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This paper describes design specifications and performance of a toroid-type high-temperature superconducting (HTS) DC reactor. The first phase operation targets of the HTS DC reactor were 400 mH and 400 A. The authors have developed a real HTS DC reactor system during the last three years. The HTS DC reactor was designed using 2G GdBCO HTS wires. The HTS coils of the toroid-type DC reactor magnet were made in the form of a D-shape. The electromagnetic performance of the toroid-type HTS DC reactor magnet was analyzed using the finite element method program. A conduction cooling method was adopted for reactor magnet cooling. The total system has been successfully developed and tested in connection with LCC type HVDC system. Now, the authors are studying a 400 mH, kA class toroid-type HTS DC reactor for the next phase research. The 1500 A class DC reactor system was designed using layered 13 mm GdBCO 2G HTS wire. The expected operating temperature is under 30 K. These fundamental data obtained through both works will usefully be applied to design a real toroid-type HTS DC reactor for grid application. [ABSTRACT FROM AUTHOR]

Conventional induction heaters have been in operation in metal and related industries with poor energy efficiencies of only 50–60%. Also, the efficiency of atmosphere furnace, one of the various heating facilities for metal billets, is about 20%. Hence, a high temperature superconducting (HTS) DC induction heating machine to heat a rotating metal billet under uniform magnetic field generated by the 2G HTS magnet with about 80–90% of the system energy efficiency has been researched in this paper. We presented practical design specification, operational characteristics, and temperature distribution on a 10 kW class HTS DC induction heating machine which had been built and tested. The saturated temperature of an HTS no-insulated(NI) coil in the cryostat fabricated with 100 A of the operating current reached 45.9 K and the magnetic field at the centre point between two iron cores measured 0.2 T. The rotating machine for 4.1 kg of the aluminum billet was tested on 1760 rpm of the rated rotating speed. The final temperature of the aluminum billet has risen up to 500 °C for 480 s. The research outcomes are expected to be useful for the design of a large scale HTS DC induction heating machine in industries. [ABSTRACT FROM AUTHOR]

This paper describes the design specifications and performance of a real toroid-type high temperature superconducting (HTS) DC reactor. The HTS DC reactor was designed using 2G HTS wires. The HTS coils of the toroid-type DC reactor magnet were made in the form of a D-shape. The target inductance of the HTS DC reactor was 400 mH. The expected operating temperature was under 20 K. The electromagnetic performance of the toroid-type HTS DC reactor magnet was analyzed using the finite element method program. A conduction cooling method was adopted for reactor magnet cooling. Performances of the toroid-type HTS DC reactor were analyzed through experiments conducted under the steady-state and charge conditions. The fundamental design specifications and the data obtained from this research will be applied to the design of a commercial-type HTS DC reactor. [ABSTRACT FROM AUTHOR]

Abstract: We have discovered and demonstrated the in vitro and in vivo PPARδ-selective activity of novel Y-shaped agonists. These compounds activated hPPARδ with EC50 values between 1 and 523 nM. Surprisingly, compounds 10a, 11d, 11e and 11f were the most potent and most selective hPPARδ agonists with 104-fold selectivity over the other two subtypes, namely, hPPARα and hPPARγ. The PPARδ ligands 10a, 11e and 11f showed good bioavailability and in vivo efficacy. [Copyright &y& Elsevier]

Abstract: A detachable thermosiphon, as a transient thermal switch for conduction-cooled superconducting magnet, is designed, fabricated and tested. A thermosiphon between the first and second stages of a cryocooler can reduce the cool-down time of a conduction-cooled superconducting magnet by using the large cooling capacity of the first stage. The thermosiphon is a very efficient heat transfer device until all the working fluid in it freezes (off-state). After the working fluid freezes and the second stage temperature becomes lower than that of the first stage, however, the thermosiphon then becomes a conduction heat leak path between two stages of the cryocooler. Considering a very small cooling capacity of the second stage of the cryocooler around 4.2K, the conduction heat loss is not negligible. Therefore, a detachable thermosiphon, made of a metal bellows, is considered to be able to eliminate such a conduction heat leak. The mock-up magnet is cooled down with the thermosiphon and the thermodynamic states of the thermosiphon and the mock-up magnet are precisely examined during the whole cool-down process. At off-state, the thermosiphon is detached mechanically from the magnet. In this way, the conduction heat leak path through the thermosiphon wall is completely eliminated. This paper describes the detailed transient operation of the detachable thermosiphon using nitrogen as the working fluid. [Copyright &y& Elsevier]

Abstract: HTS power transmission cables appear to be the replacement and retrofitting of underground cables in urban areas and HTS power transmission cable offers a number of technical and economic merits compared to the normal conductor cable system. A 30m long, single-phase 22.9kV class HTS power transmission cable system has been developed by Korea Electrotechnology Research Institute (KERI), LS Cable Ltd., and Korea Institute of Machinery and Materials (KIMM), which is one of the 21st century frontier project in Korea since 2001. The HTS power cable has been developed, cooled down and tested to obtain realistic thermal and electrical data on HTS power cable system. The evaluation results clarified such good performance of HTS cable that DC critical current of the HTS cable was 3.6kA and AC loss was 0.98W/m at 1260Arms and shield current was 1000Arms. These results proved the basic properties for 22.9kV HTS power cable. As a next step, we have been developing a 30m, three-phase 22.9kV, 50MVA HTS power cable system and long term evaluation is in progress now. [Copyright &y& Elsevier]

