Characterization of Immune-Related Genes and Immune Infiltration Features in Epilepsy by Multi-Transcriptome Data.

Background: Epilepsy encompasses a group of heterogeneous brain diseases that afflict about 1% of the world's population. Accumulating evidence shows that the immune system plays a key role in epileptogenesis. Nevertheless, the immune-related mechanisms remain not been precisely understood. Methods: Three epilepsy datasets (GSE16969, GSE32534 and GSE143272) were screened to obtain differentially expressed immune-related genes (DEIRGs). Random forest (RF) and protein-protein interaction (PPI) network were constructed to identify core genes. Another dataset (GSE31718) and 60 clinical samples via quantitative real-time polymerase chain reaction (qRT-PCR) were utilized to validate core genes. Immune cell infiltration score was performed with CIBERSORTx tools and single-sample gene set enrichment analysis (ssGSEA). Gene set variation analysis (GSVA) and ssGSEA were conducted to determine the pathways that are significantly enriched during normal and epilepsy. The correlation between hub genes, immune cells, and enriched molecular pathways was evaluated by Pearson correlation analysis. Results: Based on RF and PPI, 4 DEIRGs (CSF1R, IL6R, TLR2, and TNFRSF1A) were identified as hub genes. Results of qRT-PCR validated that higher expression levels of CSF1R, IL6R, TLR2, and TNFRSF1A in epilepsy samples compared to control sample. Immune infiltration analysis by CIBERSORTx displayed immune signatures that are significantly richer in epilepsy, T cell subsets in particular. Notably, ssGSEA found that Th1 signatures were more abundant in normal tissues; yet Th2 signatures were more abundant in epilepsy tissues. Cytokine cytokine receptor interaction (CCR) was significantly enriched in epilepsy based on multi-transcriptome data. Additionally, hub genes were significantly correlated with score of Th1/Th2 signatures and enrichment score of CCR in multi-transcriptome data. Conclusion: Four IRGs (CSF1R, IL6R, TLR2, and TNFRSF1A) were closely correlated pathogenesis of epilepsy, which may be by impacting CCR and the balance of Th1/Th2 signatures involved in the occurrence of epilepsy. Our data offer compelling insights into the pathogenesis and promising therapeutic targets for epilepsy.

Curvilinear Effects of Extraversion on Socialization Outcomes Among Chinese College Students.

The authors examine the too-much-of-a-good-thing effect (TMGT effect) in a model showing that extraversion has a curvilinear relationship with social acceptance and depression. A study of 371 freshmen in a Chinese university showed that extraversion had a curvilinear relationship with social acceptance, such that the relationship was significantly positive from lower to moderate levels of extraversion, but the positive relationship leveled off at higher levels of extraversion. Extraversion also had a curvilinear relationship with depression, such that the relationship was significantly negative from lower to moderate levels of extraversion, but the negative relationship leveled off at higher levels of extraversion. The study indicates that beyond a certain point, the beneficial effects of extraversion on socialization outcomes were diminished. That is, higher levels of extraversion were not associated with more positive socialization outcomes (though they were not associated with worse outcomes either) when extraversion exceeded a certain point. Implications of theory and practice, and limitations and directions for future research, are discussed.

Efficacy and safety of haloperidol for delirium prevention in adult patients: An updated meta-analysis with trial sequential analysis of randomized controlled trials.

