Association of ultra-early diffusion-weighted magnetic resonance imaging with neurological outcomes after out-of-hospital cardiac arrest.

BACKGROUND: This study aimed to investigate the association between ultra-early (within 6 h after return of spontaneous circulation [ROSC]) brain diffusion-weighted magnetic resonance imaging (DW-MRI) and neurological outcomes in comatose survivors after out-of-hospital cardiac arrest. METHODS: We conducted a registry-based observational study from May 2018 to February 2022 at a Chungnam national university hospital in Daejeon, Korea. Presence of high-signal intensity (HSI) (PHSI) was defined as a HSI on DW-MRI with corresponding hypoattenuation on the apparent diffusion coefficient map irrespective of volume after hypoxic ischemic brain injury; absence of HSI was defined as AHSI. The primary outcome was the dichotomized cerebral performance category (CPC) at 6 months, defined as good (CPC 1-2) or poor (CPC 3-5). RESULTS: Of the 110 patients (30 women [27.3%]; median (interquartile range [IQR]) age, 58 [38-69] years), 48 (43.6%) had a good neurological outcome, time from ROSC to MRI scan was 2.8 h (IQR 2.0-4.0 h), and the PHSI on DW-MRI was observed in 46 (41.8%) patients. No patients in the PHSI group had a good neurological outcome compared with 48 (75%) patients in the AHSI group. In the AHSI group, cerebrospinal fluid (CSF) neuron-specific enolase (NSE) levels were significantly lower in the group with good neurological outcome compared to the group with poor neurological outcome (20.1 [14.4-30.7] ng/mL vs. 84.3 [32.4-167.0] ng/mL, P < 0.001). The area under the curve for PHSI on DW-MRI was 0.87 (95% confidence interval [CI] 0.80-0.93), and the specificity and sensitivity for predicting a poor neurological outcome were 100% (95% CI 91.2%-100%) and 74.2% (95% CI 62.0-83.5%), respectively. A higher sensitivity was observed when CSF NSE levels were combined (88.7% [95% CI 77.1-95.1%]; 100% specificity). CONCLUSIONS: In this cohort study, PHSI findings on ultra-early DW-MRI were associated with poor neurological outcomes 6 months following the cardiac arrest. The combined CSF NSE levels showed higher sensitivity at 100% specificity than on DW-MRI alone. Prospective multicenter studies are required to confirm these results.

Effects of Icariin and Its Metabolites on GPCR Regulation and MK-801-Induced Schizophrenia-Like Behaviors in Mice.

Icariin, a major bioactive compound found in the Epimedium genus, has been reported to exert protective effects against neurodegenerative disorders. In the current study, we aimed to investigate the regulatory effect of icariin and its active metabolites (icariside II and icaritin) against prime G-protein-coupled receptor targets, considering their association with neuronal disorders. Icariside II exhibited selective agonist activity towards the dopamine D3 receptor (D3R), with half-maximal effective concentrations of 13.29 µM. Additionally, they effectively inhibited the specific binding of radioligands to D3R. Molecular docking analysis revealed that icariside II potentially exerts its agonistic effect through hydrogen-bonding interaction with Asp110 of the D3R, accompanied by negative binding energy. Conversely, icaritin demonstrated selective antagonist effects on the muscarinic acetylcholine M2 receptor (M2R). Radioligand binding assay and molecular docking analysis identified icaritin as an orthosteric ligand for M2R. Furthermore, all three compounds, icariin and its two metabolites, successfully mitigated MK-801-induced schizophrenia-like symptoms, including deficits in prepulse inhibition and social interaction, in mice. In summary, these findings highlight the potential of icariin and its metabolites as promising lead structures for the discovery of new drugs targeting cognitive and neurodegenerative disorders.

Induction of apoptosis through inactivation of ROS-dependent PI3K/Akt signaling pathway by platycodin D in human bladder urothelial carcinoma cells.

