Realizing Ultrathin LiSn Alloy Anode by Tuning the Wettability of Molten Li for High-Energy-Density Batteries.

Despite being heralded as the "holy grail" of anodes for their high theoretical specific capacity, lithium (Li) metal anodes still face practical challenges due to difficulties in fabricating ultrathin Li with controllable thickness and suppressing Li dendrites growth. Herein, we introduce a simple and cost-effective dip-coating method to fabricate ultrathin lithium-tin (LiSn) anode with adjustable thicknesses ranging from 4.5 to 45 µm. The in situ formation of Li22Sn5 alloy improves the wettability of the molten Li, enabling the casting of ultrathin Li metal layers on different substrates. More importantly, the abundant Li22Sn5 lithiophilic sites significantly lower the nucleation overpotential, inducing uniform Li deposition and accelerating the electrochemical reaction at the interface. As a result, the symmetric cell assembled with LiSn-Cu electrodes can cycle stably for more than 120 h with a charge/discharge depth of 50%, which is 1.5 times longer than the lifespan of the pure Li anode. In the full cells paired with NCM cathode, the discharge specific capacity is improved from 13.84 to 70.31 mA h g-1 with the LiSn-Cu anode at 8 C. The LiSn-Cu||NCM full cell realized a high energy density of 724.9 Wh kg-1 at the active material level with an N/P ratio of 1.4.

Uric acid, high density lipoprotein cholesterol levels and their ratio are related to microbial enterotypes and serum metabolites in females with a blood stasis constitution.

BACKGROUND: Blood stasis constitution in traditional Chinese medicine (TCM) is believed to render individuals more susceptible to metabolic diseases. However, the biological underpinnings of this constitutional imbalance remain unclear. METHODS: This study explored the association between blood stasis constitution, serum metabolic markers including uric acid (UA), high-density lipoprotein cholesterol (HDLC), their ratio (UHR), serum metabolites, and gut microbiota. Clinical data, fecal and serum samples were acquired from 24 individuals with a blood stasis constitution and 80 individuals with a balanced constitution among healthy individuals from Guangdong. Gut microbiota composition analysis and serum metabolomics analysis were performed. RESULTS: Females with a blood stasis constitution had higher UA levels, lower HDLC levels, and higher UHR in serum, suggesting a higher risk of metabolic abnormalities. Analysis of the gut microbiome revealed two distinct enterotypes dominated by Bacteroides or Prevotella. Intriguingly, blood stasis subjects were disproportionately clustered within the Bacteroides-rich enterotype. Metabolomic analysis identified subtle differences between the groups, including lower phenylalanine and higher trimethylaminoacetone levels in the blood stasis. Several differential metabolites displayed correlations with HDLC, UA, or UHR, unveiling potential new markers of metabolic dysregulation. CONCLUSIONS: These findings elucidate the intricate interplay between host constitution, gut microbiota, and serum metabolites. The concept of blood stasis offers a unique perspective to identify subtle alterations in microbiome composition and metabolic pathways, potentially signaling underlying metabolic vulnerability, even in the presence of ostensibly healthy profiles. Continued investigation of this TCM principle may reveal critical insights into the early biological processes that foreshadow metabolic deterioration.

Effect of miniscrew placement height on the distribution of biological forces produced by clear aligner for mandibular molar distalization / 口腔疾病防治

Objective@#To explore the effect of different miniscrew placement heights on the distribution of biological forces produced by clear aligner combined with intramaxillary traction for mandibular molar distalization, to identify the miniscrew location that is conducive to the protection of lower anterior tooth anchorage and to provide a reference that can be used when designing clinical treatments.@*Methods@#Mimics, GeomagicStudio 2017, SolidWorks 2016, and Ansys workbench were used to establish finite element analysis models and perform mechanical analysis under the following six working conditions: working condition 1 was the control group without miniscrews; working conditions 2 to 5 had miniscrew in the buccal bone cortex between the first and second molars of the lower jaw 10 mm, 7 mm, 4 mm, and 1 mm from the top of the alveolar crest, respectively; working condition 6 had the miniscrew in the center of the buccal tongue at the anterior edge of the ascending branch of the lower jaw 5 mm above the occlusal plane.@*Results@#On the sagittal axis, miniscrew anchorage caused distal displacement of all teeth. Compared to the control group, in the miniscrew group, the displacement of the anterior molars exceeded that of the second molars. On the vertical axis, the result in the control group was similar to backward bending; the results in the miniscrew groups resembled the effect of a lever, lowering the lateral incisors and canines and raising the central incisors and first premolars. On the coronal axis, the second premolars and the first molars showed lingual displacement in the control group, and only the premolars and first molars showed lingual displacementin the miniscrew groups. The canines were the teeth that were most strongly affected by the change in miniscrew placement height.@*Conclusion@#The higher the miniscrew position is, the stronger the protective effect on the anterior anchorage. According to the miniscrew placement height, the mandibular arch should be properly narrowed, the central incisors and first premolars should be lowered, and the lateral incisors and canines should be raised when designing clinical treatments.

