Significant Stimuli Research Articles

A new EEG determinism analysis method based on multiscale dispersion recurrence plot

Mild cognitive impairment (MCI) represents the preliminary stage of Alzheimer's disease. Excavating effective electroencephalography (EEG) markers for the timely diagnosis of MCI remain an urgent scientific issue that is of great significance for preventing the deterioration of the disease. In this study, we proposed a novel method, multiscale dispersion recurrence plot (MDRP), to analyze the multiscale recursive information of signals. First, the Logistic model was used to generate stimulus signals. The performance of MDRP and multiscale order recurrence plot (MORP) algorithms were analyzed in data length, embedding dimension, signal complexity, signal-to-noise ratio, and scale factor. The results indicate the MDRP algorithm is less sensitive to the data length, embedding dimension, and noise, and can reflect the nonlinear characteristics of the chaotic model more accurately. Next, we implemented the MDRP algorithm to evaluate EEG data with normal cognition and mild cognitive impairment and calculated the determinism (DET) values on multiple time scales to explore the nonlinear dynamic characteristics of the EEG data. The results showed that the short-scale DET values of MCI patients were significantly lower than those of the control group. In addition, we performed the Pearson correlation analysis between cognitive scale score and EEG DET values. The results demonstrate the DET based on MDRP is an EEG marker associated with cognitive impairment. In conclusion, MDRP provides a new way to effectively characterize the nonlinear characteristics of MCI EEG signals at various scales.

Extracellular Ca2+ aggravates IgE-induced allergic reaction in mast cells through GPRC6A, a novel family C G-protein-coupled receptor

AimsAs an essential indicator of allergic reactions, mast cell (MC) activation involves FcεRI-mediated signaling and the release of allergic mediators. In FcεRI signaling, Ca2+ is located at the intersection of multiple cellular signaling pathways. However, the effect of extracellular Ca2+ (exCa2+) on MCs during anaphylaxis remains unclear, along with its exact mechanisms. Therefore, we sought to determine whether and how elevated exCa2+ amplifies allergic reactions. Main methodsIn vitro experiments used immunoglobulin E (IgE)/antigen (Ag)-induced activation of rat and mouse MCs in vitro. The levels of MC degranulation mediators were used to evaluate the effect of exCa2+. In vivo experiments used MC-mediated passive systemic anaphylaxis (PCA) Balb/c mice. After stimulation, anaphylaxis indexes such as rectal temperature and allergic symptom score were detected. Key findingsIn vitro experiments revealed that exCa2+ is a stimulus signal for the aggravation of allergic reactions in MCs. When antagonists or siRNA inhibited GPRC6, MCs released fewer inflammatory mediators. Moreover, in vivo experiments confirmed in vitro results. Allergic symptoms were alleviated by antagonists NPS2143 in PCA mice, demonstrating that exCa2+ aggravates allergic reactions through GPRC6A. SignificanceOur study provides an essential theoretical basis for targeting Ca2+ and GPRC6A as therapeutic options for allergies.

A Novel mHealth Approach for the Monitoring and Assisted Therapeutics of Obstructive Sleep Apnea

Obstructive sleep apnea is a respiratory problem that has serious consequences for physical and mental health, but also in monetary terms, since traffic accidents and poor work performance, among other direct consequences, are attributed to it. It is estimated that between 9% and 38% of the world’s population has this disease. This is a multifactorial disease, therefore, there are several methods of detection and treatment; however, all of them cause discomfort to the patient, or to those around them. In this article we propose a system for the detection and control of obstructive sleep apnea that promises to overcome the drawbacks of the existing therapies, therefore, potentially making it a practical and effective solution for this disease. The proof of concept presented in this paper makes use of an electromyography sensor to collect the myoelectric signal produced by the genioglossus muscle. Surface electrodes provide the electromyography signals to an ESP32 microcontroller, which has the function of analyzing and comparing the data obtained with a predefined value of the apnea threshold. After the detection of an apnea, the circuit is able to create a stimulus signal that is applied directly to the muscle, so that airway occlusion does not occur, and the user does not wake up. The data from each use are automatically sent to a database to be viewed and analyzed at a later point.