Platycodin D (PD) is a triterpenoid saponin, a major bioactive constituent of the roots of Platycodon grandiflorum, which is well known for possessing various pharmacological properties. However, the anti-cancer mechanism of PD in bladder cancer cells remains poorly understood. In the current study, we investigated the effect of PD on the growth of human bladder urothelial carcinoma cells. PD treatment significantly reduced the cell survival of bladder cancer cells associated with induction of apoptosis and DNA damage. PD inhibited the expression of inhibitor of apoptosis family members, activated caspases, and induced cleavage of poly (ADP-ribose) polymerase. PD also increased the release of cytochrome c into the cytoplasm by disrupting the mitochondrial membrane potential while upregulating the expression ratio of Bax to Bcl-2. The PD-mediated anti-proliferative effect was significantly inhibited by pre-treatment with a pancaspase inhibitor, but not by an inhibitor of necroptosis. Moreover, PD suppressed the phosphoinositide 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) signaling pathway, and the apoptosis-inducing effect of PD was further enhanced by a PI3K inhibitor. In addition, PD increased the accumulation of reactive oxygen species (ROS), whereas N-acetyl cysteine (NAC), an ROS inhibitor, significantly attenuated the growth inhibition and inactivation of the PI3K/Akt/mTOR signaling caused by PD. Furthermore, NAC significantly suppressed apoptosis, DNA damage, and decreased cell viability induced by PD treatment. Collectively, our findings indicated that PD blocked the growth of bladder urothelial carcinoma cells by inducing ROS-mediated inactivation of the PI3K/Akt/mTOR signaling.

Classification of the Sidewalk Condition Using Self-Supervised Transfer Learning for Wheelchair Safety Driving.

The demand for wheelchairs has increased recently as the population of the elderly and patients with disorders increases. However, society still pays less attention to infrastructure that can threaten the wheelchair user, such as sidewalks with cracks/potholes. Although various studies have been proposed to recognize such challenges, they mainly depend on RGB images or IMU sensors, which are sensitive to outdoor conditions such as low illumination, bad weather, and unavoidable vibrations, resulting in unsatisfactory and unstable performance. In this paper, we introduce a novel system based on various convolutional neural networks (CNNs) to automatically classify the condition of sidewalks using images captured with depth and infrared modalities. Moreover, we compare the performance of training CNNs from scratch and the transfer learning approach, where the weights learned from the natural image domain (e.g., ImageNet) are fine-tuned to the depth and infrared image domain. In particular, we propose applying the ResNet-152 model pre-trained with self-supervised learning during transfer learning to leverage better image representations. Performance evaluation on the classification of the sidewalk condition was conducted with 100% and 10% of training data. The experimental results validate the effectiveness and feasibility of the proposed approach and bring future research directions.

Light-FER: A Lightweight Facial Emotion Recognition System on Edge Devices.

Facial emotion recognition (FER) systems are imperative in recent advanced artificial intelligence (AI) applications to realize better human-computer interactions. Most deep learning-based FER systems have issues with low accuracy and high resource requirements, especially when deployed on edge devices with limited computing resources and memory. To tackle these problems, a lightweight FER system, called Light-FER, is proposed in this paper, which is obtained from the Xception model through model compression. First, pruning is performed during the network training to remove the less important connections within the architecture of Xception. Second, the model is quantized to half-precision format, which could significantly reduce its memory consumption. Third, different deep learning compilers performing several advanced optimization techniques are benchmarked to further accelerate the inference speed of the FER system. Lastly, to experimentally demonstrate the objectives of the proposed system on edge devices, Light-FER is deployed on NVIDIA Jetson Nano.

Enhanced interfacial reaction of silicon carbide fillers onto the metal substrate in carbon nanotube paste for reliable field electron emitters.

