Fourth dose of microneedle array patch of SARS-CoV-2 S1 protein subunit vaccine elicits robust long-lasting humoral responses in mice.

The COVID-19 pandemic has underscored the pressing need for safe and effective booster vaccines, particularly in considering the emergence of new SARS-CoV-2 variants and addressing vaccine distribution inequalities. Dissolving microneedle array patches (MAP) offer a promising delivery method, enhancing immunogenicity and improving accessibility through the skin's immune potential. In this study, we evaluated a microneedle array patch-based S1 subunit protein COVID-19 vaccine candidate, which comprised a bivalent formulation targeting the Wuhan and Beta variant alongside a monovalent Delta variant spike proteins in a murine model. Notably, the second boost of homologous bivalent MAP-S1(WU + Beta) induced a 15.7-fold increase in IgG endpoint titer, while the third boost of heterologous MAP-S1RS09Delta yielded a more modest 1.6-fold increase. Importantly, this study demonstrated that the administration of four doses of the MAP vaccine induced robust and long-lasting immune responses, persisting for at least 80 weeks. These immune responses encompassed various IgG isotypes and remained statistically significant for one year. Furthermore, neutralizing antibodies against multiple SARS-CoV-2 variants were generated, with comparable responses observed against the Omicron variant. Overall, these findings emphasize the potential of MAP-based vaccines as a promising strategy to combat the evolving landscape of COVID-19 and to deliver a safe and effective booster vaccine worldwide.

Prognostic Implication of Platelet Reactivity According to Left Ventricular Systolic Dysfunction Status in Patients Treated With Drug-Eluting Stent Implantation: Analysis of the PTRG-DES Consortium.

BACKGROUND: Coronary artery disease patients undergoing percutaneous coronary intervention (PCI) often exhibit reduced left ventricular ejection fraction (LVEF). However, the impact of LV dysfunction status in conjunction with platelet reactivity on clinical outcomes has not been previously investigated. METHODS: From the multicenter PTRG-DES (Platelet function and genoType-Related long-term prognosis in DES-treated patients) consortium, the patients were classified as preserved-EF (PEF: LVEF ≥ 50%) and reduced-EF (REF: LVEF< 5 0%) group by echocardiography. Platelet reactivity was measured using VerifyNow P2Y12 assay and high platelet reactivity (HPR) was defined as PRU ≥ 252. The major adverse cardiac and cerebrovascular events (MACCEs) were a composite of death, myocardial infarction, stent thrombosis and stroke at 5 years after PCI. Major bleeding was defined as Bleeding Academic Research Consortium bleeding types 3-5. RESULTS: A total of 13,160 patients from PTRG-DES, 9,319 (79.6%) patients with the results of both PRU and LVEF were analyzed. The incidence of MACCE and major bleeding was higher in REF group as compared with PEF group (MACCEs: hazard ratio [HR] 2.17, P < 0.001, 95% confidence interval [CI] 1.85-2.55; major bleeding: HR 1.78, P < 0.001, 95% CI 1.39-2.78). The highest rate of MACCEs was found in patients with REF and HPR, and the difference between the groups was statistically significant (HR 3.14 in REF(+)/HPR(+) vs. PEF(+)/HPR(-) group, P < 0.01, 95% CI 2.51-3.91). The frequency of major bleeding was not associated with the HPR in either group. CONCLUSION: LV dysfunction was associated with an increased incidence of MACCEs and major bleeding in patients who underwent PCI. The HPR status further exhibited significant increase of MACCEs in patients with LV dysfunction in a large, real-world registry. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04734028.

Operando spectroscopic characterization of formamidinium lead iodide perovskite quantum dots for tracking electrochemical reactions.

Multidimensional ABX3 hybrid perovskites three-dimensionally confined dot-shaped structure demonstrate versatile potential to photoelectrochemical cells for water splitting, hydrogen generation, solar cells, and light-emitting diodes. To apply perovskite quantum dots (PQDs) to solar-driven chemistry and optoelectronic devices, understanding the photoinduced charge carrier dynamics of PQDs under electrochemical conditions or applied bias are important. In this study, the detailed transformation mechanism of formamidinium lead iodide perovskite quantum dots under electrochemical conditions was studied by tracking the products of the reaction through cyclic voltammetry, X-ray photoemission spectroscopy, in-situ UV-visible spectroelectrochemistry, etc. Through comprehensive characterizations, the mechanism of irreversible oxidative transformation of perovskite quantum dots was presented. This study provides deeper insight into the electrochemical behavior of PQDs for successful solar-driven chemistry and optoelectronic device applications.

