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This study focused on achieving high ionic conductivity in Li-La-TiO (LLTO) solid electrolyte. To enhance ionic conductivity, the synthesis reaction was optimized by controlling the composite crystal structure of TiO2 at the B-site of the perovskite (ABO3) structured LLTO, incorporating rutile, brookite, and anatase phases. The solid-phase LLTO, synthesized utilizing the core – shell structured composite-phase TiO2 developed in this study for the first time, successfully transformed its crystal structure to β-LLTO (tetragonal to cubic). This resulted in a significant improvement in ionic conductivity (i.e. 1.11 × 10−4 Scm−1). The study findings confirmed that the composite crystal structure TiO2 used in the solid-phase synthesis of LLTO induced an increase in oxygen vacancies during the synthesis process, thereby reducing the step-free energy required for the final synthesis.

Abstract Background Electrocardiograms (ECGs) in athletes commonly reveal findings related to physiologic adaptations to exercise, that may be difficult to discern from true underlying cardiovascular abnormalities. North American and European societies have published consensus statements for normal, borderline, and abnormal ECG findings for athletes, but these criteria are not based on established correlation with disease states. Additionally, data comparing ECG findings in athletes to non-athlete control subjects are lacking. Our objective was to compare the ECGs of collegiate athletes and non-athlete controls using Z-scores for digital ECG variables to better identify significant differences between the groups and to evaluate the ECG variables in athletes falling outside the normal range. Methods Values for 102 digital ECG variables on 7206 subjects aged 17–22 years, including 672 athletes, from Hawaii Pacific Health, University of Hawaii, and Rady Children’s Hospital San Diego were obtained through retrospective review. Age and sex-specific Z-scores for ECG variables were derived from normal subjects and used to assess the range of values for specific ECG variables in young athletes. Athletes with abnormal ECGs were referred to cardiology consultation and/or echocardiogram. Results Athletes had slower heart rate, longer PR interval, more rightward QRS axis, longer QRS duration but shorter QTc duration, larger amplitude and area of T waves, prevalent R’ waves in V1, and higher values of variables traditionally associated with left ventricular hypertrophy (LVH): amplitudes of S waves (leads V1-V2), Q waves (V6, III) and R waves (II, V5, V6). Z-scores of these ECG variables in 558 (83%) of the athletes fell within − 2.5 and 2.5 range derived from the normal population dataset, and 60 (8.9%) athletes had a Z-score outside the − 3 to 3 range. While 191 (28.4%) athletes met traditional voltage criteria for diagnosis of LVH on ECG, only 53 athletes (7.9%) had Z-scores outside the range of -2.5 to 2.5 for both S amplitude in leads V1-V2 and R amplitude in leads V5-6. Only one athlete was diagnosed with hypertrophic cardiomyopathy with a Z-score of R wave in V6 of 2.34 and T wave in V6 of -5.94. Conclusion The use of Z-scores derived from a normal population may provide more precise screening to define cardiac abnormalities in young athletes and reduce unnecessary secondary testing, restrictions and concern.

Abstract Strabismus is prevalent among preterm infants of low gestational age and birth weight in Southeast Asian countries, with intermittent exotropia (IXT) being the most common type in South Korea. In this retrospective, cross-sectional study, we investigated the differences between full-term and premature infants with IXT. IXT patients with available childbirth history were divided into two groups: preterm vs. full-term and low birth weight (LBW) vs. normal birth weight (NBW). Parameters related to exotropia including parental heredity, surgical history, and treatment options were investigated. In univariate regression for gestational age, a result of ≥ 100 s in the Titmus test was 1.352 times more frequent in preterm than in full-term infants. When birth weight was considered instead, a result of ≥ 100 s in the Titmus test was 1.412 times more frequent in the LBW compared to the NBW group. In multivariate regression for birth weight, the frequency of a result of ≥ 100 s in the Titmus test for the LBW group was 2.032 times higher than that for the NBW group. It is particularly important to examine stereopsis in preterm and LBW patients affected by IXT to ensure timely surgical planning and avoid potential recurrence after surgery.

Embryo transfer plays a crucial role in enhancing the breeding value of livestock; it has been applied in Hanwoo cattle, which is a popular breed for beef production in Korea. Both in vivo-derived (IVD) and in vitro-produced (IVP) embryos are used for this purpose; however, IVP embryos have been preferred recently owing to advancements in ovum pick-up (OPU) technology and genomic selection. Despite technological advancements, comprehensive data on large-scale OPU/IVEP/embryo transfer in Hanwoo cows are lacking. In this study, 16 elite Hanwoo donor cows were selected on the basis of specific criteria. Oocytes were retrieved from 241 cows using OPU. The collected cumulus-oocyte complexes (COCs) were matured, fertilized, and cultured in vitro to produce transferable embryos. Embryos were classified according to their developmental stage and then transferred to 675 recipient cows. A total of 3,317 COCs were collected, with an average of 13.76 COCs per cow. The number of transferable embryos produced per cow was 3.7. Hanwoo OPU-derived IVP embryos exhibited a higher production yield than the global average, indicating a stable IVEP environment. Both fresh and frozen IVP embryos yielded similar conception rates; hence, the use of vitrified-thawed embryos in transfer plans feasible. However, frozen-thawed embryos at Stage 7 had a lower conception rate than those at earlier stages. There was no significant difference between the conception rates of sexually mature heifers and postpartum cows used as recipients. The male-to-female offspring ratio increased as the developmental stage progressed. Seasonal effects on conception rates were not observed; however, higher abortion rates and a higher proportion of male offspring were observed during winter. This study provides valuable data for the Korean embryo transfer industry, enabling more strategic growth of the domestic Hanwoo embryo industry.

Music identification is widely regarded as a solved problem for music searching in quiet environments, but its performance tends to degrade in TV broadcast audio owing to the presence of dialogue or sound effects. In addition, constructing an accurate dataset for measuring the performance of background music monitoring in TV broadcast audio is challenging. We propose a framework for monitoring background music by automatic identification and introduce a background music cue sheet. The framework comprises three main components: music identification, music-speech separation, and music detection. In addition, we introduce the Cue-K-Drama dataset, which includes reference songs, audio tracks from 60 episodes of five Korean TV drama series, and corresponding cue sheets that provide the start and end timestamps of background music. Experimental results on the constructed and existing datasets demonstrate that the proposed framework, which incorporates music identification with music–speech separation and music detection, effectively enhances TV broadcast audio monitoring.

