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Yunqi Hou,1,* Zhen Chen,2,* Liping Wang,3 Yingxin Deng,1 Genglong Liu,4 Yongfen Zhou,1 Haiqin Shi,1 Xiangqun Shi,1 Qianhua Jiang2 1Department of Neurology, Shunde Hospital, Southern Medical University (The First People’s Hospital of Shunde), Foshan, Guangdong Province, 528308, People’s Republic of China; 2Department of Intensive Care Unit, Shunde Hospital, Southern Medical University (The First People’s Hospital of Shunde), Foshan, Guangdong Province, 528308, People’s Republic of China; 3Department of Otorhinolaryngology Head and Neck Surgery, The First Affiliated Hospital of Hainan Medical University, Haikou, Hainan Province, 570102, People’s Republic of China; 4Department of Pathology, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou, Guangdong Province, 510095, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yunqi Hou, Department of Neurology, Shunde Hospital, Southern Medical University (The First People’s Hospital of Shunde), Foshan, Guangdong Province, 528308, People’s Republic of China, Email drhouyunqi@163.comBackground: 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.Keywords: epilepsy, immune-related genes, immune infiltration, Th1/Th2 signatures, CCR

This paper focuses on the in-depth analysis of the physical mechanism of the broadband frequency domain spectroscopy of oil-paper insulation. The complex permittivity shows two low-frequency dispersion phenomena, and the real part of the complex conductivity exhibits two slope changes under the synergistic effect of aging and moisture. The two slope changes are mainly attributed to the migration characteristics of water molecules and polar aging products with a degradation of the oil-paper insulation, resulting in the transition of the frequency dependence between the DC conductivity and AC conductivity. When the oil-paper insulation deteriorates seriously, the imaginary part of the dielectric modulus shows double relaxation peaks. Physical models of parasitic capacitance and molecular polarity interface polarization are proposed to reveal the physical mechanism of the double relaxation peaks. The left peak of the double relaxation peaks is caused by the accumulation of water molecules and polar aging products at the electrode/insulation interface, and the right peak is due to the charge disturbance of the cellulose molecular chain surface. This paper can provide theoretical support and technical guidance for the condition diagnosis and evaluation of oil-paper insulation.

Whether team task conflict is beneficial or harmful to team innovation has long been controversial, and empirical studies on the team task conflict–team innovation relationship were inconsistent. Drawing on the contingency model of team innovation, the current study examined how team task conflict interacts with two types of team supportive climates, namely team support for innovation (TSFI) and team psychological safety (TPS), in predicting team innovation via team information elaboration. We tested our hypotheses using multi-source and lagged data collected from 361 employees working in 98 research and development teams. As expected, team information elaboration mediated the interaction effects between team task conflict and team supportive climates on team innovation. In particular, team task conflict had a positive indirect effect on team innovation via team information elaboration when TSFI or TPS was high. However, such indirect effect was negative when TSFI was low and was not significant when TPS was low. Residualized relative weight analysis comparing the moderation effects further suggests that TFSI and TPS are equally important team climates in activating the beneficial effect of team task conflict. Theoretical and practical implications are discussed.

Drawing on the reciprocal determinism of self-regulation system, a process-based model is used to examine the relationship of learning goal orientation (LGO) among university students with their academic performance, via reciprocal relationships between initial status and change trajectories in academic self-efficacy and feedback-seeking behaviors. A longitudinal study of 316 Chinese university students throughout their first year in college reveals that students who have high LGO in their first month after entering the university generally have higher academic self-efficacy and seek more feedback. Moreover, initial levels of feedback seeking are positively related to academic performance via linear change in academic self-efficacy over time. Limitations of the study and practical implications are discussed.

