Human β-defensins (hBDs) stimulate degranulation in rat peritoneal mast cells in vitro and cause increased vascular permeability in rats in vivo. Here, we sought to determine if hBDs activate murine and human mast cells and to delineate the mechanisms of their regulation. hBD2 and hBD3 did not induce degranulation in murine peritoneal or bone marrow-derived mast cells (BMMC) in vitro and had no effect on vascular permeability in vivo. By contrast, these peptides induced sustained Ca2+ mobilization and substantial degranulation in human mast cells with hBD3 being more potent. Pertussis toxin (PTx) had no effect on hBD-induced Ca2+ mobilization but La3+ and 2-Aminoethoxydiphenyl borate (2-APB; a dual inhibitor of IP3 receptor and transient receptor potential (TRP) channels caused substantial inhibition of this response. Interestingly, degranulation induced by hBDs was substantially inhibited by PTx, La3+ or 2-APB. While human mast cells endogenously express G protein coupled receptor (GPCR); Mas-related gene X2 (MrgX2), rat basophilic leukemia, RBL-2H3 cells and murine BMMCs do not. Silencing the expression of MrgX2 in human mast cells inhibited hBD-induced degranulation but had no effect on anaphylatoxin C3a-induced response. Furthermore, ectopic expression of MrgX2 in RBL-2H3 and murine BMMCs rendered these cells responsive to hBDs for degranulation. This study demonstrates that hBDs activate human mast cells via MrgX2, which couples to both PTx sensitive and insensitive signaling pathways likely involving Gαq and Gαi to induce degranulation. Furthermore, murine mast cells are resistant to hBDs for degranulation and this reflect the absence of MrgX2 in these cells.

To implement a SNN using a hardware system, an integrate and fire (I&F) neuron is commonly adopted as a spiking neuron owing to its simplicity. An I&F neuron integrates the input synaptic current and the membrane potential is charged, as shown in Figure 1a. When the membrane potential reaches the threshold voltage of the neuron, the neuron generates spikes to the next synapse layer and resets the membrane potential. Unfortunately, it is becoming burdensome to use conventional CMOS-based neurons in massive neuromorphic hardware due to their large areas and high power consumption. [6] In this regard, volatile thershold switching (TS) devices [7][8][9][10][11] and nonvolatile memory such as resistive random access memory (RRAM) , [12] phase change random access memory (PRAM), [13] ferromagnetic material, [14] and floating body transistor [15] based I&F neurons have been reported to overcome the limitations of conventional CMOS-based neurons. In nonvolatile memory device based I&F neurons wherein the memory device is used for integrating the input synaptic current, an additional circuit is required to return memory device to its initial state in the reset process of the neuron. However, in a TS-based I&F neuron, due to the volatile voltage hysteric switch characteristic of the TS device, a self-reset process is performed without a reset circuit. Thus, it enables the realization of a compact and low power consumption neuron. Although many TS-based I&F neurons have been studied, only the operations of I&F neuron and their biological plausibility have been reported. However, it is necessary to study and understand the correlation between the switching parameter of a TS device and the neuron characteristics for practical application of TS-based I&F neurons in various SNN-based hardware.Therefore, in this work, we investigated the effect of the switching parameters of the TS devices on the characteristics of TS-based I&F neurons through electrical measurements and computational simulation of three different types of neurons using a NbO 2 -based insulator-to-metal transition device (IMT), [16] a B-Te-based ovonic threshold switching (OTS) device, [17] and a Ag/HfO 2 -based atomic-switching TS device. [18] In addition, we confirmed the feasibility of TS-based neuron by simulating SNN, which converted from analog-based ANN prelearned by backpropagation.This study demonstrates an integrate and fire (I&F) neuron using threshold switching (TS) devices to implement spike-based neuromorphic system. An I&F neuron can be realized using the hysteric voltage switch characteristics of a TS device. To investigate the effects of various TS devices on neuron behavior, neurons are compared using three different types of TS device: NbO 2 -based insulator-to-metal transition (IMT) device, B-Te-based ovonic threshold switching device, and Ag/HfO 2 -based atomic-switching TS device. The results show that the off-state resistance and switching time of the TS devices determine the leaky/nonleaky characteristics and types of activation function ...