The displacement of teeth and stress distribution on periodontal ligament under different upper incisors proclination with clear aligner in cases of extraction: a finite element study.

OBJECTIVES: To investigate the displacement of dentition and stress distribution on periodontal ligament (PDL) during retraction and intrusion of anterior teeth under different proclination of incisors using clear aligner (CA) in cases involving extraction of the first premolars. METHODS: Models were constructed, consisting of the maxilla, PDLs, CA and maxillary dentition without first premolars. These models were then imported to finite element analysis (FEA) software. The incisor proclination determined the division of the models into three groups: Small torque (ST) with U1-SN = 100°, Middle torque (MT) with U1-SN = 110°, and High torque (HT) with U1-SN = 120°. Following space closure, a 200 g intrusion force was applied at angles of 60°, 70°, 80°, and 90° to the occlusal plane, respectively. RESULTS: CA therapy caused lingual tipping and extrusion of incisors, mesial tipping and intrusion of canines, and mesial tipping of posterior teeth in each group. As the proclination of incisors increased, the incisors presented more extrusion and minor retraction, and the teeth from the canine to the second molar displayed an increased tendency of intrusion. The peak Von Mises equivalent stress (VMES) value successively decreased from the central incisor to the canine and from the second premolar to the second molar, and the VMES of the second molar was the lowest among the three groups. When the angle between the intrusion force and occlusal plane got larger, the incisors exhibited greater intrusion but minor retraction. CONCLUSIONS: The "roller coaster effect" usually occurred in cases involving premolar extraction with CA, especially in patients with protruded incisors. The force closer to the vertical direction were more effective in achieving incisor intrusion. The stress on PDLs mainly concentrated on the cervix and apex of incisors during the retraction process, indicating a possibility of root resorption.

Hyperloop-like diffusion of long-chain molecules under confinement.

The ultrafast transport of adsorbates in confined spaces is a goal pursued by scientists. However, diffusion will be generally slower in nano-channels, as confined spaces inhibit motion. Here we show that the movement of long-chain molecules increase with a decrease in pore size, indicating that confined spaces promote transport. Inspired by a hyperloop running on a railway, we established a superfast pathway for molecules in zeolites with nano-channels. Rapid diffusion is achieved when the long-chain molecules keep moving linearly, as well as when they run along the center of the channel, while this phenomenon do not exist for short-chain molecules. This hyperloop-like diffusion is unique for long-chain molecules in a confined space and is further verified by diffusion experiments. These results offer special insights into molecule diffusion under confinement, providing a reference for the selection of efficient catalysts with rapid transport in the industrial field.

Enhance Hydrogen Isotopes Separation by Alkali Earth Metal Dopant in Metal-Organic Framework.

Kinetic quantum sieving (KQS) based on pore size and chemical affinity quantum sieving (CAQS) based on adsorption site are two routes of porous materials to separate hydrogen isotope mixtures. Alkali earth metals (Be, Mg, and Ca) were doped into UiO-67 to explore whether these metal sites can promote H2/D2 separation. Based on the zero-point energy and adsorption enthalpy calculated by density functional theory calculations, the Be dopant shows better H2/D2 separation performance than other alkali earth metal dopants and unsaturated metal sites in metal-organic frameworks based on CAQS. Orbital interaction strongly relates to the chemical affinity and further influences the D2/H2 selectivity. Moreover, the predicted D2/H2 selectivity of Be-doped sites (49.4) at 77 K is even larger than the best experimental result (26). Finally, the different dynamic behaviors of H2 and D2 on Be-doped UiO-67 indicate its strong H2/D2 separation performance via KQS.

