Electrical Signal Transduction Research Articles

Oligodendrocytes: Myelination, Plasticity, and Axonal Support.

The myelination of axons has evolved to enable fast and efficient transduction of electrical signals in the vertebrate nervous system. Acting as an electric insulator, the myelin sheath is a multilamellar membrane structure around axonal segments generated by the spiral wrapping and subsequent compaction of oligodendroglial plasma membranes. These oligodendrocytes are metabolically active and remain functionally connected to the subjacent axon via cytoplasmic-rich myelinic channels for movement of metabolites and macromolecules to and from the internodal periaxonal space under the myelin sheath. Increasing evidence indicates that oligodendrocyte numbers, specifically in the forebrain, and myelin as a dynamic cellular compartment can both respond to physiological demands, collectively referred to as adaptive myelination. This review summarizes our current understanding of how myelin is generated, how its function is dynamically regulated, and how oligodendrocytes support the long-term integrity of myelinated axons.

Conjugated Polymers for Aptasensing Applications.

Rapid and specific assaying of molecules that report on a pathophysiological condition, environmental pollution, or drug concentration is pivotal for establishing efficient and accurate diagnostic systems. One of the main components required for the construction of these systems is the recognition element (receptor) that can identify target analytes. Oligonucleotide switching structures, or aptamers, have been widely studied as selective receptors that can precisely identify targets in different analyzed matrices with minimal interference from other components in an antibody-like recognition process. These aptasensors, especially when integrated into sensing platforms, enable a multitude of sensors that can outperform antibody-based sensors in terms of flexibility of the sensing strategy and ease of deployment to areas with limited resources. Research into compounds that efficiently enhance signal transduction and provide a suitable platform for conjugating aptamers has gained huge momentum over the past decade. The multifaceted nature of conjugated polymers (CPs), notably their versatile electrical and optical properties, endows them with a broad range of potential applications in optical, electrical, and electrochemical signal transduction. Despite the substantial body of research demonstrating the enhanced performance of sensing devices using doped or nanostructure-embedded CPs, few reviews are available that specifically describe the use of conjugated polymers in aptasensing. The purpose of this review is to bridge this gap and provide a comprehensive description of a variety of CPs, from a historical viewpoint, underpinning their specific characteristics and demonstrating the advances in biosensors associated with the use of these conjugated polymers.

Pentameric ligand gated ion channels' intracellular domain interaction with RIC3 chaperone.

Pentameric ligand-gated ion channels (pLGICs) are cys-loop receptors important in transduction of electrical signals between neurons in the peripheral and central nervous system. Their significant role in neurotransmission has increased the research in neuropharmacology. Members of this protein family are found in mammals, but also in prokaryotes that can often incorporate additional domains whose roles are largely uncharacterized. pLGICs include nicotinic acetylcholinereceptors, gamma-amino butyric acid A receptors, glycine receptors and type 3 serotonin receptors (5HT3). These receptors are integral membrane protein complexes composed of five subunits that surround the central pore. Each subunit incorporates a large extracellular domain which contains the agonist-binding site, four transmembrane segments (TM1-4) which form the ion pore, a large intracellular domain (ICD) between TM3 and TM4, and a short extracellular C-terminal region. The ionotropic serotonin subtype-3 (5-HT3) receptor is of current interest as a therapeutic target in the treatment of alcohol abuse. Selective pharmacological antagonists reduce alcohol consumption in preclinical and clinical models. To date only two applications have been fully realized in the clinic: the treatment of emesis and irritable-bowel syndrome. Competitive antagonists, called setrons, target 5HT3R, are used in the management of nausea and vomiting associated with radiation and chemotherapies in cancer patients. These drugs interact with off-target subunits of the receptor and consequently lead to many undesired effects including headache and drowsiness. In order to understand and characterize effective control of neurotransmitter-gated pLGICs, we have explored the interaction of 5HT3R with RIC-3 chaperone which mediates functional expression of the channels. In the present study, synthetic pLGIC peptides were used to probe and characterize the interaction with RIC-3 in native sources such as mouse brains and neuronal cell lines.

