Aortic carboxypeptidase-like protein, a putative myokine, stimulates the differentiation and survival of bone-forming osteoblasts.

A new target that stimulates bone formation is needed to overcome limitations of current anti-osteoporotic drugs. Myokines, factors secreted from muscles, may modulate it. In this study, we investigated the role of aortic carboxypeptidase-like protein (ACLP), which is highly expressed in skeletal muscles, on bone formation. MC3T3-E1 cells and/or calvaria osteoblasts were treated with recombinant N-terminal mouse ACLP containing a signal peptide [rmACLP (N)]. The expression and secretion of ACLP were higher in skeletal muscle and differentiated myotube than in other tissues and undifferentiated myoblasts, respectively. rmACLP (N) increased bone formation, ALP activity, and phosphorylated p38 mitogen-activated protein (MAP) kinase in osteoblasts; reversal was achieved by pre-treatment with a TGF-ß receptor inhibitor. Under H2 O2 treatment, rmACLP (N) increased osteoblast survival, phosphorylated p38 MAP kinase, and the nuclear translocation of FoxO3a in osteoblasts. H2 O2 treatment caused rmACLP (N) to suppress its apoptotic, oxidative, and caspase-9 activities. rmACLP (N)-stimulated osteoblast survival was reversed by pre-treatment with a p38 inhibitor, a TGF-ß-receptor II blocking antibody, and a FoxO3a shRNA. Conditioned media (CM) from muscle cells stimulated osteoblast survival under H2 O2 treatment, in contrast to CM from ACLP knockdown muscle cells. rmACLP (N) increased the expressions of FoxO3a target anti-oxidant genes such as Sod2, Trx2, and Prx5. In conclusion, ACLP stimulated the differentiation and survival of osteoblasts. This led to the stimulation of bone formation by the activation of p38 MAP kinase and/or FoxO3a via TGF-ß receptors. These findings suggest a novel role for ACLP in bone metabolism as a putative myokine.

Ochratoxin A triggers endoplasmic reticulum stress through PERK/NRF2 signaling and DNA damage during early embryonic developmental competence in pigs.

Ochratoxin A (OTA), a mycotoxin found in foods, has a deleterious effect on female reproduction owing to its endocrine-disrupting activity mediated through endoplasmic reticulum (ER) stress and reactive oxygen species (ROS) production. However, the mechanisms of OTA-induced ER stress in pig embryos during in vitro culture (IVC) are not yet fully understood. In the present study, porcine embryos were cultured for two days in an IVC medium supplemented with 0.5, 1.0, and 5.0 µM OTA, which led to an OTA-induced reduction in the developmental rate of blastocysts. The mRNA-seq transcriptome analysis revealed that the reduced blastocyst development ability of OTA-exposed porcine embryos was caused by ER stress, ultimately resulting in the accumulation of ROS and the occurrence of apoptosis. The expression levels of some UPR/PERK signaling-related genes (DDIT3, EIF2AK3, EIF2S1, NFE2L2, ATF4, EIF2A, and KEAP1) were found to differ in OTA-exposed pig embryos. OTA induces DNA damage by triggering an increase in RAD51/γ-H2AX levels and suppressing p-NRF2 activity. This effect is mediated through intracellular ROS and superoxide accumulation in the nuclei of porcine embryos. The cytotoxicity of OTA increased the activation of the PERK signal pathways (p-PERK, PERK, p-eIF2α, eIF2α, ATF4, and CHOP) in porcine embryos, with abnormal distribution of the ER observed around the nucleus. Collectively, our findings indicate that ER stress is a major cause of decline in the development of porcine embryos exposed to OTA. Therefore, OTA exposure induces ER stress and DNA damage via oxidative stress by disrupting PERK/NRF2 signaling activity in the developmental competence of porcine embryos during IVC.

Table-Balancing Cooperative Robot Based on Deep Reinforcement Learning.