Background: While it is known that vital signs and behaviors change during pregnancy, there is limited data on timing and scale of changes for sensor-derived health metrics across pregnancy and postpartum. Wearable technology provides an opportunity to understand physiologic and behavioral changes across pregnancy with greater detail, more frequent measurements, and improved accuracy. The aim of this study is to describe changes in physiologic and behavioral sensor-based health metrics during pregnancy and postpartum in the Apple Women's Health Study (AWHS) and their relationship to demographic factors. Methods: The Apple Women's Health Study is a digital, longitudinal, observational study that includes U.S. residents with an iPhone and Apple Watch. We evaluated changes from pre-pregnancy through delivery and postpartum for sensor-derived health metrics. Minimum required data samples per day, week and overall were data element specific, and included 12 weeks prior to pregnancy start, and 12 weeks postpartum for pregnancies lasting between 24 and 43 weeks. Findings: A total of 757 pregnancies from 733 participants were included. Resting heart rate (RHR) increased across pregnancy, peaking in the third trimester (pre-pregnancy median RHR 65.0 beats per minute [BPM], interquartile range [IQR] 60.0–70.2 B.M. third trimester median RHR 75.5 B.M. IQR 69.0–82.0 B.M., with a decrease prior to delivery and nadir postpartum (postpartum median RHR 62.0 B.M. IQR 57.0–66.0 B.M.. Heart rate variability (HRV) decreased from pre-pregnancy (39.9 milliseconds, IQR 32.6–48.3 milliseconds), reaching a nadir in the third trimester (29.9 milliseconds, IQR 25.2–36.4 milliseconds), before rebounding in the last weeks of pregnancy. Measures of activity, such as exercise minutes, stand minutes, step count and Cardio Fitness were all decreased in each trimester compared to pre-pregnancy, with their nadirs postpartum. Total sleep duration increased slightly in early pregnancy (pre-pregnancy 7.2 hours, IQR 6.7–7.7 hours; 1st trimester 7.4 hours, IQR 6.8–7.9 hours), with the lowest sleep duration postpartum (6.2 hours, IQR 5.4–6.8 hours). Interpretation: Resting heart rate increased during pregnancy, with a decrease prior to delivery, while heart rate variability decreased across pregnancy, with an upward trend before delivery. Behavioral metrics, such as exercise and sleep, showed decreasing trends during and after pregnancy. These data provide a foundation for understanding normal pregnancy physiology and can facilitate hypothesis generation related to physiology, behavior, pregnancy outcomes and disease.

Purpose Through their biological clocks, organisms on this rotating planet can coordinate physiological processes according to the time of the day. However, the prevalence of circadian rhythm disorders has increased in modern society with the growing number of shift workers, elevating the risk of various diseases. In this study, we employed a mouse model to investigate the effects of urinary rhythm disturbances resulting from dietary changes commonly experienced by night shift workers. Methods We established 3 groups based on feeding time and the use of restricted feeding: ad libitum, daytime, and early nighttime feeding. We then examined the urinary rhythm in each group. In addition to the bladder rhythm, we investigated changes in mRNA patterns within the tissues constituting the bladder. Additionally, we assessed the urination rhythm in Per1 and Per2 double-knockout mice and evaluated whether the injection of antioxidants modified the impact of mealtime shift on urination rhythm in wild-type mice. Results Our study revealed that a shift in mealtime significantly impacted the circadian patterns of water intake and urinary excretion. In Per2::Luc knock-in mouse bladders cultured ex vivo, this shift increased the amplitude of Per2 oscillation and delayed its acrophases by several hours. Daily supplementation with antioxidants did not influence the mealtime shift-induced changes in circadian patterns of water intake and urinary excretion, nor did it affect the modified Per2 oscillation patterns in the cultured bladder. However, in aged mice, antioxidants partially restored the urinary rhythm. Conclusions A shift in mealtime meaningfully impacted the urination rhythm in mice, regardless of the presence of circadian clock genes.

Abstract Background Lysosomal dysfunction (LD) impacts cytokine regulation, inflammation, and immune responses, influencing the development and progression of cancer. Inflammation is implicated in the pathogenesis of myeloproliferative neoplasm (MPN). With a hypothesis that LD significantly contributes to MPN carcinogenesis by inducing abnormal inflammation, our objective was to elucidate the pathophysiological mechanisms of MPN arising from an LD background. Methods Genotyping of the LD background was performed in a cohort of MPN patients (n = 190) and healthy controls (n = 461). Logistic regression modeling, utilizing genotype data, was employed to estimate the correlation between LD and MPN. Whole transcriptome sequencing (WTS) (LD carriers = 8, non‐carriers = 6) and single‐cell RNA sequencing data (LD carriers = 2, non‐carriers = 2, healthy controls = 2) were generated and analyzed. Results A higher variant frequency of LD was observed in MPN compared to healthy controls (healthy, 4.9%; MPN, 7.8%), with the highest frequency seen in polycythemia vera (PV) (odds ratio = 2.33, p = 0.03). WTS revealed that LD carriers exhibited upregulated inflammatory cytokine ligand–receptor genes, pathways, and network modules in MPNs compared to non‐carriers. At the single‐cell level, there was monocyte expansion and elevation of cytokine ligand–receptor interactions, inflammatory transcription factors, and network modules centered on monocytes. Notably, Oncostatin‐M (OSM) consistently emerged as a candidate molecule involved in the pathogenesis of LD‐related PV. Conclusions In summary, an LD background is prevalent in MPN patients and leads to increased cytokine dysregulation and inflammation. OSM, as one of the potential molecules, plays a crucial role in PV pathogenesis by impairing lysosomal function.

The prevalence of obesity in adults and children is rapidly increasing worldwide. Obesity is among the main causes of chronic diseases and various problems, including economic consequences and they can also be affected by genetic, environmental, psychological, and socioeconomic factors. Dietary modification is a well-known and important factor in weight control, in particular, dietary macronutrient composition, food selection, dietary patterns, and energy restriction can affect weight reduction. Therefore, this systematic review aims to provide basic evidence for identifying the optimal macronutrient composition for managing obesity in Korean children and adolescents. We searched literature through an international database, studies were selected using our eligibility criteria and quality was assessed via a risk of bias tool. In our results, several studies have demonstrated that dietary macronutrient modifications affect body composition and metabolic markers in children and adolescents. In contrast, hypocaloric diets, regardless of macronutrient composition, are reportedly effective for weight loss in obese children. However, these findings were based on intervention studies that examined the association between dietary macronutrient composition and obesity in non-Korean children and adolescents. Therefore, in the future, more intervention studies are needed to elucidate this relationship and evidence between macronutrients and obesity in Korean children and adolescents.

Abstract Recent studies have demonstrated that the three-dimensional conformation of the chromatin plays a crucial role in gene regulation, with aberrations potentially leading to various diseases. Advanced methodologies have revealed a link between the chromatin conformation and biological function. This review divides these methodologies into sequencing-based and imaging-based methodologies, tracing their development over time. We particularly highlight innovative techniques that facilitate the simultaneous mapping of RNAs, histone modifications, and proteins within the context of the 3D architecture of chromatin. This multimodal integration substantially improves our ability to establish a robust connection between the spatial arrangement of molecular components in the nucleus and their functional roles. Achieving a comprehensive understanding of gene regulation requires capturing diverse data modalities within individual cells, enabling the direct inference of functional relationships between these components. In this context, imaging-based technologies have emerged as an especially promising approach for gathering spatial information across multiple components in the same cell.

Abstract Objectives Since the enactment of the School Nutrition Act in 1981, school lunch programs in South Korea have grown quantitatively and qualitatively with a current student participation rate of 99.8%. Nonetheless, educational materials are needed to reduce misunderstanding and ignorance about school lunch programs. This study aimed to develop 3 educational videos that help students of various ages (kindergarteners/lower-grade elementary, upper-grade elementary, and secondary school, respectively), understand the school lunch program. Methods A scenario was created, was made, and the opinions on the scenario from experts in foodservice sectors were collected. A survey was conducted to students and parents to determine topics they wanted to know about school foodservice. The final videos were produced using this information and the expert opinions. The data were analyzed using SPSS 27.0 for Mac (IBM Corp., Armonk, NY, USA); a P-value of < 0.05 was considered significant. Results Three videos on school foodservice were developed for various age levels of students: kindergarten/lower-grade elementary, upper-grade elementary, and secondary school. Additionally, English subtitles were included for the multicultural student population. These videos, each lasting about 7 minutes, cover topics such as nutrition, hygiene, and the cultural significance of the school lunch program. The survey results showed that parents and students wanted to know the following topics about the school lunch program: “nutritionally balanced diet” (11.9%), “purchasing safe food ingredients” (10.9%), and “healthy eating habits” (9.9%). Conclusions The developed videos will serve as valuable educational resources on school foodservice, foster a deeper understanding of the school lunch program in parents and students, and potentially address their inquiries regarding production processes, nutrition, hygiene, cultural heritage, and health.