A synthetic biology tool for contact-dependent synthetic cell communication.

Cell-cell communication and signal transduction through direct cell-cell contact are found ubiquitously in biology, with examples including T-cell activation upon contact formation with antigen-presenting cell in immunological synapses and electrical signal transduction in neuronal synapses. Despite the prevalence of intercellular communication at cell-cell interfaces, it is difficult to engineer and reconstitute functional proteins at membrane-membrane interfaces. A synthetic biology tool that can recapitulate signal transduction exclusively at membrane-membrane interfaces will be useful for designing synthetic intercellular communication pathways or providing a potential replacement for damaged and malfunctional natural cell-cell communication systems. Here, we present programmable activation of a split bioluminescent protein, NanoBiT, at the membrane-membrane interface between synthetic cells. We utilize a peptide-protein pair called SpyTag and SpyCatcher as adapter proteins to mediate functional reconstitution of NanoBiT. We illustrate an example of downstream protein activation through a designed light-based communication system by using a pair of photoactivatable proteins, iLID and SspB inside synthetic cells and demonstrate iLID-SspB dimerization triggered by reconstituted NanoBiT bioluminescence.

Regulation of nerve cells using conductive nanofibrous scaffolds for controlled release of Lycium barbarum polysaccharides and nerve growth factor.

Currently, more and more patients suffer from peripheral nerve injury due to trauma, tumor and other causes worldwide. Biomaterial-based nerve conduits are increasingly recognized as a potential alternative to nerve autografts for the treatment of peripheral nerve injury. However, an ideal nerve conduit must offer topological guidance and biochemical and electrical signal transduction mechanisms. In this work, aligned conductive nanofibrous scaffolds comprising polylactic-co-glycolic acid and multiwalled carbon nanotubes (MWCNTs) were fabricated via coaxial electrospinning, and nerve growth factor (NGF) and Lycium barbarum polysaccharides (LBP) purified from the wolfberry were loaded on the core and shell layers of the nanofibers, respectively. LBP were confirmed to accelerate long-distance axon regeneration after severe peripheral nerve injury. In addition, the synergistic promotion of LBP and NGF on nerve cell proliferation and neurite outgrowth was demonstrated. MWCNTs were introduced into the aligned fibers to further increase the electrical conductivity, which promoted the directional growth and neurite extension of neurons in vitro. Further, the combination of conductive fibrous scaffolds with electrical stimulation that mimics endogenous electric fields significantly promoted the differentiation of PC12 cells and the axon outgrowth of neurons. Based on robust cell-induced behaviors, conductive composite fibers with optimized fiber alignment may be used for the promotion of nerve recovery.

Comparison of electrical and optical transduction modes of DNA-wrapped SWCNT nanosensors for the reversible detection of neurotransmitters.

In this study, we compare the electrical and optical signal transduction of nanoscale biosensors based on single-walled carbon nanotubes (SWCNTs). Solution processable single-stranded (ss) DNA-wrapped SWCNTs were used for the fabrication of the distinct sensors. For electrical measurements, SWCNTs were assembled from solution onto pre-patterned electrodes by electric-field-assisted assembly in field-effect transistor (FET) configuration. A combination of micro- and nano-fabrication and microfluidics enabled the integration into a sensing platform that allowed real-time and reversible detection. For optical measurements, the near-infrared (NIR) fluorescence of the SWCNTs was acquired directly from solution. The detection of important biomolecules was investigated in high-ionic strength solution (0.5xPBS). Increase in fluorescence intensities correlated with a decrease in the SWCNTs electrical current and enabled detection of the important biomolecules dopamine, epinephrine, and ascorbic acid. For riboflavin, however, a decrease in the fluorescence intensity could not be associated with changes in the SWCNTs electrical current, which indicates a different sensing mechanism. The combination of SWCNT-based electrical and optical transduction holds great potential for selective detection of biomarkers in next generation portable diagnostic assays.