Prevalence of stable coronary artery disease and its associated clinical factors among patients with chest pain and elevated cardiac troponin alone.

Cardiac troponin is a useful test for diagnosing cardiogenic causes in patients with chest pain. However, cardiac troponin levels are often elevated in patients with chest pain due to non-cardiac causes other than coronary artery disease. The purpose of this study was to investigate the prevalence of coronary artery disease (CAD) and its associated factors in patients with chest pain and elevated cardiac troponin I (cTnI). 104 patients (mean age, 65 ± 11 years; 60 [58%] men) who underwent coronary angiography (CAG) for chest pain and elevated cTnI levels were enrolled in this study. All patients had a normal CK-MB range and did not show any ischemic changes on electrocardiography or echocardiography. Patients were classified into two groups according to the presence of CAD (Group 1, n = 62) and the absence of CAD (Group 2, n = 42). Patients were classified into subgroups according to the presence (Group 2a, microvascular angina [MVA], n = 18) and absence (Group 2b, non-angina [NA], n = 25) of angina. CAD was diagnosed in 62 (60%) patients and MVA was suspected in 18 (17%) patients without CAD. Patients with CAD showed elevated blood pressure and slightly decreased heart rate. Diabetes mellitus was more prevalent in patients with CAD and patients without CAD (esp. with MVA) were more likely to be common drinkers. Increased relative wall thickness (RWT) and reduced E' velocity were associated with CAD. High-density lipoprotein (HDL) levels were reduced in patients with CAD and MVA but were higher in patients with NA. Lower HDL level was found to be independently associated with the presence of CAD. Elevated cTn1 levels without other evidence of myocardial ischemia are sufficient for performing CAG in patients with stable chest pain.

In Situ Confocal Fluorescence Lifetime Imaging of Nanopore Electrode Arrays with Redox Active Fluorogenic Amplex Red.

Direct imaging of electrochemical processes on electrode surfaces is a central part of understanding spatially heterogeneous electrochemical processes on the surfaces. Herein, we report a strategy for the spatially resolved imaging of local faradaic processes on nanoscale electrochemical interfaces. This strategy is based on fluorescence lifetime imaging microscopy (FLIM) with the use of Amplex Red as a fluorogenic redox probe. After verifying the capability of Amplex Red for fluorescence lifetime imaging, we demonstrated the turn-on FLIM-based imaging of faradaic processes on the electrochemical interfaces of different dimensions. In particular, we achieved spatially resolved visualization of the local electrochemical processes occurring on even nanopore electrode arrays as well as conventional microelectrodes, including disk-shaped ultramicroelectrodes and interdigitated array microelectrodes.

Review of History of Basic Principles of Burn Wound Management.

Thermal energy is an essential and useful resource to humans in modern society. However, a consequence of using heat carelessly is burns. Burn injuries have various causes, such as exposure to flame, radiation, electrical, and chemical sources. In this study, we reviewed the history of burn wound care while focusing on the basic principles of burn management. Through this review, we highlight the need for careful monitoring and customization when treating burn victims at each step of wound care, as their individual needs may differ. We also propose that future research should focus on nanotechnology-based skin grafts, as this is a promising area for further improvement in wound care.

Electrochemical Zero-Mode Waveguide Potential-Dependent Fluorescence of Glutathione Reductase at Single-Molecule Occupancy.