Multiscale dynamical cross-talk in zeolite-catalyzed methanol and dimethyl ether conversions.

Establishing a comprehensive understanding of the dynamical multiscale diffusion and reaction process is crucial for zeolite shape-selective catalysis and is urgently demanded in academia and industry. So far, diffusion and reaction for methanol and dimethyl ether (DME) conversions have usually been studied separately and focused on a single scale. Herein, we decipher the dynamical molecular diffusion and reaction process for methanol and DME conversions within the zeolite material evolving with time, at multiple scales, from the scale of molecules to single catalyst crystal and catalyst ensemble. Microscopic intracrystalline diffusivity is successfully decoupled from the macroscopic experiments and verified by molecular dynamics simulation. Spatiotemporal analyses of the confined carbonaceous species allow us to track the migratory reaction fronts in a single catalyst crystal and the catalyst ensemble. The constrained diffusion of DME relative to methanol alleviates the high local chemical potential of the reactant by attenuating its local enrichment, enhancing the utilization efficiency of the inner active sites of the catalyst crystal. In this context, the dynamical cross-talk behaviors of material, diffusion and reaction occurring at multiple scales is uncovered. Zeolite catalysis not only reflects the reaction characteristics of heterogeneous catalysis, but also provides enhanced, moderate or suppressed local reaction kinetics through the special catalytic micro-environment, which leads to the heterogeneity of diffusion and reaction at multiple scales, thereby realizing efficient and shape-selective catalysis.

Valid and Convenient Questionnaire Assessment of Chinese Body Constitution: Item Characteristics, Reliability, and Construct Validation.

Background: Body constitution is a fundamental concept in traditional Chinese medicine (TCM) for clinical diagnosis, treatment of illness, and community-based health promotion. Clinical assessment of patients' body constitutions, however, has never been easy and consistent, even by well-trained clinicians and TCM practitioners. Therefore, questionnaires such as the popular Constitution in Chinese Medicine Questionnaire (CCMQ) can be an appealing and convenient assessment alternative. The present research borrowed advanced methodologies for questionnaire development in psychology and other social sciences to examine the performance of the CCMQ in terms of (i) the strength of relations of each item with its designated constitution, (ii) the reliabilities of each constitution, and (iii) the overall 9-constitution structure. This research provided empirical evidence to support the use of the CCMQ and proposed directions for refinement in future revisions of the CCMQ or similar measures. Methods: A total of 1571 volunteers from three villages in southern China participated in the CCMQ survey. The item characteristics, reliabilities, interconstitution correlations, and confirmatory factor analysis of the 9-body-constitution structure were examined. Results: The results generally supported the appropriateness of the clinical observations (the questionnaire items) and the CCMQ 9-constitution classification structure. Nevertheless, some relatively weaker items, item pairs with similar meanings, and highly overlapping constitutions were identified for future CCMQ revisions. Conclusion: The CCMQ measured the 9 constitutions efficiently and with reasonably good reliability and construct validity. Given the various challenges to assessing TCM body constitutions even by experienced clinicians, the CCMQ provides an appealing alternative to measure the Chinese body constitutions of healthy participants in large-scale research or community health promotion programs. The present study also demonstrated how advanced methodologies in social sciences can help validate and refine the CCMQ and similar complementary medicine measures.

Evaluating the efficacy and safety of percutaneous coronary intervention (PCI) versus the optimal drug therapy (ODT) for stable coronary heart disease: a systematic review and meta-analysis.