(Invited) Multi-Modality Input/Output Interfaces with Tissue and Cells Using Nanocarbons

My team’s efforts are focused on three major thrusts: (i) synthesis and in depth mechanistic investigation of the unique emergent optical, thermal, electrical and electrochemical properties of novel hybrid-nanomaterials and nanomaterials topologies composed on one-dimensional and two-dimensional building blocks, (ii) application and characterization of hybrid-nanomaterials interfaces with cells and tissue, and (iii) development and engineering of nanomaterials-based platforms to interrogate and affect the electrical properties of tissue and cells such as cardiomyocytes, and neurons, with a specific focus to understand electrical signal transduction in complex 3D cellular assemblies. Major questions we strive to answer are: Can we make materials and platforms that are tailored to allow seamless and stable integration with cells and tissue enabling sensing and actuation? Can hybrid-nanomaterials allow new insights about biological processes, e.g., tissue development and disease progression?In this talk I will describe our recent efforts in tackling these challenges. Our highly flexible bottom-up nanomaterials synthesis capabilities allow us to form unique hybrid-nanomaterials that can be used in various input/output bioelectrical interfaces, i.e., bioelectrical platforms for chemical and physical sensing and actuation. We developed a breakthrough bioelectrical interface, a 3D self-rolled biosensor arrays (3D-SR-BAs) of either active field effect transistors or passive microelectrodes to measure both cardiac and neural spheroids electrophysiology in 3D. This approach enables electrophysiological investigation and monitoring of the complex signal transduction in 3D cellular assemblies toward an organ-on-an-electronic-chip (organ-on-e-chip) platform for tissue maturation investigations and development of drugs for disease treatment. Utilizing graphene, a two-dimensional (2D) atomically thin carbon allotrope, we demonstrated a new technique to simultaneously record the intracellular electrical activity of multiple excitable cells with ultra-microelectrodes that can be as small as the size as an axon ca. 2µm in size. The outstanding electrochemical properties of our hybrid-nanomaterials allowed us to develop electrical sensors and actuators, e.g., sensors to explore the brain chemistry and sensors/actuators that are deployed in a large volumetric muscle loss animal model. Finally, using the unique optical properties of nanocarbons, e.g., graphene-based hybrid-nanomaterials and 2D nanocarbides (MXene), we have formed remote, non-genetic bioelectrical interfaces with excitable cells and modulated cellular and network activity with high precision and low needed energy. In summary, the exceptional synthetic control and flexible assembly of nanomaterials provide powerful tools for fundamental studies and applications in life science and potentially seamlessly merge nanomaterials-based platforms with cells, fusing nonliving and living systems together.

Corrected Serum Ionized Calcium as a Risk Factor Related to Adult Dyslipidemia.

