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Science Advances Sep 2021The biophysical characteristics of the extracellular matrix (ECM), such as a three-dimensional (3D) network and bioelectricity, have a profound influence on cell...
The biophysical characteristics of the extracellular matrix (ECM), such as a three-dimensional (3D) network and bioelectricity, have a profound influence on cell development, migration, function expression, etc. Here, inspired by these biophysical cues of ECM, we develop an electromechanical coupling bio-nanogenerator (bio-NG) composed of highly discrete piezoelectric fibers. It can generate surface piezopotential up to millivolts by cell inherent force and thus provide in situ electrical stimulation for the living cells. Besides, the unique 3D space in the bio-NGs provides an ECM-like growth microenvironment for cells. As a result, our bio-NGs effectively promote cell viability and development and, more importantly, maintain its specific functional expression. These advanced in vitro bio-NGs are expected to fill the gap between the inaccurate 2D systems and the expensive and time-consuming animal models, mimicking the complexity of the ECM and the physiological relevance of an in vivo biological system.
PubMed: 34559554
DOI: 10.1126/sciadv.abh2350 -
Journal of Medical Internet Research Sep 2021Measuring weight bearing is an essential aspect of clinical care for lower limb injuries such as sprains or meniscopathy surgeries. This care often involves the use of... (Observational Study)
Observational Study
Versatile GCH Control Software for Correction of Loads Applied to Forearm Crutches During Gait Recovery Through Technological Feedback: Development and Implementation Study.
BACKGROUND
Measuring weight bearing is an essential aspect of clinical care for lower limb injuries such as sprains or meniscopathy surgeries. This care often involves the use of forearm crutches for partial loads progressing to full loads. Therefore, feasible methods of load monitoring for daily clinical use are needed.
OBJECTIVE
The main objective of this study was to design an innovative multifunctional desktop load-measuring software that complements GCH System 2.0-instrumented forearm crutches and monitors the applied loads, displaying real-time graphical and numerical information, and enabling the correction of inaccuracies through feedback technology during assisted gait. The secondary objective was to perform a preliminary implementation trial.
METHODS
The software was designed for indoor use (clinics/laboratories). This software translates the crutch sensor signal in millivolts into force units, records and analyzes data (10-80 Hz), and provides real-time effective curves of the loads exerted on crutches. It covers numerous types of extrinsic feedback, including visual, acoustic (verbal/beeps), concurrent, terminal, and descriptive feedback, and includes a clinical and research use database. An observational descriptive pilot study was performed with 10 healthy subjects experienced in bilateral assisted gait. The Wilcoxon matched-pairs signed-rank test was used to evaluate the load accuracy evolution of each subject (ie, changes in the loads exerted on crutches for each support) among various walks, which was interpreted at the 95% confidence level.
RESULTS
GCH Control Software was developed as a multifunctional desktop tool complementing GCH System 2.0-instrumented forearm crutches. The pilot implementation of the feedback mechanism observed 96/100 load errors at baseline (walk 0, no feedback) with 7/10 subjects exhibiting crutch overloading. Errors ranged from 61.09% to 203.98%, demonstrating heterogeneity. The double-bar feedback found 54/100 errors in walk 1, 28/100 in walk 2, and 14/100 in walk 3. The first walk with double-bar feedback (walk 1) began with errors similar to the baseline walk, generally followed by attempts at correction. The Wilcoxon matched-pairs signed-rank test used to evaluate each subject's progress showed that all participants steadily improved the accuracy of the loads applied to the crutches. In particular, Subject 9 required extra feedback with two single-bar walks to focus on the total load. The participants also corrected the load balance between crutches and fluency errors. Three subjects made one error of load balance and one subject made six fluctuation errors during the three double-bar walks. The latter subject performed additional feedback with two balance-bar walks to focus on the load balance.
CONCLUSIONS
GCH Control Software proved to be useful for monitoring the loads exerted on forearm crutches, providing a variety of feedback for correcting load accuracy, load balance between crutches, and fluency. The findings of the complementary implementation were satisfactory, although clinical trials with larger samples are needed to assess the efficacy of the different feedback mechanisms and to select the best alternatives in each case.
Topics: Crutches; Feedback; Forearm; Gait; Humans; Pilot Projects; Software; Technology
PubMed: 34550073
DOI: 10.2196/27602 -
Saudi Journal of Biological Sciences Aug 2021Asthma as chronic airway disease has high prevalence in children and imbalance of Th1/Th2 is a critical mechanism in pathogenesis of the asthma. Baicalein as a cell...