Adhesion of carbon nanotube (CNT) onto a cathode substrate is very crucial for field electron emitters that are operating under high electric fields. As a supporting precursor of CNT field emitters, we adopted silicon carbide (SiC) nano-particle fillers with Ni particles and then enhanced interfacial reactions onto Kovar-alloy substrates through the optimized wet pulverization process of SiC aggregates for reliable field electron emitters. As-purchased SiC aggregates were efficiently pulverized from 20 to less than 1 micro-meter in a median value (D50). CNT pastes for field emitters were distinctively formulated by a mixing process of the pulverized SiC aggregates and pre-dispersed CNTs. X-ray photoelectron spectroscopy studies showed that the optimally pulverized SiC-CNT paste-emitter had a stronger Si 2p3/2 signal in the Ni2Si phase than the as-purchased one. The Si 2p3/2 signal would represent interfacial reaction of the SiC nano-particle onto Ni from the CNT paste and the Kovar substrate, forming the supporting layer for CNT emitters. The optimal paste-emitter even in a vacuum-sealed tube exhibited a highly reliable field emission current with a high current density of 100 mA cm-2 for over 50 h along with good reproducibility. The enhanced interfacial reaction of SiC filler onto the metal substrates could lead to highly reliable field electron emitters for vacuum electronic devices.

Loganin Inhibits Lipopolysaccharide-Induced Inflammation and Oxidative Response through the Activation of the Nrf2/HO-1 Signaling Pathway in RAW264.7 Macrophages.

Inflammation caused by the excessive secretion of inflammatory mediators in abnormally activated macrophages promotes many diseases along with oxidative stress. Loganin, a major iridoid glycoside isolated from Cornus officinalis, has recently been reported to exhibit anti-inflammatory and antioxidant effects, whereas the underlying mechanism has not yet been fully clarified. Therefore, the aim of the present study is to investigate the effect of loganin on inflammation and oxidative stress in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages. Our results indicated that loganin treatment markedly attenuated the LPS-mediated phagocytic activity and release of nitric oxide (NO) and prostaglandin E2, which was associated with decreased the expression of inducible NO synthase and cyclooxygenase-2. In addition, loganin suppressed the expression and their extracellular secretion of LPS-induced pro-inflammatory cytokines, such as tumor necrosis factor-α and interleukin-1ß. Furthermore, loganin abolished reactive oxygen species (ROS) generation, and promoted the activation of nuclear factor-E2-related factor 2 (Nrf2) and the expression of heme oxygenase-1 (HO-1) in LPS-stimulated macrophages. However, zinc protoporphyrin, a selective HO-1 inhibitor, reversed the loganin-mediated suppression of pro-inflammatory cytokines in LPS-treated macrophages. In conclusion, our findings suggest that the upregulation of the Nrf2/HO-1 signaling pathway is concerned at least in the protective effect of loganin against LPS-mediated inflammatory and oxidative stress, and that loganin can be a potential functional agent to prevent inflammatory and oxidative damage.

Inhibition of Lipopolysaccharide-Induced Inflammatory and Oxidative Responses by Trans-cinnamaldehyde in C2C12 Myoblasts.

Background: Trans-cinnamaldehyde (tCA), a bioactive component found in Cinnamomum cassia, has been reported to exhibit anti-inflammatory and antioxidant effects, but its efficacy in muscle cells has yet to be found. In this study, we investigated the inhibitory effect of tCA on inflammatory and oxidative stress induced by lipopolysaccharide (LPS) in C2C12 mouse skeletal myoblasts. Methods: To investigate the anti-inflammatory and antioxidant effects of tCA in LPS-treated C2C12 cells, we measured the levels of pro-inflammatory mediator, cytokines, and reactive oxygen species (ROS). To elucidate the mechanism underlying the effect of tCA, the expression of genes involved in the expression of inflammatory and oxidative regulators was also investigated. We further evaluated the anti-inflammatory and antioxidant efficacy of tCA against LPS in the zebrafish model. Results: tCA significantly inhibited the LPS-induced release of pro-inflammatory mediators and cytokines, which was associated with decreased expression of their regulatory genes. tCA also suppressed the expression of Toll-like receptor 4 (TLR4) and myeloid differentiation factor, and attenuated the nuclear translocation of nuclear factor-kappa B (NF-κB) and the binding of LPS to TLR4 on the cell surface in LPS-treated C2C12 cells. Furthermore, tCA abolished LPS-induced generation of ROS and expression levels of ROS producing enzymes, NADPH oxidase 1 (NOX1) and NOX2. However, tCA enhanced the activation of nuclear translocation of nuclear factor-E2-related factor 2 (Nrf2) and the expression of heme oxygenase-1 (HO-1) in LPS-stimulated C2C12 myoblasts. In addition, tCA showed strong protective effects against NO and ROS production in LPS-injected zebrafish larvae. Conclusions: Our findings suggest that tCA exerts its inhibitory ability against LPS-induced inflammatory and antioxidant stress in C2C12 myoblasts by targeting the TLR4/NF-κB, which might be mediated by the NOXs and Nrf2/HO-1 pathways.