The rising demand for electric vehicles (EVs) underscores the need for enhancing electric motor efficiency. Utilizing hairpin coils with a rectangular cross-section has emerged as an alternative approach to increase conductor density in motor stator slots. However, the manufacturing process for hairpin coil motors presents challenges such as springback, which stems from wire shaping processes such as leveling and bending with plastic deformation. These challenges are closely tied to mechanical properties of the Young’s modulus and yield stress. This study investigates uncertainties in mechanical property evaluation using a combination of tensile tests, analytic solutions, numerical simulations, and a present double-sided four-point bending method. The results show significant variations in the Young’s modulus, which affect the determination of yield stress in tensile tests. It has been revealed that in order to obtain stable mechanical properties of hairpin coils in tensile tests, the conditions should be restricted to a very slow strain rate, slower than $10^{-3}~\text{s}^{-1}$ . To address this, this study introduces an alternative method that combines double-sided four-point bending and tensile tests, allowing for the acquisition of Young’s modulus without prior information on material properties. This approach reduces uncertainties in determination of the mechanical properties with much less time cost.

Abstract Mycobacterium tuberculosis CuvA (Rv1422, MtCuvA) has previously been suggested that it may play a critical role in nutrient utilization and cell wall synthesis required for physiological adaptation in a host cell, but its biochemical details remain unclear. Our previous studies showed that MtCuvA can bind to uridine diphosphate (UDP) sugars as a cell wall precursor component. To verify its functional roles, we report here the biochemical properties of MtCuvA for the binding of UDP-N-acetylglucosamine (GlcNAc) using site-directed mutagenesis and docking simulation. The K D values for UDP-sugars indicate that MtCuvA prefers to bind UDP-GlcNAc as a physiological ligand compared to UDP-glucose. Mutational studies of MtCuvA showed that H12A, T33A, D36A, Q154A, S196, T199A, N226A, and H298A mutants significantly affected the binding to UDP-GlcNAc. We also observed that UDP, but not GlcNAc, could bind to MtCuvA. These results imply that the presence of UDP moiety in the ligand is necessary for interaction with MtCuvA. Moreover, mutational studies of MtCuvA with UDP showed that residues H12, S196, T199, N226, and H298 may be involved in its binding to the UDP moiety, almost consistent with the docking simulation results. Our results provide an insight into the interaction of MtCuvA with UDP-GlcNAc as a key precursor of peptidoglycan.

Understanding energy demand and supply flow at a large urban scale is an essential step for urban designers, planners and policymakers in investigating how buildings within an existing urban context could be designed as a whole to support the future sustainable built environment. The contemporary approach is to model energy use activities at various building and urban scales. This, albeit a practical approach, poses significant challenges in acquiring good quality data concerning buildings and their interactions at an urban scale at an affordable price. This paper presents a streamlined benchmarking methodology with a parametric modelling workflow to complement the mainstream urban building energy modelling (UBEM) approach. The proposed building energy benchmarking workflow integrates multiple databases concerning building energy consumption, energy generation and underlying grid infrastructure. Parametric modelling serves as a tool for integrating databases through the underlying sortable geometric characteristics. This is envisaged to afford stockholders, such as policymakers or urban planners, greater flexibility to investigate energy demand and supply scenarios at an urban neighbourhood scale and further explore potential applications. Using the proposed workflow, we look at renewable solar energy to experiment with offsetting urban building energy consumption through reconfiguring existing electricity microgrids in the Sheffield city centre. The result of this study demonstrates how the presented urban building energy benchmarking (UBEB) workflow would afford capabilities and flexibility to support stakeholders, e.g., urban planners, policymakers, and end-users, to better understand existing barriers and explore actionable opportunities via re-configurable electricity microgrids.

Biophilic design has gained prominence in architecture as a strategy to integrate natural elements into built environments, aiming to improve human comfort, well-being, and environmental sustainability. This paper critically reviews existing biophilic design frameworks, identifying gaps in their integration of health outcomes and the relationship between indoor and outdoor environments, with a primary focus on indoor environmental quality (IEQ) factors such as air quality, natural light, thermal comfort, and acoustics. The review was conducted systematically, comparing frameworks using criteria such as health benefits, human–nature connections, and user satisfaction. Key findings highlight a lack of comprehensive frameworks that explicitly link biophilic design to measurable improvements in human health, comfort, and satisfaction. To address this gap, the study proposes an enhanced biophilic design framework that bridges IEQ-focused indoor environments with urban outdoor elements, prioritizing human comfort alongside environmental sustainability. The framework also emphasizes the role of post-occupancy evaluation (POE) in assessing the real-world performance of biophilic interventions, particularly in achieving user satisfaction and ensuring long-term effectiveness. This research contributes to the advancement of biophilic design by offering actionable strategies for architects, urban planners, and policymakers to adopt biophilic principles that create resilient, healthy, and sustainable spaces. Additionally, the study emphasizes the need for empirical testing and validation of the proposed framework, including POE and user surveys, to assess its real-world impact on human well-being and satisfaction, thus setting the stage for future research.

In recent decades, the issue of building energy usage has become increasingly significant, and U-values for building envelopes have been key parameters in predicting building energy consumption. This study comprehensively reviews the U-values (thermal transmittances) of building envelopes made from conventional and bio-based materials. First, it introduces existing studies related to the theoretical and measured U-values for four types of building envelopes: concrete, brick, timber, and straw bale envelopes. Compared with concrete and brick envelopes, timber and straw bale envelopes have lower U-values. The differences between the measured and theoretical U-values of timber and straw bale envelopes are minor. The theoretical U-values of concrete and brick envelopes ranged from 0.12 to 2.09 W/m2K, and the measured U-values of concrete and brick envelopes ranged from 0.14 to 5.45 W/m2K. The theoretical U-values of timber and straw bale envelopes ranged from 0.092 to 1.10 W/m2K, and the measured U-values of timber and straw bale envelopes ranged from 0.04 to 1.30 W/m2K. Second, this paper analyses the environmental factors influencing U-values, including temperature, relative humidity, and solar radiation. Third, the relationship between U-values and building energy consumption is also analysed. Finally, the theoretical and measured U-values of different envelopes are compared. Three research findings in U-values for building envelopes are summarised: (1) the relationship between environmental factors and U-values needs to be studied in detail; (2) the gaps between theoretical and measured U-values are significant, especially for concrete and brick envelopes; (3) the accuracy of both theoretical and the measured U-values needs to be verified.

Abstract Lead‐acid batteries (LABs) are widely used as a power source in many applications due to their affordability, safety, and recyclability. However, as the demand for better electrochemical energy storage increases in various fields, there is a growing need for more advanced battery technologies. To meet this need, the application of LABs in hybrid electric vehicles and renewable energy storage has been explored, and the development of lead–carbon batteries (LCBs) has garnered significant attention as a promising solution. LCBs incorporate carbon materials in the negative electrode, successfully addressing the negative irreversible sulfation issue that plagues traditional LABs. Composite material additives and Pb–C composite electrodes have also gained popularity as effective ways to enhance negative electrode performance. This review article focuses on the role of carbon additives in the negative electrode of LCBs and discusses potential future additives that may be incorporated into the development of LCBs. Overall, this article provides insights into the potential of LCBs to offer more efficient and reliable energy storage.

