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Despite clinical data stretching over millennia, the neurobiological basis of the effectiveness of acupuncture in treating diseases of the central nervous system has remained elusive. Here, using an established model of acupuncture treatment in Parkinson's disease (PD) model mice, we show that peripheral acupuncture stimulation activates hypothalamic melanin-concentrating hormone (MCH) neurons via nerve conduction. We further identify two separate neural pathways originating from anatomically and electrophysiologically distinct MCH neuronal subpopulations, projecting to the substantia nigra and hippocampus, respectively. Through chemogenetic manipulation specifically targeting these MCH projections, their respective roles in mediating the acupuncture-induced motor recovery and memory improvements following PD onset are demonstrated, as well as the underlying mechanisms mediating recovery from dopaminergic neurodegeneration, reactive gliosis, and impaired hippocampal synaptic plasticity. Collectively, these MCH neurons constitute not only a circuit-based explanation for the therapeutic effectiveness of traditional acupuncture, but also a potential cellular target for treating both motor and non-motor PD symptoms.
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Excessive neutrophil infiltration into the tumor microenvironment (TME) is an important factor that contributes to tumor overgrowth and limited immunotherapy efficacy. Neutrophils activate various receptors involved in tumor progression, while suppressing the infiltration and activity of cytotoxic T cells and creating optimal conditions for tumor growth. Therefore, the appropriate control of neutrophil infiltration is an effective strategy for tumor treatment. In the present study, 1-palmitoyl-2-linoleoyl-3-acetyl-rac-glycerol (PLAG) inhibited tumor overgrowth by suppressing excessive neutrophil infiltration, resulting in >74.97â¯% reduction in tumor size in a Lewis lung carcinoma (LLC-1) mouse model. All subjects in the positive control group died during the 90-day survival period, whereas only four subjects in the PLAG treatment group survived. PLAG had a significantly higher tumor growth inhibitory effect and survival rate than other neutrophil infiltration-targeting inhibitors (e.g., Navarixin, lymphocyte antigen 6 complex locus G6D antibody [aLy6G]). The ability of PLAG to regulate neutrophil infiltration and inhibit tumor growth depends on thioredoxin-interacting protein (TXNIP). In tumors lacking TXNIP expression, PLAG failed to control neutrophil infiltration and infiltration-related factor release, and the inhibitory effect of PLAG on tumor growth was reduced. PLAG-mediated inhibition of neutrophil infiltration enhances the efficacy of immune checkpoint inhibitors (ICIs), increasing the antitumor efficacy and survival rate by 30â¯%. In conclusion, PLAG could be a novel alternative to anti-tumor drugs that effectively targets excessive neutrophil infiltration into cancer tissues.
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Carcinoma Pulmonar de Lewis , Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Ratones Endogámicos C57BL , Infiltración Neutrófila , Microambiente Tumoral , Animales , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/inmunología , Carcinoma Pulmonar de Lewis/tratamiento farmacológico , Carcinoma Pulmonar de Lewis/patología , Carcinoma Pulmonar de Lewis/inmunología , Ratones , Infiltración Neutrófila/efectos de los fármacos , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Pulmón de Células no Pequeñas/inmunología , Microambiente Tumoral/efectos de los fármacos , Diglicéridos/farmacología , Línea Celular Tumoral , Neutrófilos/efectos de los fármacos , Neutrófilos/inmunología , Neutrófilos/metabolismo , Modelos Animales de Enfermedad , Masculino , Antineoplásicos/farmacología , GlicéridosRESUMEN
In this study, we investigated the effects of whey protein hydrolysate (WPH) fermented with Lactobacillus brevis on sleep behavior and GABAergic mechanisms in rodent models. Fermentation converted the glutamate in WPH to high (3.15 ± 0.21 mg/mL) levels of γ-aminobutyric acid (GABA). Fermented WPH (WP-SF) enhanced sleep duration in mice by increasing GABA content in the brain. The increase in sleep duration induced by WP-SF resulted from an increase in delta wave activity during non-rapid eye movement sleep, and its sleep-promoting effect in a caffeine-induced insomnia model was characterized by an increase in delta waves. WP-SF increased GABAergic receptors at both mRNA and protein levels. Cotreatment with GABAA receptor antagonists abolished the sleep-promoting effects of WP-SF, indicating that WP-SF shares binding sites with antagonists on GABAA receptors. Collectively, WP-SF effectively increased sleep duration by enhancing delta wave activity through GABAergic activation; thus, it is suggested as a functional food-grade ingredient for promoting sleep.