Reinforcement learning is one of the artificial intelligence methods that enable robots to judge and operate situations on their own by learning to perform tasks. Previous reinforcement learning research has mainly focused on tasks performed by individual robots; however, everyday tasks, such as balancing tables, often require cooperation between two individuals to avoid injury when moving. In this research, we propose a deep reinforcement learning-based technique for robots to perform a table-balancing task in cooperation with a human. The cooperative robot proposed in this paper recognizes human behavior to balance the table. This recognition is achieved by utilizing the robot's camera to take an image of the state of the table, then the table-balance action is performed afterward. Deep Q-network (DQN) is a deep reinforcement learning technology applied to cooperative robots. As a result of learning table balancing, on average, the cooperative robot showed a 90% optimal policy convergence rate in 20 runs of training with optimal hyperparameters applied to DQN-based techniques. In the H/W experiment, the trained DQN-based robot achieved an operation precision of 90%, thus verifying its excellent performance.

Changes Over Time in Parental Self-identity After the Loss of an Adolescent Child.

This study explored bereaved parents' responses to their child's death in the 2014 Sewol Ferry sinking incident, focusing on identifying changes in parental self-identity two and five years after their loss. To understand the unique meaning of their loss and its impact on their self-perception, in-depth interviews were conducted with eight mothers and four fathers at two timepoints. Three patterns of parental self-identity: reintegration, disintegration, and coexistence emerged. Patterns emerged in five domains: (a) relational identity, (b) physical identity, (c) financial identity, (d) professional identity and (e) spiritual identity. Each of these domain-associated themes provided insights into the patterns and characteristics of the changes in bereaved parents' self-identity following their loss. Recommendations for future research and potential implications are discussed.

Enhanced Performance of WS2 Field-Effect Transistor through Mono and Bilayer h-BN Tunneling Contacts.

Transition metal dichalcogenides (TMDs) are of great interest owing to their unique properties. However, TMD materials face two major challenges that limit their practical applications: contact resistance and surface contamination. Herein, a strategy to overcome these problems by inserting a monolayer of hexagonal boron nitride (h-BN) at the chromium (Cr) and tungsten disulfide (WS2 ) interface is introduced. Electrical behaviors of direct metal-semiconductor (MS) and metal-insulator-semiconductor (MIS) contacts with mono- and bilayer h-BN in a four-layer WS2 field-effect transistor (FET) are evaluated under vacuum from 77 to 300 K. The performance of the MIS contacts differs based on the metal work function when using Cr and indium (In). The contact resistance is significantly reduced by approximately ten times with MIS contacts compared with that for MS contacts. An electron mobility up to ≈115 cm2  V-1  s-1 at 300 K is achieved with the insertion of monolayer h-BN, which is approximately ten times higher than that with MS contacts. The mobility and contact resistance enhancement are attributed to Schottky barrier reduction when h-BN is introduced between Cr and WS2 . The dependence of the tunneling mechanisms on the h-BN thickness is investigated by extracting the tunneling barrier parameters.

A Longitudinal Perspective on Bereaved Parent's Changes in Life Experience after the 2014 Sewol Ferry Sinking.

This study compared reports of parental life experiences from bereaved parents at two and five years after the death of their adolescent children due to the sinking of the Sewol Ferry in South Korea. Twelve bereaved parents (eight mothers and four fathers from eight families) were interviewed regarding the changes and stabilities they experienced over time at two time points of data collection. Twenty-eight in-depth interviews were transcribed verbatim and analyzed using qualitative content analysis. Outcomes of parental bereavement and changes in life over time may be classified into four main categories: (a) personal changes, (b) changes in perspectives, (c) changes in family relationship, and (d) changes in social relationship and work attitude. This study includes a detailed examination of the phenomenon among the bereaved parents. Discussions and implications are provided based on the results.

Oxidative activation of type III CD38 by NADPH oxidase-derived hydrogen peroxide in Ca2+ signaling.

