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A metamaterial-based non-uniform dipole array antenna is presented for high gain 5G millimeter-wave applications with a wideband characteristic. Initially, a non-uniform dipole array is designed on a 0.202 mm thick Rogers RO4003C substrate, offering a wide operating bandwidth ranging from 23.1 GHz to 44.8 GHz. The dipole array antenna emits unidirectional end-fire radiation with a maximum gain of 8.1 dBi and an average gain of 6.7 dBi. Subsequently, to achieve high gain performance, a 5 × 7 metamaterial structure is designed in the direction of the antenna radiation. The implemented metamaterial structure is optimized for the operating frequency, enhancing the directivity of the antenna radiation and resulting in a gain increment of more than 3 dBi compared to the dipole array alone. The developed metamaterial-integrated dipole array antenna offers an operating bandwidth (S11 < −10 dB) of more than 21 GHz (63.92%), ranging from 23.1 GHz to 44.8 GHz, covering the most commonly used 5G millimeter-wave frequency bands (n257, n258, n259, n260, and n261). Furthermore, the presented antenna yields a stable high gain with a peak gain of 11.21 dBi and a good radiation efficiency of more than 64%. The proposed antenna is an excellent option for millimeter-wave 5G systems due to its overall properties, particularly its high gain and end-fire radiation characteristics, combined with a wide operating bandwidth.

Modern subway systems have increased in size and complexity, and this growth presents significant challenges for planners of emergency evacuations. In this study, the effectiveness of the simplified and advanced evacuation analysis methods recommended by the International Maritime Organization (IMO) are evaluated for Guryong Station in Seoul, South Korea. The simplified evacuation analysis method facilitates rapid assessments by using general parameters, while the advanced evacuation analysis entails performing detailed simulations of human behavior and physical interactions. Our findings indicate that the results of the simplified evacuation analysis method are reasonably close to those of the more time-consuming advanced evacuation analysis method, thereby demonstrating the practical applicability of the former method for conducting initial evacuation safety assessments. Specifically, both the simplified and advanced methods showed a 20% reduction in Total Evacuation Time when tunnel evacuation routes were utilized. This finding demonstrates that the simplified method can produce results comparable to the advanced method, making it a reliable tool for initial assessments and for evaluating alternative strategies to reduce evacuation time. By demonstrating that the simplified evacuation analysis method can yield reliable results, we provide valuable insights for developing smart, resilient cities with efficient emergency-response capabilities.

Recently, grid composites have drawn considerable attention in various engineering applications due to their customizable mechanical properties, stemming from a wide spectrum of available configurations. Advanced additive manufacturing techniques have made the production of these configurations more feasible. While much research has focused on optimizing for stiffness and strength, there has been a relative lack of studies targeting toughness optimization, mainly due to the intricate unpredictability arising from the complexity of crack propagation mechanisms. This study seeks to fill that gap by leveraging a hierarchical deep neural network (DNN) model, integrated with finite element method (FEM) simulations, to maximize grid composite toughness. DNN model incorporates both structural configuration and stress field data, improving prediction accuracy for unseen domains. Using a genetic algorithm informed by the DNN model, a substantial 60% increase in toughness was achieved while investigating only 3.5% of the original dataset. Subsequent analyses of the stress field and crack phase field elucidated the mechanisms contributing to this increased toughness. Finally, the optimized configuration was experimentally validated by fabricating specimens using a polyjet 3D printer. The results represent a significant advancement in maximizing energy absorption, offering a substantial contribution to the field of composite material optimization.

In this article, an ultra-wideband (UWB) antenna featuring two reconfigurable quasi-perfect stop bands at WLAN (5.25–5.75 GHz) and lower 5G (3.4–3.8 GHz) utilizing electromagnetic bandgaps (EBGs) and positive-intrinsic-negative (P-I-N) diodes is proposed. A pair of EBG structures are applied to generate sharp notch bands in the targeted frequency spectrum. Each EBG creates a traditional notch, while two regular notches are combined to make a quasi-perfect, sharp, notch band. Four P-I-N diodes are engraved into the EBG structures to enable notch band reconfigurability. By switching the operational condition of the four diodes, the UWB antenna can dynamically adjust its notching characteristics to enhance its adaptability to various communication standards and applications. The antenna can be reconfigured as a UWB (3–11.6 GHz) without any notch band, a UWB with a single sharp notch (either at WLAN or 5G), or a UWB with two quasi-perfect notch bands. Moreover, the antenna’s notch bands can also be switched from a traditional notch to a quasi-perfect notch and vice versa. To confirm the validity of the simulated outcomes, the proposed reconfigurable UWB antenna is fabricated and measured. The experimental findings are aligned closely with simulation results, and the antenna offers notch band reconfigurability. The antenna shows a consistently favorable radiation pattern and gain. The dimension of the presented antenna is 20 × 27 × 1.52 mm3 (0.45 λc × 0.33 λc × 0.025 λc, where λc is the wavelength in free space).

Abstract Background During the coronavirus disease (COVID-19) pandemic, the amount of moderate- to high-intensity physical activity significantly decreased. Therefore, the epidemiology of musculoskeletal diseases could possibly have changed. We assessed changes in the incidence of and variance in non-traumatic orthopedic diseases before and after the COVID-19 pandemic in Korea. Methods This study included data from the Korea National Health Insurance Service, which covers the entire Korean population (approximately 50 million), from January 2018 to June 2021. Using International Classification of Diseases, Tenth Revision codes, 12 common orthopedic diseases were evaluated, including cervical disc disorders, lumbar disc disorders, forward head posture, myofascial pain syndrome, carpal tunnel syndrome, tennis elbow, frozen shoulder, rheumatoid arthritis, gout, hip fracture, distal radius fracture, and spine fracture diseases. “Pre-COVID-19” was the period until February 2020, and “COVID-19 pandemic period” was the period starting March 2020. Differences in the mean incidence and variance of diseases before and during the COVID-19 pandemic were compared. Results In most cases, the incidence of orthopedic diseases decreased at the beginning of the pandemic and then increased thereafter. Among the 12 diseases, the incidence of three diseases showed a statistically significant change. The incidence of myofascial pain syndrome (P

BackgroundOsteoporotic vertebral compression fractures commonly involve the superior vertebral body; however, their associated causes have not yet been clearly established. This study aimed to determine the trabecular structural differences between the superior and inferior regions of the vertebral body using cadaveric and clinical studies.Materials and methodsFirst, five vertebrae were collected from three human cadavers. The trabecular structures of the superior and inferior regions of each vertebral body were analyzed using micro-computed tomography (micro-CT), finite element analysis (FEA), and biomechanical test. Based on the results of the ex vivo study, we conducted a clinical study. Second, spine CT images were retrospectively collected. Bone volume and Hounsfield unit were analyzed for 192 vertebral bodies. Finally, after sample size calculation based on the pilot study, prospectively, 200 participants underwent dual-energy X-ray absorptiometry (DXA) of the lateral spine. The bone mineral densities (BMDs) of the superior and inferior regions of each lumbar vertebral body were measured. The paired t-test and Wilcoxon signed-rank test were used for the statistical analyses, and p-value < 0.05 was considered significant.ResultsCadaver studies revealed differences between the superior and inferior trabecular bone structures. The bone volume ratio, BMD, and various other trabecular parameters advocated for decreased strength of the superior region. Throughout the biomechanical study, the limitations of the compression force were 3.44 and 4.63 N/m2 for the superior and inferior regions, respectively. In the FEA study, the inferior region had a lower average displacement and higher von Mises stress than the superior region. In the clinical spine CT-based bone volume and BMD study, the bone volume was significantly higher in the inferior region than in the superior region. In the lateral spine DXA, the mean BMD of the superior region of vertebral bodies was significantly lower compared with that of the inferior region.ConclusionThe superior trabecular structure of the lumbar vertebral bodies possesses more biomechanical susceptibility compared with the inferior trabecular structure, confirming its dominant role in causing osteoporotic vertebral fractures. Physicians should also focus on the BMD values of the superior region of the vertebral body using lateral spine DXA to evaluate osteoporosis.