Dynamic Impedance Spectroscopy of Lithium Plating from Next Generation Electrolytes

The anode-free cells have emerged due to the need to maximize Li metal batteries' energy density. However, anode-free Li batteries suffer from short cycle life because of the lack of Li inventory at the anode. Freshly deposited Li metal anodes usually take hundreds of cycles to reach initial SEI stabilization optimum coulombic efficiency (CE) due to initial SEI stabilization and electrode activation. The anode-free cell design requires high Li metal CE over the whole cycling life, particularly during the initial activation cycles. A holistic approach to electrolyte design, mechanism understanding, and battery engineering is needed to fulfill these requirements. Here, we present a mechanistic study on lithium plating and stripping from next generation electrolytes.We conducted dynamic impedance spectroscopy (dEIS) to probe the formation and evolution of the SEI during Li plating and stripping on copper current collectors. dEIS superimposes a multisine waveform atop the dc stimulus signal, as shown by the lightly shaded curves in Fig 1 (top left). We applied a sliding window FFT protocol that takes the complex ratio of the measured potential and current signals obtained from Fig 1 (top right) and transforms it into complex impedance. We will discuss two Li platting systems, Lipon (an amorphous ceramic) and a liquid electrolyte with stabilizing additives. We observed drastic changes in the cells' impedance during plating and stripping, Figure 1 (bottom plots). We will show how the passivation layer's impedance continues to evolve during Li cycling and accounts for a significant amount of the overall cell resistance.The US Department of Energy’s Energy Efficiency and Renewable Energy Vehicles Technologies Office provided funding for this work under the US-German Cooperation on Energy Storage: Lithium-Solid-Electrolyte Interfaces program. Figure 1

DESIGN AND DEVELOPMENT OF A NOVEL PORTABLE TCM MUSIC ELECTROACUPUNCTURE APPARATUS

Electroacupuncture is an effective therapy method in Traditional Chinese Medicine (TCM), but the monotonic repeatability of stimulus signals may face problems due to the body’s tolerance. Music therapy is a widely used method for targeting mental and neurological diseases. Music electroacupuncture combines the advantages of these two therapies by using the variability of music to deal with the tolerance problem. Presently, the stimulus signals of the music electroacupuncture devices are filtered from music, and the frequency of the electric plus is not easy to control. In this pursuit, a new processing circuit of music electroacupuncture signal was proposed using a novel portable music electroacupuncture apparatus based on the Chinese Medical music therapy. Specifically, as the stimulus signal changes synchronously with the music, the frequency of the stimulus plus signal can be flexibly controlled. Using headphones, a selected synchronous intervention music and electrical stimulation worked synchronously to achieve the therapeutic effect of physical and mental harmony. Experiments and measurements confirmed that the stimulation parameters of the proposed electroacupuncture apparatus in this study met the provisions of relevant standards, and the stimulation output was safe and reliable. Furthermore, it offered better and more comfortable body feelings, compared to other music electroacupuncture methods.

PREFACE: A SPECIAL SELECTION ON EMERGING TECHNIQUES FOR BIOMECHANICS–PART II

PREFACE: A SPECIAL SELECTION ON EMERGING TECHNIQUES FOR BIOMECHANICS–PART II

2D Metal–Organic Framework Based Optoelectronic Neuromorphic Transistors for Human Emotion Simulation and Neuromorphic Computing

2D metal–organic frameworks (2D‐MOFs) have been extensively studied as promising materials in the fields of electrocatalysis, drug delivery, electronic devices, etc. However, few studies have explored the application potential of 2D‐MOFs in novel neuromorphic computing devices. Herein, an optoelectronic neuromorphic transistor based on a 2D‐MOF/polymer charge‐trapping layer is reported. It is found that the large specific surface area, stable crystal structure, and highly accessible active sites in 2D‐MOFs make them excellent charge‐trapping materials for the devices, which are beneficial for mimicking the memory and learning functions observed in the organism's nervous systems. Different types of synaptic behaviors have been realized in the 2D‐MOF‐based neuromorphic devices under stimuli signal, e.g., paired‐pulse facilitation, excitatory postsynaptic current, short‐term memory, and long‐term memory. More interestingly, emotion‐adjustable learning behavior is realized by changing the value of the source–drain voltage. This work can shed light on the application of 2D‐MOFs in neuromorphic computing and will contribute to the further development of neuromorphic computing devices. An interactive preprint version of the article can be found at DOI: https://doi.org/10.22541/au.165530836.62586068/v1.

