Impact of Impedance Levels on Recording Quality in Flexible Neural Probes.

Flexible neural probes are attractive emerging technologies for brain recording because they can effectively record signals with minimal risk of brain damage. Reducing the electrode impedance of the probe before recording is a common practice of many researchers. However, studies investigating the impact of low impedance levels on high-quality recordings using flexible neural probes are lacking. In this study, we electrodeposited Pt onto a commercial flexible polyimide neural probe and investigated the relationship between the impedance level and the recording quality. The probe was inserted into the brains of anesthetized mice. The electrical signals of neurons in the brain, specifically the ventral posteromedial nucleus of the thalamus, were recorded at impedance levels of 50, 250, 500 and 1000 kΩ at 1 kHz. The study results demonstrated that as the impedance decreased, the quality of the signal recordings did not consistently improve. This suggests that extreme lowering of the impedance may not always be advantageous in the context of flexible neural probes.

Differential effect of cancer-associated fibroblast-derived extracellular vesicles on cisplatin resistance in oral squamous cell carcinoma via miR-876-3p.

Rationale: Platinum-based chemotherapy is commonly used for treating solid tumors, but drug resistance often limits its effectiveness. Cancer-associated fibroblast (CAF)-derived extracellular vesicle (EV), which carry various miRNAs, have been implicated in chemotherapy resistance. However, the molecular mechanism through which CAFs modulate cisplatin resistance in oral squamous cell carcinoma (OSCC) is not well understood. We employed two distinct primary CAF types with differential impacts on cancer progression: CAF-P, representing a more aggressive cancer-promoting category, and CAF-D, characterized by properties that moderately delay cancer progression. Consequently, we sought to investigate whether the two CAF types differentially affect cisplatin sensitivity and the underlying molecular mechanism. Methods: The secretion profile was examined by utilizing an antibody microarray with conditioned medium obtained from the co-culture of OSCC cells and two types of primary CAFs. The effect of CAF-dependent factors on cisplatin resistance was investigated by utilizing conditioned media (CM) and extracellular vesicle (EVs) derived from CAFs. The impacts of candidate genes were confirmed using gain- and loss-of-function analyses in spheroids and organoids, and a mouse xenograft. Lastly, we compared the expression pattern of the candidate genes in tissues from OSCC patients exhibiting different responses to cisplatin. Results: When OSCC cells were cultured with conditioned media (CM) from the two different CAF groups, cisplatin resistance increased only under CAF-P CM. OSCC cells specifically expressed insulin-like growth factor binding protein 3 (IGFBP3) after co-culture with CAF-D. Meanwhile, IGFBP3-knockdown OSCC cells acquired cisplatin resistance in CAF-D CM. IGFBP3 expression was promoted by GATA-binding protein 1 (GATA1), a transcription factor targeted by miR-876-3p, which was enriched only in CAF-P-derived EV. Treatment with CAF-P EV carrying miR-876-3p antagomir decreased cisplatin resistance compared to control miRNA-carrying CAF-P EV. On comparing the staining intensity between cisplatin-sensitive and -insensitive tissues from OSCC patients, there was a positive correlation between IGFBP3 and GATA1 expression and cisplatin sensitivity in OSCC tissues from patients. Conclusion: These results provide insights for overcoming cisplatin resistance, especially concerning EVs within the tumor microenvironment. Furthermore, it is anticipated that the expression levels of GATA1 and miR-876-3p, along with IGFBP3, could aid in the prediction of cisplatin resistance.

Impedance-based polymer microneedle patch sensor for continuous interstitial fluid glucose monitoring.

Early detection and effective blood glucose control are critical for preventing and managing diabetes-related complications. Conventional glucometers provide point-in-time measurements but are painful and cannot facilitate continuous monitoring. Continuous glucose monitoring systems are comfortable but face challenges in terms of accuracy, cost, and sensor lifespan. This study aimed to develop a microneedle-based sensor patch for minimally invasive, painless, and continuous glucose monitoring in the interstitial fluid to address these limitations. Experimental results confirm painless and minimally invasive penetration of the skin tissue with cylindrical microneedles (3 × 3 array) to a depth of approximately 520 µm with minimal loading. The microneedle sensors fabricated with precision using the complementary metal-oxide semiconductor process were immobilized with glucose oxidase, as confirmed through phase angle analysis. Long-term tests confirmed the effective operation of the sensor for up to seven days. Glucose concentrations determined from the fitted concentration-impedance curves correlated well with those measured using commercial glucometers, indicating the reliability and precision of the microneedle sensor. The flexible and minimally invasive sensor developed in this study facilitates painless and continuous glucose monitoring.