Extracellular vesicles, also known as exosomes, influence numerous cellular functions by regulating different signaling pathways. However, their role in animal reproduction remains understudied. This study aimed to evaluate the effects of porcine follicular fluid-derived exosomes (pff-Exos) on porcine oocyte in vitro maturation and parthenogenetic embryo development. We obtained pff-Exos through mixed-method ultracentrifugation and size-exclusion chromatography. Transmission electron microscopy revealed an increase in the expression of exosome markers in the first four of thirteen fractions. The number of pff-Exo was 2.2 × 10 6 particles per microliter. The highest maturation rate of porcine oocytes treated with pff-Exo was observed with 1.1 × 10 7 particles of pff-Exo in the absence of porcine follicular fluid (pFF) culture conditions. Moreover, increased expression of Gdf9 and Bmp15 was observed. The developmental rate was the highest upon treatment with 1.1 × 10 7 particles of pff-Exo, which increased the total cell number in blastocysts. Embryonic development to the 2-cell stage was similar between the control and pff-Exo groups; however, development to the 4-cell stage and blastocyst was significantly increased in the pff-Exo group (61.6 ± 6.08 % and 29.72 ± 1.41 %, respectively; P < 0.05) compared with that in the control group (42.0 ± 5.19 % and 18.14 ± 1.78 %, respectively). The expression levels of Oct4, Sox2, Bcl2, Elf4, and Gcn5 significantly increased at the pff-Exo 2-cell stage, whereas those of Bax, Hdac1, Hdac6, and Sirt6 decreased. Specifically, the Oct4, Sox2, Elf4, Gcn5, and Hdac6 levels remained stable in pff-Exo 4-cell embryos, whereas those of p53 and Hat1 were reduced and increased, respectively. Treatment with pffExos significantly increased H3K9 and H3K14 acetylation levels. These results demonstrate that pff-Exo affects the in vitro maturation of porcine oocytes and early embryonic development by regulating gene expression., Competing Interests: Declaration of competing interest The authors have no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

This study introduces the time-gated analysis of room-temperature phosphorescence (RTP) for the in-situ analysis of the visible and spectral information of photons. Time-gated analysis is performed using a microscopic system consisting of a spectrometer, which is advantageous for in-situ analysis since it facilitates the real-time measurement of luminescence signal changes. An RTP material hybridized with a DNA aptamer that targets a specific protein enhances the intensity and lifetime of phosphorescence after selective recognition with the target protein. In addition, time-gated analysis allows for the millisecond-scale imaging of phosphorescence signals, excluding autofluorescence, and improves the signal-to-background ratio (SBR) through the accumulation of signals. While collecting the time-gated images and spectra of RTP and autofluorescent materials simultaneously, we develop a method for obtaining phosphorescence signals by means of selective exclusion of autofluorescence signals in simulated or real cell conditions. It is confirmed that the accumulated time-gated analysis can provide ample information about luminescence signals for bioimaging and biosensing applications., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Acorus gramineus has a number of beneficial effects, including protective effects against age-related disorders. In this study, the effects of A. gramineus on testosterone production and andropause symptoms were evaluated. We first treated TM3 mouse Leydig cells, responsible for testosterone production, with A. gramineus aqueous extract at different concentrations. In TM3 cells, the testosterone concentration increased in a concentration-dependent manner compared with those in the control. In addition, at 400 μg/mL extract, the mRNA expression level of the steroidogenic enzyme CYP11A1 was increased. Subsequently, 23-week-old Sprague-Dawley (SD) rats exhibiting an age-related reduction in serum testosterone (approximately 80% lower than that in 7-week-old SD rats) were administered A. gramineus aqueous extract for 8 weeks. Serum total testosterone and free testosterone levels were higher and serum estradiol, prostate-specific antigen levels, and total cholesterol levels were lower in the AG50 group ( A. gramineus aqueous extract 50 mg/kg of body weight/day) than in the OLD (control group). The AG50 group also showed significant elevations in sperm count, grip strength, and mRNA expression of StAR , CYP11A1 , 17β-HSD , and CYP17A1 compared with those in the OLD group. In conclusion, A. gramineus aqueous extract facilitated steroidogenesis in Leydig cells, elevated testosterone levels, lowered serum estradiol and total cholesterol levels, and increased muscle strength and sperm count, thus alleviating the symptoms of andropause. These findings suggest that A. gramineus aqueous extract is a potentially effective therapeutic agent against various symptoms associated with andropause.