Reactive oxygen species (ROS) derived from NADPH oxidase (Nox) has been shown to activate ADP-ribosyl cyclase (ARC), which produces the Ca2+ mobilizing second messenger, cyclic ADP-ribose (cADPR). In the present study, we examined how ROS activates cluster of differentiation (CD)38, a mammalian prototype of ARC. CD38 exists in type II and III forms with opposing membrane orientation. This study showed the coexpression of type II and III CD38 in lymphokine-activated killer (LAK) cells. The catalytic site of the constitutively active type II CD38 faces the outside of the cell or the inside of early endosomes (EEs), whereas the basally inactive type III CD38 faces the cytosol. Type III CD38 interacted with Nox4/phosphorylated-p22phox (p-p22phox) in EEs of LAK cells upon IL-8 treatment. H2O2 derived from Nox4 activated type III CD38 by forming a disulfide bond between Cys164 and Cys177, resulting in increased cADPR formation. Our study identified the mechanism by which type III CD38 is activated in an immune cell (LAK), in which H2O2 generated by Nox4 oxidizes and activates type III CD38 to generate cADPR. These findings provide a novel model of cross-talk between ROS and Ca2+ signaling.-Park, D.-R., Nam, T.-S., Kim, Y.-W., Bae, Y. S., Kim, U.-H. Oxidative activation of type III CD38 by NADPH oxidase-derived hydrogen peroxide in Ca2+ signaling.

Prognostic value of the posterior cricoarytenoid muscle atrophy in computerized tomography scans for unilateral vocal fold paralysis recovery.

OBJECTIVES: To evaluate the prognostic value of the posterior cricoarytenoid (PCA) muscle atrophy observed on neck computed tomography (CT) in patients with unilateral vocal fold paralysis. METHODS: CT images of 87 subjects with unilateral vocal fold paralysis (UVFP) were evaluated to analyze the PCA muscle atrophy and to measure the severity of the PCA muscle atrophy in semi-quantitative manner. The grading of the PCA muscle atrophy was compared with the recruitment pattern of laryngeal electromyography (LEMG) and restoration of vocal fold movement. RESULTS: The PCA muscle was identifiable on CT in 73 subjects. Using the PCA muscle atrophy as an indicator of UVFP, we correctly predicted the paralysis in 69 (94.5%). Grade of the PCA muscle atrophy is significantly correlated with recruitment pattern of LEMG. If the positive result is defined as the PCA muscle showed moderate to severe degree of atrophy, we could predict the persistent UVFP in 88% of patients. CONCLUSIONS: PCA muscle atrophy identified on CT scan in patients with UVFP, is associated with low rates of return of mobility in the affected vocal fold.

Uncertainty Estimation of the Dose Rate in Real-Time Applications Using Gaussian Process Regression.

Major standard organizations have addressed the issue of reporting uncertainties in dose rate estimations. There are, however, challenges in estimating uncertainties when the radiation environment is considered, especially in real-time dosimetry. This study reports on the implementation of Gaussian process regression based on a spectrum-to-dose conversion operator (i.e., G(E) function), the aim of which is to deal with uncertainty in dose rate estimation based on various irradiation geometries. Results show that the proposed approach provides the dose rate estimation as a probability distribution in a single measurement, thereby increasing its real-time applications. In particular, under various irradiation geometries, the mean values of the dose rate were closer to the true values than the point estimates calculated by a G(E) function obtained from the anterior-posterior irradiation geometry that is intended to provide conservative estimates. In most cases, the 95% confidence intervals of uncertainties included those conservative estimates and the true values over the range of 50-3000 keV. The proposed method, therefore, not only conforms to the concept of operational quantities (i.e., conservative estimates) but also provides more reliable results.

The management of malignant lower limb ulcers: clinical considerations.

Lower limb malignant ulcers are an uncommon finding, making diagnosis complex and their management costly. Yet, despite this, the increase in skin cancers over the past 30 years means that clinicians require an awareness and understanding of their existence, particularly in the primary care setting. Familiarity with common aetiologies and presentations is vital for prompt recognition, diagnosis and referral of wounds suspicious for malignancy. Lower limb malignant wounds often develop insidiously, with a wide variation in clinical presentation that overlaps between entities. Therefore, a fundamental algorithm for approaching lower limb ulcers that raise suspicion of malignancy should be possessed by all clinicians. This article reviews the clinical features of malignant wounds that should alert clinicians to the need for further evaluation, such as atypical location and appearance. The authors also highlight the various diagnostic and therapeutic modalities available and review current clinical guidelines for the referral and follow-up of suspicious lesions.

Parental Perceptions of Surviving Sibling Grief Responses to an Adolescent's Violent and Sudden Death by the Sewol Ferry Disaster in South Korea.