Background: Many studies have reported potential benefits of percutaneous coronary intervention (PCI) versus optimal drug therapy (ODT) for patients with stable coronary heart disease but with inconsistent results. To examine this, an explicit systematic review and meta-analysis was conducted to compared the clinical outcomes of PCI and ODT in these patients. Methods: The following terms were combined to search relative articles through databases PubMed, Cochrane Central Register of Controlled Trials, Embase, and Web of Science published from January 2010 to November 2021 according to Participants, Intervention, Control, Outcomes, Study (PICOS) criteria: "coronary heart disease", "stable coronary heart disease", "stable angina pectoris", "percutaneous coronary intervention", "PCI", "percutaneous transluminal coronary angioplasty", "drug therapy", "optimized drug treatment", and "optimized drug therapy". The meta-analysis was performed by RevMan 5.2, and the Cochrane risk of bias tool was used to evaluate the quality of the included studies. Results: A total of 12 articles were included in the final analysis. There were 4,288 cases of PCI patients and 4,261 cases of ODT patients. The results showed that, when comparing PCI with ODT, there was a significant difference in the probability of myocardial infarction [relative risk (RR) =0.63; 95% confidence intervals (CI): 0.45-0.90] and the patient mortality (RR =0.51; 95% CI: 0.40-0.64). However, there was no significant difference in the prevalence of stroke (RR =1.33; 95% CI: 0.82-2.17), revascularization (RR =0.86; 95% CI: 0.46-1.62) and patient quality of life (MD =10.44; 95% CI: -1.84 to 22.73). Performance bias and detection bias were all unclear in the included studies and should be warned. Discussion: Compared with ODT, PCI reduced the mortality and myocardial infarction rate of patients with CTO or severe coronary artery stenosis. However, the incidence of stroke, revascularization, and quality of life of patients were not significant different between PCI and ODT. Performance bias and detection bias should be cautioned.

Diffusive Skin Effect in Zeolites.

Effective contact and collision between reactants and active sites are essential for heterogeneous catalysis. Herein, we investigated molecular diffusion in more than 200 kinds of zeolites, and an intriguing "diffusive skin effect" was observed, whereby molecules migrated along the pore walls of zeolites (i.e., diffusion trajectories) because of the effect of the guest-host interaction and diffusion barrier. Furthermore, it was found that such a "diffusive skin effect" of zeolites would strongly promote the contacts and collisions between reactants and active sites in the reaction process, which might effectively promote the zeolite-catalyzed performance. These new findings will provide some new fundamental understanding of zeolite catalytic mechanisms under confinement effect.

Thermal resistance effect on anomalous diffusion of molecules under confinement.

Diffusion is generally faster at higher temperatures. Here, a counterintuitive behavior is observed in that the movement of long-chain molecules slows as the temperature increases under confinement. This report confirms that this anomalous diffusion is caused by the "thermal resistance effect," in which the diffusion resistance of linear-chain molecules is equivalent to that with branched-chain configurations at high temperature. It then restrains the molecular transportation in the nanoscale channels, as further confirmed by zero length column experiments. This work enriches our understanding of the anomalous diffusion family and provides fundamental insights into the mechanism inside confined systems.

Gating control effect facilitates excellent gas selectivity in a novel Na-SSZ-27 zeolite.

A novel Na-SSZ-27 zeolite was demonstrated to possess excellent H2/CO2 diffusion selectivity of more than 100. This investigation highlights the crucial effect of the "gating control" of the 8-ring windows on the separation, where sodium cations act as gates to selectively control the diffusion of CO2 and promote the selectivity for H2.

Synergistically enhance confined diffusion by continuum intersecting channels in zeolites.

In separation and catalysis applications, adsorption and diffusion are normally considered mutually exclusive. That is, rapid diffusion is generally accompanied by weak adsorption and vice versa. In this work, we analyze the anomalous loading-dependent mechanism of p-xylene diffusion in a newly developed zeolite called SCM-15. The obtained results demonstrate that the unique system of "continuum intersecting channels" (i.e., channels made of fused cavities) plays a key role in the diffusion process for the molecule-selective pathways. At low pressure, the presence of strong adsorption sites and intersections that provide space for molecule rotation facilitates the diffusion of p-xylene along the Z direction. Upon increasing the molecular uptake, the adsorbates move faster along the X direction because of the effect of continuum intersections in reducing the diffusion barriers and thus maintaining the large diffusion coefficient of the diffusing compound. This mechanism synergistically improves the diffusion in zeolites with continuum intersecting channels.

Serum protein complex profiling reveals heterogeneity of Balanced constitutional population in traditional Chinese medicine through blue native polyacrylamide gel electrophoresis.