Abstract Despite the capability of extracellular vesicles (EVs) derived from Gram‐negative and Gram‐positive bacteria to induce potent anti‐tumour responses, large‐scale production of bacterial EVs remains as a hurdle for their development as novel cancer immunotherapeutic agents. Here, we developed manufacturing processes for mass production of Escherichia coli EVs, namely, outer membrane vesicles (OMVs). By combining metal precipitation and size‐exclusion chromatography, we isolated 357 mg in total protein amount of E. coli OMVs, which was equivalent to 3.93 × 1015 particles (1.10 × 1010 particles/μg in total protein amounts of OMVs) from 160 L of the conditioned medium. We show that these mass‐produced E. coli OMVs led to complete remission of two mouse syngeneic tumour models. Further analysis of tumour microenvironment in neoantigen‐expressing tumour models revealed that E. coli OMV treatment causes increased infiltration and activation of CD8+ T cells, especially those of cancer antigen‐specific CD8+ T cells with high expression of TCF‐1 and PD‐1. Furthermore, E. coli OMVs showed synergistic anti‐tumour activity with anti‐PD‐1 antibody immunotherapy, inducing substantial tumour growth inhibition and infiltration of activated cancer antigen‐specific stem‐like CD8+ T cells into the tumour microenvironment. These data highlight the potent anti‐tumour activities of mass‐produced E. coli OMVs as a novel candidate for developing next‐generation cancer immunotherapeutic agents.

Last 5 years, the deterioration of water quality caused by algal bloom has emerged as a serious issue in Korea. The method of on-site water sampling to check algal bloom and cyanobacteria is problematic by only partially measuring the site and not fully representing the field, while at the same time, consuming a lot of time and manpower to complete it. In this study, the different spectral indices reflecting the spectral characteristics of photosynthetic pigments were compared. We monitored harmful algal bloom and cyanobacteria in Nakdong rivers with multispectral sensor images from unmanned aerial vehicles (UAVs). The multispectral sensor images were used to assess the applicability of estimating cyanobacteria concentration based on field sample data. Several wavelength analysis techniques were conducted in June, August, and September 2021, when algal bloom intensified, including the analysis of images from multispectral cameras using normalized difference vegetation index (NDVI), green normalized difference vegetation index (GNDVI), blue normalized difference vegetation index (BNDVI), and normalized difference red edge index (NDREI). Radiation correction was performed using the reflection panel to minimize interference that could distort the analysis results of the UAVs image. Regarding field application and correlation analysis, correlation value of NDREI was the highest at 0.7203 in June. And NDVI was the highest at 0.7607 and 0.7773 in August and September, respectively. Based on the results obtained from this study, it is found that it is possible to quickly measure and judge the distribution status of cyanobacteria. In addition, the multispectral sensor installed to the UAV can be considered as a basic technology for monitoring the underwater environment.

An accurate humidity measurement is essential in various industries, including product stability, pharmaceutical and food preservation, environmental control, and precise humidity management in experiments and industrial processes. Crafting effective humidity sensors through precise material selection is crucial for detecting minute humidity levels across various fields, ultimately enhancing productivity and maintaining product quality. Metal–organic frameworks (MOFs), particularly zeolitic imidazolate frameworks (ZIFs), exhibit remarkable properties and offer a wide range of applications in catalysis, sensing, and gas storage due to their structural stability, which resembles zeolites. The previous research on MOF-based humidity sensors have primarily used electrical resistance-based methods. Recently, however, interest has shifted to capacitive-based sensors using MOFs due to the need for humidity sensors at low humidity and the resulting high sensitivity. Nevertheless, further studies are required to optimize particle structure and size. This study analyzes ZIF-8, a stable MOF synthesized in varying particle sizes, to evaluate its performance as a humidity sensor. The structural, chemical, and sensing properties of synthesized ZIF-8 particles ranging from 50 to 200 nanometers were examined through electron microscopy, spectroscopic, and electrochemical analyses. The fabricated copper electrodes combined with these particles demonstrated stable and linear humidity sensing capabilities within the range of 3% to 30% relative humidity (RH).

In this article, a 4-port circularly polarized (CP) multiple-input multiple-output (MIMO) antenna at 5.9 GHz is presented for the vehicle to everything (V2X) communications. A novel hybrid decoupling structure consisting of circular ring parasites and defected ground structure (DGS) is used to reduce the mutual coupling between the MIMO elements. The circular ring parasites are incorporated between the antennas to reduce the mutual coupling between perpendicular antennas. Whereas, the DGS significantly reduces the mutual coupling between adjacent antennas. These circular ring parasites and DGS affect the electromagnetic field distribution and consequently reduce the mutual coupling. The effectiveness of the decoupling structure is explained through transmission coefficient and surface current distribution. The simulated and measured results show that the proposed MIMO antenna provides overlapping $\text{S}_{\mathrm {11 {}}}$ (−10 dB) and axial ratio (3-dB) bandwidth of 2.04% (5.82 – 5.94 GHz) with a peak gain of 7.68 dBic. Moreover, the fabricated MIMO antenna offers excellent diversity performance, isolation between antenna elements is very high (>34dB), envelope correlation coefficient (ECC) is lower than 0.001, and diversity gain is 9.99 dB, very close to the ideal value of 10 dB. Furthermore, the link budget for the proposed MIMO system is calculated to check the suitability for V2X communications which shows that the antenna can communicate between them over a distance of 1.5 kilometers with a 21 dBm of transmit power. Owing to these qualities, the proposed MIMO antenna can be an excellent choice for V2X MIMO communications.

This study demonstrates tunable coil links for a wireless power transfer system with arbitrarily-located multiple receivers and arbitrary power division between them. Both the Tx and Rx coils are composed of a main coil and an array of assistant coils loaded with varactors. By tuning the varactors to control the resonant characteristics of each assistant coil, the Tx coil can steer the near field, and the Rx coil can reconfigure its electrical size. Consequently, the proposed system maintains the high overall efficiency regardless of the position of the receivers and the power division ratio. For the verification, a two-receiver system at 6.78 MHz is designed and fabricated with a $2\times 1$ assistant coil array. A thorough investigation is performed for various cases, which include when the two receivers of the same size are located symmetrically with respect to the center of the Tx coil and two receivers of different sizes, located asymmetrically. For all cases, the overall efficiency is evaluated for various receiver locations and power division ratios when the tunable coil links are adopted on both Tx and Rx coils, only on either Tx or Rx coil. The conventional system provides the minimum transfer efficiency of 0% for symmetric case, as well as 12.8% for asymmetric case with respect to the receiver locations. On the other hand, results of the proposed system show minimum efficiency of 83.7% and 83.5% for symmetric and asymmetric case, respectively. More importantly, while the conventional system showed strong dependence not only on the Rx locations but also the power division ratio, the proposed system maintains the efficiency with little, if any, variation regardless of the two. For example, while the power division ratio is varied from 5:1 to 1:5, the proposed system remains a very high efficiency of up to 91.0% with only 0.3% variation.