In this work, the extended Debye model or Fourier transform is adopted to convert the polarization and depolarization current test results from the time domain into the frequency domain at low frequencies, thereby shortening the test time but producing large errors when the oil-paper insulation exhibits nonlinear characteristics. The voltage-current response characteristics of samples with three different moisture contents are tested to study the influence of moisture on the nonlinear characteristics. Hammerstein-Wiener (H-W) equivalent mathematical model is proposed for time-frequency domain conversion, and the results from this model and two formal methods are compared. The findings show that the errors of the two conventional methods increase with nonlinearity. The H-W model accurately depicts the nonlinear dielectric response of oil-paper insulation and thus can provide high-precision time-frequency domain conversion data.

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.

This article reports results of a study observing how big-five personality traits influence the trajectories of information-seeking adaptive behaviors among university freshmen. Data are collected from 409 freshmen at a Chinese university at 3, 5, 7, and 9 months after university enrollment. A latent growth mixture model is applied to reveal four trajectories of information-seeking behaviors: high or low maintaining, downward or upward. When the information-seeking trajectories are related to personality traits, openness and agreeableness are associated with high maintaining, while agreeableness is associated with downward trajectories. The study provides strong empirical evidence supporting the Minnesota theory of work adjustment and provides important insights to practitioners who want to enhance newcomer adjustment at all organizations.

In bioelectronic medicine and electroceuticals, electronic devices that conduct electrons are used to monitor and control ion-based biochemical reactions in order to detect and treat medical conditions. Advancing these devices will require a thorough understanding of the electrochemical pathways that transduce electronic currents into the ionic currents that interact with the natural system. Here, we analyze the tranduction of electronic current into a protonic current (H+) using Pd/PdHx contacts and a model proton conductor, chitosan. Linear sweep voltammetry and electrochemical impedance spectroscopy data indicate that, for Pd, limited proton injection occurs at the interface aided by water oxidation. For PdHx, H desorption and electrochemical oxidation to H+ lead to sustainable proton injection and transfer to the chitosan protonic conductor. We have developed electroanalytical expressions and predictive digital simulations that match the experimental results. This work confirms that PdHx contacts integrated in DC devices, in parallel with electrochemical impedance spectroscopy, comprise a suitable means for measuring H+ currents and interrogating the proton conductivity in biomaterials.

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.

Based on the conservation of resources perspective of person-environment (P-E) fit, the present research integrates P-E fit theory with the socialization literature to examine lagged reciprocal relationships between student-university fit and proactive socialization behaviors (i.e., feedback seeking, relationship building with instructors, general socializing, and positive framing). A six-month longitudinal study of 428 freshmen in a Chinese university revealed that relationship building with instructors and positive framing were positively related to subsequent student-university fit, while student-university fit was positively related to subsequent relationship building with instructors, general socializing, and positive framing. Both relationship building with instructors and positive framing had reciprocal relationships with student-university fit. Theoretical and practical implications were discussed.

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.

The electrical properties of eumelanin, a ubiquitous natural pigment, have fascinated scientists since the late 1960s. For several decades, the hydrationdependent electrical properties of eumelanin have mainly been interpreted within the amorphous semiconductor model. Recent works undermined this paradigm. Here we study protonic and electronic charge carrier transport in hydrated eumelanin in thin film form. Thin films are ideal candidates for these studies since they are readily accessible to chemical and morphological characterization and potentially amenable to device applications. Current−voltage (I-V) measurements, transient current measurements with proton-transparent electrodes, and electrochemical impedance spectroscopy (EIS) measurements are reported and correlated with the results of the chemical characterization of the films, performed by X-ray photoelectron spectroscopy. We show that the electrical response of hydrated eumelanin films is dominated by ionic conduction (10−4−10−3 S cm−1), largely attributable to protons, and electrochemical processes. To propose an explanation for the electrical response of hydrated eumelanin films as observed by EIS and I-V, we considered the interplay of proton migration, redox processes, and electronic transport. These new insights improve the current understanding of the charge carrier transport properties of eumelanin opening the possibility to assess the potential of eumelanin for organic bioelectronic applications, e.g. protonic devices and implantable electrodes, and to advance the knowledge on the functions of eumelanin in biological systems.