The Prevalence and Emergency Department Utilization of Patients Who Underwent Single and Double Inter-hospital Transfers in the Emergency Department: a Nationwide Population-based Study in Korea, 2016-2018.

BACKGROUND: Inter-hospital transfer (IHT) for emergency department (ED) admission is a burden to high-level EDs. This study aimed to evaluate the prevalence and ED utilization patterns of patients who underwent single and double IHTs at high-level EDs in South Korea. METHODS: This nationwide cross-sectional study analyzed data from the National Emergency Department Information System for the period of 2016-2018. All the patients who underwent IHT at Level I and II emergency centers during this time period were included. The patients were categorized into the single-transfer and double-transfer groups. The clinical characteristics and ED utilization patterns were compared between the two groups. RESULTS: We found that 2.1% of the patients in the ED (n = 265,046) underwent IHTs; 18.1% of the pediatric patients (n = 3,556), and 24.2% of the adult patients (n = 59,498) underwent double transfers. Both pediatric (median, 141.0 vs. 208.0 minutes, P < 0.001) and adult (median, 189.0 vs. 308.0 minutes, P < 0.001) patients in the double-transfer group had longer duration of stay in the EDs. Patient's request was the reason for transfer in 41.9% of all IHTs (111,076 of 265,046). Unavailability of medical resources was the reason for transfer in 30.0% of the double transfers (18,920 of 64,054). CONCLUSION: The incidence of double-transfer of patients is increasing. The main reasons for double transfers were patient's request and unavailability of medical resources at the first-transfer hospitals. Emergency physicians and policymakers should focus on lowering the number of preventable double transfers.

A Real-Time Wearable Physiological Monitoring System for Home-Based Healthcare Applications.

The acquisition of physiological data are essential to efficiently predict and treat cardiac patients before a heart attack occurs and effectively expedite motor recovery after a stroke. This goal can be achieved by using wearable wireless sensor network platforms for real-time healthcare monitoring. In this paper, we present a wireless physiological signal acquisition device and a smartphone-based software platform for real-time data processing and monitor and cloud server access for everyday ECG/EMG signal monitoring. The device is implemented in a compact size (diameter: 30 mm, thickness: 4.5 mm) where the biopotential is measured and wirelessly transmitted to a smartphone or a laptop for real-time monitoring, data recording and analysis. Adaptive digital filtering is applied to eliminate any interference noise that can occur during a regular at-home environment, while minimizing the data process time. The accuracy of ECG and EMG signal coverage is assessed using Bland-Altman analysis by comparing with a reference physiological signal acquisition instrument (RHS2116 Stim/Recording System, Intan). Signal coverage of R-R peak intervals showed almost identical outcome between this proposed work and the RHS2116, showing a mean difference in heart rate of 0.15 ± 4.65 bpm and a Wilcoxon's p value of 0.133. A 24 h continuous recording session of ECG and EMG is conducted to demonstrate the robustness and stability of the device based on extended time wearability on a daily routine.

Development and validation of a scoring system for mortality prediction and application of standardized W statistics to assess the performance of emergency departments.