Periodontitis promotes bacterial extracellular vesicle-induced neuroinflammation in the brain and trigeminal ganglion.

Gram-negative bacteria derived extracellular vesicles (EVs), also known as outer membrane vesicles, have attracted significant attention due to their pathogenic roles in various inflammatory diseases. We recently demonstrated that EVs secreted by the periodontopathogen Aggregatibacter actinomycetemcomitans (Aa) can cross the blood-brain barrier (BBB) and that their extracellular RNA cargo can promote the secretion of proinflammatory cytokines, such as IL-6 and TNF-α, in the brain. To gain more insight into the relationship between periodontal disease (PD) and neuroinflammatory diseases, we investigated the effect of Aa EVs in a mouse model of ligature-induced PD. When EVs were administered through intragingival injection or EV-soaked gel, proinflammatory cytokines were strongly induced in the brains of PD mice. The use of TLR (Toll-like receptor)-reporter cell lines and MyD88 knockout mice confirmed that the increased release of cytokines was triggered by Aa EVs via TLR4 and TLR8 signaling pathways and their downstream MyD88 pathway. Furthermore, the injection of EVs through the epidermis and gingiva resulted in the direct retrograde transfer of Aa EVs from axon terminals to the cell bodies of trigeminal ganglion (TG) neurons and the subsequent activation of TG neurons. We also found that the Aa EVs changed the action potential of TG neurons. These findings suggest that EVs derived from periodontopathogens such as Aa might be involved in pathogenic pathways for neuroinflammatory diseases, neuropathic pain, and other systemic inflammatory symptoms as a comorbidity of periodontitis.

Vertical Conductivity and Topography in Electrostrictive Germanium Sulfide Microribbon via Conductive Atomic Force Microscopy.

Layered group IV monochalcogenides are two-dimensional (2D) semiconducting materials with unique crystal structures and novel physical properties. Here, we report the growth of single crystalline GeS microribbons using the chemical vapor transport process. By using conductive atomic force microscopy, we demonstrated that the conductive behavior in the vertical direction was mainly affected by the Schottky barriers between GeS and both electrodes. Furthermore, we found that the topographic and current heterogeneities were significantly different with and without illumination. The topographic deformation and current enhancement were also predicted by our density functional theory (DFT)-based calculations. Their local spatial correlation between the topographic height and current was established. By virtue of 2D fast Fourier transform power spectra, we constructed the holistic spatial correlation between the topographic and current heterogeneity that indicated the diminished correlation with illumination. These findings on layered GeS microribbons provide insights into the conductive and topographic behaviors in 2D materials.

Use of Bacterial Extracellular Vesicles for Gene Delivery to Host Cells.

Extracellular vesicles (EVs), which are nanosized membranous particles secreted from both prokaryotic and eukaryotic cells, can deliver various biological molecules, such as nucleic acids, proteins, and lipids, into recipient cells. However, contrary to what is known about eukaryotic EVs, whether bacterial EVs (bEVs) can be used as transporters for bioactive molecules is becoming a hot area of research. In this study, we electroporated enhanced green fluorescent protein (EGFP) genes and precursor microRNA of Cel-miR-39 (pre-Cel-miR-39) from isolated bEVs of Escherichia coli and Lactobacillus reuteri. The EGFP plasmid, synthetic EGFP RNA, and pre-Cel-miR-39 were successfully delivered into the murine microglial BV2 cells via bEVs. PCR and confocal microscopy analysis confirmed the transfer of the EGFP plasmid and RNA. The bEV-delivered exogenous pre-Cel-miR-39 was further processed into the mature form of Cel-miR-39; its incorporation into Ago2-a major component of the RNA-induced silencing complex-was assessed using RNA-immunoprecipitation-PCR. Taken together, bEVs can be used as vehicles to deliver genetic materials and for novel biotechnological applications, such as gene transfer and mRNA vaccines.

Enhanced osteogenic differentiation of mesenchymal stem cells by surface lithium modification in a sandblasted/acid-etched titanium implant.