This study aimed to assess the effects of embryonic developmental stage, quality grade, and fresh or frozen/thawed conditions on the pregnancy rate and sex ratio of live offspring in Hanwoo (Bos taurus coreanae) cows. The quality and developmental stage of in vivo-derived (IVD) transferred embryos were evaluated using the standard criteria of the International Embryo Technology Society. The recipient cows were synchronized using conventional (estradiol benzoate and progesterone) protocols before embryo transfer. Embryos were transferred to 297 cows, and pregnancy was monitored for 60–70 days after embryo transfer. The pregnancy rates of fresh and frozen/thawed embryos were 56.90% and 52.49%, respectively. Pregnancy rates varied according to embryo quality (56.18% for grade 1 vs. 36.67% for grade 2). Pregnancy rates also varied by developmental stage and cryopreservation (67.86% vs. 63.49% for stage 4-1, 64.00% vs. 54.72% for 5-1, and 50.00% vs. 47.83% for 6-1, in fresh embryos vs. frozen/thawed embryos, respectively). For stage 7-1, the pregnancy rates were 72.73% for fresh embryos and 20.00% for frozen/thawed embryos. In 66 fresh embryos, the sex ratio of live offspring was 5:5, whereas it was 4(female):6(male) for frozen/thawed embryos among the 95 frozen/thawed embryos. The miscarriage rate was approximately 3% higher for frozen/thawed embryos than for fresh embryos (18.1% for fresh vs. 21.1% for frozen). Seasonal fertility rates were 33.3% in spring, 55.67% in summer, 52.8% in autumn, 60.0% in winter. The following male-to-female ratios were observed in different seasons: 6.7:3.3 in spring, 4.0:6.0 in summer, 5.5:4.5 in autumn, and 3.3:6.7 in winter. The current data revealed no significant differences in pregnancy rates between fresh and frozen/thawed IVD embryos. However, there was a lower pregnancy rate with advanced-stage frozen/thawed embryos (stage 7-1). The current study provides comprehensive results for the better optimization of embryo transfer in Hanwoo cattle to obtain the desired fertility rate, pregnancy rate, and sex ratio of calves. These results provide important insights into the factors that influence the viability and success of IVD embryo transfer in Hanwoo cows and may have practical applications for improving breeding programs and reducing production costs.

Abstract Background Although most patients with diffuse large B-cell lymphoma (DLBCL) achieve complete remission after first-line rituximab-containing immunochemotherapy, up to 40% of patients relapse and require salvage therapy. Among those patients, a substantial proportion remain refractory to salvage therapy due to insufficient efficacy or intolerance of toxicities. A hypomethylating agent, 5-azacytidine, showed a chemosensitizing effect when primed before chemotherapy in lymphoma cell lines and newly diagnosed DLBCL patients. However, its potential to improve outcomes of salvage chemotherapy in DLBCL has not been investigated. Results In this study, we demonstrated the mechanism of 5-azacytidine priming as a chemosensitizer in a platinum-based salvage regimen. This chemosensitizing effect was associated with endogenous retrovirus (ERV)-induced viral mimicry responses via the cGAS-STING axis. We found deficiency of cGAS impaired the chemosensitizing effect of 5-azacytidine. Furthermore, combining vitamin C and 5-azacytidine to synergistically activate STING could be a potential remedy for insufficient priming induced by 5-azacytidine alone. Conclusions Taken together, the chemosensitizing effect of 5-azacytidine could be exploited to overcome the limitations of the current platinum-containing salvage chemotherapy in DLBCL and the status of cGAS-STING has the potential to predict the efficacy of 5-azacytidine priming.

Matrix-assisted laser desorption/ionization time-of-flight-time-of-flight (MALDI-TOF-TOF) tandem mass spectrometry (MS/MS) is a rapid technique for identifying intact proteins from unfractionated mixtures by top-down proteomic analysis. MS/MS allows isolation of specific intact protein ions prior to fragmentation, allowing fragment ion attribution to a specific precursor ion. However, the fragmentation efficiency of mature, intact protein ions by MS/MS post-source decay (PSD) varies widely, and the biochemical and structural factors of the protein that contribute to it are poorly understood. With the advent of protein structure prediction algorithms such as Alphafold2, we have wider access to protein structures for which no crystal structure exists. In this work, we use a statistical approach to explore the properties of bacterial proteins that can affect their gas phase dissociation via PSD. We extract various protein properties from Alphafold2 predictions and analyze their effect on fragmentation efficiency. Our results show that the fragmentation efficiency from cleavage of the polypeptide backbone on the C-terminal side of glutamic acid (E) and asparagine (N) residues were nearly equal. In addition, we found that the rearrangement and cleavage on the C-terminal side of aspartic acid (D) residues that result from the aspartic acid effect (AAE) were higher than for E- and N-residues. From residue interaction network analysis, we identified several local centrality measures and discussed their implications regarding the AAE. We also confirmed the selective cleavage of the backbone at D-proline bonds in proteins and further extend it to N-proline bonds. Finally, we note an enhancement of the AAE mechanism when the residue on the C-terminal side of D-, E- and N-residues is glycine. To the best of our knowledge, this is the first report of this phenomenon. Our study demonstrates the value of using statistical analyses of protein sequences and their predicted structures to better understand the fragmentation of the intact protein ions in the gas phase.

The Indonesiancrime rate until May 2020 increased due to public orders and crime disturbances in the last 22 weeks.Data from correctional institutions in February 2021 showed that some regional offices were over capacity while others were normal. The 1945 IndonesianConstitution recognises traditional institutions in the criminal justice system and requires judges to consider legal values and a sense of justice in society. This study aims to determine Indonesia's customary criminal justice system as a form of restorative justice. This research used a socio-legal approach and found that public participation in Indonesia, through customary groups, can help prevent crime and solve problems through discussion and following applicable customary law processes. As a result, Indonesian researchers have regulated and recognised customary justice's existence and implemented it to deal with cases in their environment. Restorative justice is a criminal mechanism that aims to restore the relationship of the conflicting parties to the state before the conflict and is carried out informally. This concept is also an acknowledgement of oriental legal philosophy which, in resolving any conflict, always seeks to restore relations; macro stability or society can even affect the stability of the universe. The practice of Restorative Justice occurs in customary law. As a legal philosophy, the legal policy of implementing Restorative justice should be interpreted mainly as revitalising customary law if conflicts occur between fellow supporters of the same customary law. The settlement of cases in the Baduy community is straightforward. The settlement prioritises forgiving each other. Restorative justice is performed by combining criminal justice mechanisms with public participation in a discussion mediation.

Soft, stretchable, conductive thin films have propelled to the forefront of applications in stretchable sensors for on-skin health monitoring. Stretchable conductive films require high conformability, stretchability, and mechanical/chemical stability when integrated into the skin. Here, we present a highly stretchable, conductive, and transparent natural rubber/silver nanowire (AgNW)/poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) composite film. Overcoating the PEDOT:PSS layer results in outstanding mechanical robustness and chemical stability by suppressing the mechanical and chemical degradation of the nanowire networks. Moreover, the introduction of the organic surface modifier enhances the bonding strength between the natural rubber substrate and AgNW at the interface. The highly conformable composite films are integrated into multifunctional on-skin sensors for monitoring various human motions and biological signals with low-power consumption. We believe that the highly stretchable, robust, and conformable natural rubber/AgNW/PEDOT:PSS composite film can offer new opportunities for next-generation wearable sensors for body motion and physiological monitoring.