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This study characterized the sleep activity, sleep mechanism, and active peptides of whey protein hydrolysates selected through behavioral analysis of fruit-flies (Drosophila melanogaster). Sleep-inducing whey protein (WP) hydrolysate was selected through fruit fly behavior analysis, and sleep activity was measured using a pentobarbital model and electroencephalographic analysis. The mechanism of action was confirmed using a γ-aminobutyric acid (GABA) receptor antagonist, and the active peptide was identified using liquid chromatography-mass spectroscopy. Whey protein hydrolysate, prepared using Alcalase and Prozyme (WP-AP), increased sleep time in a dose-dependent manner. WP-AP significantly increased not only sleep time but also slow-wave sleep and showed an insomnia-alleviating effect in a caffeine-induced insomnia mouse model. In addition, the gene and protein expression levels of GABA sub-type A (GABAA) receptors increased in the brains of mice orally administered with WP-AP. Through peptide analysis, the mixture of DIQK, VPPF peptide, and GABA contained in WP-AP was estimated to exhibit sleep activity, and due to its high content, DIQK was speculated to be the main sleep -inducing ingredient. These results indicate that WP-AP has the potential to be used as a new ingredient to improve sleep quality.
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Photosensitizers cause oxidative damages in various biological systems under light. In this study, the method for analyzing photosensitizing activity of various dietary and medicinal sources was developed using 1-(4,5-dimethylthiazol-2-yl)-3,5-diphenylformazan (thiazolyl blue formazan; MTT-F) as a probe. Significant and quantitative decolorization of MTT-F was observed in the presence of photosensitizers used in this study under light but not under dark conditions. The decolorization of MTT-F occurred irradiation time-, light intensity-, and photosensitizer concentration-dependently. The decolorized MTT-F was reversibly reduced by living cells; the LC-MS/MS results indicated the formation of oxidized products with -1 m/z of base peak from MTT-F, suggesting that MTT-F decolorized by photosensitizers was its corresponding tetrazolium. The present results indicate that MTT-F is a reliable probe for the quantitative analysis of photosensitizing activities, and the MTT-F-based method can be an useful tool for screening and evaluating photosensitizing properties of various compounds used in many industrial purposes.
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Formazáns , Fármacos Fotosensibilizantes , Sales de Tetrazolio , Fármacos Fotosensibilizantes/química , Fármacos Fotosensibilizantes/farmacología , Humanos , Sales de Tetrazolio/química , Formazáns/química , Espectrometría de Masas en Tándem/métodos , Tiazoles/química , Luz , Cromatografía Liquida/métodos , Colorantes/químicaRESUMEN
The increasing need for precise dietary monitoring across various health scenarios has led to innovations in wearable sensing technologies. However, continuously tracking food and fluid intake during daily activities can be complex. In this study, we present a machine-learning-powered smart neckband that features wireless connectivity and a comfortable, foldable design. Initially considered beneficial for managing conditions such as diabetes and obesity by facilitating dietary control, the device's utility extends beyond these applications. It has proved to be valuable for sports enthusiasts, individuals focused on diet control, and general health monitoring. Its wireless connectivity, ergonomic design, and advanced classification capabilities offer a promising solution for overcoming the limitations of traditional dietary tracking methods, highlighting its potential in personalized healthcare and wellness strategies.