This study investigated the osteogenesis-related cell functions of osteoprogenitor cells modulated by surface chemistry modification using lithium (Li) ions in a current clinical oral implant surface in order to gain insights into the future development of titanium (Ti) implants with enhanced osteogenic capacity. Wet chemical treatment was performed to modify a sandblasted/acid-etched (SLA) Ti implant surface using Li ions. The osteogenesis-related cell response to the surface Li ion-modified SLA sample was evaluated using two kinds of murine bone marrow stem cells, bipotent ST2 cells and primary multipotent mesenchymal stem cells (MSCs). The modified surface exhibited the formation of an Li-containing Ti oxide layer with plate-like nanostructures. The Li-incorporated surface enhanced early cellular events, including spreading, focal adhesion formation and integrin mRNA expression (α2, α5, αv and ß3), and accelerated osteogenic differentiation of bipotent ST2 cells compared with unmodified SLA surface. Surface Li modification significantly increased GSK-3ß phosphorylation and suppressed ß-catenin phosphorylation, and promoted the subsequent osteogenic differentiation of primary MSCs. These results indicate that surface chemistry modification of SLA implants by wet chemical treatment with Li ions induces a more favorable osseointegration outcome through the promotion of the osteogenic differentiation of bone marrow MSCs via the positive regulation of GSK-3ß and ß-catenin activity.

Differential expression and sorting of exosomal microRNAs upon activation of the human monocyte-like cell line U937.

Extracellular vesicles such as exosomes in eukaryotes have drawn scrutiny due to their various roles in intercellular communication. Small RNAs, including microRNAs (miRNAs), are more abundant among the cargo of exosomes than other RNA types. MiRNAs loaded in secreted exosomes (or extracellular microRNAs) can be transported to recipient cells and may play a regulatory role although the miRNA loading (or sorting) mechanism in exosomes has not been clearly elucidated. Therefore, this study analyzed exosomal miRNA sequencing data from human myeloid U937 cells treated with phorbol 12-myristate 13-acetate (PMA) and compared it with data from PMA-untreated U937 cells. MiR-24 was highly expressed in the cytoplasm and exosomes of PMA-treated U937 cells. Also, miRNA pull-down and mass spectrophotometry analysis of PMA-treated U937 cells revealed that miR-24 was specifically associated with α-tubulin and hnRNP-E1 proteins. Furthermore, exosomal miR-24 was dramatically reduced when those proteins were inactivated with siRNAs, whereas cellular miR-24 showed no significant effect. We conclude that miR-24 is transported into exosomes from activated macrophages with the support of α-tubulin and hnRNP-E1.

Bottom-Up Evolution of Diamond-Graphite Hybrid Two-Dimensional Nanostructure: Underlying Picture and Electrochemical Activity.

The diamond-graphite hybrid thin film with low-dimensional nanostructure (e.g., nitrogen-included ultrananocrystalline diamond (N-UNCD) or the alike), has been employed in many impactful breakthrough applications. However, the detailed picture behind the bottom-up evolution of such intriguing carbon nanostructure is far from clarified yet. Here, the authors clarify it, through the concerted efforts of microscopic, physical, and electrochemical analyses for a series of samples synthesized by hot-filament chemical vapor deposition using methane-hydrogen precursor gas, based on the hydrogen-dependent surface reconstruction of nanodiamond and on the substrate-temperature-dependent variation of the growth species (atomic hydrogen and methyl radical) concentration near substrate. The clarified picture provides insights for a drastic enhancement in the electrochemical activities of the hybrid thin film, concerning the detection of important biomolecule, that is, ascorbic acid, uric acid, and dopamine: their limits of detections are 490, 35, and 25 nm, respectively, which are among the best of the all-carbon thin film electrodes in the literature. This work also enables a simple and effective way of strongly enhancing AA detection.

Targeting integrated epigenetic and metabolic pathways in lethal childhood PFA ependymomas.