Abstract Ulcerative colitis (UC) is a chronic inflammatory bowel disease. Several studies have demonstrated that α7 nicotinic acetylcholine receptors (α7nAChRs) exert anti-inflammatory effects on immune cells and nicotine suppress UC onset and relapse. Plasmacytoid dendritic cells (pDCs) reportedly accumulate in the colon of UC patients. Therefore, we investigated the pathophysiological roles of α7nAChRs on pDCs in the pathology of UC using oxazolone (OXZ)-induced Th2-type colitis with BALB/c mice. 2-deoxy-D-glucose, a central vagal stimulant suppressed OXZ colitis, and nicotine also ameliorated OXZ colitis with suppressing Th2 cytokines, which was reversed by α7nAChR antagonist methyllycaconitine. Additionally, α7nAChRs were expressed on pDCs, which were located very close to cholinergic nerve fibers in the colon of OXZ mice. Furthermore, nicotine suppressed CCL21-induced bone marrow-derived pDC migration due to Rac 1 inactivation, which was reversed by methyllycaconitine, a JAK2 inhibitor AG490 or caspase-3 inhibitor AZ-10417808. CCL21 was mainly expressed in the isolated lymphoid follicles (ILFs) of the colon during OXZ colitis. The therapeutic effect of cholinergic pathway on OXZ colitis probably through α7nAChRs on pDCs were attributed to the suppression of pDC migration toward the ILFs. Therefore, the activation of α7nAChRs has innovative therapeutic potential for the treatment of UC.

The present study aimed to determine a method for estimating a potential prognostic factor in alternating electric fields for the treatment of solid tumors based on cell survival curves that evaluate cell proliferation capability. In AGS, B16F10, U373, and HPAF-II cancer cell lines, the proportional relationships of the electric field magnitude and the duration of application with the proliferation of cancer cell lines was identified by in vitro alternating current electric field experiments performed under various conditions. A prognostic factor applicable to alternating electric field therapy was developed by identifying proportional relationships of the electric field magnitude and the duration of application with the proliferation of the four cancer cell lines. Through the experimental results, the absorbed energy in tissue has been suggested as a potential prognostic factor in alternating electric field therapy. The absorbed energy in tissue can be used as a reference to quantify the inhibition of cell proliferation related to control, enabling systematic assessment of alternating electric field therapy which, to date, has not been possible.

Plastic deformation of metallic glasses, which show no long-range structural order, proceeds by shear transformation of a local group of atoms referred to as the shear transformation zone (STZ). Unlike crystalline solids, it is difficult to identify STZs and predict the onset of plasticity from a random atomic configuration under a given loading. Recently, significant efforts have been made to predict the shear transformation with initial atomic properties using machine learning. However, despite the class imbalance, where the atoms participating in shear transformation is much rarer compared to the others, few studies have explored the issue of the proper predictive metric choice, with most studies considering widely used metrics such as Recall or AUC in the machine learning community. Therefore, here we train a graph neural network that predicts the initially activated STZ and evaluate its predictive power using various metrics considered to be proper for handling imbalanced datasets. We find that the AUC value is significantly overestimated due to the class imbalance and too many atoms are misclassified as initial STZ, so other metrics such as the precision, f1, MCC, and AP indicate very low predictive power close to zero. Additionally, we reveal that the predictive performance changes significantly over the threshold value of non-affine displacement, above which an atom is classified as the initially activated STZ, due to the change in the degree of class imbalance. Our study implies that it is crucial to use an identical threshold for this type of classification (i.e., the class ratio) for a fair assessment of ML models adapted in different studies and to holistically evaluate the predictive performance based on various metrics.

ObjectiveNumerous attempts have been made to devise treatments for ischemic foot ulcer (IFU), which is one of the most severe and fatal consequences of diabetes mellitus (DM). Pericytes, which are perivascular multipotent cells, are of interest as a treatment option for IFU because they play a critical role in forming and repairing various tissues. In this study, we want to clarify the angiogenic potential of pericytes in DM-induced wounds.MethodsWe evaluated pericyte stimulation capability for tube formation, angiogenesis, and wound healing (cell migration) in human umbilical vein endothelial cells (HUVECs) with in-vivo and in-vitro models of high glucose conditions.ResultsWhen HUVECs were co-cultured with pericytes, their tube-forming capacity and cell migration were enhanced. Our diabetic mouse model showed that pericytes promote wound healing via increased vascularization.ConclusionThe findings of this study indicate that pericytes may enhance wound healing in high glucose conditions, consequently making pericyte transplantation suitable for treating IFUs.

This study demonstrates the successful 3D printing of dental resin-based composites (DRCs) containing ceramic particles using the digital light processing (DLP) technique. The mechanical properties and oral rinsing stability of the printed composites were evaluated. DRCs have been extensively studied for restorative and prosthetic dentistry due to their clinical performance and aesthetic quality. They are often subjected to periodic environmental stress, and thus can easily undergo undesirable premature failure. Here, we investigated the effects of two different high-strength and biocompatible ceramic additives, carbon nanotube (CNT) and yttria-stabilized zirconia (YSZ), on the mechanical properties and oral rinsing stabilities of DRCs. Dental resin matrices containing different wt.% of CNT or YSZ were printed using the DLP technique after analyzing the rheological behavior of slurries. Mechanical properties such as Rockwell hardness and flexural strength, as well as the oral rinsing stability of the 3D-printed composites, were systematically investigated. The results indicated that a DRC with 0.5 wt.% YSZ exhibits the highest hardness of 19.8 ± 0.6 HRB and a flexural strength flexural strength of 50.6 ± 6 MPa, as well as reasonable oral rinsing steadiness. This study provides a fundamental perspective for designing advanced dental materials containing biocompatible ceramic particles.