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AIMS: γ-aminobutyric acid (GABA) from reactive astrocytes is critical for the dysregulation of neuronal activity in various neuroinflammatory conditions. While Scutellaria baicalensis Georgi (S. baicalensis) is known for its efficacy in addressing neurological symptoms, its potential to reduce GABA synthesis in reactive astrocytes and the associated neuronal suppression remains unclear. This study focuses on the inhibitory action of monoamine oxidase B (MAO-B), the key enzyme for astrocytic GABA synthesis. METHODS: Using a lipopolysaccharide (LPS)-induced neuroinflammation mouse model, we conducted immunohistochemistry to assess the effect of S. baicalensis on astrocyte reactivity and its GABA synthesis. High-performance liquid chromatography was performed to reveal the major compounds of S. baicalensis, the effects of which on MAO-B inhibition, astrocyte reactivity, and tonic inhibition in hippocampal neurons were validated by MAO-B activity assay, qRT-PCR, and whole-cell patch-clamp. RESULTS: The ethanolic extract of S. baicalensis ameliorated astrocyte reactivity and reduced excessive astrocytic GABA content in the CA1 hippocampus. Baicalin and baicalein exhibited significant MAO-B inhibition potential. These two compounds downregulate the mRNA levels of genes associated with reactive astrogliosis or astrocytic GABA synthesis. Additionally, LPS-induced aberrant tonic inhibition was reversed by both S. baicalensis extract and its key compounds. CONCLUSIONS: In summary, baicalin and baicalein isolated from S. baicalensis reduce astrocyte reactivity and alleviate aberrant tonic inhibition of hippocampal neurons during neuroinflammation.
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Astrocitos , Flavanonas , Flavonoides , Lipopolisacáridos , Neuronas , Extractos Vegetales , Scutellaria baicalensis , Ácido gamma-Aminobutírico , Animales , Astrocitos/efectos de los fármacos , Astrocitos/metabolismo , Flavanonas/farmacología , Scutellaria baicalensis/química , Ratones , Ácido gamma-Aminobutírico/metabolismo , Neuronas/efectos de los fármacos , Neuronas/metabolismo , Masculino , Flavonoides/farmacología , Extractos Vegetales/farmacología , Lipopolisacáridos/toxicidad , Lipopolisacáridos/farmacología , Ratones Endogámicos C57BL , Monoaminooxidasa/metabolismo , Inhibición Neural/efectos de los fármacos , Hipocampo/efectos de los fármacos , Hipocampo/metabolismoRESUMEN
Strain gauges, particularly for wearable sensing applications, require a high degree of stretchability, softness, sensitivity, selectivity, and linearity. They must also steer clear of challenges such as mechanical and electrical hysteresis, overshoot behavior, and slow response/recovery times. However, current strain gauges face challenges in satisfying all of these requirements at once due to the inevitable trade-offs between these properties. Here, we present an innovative method for creating strain gauges from spongy Ag foam through a steam-etching process. This method simplifies the traditional, more complex, and costly manufacturing techniques, presenting an eco-friendly alternative. Uniquely, the strain gauges crafted from this method achieve an unparalleled gauge factor greater than 8 × 103 at strains exceeding 100%, successfully meeting all required attributes without notable trade-offs. Our work includes systematic investigations that reveal the intricate structure-property-performance relationship of the spongy Ag foam with practical demonstrations in areas such as human motion monitoring and human-robot interaction. These breakthroughs pave the way for highly sensitive and selective strain gauges, showing immediate applicability across a wide range of wearable sensing applications.
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Self-healing hydrogels are in high demand for wearable sensing applications due to their remarkable deformability, high ionic and electrical conductivity, self-adhesiveness to human skin, as well as resilience to both mechanical and electrical damage. However, these hydrogels face challenges such as delayed healing times and unavoidable electrical hysteresis, which limit their practical effectiveness. Here, we introduce a self-healing hydrogel that exhibits exceptionally rapid healing with a recovery time of less than 0.12 s and an ultralow electrical hysteresis of less than 0.64% under cyclic strains of up to 500%. This hydrogel strikes an ideal balance, without notable trade-offs, between properties such as softness, deformability, ionic and electrical conductivity, self-adhesiveness, response and recovery times, durability, overshoot behavior, and resistance to nonaxial deformations such as twisting, bending, and pressing. Owing to this unique combination of features, the hydrogel is highly suitable for long-term, durable use in wearable sensing applications, including monitoring body movements and electrophysiological activities on the skin.