BackgroundDyslipidemia is a significant threat to global public health due to its pivotal role as a cardiovascular disease (CVD) risk factor. Calcium is a critical nutritional element required for electrical signal transduction and muscle and heart function, and calcium supplementation is widespread in the general population. However, associations between serum calcium and serum lipid profiles remain conflicting. Considering ionized calcium [Ca(2+)] is the best measure of active serum calcium and the lack of Ca(2+) analyzers, we aimed to examine the independent and joint associations between serum ionized calcium corrected by albumin ([Ca2+]corr) and the known modifiable risk factors and dyslipidemia.MethodsWe collected physical examination records, including demographic, anthropometric, laboratory tests, and clinical characteristics from individuals who had health checkups in 2019 at the health examination center of the First Affiliated Hospital of China Medical University. Subjects were categorized into Q1–Q4 groups using [Ca2+]corr quartiles, and odds ratios (ORs) with 95% confidence intervals (CIs) for dyslipidemia and associated components were calculated using logistic regression. We also performed non-linear and threshold effect analyses of [Ca2+]corr and triglyceride (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and non-high-density lipoprotein cholesterol (Non-HDL-C) levels.FindingsOf 5,416 individuals aged 18–92 years, multivariable-adjusted models showed that ORs for dyslipidemia increased gradually with elevated [Ca2+]corr levels. Logistic regression analyses demonstrated that [Ca2+]corr levels were associated with the increased odds of dyslipidemia (per 1 mmol/L increase: OR = 3.53, 95% CI: 1.56–8.00, P < 0.001). When compared with individuals in the Q1 group, those in groups Q3 and Q4 had significantly higher dyslipidemia odds (ORQ3 vs. Q1 = 1.20, 95% CI: 1.01–1.42; ORQ4 vs. Q1 = 1.31, 95% CI: 1.10–1.56, all P < 0.05). Furthermore, a linear, positive relationship between [Ca2+]corr levels and dyslipidemia odds was observed (P for non-linear trend = 0.506), and the optimal cut-off point of [Ca2+]corr for dyslipidemia management was 2.26 mmol/L. A modifiable effect of albumin on the relationship between [Ca2+]corr and dyslipidemia odds was also found (P for interaction = 0.014). High [Ca2+]corr levels were positively associated with elevated TC, LDL-C, and Non-HDL-C but inversely associated with decreased HDL-C odds. Moreover, Locally weighted regression (Loess) analyses showed a non-linear, positive relationship between [Ca2+]corr and TG, TC, HDL-C, LDL-C, and Non-HDL-C levels.InterpretationCorrected serum ionized calcium was positively associated with increased odds of dyslipidemia and elevated TC, LDL-C, and Non-HDL-C, but inversely associated with the odds of decreased HDL-C.

Recent advances and challenges in graphene-based nanocomposite scaffolds for tissue engineering application.

Graphene-based nanocomposites have recently attracted increasing attention in tissue engineering because of their extraordinary features. These biocompatible substances, in the presence of an apt microenvironment, can stimulate and sustain the growth and differentiation of stem cells into different lineages. This review discusses the characteristics of graphene and its derivatives, such as their excellent electrical signal transduction, carrier mobility, outstanding mechanical strength with improving surface characteristics, self-lubrication, antiwear properties, enormous specific surface area, and ease of functional group modification. Moreover, safety issues in the application of graphene and its derivatives in terms of biocompatibility, toxicity, and interaction with immune cells are discussed. We also describe the applicability of graphene-based nanocomposites in tissue healing and organ regeneration, particularly in the bone, cartilage, teeth, neurons, heart, skeletal muscle, and skin. The impacts of special textural and structural characteristics of graphene-based nanomaterials on the regeneration of various tissues are highlighted. Finally, the present review gives some hints on future research for the transformation of these exciting materials in clinical studies.

Synthesis of lysozyme-reduced graphene oxide films for biosensor applications

Graphene-based materials present a high surface area and can present several structural defects or heteroatoms depending on the fabrication method. Such properties facilitate the graphene interaction with biomolecules leading to high electrochemical activity. In this context, we synthesize a high-quality dispersed reduced graphene oxide using Lysozyme as a dispersant (Ly-RGO). In this study, we have investigated the graphite oxidation-reduction fabrication process using X-ray Photoelectron Spectroscopy, X-ray Diffraction, and Raman Spectroscopy. We have used the Ly-RGO to fabricate an electrode on an electrochemical cell in which voltammograms show significant transduction of electrical signals. Finally, cyclic voltammetry and chronoamperometry measurements were performed with human saliva and SARS-CoV-2 RNA samples, to calibrate our biosensor. The results indicate that Ly-RGO has great potential in biosensor devices.

A Flexible Microfluidic Chip-Based Universal Fully Integrated Nanoelectronic System with Point-of-Care Raw Sweat, Tears, or Saliva Glucose Monitoring for Potential Noninvasive Glucose Management.