Abstract We measured the concentrations of dissolved inorganic and organic nutrients, dissolved organic carbon (DOC), total hydrolyzable amino acids (THAA), fluorescent dissolved organic matter (FDOM), phytoplankton pigments, and δ13C-DOC during the summer of 2019 in the harmful dinoflagellate bloom regions of the southern coast of Korea. In the harmful dinoflagellate bloom region, the concentrations of inorganic nitrogen were depleted, inhibiting the growth of diatoms, while the concentrations of dissolved organic components (nutrients, DOC, FDOM, and amino acids) which fuel dinoflagellates were unusually high. Thus, we attempted to investigate the origins and characteristics of DOM which fuels the harmful dinoflagellate blooms. The δ13C-DOC values (− 22.2‰ to − 18.2‰) indicate that the elevated DOC concentrations result from in-situ biological production rather than terrestrial inputs. The enantiomeric (D/L) ratios of THAA indicate that dissolved organic nitrogen was more labile in the early stage of harmful dinoflagellate bloom and became more refractory in the final stage. Our results suggest that the marine production of bioavailable DOM plays an important role in initiating and sustaining harmful dinoflagellate blooms.

Photochromic materials have attracted considerable interest because of their ability to undergo reversible color switching. We report highly conductive and flexible spiropyran-embedded cellulose films with multiple optical and electrical functionalities, showing negative photo- and thermochromism. Combining silver nanowires and conductive polymer with cellulose/spiropyran films achieves a very low sheet resistance of 6.7 ohm/sq. The optimized films show outstanding mechanical stability with negligible electrical loss (resistance change < 2%) after 1000 bending cycles. The photo- and thermal-responsive conductive cellulose/spiropyran films can be used to directly visualize information and as flexible heating devices, pressure-responsive sensors, and colorimetric thermometers with high device performance.

This paper aims to compare the sustainability assessment methods of DGNB and G-SEED, the two domestic green building rating systems, focusing on indoor environmental evaluation and reviewing recent laws, certifications systems, and guidelines from Germany and South Korea. According to existing studies, Korea’s green building certification has similar evaluation items, environmental (62.6%), social aspects (25.4%), and economic aspects (3.0%) compared with DGNB. Continuing research comparing DGNB and G-SEED, this paper will present an insight into the DGNB and G-SEED green building rating systems’ aspects and motives; furthermore, we intend to equate the sustainability assessment methods of the DGNB and G-SEED certification systems, in order to improve certification systems by comparing and finding solutions to differences, thereby making international systems more adaptable to each country. This analysis will unify property categorization systems and will promote green building and sustainable development globally. Findings: Regarding similarities and differences, the certification criteria for air, thermal, visual/light, and acoustic quality are based on domestic laws in both countries. DGNB and G-SEED are similar in terms of the requirements but differ in methods and domestic laws. Some findings regarding differences are that DGNB requires low VOC-emitting products, while G-SEED focuses on natural ventilation. Thermal comfort is measured through design-phase simulation in DGNB, while G-SEED lighting is evaluated on the basis of saving light energy. Finally, in G-SEED, acoustic quality is measured via indoor soundproofing performance, while DGNB takes room size into account.

Abstract We aimed to analyze the relationship of the distribution of body fat mass (FM) and fat-free mass (FFM) in the limbs and trunk with the prevalence of cardiovascular disease risk factors (CVD-RF). In total, 13,032 adults were selected from the KNHANES (2008–2011). The prevalence of hypertension, diabetes mellitus (DM), dyslipidemia, and metabolic syndrome (MetS) according to the arm-to-leg ratio and limbs-to-trunk ratio for FM and FFM was compared, respectively. The higher the arm-to-leg FM ratio, the higher the prevalence of CVD-RF (DM-male-OR 7.04, 95% CI 4.22–11.74; DM-female-OR 10.57, 95% CI 5.80–19.26; MetS-male-OR 4.47, 95% CI 3.41- 5.86; MetS-female-OR 8.73, 95% CI 6.38–11.95). The higher the limbs-to-trunk FM ratio (DM-male-OR 0.12, 95% CI 0.07–0.21; DM-female-OR 0.12, 95% CI 0.06–0.23; MetS-male-OR 0.06, 95% CI 0.04–0.08; MetS-female-OR 0.02, 95% CI 0.01–0.04), the higher the limbs-to-trunk FFM ratio (DM-male-OR 0.19, 95% CI 0.11–0.31; DM-female-OR 0.46, 95% CI 0.30–0.70; MetS-male-OR 0.39, 95% CI 0.31–0.50; MetS-female-OR 0.62, 95% CI 0.50–0.78), and the higher the arm-to-leg FFM ratio (MetS-male-OR 0.75, 95% CI 0.59–0.94; MetS-female-OR 0.73, 95% CI 0.58–0.92), the lower the prevalence of CVD-RF. The higher the FM of the legs compared to the arms, FFM of the arms compared to the legs, and FM or FFM of the limbs compared to the trunk, the lower the prevalence of CVD-RF.

We investigated the effects of eddies and typhoons on the biogeochemistry of the tropical northwest Pacific by examining the distribution of nutrients, dissolved oxygen (DO), chlorophyll-a (Chl-a), gross primary production (GPP), dissolved organic carbon (DOC), and fluorescent dissolved organic matter (FDOM). Water samples were collected from anticyclonic and cyclonic eddies in September 2019 and 2020, and before and after the passage of a Category 2 typhoon in 2019. The study region was characterized by a deep nitracline (~150 m), which was deeper than both the pycnocline (~50 m) and the FDOM-depleted layer (~75 m). A subsurface chlorophyll maximum layer was observed at 100–150 m depth. No clear differences in Chl-a, DO, GPP, DOC, and FDOM were observed for the anticyclonic and cyclonic eddies, indicating that the eddies did not have a significant influence on biological production. Similarly, there were no discernable changes in Chl-a concentrations or other biogeochemical parameters after the passage of the typhoon, which induced water mixing to a depth of ~60 m. We conjecture that the nutrient-depleted layer was too deep for any eddy- or typhoon-induced vertical mixing to cause upwelling of nutrients to the euphotic zone. Our results imply that the disturbances caused by mesoscale processes in the upper layer of the highly oligotrophic northwest Pacific may have a smaller effect than in oceans in other parts of the world.