Background: RNA-binding proteins (RBPs) perform various biological functions in humans and are associated with several diseases, including cancer. Therefore, RBPs have emerged as novel therapeutic targets. Although recent investigations have shown that RBPs have crucial functions in breast cancer (BC), detailed research is underway to determine the RBPs that are closely related to cancers., Objective: To provide an insight into estrogen receptor (ER) regulation by cold-inducible RNA binding protein (CIRBP) as a novel therapeutic target., Results: By analyzing the genomic data, we identified a potential RBP in BC. We found that CIRBP is highly correlated with ER function and influences clinical outcomes, such as patient survival and endocrine therapy responsiveness. In addition, CIRBP influences the proliferation of BC cells by directly binding to ER-RNA., Conclusion: Our results suggest that CIRBP is a novel upstream regulator of ER and that the interplay between CIRBP and ER may be associated with the clinical relevance of BC., (© 2024. The Author(s) under exclusive licence to The Genetics Society of Korea.)

The gut microbiota is a key factor significantly impacting host health by influencing metabolism and immune function. Its composition can be altered by genetic factors, as well as environmental factors such as the host's surroundings, diet, and antibiotic usage. This study aims to examine how the characteristics of the gut microbiota in pigs, used as source animals for xenotransplantation, vary depending on their rearing environment. We compared the diversity and composition of gut microbiota in fecal samples from pigs raised in specific pathogen-free (SPF) and conventional (non-SPF) facilities. The 16S RNA metagenome sequencing results revealed that pigs raised in non-SPF facilities exhibited greater gut microbiota diversity compared to those in SPF facilities. Genera such as Streptococcus and Ruminococcus were more abundant in SPF pigs compared to non-SPF pigs, while Blautia, Bacteroides, and Roseburia were only observed in SPF pigs. Conversely, Prevotella was exclusively present in non-SPF pigs. It was predicted that SPF pigs would show higher levels of processes related to carbohydrate and nucleotide metabolism, and environmental information processing. On the other hand, energy and lipid metabolism, as well as processes associated with genetic information, cell communication, and diseases, were predicted to be more active in the gut microbiota of non-SPF pigs. This study provides insights into how the presence or absence of microorganisms, including pathogens, in pig-rearing facilities affects the composition and function of the pigs' gut microbiota. Furthermore, this serves as a reference for tracing whether xenotransplantation source pigs were maintained in a pathogen-controlled environment.

Objective: To examine the prevalence of embitterment by following individuals over time and to statistically evaluate how factors known as correlates of embitterment affect different groups with or without changes in embitterment over time., Method: Responses for the posttraumatic embitterment disorder (PTED) self-rating Scale were collected from the same 1,153 adults who participated in a follow-up survey delivered 14 months apart. Suggested cutoff points were applied to identify changes in embitterment and four groups were identified. For each group, the relative impacts of factors that affect changes in or maintenance of embitterment, such as negative life events (NLEs), belief in a just world (BJW), social support, relative deprivation, and resilience, were statistically analyzed., Results: The average PTED scores were relatively high for both surveys ( M = 1.73 and 1.58, respectively). "Persistent" or "increased" in embitterment was seen for 47.3% of the participants. In particular, 15.3% (Wave 1) and 12.1% (Wave 2) of participants experienced clinically relevant levels of embitterment. NLEs, BJW, relative deprivation, and resilience showed significant associations with the risk of persistence or deterioration of embitterment., Conclusions: Our study highlights embitterment as a dynamic emotion that can either be aggravated or moderated over time. Embitterment can be elicited by joint effects of multiple social and interactional factors including known embitterment correlates, and relative deprivation is confirmed as a possible core elicitor of embitterment in the context of comparative justice. These findings imply that additional longitudinal research and development of practices for mental health prevention in general populations are needed. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Hepatocellular carcinoma (HCC) is the most common form of liver cancer and the 5-year relative overall survival (OS) rate is less than 20%. Since there are no specific symptoms, most patients with HCC are diagnosed in an advanced stage with poor prognosis. Therefore, identifying novel prognostic biomarkers to improve the survival of patients with HCC is urgently needed. In the present study, we attempted to identify SAMD13 (Sterile Alpha Motif Domain-Containing Protein 13) as a novel biomarker associated with the prognosis of HCC using various bioinformatics tools. SAMD13 was found to be highly expressed pan-cancer; however, the SAMD13 expression was significantly correlated with the worst prognosis in HCC. Clinicopathological analysis revealed that SAMD13 upregulation was significantly associated with advanced HCC stage and high-grade tumor type. Simultaneously, high SAMD13 expression resulted in association with various immune markers in the immune cell subsets by TIMER databases and efficacy of immunotherapy. Methylation analysis showed SAMD13 was remarkably associated with prognosis. Furthermore, a six-hub gene signature associated with poor prognosis was correlated with the cell cycle, transcription, and epigenetic regulation and this analysis may support the connection between SAMD13 expression and drug-resistance. Our study illustrated the characteristics of SAMD13 role in patients with HCC using various bioinformatics tools and highlights its potential role as a therapeutic target and promising biomarker for prognosis in HCC., (© 2023. The Author(s).)