This paper investigates an ultra-wideband (UWB) antenna with a triple-rectangular notch band at 5G, WLAN, and Satellite downlink bands. The 5G and WLAN bands are notched by using a pair of electromagnetic bandgap (EBG) structures while the satellite downlink band is notched by using two split-ring resonators (SRRs). The EBG structure is a metallic conductor loaded on the backside of the radiator which is connected to the patch via a shorting pin. The SRRs consist of a pair of metallic rings etched on the backside of the feedline. The simulated and measured results show that the proposed antenna has an operational bandwidth from 3.1 - 11.8 GHz for |S11|

The Ensemble and mixture of expertise method is the most intuitive and simple way to improve performance in the field of recognition using convolutional neural networks (CNNs). However, Ensemble is difficult to apply in real-time operation applications because the amount of computational overhead and parameters increase in proportion to the number of models. In another, a mixture of expertise that extracts various expertise and combines it is cumbersome to apply because it requires a large change in the network. In this study, we propose Sequential Feature Filtering Classifier (FFC), a simple but effective classifier for CNNs. Using sequential LayerNorm and ReLU, FFC zeroes out low-activation units and preserves high-activation units. The sequential feature filtering process generates multiple features, which are transmitted to a shared classifier, yielding multiple outputs (multiple expertise). FFC can be applied to any CNN with a classifier and it significantly improves the performance with negligible overhead. In this study, the efficacy of FFC is validated extensively on various tasks—ImageNet-1K classification, MS COCO detection, Cityscapes segmentation, and HMDB51 action recognition. Moreover, it is empirically established that FFC can further improve performances using additional techniques, including attention modules. Code is available at https://github.com/seominseok0429/Sequential-Feature-Filtering-Classifier.

Background The occurrence of multidrug-resistant (MDR) bacteremia in ventilated patients may be associated with a high mortality rate. We evaluated whether Sequential Organ Failure Assessment (SOFA) score on the day of bacteremia could predict 90-day mortality in these patients. Methods Data were obtained retrospectively from 202 patients (male, 60.4%; median age, 64 years) hospitalized at a single university-affiliated tertiary care hospital. All adult patients who had were ventilated and had one of the following six MDR bacteremias between March 2011 and February 2018 were enrolled: methicillin-resistant Staphylococcus aureus, extended-spectrum β-lactamase-producing Gram-negative bacteria (Escherichia coli and Klebsiella pneumonia), carbapenem-resistant Gram-negative rods (Acinetobacter baumannii and Pseudomonas aeruginosa), or vancomycin-resistant Enterococcus faecium. Results The overall 90-day mortality rate after the day of bacteremia was 59.9%. The areas under the receiver operating characteristic curves for the SOFA and Acute Physiology and Chronic Health Evaluation (APACHE) II scores were 0.732 (95% confidence interval [CI], 0.666 to 0.792; P

Passengers escaping from a sinking or inclined ship inevitably choose the transversal, upward, and downward routes and the coupled route where two statuses coexist. A passenger's travel speed varies greatly depending on individual characteristics, as well as the environmental factors, such as the inclination of the ship and the route status. In this study, the walking speed reduction coefficient that considers the coupled effect of trim and heel was applied according to the route status for realistic escape simulation. To calculate the walking speed reduction, the coupling coefficient is introduced to assign weighted values to the coupled route where two route statuses exist. To establish the necessity of reflecting upon the passenger's route status in the escape simulation, simulations were performed on tests 6, 10, and 11 of IMO MSC.1/Circ.1533 ANNEX 3. We believe more accurate ship evacuation simulation can be performed considering the coupled effect of trim and heel.

This paper proposes an online gain adaptation approach to enhance the robustness of whole-body control (WBC) framework for legged robots under unknown external force disturbances. Without properly accounting for external forces, the closed-loop control system incorporating WBC may become unstable, and therefore the desired task goals may not be achievable. To study the effects of external disturbances, we analyze the behavior of our current WBC framework via the use of both full-body and centroidal dynamics. In turn, we propose a way to adapt feedback gains for stabilizing the controlled system automatically. Based on model approximations and stability theory, we propose three conditions to ensure that the adjusted gains are suitable for stabilizing a robot under WBC. The proposed approach has four contributions. We make it possible to estimate the unknown disturbances without force/torque sensors. We then compute adaptive gains based on theoretic stability analysis incorporating the unknown forces at the joint actuation level. We demonstrate that the proposed method reduces task tracking errors under the effect of external forces on the robot. In addition, the proposed method is easy-to-use without further modifications of the controllers and task specifications. The resulting gain adaptation process is able to run in real-time. Finally, we verify the effectiveness of our method both in simulations and experiments using the bipedal robot Draco2 and the humanoid robot Valkyrie.

Abstract Extracellular vesicles (EVs) are nano‐sized vesicles composed of proteolipid bilayers carrying various molecular signatures of the cells. As mediators of intercellular communications, EVs have gained great attention as new therapeutic agents in the field of nanomedicine. Therefore, many studies have explored the roles of cell‐derived EVs isolated from cultured hepatocytes or stem cells as inducer of liver proliferation and regeneration under various pathological circumstances. However, study investigating the role of EVs directly isolated from liver tissue has not been performed. Herein, to understand the pathophysiological role and to investigate the therapeutic potential of in vivo liver EVs, we isolated EVs from both normal and carbon tetrachloride (CCl4)‐induced damaged in vivo liver tissues. The in vivo EVs purified from liver tissues display typical features of EVs including spherical morphology, nano‐size, and enrichment of tetraspanins. Interestingly, administration of both normal and damaged liver EVs significantly accelerated the recovery of liver tissue from CCl4‐induced hepatic necrosis. This restorative action was through the induction of hepatocyte growth factor at the site of the injury. These results suggest that not only normal liver EVs but also damaged liver EVs play important pathophysiological roles of maintaining homeostasis after tissue damage. Our study, therefore, provides new insight into potentially developing in vivo EV‐based therapeutics for preventing and treating liver diseases.

Accumulating evidence has shown that sirtuin 7 (SIRT7), a mediator of various cellular activities, plays an important role in the pathogenesis of various immune-mediated inflammatory disorders. However, information remains limited regarding the role of SIRT7 in intestinal inflammation. We used a murine colitis model to investigate the role of SIRT7 in intestinal immunity and whether SIRT7 inhibitors could attenuate the intestinal inflammatory response. Mice were divided into three groups: control, colitis-induced, and SIRT7-inhibitor-treated. A colitis mouse model was established by intraperitoneal injection and nasal challenge with ovalbumin, as in our previous study. Quantitative analyses of inflammatory cytokines and SIRT7 levels in the colonic mucosa were performed to compare the changes in inflammatory responses between the three groups. The colitis group showed increased levels of inflammatory cytokines and SIRT7 in the colonic mucosa. The inflammatory reaction was suppressed in colitis-induced mice administered the SIRT7 inhibitor. The qRT-PCR results showed normalization of inflammatory cytokines in the SIRT7 inhibitor-treated group. Histologic study revealed a decrease in the extent of inflammation after SIRT7 treatment. We also observed that the degree of clinical inflammation was improved in SIRT7-treated mice. Our study demonstrated that SIRT7 inhibition attenuated the inflammatory response in the colon of mice, suggesting a possible role for SIRT7 in the pathogenesis of immune-mediated intestinal inflammation.

Staphylococcal enterotoxin B (SEB) is a potent bacterial toxin that causes inflammatory stimulation and toxic shock, thus it is necessary to detect SEB in food and environmental samples. Here, we developed a sensitive immunodetection system using monoclonal antibodies (mAbs). Our study is the first to employ a baculovirus expression vector system (BEVS) to produce recombinant wild-type SEB. BEVS facilitated high-quantity and pure SEB production from suspension-cultured insect cells, and the SEB produced was characterized by mass spectrometry analysis. The SEB was stable at 4 °C for at least 2 years, maintaining its purity, and was further utilized for mouse immunization to generate mAbs. An optimal pair of mAbs non-competitive to SEB was selected for sandwich enzyme-linked immunosorbent assay-based immunodetection. The limit of detection of the immunodetection method was 0.38 ng/mL. Moreover, it displayed higher sensitivity in detecting SEB than commercially available immunodetection kits and retained detectability in various matrices and S. aureus culture supernatants. Thus, the results indicate that BEVS is useful for producing pure recombinant SEB with its natural immunogenic property in high yield, and that the developed immunodetection assay is reliable and sensitive for routine identification of SEB in various samples, including foods.