The aim of this study was to provide empirical descriptions of responses to the death of a sibling to the sinking of the Sewol ferry in South Korea. 16 bereaved parents are interviewed regarding their surviving children's grief responses at approximately 2 years after the death. The surviving siblings described by the bereaved parents are 14 in total, including 8 teens in their 10s and 4 young adults in their 20s. Interviews were transcribed verbatim and analyzed using a qualitative content analysis method. The following themes emerged: (a) negative behavioral changes, (b) expressions of grief, (c) change in relationship with parents, (d) school adjustment problems, and (e) social changes. Unique aspects of the grief responses among the surviving siblings in this study are noted. Discussions and implications are provided based on the results.

CD38-cADPR-SERCA Signaling Axis Determines Skeletal Muscle Contractile Force in Response to ß-Adrenergic Stimulation.

BACKGROUND/AIMS: Cyclic ADP-ribose (cADPR) is a Ca2+ -mobilization messenger that acts on ryanodine-sensitive Ca2+ channels in the sarcoplasmic reticulum (SR) Ca2+ stores. Moreover, it has been proposed that cADPR serves an additional role in activating the sarcoendoplasmic reticulum Ca2+ -ATPase (SERCA) pump. The aim of this study was to determine the exact mechanism by which cADPR regulates SR Ca2+ stores in physiologically relevant systems. METHODS: We analyzed Ca2+ signals as well as the production of Ca2+ mobilizing messengers in the skeletal muscle cells of mice subjected to intensive exercise or in the SR fractions from skeletal muscle cells after ß-adrenergic receptor (ß-AR) stimulation. RESULTS: We show that cADPR enhances SERCA activity in skeletal muscle cells in response to ß-AR agonists, increasing SR Ca2+ uptake. We demonstrate that cADPR is generated by CD38, a cADPR-synthesizing enzyme, increasing muscle Ca2+ signals and contractile force during exercise. CD38 is upregulated by the cAMP response element-binding protein (CREB) transcription factor upon ß-AR stimuli and exercise. CD38 knockout (KO) mice show defects in their exercise and cADPR synthesis capabilities, lacking a ß-AR agonist-induced muscle contraction when compared to wild-type mice. The skeletal muscle of CD38 KO mice exhibits delayed cytosolic Ca2+ clearance and reduced SERCA activity upon exercise. CONCLUSION: These findings provide insight into the physiological adaptive mechanism by which the CD38- cADPR-SERCA signaling axis plays an essential role in muscle contraction under exercise, and define cADPR as an endogenous activator of SERCA in enhancing the SR Ca2+ load.

Highly luminescent silica-coated CdS/CdSe/CdS nanoparticles with strong chemical robustness and excellent thermal stability.

We present facile synthesis of bright CdS/CdSe/CdS@SiO2 nanoparticles with 72% of quantum yields (QYs) retaining ca 80% of the original QYs. The main innovative point is the utilization of the highly luminescent CdS/CdSe/CdS seed/spherical quantum well/shell (SQW) as silica coating seeds. The significance of inorganic semiconductor shell passivation and structure design of quantum dots (QDs) for obtaining bright QD@SiO2 is demonstrated by applying silica encapsulation via reverse microemulsion method to three kinds of QDs with different structure: CdSe core and 2 nm CdS shell (CdSe/CdS-thin); CdSe core and 6 nm CdS shell (CdSe/CdS-thick); and CdS core, CdSe intermediate shell and 5 nm CdS outer shell (CdS/CdSe/CdS-SQW). Silica encapsulation inevitably results in lower photoluminescence quantum yield (PL QY) than pristine QDs due to formation of surface defects. However, the retaining ratio of pristine QY is different in the three silica coated samples; for example, CdSe/CdS-thin/SiO2 shows the lowest retaining ratio (36%) while the retaining ratio of pristine PL QY in CdSe/CdS-thick/SiO2 and SQW/SiO2 is over 80% and SQW/SiO2 shows the highest resulting PL QY. Thick outermost CdS shell isolates the excitons from the defects at surface, making PL QY relatively insensitive to silica encapsulation. The bright SiO2-coated SQW sample shows robustness against harsh conditions, such as acid etching and thermal annealing. The high luminescence and long-term stability highlights the potential of using the SQW/SiO2 nanoparticles in bio-labeling or display applications.