STUDY OBJECTIVE: To identify the efficacy and safety of haloperidol prophylaxis in adult patients with a high risk for delirium. DESIGN: A meta-analysis with trial sequential analysis of randomized controlled trials. INTERVENTION: A comprehensive search was performed in PubMed, the ISI Web of Knowledge, the Cochrane Library, and Embase databases from inception through to March 2019.Citation screening, data abstraction and quality assessment were performed in duplicate. Meta-analysis with trial sequential analysis (TSA) were used to assess the primary and secondary outcomes. In addition, we used the Grading of Recommendations Assessment Development and Evaluation (GRADE) to evaluate the certainty of the body of evidence. MAIN RESULTS: We appraised 8 RCTs involving 3034 patients that that were in compliance with inclusion and exclusion criterion. Pooled analyses indicated patients receiving haloperidol prophylaxis and placebo or normal saline did not significantly differ in incidence of delirium (relative risk [RR] = 0.90, 95% confidence interval [CI] = 0.70 to 1.15), with TSA inconclusive. Notably, compared with the control group, use of haloperidol significantly decreased the duration of delirium (Mean difference [MD] -0.94; 95% CI -1.82 to -0.06 days), with a marked heterogeneity. Additionally, haloperidol prophylaxis does not significantly affect duration of mechanical ventilation, length of intensive care unit (ICU) stay, length of hospital stay and mortality. In terms of safety profiles, haloperidol was not associated with increased risk for QTc prolongation, extrapyramidal symptoms, or adverse events. GRADE indicated the level of evidence was very low for a benefit from haloperidol prophylaxis. CONCLUSIONS: The results of our meta-analysis suggested the use of prophylactic haloperidol compared with placebo had no beneficial impacts on incidence of delirium, duration of mechanical ventilation, length of intensive care unit (ICU) stay, length of hospital stay and mortality in adult patients. It appeared to have a positive effect on duration of delirium, while with a significant heterogeneity. These findings do not support the routine usage of haloperidol for delirium prevention. TRIAL REGISTRATION: PROSPERO registration number: CRD42018100511. Registered on 17 July 2018.

Measuring Proton Currents of Bioinspired Materials with Metallic Contacts.

Charge transfer at the interface between the active layer and the contact is essential in any device. Transfer of electronic charges across the contact/active layer interface with metal contacts is well-understood. To this end, noble metals, such as gold or platinum, are widely used. With these contacts, ionic currents (especially protonic) are often neglected because ions and protons do not transfer across the interface between the contact and the active layer. Palladium hydride contacts have emerged as good contacts to measure proton currents because of a reversible redox reaction at the interface and subsequent absorption/desorption of H into palladium, translating the proton flow reaching the interface into an electron flow at the outer circuit. Here, we demonstrate that gold and palladium contacts also collect proton currents, especially under high relative humidity conditions because of electrochemical reactions at the interface. A marked kinetic isotope effect, which is a signature of proton currents, is observed with gold and palladium contacts, indicating both bulk and contact processes involving proton transfer. These phenomena are attributed to electrochemical processes involving water splitting at the interface. In addition to promoting charge transfer at the interface, these interfacial electrochemical processes inject charge carriers into the active layer and hence can also modulate the bulk resistivity of the materials, as was found for the studied peptide fibril films. We conclude that proton currents may not be neglected a priori when performing electronic measurements on biological and bioinspired materials with gold and palladium contacts under high humidity conditions.

Electrical Probes of DNA-Binding Proteins.

A DNA electrochemistry platform has been developed to probe proteins bound to DNA electrically. Here gold electrodes are modified with thiol-modified DNA, and DNA charge transport chemistry is used to probe DNA binding and enzymatic reaction both with redox-silent and redox-active proteins. For redox-active proteins, the electrochemistry permits the determination of redox potentials in the DNA-bound form, where comparisons to DNA-free potentials can be made using graphite electrodes without DNA modification. Importantly, electrochemistry on the DNA-modified electrodes facilitates reaction under aqueous, physiological conditions with a sensitive electrical measurement of binding and activity.

Proton conductivity in ampullae of Lorenzini jelly.

In 1678, Stefano Lorenzini first described a network of organs of unknown function in the torpedo ray-the ampullae of Lorenzini (AoL). An individual ampulla consists of a pore on the skin that is open to the environment, a canal containing a jelly and leading to an alveolus with a series of electrosensing cells. The role of the AoL remained a mystery for almost 300 years until research demonstrated that skates, sharks, and rays detect very weak electric fields produced by a potential prey. The AoL jelly likely contributes to this electrosensing function, yet the exact details of this contribution remain unclear. We measure the proton conductivity of the AoL jelly extracted from skates and sharks. The room-temperature proton conductivity of the AoL jelly is very high at 2 ± 1 mS/cm. This conductivity is only 40-fold lower than the current state-of-the-art proton-conducting polymer Nafion, and it is the highest reported for a biological material so far. We suggest that keratan sulfate, identified previously in the AoL jelly and confirmed here, may contribute to the high proton conductivity of the AoL jelly with its sulfate groups-acid groups and proton donors. We hope that the observed high proton conductivity of the AoL jelly may contribute to future studies of the AoL function.

