. Results: The results showed that moricizine significantly inhibited Ang II-mediated atrial enlargement and reduced AF vulnerability. We found that the densities of INaL were enhanced in Ang II-treated left and right atrial cardiomyocytes. Simultaneously, the Ang II-induced increase in INaL currents density was alleviated by the administration of moricizine, and no alteration in Nav1.5 expression was observed. In normal isolated atrial myocytes, moricizine significantly reduced Sea anemone toxin II (ATX II)-enhanced INaL density with a reduction of peak sodium currents. In addition, moricizine reduced the Ang II-induced upregulation of phosphorylated calcium/calmodulin-dependent protein kinase-II (p-CaMKII) in both the left and right atria. In HL-1 cells, moricizine also reduced the upregulation of p-CaMKII with Ang II and ATX II intervention, respectively. Conclusions: Our results indicate that Ang II enhances the INaL via activation of CaMKII. Moricizine inhibits INaL and reduces CaMKII activation, which may be one of the mechanisms of moricizine suppression of AF.

The effects of acute amiodarone on short- and long-duration ventricular defibrillation threshold in canines.

INTRODUCTION: Some studies have shown that the defibrillation threshold (DFT) differs between short-duration ventricular fibrillation (SDVF, <1 minute) and long-duration ventricular fibrillation (LDVF > 1 minute). The goal of this study is to evaluate the effects of acute intravenous amiodarone on SDVF-DFT and LDVF-DFT and its possible mechanism as well. METHODS: Twelve open-chest dogs were randomly divided into 2 groups (control group, normal saline, 10 mL·kg·h maintenance, n = 6; amiodarone group, loading dose 10 mg/kg over 10 minutes, maintenance dose 5 mg·kg·h, n = 6). VF was electrically induced and recorded with a 12 × 12 unipolar electrode plaque (2-mm spacing) sutured on the left ventricular epicardium and a plunge needle (6 unipolar electrode) inserted in the left ventricular apex. The DFTs of SDVF and LDVF were determined 20 seconds and 3 minutes after VF induction, respectively. Restitution was estimated from activation recovery intervals during pacing from the plaque and plunge needle electrodes. The activation rate was estimated by Fast Fourier Transform analysis of VF at same electrodes. The VF cycle length was defined as the reciprocal of the activation rate. The epicardial and transmural dispersion of the maximal slope of the restitution curve and VF cycle length of SDVF and LDVF were calculated, respectively. RESULTS: : In controls, LDVF-DFT was higher than SDVF-DFT (645 ± 61 vs. 520 ± 63 V, P < 0.01). Amiodarone did not significantly alter SDVF-DFTs (496 ± 49 vs. 552 ± 69 V, P > 0.05) but decreased LDVF-DFT by 31% (P < 0.01). Compared with control, amiodarone significantly reduced the maximum slope of the restitution curve (1.12 ± 0.35 vs. 0.81 ± 0.25, P = 0.03) and its epicardial dispersion (0.32 ± 0.07 vs. 0.24 ± 0.04,coefficient of variation, P = 0.017). Amiodarone significantly increased the SDVF-CL (92 ± 8 vs. 99 ± 10 milliseconds, P < 0.01) and epicardial dispersion 0.14 ± 0.06 vs. 0.18 ± 0.05, P < 0.01. Amiodarone did not change the LDVF-CL (228 ± 12 vs. 226 ± 10 milliseconds, P > 0.05) or epicardial dispersion (0.17 ± 0.03 vs. 0.15 ± 0.02, P > 0.05) compared with control. However, the drug significantly decreased the transmural dispersion of LDVF-CL (68 ± 28 vs. 39 ± 14 milliseconds, P < 0.01) without changing the transmural dispersion of SDVF-CL (29 ± 22 vs. 32 ± 30 milliseconds, P > 0.05). CONCLUSIONS: Acute amiodarone significantly decreased the LDVF-DFT. The decreased transmural dispersion of LDVF-CL by amiodarone might contribute to the decreased LDVF-DFT.