Understanding functional states of individual redox enzymes is important because electron-transfer reactions are fundamental to life, and single-enzyme molecules exhibit molecule-to-molecule heterogeneity in their properties, such as catalytic activity. Zero-mode waveguides (ZMW) constitute a powerful tool for single-molecule studies, enabling investigations of binding reactions up to the micromolar range due to the ability to trap electromagnetic radiation in zeptoliter-scale observation volumes. Here, we report the potential-dependent fluorescence dynamics of single glutathione reductase (GR) molecules using a bimodal electrochemical ZMW (E-ZMW), where a single-ring electrode embedded in each of the nanopores of an E-ZMW array simultaneously serves to control electrochemical potential and to confine optical radiation within the nanopores. Here, the redox state of GR is manipulated using an external potential control of the Au electrode in the presence of a redox mediator, methyl viologen (MV). Redox-state transitions in GR are monitored by correlating electrochemical and spectroscopic signals from freely diffusing MV/GR in 60 zL effective observation volumes at single GR molecule average pore occupancy, ⟨n⟩ ∼ 0.8. Fluorescence intensities decrease (increase) at reducing (oxidizing) potentials for MV due to the MV-mediated control of the GR redox state. The spectroelectrochemical response of GR to the enzyme substrate, i.e., glutathione disulfide (GSSG), shows that GSSG promotes GR oxidation via enzymatic reduction. The capabilities of E-ZMWs to probe spectroelectrochemical phenomena in zL-scale-confined environments show great promise for the study of single-enzyme reactions and can be extended to important technological applications, such as those in molecular diagnostics.

Role of electrochemical reactions in the degradation of formamidinium lead halide hybrid perovskite quantum dots.

Organic-inorganic hybrid perovskites are widely utilized in solar driven chemistry such as photocatalysis, hydrogen evolution, and oxygen reduction. Hybrid perovskites contain various components with high polarity and/or charge values, which undergo transformations due to ion exchange, photoinduced phase segregation, or ion migration. These variable characteristics make perovskites "soft materials". Meanwhile, optoelectronic devices often operate under electrochemical reactions in the presence of an electrical field. To examine the effect of this field on the material/photophysical properties of hybrid perovskites, hybrid FAPbBr3 (FA+: CH(NH2)2+) perovskite quantum dots (PQDs) were synthesized. In this study, we report the spectroelectrochemical investigation of the hybrid FAPbBr3 PQDs to understand the electrochemical stability and degradation process. We also found that the electrochemical condition played an important role in inducing defect-mediated oxidation/reduction reactions, changing the photophysical properties of hybrid PQDs, and causing their irreversible transformations to various lead halide plumbate complexes. These findings can help develop a strategy for enhancing the operational performance of PQDs for the solar driven chemistry.

Attenuation of ischemia-reperfusion injury by intracoronary chelating agent administration.

Ischemia-reperfusion (IR) injury accelerates myocardial injury sustained during the myocardial ischemic period and thus abrogates the benefit of reperfusion therapy in patients with acute myocardial infarction. We investigated the efficacy of intracoronary ethylenediaminetetraacetic acid (EDTA) administration as an adjunctive treatment to coronary intervention to reduce IR injury in a swine model. We occluded the left anterior descending artery for 1 h. From the time of reperfusion, we infused 50 mL of EDTA-based chelating agent via the coronary artery in the EDTA group and normal saline in the control group. IR injury was identified by myocardial edema on echocardiography. Tetrazolium chloride assay revealed that the infarct size was significantly lower in the EDTA group than in the control group, and the salvage percentage was higher. Electron microscopy demonstrated that the mitochondrial loss in the cardiomyocytes of the infarcted area was significantly lower in the EDTA group than in the control group. Echocardiography after 4 weeks showed that the remodeling of the left ventricle was significantly less in the EDTA group than in the control group: end-diastolic dimension 38.8 ± 3.3 mm vs. 43.9 ± 3.7 mm (n = 10, p = 0.0089). Left ventricular ejection fraction was higher in the EDTA group (45.3 ± 10.3 vs. 34.4 ± 11.8, n = 10, respectively, p = 0.031). In a swine model, intracoronary administration of an EDTA chelating agent reduced infarct size, mitochondrial damage, and post-infarct remodeling. This result warrants further clinical study evaluating the efficacy of the EDTA chelating agent in patients with ST-segment elevation myocardial infarction.

Enlarged left atrium and decreased left atrial strain are associated with atrial fibrillation in patients with hyperthyroidism irrespective of conventional risk factors.