Immigration data form a substantial part of the border protection between countries. However, the quality and integrity of each country’s immigration data varies greatly in terms of technology and regulation. A country that has a weak a legal framework on data protection has proven to be easily abused by irresponsible parties. Including when Indonesia tries to carry out tracing by synchronizing the data in the Peduli Lindungi application with immigration data, there will be a potential violation of the privacy rights of individuals. Hence, this study applies a normative and empirical (mix) legal research methodology to analyze two keys issues: what are the advantages of synchronizing the domestic tracing application called Peduli Lindungi to the immigration data? and what kind of legal framework to prevent the misuse of personal data in Indonesia? With regulatory and comparative approaches, this study concludes without powerful legal framework, there will be no legal assurance to the promotion of privacy rights in the synchronization and the use of immigration data for health tracing purposes. From the empirical side, Indonesian’s current policy does not enable monitoring or evaluating authority to scrutinize ministerial activities in collecting and utilizing personal data. Moreover, by considering several problems of data breach in Indonesia, a single and unified data protection law is needed to integrate and provide uniformity of implementation for data protection. Keywords: data protection law, immigration, privacy rights. Mendukung Undang-Undang Perlindungan Data Keimigrasian Di Indonesia Dan Pemanfaatannya Untuk Pelacakan Kontak Abstrak Data imigrasi merupakan bagian penting dari perlindungan perbatasan antar negara. Namun, kualitas dan integritas data keimigrasian masing-masing negara sangat bervariasi dari segi teknologi dan regulasi. Negara yang memiliki kerangka hukum perlindungan data yang lemah terbukti mudah disalahgunakan oleh pihak-pihak yang tidak bertanggung jawab. Termasuk ketika Indonesia mencoba melakukan tracing dengan menyinkronkan data pada aplikasi Peduli Lindungi dengan data keimigrasian, maka akan berpotensi terjadi pelanggaran terhadap hak privasi individu. Oleh karena itu, penelitian ini menggunakan metodologi penelitian hukum normatif dan empiris (campuran) untuk menganalisis dua masalah utama: apa keuntungan dari sinkronisasi aplikasi penelusuran dalam negeri bernama Peduli Lindungi terhadap data keimigrasian? dan apa kerangka hukum untuk mencegah penyalahgunaan data pribadi di Indonesia? Dengan pendekatan regulasi dan komparatif, studi ini menyimpulkan tanpa kerangka hukum yang kuat, tidak akan ada jaminan hukum untuk promosi hak privasi dalam sinkronisasi dan penggunaan data imigrasi untuk tujuan penelusuran kesehatan. Dari sisi empiris, kebijakan Indonesia saat ini tidak memungkinkan kewenangan pemantauan atau evaluasi untuk meneliti kegiatan kementerian dalam mengumpulkan dan memanfaatkan data pribadi. Selain itu, dengan mempertimbangkan beberapa masalah pelanggaran data di Indonesia, diperlukan undang-undang perlindungan data yang tunggal dan terpadu untuk mengintegrasikan dan memberikan keseragaman implementasi perlindungan data. Kata kunci: undang-undang perlindungan data, keimigrasian, hak privasi.

Abstract Disrupted-in-schizophrenia 1 (DISC1) is a scaffold protein that has been implicated in multiple mental disorders. DISC1 is known to regulate neuronal proliferation, signaling, and intracellular calcium homeostasis, as well as neurodevelopment. Although DISC1 was linked to sleep-associated behaviors, whether DISC1 functions in the circadian rhythm has not been determined yet. In this work, we revealed that Disc1 expression exhibits daily oscillating pattern and is regulated by binding of circadian locomotor output cycles kaput (CLOCK) and Brain and muscle Arnt-like protein-1 (BMAL1) heterodimer to E-box sequences in its promoter. Interestingly, Disc1 deficiency increases the ubiquitination of BMAL1 and de-stabilizes it, thereby reducing its protein levels. DISC1 inhibits the activity of GSK3β, which promotes BMAL1 ubiquitination, suggesting that DISC1 regulates BMAL1 stability by inhibiting its ubiquitination. Moreover, Disc1-deficient cells and mice show reduced expression of other circadian genes. Finally, Disc1-LI (Disc1 knockout) mice exhibit damped circadian physiology and behaviors. Collectively, these findings demonstrate that the oscillation of DISC1 expression is under the control of CLOCK and BMAL1, and that DISC1 contributes to the core circadian system by regulating BMAL1 stability.

The purpose of this study was to examine the outcomes of the National Assessment of Educational Achievement (NAEA) 2015-2018 when the 2009 Revised National Curriculum was applied and suggested for future curriculum revisions. The characteristics of students’ academic achievement were analyzed based on the results of evaluating test items developed by the achievement standards of the 2009 Revised National Curriculum. The analysis showed that students’ academic achievement was low in the ‘Function’, ‘Probability and Statistics’, and ‘Geometry’ domain. In addition, many achievement standards could be mastered only by the above average group of students. Accordingly, it is necessary to reinforce customized teaching and learning activities in relation to achievement standards which were under achieved. To improve the achievement characteristics, it is necessary to specify detailed achievement standards and to strengthen the linkage between achievement standards.

Abstract Student clickstream data—time-stamped records of click events in online courses—can provide fine-grained information about student learning. Such data enable researchers and instructors to collect information at scale about how each student navigates through and interacts with online education resources, potentially enabling objective and rich insight into the learning experience beyond self-reports and intermittent assessments. Yet, analyses of these data often require advanced analytic techniques, as they only provide a partial and noisy record of students’ actions. Consequently, these data are not always accessible or useful for course instructors and administrators. In this paper, we provide an overview of the use of clickstream data to define and identify behavioral patterns that are related to student learning outcomes. Through discussions of four studies, we provide examples of the complexities and particular considerations of using these data to examine student self-regulated learning.

Freeman-Sheldon syndrome (FSS) is a rare distal arthrogryposis syndrome. There are few reports on the respiratory insufficiency of FSS. Additionally, there is no detailed information on pulmonary functional evaluation. A 17-year-old male patient with FSS developed respiratory failure, leading him to be admitted to hospital several times for evaluation and treatment. Of those times he was admitted, two were due to pneumonia. His pulmonary functions were indicative of a restrictive lung disease potentially caused by severe scoliosis. After a non-invasive ventilatorwas applied correctly to the patient, pulmonary hypertension was normalized. His pulmonary function has been maintained for 13 years. Since receiving proper respiratory care, which includes assisted coughing methods, the patient has not developed pneumonia. It is important to properly evaluate the pulmonary function of patients who have FSS and scoliosis to eliminate the risk of long-term respiratory complications.

Abstract Shift work disorders have become an emerging concern worldwide. Shift disorders encompass a wide range of illnesses that have yet to be identified. The study focused on the relationship between shift work disorders and insulin resistance. Previously, it was reported that advancing the usual mealtime of mice triggered insulin resistance. Here, the hypothesis that chronic mealtime shifts induce oxidative damage leading to chronic diseases such as type 2 diabetes was tested. It was found that mealtime shift causes imbalances between anti‐oxidative capacity and reactive oxygen species (ROS) levels, indicating increased oxidative damage during the light/rest phase. This study further demonstrated that daily supplementation of antioxidants at the appropriate time of day inhibited insulin resistance caused by chronic mealtime shifts, suggesting significant and chronic health implications for shift workers. In conclusion, it was confirmed that increased ROS levels caused by mealtime shift induce insulin resistance, which is inhibited by the antioxidant melatonin.

BackgroundInternet or mobile device use as a form of information and communication technology (ICT) can be more effective in weight loss and weight maintenance than traditional obesity interventions. ObjectiveThe study aims to assess the effectiveness of child-centered ICT interventions on obesity-related outcomes. MethodsArticles were retrieved from the Cochrane Central Register of Controlled Trials, Embase, and PubMed web-based databases. We selected randomized controlled trials in which the participants were aged

The ERK signalling pathway is activated in many cancers, however ERK1 and ERK2 are difficult to target pharmacologically. Here, the authors identify a small molecule inhibitor that binds covalently to the D-recruitment site of ERK and induces cell death and reduces tumour growth in mice.

Occurrence of DNA double-strand break (DSB) repair is important for genome integrity. Here, the authors reveal that Pellino1 is a DSB-responsive ubiquitin ligase required for promoting the accumulation of ATM and MRN complex at DSB sites via NBS1 ubiquitination.