By combining the distinctive noninvasive feature with the peculiar complete functional implementation trait, fully integrated raw noninvasive biofluid glucose biosensors offer active and remote glucose monitoring while posing minimal harm or infection risks compared to the traditional invasive manner. However, each previously reported fully integrated raw noninvasive biofluid glucose biosensor is solely focused on single-type raw noninvasive biofluid analysis. Given the diversity and complexity of subjects' physical conditions, single-type raw noninvasive biofluids are inappropriate to all crowds (e.g., sweat collection/analysis could be inapplicable for dermatopathic subjects). Here, we demonstrate the first example of a universal fully integrated nanoelectronic system with the unique capability to point-of-care and universally monitor diverse raw noninvasive biofluid (i.e., sweat, tears, and saliva) glucose by combining a flexible and disposable microfluidic enzymatic biosensor (named iezSlice) for raw biofluid pump-free sampling and measurement with a customized, handheld, and reusable wireless electronic device (named iezBar) for electrical signal transduction, conditioning, processing, and wireless transmission. We employed the specially designed high-concentration-buffer powder-loaded Kimwipes (HBP-KWs) as the microfluidic channel (microchannel) of iezSlice, guaranteeing a high-accuracy glucose analysis in various raw noninvasive biofluids. We also evaluated the potential utility of the universal fully integrated nanoelectronic system for noninvasive glucose management in healthy and diabetic subjects with the assistance of the proposed volatility-derived blood glucose concentration-free protocol. Although we focus on raw noninvasive biofluid glucose analysis in this work, the universal fully integrated nanoelectronic system may readily realize accurate monitoring of various biomolecules in raw noninvasive biofluids by introducing corresponding bioreceptors.

Epidural spinal cord stimulation as an intervention for motor recovery after motor complete spinal cord injury.

Spinal cord injury (SCI) commonly results in permanent loss of motor, sensory, and autonomic function. Recent clinical studies have shown that epidural spinal cord stimulation may provide a beneficial adjunct for restoring lower extremity and other neurological functions. Herein, we review the recent clinical advances of lumbosacral epidural stimulation for restoration of sensorimotor function in individuals with motor complete SCI and we discuss the putative neural pathways involved in this promising neurorehabilitative approach. We focus on three main sections: review recent clinical results for locomotor restoration in complete SCI; discuss the contemporary understanding of electrical neuromodulation and signal transduction pathways involved in spinal locomotor networks; and review current challenges of motor system modulation and future directions toward integrative neurorestoration. The current understanding is that initial depolarization occurs at the level of large diameter dorsal root proprioceptive afferents that when integrated with interneuronal and latent residual supraspinal translesional connections can recruit locomotor centers and augment downstream motor units. Spinal epidural stimulation can initiate excitability changes in spinal networks and supraspinal networks. Different stimulation parameters can facilitate standing or stepping, and it may also have potential for augmenting myriad other sensorimotor and autonomic functions. More comprehensive investigation of the mechanisms that mediate the transformation of dysfunctional spinal networks to higher functional states with a greater focus on integrated systems-based control system may reveal the key mechanisms underlying neurological augmentation and motor restoration after severe paralysis.

Active topolectrical circuits

The transfer of topological concepts from the quantum world to classical mechanical and electronic systems has opened fundamentally different approaches to protected information transmission and wave guidance. A particularly promising emergent technology is based on recently discovered topolectrical circuits that achieve robust electric signal transduction by mimicking edge currents in quantum Hall systems. In parallel, modern active matter research has shown how autonomous units driven by internal energy reservoirs can spontaneously self-organize into collective coherent dynamics. Here, we unify key ideas from these two previously disparate fields to develop design principles for active topolectrical circuits (ATCs) that can self-excite topologically protected global signal patterns. Realizing autonomous active units through nonlinear Chua diode circuits, we theoretically predict and experimentally confirm the emergence of self-organized protected edge oscillations in one- and two-dimensional ATCs. The close agreement between theory, simulations, and experiments implies that nonlinear ATCs provide a robust and versatile platform for developing high-dimensional autonomous electrical circuits with topologically protected functionalities.

Signaling and transport processes related to the carnivorous lifestyle of plants living on nutrient-poor soil.