Asthma as chronic airway disease has high prevalence in children and imbalance of Th1/Th2 is a critical mechanism in pathogenesis of the asthma. Baicalein as a cell protective and anti-inflammatory flavonoid may have anti-asthma effect. Therefore, for better using lung, baicalein was used in chitosan-nanoparticle as anti-asthma treatment. Baicalein was loaded and encapsulated in chitosan nanoparticle. The morphology, physical characters (particle size, zeta potential and FT-IR) were analyzed. Drug encapsulation and loading capacity, accumulative release-time were studied. After asthma model producing, the mice were treated with L-B-NP and E-B-NP. At least, MCh challenge test, Cytokines measurement and Lung Histopathology were done. Nanoparticles had average size 285 ± 25 nm with negative charge -2.5 mV. The L-B-NP decreased penh value and E-B-NP decreased inflammation. Both nanoparticles increased IL-12 and decreased IL-5. Also, L-B-NP decreased mucus secretion in bronchi. L-B-NP and E-B-NP control immune-allergo-inflammatory response of asthma. L-B-NP controlled AHR and E-B-NP controlled inflammation that can be used as controlling anti-asthma drug.
PubMed: 34354413
DOI: 10.1016/j.sjbs.2021.04.009 -
Methods in Enzymology 2021Membrane potential is a fundamental biophysical parameter common to all of cellular life. Traditional methods to measure membrane potential rely on electrodes, which are...
Membrane potential is a fundamental biophysical parameter common to all of cellular life. Traditional methods to measure membrane potential rely on electrodes, which are invasive and low-throughput. Optical methods to measure membrane potential are attractive because they have the potential to be less invasive and higher throughput than classic electrode based techniques. However, most optical measurements rely on changes in fluorescence intensity to detect changes in membrane potential. In this chapter, we discuss the use of fluorescence lifetime imaging microscopy (FLIM) and voltage-sensitive fluorophores (VoltageFluors, or VF dyes) to estimate the millivolt value of membrane potentials in living cells. We discuss theory, application, protocols, and shortcomings of this approach.
Topics: Fluorescent Dyes; Membrane Potentials; Microscopy, Fluorescence; Optical Imaging
PubMed: 34099175
DOI: 10.1016/bs.mie.2021.02.009 -
Nature Communications May 2021Oxygen release and irreversible cation migration are the main causes of voltage fade in Li-rich transition metal oxide cathode. But their correlation is not very clear...
Oxygen release and irreversible cation migration are the main causes of voltage fade in Li-rich transition metal oxide cathode. But their correlation is not very clear and voltage decay is still a bottleneck. Herein, we modulate the oxygen anionic redox chemistry by constructing LiZrO slabs into LiMnO domain in LiNiMnO, which induces the lattice strain, tunes the chemical environment for redox-active oxygen and enlarges the gap between metallic and anionic bands. This modulation expands the region in which lattice oxygen contributes capacity by oxidation to oxygen holes and relieves the charge transfer from anionic band to antibonding metal-oxygen band under a deep delithiation. This restrains cation reduction, metal-oxygen bond fracture, and the formation of localized O molecule, which fundamentally inhibits lattice oxygen escape and cation migration. The modulated cathode demonstrates a low voltage decay rate (0.45 millivolt per cycle) and a long cyclic stability.
PubMed: 34031408
DOI: 10.1038/s41467-021-23365-9 -
Nature Communications Feb 2021A graphdiyne-based artificial synapse (GAS), exhibiting intrinsic short-term plasticity, has been proposed to mimic biological signal transmission behavior. The impulse...
A graphdiyne-based artificial synapse (GAS), exhibiting intrinsic short-term plasticity, has been proposed to mimic biological signal transmission behavior. The impulse response of the GAS has been reduced to several millivolts with competitive femtowatt-level consumption, exceeding the biological level by orders of magnitude. Most importantly, the GAS is capable of parallelly processing signals transmitted from multiple pre-neurons and therefore realizing dynamic logic and spatiotemporal rules. It is also found that the GAS is thermally stable (at 353 K) and environmentally stable (in a relative humidity up to 35%). Our artificial efferent nerve, connecting the GAS with artificial muscles, has been demonstrated to complete the information integration of pre-neurons and the information output of motor neurons, which is advantageous for coalescing multiple sensory feedbacks and reacting to events. Our synaptic element has potential applications in bioinspired peripheral nervous systems of soft electronics, neurorobotics, and biohybrid systems of brain-computer interfaces.
Topics: Dendrites; Density Functional Theory; Diffusion; Graphite; Ions; Nerve Net; Neuronal Plasticity; Neurons, Efferent; Signal Transduction; Synapses; Temperature
PubMed: 33594066
DOI: 10.1038/s41467-021-21319-9 -
PLoS Computational Biology Feb 2021Axonal connections are widely regarded as faithful transmitters of neuronal signals with fixed delays. The reasoning behind this is that extracellular potentials caused...
Axonal connections are widely regarded as faithful transmitters of neuronal signals with fixed delays. The reasoning behind this is that extracellular potentials caused by spikes travelling along axons are too small to have an effect on other axons. Here we devise a computational framework that allows us to study the effect of extracellular potentials generated by spike volleys in axonal fibre bundles on axonal transmission delays. We demonstrate that, although the extracellular potentials generated by single spikes are of the order of microvolts, the collective extracellular potential generated by spike volleys can reach several millivolts. As a consequence, the resulting depolarisation of the axonal membranes increases the velocity of spikes, and therefore reduces axonal delays between brain areas. Driving a neural mass model with such spike volleys, we further demonstrate that only ephaptic coupling can explain the reduction of stimulus latencies with increased stimulus intensities, as observed in many psychological experiments.