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Hidrogeles , Dispositivos Electrónicos Vestibles , Humanos , Electricidad , Conductividad Eléctrica , MovimientoRESUMEN
The vagus nerve (VN) plays an important role in regulating physiological conditions in the gastrointestinal (GI) tract by communicating via the parasympathetic pathway to the enteric nervous system (ENS). However, the lack of knowledge in the neurophysiology of the VN and GI tract limits the development of advanced treatments for autonomic dysfunctions related to the VN. To better understand the complicated underlying mechanisms of the VN-GI tract neurophysiology, it is necessary to use an advanced device enabled by microfabrication technologies. Among several candidates including intraneural probe array and extraneural cuff electrodes, microchannel electrode array devices can be used to interface with smaller numbers of nerve fibers by securing them in the separate channel structures. Previous microchannel electrode array devices to interface teased nerve structures are relatively bulky with thickness around 200 µm. The thick design can potentially harm the delicate tissue structures, including the nerve itself. In this paper, we present a flexible thin film based microchannel electrode array device (thickness: 11.5 µm) that can interface with one of the subdiaphragmatic nerve branches of the VN in a rat. We demonstrated recording evoked compound action potentials (ECAP) from a transected nerve ending that has multiple nerve fibers. Moreover, our analysis confirmed that the signals are from C-fibers that are critical in regulating autonomic neurophysiology in the GI tract.
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Opioid-induced overdose is one of the leading causes of death among the US population under the age of 50. In 2021 alone, the death toll among opioid users rose to a devastating number of over 80,000. The overdose process can be reversed by the administration of naloxone, an opioid antagonist that rapidly counteracts the effects of opioid-induced respiratory depression. The idea of a closed-loop opioid overdose detection and naloxone delivery has emerged as a potential engineered solution to mitigate the deadly effects of the opioid epidemic. In this work, we introduce a wrist-worn wearable device that overcomes the portability issues of our previous work to create a closed-loop drug-delivery system, which includes (1) a Near-Infrared Spectroscopy (NIRS) sensor to detect a hypoxia-driven opioid overdose event, (2) a MOSFET switch, and (3) a Zero-Voltage Switching (ZVS) electromagnetic heater. Using brachial artery occlusion (BAO) with human subjects (n = 8), we demonstrated consistent low oxygenation events. Furthermore, we proved our device's capability to release the drug within 10 s after detecting a hypoxic event. We found that the changes in the oxyhemoglobin, deoxyhemoglobin and oxygenation saturation levels ( SpO2) were different before and after the low-oxygenation events ( 0.001). Although additional human experiments are needed, our results to date point towards a potential tool in the battle to mitigate the effects of the opioid epidemic.