The ability of bioelectronic devices to conduct protons and other ions opens up opportunities to interface with biology. In this research highlight, we report on our recent efforts in bioprotonic devices. These devices monitor and modulate a current of protons with an applied voltage. Voltage-controlled proton flow mimics semiconductor devices with complementary transistors or biological behaviors such as synaptic-like memories and enzyme logic.

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.

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.

The euphoria from drinking alcoholic beverages makes them popular worldwide. Abuse in alcohol (ethanol) consumption leads to dependence, behavioral problems, and fatal accidents1. In 2013, 10,076 people lost their lives in alcohol-related-driving accidents in the United States alone, accounting for nearly 31% of all traffic related deaths1. Driving under the influence is illegal and the maximum allowed blood alcohol concentration (BAC) is 0.05–0.08%, in most countries2. A breathalyzer measures the concentration of ethanol in the breath to estimate the BAC of an individual. The first generation of breathalyzers uses a liquid dye sensitive to ethanol exposure, potassium dichromate, and a photodetector3. Reliability of these detectors is a challenge and potassium dichromate is environmentally toxic3. A new generation of breathalyzers uses the ethanol in the breath to power a fuel cell whose output is proportional to the ethanol concentration4. These breathalyzers are connected directly to smart phones to test one’s alcohol level before attempting to drive. However, these breathalyzers are still impractical because they require constant recalibration4. To-date the most reliable BAC tests and the only one that is admissible in court is the blood test, which is difficult to administer on site or for preventative purposes. A breathalyzer as easy to use as an inexpensive and disposable glucose paper-strip sensor would greatly simplify BAC testing5. Organic electrochemical transistors (OECTs) are excellent candidates for disposable biosensors because they are inexpensive, they can be made on flexible substrates, and they can be printed on paper6,7. OECTs are typically made with poly(3,4-ethylenedioxythiophene) doped with poly(styrenesulfonate) PEDOT:PSS. PEDOT:PSS is a p-type organic semiconductor with several applications in bioelectronics8,9. Coupled with enzymes in the electrolyte, PEDOT:PSS OECTs are able to detect micro molar glucose concentration in human blood and sweat10. OECTs sensors are amenable to screen-printing11 and inkjet printing12 for rapid and inexpensive manufacturing. Here, we demonstrate an early stage proof-of-concept OECT-breathalyzer on paper by integrating a PEDOT:PSS OECT with the enzyme alcohol dehydrogenase. This proof-of-concept OECT-breathalyzer may aid the development of a breathalyzer that is easy-to-use, inexpensive, easily calibrated, and can be coupled with a cell-phone or a smart watch for BAC self-testing to reduce alcohol related traffic accidents.

Researchers find the proton conductivity of jelly found in the Ampullae of Lorenzini of sharks and skates to be unusually high., 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.

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.

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.

With the recent physical demonstration of memristive-based devices low-power two terminal devices with memory and learning functions have advanced electronics and neuromorphic computing. To this end, typically slow moving ions are coupled with fast moving electrons. Ionic motion affords memory, with electronic current as the output signal. Here, we introduce fully ionic two-terminal devices in which protons provide both memory and output signal. These devices exhibit synaptic-like reversible short-term depression, memory, and can be turned “ON” and “OFF” with as little as 30 fJ of energy per bit if appropriately miniaturized.

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.

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.

Translating ionic currents into measureable electronic signals is essential for the integration of bioelectronic devices with biological systems. We demonstrate the use of a Pd/PdHx electrode as a bioprotonic transducer that connects H+ currents in solution into an electronic signal. This transducer exploits the reversible formation of PdHx in solution according to PdH↔Pd + H+ + e−, and the dependence of this formation on solution pH and applied potential. We integrate the protonic transducer with glucose dehydrogenase as an enzymatic and gate for glucose and NAD+. PdHx formation and associated electronic current monitors the output drop in pH, thus transducing a biological function into a measurable electronic output.