BACKGROUND: Pulse-taking is widely used for diagnosis and treatment in traditional Chinese medicine (TCM), and protein complexes in serum perform various biological functions. The Balanced constitution is one of the major constitutions in TCM, people with Balanced constitution can also share some common characteristics with unbalanced constitution types. METHODS: Blue native polyacrylamide gel electrophoresis (BN-PAGE) was applied to the serum of 25 people with balanced constitutions. The patterns of the protein complexes could be recognized according to the number, molecular weight, and intensity of the gel bands. All of the individual bands from these patterns were cut and in-gel-digested with trypsin, followed by liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS) analysis for protein identification and biological function analysis. RESULTS: The protein complex patterns were roughly categorized as type A and B with high stability and reproducibility, and there were 15 and 16 gel bands in type A and type B, respectively. Among the 25 serum samples, 14 belonged to type A, and 11 belonged to type B. High-abundance proteins significantly decreased from 99% to 44% after BN-PAGE separation. The unique proteins in type A were mainly related to lipid metabolism, while the unique proteins in type B were involved in biological processes related to immune response and inflammatory regulation. The Qi-deficiency constitution converted score of type A was higher than that of type B, while the Damp-heat constitution converted score of type A was lower than that of type B. CONCLUSIONS: Our study provided an objective reference for diagnosis and prognosis, which might lay a foundation for establishing the characteristic protein complex spectra of all of the TCM constitutions.

CLOCK-BMAL1 regulates circadian oscillation of ventricular arrhythmias in failing hearts through ß1 adrenergic receptor.

The incidence of ventricular arrhythmias (VAs) in chronic heart failure (CHF) exhibits a notable circadian rhythm, for which the underlying mechanism has not yet been well defined. Thus, we aimed to investigate the role of cardiac core circadian genes on circadian VAs in CHF. First, a guinea pig CHF model was created by transaortic constriction. Circadian oscillation of core clock genes was evaluated by RT-PCR and was found to be unaltered in CHF (P > 0.05). Using programmed electrical stimulation in Langendorff-perfused failing hearts, we discovered that the CHF group exhibited increased VAs with greater incidence at CT3 compared to CT15 upon isoproterenol (ISO) stimulation. Circadian VAs was blunted by a ß1-AR-selective blocker rather than a ß2-AR-selective blocker. Circadian oscillation of ß1-AR was retained in CHF (P > 0.05) and a 4-h phase delay between ß1-AR and CLOCK-BMAL1 was recorded. Therefore, when CLOCK-BMAL1 was overexpressed using adenovirus infection, an induced overexpression of ß1-AR also ensued, which resulted in prolonged action potential duration (APD) and enhanced arrhythmic response to ISO stimulation in cardiomyocytes (P < 0.05). Finally, chromatin immunoprecipitation and luciferase assays confirmed that CLOCK-BMAL1 binds to the enhancer of ß1-AR gene and upregulates ß1-AR expression. Therefore, in this study, we discovered that CLOCK-BMAL1 regulates the expression of ß1-AR on a transcriptional level and subsequently modulates circadian VAs in CHF.

Differences in serum proteins in traditional Chinese medicine constitutional population: Analysis and verification.

Traditional Chinese medicine assigns individuals into different categories called "constitutions" to help guide the clinical treatment according to subjective physiologic, psychologic analyses, large-scale clinical observations, and epidemiologic studies. To further explore more objective expressions of constitutions, antibody microarrays were used to analyze the serologic protein profiles of two different constitutions, a balanced (or healthy) constitution (BC) and the dampness constitution (DC) comprising phlegm-dampness and damp-heat constitutions. The profiles of changing constitutions across time were also analyzed. Nineteen differentially expressed proteins between the two groups were identified, with known biologic functions involved in immunity and inflammation. This proteomic study may provide a biologic explanation why the BC is different than the dampness constitution.

QTc Interval Predicts Disturbed Circadian Blood Pressure Variation.

BACKGROUND: The relationship between electrocardiographic evaluation and circadian blood pressure (BP) variation in young and middle-aged hypertensive patients remains unknown. METHODS: A total of 171 hypertensive patients were included in the study. First, patients were divided into a young and middle-aged group and an elderly group. The two groups were then separately classified into three subgroups on the basis of circadian variation of BP as dippers, non-dippers and reverse-dippers. The electrocardiographic evaluation was calculated from 12-lead electrocardiography (ECG). RESULTS: QTc intervals were shortest in the dippers and longest in the reverse-dippers in the young and middle-aged group (QTc dipper: 416.53±18.37ms; non-dipper: 438.30±29.71ms; reverse-dipper: 444.93±25.47ms; for dipper vs non-dipper, and dipper vs reverse-dipper P<0.05). QTc interval was found to be an independent risk factor for the non-dipper BP pattern (Odds ratio 1.049; 95% CI 1.01-1.089; P=0.012) and reverse-dipper BP pattern (Odds ratio 1.051; 95% CI 1.007-1.098; P=0.023) in young and middle-aged hypertensive patients. No significant differences in other ECG parameters were found among the three subgroups in the young and middle-aged group. CONCLUSION: Our study suggested that QTc interval might serve as a risk factor for non-dipper BP pattern and reverse-dipper BP pattern in young and middle-aged hypertensive patients.