Objective Paraoxonase 1 (PON1), a calcium-dependent serum enzyme, has been shown to be involved in lipid metabolism. In this study, we examined the putative correlation of the serum PON1 level of Hanwoo, Korean native cattle, with gender and meat quality grade. Methods PON1 levels were estimated by determining the arylesterase and paraoxonase activities (AE and PO, respectively) in serum samples from Hanwoo individuals (n = 56). Serum PON1 levels were analyzed in different gender groups (female [n = 21], castrated male [n = 17], and male [n = 18]), and meat quality grades (≥1 [n = 23], 2 [n = 21], and 3 [n = 12]). Results Serum PON1 levels were similar in female (AE = 120±55 U/mL, PO = 84±43 mU/mL) and castrated male (123±44 U/mL, PO = 89±30 mU/mL), while male showed a significantly lower level (AE = 65±43 U/mL, PO = 44±34 mU/mL). Furthermore, analysis of serum PON1 levels in three different grades of meat quality showed similar levels in the grades ≥1 (AE = 118±49 U/mL, PO = 84±37 mU/mL) and 2 (AE = 116±54 U/mL, PO = 82±43 mU/mL), while the level was significantly lower in the grade 3 (AE = 58±35 U/mL, PO = 39±27 mU/mL) of lower meat quality. Conclusion We discovered the gender-dependent differences in serum PON1 levels of Hanwoo and a positive association of the serum PON1 level with meat quality. Results in this study suggest that PON1 would be a useful serum marker for preliminary screening of Hanwoo individuals with high-quality meat and applicable for genetic improvement.

In this paper, the characteristics of the Excellence in Design for Greater Efficiencies (EDGE) green building certification system in terms of the scope of certification, and environmental and social strategies focused on 6024 units in the 17 EDGE-certified residential buildings in South Africa was investigated. This research analyzed the efficiency of energy, water, embodied energy in materials, and annual CO2 emissions and their contribution to solving housing issues in the given context. This research revealed that the design of EDGE-certified buildings focuses on the “efficiency first” approach and reduced energy and water demand more than on-site energy production. In energy-saving strategies, energy-saving solutions are three times (69.2%) higher than energy-generating solutions (23.1%). The results on resource savings showed that, on average, embodied energy in materials (54%) is the most reduced resource, followed by water (31%) and energy (29.7%). The statistical analysis indicated that there is no statistically significant correlation between energy, water, embodied energy in materials, and CO2 savings with floor areas of the buildings. In addition, this research highlighted how EDGE certification has positively contributed to solving South Africa’s resource shortage and affordable housing scarcity problems.

Conducting lighting simulations to investigate lighting performance, such as glare, is widely accepted and of particular interest in the design development stage. However, the main challenge remains in integrating lighting performance metrics into a streamlined modelling and evaluation workflow. With the advancement in digital and modelling technologies, an automatic workflow of modelling parametric design studies with lighting performance evaluation becomes feasible. This study investigates a parametric modelling approach to facilitate glare evaluation using China Green Building Standard as an example. Their glare evaluation adopted the known daylight glare index (DGI) with a revised glare source definition in the calculation. An evaluation toolkit is presented, demonstrating its applications with the sky model. Compared with DGI, the results articulate how a parametric modelling workflow can automate lighting performance evaluation and facilitate technical investigation and clarifications for glare evaluation. Through the parametric simulation studies, the differences in the limited metric scale and the sensitivity of capturing window sizes on the glare evaluation suggest future evaluation protocols for the environmental standard development.

Lyocell is a biodegradable filament yarn obtained by directly dissolving cellulose in a mixture of N-methylmorpholine-N-oxide and a non-toxic solvent. Therefore, herein, lyocell fabrics were employed as eco-friendly carbon-precursor substitutes for use as electromagnetic interference (EMI) shielding materials. First, a lyocell fabric treated with polyacrylamide via electron beam irradiation reported in a previous study to increase carbon yields and tensile strengths was carbonized by heating to 900, 1100, and 1300 °C. The carbonization transformed the fabric into a graphitic crystalline structure, and its electrical conductivity and EMI shielding effectiveness (SE) were enhanced despite the absence of metals. For a single sheet, the electrical conductivities of the lyocell-based carbon fabric samples at the different carbonization temperatures were 3.57, 5.96, and 8.91 S m−1, leading to an EMI SE of approximately 18, 35, and 82 dB at 1.5–3.0 GHz, respectively. For three sheets of fabric carbonized at 1300 °C, the electrical conductivity was 10.80 S m−1, resulting in an excellent EMI SE of approximately 105 dB. Generally, EM radiation is reduced by 99.9999% in instances when the EMI SE was over 60 dB. The EMI SE of the three lyocell-based carbon fabric sheets obtained at 1100 °C and that of all the sheets of the sample obtained at 1300 °C exceeded approximately 60 dB.

Indoor acoustic quality is one of the critical indicators for occupants’ health, comfort, and productivity in contemporary office environments. Post-occupancy evaluation (POE) is usually employed to examine in situ acoustic measurements to ensure indoor acoustic quality. However, prevailing acoustic performance evaluation does not often consider the technical attributes of building systems (TABS) to holistically investigate the significant correlations between objective acoustic field measurements and subjective POE. As such, this study proposes to cross-examine in situ and perceived acoustic quality indices with TABS to quantify critical factors leading to enhanced occupant satisfaction. Statistical analyses suggest that technical building attributes can significantly influence occupants’ acoustic satisfaction compared to sound levels recorded in contemporary offices. For instance, lowering the distributed noise level from above 40% to 2% can lead to an average 21% increase in occupant satisfaction. Ultimately, incorporating environmental measurements with physical building attributes from an occupant-centric perspective can uncover applicable design guidelines for achieving optimal acoustic quality with the highest occupant satisfaction.

Chaga mushroom (Inonotus obliquus) comprises polyphenolic compounds, triterpenoids, polysaccharides, and sterols. Among the triterpenoid components, inotodiol has been broadly examined because of its various biological activities. The purpose of this study is to examine inotodiol from a safety point of view and to present the potential possibilities of inotodiol for medical usage. From chaga mushroom extract, crude inotodiol (INO20) and pure inotodiol (INO95) were produced. Mice were treated with either INO20 or INO95 once daily using oral administration for repeated dose toxicity evaluation. Serum biochemistry parameters were analyzed, and the level of pro-inflammatory cytokines in the serum was quantified. In parallel, the effect of inotodiol on food allergic symptoms was investigated. Repeated administration of inotodiol did not show any mortality or abnormalities in organs. In food allergy studies, the symptoms of diarrhea were ameliorated by administration with INO95 and INO20. Furthermore, the level of MCPT-1 decreased by treatment with inotodiol. In this study, we demonstrated for the first time that inotodiol does not cause any detrimental effect by showing anti-allergic activities in vivo by inhibiting mast cell function. Our data highlight the potential to use inotodiol as an immune modulator for diseases related to inflammation.