BACKGROUND: In-hospital mortality and short-term mortality are indicators that are commonly used to evaluate the outcome of emergency department (ED) treatment. Although several scoring systems and machine learning-based approaches have been suggested to grade the severity of the condition of ED patients, methods for comparing severity-adjusted mortality in general ED patients between different systems have yet to be developed. The aim of the present study was to develop a scoring system to predict mortality in ED patients using data collected at the initial evaluation and to validate the usefulness of the scoring system for comparing severity-adjusted mortality between institutions with different severity distributions. METHODS: The study was based on the registry of the National Emergency Department Information System, which is maintained by the National Emergency Medical Center of the Republic of Korea. Data from 2016 were used to construct the prediction model, and data from 2017 were used for validation. Logistic regression was used to build the mortality prediction model. Receiver operating characteristic curves were used to evaluate the performance of the prediction model. We calculated the standardized W statistic and its 95% confidence intervals using the newly developed mortality prediction model. RESULTS: The area under the receiver operating characteristic curve of the developed scoring system for the prediction of mortality was 0.883 (95% confidence interval [CI]: 0.882-0.884). The Ws score calculated from the 2016 dataset was 0.000 (95% CI: - 0.021 - 0.021). The Ws score calculated from the 2017 dataset was 0.049 (95% CI: 0.030-0.069). CONCLUSIONS: The scoring system developed in the present study utilizing the parameters gathered in initial ED evaluations has acceptable performance for the prediction of in-hospital mortality. Standardized W statistics based on this scoring system can be used to compare the performance of an ED with the reference data or with the performance of other institutions.

Gamma-Aminobutyric Acid (GABA) Inhibits α-Melanocyte-Stimulating Hormone-Induced Melanogenesis through GABAA and GABAB Receptors.

Gamma-aminobutyric acid (GABA) is considered the primary inhibitory neurotransmitter in the human cortex. However, whether GABA regulates melanogenesis has not been comprehensively elucidated. In this study, we reveal that GABA (20 mM) significantly inhibited α-melanocyte-stimulating hormone (α-MSH)-induced extracellular (from 354.9% ± 28.4% to 126.5% ± 16.0%) and intracellular melanin contents (from 236.7% ± 11.1% to 102.7% ± 23.1%) in B16F10 melanoma cells, without inducing cytotoxicity. In addition, α-MSH-induced hyperpigmentation in zebrafish larvae was inhibited from 246.3% ± 5.4% to 116.3% ± 3.1% at 40 mM GABA, displaying no apparent cardiotoxicity. We also clarify that the GABA-mediated antimelanogenic properties were related to the direct inhibition of microphthalmia-associated transcription factor (MITF) and tyrosinase expression by inhibiting cyclic adenosine monophosphate (cAMP) and cAMP response element-binding protein (CREB). Furthermore, under α-MSH stimulation, GABA-related antimelanogenic effects were mediated through the GABAA and GABAB receptors, with subsequent inhibition of Ca2+ accumulation. In B16F10 melanoma cells and zebrafish larvae, pretreatment with bicuculline, a GABAA receptor antagonist, and CGP 46381, a GABAB receptor antagonist, reversed the antimelanogenic effect of GABA following α-MSH treatment by upregulating Ca2+ accumulation. In conclusion, our results indicate that GABA inhibits α-MSH-induced melanogenesis. Hence, in addition to the health benefits of GABA in the central nervous system, it could ameliorate hyperpigmentation disorders.

ROS-Mediated Anti-Tumor Effect of Coptidis Rhizoma against Human Hepatocellular Carcinoma Hep3B Cells and Xenografts.