Contribution of mechanical homeostasis to epithelial-mesenchymal transition.

Metastasis refers to the spread of cancer cells from a primary tumor to other parts of the body via the lymphatic system and bloodstream. With tremendous effort over the past decades, remarkable progress has been made in understanding the molecular and cellular basis of metastatic processes. Metastasis occurs through five steps, including infiltration and migration, intravasation, survival, extravasation, and colonization. Various molecular and cellular factors involved in the metastatic process have been identified, such as epigenetic factors of the extracellular matrix (ECM), cell-cell interactions, soluble signaling, adhesion molecules, and mechanical stimuli. However, the underlying cause of cancer metastasis has not been elucidated. In this review, we have focused on changes in the mechanical properties of cancer cells and their surrounding environment to understand the causes of cancer metastasis. Cancer cells have unique mechanical properties that distinguish them from healthy cells. ECM stiffness is involved in cancer cell growth, particularly in promoting the epithelial-mesenchymal transition (EMT). During tumorigenesis, the mechanical properties of cancer cells change in the direction opposite to their environment, resulting in a mechanical stress imbalance between the intracellular and extracellular domains. Disruption of mechanical homeostasis may be one of the causes of EMT that triggers the metastasis of cancer cells.

Cortical mechanisms of visual brightness.

SUMMARYThe primary visual cortex signals the onset of light and dark stimuli with ON and OFF cortical pathways. Here, we demonstrate that both pathways generate similar response increments to large homogeneous surfaces and their response average increases with surface brightness. We show that, in cat visual cortex, response dominance from ON or OFF pathways is bimodally distributed when stimuli are smaller than one receptive field center but unimodally distributed when they are larger. Moreover, whereas small bright stimuli drive opposite responses from ON and OFF pathways (increased versus suppressed activity), large bright surfaces drive similar response increments. We show that this size-brightness relation emerges because strong illumination increases the size of light surfaces in nature and both ON and OFF cortical neurons receive input from ON thalamic pathways. We conclude that visual scenes are perceived as brighter when the average response increments from ON and OFF cortical pathways become stronger.

Pain and nociception bioinspiration for the development of a micellar-based screening test for antinociceptive drugs

Pain is a signal of harmful stimuli generated by the nociceptive system through the activation of receptors or channels present on the surface of the nociceptors. For example, the acid-sensing ion channels (ASICs) are activated by minor pH variations related to many different disorders. Drugs that cease the stimulus (and pain) antagonize this process. The treatment of pain is a serious public health issue and because of that, there has been a huge effort to develop new antinociceptive drugs. The main objective of this article was to develop a screening test bioinspired by ASIC channels to accelerate the development of new antinociceptive drugs and reduce the number of experiments conducted in animals. For that, a micellar dispersion of polystyrene-b-poly (acrylic acid) (PS-b-PAA) was tested encapsulating p-nitrophenyl butyrate (p-NFB) in the presence of lipase isolated from Pseudomonas fluorescens. When the p-NFB is released, the lipase hydrolyses it to the corresponding phenol, which can be detected in a clear analytical response. The system was pH-responsive between pH 7.4 and 7.0, and the signal was suppressed by ibuprofen as expected for an ASICs bioinspired system. The developed system seems to be effective for screening new drugs in the physiological pH range, proved to be stable, with associated low cost, and is easy to use.

Regulation of immune complex formation and signalling by FERONIA, a busy goddess in plant-microbe interactions.