In this study, we built on our previous research that discovered that autophagy activated the metaphase I stage during porcine oocytes in vitro maturation. We investigated the relationship between autophagy and oocyte maturation. First, we confirmed whether autophagy was activated differently by different media (TCM199 and NCSU-23) during maturation. Then, we investigated whether oocyte maturation affected autophagic activation. In addition, we examined whether the inhibition of autophagy affected the nuclear maturation rate of porcine oocytes. As for the main experiment, we measured LC3-II levels using western blotting after inhibition of nuclear maturation via cAMP treatment in an in vitro culture to clarify whether nuclear maturation affected autophagy. After autophagy inhibition, we also counted matured oocytes by treating them with wortmannin or a E64d and pepstatin A mixture. Both groups, which had different treatment times of cAMP, showed the same levels of LC3-II, while the maturation rates were about four times higher after cAMP 22 h treatment than that of the 42 h treatment group. This indicated that neither cAMP nor nuclear status affected autophagy. Autophagy inhibition during in vitro oocyte maturation with wortmannin treatment reduced oocyte maturation rates by about half, while autophagy inhibition by the E64d and pepstatin A mixture treatment did not significantly affect the oocyte maturation. Therefore, wortmannin itself, or the autophagy induction step, but not the degradation step, is involved in the oocyte maturation of porcine oocytes. Overall, we propose that oocyte maturation does not stand upstream of autophagy activation, but autophagy may exist upstream of oocyte maturation.

The green organic semiconductor, tris-(8-hydroxyquinoline)aluminum (Alq 3 ), was hybridized with DNA growing in the shape of hexagonal prismatic crystals. In this study, we applied hydrodynamic flow to the fabrication of Alq 3 crystals doped with DNA molecules. The hydrodynamic flow in the Taylor-Couette reactor induced nanoscale pores in the Alq 3 crystals, especially at the side part of the particles. The particles exhibited distinctly different photoluminescence emissions divided into three parts compared to common Alq 3 -DNA hybrid crystals. We named this particle a "three-photonic-unit". After treatment with complementary target DNA, the three-photonic-unit Alq 3 particles doped with DNAs were found to emit depressed luminescence from side parts of the particles. This novel phenomenon would expand the technological value of these hybrid crystals with divided photoluminescence emissions toward a wider range of bio-photonic applications.

The charge transfer (CT) process has attracted much attention due to its contribution to the improvement of spectroscopic phenomena such as Raman scattering and fluorescence. A current challenge is understanding what factors can influence CT. Here, it is demonstrated that the enhancement factor (EF) of CT (∼2000) can reach the level of electromagnetic enhancement (∼1680) when resonant CT is carried out by (Fermi level energy) band alignment between a metal nanoparticle (NP) and conjugated polymer (polypyrrole (PPy)) nanowire (NW). This band alignment results in an on- or off-resonant CT. As a proof of concept for CT based surface enhanced Raman scattering (SERS) template, the Ag NPs-decorated PPy NW is utilized to effectively enhance the Raman signal of rhodamine 6G (EF of 5.7 × 10 5 ). Hence, by means of our demonstration, it is proposed that controlling the band alignment should be considered an important parameter for obtaining a large EF of spectroscopic phenomena.

Dietary restriction (DR) delays aging and the onset of age-associated diseases. However, it is yet to be determined whether and how restriction of specific nutrients promote longevity. Previous genome-wide screens isolated several Escherichia coli mutants that extended lifespan of Caenorhabditis elegans. Here, using 1 H-NMR metabolite analyses and inter-species genetics, we demonstrate that E. coli mutants depleted of intracellular glucose extend C. elegans lifespans, serving as bona fide glucose-restricted (GR) diets. Unlike general DR, GR diets don't reduce the fecundity of animals, while still improving stress resistance and ameliorating neuro-degenerative pathologies of Aβ 42 . Interestingly, AAK-2a, a new AMPK isoform, is necessary and sufficient for GR-induced longevity. AAK-2a functions exclusively in neurons to modulate GR-mediated longevity via neuropeptide signaling. Last, we find that GR/AAK-2a prolongs longevity through PAQR-2/NHR-49/Δ9 desaturases by promoting membrane fluidity in peripheral tissues. Together, our studies identify the molecular mechanisms underlying prolonged longevity by glucose specific restriction in the context of whole animals., (© 2023. The Author(s).)

Cells secrete extracellular vesicles (EVs) carrying cell-of-origin markers to communicate with surrounding cells. EVs regulate physiological processes ranging from intercellular signaling to waste management. However, when senescent cells (SnCs) secrete EVs, the EVs, which are newly regarded as senescence-associated secretory phenotype (SASP) factors, can evoke inflammation, senescence induction, and metabolic disorders in neighboring cells. Unlike other soluble SASP factors, the biophysical properties of EVs, including small EVs (sEVs), derived from SnCs have not yet been investigated. In this study, sEVs were extracted from a human IMR90 lung fibroblast in vitro senescence model. Their biomechanical properties were mapped using atomic force microscopy-based quantitative nanomechanical techniques, surface potential microscopy, and Raman spectroscopy. The surfaces of sEVs derived from SnCs are slightly stiffer but their cores are softer than those of sEVs secreted from non-senescent cells (non-SnCs). This inversely proportional relationship between deformation and stiffness, attributed to a decrease in the concentration of genetic and protein materials inside the vesicles and the adsorption of positively charged SASP factors onto the vesicle surfaces, respectively, was found to be a peculiar characteristic of SnC-derived sEVs. Our results demonstrate that the biomechanical properties of SnC-derived sEVs differ from those of non-SnC-derived sEVs and provide insight into the mechanisms underlying their formation and composition.