Childhood posterior fossa group A ependymomas (PFAs) have limited treatment options and bear dismal prognoses compared to group B ependymomas (PFBs). PFAs overexpress the oncohistone-like protein EZHIP (enhancer of Zeste homologs inhibitory protein), causing global reduction of repressive histone H3 lysine 27 trimethylation (H3K27me3), similar to the oncohistone H3K27M. Integrated metabolic analyses in patient-derived cells and tumors, single-cell RNA sequencing of tumors, and noninvasive metabolic imaging in patients demonstrated enhanced glycolysis and tricarboxylic acid (TCA) cycle metabolism in PFAs. Furthermore, high glycolytic gene expression in PFAs was associated with a poor outcome. PFAs demonstrated high EZHIP expression associated with poor prognosis and elevated activating mark histone H3 lysine 27 acetylation (H3K27ac). Genomic H3K27ac was enriched in PFAs at key glycolytic and TCA cycle­related genes including hexokinase-2 and pyruvate dehydrogenase. Similarly, mouse neuronal stem cells (NSCs) expressing wild-type EZHIP (EZHIP-WT) versus catalytically attenuated EZHIP-M406K demonstrated H3K27ac enrichment at hexokinase-2 and pyruvate dehydrogenase, accompanied by enhanced glycolysis and TCA cycle metabolism. AMPKα-2, a key component of the metabolic regulator AMP-activated protein kinase (AMPK), also showed H3K27ac enrichment in PFAs and EZHIP-WT NSCs. The AMPK activator metformin lowered EZHIP protein concentrations, increased H3K27me3, suppressed TCA cycle metabolism, and showed therapeutic efficacy in vitro and in vivo in patient-derived PFA xenografts in mice. Our data indicate that PFAs and EZHIP-WT­expressing NSCs are characterized by enhanced glycolysis and TCA cycle metabolism. Repurposing the antidiabetic drug metformin lowered pathogenic EZHIP, increased H3K27me3, and suppressed tumor growth, suggesting that targeting integrated metabolic/epigenetic pathways is a potential therapeutic strategy for treating childhood ependymomas.

Overexpression of Lin28a Aggravates Psoriasis-Like Phenotype by Regulating the Proliferation and Differentiation of Keratinocytes.

PURPOSE: Psoriasis is a common and well-studied autoimmune skin disease, which is characterized by plaques. The formation of psoriasis plaques occurs through the hyperproliferation and abnormal differentiation of keratinocytes, infiltration of numerous immune cells into the dermis, increased subepidermal angiogenesis, and various autoimmune-associated cytokines and chemokines. According to previous research, Lin28 regulates the let-7 family, and let-7b is associated with psoriasis. However, the link between Lin28 and psoriasis is unclear. In this study, an association was identified between Lin28a and psoriasis progression, which promoted the pathological characteristic of psoriasis in epidermal keratinocytes. PATIENTS AND METHODS: This study aims to investigate the role of Lin28a and its underlying mechanism in psoriasis through in vivo and in vitro models, which include the Lin28a-overexpressing transgenic (TG) mice and Lin28a-overexpressing human keratinocyte (HaCaT) cell lines, respectively. RESULTS: In vivo and in vitro results revealed that overexpression of Lin28a downregulated microRNA let-7 expression levels and caused hyperproliferation and abnormal differentiation in keratinocytes. In imiquimod (IMQ)-induced psoriasis-like inflammation, Lin28a overexpressing transgenic (TG) mice exhibited more severe symptoms of psoriasis. CONCLUSION: Mechanistically, Lin28a exacerbated psoriasis-like inflammation through the activation of the extracellular-signal-regulated kinase (ERK) and signal transducer and activator of transcription 3 signaling (STAT 3) by targeting proinflammatory cytokine interleukin-6 (IL-6).

Differential Angiogenic Potential of 3-Dimension Spheroid of HNSCC Cells in Mouse Xenograft.

The experimental animal model is still essential in the development of new anticancer drugs. We characterized mouse tumors derived from two-dimensional (2D) monolayer cells or three-dimensional (3D) spheroids to establish an in vivo model with highly standardized conditions. Primary cancer-associated fibroblasts (CAFs) were cultured from head and neck squamous cell carcinoma (HNSCC) tumor tissues and co-injected with monolayer cancer cells or spheroids into the oral mucosa of mice. Mice tumor blood vessels were stained, followed by tissue clearing and 3D Lightsheet fluorescent imaging. We compared the effect of exosomes secreted from 2D or 3D culture conditions on the angiogenesis-related genes in HNSCC cells. Our results showed that both the cells and spheroids co-injected with primary CAFs formed tumors. Interestingly, vasculature was abundantly distributed inside the spheroid-derived but not the monolayer-derived mice tumors. In addition, cisplatin injection more significantly decreased spheroid-derived but not monolayer-derived tumor size in mice. Additionally, exosomes isolated from co-culture media of FaDu spheroid and CAF upregulated angiogenesis-related genes in HNSCC cells as compared to exosomes from FaDu cell and CAF co-culture media under in vitro conditions. The mouse tumor xenograft model derived from 3D spheroids of HNSCC cells with primary CAFs is expected to produce reliable chemotherapy drug screening results given the robust angiogenesis and lack of necrosis inside tumor tissues.