Being sessile in soil, plant cells rely on cell‐surface receptors to sense and transduce environmental stimulus signals into intracellular responses. FERONIA (FER), a Catharanthus roseus receptor‐like kinase 1‐like protein, has emerged as a versatile regulator of plant growth, development, and stress responses. In recent years, accumulating studies have witnessed rapid advances in dissecting the mechanisms underlying the interaction between FER and its partners in response to pathogen invasion, particularly regulation of immune complex formation and signalling. Moreover, hormonal signalling, rhizosphere microbiota and other constituents are also extensively involved in these processes.

A Self‐Powered, Single‐Mode Tactile Sensor Based on Sensory Adaptation Using Piezoelectric‐Driven Ion Migration

AbstractA piezoelectric tactile sensor is beneficial for creating a self‐powered system with a compact design, which is essential in electronic‐skin technology. However, piezoelectricity is only capable of dynamic pressure detection because it responds to sudden environmental changes. Since it is common to add another sensing unit to detect static pressure that accompanies bulkiness, including a measuring apparatus, we demonstrate a self‐powered, single‐mode piezoelectric tactile sensor by fabricating a piezoelectric gel through the electrospinning technique. As piezoelectricity senses the dynamic pressure without an external power supply, ions detect the static pressure by maintaining the potential difference upon sustained pressure. Since each component outputs a voltage signal of the same type but different profiles upon pressure, it is possible to distinguish dynamic and static pressure in a single mode. Moreover, inspired by the sensory adaptation of mammalian skin, an ion‐assisted piezoelectric tactile sensor efficiently detects concurrently stacked stimuli by decreasing the output signal for sustained stimuli. The sensitivity for superimposed pressure upon initial 14.7 kPa increases by more than four times compared to that without sensory adaptation for both dynamic and static pressure.

CuCo2S4 nanozyme-based stimulus-responsive hydrogel kit for rapid point-of-care testing of uric acid.

An efficient analysis platform composed of nanozyme-based hydrogel kit and smartphone was constructed for on-site detection of uric acid (UA) in a rapid and realiable manner. CuCo2S4 nanoparticles (CuCo2S4 NPs) as a peroxidase mimic were successfully prepared and the peroxidase-like activity and catalytic mechanism were studied in detail. The hydrogen peroxide (H2O2) stimulus-responsive nanozyme-based hydrogel kit was manufactured by integrating agarose, CuCo2S4 NPs, and 3,3',5,5'-tetramethylbenzidine (TMB) into the cap of centrifuge tube. H2O2 generated via UA oxidation acts as stimulus signal, which triggers the oxidation of TMB to form blue product (oxTMB) under the catalysis of CuCo2S4 NPs, resulting in the color response of the constructed kit. The color image of the kit was captured by a smartphone built-in camera and converted into color intensity using ImageJ software, thus achieving the quantitative determination of UA. The portable kit possesses high selectivity and was used to monitor UA in human serum with satisfactory results (recovery was in the range 95.8-107.3% and RSD was not greater than 4.6%). The established sensing platform is convenient and reliable, which provides a new strategy for point-of-care testing of UA and has a broad prospect in the fields of chemical sensing and biomedical.

Structural signatures of Escherichia coli chemoreceptor signaling states revealed by cellular crosslinking

The chemotaxis machinery of Escherichia coli has served as a model for exploring the molecular signaling mechanisms of transmembrane chemoreceptors known as methyl-accepting chemotaxis proteins (MCPs). Yet, fundamental questions about signal transmission through MCP molecules remain unanswered. Our work with the E. coli serine chemoreceptor Tsr has developed invivo reporters that distinguish kinase-OFF and kinase-ON structures in the cytoplasmic methylation helix (MH) cap, which receives stimulus signals from an adjoining, membrane-proximal histidine kinase, adenylyl cyclases, MCPs, and phosphatases (HAMP) domain. The cytoplasmic helices of the Tsr homodimer interact mainly through packing interactions of hydrophobic residues at a and d heptad positions. We investigated the invivo crosslinking properties of Tsr molecules bearing cysteine replacements at functionally tolerant g heptad positions in the N-terminal and C-terminal cap helices. Upon treatment of cells with bismaleimidoethane (BMOE), a bifunctional thiol-reagent, Tsr-G273C/Q504C readily formed a doubly crosslinked product in the presence of serine but not in its absence. Moreover, a serine stimulus combined with BMOE treatment during invivo Förster resonance energy transfer-based kinase assays locked Tsr-G273C/Q504C in kinase-OFF output. An OFF-shifting lesion in MH1 (D269P) promoted the formation of the doubly crosslinked species in the absence of serine, whereas an ON-shifting lesion (G268P) suppressed the formation of the doubly crosslinked species. Tsr-G273C/Q504C also showed output-dependent crosslinking patterns in combination with ON-shifting and OFF-shifting adaptational modifications. Our results are consistent with a helix breathing-axial rotation-bundle repacking signaling mechanism and imply that invivo crosslinking tools could serve to probe helix-packing transitions and their output consequences in other regions of the receptor molecule.