The purpose of this study was to investigate factors associated with AF in patients with hyperthyroidism beyond heart failure (HF), coronary heart disease (CHD), or valvular diseases. A total of 136 patients (mean age, 52 ± 15 years; 86 [63%] female) who were diagnosed with hyperthyroidism for the first time were enrolled. Patients who had HF, CHD, or significant valvular diseases were excluded. Patients were classified into two groups according to the presence (group 1, n = 40) and absence of AF (group 2, n = 96). AF occurred in 40 (29%) patients and 23 (58%) of these patients showed paroxysmal AF. Among the symptoms of hyperthyroidism, the most common chief complaint was palpitation (30%). Advanced age, presence of prior cerebrovascular events, and presence of palpitations were associated with AF. Larger left atrial volume index (LAVI), increased left ventricular mass index, and decreased left ventricular ejection fraction (LVEF) and S' velocity were associated with AF. Among them, presence of palpitations and increased LAVI were independently associated with the occurrence of AF. In addition, strain analysis, decreased LA expansion index (EI), ejection fraction (EF), peak atrial longitudinal strain, contraction strain, and late diastolic strain rate (A sr) and systolic strain rate (S sr) were associated with the occurrence of AF and LAVI. Presence of palpitations and enlarged left atrium were associated with the occurrence of AF in patients with hyperthyroidism irrespective of conventional risk factors. Additional LA analysis revealed that decreased LA function was associated with AF and enlarged left atrium.

Vasodilator agents improve hemodialysis vascular access patency: A population-based study from Korea.

ABSTRACT: Vascular access (VA) failure is an important problem for patients undergoing hemodialysis, and maintaining VA patency is challenging. In this study, we used a nationwide database to investigate the effects of nitrate, as a vasodilator, on VA failure in hemodialysis patients.We investigated the Korean insurance claims data of hemodialysis patients who underwent angioplasty for VA failure between January 2012 and December 2017. The patients were divided into 2 groups: those not receiving vasodilator therapy (controls) and those receiving any vasodilator administration (vasodilator treatment, VDT). The primary endpoint was VA primary patency, defined as the time between arteriovenous dialysis access creation and the first percutaneous transluminal angioplasty (PTA).During the study period, a total of 6350 patients were recruited, 409 (6.4%) patients assigned to the VDT group and 5941 (93.6%) controls. PTA was performed in 998 patients (15.7%), including 8 in the VDT group and 990 controls. The VA site PTA rate was significantly lower in the VDT group (2.0%) than in the control group (16.7%, P < .001). In the subgroup analysis, the patency rates associated with the different vasodilators were similar (P = .736). All vasodilators, except molsidomine, improved the patency rate by approximately 20%.In this large national database study, vasodilator administration was associated with higher VA primary patency, compared with controls, in hemodialysis patients. VDT may have a beneficial effect on maintaining VA patency in patients undergoing hemodialysis.

Features of Patients Receiving Extracorporeal Membrane Oxygenation Relative to Cardiogenic Shock Onset: A Single-Centre Experience.

Background and Objectives: Extracorporeal membrane oxygenation (ECMO) can be helpful in patients with cardiogenic shock associated with myocardial infarction, and its early use can improve the patient survival rate. In this study, we report a mortality rate-difference analysis that examined the time and location of shock occurrence. Materials and Methods: We enrolled patients who underwent ECMO due to cardiogenic shock related to myocardial infarction and assigned them to either a pre- or post-admission shock group. The primary outcome was the 1-month mortality rate; a subgroup analysis was conducted to assess the effect of bailout ECMO. Results: Of the 113 patients enrolled, 67 (38 with pre-admission shock, 29 with post-admission shock) were analysed. Asystole was more frequently detected in the pre-admission shock group than in the post-admission group. In both groups, the commonest culprit lesion location was in the left anterior descending artery. Cardiopulmonary resuscitation was performed significantly more frequently and earlier in the pre-admission group. The 1-month mortality rate was significantly lower in the pre-admission group than in the post-admission group. Male sex and ECMO duration (≥6 days) were factors significantly related to the reduced mortality rate in the pre-admission group. In the subgroup analysis, the mortality rate was lower in patients receiving bailout ECMO than in those not receiving it; the difference was not statistically significant. Conclusions: ECMO application resulted in lower short-term mortality rate among patients with out-of-hospital cardiogenic shock onset than with in-hospital shock onset; early cardiopulmonary resuscitation and ECMO might be helpful in select patients.

Complications associated with the Rotarex® wire in a patient with peripheral artery disease.

The Rotarex® device is used for thrombectomy as well as atherectomy in patients with PAD. It is important to carefully consider the wire position of the Rotarex® device during the procedure. As possible as the wire should be located in a lesion-free area.

Characteristics and prognosis of patients with cryptogenic stroke and suggestive of patent foramen ovale.