Research interest has increasingly focused on the psychosocial factors related to online game addiction. This study examines the relationship of various psychosocial variables to online game addiction, and the mediation effect of avatar identification on the relationship. Questionnaires assessing self-esteem, depression, social skills, game addiction, and avatar identification were completed by 163 third-year middle school students. Correlation and structural equation modeling analyses were conducted. Results indicated (a) that self-esteem and social skills had significant negative correlations with game addiction, while depression had a significant positive correlation with game addiction, (b) that depression had an indirect effect on game addiction via avatar identification, and (c) that social skills had both indirect (via avatar identification) and direct effects on game addiction. Implications and future directions are discussed.

Porphyromonas gingivalis is a keystone pathogen that contributes to periodontal pathogenesis by disrupting host-microbe homeostasis and promoting dysbiosis. The virulence of P. gingivalis likely reflects an alteration in the lipid A composition of its lipopolysaccharide (LPS) from the penta-acylated (PgLPS1690) to the tetra-acylated (PgLPS1435/1449) form. Mast cells play an important role in periodontitis, but the mechanisms of their activation and regulation remain unknown. The expression of epithelium- and neutrophil-derived host defense peptides (HDPs) (LL-37 and human β-defensin-3), which activate mast cells via Mas-related G protein-coupled receptor X2 (MRGPRX2), is increased in periodontitis. We found that MRGPRX2-expressing mast cells are present in normal gingiva and that their numbers are elevated in patients with chronic periodontitis. Furthermore, HDPs stimulated degranulation in a human mast cell line (LAD2) and in RBL-2H3 cells stably expressing MRGPRX2 (RBL-MRGPRX2). PgLPS1690 caused substantial inhibition of HDP-induced mast cell degranulation, but PgLPS1435/1449 had no effect. A fluorescently labeled HDP (FAM-LL-37) bound to RBL-MRGPRX2 cells, and PgLPS1690 inhibited this binding, but PgLPS1435/1449 had no effect. These findings suggest that low-level inflammation induced by HDP/MRGPRX2-mediated mast cell degranulation contributes to gingival homeostasis but that sustained inflammation due to elevated levels of both HDPs and MRGPRX2-expressing mast cells promotes periodontal disease. Furthermore, differential regulation of HDP-induced mast cell degranulation by PgLPS1690 and PgLPS1435/1449 may contribute to the modulation of disease progression.

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Lead-free cesium bismuth bromide perovskite nanocrystals are synthesized via the heating-up method with tailored morphology and optical properties.

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The aim of this study was to investigate risk grouping for surgical outcome in patients with severe traumatic acute subdural hematoma (ASDH). Methods: Seventy-five patients showing low Glasgow Coma Scale (GCS) 3 to 8 were enrolled in this retrospective study. Clinico-radiologic findings were retrieved from electronic medical record and computed tomography. Prognostic factors from univariate and multivariate statistical methodology were included in a recursive partitioning analysis for risk stratification. Results: One month after surgery, 54 patients (72%) had poor Glasgow Outcome Scale (GOS) 1 to 2 (unfavorable outcome). The surgical outcomes were stratified into three homogenous risk groups according to preoperative GCS and presence of basal cistern obliteration. The rate of favorable outcome and mortality significantly differ between the groups: 4.9% and 68.3% in patients with GCS 3 to 5, 23.1% and 53.8% in patients with GCS 6 to 8 and basal cistern obliteration, and 76.2% and 0% in patients with GCS 6 to 8 and without basal cistern obliteration. Conclusion: The surgical outcomes of severe traumatic ASDH patients could be stratified preoperative GCS score and the presence of basal cistern obliteration. It is expected that this model will not only provide objective information when we make decisions about treatment, but it can also be a useful tool when discussing the patient's prognosis with the patient's caregivers.