Is Self-Determined Motivation a Useful Agent to Overcome Perceived Exercise Barriers in Patients With Type 2 Diabetes Mellitus?

Background: Devising a program to increase physical activity (PA)/exercise behavior in patients with type 2 diabetes mellitus (T2DM) can meet with limited effectiveness in real-world settings because of the variety of barriers to PA/exercise that individuals need to overcome. An alternative approach is to explore whether targeting motivation as a facilitator may be effective to increase PA/exercise. This study aimed to understand attitudes toward perceived barriers to PA/exercise by examining individual levels of motivation, grounded on self-determination theory, in patients with T2DM. Methods: This study used an integrated approach combining qualitative and quantitative analysis. Sixteen patients with T2DM were grouped (n = 8 for each group) into either a higher self-motivation (HSM) or lower self-motivation (LSM) group via the Relative Autonomy Index. Thematic and deductive analysis were used to identify attitudes based on ten preconceived barrier themes: apathy, dislike, no priority, lack of support, health problems, lack of knowledge, unfavorable environment, tiredness, lack of time, and financial constraints. Quantitative analysis was to assess statistical differences in the volume of PA/exercise across the two groups, and a mixed-methods analysis was employed to highlight unique cases. Results: Patients in the HSM group expressed positive attitudes toward barriers to PA/exercise, while patients in the LSM group expressed a greater degree of hindrance. Although regular PA/exercise is necessary for T2DM management, patients with LSM considered PA/exercise a lesser priority displaying negative attitudes such as apathy and dislike. Conversely, patients with HSM placed greater emphasis on the benefits of PA/exercise regardless of apathy and dislike. Lack of time and health problems were commonly reported in both groups. The volume of PA/exercise corresponded to motivation levels, but there were some unique cases which arose from active commuting habits and severe health problems. Conclusion: These findings provide insights on how attitudes to perceived barriers to PA/exercise differ by levels of motivation. One insight was that examining motivation should be an essential consideration when designing practical strategies to overcome PA/exercise barriers in patients with T2DM. Lack of time and health problems exist regardless of motivation levels. Future research requires a tailored approach to managing barriers to PA/exercise in patients with T2DM.

Vertical Nanowire Electrode Array for Enhanced Neurogenesis of Human Neural Stem Cells via Intracellular Electrical Stimulation.

Extracellular electrical stimulation (ES) can provide electrical potential from outside the cell membrane, but it is often ineffective due to interference from external factors such as culture medium resistance and membrane capacitance. To address this, we developed a vertical nanowire electrode array (VNEA) to directly provide intracellular electrical potential and current to cells through nanoelectrodes. Using this approach, the cell membrane resistivity and capacitance could be excluded, allowing effective ES. Human fetal neural stem cells (hfNSCs) were cultured on the VNEA for intracellular ES. Combining the structural properties of VNEA and VNEA-mediated ES, transient nanoscale perforation of the electrode was induced, promoting cell penetration and delivering current to the cell. Intracellular ES using VNEA improved the neuronal differentiation of hfNSCs more effectively than extracellular ES and facilitated electrophysiological functional maturation of hfNSCs because of the enhanced voltage-dependent ion-channel activity. The results demonstrate that VNEA with advanced nanoelectrodes serves as a highly effective culture and stimulation platform for stem-cell neurogenesis.

Cancer-Associated Fibroblast Subgroups Showing Differential Promoting Effect on HNSCC Progression.

Background: The critical effect of the tumor microenvironment on cancer progression is well recognized. Recent research suggests that the cancer-promoting properties of the tumor stroma may be attributed to fibroblasts. However, the effect of cancer-associated fibroblast (CAF) on the progression of head and neck squamous cell carcinoma (HNSCC) is not well known. Methods: From the immunohistochemical analysis of head and neck squamous cell carcinoma (HNSCC) tissues, we divided CAF into two groups depending on the presence or absence of a well-demarcated boundary between epithelial cancer cells and the surrounding extracellular matrix (ECM). Primary culture of CAF was performed, followed by co-transplantation with HNSCC cells into mice oral mucosa, and the tumorigenesis was compared. The mRNA expression patterns between these two CAF groups were compared using DNA microarray analysis. Results: CAFs from cancer tissues that showed no demarcation between ECM and epithelial cancer cells (CAF-Promote) tended to stimulate Matrigel invasion of HNSCC cells. Conversely, CAFs from cancer tissues that showed a boundary with epithelial cancer cells (CAF-Delay) caused no remarkable increase in Matrigel invasion. Compared with CAF-P, CAF-D is less effective in promoting FaDu tumorigenicity in the mouse model. In DNA microarray analysis, COL3A1 and COL6A6 showed particularly high expression in the CAF-D group. Conclusions: These cancer stroma-derived collagen proteins might delay the HNSCC progression. These findings are expected to provide vital information for predicting HNSCC prognosis and developing drug targets in the future.