In Eukaryotes, long-distance and rapid signal transmission is required in order to be able to react fast and flexibly to external stimuli. This long-distance signal transmission cannot take place by diffusion of signal molecules from the site of perception to the target tissue, as their speed is insufficient. Therefore, for adequate stimulus transmission, plants as well as animals make use of electrical signal transmission, as this can quickly cover long distances. This update summarises the most important advances in plant electrical signal transduction with a focus on the carnivorous Venus flytrap. It highlights the different types of electrical signals, examines their underlying ion fluxes and summarises the carnivorous processes downstream of the electrical signals.

Self-Adhesion Conductive Sub-micron Fiber Cardiac Patch from Shape Memory Polymers to Promote Electrical Signal Transduction Function.

Myocardial infarction (MI) constitutes the first cause of morbidity and mortality in our life, so using highly conductive and elastic materials to produce an engineered cardiac patch is an effective way to improve the myocardium infarction area function. Here, shape memory polymers of the polyurethane/polyaniline/silicon oxide (PU/PANI/SiO2) electrospinning sub-micron fiber patch were precisely produced in the case of the hydrogen bonding effect and interaction between the carboxyl groups to provide compatibility, phase mixing/miscibility, and stability. The sub-micron fiber patch prepared by our group has some remarkable characteristics, such as sub-micron fibers, 3D porous structure, special thickness to simulate the extracellular matrix (ECM), elastic deformation, good properties in conducting weak electrical signals, stability to maintain the whole structure, and self-adhesion. This sub-micron fiber material has been proven to be effective, easy, and reliable. Through precise design of the material system, structure regulation, and performance optimization, the aim is to produce a sub-micron fiber cardiac patch to simulate the myocardium ECM and improve conductive signal transduction for potential MI therapy.

A highly-sensitive vascular endothelial growth factor-A(165) immunosensor, as a tool for early detection of cancer.

Biomarkers can be ideal indicators for assessing the risk of the presence of a disease. In this study, a label-free electrochemical biosensor was designed to quantify the vascular endothelial growth factor A (165) (VEGF-A(165)) antigen, using reduced graphene oxide-gold nanoparticle for early detection of breast cancer. The conductivity of gold nanoparticle along with its biocompatibility provide an enhanced surface, suitable for anti-VEGF antibody immobilization. 11-mercaptoundecanoic acid was used to facilitate a single-step and convenient bonding of the antibodies to the surface, compared to previous studies. The dynamic range of the biosensor was between 20 to 120 pg/ml and its limit of detection of the biomarker VEGF-A(165) was obtained to be about 0.007 pg/ml, using different electric signal transduction modes. Hence, the biosensor is a beneficial immunosensor with high sensitivity and ideal dynamic range for early-stage diagnosis of breast cancer and other cancers diseases associated with expression of VEGF-A(165). The as-prepared immunosensor could be efficiently employed for designing a point-of-care diagnostic platform.

Microplastics impair olfactory-mediated behaviors of goldfish Carassius auratus

Recently, the ubiquitous presence of microplastics (MPs) has drawn worldwide concern over its potential threat to aquatic organisms. However, the effects of MPs on the olfactory ability of fish and the subsequent odorant evoked behaviors remain elusive. In the present study, we analyzed the potential olfactory toxicity of polystyrene (PS) MPs by assessing olfactory-driven behaviors of goldfish in response to odorants. Our results showed that the olfactory-driven behavioral responses of goldfish to L-cysteine and taurocholic acid were significantly hampered by a 28-day MP exposure. Further analysis demonstrated that exposure to MPs may suppress the expression of genes encoding olfactory G protein-coupled receptors, inhibit the enzyme activities of cation transport ATPases crucial for action potential generation, alter the in vivo contents of neurotransmitters as well as metabolites involved in the transduction of electrical signals, and cause olfactory bulb injury and neurotoxicity closely related to the processing of electrical signals. In conclusion, the results obtained in the present study suggest that MPs at environmentally relevant concentrations could impair the olfactory-mediated behavioral responses of goldfish, probably through hampering odorant identification, action potential generation, olfactory neural signal transduction, and olfactory information processing.