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Sobredosis de Droga , Sobredosis de Opiáceos , Humanos , Analgésicos Opioides/uso terapéutico , Sobredosis de Opiáceos/tratamiento farmacológico , Antagonistas de Narcóticos/uso terapéutico , Naloxona/uso terapéutico , Sobredosis de Droga/tratamiento farmacológicoRESUMEN
Continuous real-time monitoring of biomarkers in interstitial fluid is essential for tracking metabolic changes and facilitating the early detection and management of chronic diseases such as diabetes. However, developing minimally invasive sensors for the in situ analysis of interstitial fluid and addressing signal delays remain a challenge. Here, we introduce a wearable sensor patch incorporating hydrogel microneedles for rapid, minimally invasive collection of interstitial fluid from the skin while simultaneously measuring biomarker levels in situ. The sensor patch is stretchable to accommodate the swelling of the hydrogel microneedles upon extracting interstitial fluid and adapts to skin deformation during measurements, ensuring consistent sensing performance in detecting model biomarker concentrations, such as glucose and lactate, in a mouse model. The sensor patch exhibits in vitro sensitivities of 0.024 ± 0.002 µA mM-1 for glucose and 0.0030 ± 0.0004 µA mM-1 for lactate, with corresponding linear ranges of 0.1-3 and 0.1-12 mM, respectively. For in vivo glucose sensing, the sensor patch demonstrates a sensitivity of 0.020 ± 0.001 µA mM-1 and a detection range of 1-8 mM. By integrating a predictive model, the sensor patch can analyze and compensate for signal delays, improving calibration reliability and providing guidance for potential optimization in sensing performance. The sensor patch is expected to serve as a minimally invasive platform for the in situ analysis of multiple biomarkers in interstitial fluid, offering a promising solution for continuous health monitoring and disease management.
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The development of micro- and nanotechnology for biomedical applications has defined the cutting edge of medical technology for over three decades, as advancements in fabrication technology developed originally in the semiconductor industry have been applied to solving ever-more complex problems in medicine and biology. These technologies are ideally suited to interfacing with life sciences, since they are on the scale lengths as cells (microns) and biomacromolecules (nanometers). In this paper, we review the state of the art in bionanotechnology and bioMEMS (collectively BNM), including developments and challenges in the areas of BNM, such as microfluidic organ-on-chip devices, oral drug delivery, emerging technologies for managing infectious diseases, 3D printed microfluidic devices, AC electrokinetics, flexible MEMS devices, implantable microdevices, paper-based microfluidic platforms for cellular analysis, and wearable sensors for point-of-care testing.
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Sistemas Microelectromecánicos , Sistemas de Liberación de Medicamentos , Microfluídica , Dispositivos Laboratorio en un Chip , NanotecnologíaRESUMEN
Digital therapeutics based on software, such as artificial intelligence, virtual reality, games, and smartphone applications, are in the spotlight as new therapeutic alternatives in child and adolescent psychiatry. It draws attention to overcoming conventional therapeutics' limitations, such as toxicity, cost, and accessibility, and encourages patients to participate in the treatment attractively. The growth potential of the digital therapeutics market for psychiatric disorders in children and adolescents in Korea and abroad has been highlighted. Clinical studies and Food and Drug Administration approvals for digital therapeutics have increased, and cases approved by the Ministry of Food and Drug Safety have emerged in Korea. As seen above, digital transformation in child and adolescent psychiatry will change treatment paradigms significantly. Therefore, as this new field has just begun to emerge, it is necessary to verify the effectiveness and scope of the application of digital therapeutics and consider preparing a compensation system and institutional arrangements. Accordingly, this study analyzed the development trends and application status of digital therapeutics in children and adolescents and presented limitations and development directions from the perspective of application in healthcare. Further, the study is expected to identify the utility and limitations of digital therapeutics for children and adolescents and establish effective application measures.
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Background The relationship between overweight or obesity and low back pain (LBP) has previously been investigated. Several recent studies have focused on the relationship between other indicators of obesity, particularly indicators of fat and the risk of LBP. However, the results of body composition and LBP have been inconsistent. Methods All data for the present retrospective, cross-sectional study was extracted from the Korea National Health and Nutrition Examination Survey (KNHANES) versions V-1 and 2 conducted in 2010 and 2011 by the Korean Centers for Disease Control and Prevention. In KNHANES V-1 (2010) and V-2 (2011), those over 50 years of age completed the surveys on LBP, body weight, and body composition assessed using dual-energy X-ray absorptiometry (DXA) were included. The multivariable logistic regression analysis was used to examine the relationship between the presence of chronic LBP and body composition adjusting for confounders. Results We analyzed 3,579 persons who completed the question. In the multivariable analyses adjusting for age and sex, none of the variables, including fat mass and fat-free mass, remained positively or negatively associated with LBP. Additionally, when depression, smoking, alcohol intake, physical activity, diabetes mellitus, and fat or lean tissue mass were included in the multivariable logistic model, no significant associations were found between all measures of fat mass, fat-free mass, and LBP Conclusion This study is contrary to previous studies that concluded that there is a correlation between obesity and fat mass and LBP. LBP is not associated with increased levels of obesity and fat mass.