P-759 Comparison of DNA methylation profiles of human embryo cultured in either uninterrupted or interrupted incubators

Abstract Study question Are there are differences in the DNA methylation profiles of human embryos cultured in Time-lapse imaging (TLI) and standard incubators (SI)? Summary answer The genome-wide DNA methylation landscape was globally similar between the SI and TLI groups. What is known already Early embryonic development is a special biological process, along with dynamic changes of DNA methylation. In vitro culturing ensured the successful development of human embryo, and is the most important step of ART cycle. TLI is one type of newly developed ART embryo culture systems, which allows for continuous assessment of embryonic development. Our previous study performed transcriptome analysis to compare SI and TLI and found that the global transcriptomic profiles were similar between the two groups. However, whether there are differences in the DNA methylation profiles of human embryos cultured in TLI and SI still unknown. Study design, size, duration This study was designed to explore the influence of SI and TLI incubator culturing on genome-wide DNA methylation of human eight-cell embryos. A total of 9 women who received IVF treatment, ≤ 30 years old (range: 20–30 years), without a history of genetic diseases or smoking were included in this study. Participants/materials, setting, methods Transvaginal oocyte retrieval was performed 36 h after HCG injection. Cumulus-enclosed oocytes were collected in 2.5 mL IVF medium and incubated in 5% O2, 6% CO2, and 37 °C incubators for insemination. The fertilized oocytes were transferred into pre-equilibrated Embryoslides. Then the embryoslides were cultured in either TLI or SI at 37 °C with 5% O2 and 6% CO2 until embryo transfer on Day 3. Samples were sequenced by the Illumina HiSeq 4000 with a 150-bp paired-end. Main results and the role of chance The genome-wide methylation patterns and CpG methylation levels in transposable elements and imprinting control regions of TLI-cultured embryos were similar to those of the SI-cultured embryos. However, a small number of differentially methylated regions (DMRs) were detected, and these DMRs mainly occurred in exons other than promoters. Functional annotation revealed that the genes in DMRs tended to execute functions such as cell cycle, DNA damage stimulus, histone modification, mitochondrial, glucose import, and MAPK signaling pathway. Limitations, reasons for caution Small sample size. Wider implications of the findings Evaluated the safety of TLI culture system from the perspective of DNA methylation at single-cell level, and provided an important reference for understanding the association between embryo culture condition and epigenetic regulation. Trial registration number not applicable

Recent Progress in Bio-Responsive Drug Delivery Systems for Tumor Therapy.

Spatially- and/or temporally-controlled drug release has always been the pursuit of drug delivery systems (DDSs) to achieve the ideal therapeutic effect. The abnormal pathophysiological characteristics of the tumor microenvironment, including acidosis, overexpression of special enzymes, hypoxia, and high levels of ROS, GSH, and ATP, offer the possibility for the design of stimulus-responsive DDSs for controlled drug release to realize more efficient drug delivery and anti-tumor activity. With the help of these stimulus signals, responsive DDSs can realize controlled drug release more precisely within the local tumor site and decrease the injected dose and systemic toxicity. This review first describes the major pathophysiological characteristics of the tumor microenvironment, and highlights the recent cutting-edge advances in DDSs responding to the tumor pathophysiological environment for cancer therapy. Finally, the challenges and future directions of bio-responsive DDSs are discussed.