AIMS: The purpose of this study were to identify the usefulness of screening for PFO using agitated saline echocardiography (ASE) and characteristics and prognosis of patients with suggestive of patent foramen ovale (PFO). METHODS: Three hundred three patients (mean age, 53 ± 9 years; 199 [66%] men) admitted with acute stroke or suspicion of stroke were included. Patients were classified into those with and without right-to-left shunt (RLS) according to the ASE results (positive ASE [n = 92] vs. negative ASE [n = 211]). Fifty-one out of ninety-two patients with positive ASE and twenty-one out of two hundred eleven patients with negative ASE underwent TEE with ASE to confirm PFO. RESULTS: Ninety-two were positive for ASE and thirty-six of the fifty-one patients who underwent TEE were confirmed as having PFO. Of the patients with RLS grade 1, 50% were diagnosed with PFO and all patients with RLS grade ≥ 2 were diagnosed with PFO. All patients with negative ASE had no PFO (sensitivity of 100% and specificity of 58%). Patients with positive ASE were younger, had a lower body mass, and a lower prevalence of hypertension. The positive ASE patients had a higher mean S' velocity and better diastolic function. Four of ninety-one patients with positive ASE and thirteen of one hundred seventy-seven showed recurrence of stroke and suspicion of stroke. CONCLUSION: Transthoracic ASE is a good method to screen for PFO. Patients with suggestive of PFO had lower risk factors, less atherosclerosis, and better cardiac performance.

Oligonucleotide-Based Reusable Electrochemical Silver(I) Sensor and Its Optimization via Probe Packing Density.

We report herein a selective, sensitive, and reusable electrochemical sensor for the detection of silver(I) ions. This sensor detects Ag+ through a structure-switching electrode-bound DNA by measuring the changes in the electron-transfer efficiency. A single-stranded DNA, featuring a methylene blue (MB)-tagged DNA hairpin structure, strategically provides selective binding for the silver-mediated coordination of cytosine-Ag+-cytosine complexes. The DNA-modified electrode produces a change in the electrochemical signal due to the redox current of the surface-confined MB tag. The "turn-on" signaling upon silver(I) ion binding could be attributed to a conformational change in the MB-tagged DNA from an open structure to a target-induced folding structure. Differential pulse voltammetry of the DNA-modified electrode showed that the MB reduction signal increased linearly with an increase in Ag+ concentrations in a range of 10-200 nM, with a detection limit of 10 nM. The structure-switching silver(I) ion sensor was amenable to regeneration by simply unfolding the electrode-bound MB-tagged DNA in 100 mM ethylenediaminetetraacetic acid, and it could be regenerated with no loss in signal gain upon subsequent silver(I) ion binding. We also demonstrated that by controlling the probe packing density on the electrode surface, the fabrication parameters can be varied to achieve optimal sensor performance.

Low-temperature fabrication of crystalline MnCoO spinel film on porous carbon paper for efficient oxygen evolution reaction.

Cubic MnxCo3-xO4 (x = 0-0.5) spinel nanocrystal thin films were fabricated on carbon fibre electrodes via one-step topotactic catalysis using Co(OH)2 nanosheets under aqueous and mild reaction conditions (<120 °C). The MnCo3O4 (Mn = 0.01)/CFP catalyst showed the best charge transport efficiency, exhibiting excellent OER activity and stability.

Clinical significance of high on-treatment platelet reactivity in patients with prolonged clopidogrel therapy.

BACKGROUND/AIMS: Prolonged dual antiplatelet therapy (DAPT) with aspirin and clopidogrel beyond 1 year has been shown to reduce ischemic events at the expense of increased bleeding. However, limited data are available on the clinical significance of platelet reactivity (PR) at 1 year. METHODS: We retrospectively identified 331 patients who underwent percutaneous coronary intervention (PCI) and assessed the on-clopidogrel PR using VerifyNow P2Y12 assay at 1 year in a single center. Two hundred eleven patients were on DAPT for > 1 year. The relationship between high on-treatment platelet reactivity (HPR) at 1 year and clinical outcomes beyond 1 year, as well as the longitudinal change in PR was analyzed. RESULTS: At 1 year, 135 (64%) patients showed HPR and 76 (36%) did not. There was a significant increase in ischemic endpoint events, including cardiovascular death, non-fatal myocardial infarction, and stroke/transient ischemic attack in patients with compared to without HPR at 1 year (hazard ratio [HR], 2.68; 95% confidence interval [CI], 1.06 to 6.77; p = 0.036). However, the incidence of any Bleeding Academic Research Consortium bleeding was significantly lower in the HPR group (HR, 0.11; 95% CI, 0.02 to 0.65; p = 0.015). In the longitudinal analysis, PR significantly decreased from post-load to 1 year after index PCI in the non-HPR group. Conversely, the HPR group showed high PR from baseline through 1 year. CONCLUSION: HPR at 1 year may be a useful surrogate for predicting ischemic and bleeding events in patients on prolonged DAPT. Patients with and without HPR at 1 year showed different patterns of longitudinal change in PR.