Coptidis Rhizoma is the dried rhizome from the Coptis chinensis Franch. that has been shown to have a number of beneficial pharmacological properties including antioxidant, anti-inflammatory, and anti-cancer effects. However, the anti-cancer effects of Coptidis Rhizoma on hepatocellular carcinoma (HCC) remain unclear. In this study, we investigated the anti-cancer properties of Coptidis Rhizoma ethanol extract (CR) in HCC Hep3B cells and in a xenograft mouse model. Our results showed that the CR significantly inhibited cell growth and induced apoptosis in Hep3B cells through increased expression of Bcl-2 associated x-protein (Bax) and cleavage of poly-ADP ribose polymerase (PARP), reduced expression of Bcl-2, and activated caspases. CR also increased the generation of intracellular reactive oxygen species (ROS), which caused a loss of mitochondrial membrane potential (MMP, ΔΨm) and activation of the mitochondria-mediated intrinsic apoptosis pathway. Moreover, N-acetylcysteine (NAC), a ROS inhibitor, markedly blocked the effects of CR on apoptotic pathways. CR also induced the expression of light chain 3 (LC3)-I/II, a key autophagy regulator, whereas CR-mediated autophagy was significantly suppressed by NAC. In addition, pre-treatment with NAC perfectly attenuated the inhibition of cell invasion and migration of CR-stimulated Hep3B cells. Furthermore, oral administration of CR suppressed Hep3B tumor growth in xenograft mice without toxicity, alterations to body weight, or changes in hematological and biochemical profiles. Taken together, our findings suggest that CR has anti-tumor effects that result from ROS generation, and may be a potential pharmacological intervention for HCC.

Gaze in the Dark: Gaze Estimation in a Low-Light Environment with Generative Adversarial Networks.

In smart interactive environments, such as digital museums or digital exhibition halls, it is important to accurately understand the user's intent to ensure successful and natural interaction with the exhibition. In the context of predicting user intent, gaze estimation technology has been considered one of the most effective indicators among recently developed interaction techniques (e.g., face orientation estimation, body tracking, and gesture recognition). Previous gaze estimation techniques, however, are known to be effective only in a controlled lab environment under normal lighting conditions. In this study, we propose a novel deep learning-based approach to achieve a successful gaze estimation under various low-light conditions, which is anticipated to be more practical for smart interaction scenarios. The proposed approach utilizes a generative adversarial network (GAN) to enhance users' eye images captured under low-light conditions, thereby restoring missing information for gaze estimation. Afterward, the GAN-recovered images are fed into the convolutional neural network architecture as input data to estimate the direction of the user gaze. Our experimental results on the modified MPIIGaze dataset demonstrate that the proposed approach achieves an average performance improvement of 4.53%-8.9% under low and dark light conditions, which is a promising step toward further research.

Prediction of Visual Memorability with EEG Signals: A Comparative Study.

Visual memorability is a method to measure how easily media contents can be memorized. Predicting the visual memorability of media contents has recently become more important because it can affect the design principles of multimedia visualization, advertisement, etc. Previous studies on the prediction of the visual memorability of images generally exploited visual features (e.g., color intensity and contrast) or semantic information (e.g., class labels) that can be extracted from images. Some other works tried to exploit electroencephalography (EEG) signals of human subjects to predict the memorability of text (e.g., word pairs). Compared to previous works, we focus on predicting the visual memorability of images based on human biological feedback (i.e., EEG signals). For this, we design a visual memory task where each subject is asked to answer whether they correctly remember a particular image 30 min after glancing at a set of images sampled from the LaMemdataset. During the visual memory task, EEG signals are recorded from subjects as human biological feedback. The collected EEG signals are then used to train various classification models for prediction of image memorability. Finally, we evaluate and compare the performance of classification models, including deep convolutional neural networks and classical methods, such as support vector machines, decision trees, and k-nearest neighbors. The experimental results validate that the EEG-based prediction of memorability is still challenging, but a promising approach with various opportunities and potentials.

Cordycepin Resensitizes T24R2 Cisplatin-Resistant Human Bladder Cancer Cells to Cisplatin by Inactivating Ets-1 Dependent MDR1 Transcription.