Noise radar has become attractive owing to progress in hardware technology. Aside from the low probability of exploitation, the use of noise waveform is likely to grow due to its low interference features, especially in circumstances where multiple radars operate in the same band. In this study, we developed and tested a wideband noise radar for a ground-moving vehicle. It operates in the X-band with an instantaneous bandwidth of 1.5 GHz. The true time delay (TTD) was applied to correct the distortion of the beam pattern by the wide bandwidth, and the correlators were implemented by high-speed parallel processing using a field programmable gate array (FPGA). The outdoor experimental results were presented.

This paper presents a compact two-element MIMO antenna with improved isolation for triple-band applications. The antenna consists of two radiating elements with the shared ground plane and a novel decoupling structure. Each antenna element has three stubs with different lengths, which work as quarter-wavelength monopoles to give a triple-band operation. The decoupling system is made by etching various slots in an inverted H-shape stub attached to two quarter-circles at its lower ends. The simulated and measured results show that the antenna operates (|S11| < −10 dB) at the key frequency bands of 2.4 GHz (2.29–2.47 GHz), 3.5 GHz (3.34–3.73 GHz), and 5.5 GHz (4.57–6.75 GHz) with a stable gain and radiation patterns. Moreover, the MIMO antenna shows good isolation characteristics. The isolation is more than 20 dB, the envelope correlation coefficient is

Neurodegenerative diseases are inseparably linked with aging and increase as life expectancy extends. There are common dysfunctions in various cellular events shared among neurogenerative diseases, such as calcium dyshomeostasis, neuroinflammation, and age-associated decline in the autophagy-lysosome system. However, most of all, the prominent pathological feature of neurodegenerative diseases is the toxic buildup of misfolded protein aggregates and inclusion bodies accompanied by an impairment in proteostasis. Recent studies have suggested a close association between endoplasmic reticulum (ER) stress and neurodegenerative pathology in cellular and animal models as well as in human patients. The contribution of mutant or misfolded protein-triggered ER stress and its associated signaling events, such as unfolded protein response (UPR), to the pathophysiology of various neurodegenerative disorders, including Alzheimer’s, Parkinson’s, and Huntington’s disease, amyotrophic lateral sclerosis, and prion disease, is described here. Impaired UPR action is commonly attributed to exacerbated ER stress, pathogenic protein aggregate accumulation, and deteriorating neurodegenerative pathologies. Thus, activating certain UPR components has been shown to alleviate ER stress and its associated neurodegeneration. However, uncontrolled activation of some UPR factors has also been demonstrated to worsen neurodegenerative phenotypes, suggesting that detailed molecular mechanisms around ER stress and its related neurodegenerations should be understood to develop effective therapeutics against aging-associated neurological syndromes. We also discuss current therapeutic endeavors, such as the development of small molecules that selectively target individual UPR components and address ER stress in general.

Abstract Background The ratio of T helper 1 (Th1) to T helper 2 (Th2) as well as T helper 17 (Th17) to regulatory T cells (Treg) represents the state and direction of immune response. Recent studies demonstrated that dexmedetomidine reduced the secretion of inflammatory cytokines. We performed this study to investigate the effect of different doses of intraoperative dexmedetomidine on the expression of Th1, Th2, T17 and Treg cytokines and their ratios. Methods Seventy-five patients undergoing laparoscopic cholecystectomy were randomly separated into one of three groups: the full dose group (n = 25), in which dexmedetomidine was infused with a 1.0 μg/kg loading followed by an infusion of 0.5 μg/kg/min after anaesthetic induction, or the half dose group (n = 26), in which the dose was half of that of full dose group, or the saline group (n = 24) which was control. T cell cytokines were quantified by sandwich enzyme-linked immunoassay for blood samples taken after anaesthetic induction (T0), at the end of surgery (T1), and 60 min after surgery (T2). IFN-gamma/IL-4 and IL-17/IL-10, which represent the ratio of Th1/Th2 and Th17/Treg cytokines, respectively, were calculated as indices of immune cell levels based upon serum cytokines levels in place of direct measurements. C-reactive protein (CRP) concentrations were measured on the next day following surgery. Results The full dose group was associated with higher ratios of IFN-gamma/IL-4 than those of half dose group and control [10.1 vs. 1.9 at T1 (P = 0.041) compared with half dose group, and 10.1 vs. 0.2 at T1 (P = 0.031), 7.4 vs. 0.1 at T2 (P = 0.025) compared with control]. IL-17/IL-10 ratios were higher in the full dose group than those in control [4.2 vs. 0.6 at T1 (P = 0.013), 3.0 vs. 0.3 at T2 (P = 0.011)]. The CRP levels were lower in the dexmedetomidine-treated groups in a dose-dependent manner. Conclusions Dexmedetomidine exhibits immunomodulatory effects, shifting the Th1/Th2 and T17/Treg cytokine balance toward Th1 and T17, respectively, in a dose-dependent pattern in patients with surgical and anaesthetic stress. Trial registration Clinical Research Information Service, Republic of Korea (CRIS); KCT0000503; Registration date: Aug 13, 2012.

An increased life span and accompanying nutritional affluency have led to a rapid increase in diseases associated with aging, such as obesity and type 2 diabetes, imposing a tremendous economic and health burden on society. Pancreatic β-cells are crucial for controlling glucose homeostasis by properly producing and secreting the glucose-lowering hormone insulin, and the dysfunction of β-cells determines the outcomes for both type 1 and type 2 diabetes. As the native structure of insulin is formed within the endoplasmic reticulum (ER), ER homeostasis should be appropriately maintained to allow for the proper metabolic homeostasis and functioning of β-cells. Recent studies have found that cellular senescence is critically linked with cellular stresses, including ER stress, oxidative stress, and mitochondrial stress. These studies implied that β-cell senescence is caused by ER stress and other cellular stresses and contributes to β-cells’ dysfunction and the impairment of glucose homeostasis. This review documents and discusses the current understanding of cellular senescence, β-cell function, ER stress, its associated signaling mechanism (unfolded protein response), and the effect of ER stress on β-cell senescence and dysfunction.

Since the coronavirus disease 2019 (COVID-19) pandemic, most professional sports events have been held without spectators. It is generally believed that home teams deprived of enthusiastic support from their home fans experience reduced benefits of playing on their home fields, thus becoming less likely to win. This study attempts to confirm if this belief is true in four major European football leagues through statistical analysis. This study proposes a Bayesian hierarchical Poisson model to estimate parameters reflecting the home advantage and the change in such advantage. These parameters are used to improve the performance of machine-learning-based prediction models for football matches played after the COVID-19 break. The study describes the statistical analysis on the impact of the COVID-19 pandemic on football match results in terms of the expected score and goal difference. It also shows that estimated parameters from the proposed model reflect the changed home advantage. Finally, the study verifies that these parameters, when included as additional features, enhance the performance of various football match prediction models. The home advantage in European football matches has changed because of the behind-closed-doors policy implemented due to the COVID-19 pandemic. Using parameters reflecting the pandemic’s impact, it is possible to predict more precise results of spectator-free matches after the COVID-19 break.