A decline in immune function with aging has been reported. Regulatory T cell (Treg) induction is known to decrease with age, and elucidating the underlying mechanism is important for preventing age-related diseases due to age-related chronic inflammation. In the intestine, dendritic cells (DCs) play an important role in inducing Tregs specific to oral antigens, and they efficiently induce Tregs via production of retinoic acid (RA), a vitamin A metabolite, catalyzed by the enzyme retinaldehyde dehydrogenase 2 (RALDH2). We have previously reported that in the mesenteric lymph node (MLN), a secondary lymphoid tissue in which immune responses to oral antigens are induced, four DC subsets express different levels of CD11b, CD103, and PD-L1, and we have reported that the CD11b–CD103+PD-L1high subset expresses the highest levels of the RALDH2 gene and induces Tregs in vitro. We examined Treg induction in young and aged mice using a Treg induction model by administering a food antigen, and we found that antigen-specific Treg induction was decreased in aged mice. We further investigated the MLN DCs, and a significant decrease in RALDH2 gene expression was observed in MLN DCs from aged mice. As factors, we found that the proportion of the CD11b–CD103+PD-L1high subset was decreased in aged mice compared with that in young mice and that RALDH enzyme activity was decreased in the CD11b–CD103+PD-L1high and CD11b+CD103+PD-L1high subsets. Furthermore, analysis of the methylation of the RALDH2 gene promoter region revealed that CpG motifs were more methylated in the MLN DCs of aged mice, suggesting that RALDH2 expression was suppressed by epigenetic changes. Finally, we found that RA treatment tended to increase Treg induction. These results suggest that the regulation of RA production may be involved in the age-related decrease in antigen-specific Treg induction.

In this study, we assessed the anti-inflammatory properties of spent coffee grounds. Methanolic extracts of spent coffee grounds obtained from 3 Arabica cultivars possess compounds that exerted inhibitory effects on the secretion of inflammatory mediators (TNF-α, IL-6, and IL-10) induced by a human pro-monocytic cell line differentiated with PMA and stimulated with lipopolysaccharide (LPS). Our results indicated that the cytokine suppressive activities of the spent coffee ground (SCG) extracts were different among coffee cultivars tested. Hawaiian Kona extracts exhibited inhibitory effects on the expression of 3 examined cytokines, Ethiopian Yirgacheffe extracts reduced the secretion of TNF-α and IL-6, and Costa Rican Tarrazu extracts decreased the secretion of IL-6 only. Untargeted metabolomics analyses of SCG extracts led to the putative identification of 26 metabolites with known anti-inflammatory activities. Multiple metabolites (i.e., chrysin, daidzein, eugenol, naringenin, naringin, oxyresveratrol, pectolinarin, resveratrol, tectochrysin, theaflavin, vanillic acid, and vitexin rhamnoside) identified in the SCGs represent possible novel anti-inflammatory compounds. Of the 26 identified metabolites, the 12 compounds that had high relative intensities in all of the extracts were successfully quantified using liquid chromatography-tandem mass spectrometry analyses. Results from the targeted analyses indicated that caffeine and 5-caffeoylquinic acid (CQA) were the most abundant compounds in the SCG extracts. The contents of caffeine ranged from 0.38 mg/g (Ethiopian Yirgacheffe) – 0.44 mg/g (Costa Rican Tarrazu), whereas 5-CQA concentrations were in the range of 0.24 mg/g (Costa Rican Tarrazu) – 0.34 mg/g (Ethiopian Yirgacheffe). The presence of multiple anti-inflammatory compounds in SCGs provides a promising natural source for cosmetic and pharmaceutical industries.

To transform tall goldenrods, which are invasive alien plant that destroy the ecosystem of South Korea, into useful materials, cellulose fibers isolated from tall goldenrods are applied as EMI shielding materials in this study. The obtained cellulose fibers were blended with CNTs, which were used as additives, to improve the electrical conductivity. TGCF/CNT papers prepared using a facile paper manufacturing process with various weight percent ratios and thickness were carbonized at high temperatures and investigated as EMI shielding materials. The increase in the carbonization temperature, thickness, and CNT content enhanced the electrical conductivity and EMI SE of TGCF/CNT carbon papers. TGCF/CNT-15 papers, with approximately 4.5 mm of thickness, carbonized at 1300 °C exhibited the highest electrical conductivity of 6.35 S cm−1, indicating an EMI SE of approximately 62 dB at 1.6 GHz of the low frequency band. Additionally, the obtained TGCF/CNT carbon papers were flexible and could be bent and wound without breaking.

Objective To investigate and demonstrate persistent increase of peak cough flow after mechanical in-exsufflator application, in patients with neuromuscular diseases and pneumonia. Methods A mechanical in-exsufflator was applied with patients in an upright or semi-upright sitting position (pressure setting, +40 and −40 cmH2O; in-exsufflation times, 2–3 and 1–2 seconds, respectively). Patients underwent five cycles, with 20–30 second intervals to prevent hyperventilation. Peak cough flow without and with assistive maneuvers, was evaluated before, and 15 and 45 minutes after mechanical in-exsufflator application. Results Peak cough flow was 92.6 L/min at baseline, and 100.4 and 100.7 L/min at 15 and 45 minutes after mechanical in-exsufflator application, respectively. Assisted peak cough flow at baseline, 15 minutes, and 45 minutes after mechanical in-exsufflator application was 170.7, 179.3, and 184.1 L/min, respectively. While peak cough flow and assisted peak cough flow increased significantly at 15 minutes after mechanical in-exsufflator application compared with baseline (p=0.030 and p=0.016), no statistical difference was observed between 15 and 45 minutes. Conclusion Increased peak cough flow after mechanical in-exsufflator application persists for at least 45 minutes.

Waste wood contains large amounts of cellulose fibers that have outstanding mechanical properties. These fibers can be recycled and converted into highly valuable materials of waste wood. In this study, waste wood cellulose fiber/graphene nanoplatelet (WWCF/GnP) papers were prepared according to the WWCF and GnP contents. Subsequently, the WWCF/GnP papers were varyingly carbonized for their application as electromagnetic interference (EMI) shielding materials such as state-of-the-art electronic equipment malfunction prevention, chip-level microsystem, and micro intersystem noise suppression/reduction. The increase in the GnP content and carbonization temperature enhanced electrical conductivity, thereby generating a greater EMI shielding effectiveness (EMI SE) in the high-frequency X-band. Additionally, the thickness of the WWCF/GnP carbon papers improved the electrical conductivity and EMI SE values. The electrical conductivity of the WWCF/GnP-15 carbon paper obtained at carbonization temperature of 1300 °C was approximately 5.86 S/m, leading to an EMI SE value of 43 decibels (dB) at 10.5 GHz for one sheet. Furthermore, overlapping of the three sheets increased the electrical conductivity to 7.02 S/m, leading to an EMI SE value of 72.5 dB at 10.5 GHz. Thus, we isolated WWCFs, without completely removing contaminants, for recycling and converting them into highly valuable EMI shielding materials.

Carbon fibers, which act as reinforcements in many applications, are often obtained from polyacrylonitrile (PAN). However, their production is expensive and results in waste problems. Therefore, we focused on producing carbon fibers from lyocell, a cellulose-based material, and analyzed the effects of the process parameters on their mechanical properties and carbon yields. Lyocell was initially grafted with polyacrylamide (PAM) via electron-beam irradiation (EBI) and was subsequently stabilized and carbonized. Thermal analysis showed that PAM grafting increased the carbon yields to 20% at 1000 °C when compared to that of raw lyocell, which degraded completely at about 600 °C. Stabilization further increased this yield to 55%. The morphology of the produced carbon fibers was highly dependent on PAM concentration, with fibers obtained at concentrations ≤0.5 wt.% exhibiting clear, rigid, and round cross-sections with smooth surfaces, whereas fibers obtained from 2 and 4 wt.% showed peeling surfaces and attachment between individual fibers due to high viscosity of PAM. These features affected the mechanical properties of the fibers. In this study, carbon fibers of the highest tensile strength (1.39 GPa) were produced with 0.5 wt.% PAM, thereby establishing the feasibility of using EBI-induced PAM grafting on lyocell fabrics to produce high-performance carbon fibers with good yields.