We reveal the fundamental understanding of molecular doping of DNAs into organic semiconducting tris (8-hydroxyquinoline) aluminum (Alq 3 ) crystals by varying types and numbers of purines and pyrimidines constituting DNA. Electrostatic, hydrogen bonding, and π-π stacking interactions between Alq 3 and DNAs are the major factors affecting the molecular doping. Longer DNAs induce a higher degree of doping due to electrostatic interactions between phosphate backbone and Alq 3 . Among four bases, single thymine bases induce the multisite interactions of π-π stacking and hydrogen bonding with single Alq 3 , occurring within a probability of 4.37%. In contrast, single adenine bases form multisite interactions, within lower probability (1.93%), with two-neighboring Alq 3 . These multisite interactions facilitate the molecular doping into Alq 3 particles compared to cytosines or guanines only forming π-π stacking. Thus, photoluminescence and optical waveguide phenomena of crystals were successfully tailored. This discovery should deepen our fundamental understanding of incorporating DNAs into organic semiconducting crystals., (© 2022. The Author(s).)

With aging, men inevitably encounter irreversible changes, including progressive loss of testosterone and physical strength, and increased fat mass. To assess the alleviatory effects of EUAJ on andropause symptoms, including in vivo testosterone deficiency, we administered EUAJ for 6 weeks in 22-week-old Sprague-Dawley rats. Before EUAJ (3:1) ( E. ulmoides : A. japonica = 3:1, KGC08EA) administration, testosterone decline in 22-week-old SD rats was confirmed compared to 7-week-old SD rats (NC group). After administration of EUAJ (3:1) at 20, 40, and 80 mg/kg for 6 weeks, testosterone, free testosterone, and mRNA expression levels ( Cyp11a1 and Hsd3b1 ) were significantly increased at 40 mg/kg EUAJ (3:1), whereas mRNA expression levels of Cyp19a1 and Srd5a2 were significantly reduced at this concentration, compared to the control group. Swimming retention time was significantly increased at both 40 mg/kg and 80 mg/kg. In summary, EUAJ (3:1) enhanced testosterone production by increasing bioavailable testosterone, sex hormone-binding globulin (SHBG), and enzymes related to testosterone synthesis at 40 mg/kg. In addition, 80 mg/kg EUAJ (3:1) also increased physical and testicular functions., Competing Interests: The authors declare no conflict of interest.

Background: Benign prostatic hyperplasia (BPH) is a disease characterized by abnormal proliferation of the prostate, which occurs frequently in middle-aged men. In this study, we report the effect of red ginseng oil (KGC11 o ) on BPH., Methods: The BPH-induced Sprague-Dawley rats were divided into seven groups: control, BPH, KGC11 o 25, 50, 100, 200, and finasteride groups. KGC11 o and finasteride were administered for 8 weeks. The BPH biomarkers, DHT, 5AR1, and 5AR2, androgen receptor, prostate-specific antigen (PSA), Bax, Bcl-2, and TGF-β were determined in the serum and prostate tissue. The cell viability after KGC11 o treatment was determined using BPH-1 cells, and, androgen receptor, Bax, Bcl-2, and TGF-β were confirmed by western blotting., Results: In the in vivo study, administration of KGC11 o reduced prostate weight by 18%, suppressed DHT (up to 22%) and 5AR2 (up to 12%) levels from administration of 100 mg/kg KGC11 o (P < 0.05). PSA was significantly downregulated dose-dependently from at the concentration of 50 mg/kg KGC11 o (P < 0.05). BPH-1 cell viability significantly reduced through the treatment with KGC11 o . In vitro and vivo , AR, Bcl-2 TGF-β levels reduced significantly but Bax was increased (P < 0.05)., Conclusion: These results suggest that KGC11 o may inhibit the development of BPH by significantly reducing the levels of BPH biomarkers via 5ARI, anti-androgenic effect, and anti-proliferation effect, serving as a potential functional food for treating BPH., (© 2021 The Korean Society of Ginseng. Publishing services by Elsevier B.V.)