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Objective: The NEX project has developed an integrated Internet of Things (IoT) system coupled with data analytics to offer unobtrusive health and wellness monitoring supporting older adults living independently at home. Monitoring involves visualising a set of automatically detected activities of daily living (ADLs) for each participant. ADL detection allows the incorporation of additional participants whose ADLs are detected without system re-training. Methods: Following a user needs and requirements study involving 426 participants, a pilot trial and a friendly trial of the deployment, an action research cycle (ARC) trial was completed. This involved 23 participants over a 10-week period each with â¼20 IoT sensors in their homes. During the ARC trial, participants took part in two data-informed briefings which presented visualisations of their own in-home activities. The briefings also gathered training data on the accuracy of detected activities. Association rule mining was used on the combination of data from sensors and participant feedback to improve the automatic ADL detection. Results: Association rule mining was used to detect a range of ADLs for each participant independently of others and then used to detect ADLs across participants using a single set of rules for each ADL. This allows additional participants to be added without the necessity of them providing training data. Conclusions: Additional participants can be added to the NEX system without the necessity to re-train the system for automatic detection of their ADLs.
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Diabetes is a chronic disease characterized by elevated blood glucose levels resulting from absent or ineffective insulin release from pancreatic ß-cells. ß-cell function is routinely assessed in vitro using static or dynamic glucose-stimulated insulin secretion (GSIS) assays followed by insulin quantification via time-consuming, costly enzyme-linked immunosorbent assays (ELISA). In this study, we developed a highly sensitive electrochemical sensor for zinc (Zn2+), an ion co-released with insulin, as a rapid and low-cost method for measuring dynamic insulin release. Different modifications to glassy carbon electrodes (GCE) were evaluated to develop a sensor that detects physiological Zn2+ concentrations while operating within a biological Krebs Ringer Buffer (KRB) medium (pH 7.2). Electrodeposition of bismuth and indium improved Zn2+ sensitivity and limit of detection (LOD), and a Nafion coating improved selectivity. Using anodic stripping voltammetry (ASV) with a pre-concentration time of 6 min, we achieved a LOD of 2.3 µg/L over the wide linear range of 2.5-500 µg/L Zn2+. Sensor performance improved with 10-min pre-concentration, resulting in increased sensitivity, lower LOD (0.18 µg/L), and a bilinear response over the range of 0.25-10 µg/L Zn2+. We further characterized the physicochemical properties of the Zn2+ sensor using scanning electron microscopy (SEM), cyclic voltammetry (CV), and electrochemical impedance spectroscopy (EIS). Finally, we demonstrated the sensor's capability to measure Zn2+ release from glucose-stimulated INS-1 ß-cells and primary mouse islets. Our results exhibited a high correlation with secreted insulin and validated the sensor's potential as a rapid alternative to conventional two-step GSIS plus ELISA methods.