Changes in serum serotonin levels in patients with acute coronary syndrome and stable angina undergoing percutaneous coronary intervention.

OBJECTIVE: Activated platelets release serotonin, causing platelet aggregation and vasoconstriction. Serotonin levels were investigated in patients with acute coronary syndrome (ACS) and chronic stable angina (CSA) treated with percutaneous coronary intervention (PCI). METHODS: Consecutive patients undergoing PCI for either ACS or CSA were enrolled between July 2009 and April 2010. Patients were pre-treated with dual antiplatelet agents (aspirin and clopidogrel) before PCI. Serum serotonin levels, measured at baseline, pre- and post-PCI, and at 90 min, and 6, 12, 24 and 48 h following PCI, were compared between ACS and CSA groups. RESULTS: Sixty-three patients with ACS and 60 with CSA were included. Overall baseline characteristics were similar between the two groups. Serotonin levels at post-PCI (55.2 ± 120.0 versus 20.1 ± 24.0) and at peak (regardless of timepoint; 94.0 ± 170.9 versus 38.8 ± 72.3) were significantly higher in the ACS versus CSA group. At 90 min and 6, 24 and 48 h post-PCI, serum serotonin was numerically, but not significantly, higher in patients with ACS. Serotonin levels fluctuated in both groups, showing an initial rise and fall, rebound at 24 h and drop at 48 h post-PCI. CONCLUSIONS: In patients undergoing PCI, serum serotonin was more elevated in patients with ACS than those with CSA, suggesting the need for more potent and sustained platelet inhibition, particularly in patients with ACS.

Single Entity Electrochemistry in Nanopore Electrode Arrays: Ion Transport Meets Electron Transfer in Confined Geometries.

Electrochemical measurements conducted in confined volumes provide a powerful and direct means to address scientific questions at the nexus of nanoscience, biotechnology, and chemical analysis. How are electron transfer and ion transport coupled in confined volumes and how does understanding them require moving beyond macroscopic theories? Also, how do these coupled processes impact electrochemical detection and processing? We address these questions by studying a special type of confined-volume architecture, the nanopore electrode array, or NEA, which is designed to be commensurate in size with physical scaling lengths, such as the Debye length, a concordance that offers performance characteristics not available in larger scale structures.The experiments described here depend critically on carefully constructed nanoscale architectures that can usefully control molecular transport and electrochemical reactivity. We begin by considering the experimental constraints that guide the design and fabrication of zero-dimensional nanopore arrays with multiple embedded electrodes. These zero-dimensional structures are nearly ideal for exploring how permselectivity and unscreened ion migration can be combined to amplify signals and improve selectivity by enabling highly efficient redox cycling. Our studies also highlight the benefits of arrays, in that molecules escaping from a single nanopore are efficiently captured by neighboring pores and returned to the population of active redox species being measured, benefits that arise from coupling ion accumulation and migration. These tools for manipulating redox species are well-positioned to explore single molecule and single particle electron transfer events through spectroelectrochemistry, studies which are enabled by the electrochemical zero-mode waveguide (ZMW), a special hybrid nanophotonic/nanoelectronic architecture in which the lower ring electrode of an NEA nanopore functions both as a working electrode to initiate electron transfer reactions and as the optical cladding layer of a ZMW. While the work described here is largely exploratory and fundamental, we believe that the development of NEAs will enable important applications that emerge directly from the unique coupled transport and electron-transfer capabilities of NEAs, including in situ molecular separation and detection with external stimuli, redox-based electrochemical rectification in individually encapsulated nanopores, and coupled sorters and analyzers for nanoparticles.