Tumor cell resistance to anti-cancer drugs is a major obstacle in tumor therapy. In this study, we investigated the mechanism of cordycepin-mediated resensitization to cisplatin in T24R2 cells, a T24-derived cell line. Treatment with cordycepin or cisplatin (2 µg/mL) alone failed to induce cell death in T24R2 cells, but combination treatment with these drugs significantly induced apoptosis through mitochondrial pathways, including depolarization of mitochondrial membranes, decrease in anti-apoptotic proteins Bcl-2, Bcl-xL, and Mcl-1, and increase in pro-apoptotic proteins Bak and Bax. High expression levels of MDR1 were the cause of cisplatin resistance in T24R2 cells, and cordycepin significantly reduced MDR1 expression through inhibition of MDR1 promoter activity. MDR1 promoter activity was dependent on transcription factor Ets-1 in T24R2 cells. Although correlation exists between MDR1 and Ets-1 expression in bladder cancer patients, active Ets-1, Thr38 phosphorylated form (pThr38), was critical to induce MDR1 expression. Cordycepin decreased pThr-38 Ets-1 levels and reduced MDR1 transcription, probably through its effects on PI3K signaling, inducing the resensitization of T24R2 cells to cisplatin. The results suggest that cordycepin effectively resensitizes cisplatin-resistant bladder cancer cells to cisplatin, thus serving as a potential strategy for treatment of cancer in patients with resistance to anti-cancer drugs.

Motor Imagery EEG Classification Using Capsule Networks.

Various convolutional neural network (CNN)-based approaches have been recently proposed to improve the performance of motor imagery based-brain-computer interfaces (BCIs). However, the classification accuracy of CNNs is compromised when target data are distorted. Specifically for motor imagery electroencephalogram (EEG), the measured signals, even from the same person, are not consistent and can be significantly distorted. To overcome these limitations, we propose to apply a capsule network (CapsNet) for learning various properties of EEG signals, thereby achieving better and more robust performance than previous CNN methods. The proposed CapsNet-based framework classifies the two-class motor imagery, namely right-hand and left-hand movements. The motor imagery EEG signals are first transformed into 2D images using the short-time Fourier transform (STFT) algorithm and then used for training and testing the capsule network. The performance of the proposed framework was evaluated on the BCI competition IV 2b dataset. The proposed framework outperformed state-of-the-art CNN-based methods and various conventional machine learning approaches. The experimental results demonstrate the feasibility of the proposed approach for classification of motor imagery EEG signals.

Protective Effects of Fermented Oyster Extract against RANKL-Induced Osteoclastogenesis through Scavenging ROS Generation in RAW 264.7 Cells.

Excessive bone resorption by osteoclasts causes bone loss-related diseases and reactive oxygen species (ROS) act as second messengers in intercellular signaling pathways during osteoclast differentiation. In this study, we explored the protective effects of fermented oyster extract (FO) against receptor activator of nuclear factor-κB (NF-κB) ligand (RANKL)-induced osteoclast differentiation in murine monocyte/macrophage RAW 264.7 cells. Our results showed that FO markedly inhibited RANKL-induced activation of tartrate-resistant acid phosphatase and formation of F-actin ring structure. Mechanistically, FO has been shown to down-regulate RANKL-induced expression of osteoclast-specific markers by blocking the nuclear translocation of NF-κB and the transcriptional activation of nuclear factor of activated T cells c1 (NFATc1) and c-Fos. Furthermore, FO markedly diminished ROS production by RANKL stimulation, which was associated with blocking the expression of nicotinamide adenine dinucleotide phosphate oxidase 1 (NOX1) and its regulatory subunit Rac-1. However, a small interfering RNA (siRNA) targeting NOX1 suppressed RANKL-induced expression of osteoclast-specific markers and production of ROS and attenuated osteoclast differentiation as in the FO treatment group. Collectively, our findings suggest that FO has anti-osteoclastogenic potential by inactivating the NF-κB-mediated NFATc1 and c-Fos signaling pathways and inhibiting ROS generation, followed by suppression of osteoclast-specific genes. Although further studies are needed to demonstrate efficacy in in vivo animal models, FO may be used as an effective alternative agent for the prevention and treatment of osteoclastogenic bone diseases.

Induction of Apoptosis by Citrus unshiu Peel in Human Breast Cancer MCF-7 Cells: Involvement of ROS-Dependent Activation of AMPK.