Aminoacyl-tRNA synthetases (ARSs), which are essential for protein translation, were recently shown to have non-translational functions in various pathological conditions including cancer. However, the molecular mechanism underlying the role of ARSs in cancer remains unknown. Here, we demonstrate that asparaginyl-tRNA synthetase (NRS) regulates Yorkie-mediated tumorigenesis by binding to the Hippo pathway component Salvador. NRS-RNAi and the NRS inhibitor tirandamycin B (TirB) suppressed Yorkie-mediated tumor phenotypes in Drosophila. Genetic analysis showed that NRS interacted with Salvador, and NRS activated Hippo target genes by regulating Yorkie phosphorylation. Biochemical analyses showed that NRS blocked Salvador-Hippo binding by interacting directly with Salvador, and TirB treatment inhibited NRS-Salvador binding. YAP target genes were upregulated in a mammalian cancer cell line with high expression of NRS, whereas TirB treatment suppressed cancer cell proliferation. These results indicate that NRS regulates tumor growth by interacting with Salvador in the Hippo signaling pathway.

An Mw 5.5 earthquake occurred in Pohang, South Korea on November 15, 2017, resulting in a great impact on society. Despite a lot of controversy about the cause of the earthquake in relation to the enhanced geothermal system (EGS), the location of earthquake-related active faults is poorly known. Here, we first report the results of the geochemical and isotopic analyses of dissolved gases in groundwater in the Heunghae, Yeonil, and Sinkwang areas. According to the N2-Ar-He relationship, samples from the Heunghae and Yeonil areas are contributed to the mantle, except for the Sinkwang area, where all samples are atmospheric. The Pohang samples consist mainly of N2 and CO2, and some samples of the Heunghae and Yeonil areas contain substantial CH4. Stable isotope compositions of N2 (δ15N=0.2 to 3.6‰), CO2 (δ13C=−27.3 to−16.0‰), and CH4 (δ13C=−76.1 to−70.0‰) indicate that these components are derived from organic substances in sedimentary layer of Pohang Basin. On the other hand, helium isotope ratios (3He/4He, up to 3.83 Ra) represent the significant mantle contribution in the Heunghae and Yeonil areas. Through the distribution of high 3He/4He ratios, we propose that the Heunghae, Namsong, and Jamyeong faults are the passage of mantle-derived fluids. Computed 3He fluxes of the Heunghae (120 to 3,000 atoms cm-2 sec-1), Namsong (52 to 1,300 atoms cm-2 sec-1), and Jamyeong (83 to 2,100 atoms cm-2 sec-1) faults are comparable to other major active faults around the world, reflecting either high porosity or high helium flow rates. Therefore, our results demonstrate that there are active faults near the EGS facilities, which can provide the basis for future studies.

Indoor pollutants are important problems to public health. Among indoor pollutants, indoor dust contains extracellular vesicles (EVs), which are associated with pulmonary inflammation. However, it has not been reported whether indoor dust EVs affect the cancer lung metastasis. In this study, we isolated indoor dust EVs and investigated their roles in cancer lung metastasis. Upon intranasal administration, indoor dust EVs enhanced mouse melanoma lung metastasis in a dose-dependent manner in mice. Pre-treatment or co-treatment of indoor dust EVs significantly promoted melanoma lung metastasis, whereas post-treatment of the EVs did not. In addition, the lung lysates from indoor dust EV-treated mice significantly increased tumour cell migration in vitro. We observed that tumour necrosis factor-α played important roles in indoor dust EV-mediated promotion of tumour cell migration in vitro and cancer lung metastasis in vivo. Furthermore, Pseudomonas EVs, the main components of indoor dust EVs, and indoor dust EVs showed comparable effects in promoting tumour cell migration in vitro and cancer lung metastasis in vivo. Taken together, our results suggest that indoor dust EVs, at least partly contributed by Pseudomonas EVs, are potential promoting agents of cancer lung metastasis.

Mesenchymal stem cells (MSCs) have emerged as a promising therapeutic approach for diverse diseases and injuries. The biological and clinical advantages of human fetal MSCs (hfMSCs) have recently been reported. In terms of promising therapeutic approaches for diverse diseases and injuries, hfMSCs have gained prominence as healing tools for clinical therapies. Therefore, this review assesses not the only biological advantages of hfMSCs for healing human diseases and regeneration, but also the research evidence for the engraftment and immunomodulation of hfMSCs based on their sources and biological components. Of particular clinical relevance, the present review also suggests the potential therapeutic feasibilities of hfMSCs for musculoskeletal disorders, including osteoporosis, osteoarthritis, and osteogenesis imperfecta.

Summary: Pluripotent stem cells (PSCs) represent the most promising clinical source for regenerative medicine. However, given the cellular heterogeneity within cultivation and safety concerns, the development of specific and efficient tools to isolate a pure population and eliminate all residual undifferentiated PSCs from differentiated derivatives is a prerequisite for clinical applications. In this study, we raised a monoclonal antibody and identified its target antigen as desmoglein-2 (DSG2). DSG2 co-localized with human PSC (hPSC)-specific cell surface markers, and its expression was rapidly downregulated upon differentiation. The depletion of DSG2 markedly decreased hPSC proliferation and pluripotency marker expression. In addition, DSG2-negative population in hPSCs exhibited a notable suppression in embryonic body and teratoma formation. The actions of DSG2 in regulating the self-renewal and pluripotency of hPSCs were predominantly exerted through the regulation of β-catenin/Slug-mediated epithelial-to-mesenchymal transition. Our results demonstrate that DSG2 is a valuable PSC surface marker that is essential for the maintenance of PSC self-renewal. : DSG2 is a desmosomal cadherin molecule. In this article, Min and colleagues show that DSG2 is a valuable PSC surface marker that is essential for the maintenance of PSC self-renewal and pluripotency and the acquisition of pluripotency during somatic cell reprogramming through the regulation of β-catenin-mediated EMT signaling. keywords: desmoglein-2, cell surface marker, pluripotent stem cells, monoclonal antibody, EMT

The objective of this study was to investigate the protective effect of esculetin against ethanol-induced liver injury in both HepG2 cells and mice. Treatment with esculetin significantly prevented ethanol-induced cytotoxicity in HepG2 cells by reducing the levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST). This protective effect was likely associated with antioxidant potential of esculetin, as evidenced by the attenuation of reactive oxygen species (ROS) and malondialdehyde (MDA) production and restoration of the depleted glutathione (GSH) levels in ethanol-induced HepG2 cells. Esculetin also dramatically increased the nuclear translocation of NF-E2-related factor 2 (Nrf2) and antioxidant response element (ARE) reporter gene activity, which led to the upregulation of ARE-responsive enzymes. In animal studies, esculetin markedly prevented ethanol-induced liver injury by reducing GSH depletion, MDA production, and the lipid contents in liver. Moreover, esculetin lowered the levels of serum ALT, serum AST, and the content of serum lipids.