Cytokine release syndrome (CRS) is a systemic inflammatory response resulting in overexpression of cytokines in serum and tissues, which leads to multiple-organ failure. Due to rapid aggravation of symptoms, timely intervention is paramount; however, current therapies are limited in their capacity to address CRS. Here, we find that the intravenous injection of highly purified detonation-synthesized nanodiamonds (DND) can act as a therapeutic agent for treating CRS by adsorbing inflammatory cytokines. Highly purified DNDs successfully inactivated various key cytokines in plasma from CRS patients with pneumonia, septic shock, and coronavirus disease 2019 pandemic (COVID-19). The intravenous injection of the DND samples in a mouse sepsis model by cecal ligation and puncture significantly improved survival rates and prevented tissue damage by reducing the circulating inflammatory cytokines. The results of this study suggest that the clinical application of highly purified DND can provide survival benefits for CRS patients by adsorbing inflammatory cytokines., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Yoo, Lee, Kim, Jeong, Park, Ahn, Jung, Lee, Kim, Lee, Cho and Kim.)

Aims: Non-compaction cardiomyopathy is a devastating genetic disease caused by insufficient consolidation of ventricular wall muscle that can result in inadequate cardiac performance. Despite being the third most common cardiomyopathy, the mechanisms underlying the disease, including the cell types involved, are poorly understood. We have previously shown that endothelial cell-specific deletion of the chromatin remodeller gene Ino80 results in defective coronary vessel development that leads to ventricular non-compaction in embryonic mouse hearts. We aimed to identify candidate angiocrines expressed by endocardial and endothelial cells (ECs) in wildtype and LVNC conditions in Tie2Cre;Ino80fl/fltransgenic embryonic mouse hearts, and test the effect of these candidates on cardiomyocyte proliferation and maturation., Methods and Results: We used single-cell RNA-sequencing to characterize endothelial and endocardial defects in Ino80-deficient hearts. We observed a pathological endocardial cell population in the non-compacted hearts and identified multiple dysregulated angiocrine factors that dramatically affected cardiomyocyte behaviour. We identified Col15a1 as a coronary vessel-secreted angiocrine factor, downregulated by Ino80-deficiency, that functioned to promote cardiomyocyte proliferation. Furthermore, mutant endocardial and endothelial cells up-regulated expression of secreted factors, such as Tgfbi, Igfbp3, Isg15, and Adm, which decreased cardiomyocyte proliferation and increased maturation., Conclusions: These findings support a model where coronary endothelial cells normally promote myocardial compaction through secreted factors, but that endocardial and endothelial cells can secrete factors that contribute to non-compaction under pathological conditions., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: journals.permissions@oup.com.)

Cancer cachexia is a highly debilitating condition characterized by weight loss and muscle wasting that contributes significantly to the morbidity and mortality of pancreatic cancer. The factors that induce cachexia in pancreatic cancer are largely unknown. We previously showed that pancreatic adenocarcinoma upregulated factor (PAUF) secreted by pancreatic cancer cells is responsible for tumor growth and metastasis. Here, we analyzed the relation between pancreatic cancer-derived PAUF and cancer cachexia in mice and its clinical significance. Body weight loss and muscle weight loss were significantly higher in mice with Panc-1/PAUF tumors than in those with Panc-1/Mock tumors. Direct administration of rPAUF to muscle recapitulated tumor-induced atrophy, and a PAUF-neutralizing antibody abrogated tumor-induced muscle wasting in Panc-1/PAUF tumor-bearing mice. C2C12 myotubes treated with rPAUF exhibited rapid inactivation of Akt-Foxo3a signaling, resulting in Atrogin1/MAFbx upregulation, myosin heavy chain loss, and muscle atrophy. The neutrophil-to-lymphocyte ratio and body weight loss were significantly higher in pancreatic cancer patients with high PAUF expression than in those with low PAUF expression. Analysis of different pancreatic cancer datasets showed that PAUF expression was significantly higher in the pancreatic cancer group than in the nontumor group. Analysis of The Cancer Genome Atlas data found associations between high PAUF expression or a high DNA copy number and poor overall survival. Our data identified tumor-secreted circulating PAUF as a key factor of cachexia, causing muscle wasting in mice. Neutralizing PAUF may be a useful therapeutic strategy for the treatment of pancreatic cancer-induced cachexia.

In patients with advanced-stage cancer, cancer-associated anorexia affects treatment success and patient survival. However, the underlying mechanism is poorly understood. Here, we show that Dilp8, a Drosophila homologue of mammalian insulin-like 3 peptide (INSL3), is secreted from tumour tissues and induces anorexia through the Lgr3 receptor in the brain. Activated Dilp8-Lgr3 signalling upregulated anorexigenic nucleobinding 1 (NUCB1) and downregulated orexigenic short neuropeptide F (sNPF) and NPF expression in the brain. In the cancer condition, the protein expression of Lgr3 and NUCB1 was significantly upregulated in neurons expressing sNPF and NPF. INSL3 levels were increased in tumour-implanted mice and INSL3-treated mouse hypothalamic cells showed Nucb2 upregulation and Npy downregulation. Food consumption was significantly reduced in intracerebrospinal INSL3-injected mice. In patients with pancreatic cancer, higher serum INSL3 levels increased anorexia. These results indicate that tumour-derived Dilp8/INSL3 induces cancer anorexia by regulating feeding hormones through the Lgr3/Lgr8 receptor in Drosophila and mammals.