Topics: Action Potentials; Animals; Axons; Biophysical Phenomena; Computational Biology; Computer Simulation; Extracellular Space; Humans; Models, Neurological; Nerve Fibers, Myelinated; Synaptic Transmission; White Matter
PubMed: 33556058
DOI: 10.1371/journal.pcbi.1007858 -
Proceedings of the National Academy of... Feb 2021Voltage sensing with genetically expressed optical probes is highly desirable for large-scale recordings of neuronal activity and detection of localized voltage signals...
Voltage sensing with genetically expressed optical probes is highly desirable for large-scale recordings of neuronal activity and detection of localized voltage signals in single neurons. Most genetically encodable voltage indicators (GEVI) have drawbacks including slow response, low fluorescence, or excessive bleaching. Here we present a dark quencher GEVI approach (dqGEVI) using a Förster resonance energy transfer pair between a fluorophore glycosylphosphatidylinositol-enhanced green fluorescent protein (GPI-eGFP) on the outer surface of the neuronal membrane and an azo-benzene dye quencher (D3) that rapidly moves in the membrane driven by voltage. In contrast to previous probes, the sensor has a single photon bleaching time constant of ∼40 min, has a high temporal resolution and fidelity for detecting action potential firing at 100 Hz, resolves membrane de- and hyperpolarizations of a few millivolts, and has negligible effects on passive membrane properties or synaptic events. The dqGEVI approach should be a valuable tool for optical recordings of subcellular or population membrane potential changes in nerve cells.
Topics: Action Potentials; Animals; Fluorescence Resonance Energy Transfer; Fluorescent Dyes; Green Fluorescent Proteins; HEK293 Cells; Humans; Membrane Potentials; Memory; Neurons
PubMed: 33531364
DOI: 10.1073/pnas.2020235118 -
Translational Vision Science &... Oct 2020The epithelium lining the ocular surface, which includes corneal and conjunctival epithelia, expresses the prosecretory chloride channel cystic fibrosis transmembrane...
PURPOSE
The epithelium lining the ocular surface, which includes corneal and conjunctival epithelia, expresses the prosecretory chloride channel cystic fibrosis transmembrane conductance regulator (CFTR) and the proabsorptive epithelial sodium channel (ENaC). Here, methodology was established to measure the millivolt (mV) potential differences at the ocular surface, called ocular surface potential difference (OSPD), in human subjects produced by ion transport.
METHODS
OSPD was measured in human subjects in which a fluid-filled measuring electrode contacted a fluid pool created by eversion of the lateral lower eyelid, with a reference electrode placed subcutaneously in the forearm. Through the use of a high-impedance voltmeter, OSPD was measured continuously over 10 to 15 minutes in response to a series of perfusate fluid exchanges.
RESULTS
Baseline OSPD (± SEM) in six normal human subjects was -21.3 ± 3.6 mV. OSPD depolarized by 1.7 ± 0.6 mV following the addition of the ENaC inhibitor amiloride, hyperpolarized by 6.8 ± 1.5 mV with a zero chloride solution, and further hyperpolarized by 15.9 ± 1.6 mV following CFTR activation by isoproterenol. The isoproterenol-induced hyperpolarization was absent in two cystic fibrosis subjects lacking functional CFTR. OSPD measurement produced minimal epithelial injury.
CONCLUSIONS
Our results establish the feasibility and safety of OSPD measurement in humans and demonstrate robust CFTR activity, albeit minimal ENaC activity, at the ocular surface. OSPD measurement may be broadly applicable to investigate fluid transport mechanisms and test drug candidates to treat ocular surface disorders.
TRANSLATIONAL RELEVANCE
To the best of our knowledge, this is the first measurement of the electrical potential generated by the ocular surface epithelium in human subjects, offering a new approach to study ocular surface function and health.
Topics: Amiloride; Cystic Fibrosis; Epithelial Sodium Channels; Eye; Humans; Ion Transport; Ocular Physiological Phenomena; Research Subjects
PubMed: 33117611
DOI: 10.1167/tvst.9.11.20 -
Chemical Science Jun 2020Attaining rational modulation of thermodynamic and kinetic redox parameters of metalloproteins is a key milestone towards the (re)design of proteins with new or improved...
Attaining rational modulation of thermodynamic and kinetic redox parameters of metalloproteins is a key milestone towards the (re)design of proteins with new or improved redox functions. Here we report that implantation of ligand loops from natural T1 proteins into the scaffold of a Cu protein leads to a series of distorted T1-like sites that allow for independent modulation of reduction potentials (°') and electron transfer reorganization energies (). On the one hand °' values could be fine-tuned over 120 mV without affecting . On the other, values could be modulated by more than a factor of two while affecting °' only by a few millivolts. These results are in sharp contrast to previous studies that used T1 cupredoxin folds, thus highlighting the importance of the protein scaffold in determining such parameters.
PubMed: 32953013
DOI: 10.1039/d0sc01620a