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Técnicas Biosensibles , Ratones , Animales , Insulina , Glucosa , Carbono/química , Zinc/análisis , Electrodos , Técnicas Electroquímicas/métodosRESUMEN
Reactive astrogliosis is a hallmark of Alzheimer's disease (AD). However, a clinically validated neuroimaging probe to visualize the reactive astrogliosis is yet to be discovered. Here, we show that PET imaging with 11C-acetate and 18F-fluorodeoxyglucose (18F-FDG) functionally visualizes the reactive astrocyte-mediated neuronal hypometabolism in the brains with neuroinflammation and AD. To investigate the alterations of acetate and glucose metabolism in the diseased brains and their impact on the AD pathology, we adopted multifaceted approaches including microPET imaging, autoradiography, immunohistochemistry, metabolomics, and electrophysiology. Two AD rodent models, APP/PS1 and 5xFAD transgenic mice, one adenovirus-induced rat model of reactive astrogliosis, and post-mortem human brain tissues were used in this study. We further curated a proof-of-concept human study that included 11C-acetate and 18F-FDG PET imaging analyses along with neuropsychological assessments from 11 AD patients and 10 healthy control subjects. We demonstrate that reactive astrocytes excessively absorb acetate through elevated monocarboxylate transporter-1 (MCT1) in rodent models of both reactive astrogliosis and AD. The elevated acetate uptake is associated with reactive astrogliosis and boosts the aberrant astrocytic GABA synthesis when amyloid-ß is present. The excessive astrocytic GABA subsequently suppresses neuronal activity, which could lead to glucose uptake through decreased glucose transporter-3 in the diseased brains. We further demonstrate that 11C-acetate uptake was significantly increased in the entorhinal cortex, hippocampus and temporo-parietal neocortex of the AD patients compared to the healthy controls, while 18F-FDG uptake was significantly reduced in the same regions. Additionally, we discover a strong correlation between the patients' cognitive function and the PET signals of both 11C-acetate and 18F-FDG. We demonstrate the potential value of PET imaging with 11C-acetate and 18F-FDG by visualizing reactive astrogliosis and the associated neuronal glucose hypometablosim for AD patients. Our findings further suggest that the acetate-boosted reactive astrocyte-neuron interaction could contribute to the cognitive decline in AD.
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Enfermedad de Alzheimer , Ratones , Humanos , Ratas , Animales , Enfermedad de Alzheimer/metabolismo , Fluorodesoxiglucosa F18/metabolismo , Astrocitos/metabolismo , Radioisótopos de Carbono/metabolismo , Gliosis/diagnóstico por imagen , Encéfalo/patología , Tomografía de Emisión de Positrones/métodos , Ácido gamma-Aminobutírico/metabolismoRESUMEN
Vagus nerve stimulation (VNS) has the potential to treat various peripheral dysfunctions, but the traditional cuff electrodes for VNS are susceptible to off-target effects. Microelectrodes may enable highly selective VNS that can mitigate off-target effects, but they suffer from the increased impedance. Recent studies on microelectrodes with non-Euclidean geometries have reported higher energy efficiency in neural stimulation applications. These previous studies use electrodes with mm/cm-scale dimensions, mostly targeted for myelinated fibers. This study evaluates fractal microelectrodes for VNS in a rodent model (N = 3). A thin-film device with fractal and circle microelectrodes is fabricated to compare their neural stimulation performance on the same radial coordinate of the nerve. The results show that fractal microelectrodes can activate C-fibers with up to 52% less energy (p = 0.012) compared to circle microelectrodes. To the best of the knowledge, this work is the first to demonstrate a geometric advantage of fractal microelectrodes for VNS in vivo.
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Estimulación del Nervio Vago , Estimulación del Nervio Vago/métodos , Microelectrodos , Fractales , Nervio Vago/fisiologíaRESUMEN
Continuous monitoring of intraocular pressure, particularly during sleep, remains a grand challenge in glaucoma care. Here we introduce a class of smart soft contact lenses, enabling the continuous 24-hour monitoring of intraocular pressure, even during sleep. Uniquely, the smart soft contact lenses are built upon various commercial brands of soft contact lenses without altering their intrinsic properties such as lens power, biocompatibility, softness, transparency, wettability, oxygen transmissibility, and overnight wearability. We show that the smart soft contact lenses can seamlessly fit across different corneal curvatures and thicknesses in human eyes and therefore accurately measure absolute intraocular pressure under ambulatory conditions. We perform a comprehensive set of in vivo evaluations in rabbit, dog, and human eyes from normal to hypertension to confirm the superior measurement accuracy, within-subject repeatability, and user comfort of the smart soft contact lenses beyond current wearable ocular tonometers. We envision that the smart soft contact lenses will be effective in glaucoma care.