The physiological functions of many vital tissues and organs continue to mature after birth, but the genetic mechanisms governing this postnatal maturation remain an unsolved mystery. Human pancreatic β cells produce and secrete insulin in response to physiological cues like glucose, and these hallmark functions improve in the years after birth. This coincides with expression of the transcription factors SIX2 and SIX3, whose functions in native human β cells remain unknown. Here, we show that shRNA-mediated SIX2 or SIX3 suppression in human pancreatic adult islets impairs insulin secretion. However, transcriptome studies revealed that SIX2 and SIX3 regulate distinct targets. Loss of SIX2 markedly impaired expression of genes governing β-cell insulin processing and output, glucose sensing, and electrophysiology, while SIX3 loss led to inappropriate expression of genes normally expressed in fetal β cells, adult α cells, and other non-β cells. Chromatin accessibility studies identified genes directly regulated by SIX2. Moreover, β cells from diabetic humans with impaired insulin secretion also had reduced SIX2 transcript levels. Revealing how SIX2 and SIX3 govern functional maturation and maintain developmental fate in native human β cells should advance β-cell replacement and other therapeutic strategies for diabetes., (© 2021 Bevacqua et al.; Published by Cold Spring Harbor Laboratory Press.)

Strong magnetic fields are required in many fields, such as medicine (magnetic resonance imaging), pharmacy (nuclear magnetic resonance), particle accelerators (such as the Large Hadron Collider) and fusion devices (for example, the International Thermonuclear Experimental Reactor, ITER), as well as for other diverse scientific and industrial uses. For almost two decades, 45 tesla has been the highest achievable direct-current (d.c.) magnetic field; however, such a field requires the use of a 31-megawatt, 33.6-tesla resistive magnet inside 11.4-tesla low-temperature superconductor coils 1 , and such high-power resistive magnets are available in only a few facilities worldwide 2 . By contrast, superconducting magnets are widespread owing to their low power requirements. Here we report a high-temperature superconductor coil that generates a magnetic field of 14.4 tesla inside a 31.1-tesla resistive background magnet to obtain a d.c. magnetic field of 45.5 tesla-the highest field achieved so far, to our knowledge. The magnet uses a conductor tape coated with REBCO (REBa 2 Cu 3 O x , where RE = Y, Gd) on a 30-micrometre-thick substrate 3 , making the coil highly compact and capable of operating at the very high winding current density of 1,260 amperes per square millimetre. Operation at such a current density is possible only because the magnet is wound without insulation 4 , which allows rapid and safe quenching from the superconducting to the normal state 5-10 . The 45.5-tesla test magnet validates predictions 11 for high-field copper oxide superconductor magnets by achieving a field twice as high as those generated by low-temperature superconducting magnets.