Deoxynivalenol leads to endoplasmic reticulum stress-mediated apoptosis via the IRE1/JNK/CHOP pathways in porcine embryos.

The cytotoxic mycotoxin deoxynivalenol (DON) reportedly has adverse effects on oocyte maturation and embryonic development in pigs. Recently, the interplay between cell apoptosis and endoplasmic reticulum (ER) stress has garnered increasing attention in embryogenesis. However, the involvement of the inositol-requiring enzyme 1 (IRE1)/c-jun N-terminal kinase (JNK)/C/EBP homologous protein (CHOP) pathways of unfolded protein response (UPR) signaling in DON-induced apoptosis in porcine embryos remains unknown. In this study, we revealed that exposure to DON (0.25 µM) substantially decreased cell viability until the blastocyst stage in porcine embryos, concomitant with initiation of cell apoptosis through the IRE1/JNK/CHOP pathways in response to ER stress. Quantitative PCR confirmed that UPR signaling-related transcription factors were upregulated in DON-treated porcine blastocysts. Western blot analysis showed that IRE1/JNK/CHOP signaling was activated in DON-exposed porcine embryos, indicating that ER stress-associated apoptosis was instigated. The ER stress inhibitor tauroursodeoxycholic acid protected against DON-induced ER stress in porcine embryos, indicating that the toxic effects of DON on early developmental competence of porcine embryos can be prevented. In conclusion, DON exposure impairs the developmental ability of porcine embryos by inducing ER stress-mediated apoptosis via IRE1/JNK/CHOP signaling.

Temporal variations in the surface aragonite saturation state of the Yellow Sea: Observations at the Socheongcho Ocean Research Station during 2017-2022.

Accurately constraining the natural variability of the carbonate system is essential for evaluating long-term changes in coastal areas, which result from the absorption of anthropogenic CO2. This is particularly important given the significant variation in physical and biological processes in these regions. In this regard, the analysis of surface carbonate chemistry in the Yellow Sea was conducted using discrete seawater samples obtained from the Socheongcho Ocean Research Station (37.423°N, 124.738°E) between 2017 and 2022. Our bottle data and sensor pH measurements revealed considerable seasonal variations of aragonite saturation state (ΩAR), typically ranging from 1.6 to 3.9. These variations are particularly pronounced during the summer and early winter. Our dataset serves as a baseline for understanding the long-term changes in ocean acidification in the Yellow Sea, the complex biogeochemical processes in coastal areas, and their impact on ocean acidification.

The Synergistic Effect of Carbon Black/Carbon Nanotube Hybrid Fillers on the Physical and Mechanical Properties of EPDM Composites after Exposure to High-Pressure Hydrogen Gas.

This study investigated the synergistic effect of carbon black/multi-wall carbon nanotube (CB/MWCNT) hybrid fillers on the physical and mechanical properties of Ethylene propylene diene rubber (EPDM) composites after exposure to high-pressure hydrogen gas. The EPDM/CB/CNT hybrid composites were prepared by using the EPDM/MWCNT master batch (MB) with 10 phr CNTs to enhance the dispersion of CNTs in hybrid composites. The investigation included a detailed analysis of cure characteristics, crosslink density, Payne effect, mechanical properties, and hydrogen permeation properties. After exposure to 96.3 MPa hydrogen gas, the hydrogen uptake and the change in volume and mechanical properties of the composites were assessed. We found that as the MWCNT volume fraction in fillers increased, the crosslink density, filler-filler interaction, and modulus of hybrid composites increased. The hydrogen uptake and the solubility of the composites decreased with an increasing MWCNT volume fraction in fillers. Moreover, after exposure to hydrogen gas, the change in volume and mechanical properties exhibited a diminishing trend with a higher MWCNT volume fraction. We conclude that the hybridization of CB and CNTs formed strong filler-filler networks in hybrid composites, consequently reinforcing the EPDM composites and enhancing the barrier properties of hydrogen gas.

Comparison of inorganic nitrogen concentrations in airborne particles at inshore and offshore sites in the Yellow Sea (2017-2019): Long-range transport and potential impact on marine productivity.