Phase-coherent transport in trigonal gallium nitride nanowires.

Gallium nitride nanowires (GaN NWs) with triangular cross-section exhibit universal conductance fluctuations (UCF) originating from the quantum interference of electron wave functions in the NWs. The amplitude of UCF is inversely proportional to the applied bias current. The bias dependence of UCF, combined with temperature dependence of the resistance suggests that phase coherent transport dominates over normal transport in GaN NWs. A unique temperature dependence of phase-coherent length and fluctuation amplitude is associated with inelastic electron-electron scattering in NWs. The phase-coherence length extracted from the UCF is as large as 400 nm at 1.8 K, and gradually decreases as temperature increases up to 60 K.

Delivery of Periodontopathogenic Extracellular Vesicles to Brain Monocytes and Microglial IL-6 Promotion by RNA Cargo.

Gram-negative bacterial extracellular vesicles (EVs), also known as outer membrane vesicles (OMVs), are secreted from bacterial cells and have attracted research attention due to their role in cell-to-cell communication. During OMV secretion, a variety of cargo such as extracellular RNA (exRNA) is loaded into the OMV. The involvement of exRNAs from a range of bacteria has been identified in several diseases, however, their mechanism of action has not been elucidated. We have recently demonstrated that OMVs secreted by the periodontopathogen Aggregatibacter actinomycetemcomitans can cross the blood-brain barrier (BBB) and that its exRNA cargo could promote the secretion of proinflammatory cytokines in the brain. However, it was unclear whether the brain immune cells could actually take up bacterial OMVs, which originate outside of the brain, in an appropriate immune response. In the present study, using monocyte-specific live CX3CR1-GFP mice, we visualized OMV-colocalized meningeal macrophages and microglial cells into which bacterial OMVs had been loaded and intravenously injected through tail veins. Our results suggested that meningeal macrophages uptake BBB-crossed OMVs earlier than do cortex microglia. BV2 cells (a murine microglia cell line) and exRNAs were also visualized after OMV treatment and their proinflammatory cytokine levels were observed. Interleukin (IL)-6 and NF-κB of BV2 cells were activated by A. actinomycetemcomitans exRNAs but not by OMV DNA cargo. Altogether, these findings indicate that OMVs can successfully deliver exRNAs into brain monocyte/microglial cells and cause neuroinflammation, implicating a novel pathogenic mechanism in neuroinflammatory diseases.

Disaggregation of Amyloid-ß Plaques by a Local Electric Field Generated by a Vertical Nanowire Electrode Array.

The aggregation and accumulation of amyloid-ß (Aß) peptides is a characteristic pathology for Alzheimer's disease (AD). Although noninvasive therapies involving stimulation by electric field (EF) have been reported, the efficiency of Aß disaggregation needs to be further improved for this strategy to be used in clinical settings. In this study, we show that an electrode based on a vertical nanowire electrode array (VNEA) is far more superior to a typical flat-type electrode in disaggregating Aß plaques. The enhanced disaggregation efficiency of VNEA is due to the formation of high-strength local EF between the nanowires, as verified by in silico and empirical evidence. Compared with those of the flat electrode, the simulation data revealed that 19.8-fold and 8.8-fold higher EFs are generated above and between the nanowires, respectively. Moreover, empirical cyclic voltammetry data demonstrated that VNEA had a 2.7-fold higher charge capacity than the flat electrode; this is associated with the higher surface area of VNEA. The conformational transition of Aß peptides between the ß-sheet and α-helix could be sensitively monitored in real time by the newly designed in situ circular dichroism instrument. This highly efficient EF-configuration of VNEA will lower the stimulation power for disaggregating the Aß plaques, compared to that of other existing field-mediated modulation systems. Considering the complementary metal-oxide-semiconductor-compatibility and biocompatible strength of the EF for perturbing the Aß aggregation, our study could pave the way for the potential use of electric stimulation devices for in vivo therapeutic application as well as scientific studies for AD.