The Role of Cd28 Costimulatory Receptors in Signalling Pathways

Naive T cells require extracellular stimulus signals through the T-cell receptor cascade (TCR). This TCR then recognized the antigens present on the molecules of the major histocompatibility complex (MHC) using the CD4 and CD8 receptor. Upon recognition, TCR- induced signal transduction propagates signals through different molecules and induced secondary signalling. Consequently, intracellular signaling cascades determine the characteristics of immune responses mediated by T- cells. Consequently, rigorous regulation of T-cell activation is crucial for T-cell homeostasis and appropriate immune responses. Dysregulation of TCR signalling can result in energy or autoimmunity. In this review article, we summarize current knowledge on the signalling pathways that govern how the TCR complex transmits signals into cells and the roles of effector molecules that are involved in these pathways.

The stationarity control of the average links for the Hebb complex dynamical network via external stimulus signals

The model of complex dynamical network (CDN) can be represented as the mathematic graph, in which some characteristics may emerge from the dynamic nodes group (NG) and links group (LG). This paper primarily focuses on the feature appearing from the dynamic links. The average link weight (ALW), as a novel quantitative index to describe the characteristic of dynamic links is introduced. Inspired by the Hebb’s neuroscience theory, the Hebb complex dynamical network (HCDN) is constructed. The ALW of the HCDN can track a given target via external stimulus signals with adaptive amplifiers’ proportional coefficients. In other words, the stationary network implies the ALW is a constant in time. Finally, two simulation examples are performed to validate the proposed adaptive update law’s effectiveness.

Undeserved reward but not inevitable loss biases attention: Personal control moderates evaluative attentional biases in the additional-singleton paradigm.

It is important for organisms to notice signals of opportunities (i.e., chances for performance-dependent reward) and dangers (i.e., performance-dependent risks of loss). Attentional biases towards opportunity and danger signals should therefore be functionally valuable. By contrast, the functional value of attentional biases towards signals of performance-independent (i.e., uncontrollable) rewards or losses is not obvious. The present study compares attentional biases towards positive and negative stimuli, depending on whether the stimuli signal performance-dependent or performance-independent reward or loss. Specifically, we induced colour-valence associations before engaging participants in an additional-singleton task that measures attentional bias. In the valence-induction phase, one colour signalled a potential reward, and another colour signalled a potential loss; importantly, in one group, rewards and losses were performance-dependent, whereas in another group, they were performance-independent (i.e., seemingly random). In the subsequent additional-singleton task, we found increased additional-singleton effects for colours associated with performance-dependent rewards and losses (i.e., opportunities and dangers). If, however, rewards and losses were performance-independent, the singleton effect was enhanced only for reward but not loss stimuli.

Dual-Responsive Photonic Crystal Sensors Based on Physical Crossing-Linking SF-PNIPAM Dual-Crosslinked Hydrogel.

Flexible wearable materials have frequently been used in drug delivery, healthcare monitoring, and wearable sensors for decades. As a novel type of artificially designed functional material, photonic crystals (PCs) are sensitive to the changes in the external environment and stimuli signals. However, the rigidity of the PCs limits their application in the field of biometric and optical sensors. This study selects silk fibroin (SF) and poly-N-isopropylacrylamide (PNIPAM) as principal components to prepare the hydrogel with the physical crosslinking agent lithium silicate (LMSH) and is then integrated with PCs to obtain the SF-PNIPAM dual-crosslinked nanocomposite for temperature and strain sensing. The structural colors of the PCs change from blue to orange-red by the variation in temperature or strain. The visual temperature-sensing and adhesion properties enable the SF-PNIPAM dual-crosslinked nanocomposite to be directly attached to the skin in order to monitor the real-time dynamic of human temperature. Based on its excellent optical properties and biocompatibility, the SF-PNIPAM dual-crosslinked nanocomposite can be applied to the field of visual biosensing, wearable display devices, and wound dressing materials.