Heart rate acceleration and deceleration capacities associated with circadian blood pressure variation.

BACKGROUND: Heart rate acceleration and deceleration capacities are novel parameters that can quantify sympathetic and vagal modulation. However, how acceleration and deceleration capacities associated with circadian blood pressure (BP) variation remains unknown. METHODS: A total of 141 patients with essential hypertension were included in our study. Based on the nocturnal decline rate of systolic BP (SBP), patients were divided into two groups, as dippers and nondippers. Baseline demographic characteristics, ambulatory blood pressure monitoring (ABPM) parameters, Holter recordings, and echocardiographic parameters were collected. RESULTS: The absolute values of acceleration capacity (AC) (-7.75 [-8.45 ~ -6.3] ms vs. -6.6 [-8.25 ~ -5.2] ms, p = .047) and deceleration capacity (DC) (7.35 [6.1 ~ 8.1] ms vs. 6.3 [5.1 ~ 7.6] ms, p = .042) were significantly higher in dippers than in nondippers. By multivariate logistic regression analysis, left atrial diameter (LAd) was found to be an independent risk factor for nondipper status in acceleration capacity model (odds ratio 1.174, 95% confidence interval 1.019-1.354, p = .027) and deceleration model (odds ratio 1.146, 95% confidence interval 1.003-1.309, p = .045). Sleep SBP was positively correlated to acceleration capacity (r = .256, p = .002) and negatively correlated to deceleration capacity (r = -.194, p = .021). CONCLUSIONS: The absolute values of acceleration capacity and deceleration capacity were higher in patients with dipper hypertension than in patients with nondipper hypertension. However, acceleration and deceleration capacities were not independent risk factors for blunted BP variation. Sleep SBP seemed to be better correlated to the impairment of autonomic nervous system (ANS) function than other ABPM parameters.

ß-Arrestin2 regulates the rapid component of delayed rectifier K+ currents and cardiac action potential of guinea pig cardiomyocytes after adrenergic stimulation.

A decrease in the rapid component of delayed rectifier potassium current (IKr) during chronic heart failure (CHF) prolongs action potential (AP), and plays a key role in the pathogenesis of ventricular arrhythmias. ß-Arrestin2 has been shown to restore the inotropic reserve of ß-adrenergic regulation, but little or nothing is known about its effect on intrinsic channel. This study investigated the role of ß-arrestin2 in the regulation of cardiac hERG/IKr potassium channel and AP during chronic adrenergic stimulation. Single left ventricular myocytes were isolated from guinea pig heart, and were transfected with adenovirus encoding ß-arrestin2, or ß-arrestin2 siRNA or an empty adenovirus. Cell cultures containing 10 nM isoproterenol, 1 nM phenylephrine or vehicle alone (control medium) were electro-physiologically examined after 48 h of incubation. Action potential duration at 50 and 90 % of repolarization (APD50 and APD90) were measured using whole-cell patch-clamp recording. Sustained adrenergic stimulation significantly reduced the density of the IKr current (p < 0.001). ß-Arrestin2 expression in cell cultures treated with isoproterenol or phenylephrine was significantly downregulated after adrenergic stimulation (p < 0.001). Overexpression of ß-arrestin2 significantly attenuated isoproterenol or phenylephrine-induced reduction in IKr current. It also prevented the phenylephrine-induced prolongation of AP (p < 0.05 for APD50 and p < 0.001 for APD90), but did not significantly affect AP profile after exposure of the cardiomyocytes to isoproterenol (p > 0.05). Therefore, Increased levels of ß-Arrestin2 weaken dysregulation of IKr current and prevent excessive AP prolongation, making it an effective anti-arrhythmic strategy.