The fruit of Citrus unshiu MARKOVICH used for various purposes in traditional medicine has various pharmacological properties including antioxidant, anti-inflammatory, and antibacterial effects. Recently, the possibility of anti-cancer activity of the extracts or components of this fruit has been reported; however, the exact mechanism has not yet been fully understood. In this study, we evaluated the anti-proliferative effect of water extract of C. unshiu peel (WECU) on human breast cancer MCF-7 cells and investigated the underlying mechanism. Our results showed that reduction of MCF-7 cell survival by WECU was associated with the induction of apoptosis. WECU-induced apoptotic cell death was related to the activation of caspase-8 and -9, representative initiate caspases of extrinsic and intrinsic apoptosis pathways, respectively, and increase in the Bax : Bcl-2 ratio accompanied by cleavage of poly(ADP-ribose) polymerase (PARP). WECU also increased the mitochondrial dysfunction and cytosolic release of cytochrome c. In addition, AMP-activated protein kinase (AMPK) and its downstream target molecule, acetyl-CoA carboxylase, were activated in a concentration-dependent manner in WECU-treated cells. In contrast, compound C, an AMPK inhibitor, significantly inhibited WECU-induced apoptosis, while inhibiting increased expression of Bax and decreased expression of Bcl-2 by WECU and inhibition of WECU-induced PARP degradation. Furthermore, WECU provoked the production of reactive oxygen species (ROS); however, the activation of AMKP and apoptosis by WECU were prevented, when the ROS production was blocked by antioxidant N-acetyl cysteine. Therefore, our data indicate that WECU suppresses MCF-7 cell proliferation by activating the intrinsic and extrinsic apoptosis pathways through ROS-dependent AMPK pathway activation.

Sargassum serratifolium Extract Attenuates Interleukin-1ß-Induced Oxidative Stress and Inflammatory Response in Chondrocytes by Suppressing the Activation of NF-κB, p38 MAPK, and PI3K/Akt.

Osteoarthritis (OA) is a degenerative joint disease that is characterized by irreversible articular cartilage destruction by inflammatory reaction. Among inflammatory stimuli, interleukin-1ß (IL-1ß) is known to play a crucial role in OA pathogenesis by stimulating several mediators that contribute to cartilage degradation. Recently, the marine brown alga Sargassum serratifolium has been reported to exhibit antioxidant and anti-inflammatory effects in microglial and human umbilical vein endothelial cell models using lipopolysaccharide and tumor necrosis factor-α, but its beneficial effects on OA have not been investigated. This study aimed to evaluate the anti-osteoarthritic effects of ethanol extract of S. serratifolium (EESS) in SW1353 human chondrocytes and, in parallel, primary rat articular chondrocytes. Our results showed that EESS effectively blocked the generation of reactive oxygen species in IL-1ß-treated SW1353 and rat primary chondrocytes, indicating that EESS has a potent antioxidant activity. EESS also attenuated IL-1ß-induced production of nitric oxide (NO) and prostaglandin E2, major inflammatory mediators in these cells, which was associated with the inhibition of inducible NO synthase and cyclooxygenase-2 expression. Moreover, EESS downregulated the level of gene expression of matrix metalloproteinase (MMP)-1, -3 and -13 in SW1353 chondrocytes treated with IL-1ß, resulting in their extracellular secretion reduction. In addition, the IL-1ß-induced activation of nuclear factor-kappa B (NF-κB) was restored by EESS. Furthermore, EESS reduced the activation of p38 mitogen-activated protein kinase (MAPK) and phosphatidylinositol-3-kinase (PI3K)/Akt signaling pathways upon IL-1ß stimulation. These results indicate that EESS has the potential to exhibit antioxidant and anti-inflammatory effects through inactivation of the NF-κB, p38 MAPK, and PI3K/Akt signaling pathways. Collectively, these findings demonstrate that EESS may have the potential for chondroprotection, and extracts of S. serratifolium could potentially be used in the prevention and treatment of OA.