Background: The Panax ginseng plant is used as an herbal medicine. Phytosterols of P. ginseng have inhibitory effects on inflammation-related factors in HepG2 cells. Methods: Phytosterols (e.g., stigmasterol and β-sitosterol) in the roots of P. ginseng grown under various conditions were analyzed using high-performance liquid chromatography. The P. ginseng roots analyzed in this study were collected from three cultivation areas in Korea (i.e., Geumsan, Yeongju, and Jinan) and differed by cultivation year (i.e., 4 years, 5 years, and 6 years) and production process (i.e., straight ginseng, red ginseng, and white ginseng). Results: The concentrations of stigmasterol and β-sitosterol in P. ginseng roots were 2.22–23.04 mg/g and 7.35–59.09 mg/g, respectively. The highest concentrations of stigmasterol and β-sitosterol were in the roots of 6-year-old P. ginseng cultivated in Jinan (82.14 mg/g and 53.23 mg/g, respectively). Conclusion: Six-year-old white ginseng and white ginseng cultivated in Jinan containing stigmasterol and β-sitosterol are potentially a new source of income in agriculture.

Objective: Peroxisome proliferator-activated receptor γ (PPARγ) coactivator-1α (PGC-1α) promotes hepatic gluconeogenesis by activating HNF4α and FoxO1. PGC-1α expression in the liver is highly elevated in obese and diabetic conditions, leading to increased hepatic glucose production. We previously showed that the spliced form of X-box binding protein 1 (XBP1s) suppresses FoxO1 activity and hepatic gluconeogenesis. The shared role of PGC-1α and XBP1s in regulating FoxO1 activity and gluconeogenesis led us to investigate the probable interaction between PGC-1α and XBP1s and its role in glucose metabolism. Methods: We investigated the biochemical interaction between PGC-1α and XBP1s and examined the role of their interaction in glucose homeostasis using animal models. Results: We show that PGC-1α interacts with XBP1s, which plays an anti-gluconeogenic role in the liver by suppressing FoxO1 activity. The physical interaction between PGC-1α and XBP1s leads to suppression of XBP1s activity rather than its activation. Upregulating PGC-1α expression in the liver of lean mice lessens XBP1s protein levels, and reducing PGC-1α levels in obese and diabetic mouse liver restores XBP1s protein induction. Conclusions: Our findings reveal a novel function of PGC-1α as a suppressor of XBP1s function, suggesting that hepatic PGC-1α promotes gluconeogenesis through multiple pathways as a co-activator for HNF4α and FoxO1 and also as a suppressor for anti-gluconeogenic transcription factor XBP1s. Keywords: PGC-1α, XBP1s, Glucose homeostasis, ER stress, UPR, Insulin resistance

Recent studies on the pathophysiology of irritable bowel syndrome (IBS) have focused on the role of mast cells (MCs) in intestinal mucosal immunity. A link between allergic airway diseases (AADs) and IBS has been suggested because both diseases have similar pathophysiology. We aimed to investigate whether the induction of AAD in mice could lead to inflammation of the colonic mucosa, similar to IBS. We also evaluated whether this inflammatory response could be suppressed by administering a therapeutic agent. Mice were divided into three groups: control, AAD-induced, and salbutamol-treated. An AAD mouse model was established by intraperitoneal injection and nasal challenge with ovalbumin. Mice with AAD were intranasally administered salbutamol. Analyses of cytokine levels, MC count, and tryptase levels in the intestinal mucosa were performed to compare the changes in inflammatory responses among the three groups. Inflammation was observed in the intestinal mucosa of mice in the AAD group. This inflammation in AAD mice was suppressed after salbutamol treatment. Our study demonstrates that AAD induces an inflammatory response similar to that in IBS, suggesting a possible association between IBS and AADs. In patients with IBS with such allergic components, salbutamol may have the potential to alleviate the inflammatory response.

In this article, a layered shell element-based, elastic finite element method for predicting welding distortion in multi-pass welding is developed. The welding distortion generated in each pass can be predicted by employing layer-by-layer equivalent plastic strains as thermal expansion coefficients and using the heat-affected zone (HAZ) width as the mesh size. The final distortion can be expressed as the sum of the distortions for each pass. This study focuses on extraction of the equivalent plastic strain and HAZ width through 3D thermal elastic plastic analysis (TEPA) for each pass. The input variables extracted from each pass can be converted and added to simulate the final distortion of the multi-pass welding. A 10 mm thick, multi-pass butt-welded joint, subjected to three passes, is simulated via the proposed method. The predicted welding distortion is compared with the 3D TEPA results and the measured experimental data. The outcome indicates that good agreement can be obtained.

Recently, the involvement of the nervous system in the pathology of allergic diseases has attracted increasing interest. However, the precise pathophysiological role of enteric neurons in food allergies has not been elucidated. We report the presence of functional high-affinity IgE receptors (FcεRIs) in enteric neurons. FcεRI immunoreactivities were observed in approximately 70% of cholinergic myenteric neurons from choline acetyltransferase-eGFP mice. Furthermore, stimulation by IgE-antigen elevated intracellular Ca2+ concentration in isolated myenteric neurons from normal mice, suggesting that FcεRIs are capable of activating myenteric neurons. Additionally, the morphological investigation revealed that the majority of mucosal mast cells were in close proximity to enteric nerve fibers in the colonic mucosa of food allergy mice. Next, using a newly developed coculture system of isolated myenteric neurons and mucosal-type bone-marrow-derived mast cells (mBMMCs) with a calcium imaging system, we demonstrated that the stimulation of isolated myenteric neurons by veratridine caused the activation of mBMMCs, which was suppressed by the adenosine A3 receptor antagonist MRE 3008F20. Moreover, the expression of the adenosine A3 receptor gene was detected in mBMMCs. Therefore, in conclusion, it is suggested that, through interaction with mucosal mast cells, IgE-antigen-activated myenteric neurons play a pathological role in further exacerbating the pathology of food allergy.

Abstract Mannan endo-1,4-β-mannosidase (commonly known as β-mannanase) catalyzes a random cleavage of the β-d-1,4-mannopyranosyl linkage in mannan polymers. The enzyme has been utilized in biofuel production from lignocellulose biomass, as well as in production of mannooligosaccharides (MOS) for applications in feed and food industries. We aimed to obtain a β-mannanase, for such mannan polymer utilization, from actinomycetes strains isolated in Indonesia. Strains exhibiting high mannanase activity were screened, and one strain belonging to the genus Kitasatospora was selected. We obtained a β-mannanase from this strain, and an amino acid sequence of this Kitasatospora β-mannanase showed a 58–71% similarity with the amino acid sequences of Streptomyces β-mannanases. The Kitasatospora β-mannanase showed a significant level of activity (944 U/mg) against locust bean gum (0.5% w/v) and a potential for oligosaccharide production from various mannan polymers. The β-mannanase might be beneficial particularly in the enzymatic production of MOS for applications of mannan utilization.