Atmospheric deposition of nitrogen is one of the most important external nutrient sources. We investigated the concentrations of NO3- and NH4+ in airborne particles at both an offshore and an inshore site in the Yellow Sea. At the offshore site, devoid of local sources and located downwind from the highly developed areas of Korea and China, the concentrations of atmospheric particulate NO3- and NH4+ were ∼88 ± 101 nmol m-3 and ∼102 ± 102 nmol m-3, respectively, likely due to the transboundary long-range transport of pollutants. The inshore site showed a concentration ∼2 times higher than the offshore site. Considering not only dry inorganic nitrogen deposition but also wet and organic material deposition, the total atmospheric nitrogen deposition was estimated to contribute roughly 10 % to the new production in the Yellow Sea.

Investigation of the Gas Permeation Properties Using the Volumetric Analysis Technique for Polyethylene Materials Enriched with Pure Gases under High Pressure: H2, He, N2, O2 and Ar.

Polyethylene (PE) is widely used as a gas-sealing material in packing films and gas transport pipes. A technique for evaluating the permeability of water-insoluble gases has recently been developed. This technique is a volumetric analysis that is used to calculate the gas permeability by measuring the gas uptake and diffusivity. With this technique, we investigated the permeability of pure gases, such as H2, He, N2, O2 and Ar, enriched under high pressure up to 9 MPa in low-density polyethylene (LDPE), ultrahigh molecular weight polyethylene (UHMWPE) and high-density polyethylene (HDPE). The gas uptake showed a linear pressure-dependent behavior that followed Henry's law, and the diffusivity was independent of the pressure. Furthermore, the logarithmic diffusivity values of the five gases linearly decreased as their molecular kinetic diameters increased. The logarithmic solubility values linearly increased as the critical temperatures of the gases increased. The calculated permeability results were correlated with the volume fraction of the amorphous phase and the fractional free volume. This result newly showed that the amorphous phase was directly correlated to the fractional free volume.

Wearable Liquid Metal Composite with Skin-Adhesive Chitosan-Alginate-Chitosan Hydrogel for Stable Electromyogram Signal Monitoring.

In wearable bioelectronics, various studies have focused on enhancing prosthetic control accuracy by improving the quality of physiological signals. The fabrication of conductive composites through the addition of metal fillers is one way to achieve stretchability, conductivity, and biocompatibility. However, it is difficult to measure stable biological signals using these soft electronics during physical activities because of the slipping issues of the devices, which results in the inaccurate placement of the device at the target part of the body. To address these limitations, it is necessary to reduce the stiffness of the conductive materials and enhance the adhesion between the device and the skin. In this study, we measured the electromyography (EMG) signals by applying a three-layered hydrogel structure composed of chitosan-alginate-chitosan (CAC) to a stretchable electrode fabricated using a composite of styrene-ethylene-butylene-styrene and eutectic gallium-indium. We observed stable adhesion of the CAC hydrogel to the skin, which aided in keeping the electrode attached to the skin during the subject movement. Finally, we fabricated a multichannel array of CAC-coated composite electrodes (CACCE) to demonstrate the accurate classification of the EMG signals based on hand movements and channel placement, which was followed by the movement of the robot arm.

Revisit to functional data analysis of sleeping energy expenditure.

In this paper, we consider the classification problem of functional data including the sleeping energy expenditure (SEE) data, focusing on functional classification. Many existing classification rules are not effective in distinguishing the two classes of SEE data, because the trajectories of each observation have very different patterns for each class. It is often observed that some aspect of data such as the variability of paths is helpful in classification of functional data. To reflect this issue, we introduce a variable measuring the length of path in functional data and then propose a logistic model with fused lasso that considers the behavior of fluctuation of path as well as local correlations within each path. Our proposed model shows a significant improvement over some models used in the existing literature on the classification accuracy rate of functional data such as SEE data. We carry out simulation studies to show the finite sample performance and the gain that it makes in comparison with fused lasso without considering path length. With two more real datasets studied in some existing literature, we demonstrate that the new model achieves better or similar accuracy rate than the best accuracy rates reported in those studies.