A Disposable paper breathalyzer with an alcohol sensing organic electrochemical transistor.

UNLABELLED: Breathalyzers estimate Blood Alcohol Content (BAC) from the concentration of ethanol in the breath. Breathalyzers are easy to use but are limited either by their high price and by environmental concerns, or by a short lifetime and the need for continuous recalibration. Here, we demonstrate a proof-of-concept disposable breathalyzer using an organic electrochemical transistor (OECT) modified with alcohol dehydrogenase (ADH) as the sensor. The OECT is made with the conducting polymer poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) ( PEDOT: PSS), and is printed on paper. ADH and its cofactor nicotinamide adenine dinucleotide (NAD(+)) are immobilized onto the OECT with an electrolyte gel. When the OECT-breathalyzer is exposed to ethanol vapor, the enzymatic reaction of ADH and ethanol transforms NAD(+) into NADH, which causes a decrease in the OECT source drain current. In this fashion, the OECT-breathalyzer easily detects ethanol in the breath equivalent to BAC from 0.01% to 0.2%. The use of a printed OECT may contribute to the development of breathalyzers that are disposable, ecofriendly, and integrated with wearable devices for real-time BAC monitoring.

Proton mediated control of biochemical reactions with bioelectronic pH modulation.

In Nature, protons (H(+)) can mediate metabolic process through enzymatic reactions. Examples include glucose oxidation with glucose dehydrogenase to regulate blood glucose level, alcohol dissolution into carboxylic acid through alcohol dehydrogenase, and voltage-regulated H(+) channels activating bioluminescence in firefly and jellyfish. Artificial devices that control H(+) currents and H(+) concentration (pH) are able to actively influence biochemical processes. Here, we demonstrate a biotransducer that monitors and actively regulates pH-responsive enzymatic reactions by monitoring and controlling the flow of H(+) between PdHx contacts and solution. The present transducer records bistable pH modulation from an "enzymatic flip-flop" circuit that comprises glucose dehydrogenase and alcohol dehydrogenase. The transducer also controls bioluminescence from firefly luciferase by affecting solution pH.

Two-terminal protonic devices with synaptic-like short-term depression and device memory.

Two-terminal protonic devices with PdHx proton conducting contacts and a Nafion channel achieve 25 ms spiking, short term depression, and low-energy memory switching.

H+-type and OH- -type biological protonic semiconductors and complementary devices.

Proton conduction is essential in biological systems. Oxidative phosphorylation in mitochondria, proton pumping in bacteriorhodopsin, and uncoupling membrane potentials by the antibiotic Gramicidin are examples. In these systems, H(+) hop along chains of hydrogen bonds between water molecules and hydrophilic residues - proton wires. These wires also support the transport of OH(-) as proton holes. Discriminating between H(+) and OH(-) transport has been elusive. Here, H(+) and OH(-) transport is achieved in polysaccharide- based proton wires and devices. A H(+)- OH(-) junction with rectifying behaviour and H(+)-type and OH(-)-type complementary field effect transistors are demonstrated. We describe these devices with a model that relates H(+) and OH(-) to electron and hole transport in semiconductors. In turn, the model developed for these devices may provide additional insights into proton conduction in biological systems.

A polysaccharide bioprotonic field-effect transistor.

In nature, electrical signalling occurs with ions and protons, rather than electrons. Artificial devices that can control and monitor ionic and protonic currents are thus an ideal means for interfacing with biological systems. Here we report the first demonstration of a biopolymer protonic field-effect transistor with proton-transparent PdH(x) contacts. In maleic-chitosan nanofibres, the flow of protonic current is turned on or off by an electrostatic potential applied to a gate electrode. The protons move along the hydrated maleic-chitosan hydrogen-bond network with a mobility of ~4.9×10(-3) cm(2) V(-1) s(-1). This study introduces a new class of biocompatible solid-state devices, which can control and monitor the flow of protonic current. This represents a step towards bionanoprotonics.