Background: Despite heterogeneity of older people in suicidal behavior, research identifying characteristics by age groups is scarce. We examined baseline features of older community-dwelling suicidal ideators by dichotomized age groups and the 6-month trajectory of their suicidal ideation along with its related psychopathology. Predictors of suicidal ideation within each group were investigated., Methods: Older community-dwelling suicidal ideators enrolled in the Korean Cohort for the Model Predicting a Suicide and Suicide-related Behavior study were subdivided into the "young-old (65-74 years)" and "old-old (≥75 years)" group. Baseline, 1-, and 6-month assessments were compared. Within each group, multiple regression analysis using rating scales (Patient Health Questionnaire-9, Beck Anxiety Inventory, Alcohol Use Disorders Identification Test, Stress Questionnaire for Korean National Health and Nutrition Examination Survey-Short Form, and Social Relationships Scale) was conducted to identify predictors of suicidal ideation measured with the intensity subscale of the Columbia-Suicide Severity Rating Scale. Two-way repeated-measures analysis of variance (RM-ANOVA) was used to compare changes in suicidal ideation, depression, anxiety between age groups over time, and one-way RM-ANOVA to examine changes within each age group., Results: Among 29 "young-old" and 53 "old-old" ideators, the latter were less likely to be receiving psychiatric treatment (odds ratio [OR] = 4.065) and make suicide attempts (OR = 2.874), whereas the former revealed greater levels of anxiety and stress. Baseline depression and stress in the "young-old" group and the "old-old" group, respectively, predicted the intensity of suicidal ideation at both baseline and 1-month assessments. No significant age group x time interactions on suicidal ideation and depression were found. However, within each age group, both suicidal ideation and depression significantly decreased only during the first month with no further improvement., Conclusion: We speculate cautiously that more attention may need to be paid to the "old-old" ideators in the evaluation of psychiatric issues and for referral to psychiatrists. To decrease suicidal ideation, tailored approaches involving proactive, timely management of depression in the "young-old" and interventions focusing on stress reduction in the "old-old," would be helpful., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: The Korean Cohort for the Model Predicting a Suicide and Suicide-related Behavior (K-COMPASS) study is a prospective, naturalistic, observational cohort study, aiming to identify predictors of suicide attempt and suicide characteristics in the Korean suicidal population. The findings intend to contribute to a thorough understanding of suicidal phenomena and development of suicide prevention guidelines. The present cross-section study examines the study rationale, methodology, and baseline characteristics of the participants., Methods: Participants were enrolled via the hospital and community gateways, establishing the hospital-based cohort (HC) and community-based cohort (CC), respectively. Baseline assessment was conducted on sociodemographic, clinical, diagnostic, and psychopathological aspects. The Columbia-Suicide Severity Rating Scale was used to investigate suicidality., Results: A total of 800 suicidal people aged 15 years or older were enrolled from 8 university hospitals and 8 community mental health welfare centers (CMHWCs), among whom 480 (60%) were suicidal ideators and 320 (40%) were attempters. The ideators comprised 207 CC and 273 HC participants, whereas the attempters, 34 CC and 286 HC participants. Despite their lower severity in some measures, including suicidal ideation, compared with their HC counterparts, the CC participants within each group of ideators or attempters presented clinically significant psychopathology. Moreover, alcohol use problems and past suicide attempt were more likely to be found in CC participants. Only 11.1% to 21.6% of the participants in each of the four groups (defined by the cohorts and the ideators/attempters) were on any type of psychiatric treatment., Conclusions: Suicidal visitors to CMHWCs need to be as closely monitored as suicidal patients in university hospitals, especially considering their association with problem drinking and past suicide attempt. A cautious assumption is that the high suicide rate in Korea might be partly attributable to the low proportion of patients receiving psychiatric services., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background Aims: Few studies have examined the migration pattern of natural killer (NK) cells, especially after radiation treatment for cancer. We investigated whether irradiation can modulate the expression of chemokines in cancer cells and the migration of NK cells to irradiated tumor cells., Methods: The expression of chemokine receptors (CXCR3, CXCR4 and CXCR6) on interleukin-2 (IL-2)/IL-15-activated NK cells was assessed using flow cytometry. Related chemokine ligands (CXCL11, CXCL12 and CXCL16) in human breast cancer cell lines (MCF7, SKBR3 and MDA-MB231) irradiated at various doses were assessed using reverse transcription-polymerase chain reaction (RT-PCR), fluorescence-activated cell sorting (FACS) and enzyme-linked immunosorbent assay (ELISA). The cell-free culture supernatant was collected 96 h after irradiation of breast cancer cell lines for migration and blocking assays., Results: The activated NK cells expressed CXCR6. Expression of the CXCR6 ligand CXCL16 increased in a time- and dose-dependent manner in all analyzed cancer cell lines. CXCL16 expression was statistically significantly enhanced in all breast cancer cell lines on day 3 after 20 Gy irradiation. Activated NK cells migration correlated with CXCL16 concentration (R 2  = 0.91; P <0.0001). Significantly enhanced migration of NK cells to irradiated cancer cells was observed for a dose of 20 Gy in MCF7 (P = 0.043) and SKBR3 (P = 0.043) cells, but not in MDA-MB231 (P = 0.225) cells. A blocking assay using a CXCR6 antibody showed a significant decrease in the migration of activated NK cells in all cancer cell lines., Conclusions: Our data indicate that irradiation induces CXCL16 chemokine expression in cancer cells and enhances the migration of activated NK cells expressing CXCR6 to irradiated breast cancer cells. These results suggest that radiation would improve the anti-tumor effect of NK cells through enhanced migration of NK cells to tumor site for the treatment of patients with breast cancer., (Copyright © 2016 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

Background Aims: Interleukin-21 (IL-21) can enhance the effector function of natural killer (NK) cells but also limits their proliferation when continuously combined with IL-2/IL-15. Paradoxically, membrane-bound (mb)-IL-21 has been shown to improve human NK cell proliferation when cultured with IL-2/mb-IL-15. To clarify the role of IL-21, we investigated the effect of the timing of IL-21 addition to NK cell culture., Methods: IL-2/IL-15-activated NK cells were additionally treated with IL-21 according to the following schedules; (i) control (without IL-21); (ii) first week (day 0 to day 7); (iii) intermittent (the first 3 days of each week for 7 weeks); (iv) after 1 week (day 8 to day 14); and (v) continuous (day 0 to day 49). The expression of NK receptors, granzyme B, perforin, CD107a, interferon-γ, telomere length and NK cell death were measured by flow cytometry., Results: Compared with the control (2004.2-fold; n = 10 healthy donors) and intermittent groups (2063.9-fold), a strong proliferative response of the NK cells on day 42 was identified in the "first week" group (3743.8-fold) (P < 0.05). NK cells treated with IL-21 in the "first week" group showed cytotoxicity similar to that in control cells. On day 28, there was a significant increase in cytotoxicity of "first week" NK cells that received IL-21 treatment for an additional 2 days compared with the "first week" NK cells (P < 0.05)., Conclusions: These data suggest that controlling temporal exposure of IL-21 during NK cell proliferation can be a critical consideration to improve the yields and cytotoxicity of NK cells., (Copyright © 2014 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.)