Detection and Characterization of Vesicular Gangliosides Binding to Myelin-Associated Glycoprotein on Supported Lipid Bilayers.

In the nervous system, a myelin sheath that originates from oligodendrocytes or Schwann cells wraps around axons to facilitate electrical signal transduction. The interface between an axon and myelin is maintained by a number of biomolecular interactions. Among the interactions are those between GD1a and GT1b gangliosides on the axon and myelin-associated glycoprotein (MAG) on myelin. Interestingly, these interactions can also inhibit neuronal outgrowth. Ganglioside-MAG interactions are often studied in cellular or animal models where their relative concentrations are not easily controlled or in assays where the gangliosides and MAG are not presented as part of fluid lipid bilayers. Here, we present an approach to characterize MAG-ganglioside interactions in real time, where MAG, GD1a, and GT1b contents are controlled and they are in their in vivo orientation within fluid lipid bilayers. Using a quartz crystal microbalance with dissipation monitoring (QCM-D) biosensor functionalized with a supported lipid bilayer (SLB) and MAG, we detect vesicular GD1a and GT1b binding and determine the interaction kinetics as a function of vesicular ganglioside content. MAG-bound vesicles are deformed similarly, regardless of the ganglioside or its mole fraction. We further demonstrate how MAG-ganglioside interactions can be disrupted by antiganglioside antibodies that override MAG-based neuron growth inhibition.

Topical application of Zanthoxylum piperitum extract improves lateral canthal rhytides by inhibiting muscle contractions

Facial wrinkles are the predominant phenotypes of skin aging. To date, one of the most effective ways to improve wrinkles is botulinum toxin type A (BoNT/A) injection, which inhibits muscle contractions by reducing acetylcholine release from neurons. However, since BoNT/A is a hazardous neurotoxin, the injection can only be performed by medical doctors and the procedure is only possible through invasive injection, causing inconveniences such as pain. To overcome these inconveniences, we tried to find a way to reduce wrinkles non-invasively via mechanisms similar to BoNT/A. We first designed in vitro assays to test BoNT/A-like muscle contraction inhibition in two different model systems. By using the assays, we identified Zanthoxylum piperitum (Z. piperitum) fruit extract as a BoNT-like reagent (27.7% decrease of muscle contraction rates by 1000 ppm of Z. piperitum extract treatment). Next, we determined mechanisms of how Z. piperitum extract decreases muscle contraction rates and found that the extract treatment inhibits electrical signal transduction in neurons. We also showed that among known components of Z. piperitum extract, quercitrin is responsible for muscle contraction inhibition. We further identified that Z. piperitum extract has synergistic effects with acetyl hexapeptide-8 and BoNT/A light chain, which are well-known BoNT-like peptides. Finally, we showed that topical treatment of the Z. piperitum extract indeed decreases facial wrinkles and treatment of Z. piperitum extract with acetyl hexapeptide-8 has a tendency to improve wrinkles synergistically (14.5% improvement on average). The synergistic effect of the combination is expected to improve wrinkles effectively by implementing the BoNT/A mechanisms in a non-invasive way.

Charge Propagation along the Polymer Fiber of Polyhydroxybutyrate: Is it Possible to Apply the Cable Model?

This article considers experimental data on the surface charge propagation along the dielectric polymer fibers. Nonwoven polymer materials based on polyhydroxybutyrate obtained by electrospinning technique were used as an example of dielectric fibers in our experiments. Polymer fiber charging was investigated under the electron beam in a vacuum chamber of the scanning electron microscope. The fiber electric response registration was performed in a TV mode and in dynamic conditions using oscilloscopic sectioning visualization. Digitized images were processed using specialized software by Sobel-Feldman operator (Sobel filter), visualizing isopotential lines of the electron beam-induced emission. The results obtained were analyzed in the framework of the Roll’s cable model, which has been extrapolated from the electrical signal transduction along the nerve fibers to the charge propagation along the dielectric polymer fibers.