Background: Natural Killer (NK) cell-based immunotherapy used to treat cancer requires the adoptive transfer of a large number of activated NK cells. Here, we report a new effective method to expand human NK cells ex vivo using K562 cells genetically engineered (GE) to express OX40 ligand (K562-OX40L) in combination with a short exposure to soluble IL-21. In addition, we describe a possible mechanism of the NK cell expansion through the OX40 receptor-OX40 ligand axis which is dependent on NK cell homotypic interaction.Methods: K562-OX40L cells were generated by lentiviral transduction and were used as feeder cells to expand and activate NK cells from PBMCs in the presence of IL-2/IL-15. Soluble IL-21 was also added in various concentrations only once at the beginning of the culture. NK cells were expanded for 4–5 weeks, and the purity, expansion rate, phenotype and function (cytotoxicity, antibody-dependent cell-mediated cytotoxicity (ADCC), cytokine production, CD107a degranulation) of these expanded NK cells were compared to those generated by using K562 feeder cells.Results: The culture of NK cells with K562-OX40L cells in combination with the transient exposure to IL-21 highly enhanced NK cell expansion to approximately 2,000-fold after 4 weeks of culture, compared to a 303-fold expansion using the conventional K562 cells. Mechanistically, the OX40-OX40L axis between the feeder cells and NK cells as well as the homotypic interaction between NK cells through the OX40-OX40L axis were both necessary for NK cell expansion. The short exposure of NK cells to IL-21 had a synergistic effect with OX40 signaling for NK cell expansion. Apart from their enhanced expansion, NK cells grown with K562-OX40L feeder cells were similar to those grown with conventional K562 cells in regard to the surface expression of various receptors, cytotoxicity, ADCC, cytokine secretion, and CD107 degranulation.Conclusion: Our data suggest that OX40 ligand is a potent co-stimulant for the robust expansion of human NK cells and the homotypic NK cell interactions through the OX40-OX40L axis is a mechanism of NK cell expansion.

Slab-like copper films with a thickness of 9 nm (~70 atoms) and sheet resistance of ≤ 9 Ω sq−1 are shown to exhibit remarkable long-term stability toward air-oxidation when passivated with an 0. 8 nm aluminium layer deposited by simple thermal evaporation. The sheet resistance of 9 nm Cu films passivated in this way, and lithographically patterned with a dense array of ~6 million apertures per cm2, increases by < 3.5% after 7,000 h exposure to ambient air. Using a combination of annular-dark field scanning transmission electron microscopy, nanoscale spatially resolved elemental analysis and atomic force microscopy, we show that this surprising effectiveness of this layer results from spontaneous segregation of the aluminium to grain boundaries in the copper film where it forms a ternary oxide plug at those sites in the metal film most vulnerable to oxidation. Crucially, the heterogeneous distribution of this passivating oxide layer combined with its very low thickness ensures that the underlying metal is not electrically isolated, and so this simple passivation step renders Cu films stable enough to compete with Ag as the base metal for transparent electrode applications in emerging optoelectronic devices.

Artemisia argyi is widely used as traditional medicine in East Asia. However, its effects against inflammation and gastric ulcers have not been reported yet. We analyzed anti-inflammatory activity and its molecular mechanisms of A. argyi using RAW264.7 cells line, then evaluated the curative efficacy in rats with acute gastric ulcers. Nitric oxide and IL-6 production was measured using Griess reagent and an ELISA kit. Inducible nitric oxide synthase (iNOS), interleukin (IL)-6, and mucin (MUC)1, MUC5AC, and MUC6 mRNA were determined by SYBR Green or Taqman qRT-PCR methods. The phosphorylation of ERK, JNK, p38, and c-Jun protein were detected by western blotting. RW0117 inhibited LPS-induced NO and IL-6 production. The mRNA levels of iNOS and IL-6 were strongly suppressed. The phosphorylation of ERK, JNK, and c-Jun decreased by treatment with RW0117. Oral administration of RW0117 recovered the amount of mucin mRNA and protein level that was decreased due to gastric ulcers by HCl-EtOH. A. argyi exhibited strong anti-inflammatory effects and contributed to the modulation of HCl-EtOH-induced gastric ulcer in rats.

Background/Aims This study aimed to clarify the effect of obesity on the development of hepatocellular carcinoma (HCC) in chronic hepatitis B (CHB) patients receiving antiviral treatment. Methods This study applied a retrospective analysis to a historical cohort in Bundang Jesaeng Hospital. In total, 102 CHB patients were treated with entecavir as an initial treatment for CHB and checked for obesity using a body composition analyzer. Hepatic steatosis was measured semiquantitatively using Hamaguchi’s scoring system in ultrasonography. Risk factors for the development of HCC were analyzed, including obesity-related factors (body mass index [BMI], waist circumference [WC], waist-to-hip ratio [WHR], visceral fat area [VFA], and hepatic steatosis). Results The median follow-up duration of the patients was 45.2 months (interquartile range: 36.0-58.3 months). The cumulative incidence rates of HCC at 1 year, 3 years, and 5 years were 0%, 5.3%, and 9.0%, respectively. Univariable analysis revealed that the risk factors for HCC development were a platelet count of

Background: Panax ginseng has been used as Korean medicine for various diseases. It has antioxidant, hypotensive, sedative, analgesic, and endocrine activities. Dammarane-type triterpenes from the plant have various beneficial effects. Methods: A dammarane-type triterpene saponin was isolated from P. ginseng root through chromatography such as repeated column chromatography and medium pressure liquid chromatography. Results and conclusion: New dammarane-type triterpene saponin was isolated for the first time from nature. The structure was elucidated as ginsenoside Rg12 (1) based on spectral data. There may be good materials from P. ginseng for the development of industrial applications such as nutraceutical, pharmaceutical, and cosmeceutical purposes.

In this study, modified equivalent load method for welding distortion analysis is suggested to improve its accuracy. To avoid the excessive computational time for welding distortion analysis of large welded structures, shell element-based elastic analysis methods are widely used, applying the inherent deformation approach. Equivalent nodal forces are commonly used in common FE (Finite Element) codes to enter these inherent deformation values. However, the conventional method cannot estimate precise longitudinal bending following the conventional equation. In this study, the problem of the existing equivalent load method is analyzed by a case study, and the modified equivalent load method that can estimate angular distortion, transverse shrinkage, and longitudinal bending is presented based on the FEM principle. The results show that by applying the proposed method, the shell element-based elastic FE approach for the welding distortion analysis can be achieved with improved accuracy.

The effect of deposition pattern on the temperature and global distortion of Direct Metal Tooling (DMT) based Additive Manufactured (AM) is investigated through the experimental results of laser deposited SUS316. DMT is one of the Directed Energy Deposition (DED) processes. In situ temperature measurements were used to monitor the temperature of the substrates and global distortion patterns were analyzed using CMM (coordinate Measuring Machine) after the deposition. Six different patterns combining long raster and short raster patterns were considered for the case studies. The results showed that the deposition pattern affects the temperature gradient and that the peak temperature of each layer can increase or decrease according to the sequence of the deposition pattern. Also, the pattern of the first layer had a dominant influence on the longitudinal bending deflection that occurs. Based on these results, appropriate tool path schedule can be utilized to control not only the distortion but also the peak temperature of the DMT-based AM parts.